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Reviewers
David Jonathan Kadouri
Uni vers i ty of Medi ci ne a nd Hea l th Sci ences St. Ki tts
Medi ca l Student
Cl a s s of 2013
Matthew Klairmont
Rus h Medi ca l Col l ege
Medi ca l Student
Cl a s s of 2013
Nikul Patel, MD
Uni vers i ty of Medi ci ne a nd Denti s try of New Jers ey
School of Medi ci ne

Contents
Preface
Introduction
Cross-References (for Answers) to Selected Pharmacology Texts
Generic Drug Name Recognition Guide
List of Abbreviations
General Principles of Pharmacology
Questions
Answers
The Peripheral Nervous Systems: Autonomic and Somatic Nervous System Pharmacology
Questions
Answers
Central Nervous System Pharmacology
Questions
Answers
Cardiovascular Pharmacology
Questions
Answers
Renal System and Diuretic Pharmacology
Questions
Answers
Respiratory System Pharmacology: Asthma and COPD
Questions
Answers
Autacoids and Anti-inflammatory Drug Pharmacology
Questions
Answers
Gastrointestinal and Urinary Tract Pharmacology, Nutrition (Vitamins)
Questions
Answers
Endocrine and Reproductive Pharmacology
Questions
Answers
Antimicrobial and Antiviral Pharmacology
Questions
Answers
Cancer and Immune System Pharmacology
Questions
Answers
Toxicology, Bioterrorism, and Chemical Warfare Agents
Questions
Answers
Appendices
Index

Preface
Wel come to thi s , the 14th edi ti on, of Pharmacology: PreTest Self-Assessment and Review. Im pl ea s ed to ha ve been i nvi ted ba ck to wri te thi s edi ti on
a fter doi ng the previ ous three. Whether youre s tudyi ng for Step 1 of the USMLE, or for a cours e exa m tha t i ncl udes pha rma col ogy content, I thi nk
youl l fi nd thi s hel pful .
I bel i eve thi s PreTest Self-Assessment and Review wi l l hel p you eva l ua te a nd revi ew your i ntens i ve a nd extens i ve knowl edge of pha rma col ogy
a nd thera peuti cs your knowl edge of ba s i c fa cts a nd pri nci pl es , a nd your a bi l i ty to a ppl y tha t knowl edge to s ome common cl i ni ca l s i tua ti ons .
Among the cha nges here youl l fi nd i n 14/e for pha rma col ogy a re:
Ma ny new or extens i vel y revi s ed ques ti ons , mos t ba s ed on cl i ni ca l vi gnettes or s cena ri os , mos t a l rea dy tes ted on hundreds of fi rs t- a nd s econdyea r medi ca l s tudents , a nd a l l but a s el ect few i n a forma t youl l l i kel y s ee on Step 1. Ma ny cha nges were neces s i ta ted by the a pprova l of new
drugs tha t you need to know a bout i n s ome wa y. Ma ny were ma de i n res pons e to excel l ent comments from medi ca l s tudent a nd hous e offi cer
revi ewers .
More i ntegra ti on of content between the va ri ous a rea s of pha rma col ogy a nd thera peuti cs , wi th ma ny ques ti ons tha t encoura ge you to i ntegra te
new ma teri a l wi th content pres ented ea rl i er.
A better bl end of ques ti ons tha t i ntegra te ba s i c pha rma col ogy content wi th ba s i c i nforma ti on from other precl i ni ca l di s ci pl i nes .
Cl ea rer a nd more compl ete expl a na ti ons for why correct a ns wers a re correct, a nd the others a re not.
Upda ted cros s -references to the l a tes t edi ti ons of two wi del y us ed pha rma col ogy texts , i n the a ns wers , s o you ca n fi nd a ddi ti ona l i nforma ti on or
expl a na ti ons i f you wi s h.
An upda ted res ource tha t l ets you l ook a t s uffi xes of generi c drug na mes a nd deduce wi th rea s ona bl e (or better) certa i nty the chemi ca l or
pha rma col ogi c group or cl a s s to whi ch a drug bel ongs .

Introduction
Even though your profs may tell you otherwise, pharmacology is pure memorization the ultimate challenge in medical memorization some remedy to dull the
pain of the subject is needed.
Tha t wa s the a dmoni ti on to s tudents i n a popul a r exa m s tudy a i d.
Baloney, I s a y. Bei ng a rea l i s t, there ma y be s ome truth to tha t. But, rea d on, a nd youl l s ee why I dont thi nk tha ts a n a bs ol ute truth, a nd
certa i nl y i s nt the bes t wa y to l ea rn pha rma col ogy.
My Perspectives on and Approaches to Learning Pharm
Before you get on wi th your s tudyi ng, I thought Id gi ve you a l i ttl e i ns i ght i nto who a nother otherwi s e fa cel es s a uthor mi ght be, beca us e i t mi ght
expl a i n where Im comi ng from when I prepa red the ques ti ons , a ns wers , a nd expl a na ti ons youl l fi nd here. Ive ha d a bout 35 yea rs of tea chi ng
ma ny a rea s of pha rma col ogy to more Uni vers i ty of Mi chi ga n Medi ca l School s tudents tha n I ca n count, a nd i ts a l l been a grea t pl ea s ure a nd
pri vi l ege for me. (Yup, Im a n ol d guy, but for wha t i ts worth I dri ve a bri ght yel l ow 2012 Ca ma ro converti bl e wi th a s i x-s peed ma nua l
tra ns mi s s i on! Chronol ogi c a ge i s a rel a ti ve thi ng.)
I know tha t thi ngs perta i ni ng to pha rma col ogy a nd thera peuti cs a re overwhel mi ng i n terms of brea dth, deta i l , number, a nd cons equences . A
genera ti on or s o a go the pha rma col ogi c a rma menta ri um (a nd wha t you os tens i bl y needed to know) wa s a s ma l l fra cti on of wha t i t i s now. Weve
pa s s ed the 10,000 drug ma rk, wi th new drugs comi ng a t a mi nd-boggl i ng frequency. Do you need to know a bout them a l l ? Ca n you pos s i bl y be
ta ught a bout, or be expected to l ea rn, everythi ng?
In my opi ni on, no.
Theres s i mpl y too much i nforma ti on pres ented to you i n the precl i ni ca l yea rs , a nd even though a hos t of drugs exi s t theres l i ttl e poi nt i n
knowi ng a bout them a l l expl i ci tl y. Tryi ng to do s o woul d be a futi l e a nd needl es s ta s k. But no ma tter how wel l you thi nk you know your
i nforma ti on (pha rma col ogi c or otherwi s e), no ma tter how compl etel y or comprehens i vel y youve been ta ught, a l l the content tends to become
jumbl ed a nd i ncomprehens i bl e when youre fa ced wi th the ta s k of knowi ng i t a l l a l l a t once; tha t i s , when you hi t your fi rs t of s evera l Step
exa ms , a nd get on the wa rds . You ma y l os e s i ght of the proverbi a l fores t. Knowi ng too much a bout trees a nd too l i ttl e a bout the fores t theyre i n
ma y not be s uffi ci ent once you get i nto a cl i ni ca l s i tua ti on. Its good to know ma ny i mporta nt fa cts , a nd even to be tes ted on them, but fa ct-ba s ed
knowl edge a l one i s nt s uffi ci ent. You ca nt put yours el f i n the pos i ti on of knowi ng s o much a bout the deta i l s tha t you ca nt thi nk i n broa der terms .
Borrowi ng from the l i tera ture, you a re expected to be l i ke the cheerful Ma jor Genera l i n Gi l bert a nd Sul l i va ns Pirates of Penzance. You s eemi ngl y
need to know a l l the fa cts a nd be a bl e to s pi t them ba ck a l mos t wi thout ha vi ng to s tra i n to thi nk.
It i s rewa rdi ng to a ns wer a n os tens i bl y compl i ca ted or deta i l ed ques ti on correctl y (you pos s es s the ma i n pos i ti ve a ttri butes of Gi l bert a nd
Sul l i va ns ha ppy Ma jor Genera l ), but you dont wa nt to fi nd yours el f s o bogged down i n knowi ng the deta i l s tha t you mi s s s eei ng the more
i mporta nt bi g pi cture, or how the fa cts a ppl y or rel a te to one a nother (the Ma jor Genera l s ma i n fl a w). The s i mpl es t or mos t ba s i c concepts ca n be
overl ooked wi th tea chi ng or l ea rni ng tha t i s too deta i l ed i n terms of fa ct a nd focus . You ha ve ha d a n a bunda nt (i f not exces s i ve) a mount of
i nforma ti on a bout pha rma col ogy pres ented to you, but tha ts onl y the founda ti on of a broa d knowl edge a nd experi ence ba s e upon whi ch youl l
bui l d over the comi ng yea rs . (Il l a l s o go out on a l i mb a nd s ta te tha t youve a l s o been ta ught, a nd expected to l ea rn, a ton of i nforma ti on tha t i s
tri vi a l or, a t bes t, not neces s a ry for your unders ta ndi ng a nd ul ti ma te a ppl i ca ti on of ba s i c pha rma col ogy to cl i ni ca l rea l i ty.)
One exa mpl e tha t comes to mi nd (i n fa ct, i ts i ndel i bl y etched i n my memory) i nvol ves a fa i rl y common cl i ni ca l probl em, gout. A doc i n the ER,
where I s howed up one hot s ummer da y wi th a ba d gout a tta ck, a s ked me wha t I di d for a l i vi ng. He then went on, a fter hea ri ng I ta ught pha rm, to
ci te every meta bol i c i ntermedi a te a nd enzyme i n the bi os ynthes i s of uri c a ci d by the s o-ca l l ed puri ne (ATP) degra da ti on pa thwa y. Thi s i s , of
cours e, the meta bol i c crux of the probl ems i n hyperuri cemi a a nd gout. Thi s new doc (he jus t gra dua ted from medi ca l s chool , wi th a Ph.D. degree to
boot) correctl y s ta ted tha t a l l opuri nol i nhi bi ts the l a s t two s teps i n uri c a ci d s ynthes i s by i nhi bi ti ng xa nthi ne oxi da s e. He a l s o correctl y s ta ted
tha t xa nthi ne oxi da s e genera tes oxygen free ra di ca l s a nd H 2 O2 , whi ch contri buted to the pa thophys i ol ogy. Inhi bi t xa nthi ne oxi da s e, a nd none of
thos e na s ty oxi da nts a re produced, he s a i d. Tha ts grea t. I ga ve hi m a n A for hi s i ntens i ve knowl edge.
Unfortuna tel y, tha t young phys i ci a n then dogma ti ca l l y s ta ted wha t s eemed s o mecha ni s ti ca l l y ra ti ona l but i n a ctua l i ty wa s tota l l y wrong: Gi ven
the rol e of uri c a ci d i n the pa thophys i ol ogy of gout, a nd the a bi l i ty to i nhi bi t ura te s ynthes i s wi th a l l opuri nol , hi s fi rs t choi ce thera py for my a cute
gout woul d be a l l opuri nol . (Now, of cours e, we ha ve the new a l l opuri nol -l i ke drug, febuxos ta t.) Oops . Wrong choi ce. He fl unked my cri ti ca l tes t. I
knew he ma de a s eri ous error, a nd I pol i tel y decl i ned hi s pres cri pti on a s I checked mys el f out of the hos pi ta l AMA (Aga i ns t Medi ca l Advi ce) a s he
hea ded off to fetch a pol a ri zi ng mi cros cope tha t hed us e a fter a s pi ra ti ng my hot toe. But wha t i f I di dnt know a nythi ng a bout gout, or
pha rma col ogy? Id be getti ng a deci dedl y i na ppropri a te trea tment from a deci dedl y s ma rt phys i ci a n, but a fter da ys on hi s s el ected drug Id
proba bl y be hurti ng a nd l i mpi ng wors e tha n when I ca me to the ER. Knowi ng too much does nt mea n knowi ng the ri ght s tuff. Si tua ti ons s uch a s
thi s , whether they a ppl y to gout or to a ny of hundreds of common cl i ni ca l s cena ri os , wi l l a ppl y to your pa ti ents a nd to your fa mi l y, fri ends , a nd
even to you!
What Does Epinephrine Do to Blood Pressure?
Ma ny yea rs a go I l ea rned a bout a utonomi c pha rma col ogy from Profes s or Ra ymond P. Ahl qui s t. You proba bl y ha vent hea rd a bout hi m. He i s the
pers on who i nvented the concept of a drenergi c receptors , wa y ba ck i n 1948, a nd coi ned the terms a l pha - a nd beta - a s prefi xes to a drenergi c
receptors tha t we now s o gl i bl y refer to a nd ha ve eventua l l y cha ra cteri zed on the mol ecul a r l evel . Tha t La s ker Awa rd wi nner (oh, s o cl os e to a
Nobel Pri ze) ha s proba bl y ca us ed more cons terna ti on for medi ca l a nd other hea l th ca re profes s i ons s tudents , gi ven the fa ct tha t now we ha ve
mul ti pl e a l pha - a nd beta -a drenergi c receptors , a nd you need to l ea rn a bout them, the drugs tha t a cti va te them, a nd the i ncrea s i ng number of
drugs tha t bl ock them. Dr Ahl qui s t us ed to l a ugh l oudl y, not onl y a bout how hi s concept devel oped, but a l s o a bout how there wa s (a nd s ti l l i s ) s o
much more for you to l ea rn a bout, unders ta nd, a nd a ppl y. If he were s ti l l a l i ve hed s ti l l be chuckl i ng.
Ahl qui s t ta ught ma ny s tudents a bout a utonomi c pha rma col ogy, a nd there i s much to be ta ken a wa y a nd a ppl i ed to the ba s i c yet es s enti a l
knowl edge ba s e more tha n 70 yea rs l a ter; wha t YOU need to know a bout.
Wha t i s the effect of epi nephri ne on bl ood pres s ure? he woul d a s k. Hi s s tudents woul d a ns wer tha t epi nephri ne ra i s es bl ood pres s ure. Tha t
a ns wer wa s i ncorrect. Next wed s a y tha t epi nephri ne l owers bl ood pres s ure. Tha t, too, wa s wrong. Ahl qui s ts a ns wer wa s tha t the effects of
epi nephri ne on bl ood pres s urea nd i ndeed the res pons es to a ny other drugdepends . It depends on the dos e, the a dmi ni s tra ti on route, the
condi ti on of the pa ti ent (eg, whether he or s he ha s a ny other condi ti ons , or i s ta ki ng a ny other drugs ), a nd a whol e bunch of other fa ctors .
Lea rn thi s i t depends a ns wer when you l ea rn a bout a l l drugs . But remember, the ques ti ons i n thi s text, a nd thos e youl l rea d on your med
s chool a nd Step exa ms , a re wri tten to el i ci t the mos t l i kel y correct a ns wer.
And So, A Disclaimer of Sorts

Your experi ences from the cours es a nd exa ms youve ta ken ma y be qui te di fferent from thos e of s tudents i n other medi ca l s chool s , the medi ca l
s tudents Ive ta ught, or the very s a me s tudents here or el s ewhere ta ught by s omeone el s e. And s o the focus of ques ti ons youl l s ee here ma y be
di fferent from thos e youve encountered on your exa ms , a nd the expl a na ti ons ma y di ffer too. There i s no one s ta nda rd pha rma col ogy curri cul um
for a l l medi ca l s chool s . Some ha ve s epa ra te precl i ni ca l cours es for the ba s i c s ci ences (a na tomy, phys i ol ogy, pha rm, a nd s o on). Others , s uch a s
ours , ha ve a di s ci pl i ne-ba s ed curri cul um i n whi ch, for exa mpl e, ba s i c s ci ence i nforma ti on a ppl i ca bl e to ca rdi ova s cul a r di s ea s es a re a l l i n one
s ecti on (we ca l l them s equences ).
And when we thi nk a bout i ndi vi dua l fa cul ty i ts obvi ous tha t poi nts empha s i zed by a pa rti cul a r i ns tructor ma y di ffer (s ometi mes ma rkedl y) i n
s cope a nd ori enta ti on from thos e ma de by others . Some fa cul ty pl a ce cons i dera bl e empha s i s on deta i l ed or compl ex mecha ni s ms of a cti on,
perha ps repl ete wi th s uch thi ngs a s s peci fi c pa thwa ys of drug meta bol i s m; chemi ca l s tructures , a nd perha ps s tructurea cti vi ty rel a ti ons hi ps ;
ma thema ti ca l a pproa ches to pha rma coki neti cs ; a nd s o on. Students s ometi mes l ea ve l ecture wonderi ng wha t the cl i ni ca l i mpl i ca ti ons a re.
Convers el y, other fa cul ty a ddres s the cl i ni ca l rel eva nce of certa i n drugs , but do l i ttl e more tha n s a y Your 50-yea r-ol d ma l e pa ti ent ha s recentl y
been di a gnos ed wi th Type 2 di a betes mel l i tus . Metformi n i s a good s ta rti ng drug. As Homer Si mps on mi ght s a y, duh-oh, ok. But why? When?
How does i t work?
The s a me a ppl i es to pha rma col ogy texts . Some ma y devote a pa ge or more to a pa rti cul a r drug or topi c, a nd i n others tha t i nforma ti on ma y not
a ppea r a t a l l .
Next there i s the i s s ue of newnes s or ti mel i nes s . Drugs come a nd go a l l the ti mea l though i ts cl ea r tha t new drugs a re bei ng a pproved a t a
fa s ter ra te tha n thos e tha t a re di s a ppea ri ng. Thi s pres ents s omewha t of a predi ca ment for you, a nd s o, for me. Wha t to l ea rn, wha t to a s k
ques ti ons a bout. For deca des s tudents ha ve l ea rned a bout d-tubocura ri ne (cura re) a s the prototype nondepol a ri zi ng s kel eta l neuromus cul a r
bl ocker: a competi ti ve a nta goni s t of a cetyl chol i ne a t NM (ni coti ni c-s kel eta l mus cl e) receptors . Its no l onger us ed i n the Uni ted Sta tes . Indeed, a
rel a ti vel y new cura re-l i ke drug, metocuri ne, i s no l onger a va i l a bl e here ei ther. If you were to l ook a t not-s o-ol d edi ti ons of a pha rma col ogy text
or even the previ ous edi ti on of thi s bookyoud fi nd content rel a ted to the gl i ta zones (thi a zol i di nedi ones , to be more preci s e), a nd l ea rn or be
tes ted a bout a va ri ety of drugs i n thi s cl a s s of ora l drugs for Type 2 di a betes mel l i tus . How thi ngs ha ve cha nged. Owi ng to va ri ous s eri ous s i de
effects a nd a dvers e res pons es , s ome fa ta l , onl y one gl i ta zone rema i ns : pi ogl i ta zone.
Then there i s the i s s ue of i ns ti tuti ona l preferences i n terms of drug us e whi ch, i nferenti a l l y, ma y a ffect wha t youre ta ught a nd expected to
l ea rn. Perha ps youl l l ea rn the ba s i c pha rma col ogy of ephedri ne. For yea rs i t ha s been a n outmoded drug for ca us i ng modes t bronchodi l a ti on i n
a s thma , a nd ha s ga i ned more of a reputa ti on a s a CNS s ti mul a nt a nd wei ght-l os s a i d tha t wa s often a bus ed or mi s pres cri bed. Nonethel es s ,
beca us e of a va ri ety of fa ctors ephedri ne gets rel a ti vel y l i ttl e a ttenti on, i f a ny a ttenti on a t a l l , i n ma ny pha rma col ogy l ectures a nd texts . But a t our
i ns ti tuti on, ephedri ne i s us ed frequentl y i n the opera ti ng rooms when the goa l i s to ca us e a l i ttl e upwa rd bl i p of bl ood pres s ure tha t ma y ha ve
fa l l en too much i n res pons e to certa i n a nes theti c a gents .
Youl l a l s o l ea rn a bout revers i ng s kel eta l mus cl e pa ra l ys i s ca us ed by the nondepol a ri zi ng (cura re-l i ke) drugs : revers e the bl ocka de by gi vi ng a
chol i nes tera s e i nhi bi tor (ma i nl y us i ng neos ti gmi ne), but fi rs t gi ve a tropi ne to prevent unwa nted s ti mul a ti on of mus ca ri ni c receptors when the
chol i nes tera s e i nhi bi tor does i ts ma ny thi ngs . Wel l , here a nd i n ma ny other i ns ti tuti ons , a tropi ne i s not us ed for tha t purpos e. Ins tea d, the
a nti mus ca ri ni c a gent tha ts us ed i s gl ycopyrrol a teyet a nother drug tha t ma y not be menti oned i n l ecture or gi ven much, i f a ny, di s cus s i on i n a
text.
Now, I wa nt to a l l a y your concerns a nd gi ve you confi dence tha t you ca n l ea rn thi s ma teri a l , a nd a ppl y wha t you proba bl y ha ve l ea rned a bout
fa mi l i a r (ta ught) drugs to thos e you ha vent expl i ci tl y l ea rned or rea d a bout. For exa mpl e, youl l fi nd, i n thi s book, a t l ea s t one ques ti on a bout
gl ycopyrrol a te. But i t wi l l be des cri bed i n s uch a wa y i n terms of i ts a cti ons a nd us es (eg, gi ven ri ght before a n a cetyl chol i nes tera s e i nhi bi tor i s
a dmi ni s tered to revers e neuromus cul a r bl ocka de, ca us es effects a nd s i de effects X, Y, a nd Z) tha t i f you know the ba s i cs a bout a tropi ne, youl l
be a bl e to a ns wer the ques ti on a bout gl ycopyrrol a te wi th no probl ems .
For better or wors e, I try to a i m for the mi ddl e ground i n tea chi ng a nd tes ti ng. My focus us ua l l y i s on the whys of thi ngs proba bl y more tha n the
wha ts , a nd I try to reduce the number of wha t our s tudents refer to a s ra t fa cts to a mi ni mum. I dont s pend ti me tea chi ng a bout a l l the
a ngi otens i n-converti ng enzyme i nhi bi tors when I ca n tea ch the es s enti a l s by focus i ng on ca ptopri l . I prune the tea chi ng of -bl ockers wi th a focus
on propra nol ol a s the prototype (mos t repres enta ti ve drug), a nd then s pend s ome ti me ta l ki ng a bout the s o-ca l l ed ca rdi os el ecti ve -bl ockers
(a tenol ol , metoprol ol ), thos e tha t ha ve va s odi l a tor a cti vi ty (whether by vi rtue of -bl ocka de, l i ke l a beta l ol , or ni tri c oxi de genera ti on, a s wi th
bi s oprol ol ), a nd try to s how how or why thos e drugs a re di fferent (yet i n key wa ys , s uch a s a dvers e effects or contra i ndi ca ti ons ) a nd i mporta nt
cl i ni ca l l y. No di s cus s i on or tes ti ng on the two dozen or s o other -bl ockers .
I a l s o provi de you, i n one of the a ppendi ces , wi th a na me recogni ti on gui defor exa mpl e, i f the drugs generi c na me ends i n -pri l i ts a n
a ngi otens i n-converti ng enzyme i nhi bi tor; i f the generi c na me ends i n -ol ol i ts s ome s ort of -a drenergi c bl ocker. Us e i t! Youl l fi nd i n thi s
PreTest s evera l ques ti ons a bout a drug you ma y not ha ve l ea rned a bout expl i ci tl y. But i f you know your word s tems youl l be a l l s et to a ns wer
the ques ti on correctl y. As one exa mpl e: There i s a ques ti on or two a bout the mos t l i kel y s i de effects of ta ms ul os i n, a drug us ed for ma na gi ng
beni gn pros ta ti c hypertrophy. Ha vent l ea rned a bout ta ms ul os i n expl i ci tl y? No probl em. Look a t the generi c na me: ta ms ul osin. Sa me a s pra zosin, a
s el ecti ve 1 -receptor bl ocker tha t Im s ure you ha ve l ea rned a bout. Al l the s el ecti ve -bl ockers a re l i ke pra zos i n i n mos t (but cl ea rl y a l l ) i mporta nt
wa ys .
There i s no uni vers a l l y a dopted or offi ci a l medi ca l pha rma col ogy cours e or cours e content (even though the Na ti ona l Boa rd of Medi ca l
Exa mi ners , who prepa re your Step exa ms , ha ve rel a ti vel y focus ed l ea rni ng a nd tes ti ng objecti ves ). If youre curi ous , l ook a t the text reference pa ge
numbers i n the expl a na ti ons to a ns wers i n thi s book. For s ome drugs or rel a ted ma teri a l you ma y s ee s evera l pa ges devoted to the topi c i n one
book, a nd jus t one (or perha ps jus t one fi gure or ta bl e) i n a nother. In one text the pa ge references ma y come from ea rl y pa rts of the book, a nd for
the other i t wi l l be pretty obvi ous tha t the content i s put towa rd the end. Its not tha t one text i s better tha n the other. It s i mpl y refl ects di fferent
bi a s es a nd preferences by the a uthors or edi tors .
I ha ve a certa i n job to do, res pons i bi l i ti es to ful fi l l , a s I deem a ppropri a te: pi ck a nd choos e ma teri a l I thi nk i s i mporta nt; tea ch i t cl ea rl y a nd i n
a ma nner tha t excl udes wha t I deem unneces s a ry (eg, drug s tructures ; a s a phys i ci a n youl l proba bl y never ha ve to l ook a t the chemi ca l s tructure of
a drug a nd fi gure out wha t i t i s , wha t i t i s us ed for, i ts s i de effects , a nd s o on). I try to s i mpl i fy tha t whi ch ca n be unneces s a ri l y compl i ca ted. I try to
bri dge l ea rni ng of ba s i c fa cts a nd concepts a nd a ppl yi ng them cl i ni ca l l y, a nd l a rgel y i gnore content I thi nk i s , for l a ck of a better phra s e, too over
the top or deta i l ed to be of us e for more tha n jus t s omethi ng el s e to l ea rn. My ba ckground i s l a rgel y i n s ys tems -ba s ed phys i ol ogy a nd
pa thophys i ol ogy (a s oppos ed to, s a y, bi ochem a nd mol ecul a r bi ol ogy), a nd s o ma ny of my ques ti ons a nd expl a na ti ons focus on tha t. Thi s i s wha t I
do i n cl a s s a nd on exa ms , a nd i t i s refl ected i n my ma i n a pproa ch to wri ti ng ques ti ons a nd expl a i ni ng the a ns wers i n thi s book.
Breadth and Depth of Questions and Answers: Low Yield, High Yield?
Mos t s tudents who revi ewed previ ous edi ti ons of PreTest Pharmacology found the book to be extremel y us eful . However, s ome ques ti ons were
ci ted by a few revi ewers a s bei ng l ow-yi el d, too ba s i c, too cl i ni ca l , a nd the l i ke.
Ive tri ed to a ddres s thes e cri ti ci s ms i n every edi ti on of thi s book tha t Ive wri tten, but l et me pol i tel y opi ne tha t a t thi s poi nt i n your medi ca l
educa ti on youre not i n the bes t pos i ti on to ma ke judgment ca l l s on s uch ma tters , a nd jus t beca us e you were (or werent) ta ught or tes ted on a

pa rti cul a r poi nt by your profs does nt mea n tha t other s tudents ha ve or ha vent ha d the s a me expecta ti ons . And wha t s tudents s ometi mes ci te a s a
l ow yi el d ques ti on i s a ctua l l y ba s i c a nd mus t know i nforma ti on, even though the correct a ns wer ma y be ra ther obvi ous to mos t s tudents . Tha t
does nt mea n the i nforma ti on i s uni mporta nt, or tha t your a bi l i ty to recogni ze i t s houl dnt be eva l ua ted. It coul d wel l mea n tha t youve l ea rned the
es s enti a l ba s i cs , a nd tha ts good. In a ddi ti on, s ome s tudents ha ve ca l l ed certa i n ques ti ons l ow yi el d s i mpl y beca us e they ha vent l ea rned a bout
the fa cts or concepts a ddres s ed i n the ques ti on. Its ea s y to a ttri bute l i ttl e i mporta nce to thi ngs one does nt know or unders ta nd, a nd s a y the
ques ti on i s tri vi a l .
For s ome of you i ts tempti ng to vi ew s ome of my ques ti ons a s too cl i ni ca l ; others ma y fi nd thi ngs too ba s i c or mecha ni s ti c. I ha ve been
chi ded for a s ki ng s ome ques ti ons a bout i n vi tro obs erva ti ons , when the res pons es deemed mos t i mporta nt a nd a ppropri a te s eemi ngl y a re thos e
tha t occur i n huma ns . Tha ts not neces s a ri l y true i n my opi ni on.
Ans weri ng a l l the ques ti ons i n thi s book i s rel a ti vel y s i mpl e i f you thi nk a bout the ba s i c i nforma ti on you s houl d ha ve a cqui red; i f you i ntegra te
i t wi th wha t you s houl d ha ve l ea rned i n other cours es (eg, i n a phys i ol ogy or cel l a nd mol ecul a r bi ol ogy cours e tha t ma y i ncorpora te a l ot of
knowl edge ba s ed on i n vi tro s tudi es ); a nd i f you s ta rt doi ng wha t you wi l l ha ve to do s oonma ke rea s oned judgments ba s ed on a ppl yi ng your
knowl edge to a pos s i bl y new cl i ni ca l pi cture: whi ch i s mos t l i kel y?
Breadth and Depth of Questions and Answers: Empiric Data or Mechanistically Certain Information?
Some revi ewers ha ve noted tha t s ome ques ti ons focus on empi ri c i nforma ti on: fi ndi ngs , s uch a s certa i n s i de effects , for whi ch we dont ha ve good
(l et a l one defi ni ti ve) i nforma ti on on mecha ni s ms of a cti on. The premi s e of thos e cri ti ci s ms i s Why a s k ques ti ons a bout thes e i s s ues , for whi ch
[I] ca n offer no proven mecha ni s ti c expl a na ti ons , when there i s s o much other i nforma ti on to a s k ques ti ons a bout, s o much other i nforma ti on
a bout whi ch we need to know? Some exa mpl es i ncl ude the i ncrea s ed ri s k of a s thma -rel a ted dea ths from l ong-a cti ng -a goni s ts ; the cons ti pa ti ng
effect of vera pa mi l ; the fa ci a l fl us hi ng a s s oci a ted wi th i mmedi a te-a cti ng ni a ci n; the s kel eta l mus cl e da ma ge ca us ed by s ta ti ns ; a nd ma ny more.
The rea s on why I i ncl ude s uch ques ti ons i s tha t thes e a nd ma ny other s o-fa r mecha ni s ti ca l l y unexpl a i ned s i de effects , a dvers e res pons es , a nd
rel a ted i s s ues a re cl i ni ca l l y i mporta nt a nd s ometi mes common. We ma y not be a bl e to expl a i n a l l the whys i n bi ochemi ca l terms (I ma y
s pecul a te a bout s ome publ i s hed mecha ni s ms ), but when thes e untowa rd res pons es ha ppen a nd ca us e a dvers e cons equences , a s they often do,
i ts i mporta nt for you to know.
Suggestions on How to Use This Book
Prepa re yours el f to a ns wer the ques ti ons i n ea ch cha pter by fi rs t revi ewi ng the corres pondi ng ma teri a l from your l ecture notes a nd fa vori te (or, a t
l ea s t, a s s i gned) text. Thi s vol ume tha t you hol d i n your ha nds i s , a fter a l l , a revi ew a nd s el f-a s s es s ment tool , not a n ori gi na l s ource of l ea rni ng
i nforma ti on.
Before you work on the ques ti ons a nd your s tudyi ng overa l l , try to do the fol l owi ng:
Be able to identify main drug classes, recognizing that sometimes we use more than one classification scheme (eg, chemical; by main mechanism(s) or site(s)
of action; by clinical use); and be able to cite a prototype drug for each. Conversely, given a named prototype or otherwise representative drug, be able to work
backward and know the rest of the most relevant information, including the class(es) to which it belongs.
For exa mpl e, you s houl d be a bl e to i denti fy a group of drugs tha t a re ca l l ed di hydropyri di nes a s a l a rge a nd ma i n chemi ca l cl a s s of ca l ci um
cha nnel bl ockers (CCBs ) tha t a re ma i nl y va s odi l a tors a nd a re us ed for s uch i ndi ca ti ons a s hypertens i on or other condi ti ons i n whi ch va s odi l a ti on
i s des i red. You s houl d know tha t ni fedi pi ne ca n be cons i dered a prototype of the ra ther l a rge di hydropyri di ne CCB cl a s s .
You s houl d be a bl e to ta ke the revers e a pproa ch by i denti fyi ng ni fedi pi ne a s the prototype di hydropyri di ne CCB; i denti fyi ng the ma i n a cti ons of
the drug a nd i ts overa l l cl a s s ; a nd recogni zi ng the ma i n us es a nd a dvers e effects .
And, you s houl d a l s o know how other CCBs , not cl a s s i fi ed a s di hydropyri di nes (eg, vera pa mi l , di l ti a zem), di ffer a nd work. You certa i nl y dont
need to l ook a t chemi ca l s tructures to deduce the di fferent a cti vi ty profi l es , but you certa i nl y do need to know how, for exa mpl e, the a cti ons of
ni fedi pi ne di ffer from thos e of, s a y, vera pa mi l .
Its a l s o i mporta nt to know a bout wha t mi ght be des cri bed a s s ubprototypes for exa mpl e, wha ts s peci a l a bout a tenol ol or metoprol ol , or
l a beta l ol , compa red wi th the overa l l a nd prototypi c -a drenergi c bl ocker, propra nol ol ? In thi s book Il l tel l you how you ca n never forget tha t
l a beta l ol , a wi del y us ed drug, bl ocks both - a nd -a drenergi c receptors . And Il l gi ve you l ots of other memory-enha nci ng ti ps , too.
Be able to identify the class to which a drug belongs by looking at its generic name or other name.
You s houl d ha ve s ome knowl edge of a drugs cl a s s by l ooki ng a t i ts generi c na mefor exa mpl e, a drug tha t ends i n the s uffi x -s ti gmi ne i s a
revers i bl e a cetyl chol i nes tera s e i nhi bi tor; one tha t ends i n -pri l i s a n a ngi otens i n-converti ng enzyme i nhi bi tor; a -s a rta n i s a n a ngi otens i n
receptor bl ocker; a nd s o on. Al though thi s l ook a t the generi c na me a nd youl l know the drug group techni que does nt a ppl y to a l l drugs , i t does
a ppl y to proba bl y hundreds . To tha t end, Ive i ncl uded a ta bl e a t the ba ck of the book to hel p you do tha t. You a l s o need to be a bl e to gi ve a
rea s ona bl e worki ng defi ni ti on for certa i n drug cl a s s i fi ca ti on terms , s uch a s ca techol a mi ne, SSRI, or revers e tra ns cri pta s e i nhi bi tor. You get the
poi nt, I hope. Thi s l ea rni ng tri ck does nt work a l l the ti me, of cours e, s i nce for ma ny drugs there i s nt a ny rhyme or rea s on behi nd the na mes .
Be able to state the main expected effects or side effects of major drugs or drug classes. This should give you a good idea of what the relevant precautions or
contraindications are, even if you havent been taught about the latter, even if your learning focus hasnt been too clinical.
For exa mpl e, you know tha t a l l -a drenergi c bl ockers ca n reduce ca rdi a c ra te, contra cti l i ty, a nd el ectri ca l i mpul s e conducti on vel oci ty (es peci a l l y
through the AV node), a nd s ometi mes thes e drugs a re us ed s peci fi ca l l y to ca us e one or more of thos e effects . You s houl d then rea l i ze tha t
exces s i ve dos es ma y ca us e unwa nted degrees of s uppres s i on of thos e ca rdi a c pa ra meters . And you s houl d rea l i ze tha t the effects of thes e drugs
wa rra nt extra ca uti on (or contra i ndi ca te a l together) the us e of a ny -bl ocker i n pa ti ents who a l rea dy ha ve bra dyca rdi a , s i gni fi ca ntl y reduced
ventri cul a r contra cti l i ty/ca rdi a c output, or s ome degree of hea rt bl ock. Ma ki ng thes e a s s oci a ti ons or extra pol a ti ons i s not rocket s ci ence tha t you
mus t ha ve been ta ught a bout expl i ci tl y. You s houl d be a bl e to us e your ba s i c knowl edge of pha rma col ogy a nd drug a cti on, a nd of phys i ol ogy a nd
pa thophys i ol ogy, to pi ece thi ngs together a nd get the correct (or mos t l ogi ca l or l i kel y) a ns wer.
Be able to state the most important (eg, common, serious, or life-threatening) unwanted side effects, adverse responses, and clinically relevant drug
interactions for the main drugs or drug classes.
Such mus t know a dvers e res pons es to certa i n drugs a rent neces s a ri l y common ones , but you need to know a bout them. For exa mpl e,
myopa thy a nd potenti a l rha bdomyol ys i s from s ta ti ns i s rel a ti vel y ra re, but you certa i nl y need to know a bout thes e ra ther uni que cl a s s -rel a ted
a dvers e effects , a nd thei r cl i ni ca l cons equences . (Ra re i s a n i nteres ti ng word. Sta ti n-i nduced myopa thy a ffects fa r fewer tha n 1% of pa ti ents
ta ki ng the drug, but when you cons i der the fa ct tha t mi l l i ons of pa ti ents a re ta ki ng thi s medi ca ti on, the i mpl i ca ti on i s tha t youl l proba bl y
encounter the probl em a nd need to be a bl e to recogni ze a nd properl y dea l wi th i t.) The s a me a ppl i es to gi ngi va l hyperpl a s i a from phenytoi n when
a dmi ni s tered to (ma i nl y) chi l dren; pa ra doxi ca l thrombocytopeni a from unfra cti ona ted hepa ri n; coa gul opa thi es (i ncl udi ng pa ra doxi ca l thrombos i s )
from l oa di ng dos es of wa rfa ri n, a nd embryopa thy when even otherwi s e proper dos es a re a dmi ni s tered duri ng the fi rs t 12 weeks of pregna ncy; a nd
s o on. And, a s one fi na l exa mpl e, you need to unders ta nd the potenti a l ri s ks of gl i bl y s a yi ng ta ke a ceta mi nophen to your pa ti ents who a re
ta ki ng wa rfa ri n.

Get a decent pharmacology book, read it, and learn what not to focus on when filling up your memory bank.
The expl a na ti ons for a l l the a ns wers I provi de a re cros s -referenced to two excel l ent texts . Goodma n a nd Gi l ma ns The Pharmacological Basis of
Therapeutics (12th edi ti on) i s wi thout equa l a s a n a uthori ta ti ve, current, a nd compl ete book. Dr La rry Brunton ha s done a n outs ta ndi ng job a t the
edi tors hel m for a whi l e now, a nd the book ha s been the defi ni ti ve bi bl e of pha rma col ogy for deca des . The other ci ta ti ons a re for Basic and
Clinical Pharmacology, by Drs Ka tzung, Ma s ters , a nd Trevor. To me Ka tzung s tri kes the bes t ba l a nce between ba s i c pha rma col ogy a nd drug a cti ons
wi th current thera peuti c pri nci pl es . And you dont ha ve to rea d a n exces s i ve number of pa ges to get the s a l i ent i nforma ti on. Thes e
recommenda ti ons a re not merel y pa yi ng homa ge to thi s books publ i s her, McGra w-Hi l l . They a re unbi a s ed a nd profes s i ona l l y hones t.
Ma ny drugs come a nd go. We us ed to tea ch a bout ri todri ne, a predomi na tel y 2 a goni s t, a s a uteri ne rel a xa nt drug to hel p s l ow prema ture
l a bor. Its gone, a t l ea s t here i n the Uni ted Sta tes . Cromol yn a nd nedocromi l were s ometi mes us ed (a nd your predeces s ors were tes ted a bout) a s
control meds for a s thma . Gone. It wa s ea s y to des cri be a nd a s k ques ti ons a bout tubocura ri ne, the prototypi c nondepol a ri zi ng s kel eta l mus cul a r
bl ocker. Gone, a nd now we a ddres s s uch drugs a s vecuroni um, mi va curi um, a nd others , a nd i ts rea l l y i mpos s i bl e to pi ck one of thos e drugs a s a
prototype. The drugs cl a s s i fi ed a s cycl ooxygena s e II (COX-2) i nhi bi tors ha ve been wi nnowed down to one drug, cel ecoxi b. The gl i ta zones , a
rel a ti vel y s ma l l group of drugs for Type 2 di a betes , but i mporta nt nonethel es s , ha ve onl y one drug rema i ni ng: pi ogl i ta zone.
There a re other i s s ues I thi nk I need to poi nt out to you, a nd they rel a te to wha t you ma y or ma y ha ve not l ea rned a bout. After revi ewi ng l ots of
a nonymous pa ti ent records from our i ns ti tuti on, Ive noted the fol l owi ng, for exa mpl e. Ephedri ne, norma l l y cons i dered a mi nor drug a nd s o not
often ta ught, i s a ma i ns ta y i n our opera ti ng rooms when the goa l i s to ca us e a l i ttl e upwa rd bl i p of a too l ow bl ood pres s ure. Ephedri ne i s
des cri bed i n mos t texts very bri efl y, a nd the comments us ua l l y des cri be the l i mi ta ti ons of the drug a nd rel ega te i t to s el dom us ed s ta tus . Not s o
i n the rea l worl d.
In our opera ti ng rooms , ma ny pa ti ents get pa ra l yzed wi th a nondepol a ri zi ng neuromus cul a r bl ocker (us ua l l y one of the curi nes , but not our
l ong-s ta ndi ng prototype, tubocura ri ne, s i nce i ts gone), a nd of cours e thei r neuromus cul a r bl ocka de us ua l l y needs to be revers ed pos t-op. You
ha ve no doubt l ea rned tha t revers a l of s uch mus cl e pa ra l ys i s i nvol ves trea tment wi th a tropi ne, then a chol i nes tera s e i nhi bi tor, us ua l l y
neos ti gmi ne. The di ffi cul ty here i s tha t, a t our i ns ti tuti on a nd a t ma ny others , a tropi ne i s nt us ed. We us e gl ycopyrol a te i ns tea d of a tropi ne nea rl y
a l l the ti me. Ha ve you been ta ught expl i ci tl y, or rea d expl i ci tl y, a bout gl ycopyrrol a te? Bet you the a ns wer i s no. But youl l fi nd here, i n thi s edi ti on
of PreTest Pharmacology a l l youl l need to know to gui de you to the correct a ns wers .
Using this PreTest Book
The ma jori ty of ques ti ons a re wri tten to el i ci t the one bes t or mos t l i kel y correct res pons e. Ma rk your a ns wer by ea ch ques ti on, or downl oa d,
pri nt, a nd us e the a ns wer s heets Ive pos ted on my pers ona l tea chi ng web s i te. (The URL i s www.umi ch.edu/~ms hl a fer/pha rm.html . When you
get there, cl i ck the PreTes t button a t the top of the pa ge.) Try to a l l ow yours el f a mi nute or s o for ea ch ques ti on, but dont rus h. There a re no
pena l ti es for goi ng through thi s revi ew a nd a ns weri ng i ncorrectl y, a nd no rewa rds for s peed. Then your ti me wi l l be s pent bes t goi ng through the
expl a na ti ons for the a ns wers .
Ma ny s tudents who ha ve us ed previ ous edi ti ons of PreTest Pharmacology ha ve s a i d tha t even though they ma y ha ve a ns wered ques ti ons
correctl y, theyve s ti l l l ea rned or fi na l l y unders tood s omethi ng va l ua bl e a nd perha ps even i ndel i bl e by rea di ng the expl a na ti ons . After you fi ni s h
a l l the ques ti ons i n a cha pter, s pend a s much ti me a s you need veri fyi ng your a ns wers a nd ca reful l y rea di ng the expl a na ti ons provi ded. Thi s i s
pa rti cul a rl y i mporta nt i f you chos e a wrong a ns wer, di dnt ha ve a rea l cl ue a bout wha t the ri ght a ns wer mi ght be, or jus t ma de a l ucky gues s ,
perha ps beca us e of your tes t-s a vvy s ki l l s . So, try to rea d every expl a na ti on, es peci a l l y the more l engthy ones . I wrote mos t of the expl a na ti ons to
rei nforce a nd s uppl ement the i nforma ti on s ought by the ques ti ons , a nd s ometi mes gentl y to encoura ge you to l ook a t (us ua l l y ea rl i er) pa rts of
thi s revi ew book. Do revi s i t your cl a s s notes a nd a decent pha rma col ogy text (s ee a bove a nd the references to key texts l i s ted for ea ch a ns wer
expl a na ti on) for further cl a ri fi ca ti on too.
I urge you not to do one ra ther tempti ng thi ng: rea d, or even peek, a t the a ns wers to i ndi vi dua l ques ti ons i n a cha pter before youve a ns wered
a l l the ques ti ons . I know thi s ma y be pa i nful i n a va ri ety of wa ys (but, no pa i n, no ga i n they s a y). Nonethel es s , expl a na ti ons for the a ns wer to
one ques ti on ma y gi ve you a ti p-off (i f not the outri ght correct a ns wer) to a nother ques ti on tha t mi ght a ddres s the s a me drug or drug cl a s s , but
from a di fferent pers pecti ve. In thi s s el f-s tudy a nd revi ew proces s for a s s es s i ng your knowl edge, unders ta ndi ng, a nd s ynthes i s s uch ti p-offs
ma y l ul l you a rri vi ng a t a correct a ns wer by a s hort-ci rcui ted a pproa ch, ha vi ng jus t rea d a s i mi l a r or rel a ted a ns wer to a nother ques ti on. There i s
pl a nned redunda ncy i n s ome of the ques ti ons a nd the a ns wers Ive wri tten for you.
Some Acknowledged, Up-front Caveats
As I menti oned a bove, a nd for rea s ons I bel i eve a re defens i bl e, Ive omi tted drug s tructures , or deta i l ed chemi ca l rea cti ons tha t des cri be the
s ynthes i s or degra da ti on of drugs . And, whi l e ma ny s tudents ha ve pra i s ed tha t the va ri ous cha pters hel ped them l ea rn ma teri a l for s peci fi c a rea s
of pha rma col ogy a nd thera peuti cs , a nd do wel l on thei r exa ms , I do thi ngs a l i ttl e di fferentl y here.
Look a t ques ti ons i n mos t other revi ew books or texts , or l ook a t the ques ti ons on your own exa ms , a nd youl l proba bl y fi nd tha t the s cope of
ques ti ons i s qui te l i mi ted. Ques ti ons a s s es s i ng your knowl edge a bout, for exa mpl e, a nti hypertens i ve drugs , ha ve a ns wer choi ces tha t a re ra ther
l i mi ted to knowl edge a bout a pa rti cul a r a nti hypertens i ve drug or drug cl a s s : Wha t i s the mos t l i kel y s i de effect of thi s pa rti cul a r ca l ci um cha nnel
bl ocker? Some wi l l di vers i fy a s s es s ment of your knowl edge a bi t more: Whi ch a nti hypertens i ve drug mos t l i kel y ca us ed thi s s ta ted a dvers e
res pons e? Goi ng further, a ques ti ons a ns wer choi ces ma y i ncl ude drugs repres enti ng a hos t of di vers e ca rdi ova s cul a r drugs us ed, for exa mpl e,
for a ngi na , hypertens i on, hyperchol es terol emi a , a nd s o on. Sti l l , tha ts a rel a ti vel y na rrow focus .
Such ques ti ons dont ful l y a ddres s cl i ni ca l rea l i tyyour a bi l i ty to i ntegra te a nd a ppl y knowl edge a cros s wha t mi ght s eem l i ke i ndependent
a rea s of pha rma col ogy, thera peuti cs , a nd medi ci ne. For exa mpl e, certa i n res pi ra tory drugs ma y ha ve a nega ti ve i mpa ct on your pa ti ents
ca rdi ova s cul a r di s ea s e. An os tens i bl y funda menta l a utonomi c nervous s ys tem drug ma y ha ve i mporta nt i mpl i ca ti ons to your pa ti ent wi th a certa i n
ca rdi ova s cul a r or ophtha l mi c di s ea s e, res pi ra tory di s ea s e, or a ny of s evera l di s ea s es of the centra l nervous s ys tem. And s o, ma ny ques ti ons i n
thi s book encoura ge you to i ntegra te a nd a ppl y your knowl edge a cros s s evera l s eemi ngl y di s crete a rea s of drug thera py. Doi ng s o i s wha t mos t
of you wi l l ha ve to do, a t l ea s t ea rl y on i n your ca reers . Its s i mpl y good, a nd neces s a ry, hol i s ti c i ntegra ti on of your knowl edge.
And s o now, a s you turn the pa ges a nd s ta rt your s el f-a s s es s ment a nd revi ew, do a s one of my fa vori te comi cs (La rry the Ca bl e Guy) woul d
encoura ge you to do: Gi t er done!
Good l uck!
Ma rs ha l Shl a fer
Profes s or, Depa rtment of Pha rma col ogy
Uni vers i ty of Mi chi ga n Medi ca l School
Ann Arbor, MI 48109-0632
ms hl a fer@umi ch.edu

2013

Cross-References (for Answers) to Selected Pharmacology Texts

BruntonBrunton L, Cha bner B, Knol l ma n B, eds . Goodman & Gilmans The Pharmacological Basis of Therapeutics, 12th ed. McGra w-Hi l l ,
2011.

KatzungKa tzung B, Ma s ters S, Trevor, A eds . Basic and Clinical Pharmacology, 12th ed. McGra w-Hi l l , 2012.
Expl a na ti ons for the a ns wers provi ded i n thi s edi ti on of PreTestPharmacology a re cros s -referenced to one or both of the a bove pha rma col ogy
texts .
Ea ch text excel s i n certa i n res pects , yet they di ffer i n terms of a ctua l content a nd how i t i s pres ented. Look a t the text cros s -references i n ea ch of
my a ns wers a nd youl l s ee the di fferi ng focus . One text, or a pa rti cul a r cha pter i n tha t text, ma y be more mecha ni s ti c or more deta i l ed; a nother ma y
be more cl i ni ca l ; one ma y pa i nt a di s cus s i on a bout certa i n drugs or drug groups , or a pa rti cul a r medi ca l condi ti on, wi th broa der brus h s trokes tha n
a nother. One text ma y a ddres s a pa rti cul a r poi nt on s evera l pa ges , the other on one or two, or ma y ha ve no s peci fi c covera ge a t a l l . Thi s i s not
s urpri s i ng, a nd i t pa ra l l el s the wa y you were proba bl y ta ught pha rma col ogy: no one s ta nda rd precl i ni ca l pha rma col ogy curri cul um for a l l medi ca l
s chool s , nor a ny s ta nda rd or cons i s tency i n how the content ma y be pres ented a t one s chool , or by one prof, compa red wi th a nother.

Generic Drug Name Recognition Guide

Ive compi l ed thi s l i s t wi th the hope tha t i t ma y hel p you l ook a t a drugs generi c na me a nd fi gure out the group or cl a s s to whi ch i t bel ongs . I a m
s ure there a re s ome omi s s i ons , but the l i s t i s nonethel es s qui te compl ete. Mos t of the entri es a re a rra nged a l pha beti ca l l y by s uffi xes , but i n a
coupl e of i ns ta nces the l i s ti ng i s for a prefi x (eg, ceph- for cepha l os pori ns ) or s ome s equence of l etters cons i s tentl y found i n the drugs na mes (eg,
quin i n qui ni di ne, qui ni ne, chl oroqui ne). Drug names in bold a re ones I cons i der to be a prototype or mos t i mporta nt exa mpl e(s ).
Where a nd how do generi c drugs get thei r offi ci a l na mes , a t l ea s t i n the Uni ted Sta tes ? They a re a s s i gned by the Uni ted Sta tes Adopted
Na mes Counci l (USANC). Thei r purpos e i s to provi de s i mpl e, i nforma ti ve, a nd uni que nonpropri eta ry na mes for drugs the USAN. They do thi s by
es ta bl i s hi ng l ogi ca l nomencl a ture cl a s s i fi ca ti ons ba s ed on drugs pha rma col ogi c rel a ti ons hi ps wi th others (of the s a me or s i mi l a r type) or
ba s ed on chemi ca l s i mi l a ri ti es (eg, the core chemi ca l s tructure of drugs ). In the Uni ted Sta tes the FDA ha s the fi na l s a y on whether a drug na me i s
a ccepta bl e a nd, therefore, offi ci a l .
A s i de note: a l though ma ny generi c na mes a re i denti ca l worl dwi de, there a re a l s o s ome gl a ri ng i ncons i s tenci es , s ome of whi ch youre a pt to
encounter. For exa mpl e, the Bri ti s h (a nd others ) ca l l a ceta mi nophen pa ra ceta mol , a nd meperi di ne i s pethi di ne.
Where ca n you get more i nforma ti on a bout drug na mes ? Poi nt your brows er to:
http://www.a ma -a s s n.org/a ma /pub/a bout-a ma /our-peopl e/coa l i ti ons cons orti ums /uni ted-s ta tes -a dopted-na mes -counci l .s html

List of Abbreviations
Here a re s ome common a bbrevi a ti ons you a re l i kel y to encounter i n thi s edi ti on of PreTest Pharmacology or el s ewhere when a bbrevi a ti ons rel a ted
to pha rma col ogy a nd thera peuti cs come up. Ive tri ed to s pel l out the ful l word(s ), a nd gi ve the a bbrevi a ti on pa rentheti ca l l y, a t the fi rs t occurrence
i n ea ch ques ti on or a ns wer i n thi s book. Nonethel es s , there a re other common a bbrevi a ti ons tha t dont a ppea r i n thi s book.
Ive omi tted s ymbol s for chemi ca l el ements or thei r ca ti oni c or a ni oni c forms (eg, Ca 2+, Cl ), chemi ca l formul a e (eg, Na Cl ), a bbrevi a ti ons of
common bi ochemi ca l s (ATP, ADP, DNA, etc), Greek l etters , mos t uni ts of mea s ure (vol ume, wei ght, ti me), a nd a bbrevi a ti ons for mos t common l a b
tes ts (but there a re s ome excepti ons ).
I wa nt to note tha t by l i s ti ng a bbrevi a ti ons here Im not condoni ng or encoura gi ng thei r us e when, for exa mpl e, enteri ng i nforma ti on i nto a
pa ti ents cha rt or medi ca ti on order or record. Indeed, us e of ma ny of thes e a bbrevi a ti ons i n pa ti ent-rel a ted documents s houl d be a voi ded, i n
l a rge pa rt to hel p a voi d errors i n i nterpreti ng them or thei r mea ni ngs or i ntent.
[X]ii ntra cel l ul a r concentra ti on, where X i s a n a ni on or a ca ti on
[X]Oextra cel l ul a r (outs i de) concentra ti on, where X i s a n a ni on or a ca ti on
1fi rs t degree (eg, 1 hea rt bl ock)
2s econd degree (eg, 2 hea rt bl ock)
3thi rd degree (eg, 3 hea rt bl ock, a l s o ca l l ed compl ete hea rt bl ock)
5-FU5-fl uoroura ci l
5-HT5-hydroxytrypta mi ne; s erotoni n
6-MP6-merca ptopuri ne (a cti ve meta bol i te of a za thi opri ne)
A
A-IIa ngi otens i n II
AAa ra chi doni c a ci d; a mi no a ci d
AAPMCa nti bi oti c-a s s oci a ted ps eudomembra nous col i ti s
Aba nti body
a .c.before mea l (s ) or, s i mpl y, before ea ti ng
ACa denyl yl cycl a s e
ACEa ngi otens i n-converti ng enzyme (a l s o known a s bra dyki ni na s e, ki ni na s e II)
ACha cetyl chol i ne
AChEa cetyl chol i nes tera s e
AChEIa cetyl chol i nes tera s e i nhi bi tor
ACSa cute corona ry s yndrome
ACTHa drenocorti cotropi c hormone; corti cotropi n
ADD/ADHDa ttenti on-defi ci t (/hypera cti vi ty) di s order
ADHa nti di ureti c hormone (va s opres s i n [VP]); a l dehyde dehydrogena s e
a d l i b(ta ke) freel y a s des i red, a s much a s needed, a s much a s youd l i ke
ADRa dvers e drug rea cti on(s )
AEDa nti epi l epti c (a nti convul s a nt) drug
AF (or AFIB)a tri a l fi bri l l a ti on
AFLa tri a l fl utter
Aga nti gen
AIDSa cqui red i mmunodefi ci ency s yndrome
ALLa cute l ymphocyti c l eukemi a
ALSa myotrophi c l a tera l s cl eros i s (Lou Gehri g di s ea s e)
ALTa l a ni ne a mi notra ns fera s e
AMIa cute myoca rdi a l i nfa rcti on
AMLa cute myel ogenous l eukemi a
ANAa nti nucl ea r a nti bodi es
ANSa utonomi c nervous s ys tem
APa cti on potenti a l
APAPN-a cetyl para-a mi nophenol (a ceta mi nophen)
APDa cti on potenti a l dura ti on
APTTa cti va ted pa rti a l thrombopl a s ti n ti me (eg, a mea s urement of a nti coa gul a ti on, eg, a s ca us ed by unfra cti ona ted hepa ri n)
ARBa ngi otens i n receptor bl ocker
ARCAIDS-rel a ted compl ex
ASAa cetyl s a l i cyl i c a ci d (a s pi ri n); Anes thes i ol ogy Soci ety of Ameri ca
ASTa s pa rta te a mi notra ns fera s e
AUCa rea under the (bl ood) concentra ti on vers us ti me curve (of a drug)
AV(N)a tri oventri cul a r (node)
A-Va rteri ovenous (a s i n A-V s hunt; or di fferences i n concentra ti ons of a s ubs ta nce i n a rteri a l vs . venous bl ood, a s us ed to ca l cul a te cl ea ra nce of
a drug)
AZTa zi dothymi di ne (zi dovudi ne)
B

BALBri ti s h a nti -Lewi s i te (di merca prol ; chel a tor, a nti dote for a rs eni c poi s oni ng)
BBBbundl e bra nch bl ock
bi dtwi ce da i l y; s pel l i ng out twi ce da i l y i s preferred
BMIbody ma s s i ndex (body wei ght/body s urfa ce a rea i n m 2 )
BMRba s a l meta bol i c ra te
BPbl ood pres s ure (ca rdi a c output tota l peri phera l res i s ta nce)
BPHbeni gn pros ta ti c hypertrophy
BPMbea ts per mi nute
BUNbl ood urea ni trogen
BZDbenzodi a zepi ne
C
Cava vera ge (mea n) pl a s ma concentra ti on of a drug
Cmaxma xi mum pl a s ma concentra ti on
Cminmi ni mum pl a s ma concentra ti on
Css s tea dy-s ta te pl a s ma concentra ti on
CABGcorona ry a rtery bypa s s gra ft(i ng)
CADcorona ry a rtery di s ea s e; corona ry hea rt di s ea s e (CHD)
CAIca rboni c a nhydra s e i nhi bi tor
CBCcompl ete bl ood count
CCBca l ci um cha nnel bl ocker
CDC(US) Center for Di s ea s e Control a nd Preventi on
CFcys ti c fi bros i s
CGLchroni c gra nul ocyti c l eukemi a
CHDcorona ry hea rt di s ea s e; corona ry a rtery di s ea s e (CAD)
CHFconges ti ve hea rt fa i l ure
CHIcl os ed hea d i njury
CIca rdi a c i ndex (ca rdi a c output norma l i zed to body s urfa ce a rea )
CKcrea ti ne ki na s e
Cl cl ea ra nce (of drug)
CMLchroni c myel ogenous l eukemi a
CMVcytomega l ovi rus
CNScentra l nervous s ys tem
COca rdi a c output (hea rt ra te s troke vol ume)
COLDchroni c obs tructi ve l ung di s ea s e
COMTca techol -O-methyl tra ns fera s e (ca techol a mi ne-degra di ng enzyme)
COPDchroni c obs tructi ve pul mona ry di s ea s e (eg, emphys ema , chroni c bronchi ti s )
COXcycl ooxygena s e(s ); COX-1 a nd/or COX-2
CPZchl orproma zi ne; a l s o us ed a s a bbrevi a ti on of a bra nd na me product of prochl orpera zi ne; a voi d us e of thi s a bbrevi a ti on to a voi d i mproper
s ubs ti tuti on of one drug for a nother
CREca rba penem-res i s ta nt enteroba cteri a cea e
CRFcorti cotropi n-rel ea s i ng fa ctor
CRPc-rea cti ve protei n
CSFcerebros pi na l fl ui d
Css s tea dy-s ta te drug concentra ti on
CTZchemoreceptor tri gger zone (vomi ti ng center) i n the bra i ns tem
CVAcerebrova s cul a r a cci dent (s troke)
CVPcentra l venous pres s ure
CYPcytochrome P450 (s ys tem or member of i t)
D
D 1 (D 2 )dopa mi ne D 1 (or D 2 ) receptor
DAdopa mi ne
DBHdopa mi ne -hydroxyl a s e (enzyme i nvol ved i n ca techol a mi ne s ynthes i s )
DBPdi a s tol i c bl ood pres s ure
DCdi s conti nue (a l s o D/C)
DDIdrugdrug i ntera cti on
DFXdeferoxa mi ne (chel a tor us ed ma i nl y for i ron poi s oni ng)
DHTdi hydrotes tos terone
DIG (or di g)di goxi n
Di s pdi s pens e
DKAdi a beti c ketoa ci dos i s
DMdi a betes mel l i tus
DMARDdi s ea s e-modi fyi ng a nti rheuma ti c drug (eg, methotrexa te, ma ny others , i ncl udi ng corti cos teroi ds ); s ometi mes referred to a s SAARD (s l owa cti ng a nti rheuma ti c drug)

DOPAdi hydroxyphenyl a l a ni ne
DPHdi phenyl hyda ntoi n (phenytoi n)
DPIdry powder i nha l er a dmi ni s tra ti on s ys tem for ora l i nha l a ti on of certa i n (ma i nl y pul mona ry) drugs ; a l s o s ee MDI, SPI
dP/dtra te of pres s ure cha nge (eg, l eft ventri cul a r pres s ure vers us ti me; P/t)
DPP-4di pepti dyl pepti da s e-4, the ta rget of ora l a nti di a beti c drugs known a s the gl i pti ns (eg, s a xa gl i pti n, s i ta gl i pti n)
DUduodena l ul cer
DVTdeep venous thrombos i s
Dxdi a gnos i s
E
ECGel ectroca rdi ogra m; EKG
EDeffecti ve dos e; emergency depa rtment
ED 50 medi a n effecti ve dos e
EDRFendothel i um-deri ved rel a xi ng fa ctor (ni tri c oxi de)
EEGel ectroencepha l ogra m
EKGel ectroca rdi ogra m; ECG
EPIepi nephri ne
ERPeffecti ve refra ctory peri od (eg, of a nerve); s ee a l s o RP, RRP
EtOHetha nol (a l s o ETOH)
F
FABa nti body fra gment
FDA(US) Food a nd Drug Admi ni s tra ti on
FdUMP5-fl uoro-2-dexoyuri di ne-5-monophos pha te, a cti ve a nti ca ncer (a nti )meta bol i te of fl uoroura ci l
FEVforced expi ra tory vol ume; FEV1, forced expi ra tory vol ume i n 1 s econd
FFAfree fa tty a ci ds
FH 2 7,8-di hydrofol i c a ci d
FH 4 5,6,7,8-tetra hydrofol i c a ci d
FSHfol l i cl e-s ti mul a ti ng hormone
Fxfuncti on
G
G6PDgl ucos e 6-phos pha te dehydrogena s e
GABA-a mi nobutyri c a ci d
GADgenera l i zed a nxi ety di s order
G-CSFgra nul ocyte col ony-s ti mul a ti ng fa ctor
GERDga s troes opha gea l refl ux di s ea s e
GFRgl omerul a r fi l tra ti on ra te
GHgrowth hormone
GIga s troi ntes ti na l
GLPgl uca gon-l i ke pepti de (eg, GLP-1), a n i ncreti n-l i ke a gent
GCSFgra nul ocyte col ony-s ti mul a ti ng fa ctor
GM-CSFgra nul ocyte ma cropha ge col ony-s ti mul a ti ng fa ctor
G protei ngua ni ne nucl eoti de-bi ndi ng protei n
Gp IIb/IIIa pl a tel et membra ne gl ycoprotei n receptor res pons i bl e for l i nki ng (vi a fi bri nogen) a cti va ted pl a tel ets
GSH, GSSGgl uta thi one (reduced, oxi di zed)
GTTgl ucos e tol era nce tes t (i nvol vi ng ei ther ora l [OGTT] or pa rentera l gl ucos e a dmi ni s tra ti on); drop(s ) (a s i n dos e or ra te of drug i nfus i on)
gXmembra ne conducta nce of a n i on, where X i s pota s s i um, ca l ci um, etc (eg, gK)
GUgeni touri na ry
H
H 1 hi s ta mi ne H 1 receptor
H 2 hi s ta mi ne H 2 receptor
H2RAhi s ta mi ne H 2 receptor a nta goni s t
HAARThi ghl y a cti ve a nti retrovi ra l thera py
Hbhemogl obi n (a l s o HGB)
Hb A1cgl ycos yl a ted (or gl yca ted) hemogl obi n us ed to moni tor gl ycemi c control l ong-term
hCGhuma n chori oni c gona dotropi n
Hcthema tocri t
HCTZhydrochl orothi a zi de
HDLhi gh-dens i ty l i poprotei n(s ) (chol es terol )
HEENThea d, eyes , ea rs , nos e, a nd throa t (eg, a s pa rts of a phys i ca l exa m)
HFhea rt fa i l ure (or CHF, hea rt fa i l ure wi th s i gns a nd s ymptoms of venous conges ti on)
HGBhemogl obi n (a l s o Hb)
HHNKShyperos mol a r hypergl ycemi c nonketoti c s yndrome; a l s o a bbrevi a ted HHNS
HIThepa ri n-i nduced thrombocytopeni a

HIVhuma n i mmunodefi ci ency vi rus

H +,K+,ATPa s eproton (hydrogen)pota s s i um ATPa s e (eg, the ga s tri c pa ri eta l cel l proton pump)
HLBIHea rt, Lung a nd Bl ood Ins ti tute (of the Na ti ona l Ins ti tutes of Hea l th)
HMGCoA--hydroxy--methyl gl uta ryl -coenzyme A
HPAhypotha l a mi cpi tui ta ry a xi s
h.s .a t bedti me
HSVherpes s i mpl ex vi rus
HTNhypertens i on
Hxhi s tory
I
IBDi nfl a mma tory bowel di s ea s e
ICPi ntra cra ni a l pres s ure
IDDMi ns ul i n-dependent di a betes mel l i tus ; us ua l l y mea ns Type 1 di a betes mel l i tus , however ma ny pa ti ents wi th Type 2 di a betes need (a re
dependent on) i ns ul i n, s o IDDM i s not a s ui ta bl e term nor one tha t a utoma ti ca l l y i mpl i es Type 1
IgE, G (etc)i mmunogl obul i n E, G, etc
IGFi ns ul i n-l i ke growth fa ctor
IHSSi di opa thi c hypertrophi c s uba orti c s tenos i s
IL (-1, -2, etc)i nterl euki n(s )
IMi ntra mus cul a r(l y)
INHi s oni a zi d
INRi nterna ti ona l norma l i zed ra ti o (for norma l i zi ng res ul ts of prothrombi n ti me tes ts duri ng wa rfa ri n thera py)
I&Oi nta ke a nd output (eg, of foods , fl ui ds )
INRi nterna ti ona l norma l i zed ra ti o, deri ved from a nd us ed to s ta nda rdi ze res ul ts of prothrombi n ti me mea s urements (eg, when moni tori ng
wa rfa ri n thera py)
IOM(The) Ins ti tute of Medi ci ne, a pa rt of the Na ti ona l Aca demy of Sci ences , s tudi es a nd a dvi s es on ma ny a s pects of medi ci ne a nd medi ca l ca re;
publ i s hed a l a ndma rk s tudy To Err Is Huma n, whi ch s howed us the ma gni tude, s cope, a nd cons equences of medi ca l errors ma ny of whi ch
i nvol ve drugs .
IOPi ntra ocul a r pres s ure
IP3 i nos i tol tri s phos pha te
ISAi ntri ns i c s ympa thomi meti c a cti vi ty; s ubcl a s s of -a drenergi c bl ockers tha t a l s o ha ve wea k a goni s t a cti vi ty, eg, pi ndol ol
ISMPIns ti tute for Sa fe Medi ca l Pra cti ce (hea l th ca re/s a fety a nd moni tori ng orga ni za ti on)
ITi ntra theca l (a dmi ni s tra ti on route)
ITPi di opa thi c thrombocytopeni c purpura
IVi ntra venous (l y)
IVPIV pus h (ra pi d, bol us i njecti on of a drug); i ntra venous pyel ogra m
J
JCAHOJoi nt Commi s s i on on Accredi ta ti on of Hea l thca re Orga ni za ti ons (now known s i mpl y a s the Joi nt Commi s s i on)
JNCJoi nt Na ti ona l Commi ttee (of the Na ti ona l Ins ti tutes of Hea l th), a s i n JNC-7more properl y known a s the Joi nt Na ti ona l Commi ttee on
Preventi on, Detecti on, Eva l ua ti on, a nd Trea tment of Hi gh Bl ood Pres s ure
K
keel i mi na ti on ra te cons ta nt
L
LAl eft a tri um; l oca l a nes theti c
L-DOPAl evodopa
LDl etha l dos e
LD 50 medi a n l etha l dos e
LDLl ow-dens i ty l i poprotei n(s )
LEl upus erythema tos i s (s ee a l s o SLE)
LHl utei ni zi ng hormone
LHRHl utei ni zi ng hormone-rel ea s i ng hormone (hypotha l a mi c)
LMWHl ow mol ecul a r wei ght hepa ri n (enoxa pa ri n)
L&Rnorepi nephri ne + phentol a mi ne (occa s i ona l l y us ed a s IV a l terna ti ve to dobuta mi ne for s hort-term ca rdi a c i notropi c s upport, ena bl es
norepi nephri ne to s ti mul a te hea rt wi thout ca us i ng va s ocons tri cti on)
LRl a cta ted Ri nger s ol uti on
LSDl ys ergi c a ci d di ethyl a mi de
LTl eukotri ene
LVl eft ventri cl e/ventri cul a r
LVEDPl eft ventri cul a r end-di a s tol i c pres s ure
LVHl eft ventri cul a r hypertrophy
M
MACmi ni mum a l veol a r concentra ti on (eg, of i nha l a ti on a nes theti c/a na l ges i c) expres s ed percent of a gent i n tota l ga s mi xture needed to a bol i s h
res pons e to certa i n pa i nful s ti mul i i n 50% of pa ti ents

MAPmea n a rteri a l pres s ure

MARmedi ca ti on a dmi ni s tra ti on record
MBCmi ni mum ba cteri ci da l concentra ti on
MAOmonoa mi ne oxi da s e
MAO-A, -Bmonoa mi ne oxi da s e type A, type B
MAOImonoa mi ne oxi da s e i nhi bi tor
mcgmi crogra m; noted here beca us e i t i s preferred a bbrevi a ti on, i ns tea d of g (whi ch mi ght be mi s i nterpreted a s mg), when wri ti ng
pres cri pti ons , ma ki ng notes i n the medi ca ti on a dmi ni s tra ti on or pa ti ent cha rt, etc
MDImetered-dos e i nha l er (del i very s ys tem for s ome drugs , us ua l l y pul mona ry)
MECmi ni mum effecti ve concentra ti on
MHma l i gna nt hyperthermi a
MHCma jor hi s tocompa ti bi l i ty compl ex
MImyoca rdi a l i nfa rcti on
MICmi ni mum i nhi bi tory concentra ti on (us ua l l y a ppl i ed to a nti mi crobi a l s )
mmol mi l l i mol e
MMRmea s l es , mumps , rubel l a
MOPPchemothera py combi na ti on us ed to trea t Hodgki n di s ea s e, deri ved from generi c or tra de na mes of four drugs : mechl oretha mi ne, Oncovi n
(vi ncri s ti ne), predni s one, a nd proca rba zi ne
mOs mol mi l l i os mol e
MP[6-]merca ptopuri ne
MRSAmethi ci l l i n-res i s ta nt S. aureus
MSmorphi ne s ul fa te; mul ti pl e s cl eros i s
MTXmethotrexa te
N
Na -K ATPa s ethe s odi um pump (eg, on nerve, mus cl e cel l s , a nd s ome other exci ta bl e cel l s )
NADHni coti na mi de a deni ne di nucl eoti de
NADPHni coti na mi de a deni ne di nucl eoti de phos pha te
Na +,K+,ATPa s es odi umpota s s i uma denos i ne tri phos pha ta s e (s odi um pump)
NAPAN-a cetyl proca i na mi de, meta bol i te of proca i na mi de; type of ca bba ge tha t i s a ma i n i ngredi ent i n ki m chee
NCINa ti ona l Ca ncer Ins ti tute
NEnorepi nephri ne
NETnorepi nephri ne tra ns porter
NIDDMnoni ns ul i n-dependent di a betes mel l i tus ; more properl y ca l l ed Type 2 di a betes mel l i tus , a l though s ome pa ti ents wi th Type 2 di a betes
ma y requi re (depend on) s uppl ementa l i ns ul i n (s ee IDDM a bove)
NMni coti ni c-s kel eta l mus cl e receptors (i e, thos e found pos ts yna pti ca l l y a t the s kel eta l -s oma ti c neuromus cul a r juncti on)
NNni coti ni c-neura l receptors (thos e found pos ts yna pti ca l l y i n a utonomi c ga ngl i a a nd on cel l s of the a drena l [s upra rena l ] medul l a )
NMDA N- methyl -D -a s pa rta te (gl uta ma te cha nnel receptor, a goni s t, a nta goni s t, etc)
NMSneurol epti c ma l i gna nt s yndrome
NNRTInonnucl eos i de revers e tra ns cri pta s e i nhi bi tor
NOni tri c oxi de
NOSni tri c oxi da s e s yntha s e
NPHneutra l prota mi ne Ha gedorn (type of i ntermedi a te-a cti ng i ns ul i n); i s opha ne i ns ul i n s us pens i on
NPOnothi ng by mouth (ni l per os )
NRTInucl eoti de revers e tra ns cri pta s e i nhi bi tor
NSnorma l s a l i ne (i e, 0.9% Na Cl i n s teri l e wa ter)
NSAIDnons teroi da l a nti -i nfl a mma tory drug. See a l s o t-NSAID
NSTMInon-ST (el eva ti on) myoca rdi a l i nfa rcti on
NTGni trogl yceri n
O
O2 SAToxygen s a tura ti on (eg, of bl ood s a mpl e)
OAos teoa rthri ti s
OCora l contra cepti ve
OCDobs es s i vecompul s i ve di s order
ODoverdos e; ri ght eye
OSl eft eye
OTCover-the-counter (nonpres cri pti on), eg, OTC drug
P
P450cytochrome P450 mi xed-functi on oxi da s e s ys tem
PApul mona ry a rtery; phys i ci a n-a s s i s ta nt
PAO2 a rteri a l pa rti a l pres s ure of oxygen
PABAp-a mi nobenzoi c a ci d (i ngredi ent i n s ome s uns creens , common pres erva ti ve i n s ome mul ti us e pa rentera l medi ca ti on conta i ners )
PACprema ture a tri a l contra cti on
PADperi phera l a rteri a l di s ea s e

PAFpl a tel et-a ggrega ti ng fa ctor(s )

PAM (2-PAM)pra l i doxi me (chol i nes tera s e rea cti va tor)
PASpara-a mi nos a l i cyl i c a ci d
PATpa roxys ma l a tri a l ta chyca rdi a (s ee a l s o PSVT)
PBPpeni ci l l i n-bi ndi ng protei n(s )
p.c.a fter mea l (s )
PCApercuta neous a ngi opl a s ty; a l s o us ed to denote pa ti ent-control l ed a na l ges i a , i n whi ch pa ti ents requi ri ng pa i n control , us ua l l y wi th morphi ne
or a nother opi oi d, s el f-a dmi ni s ter thei r medi ca ti on
PCO2 pa rti a l pres s ure of CO2
PCNpeni ci l l i n
PCOSpol ycys ti c ova ri a n s yndrome
PCPPneumocystis pneumoni a ; phencycl i di ne (a ngel dus t)
PCWPpul mona ry ca pi l l a ry wedge pres s ure (eg, a s mea s ured wi th Swa n-Ga nz ca theter)
PDGFpl a tel et-deri ved growth fa ctor
PFTpul mona ry functi on tes t(s )
PGpros ta gl a ndi n
PGE1 pros ta gl a ndi n E1 (a l pros ta di l )
PGE2 pros ta gl a ndi n E2 (di nopros tone)
PGI 2 pros ta gl a ndi n I 2 (pros ta cycl i n)
P-gpP-gl ycoprotei n(s ); permea bi l i ty gl ycoprotei n(s )
PIprotea s e i nhi bi tor
PICCperi phera l l y i ns erted centra l (venous ) ca theter (eg, us ed for drug del i very, often referred to a s a PICC l i ne)
PIDpel vi c i nfl a mma tory di s ea s e
PKCprotei n ki na s e c
PKUphenyl kenonuri a
PLCphos phol i pa s e C
PMSpremens trua l s yndrome
PNSpa ra s ympa theti c nervous s ys tem (not to be confus ed wi th peri phera l nervous s ys tem, for whi ch the a bbrevi a ti on i s s ometi mes us ed)
PO(a dmi ni s tra ti on route) by mouth (per os )
PO2 pa rti a l pres s ure (tens i on) of oxygen
PPARperoxi s ome prol i fera tor-a cti va ted receptor(s ), eg, PPAR-, the cel l ul a r ta rget (i n nucl ei ) of i ns ul i n-s ens i ti zi ng effects of thi a zol i di nedi ones
(gl i ta zones , i e, pi ogl i ta zone)
PPIproton-pump i nhi bi tor (ga s tri c a ci d-a nti s ecretory drug, es omepra zol e, etc)
PR(a dmi ni s ter) vi a the rectum (per rectum)
PRNa s needed (pro re na ta )
PRPpres s ure-ra te product (i e, pea k LV s ys tol i c pres s ure mul ti pl i ed by hea rt ra te); pl a tel et-ri ch pl a s ma
PSVTpa roxys ma l s upra ventri cul a r ta chyca rdi a
PTprothrombi n ti me
PUDpepti c ul cer di s ea s e
Ptpa ti ent
PTprothrombi n ti me (a l s o s ee INR); phys i ca l thera py
PTHpa ra thyroi d hormone
PTSDpos ttra uma ti c s tres s di s order
PUDpepti c ul cer di s ea s e
PVB or PVCprema ture ventri cul a r bea t, prema ture ventri cul a r contra cti on
Q
q4hevery 4 hours (or other number i ns erted)
qdea ch da y; bes t to s pel l out da i l y tha n us e a bbrevi a ti on
qi d4 ti mes da i l y, s pel l i ng out 4 ti mes a da y i s preferred
QTccorrected QT i nterva l (on el ectroca rdi ogra m)
R
RArheuma toi d a rthri ti s ; ri ght a tri um
RBCred bl ood cel l ; erythrocytes
RBFrena l bl ood fl ow
RDArecommended da i l y a l l owa nce (eg, of a nutri ent)
rDNArecombi na nt DNA, for exa mpl e, mol ecul a r bi ol ogi c technol ogy us ed to s ynthes i ze or modi fy protei n drugs s uch a s ma ny i ns ul i ns
RPrefra ctory peri od, for exa mpl e, of a nerve (a l s o s ee ERP, RRP)
RRres pi ra tory ra te
RRPrel a ti ve refra ctory peri od
Rxpres cri pti on; a bbrevi a ti on for La ti n word mea ni ng ta ke or ta ke thou
S
SAARDs l ow-a cti ng a nti rheuma ti c drug; a l s o s ee DMARD
SA(N)s i noa tri a l (node)

SBPs ys tol i c bl ood pres s ure

SCs ee s ubQ
SERMs el ecti ve es trogen receptor modi fi er
SERTs erotoni n tra ns porter
SHs ul fhydryl
SIADHs yndrome of i na ppropri a te ADH (a rgi ni ne va s opres s i n) s ecreti on, ma ni fes t a s hypervol emi a , hypona tremi a , a nd reduced bl ood os mol a l i ty
s i gwri te on pres cri pti on l a bel
SKs treptoki na s e
SLs ubl i ngua l (a dmi ni s tra ti on route)
SLEs ys temi c l upus erythema tos i s
SMBGs el f-moni tori ng (by the pa ti ent) of bl ood gl ucos e
SPIs ol i d powder i nha l er (eg, for certa i n res pi ra tory drugs )
SRs a rcopl a s mi c reti cul um (i n myocytes )
SRS-As l ow-rea cti ng s ubs ta nce of a na phyl a xi s
SSRIs el ecti ve s erotoni n reupta ke i nhi bi tor
STATi mmedi a tel y
STDs exua l l y tra ns mi tted di s ea s e
STEST el eva ti on (a s i n STE myoca rdi a l i nfa rcti on)
SubQs ubcuta neous (eg, i njecti on type), preferred to the a bbrevi a ti on SC
SuChs ucci nyl chol i ne
SVRs ys temi c va s cul a r res i s ta nce; tota l peri phera l res i s ta nce
SVTs upra ventri cul a r ta chyca rdi a , or s us ta i ned ventri cul a r ta chyca rdi a
Sxs ymptom(s )
T
T1/2 ha l f-l i fe (eg, bi ol ogi c, el i mi na ti on, pl a s ma ha l f-l i fe) of a drug
T3 tri i odothyroni ne
T4 thyroxi ne, l evothyroxi ne, tetra i odothyroni ne
TBtubercul os i s
TCAtri cycl i c a nti depres s a nt
TDPtors a des de poi ntes (from French, twi s ti ng of the poi nts )
TGtri gl yceri de(s )
TIthera peuti c i ndex (LD 50 /ED 50 )
TIAtra ns i ent i s chemi c a tta ck
ti d3 ti mes da i l y, s pel l i ng out 3 ti mes a da y i s preferred
TKOto keep open (a s a n IV i nfus i on a t a ra te jus t s uffi ci ent to keep venous a cces s open)
TNFtumor necros i s fa ctor
t-NSAIDtra di ti ona l nons teroi da l a nti -i nfl a mma tory drug, s peci fi ca l l y COX-1/COX-2 i nhi bi tors (a s pi ri n, i buprofen, ma ny others ), a s oppos ed to
di s ea s e-modi fyi ng a nti rheuma ti c drugs (DMARDs ) tha t a re not COX i nhi bi tors or corti cos teroi ds . See a l s o COX, DMARD, a nd NSAID
tPAti s s ue pl a s mi nogen a cti va tor
TPRtota l peri phera l res i s ta nce (s ys temi c va s cul a r res i s ta nce)
TRHthyrotropi n-rel ea s i ng hormone
TSHthyroi d s ti mul a ti ng hormone
TTPthromboti c thrombocytopeni c purpura (a nd ITTP: i di opa thi c TTP)
TXA2 thromboxa ne A2
TZDthi a zol i di nedi one (cl a s s of ora l a nti di a beti c drugs , i e, pi ogl i ta zone)
U
USANUni ted Sta tes Adopted Na me (offi ci a l na mi ng s ys tem for generi c drugs )
UFHunfra cti ona ted hepa ri n (s ee a l s o LMWH)
UTIuri na ry tra ct i nfecti on
V
Vdvol ume of di s tri buti on (eg, of a drug)
VIPva s oa cti ve i ntes ti na l pepti de
VLDLvery-l ow-dens i ty l i poprotei n
VPva s opres s i n (a nti di ureti c hormone [ADH])
V/Qventi l a ti on/perfus i on (a s us ed i n pul mona ry functi on tes ts )
VREva ncomyci n-res i s ta nt enterococcus
VT (VTACH)ventri cul a r ta chyca rdi a
W
WBCwhi te bl ood cel l
WPWWol ffPa rki ns onWhi te (ca rdi a c el ectrophys i ol ogi c a noma l y)
X

XDxa nthi ne dehydrogena s e

XOxa nthi ne oxi da s e
Z
ZESZol l i ngerEl l i s on s yndrome

General Principles of Pharmacology

Dos a ge regi mens a nd thei r cons equences
Dos e-res pons e rel a ti ons hi ps
Drug-receptor i ntera cti ons , s i gna l tra ns ducti on
El i mi na ti on of drugs
Fa ctors a ffecti ng drug dos a ge
Pha rma codyna mi cs (mecha ni s ms of drug a cti on)
Pha rma coki neti cs (ti me-, dos e-, a nd concentra ti on-rel a ted phenomena )
Regul a ti on of drug a pprova l a nd us e

Questions
1. You wa nt to es ti ma te, fol l owi ng drug a dmi ni s tra ti on, s ome mea s ure tha t rel i a bl y refl ects the tota l a mount of drug rea chi ng ta rget ti s s ue(s ) over
ti me. The drug i s bei ng gi ven ora l l y. Wha t woul d you a s s es s to get the des i red i nforma ti on?
a . Area under the bl ood concentra ti on-ti me curve (AUC)
b. Pea k (ma xi mum) bl ood concentra ti on
c. Product of the a ppa rent vol ume of di s tri buti on (Vd) a nd the fi rs t-order ra te cons ta nt
d. Ti me-to-pea k bl ood concentra ti on
e. Vd
2. The FDA a s s i gns the l etters A, B, C, D, a nd X to drugs i t a pproves for huma n us e. To wha t does thi s cl a s s i fi ca ti on refer or a ppl y?
a . Amount of dos a ge reducti on needed a s pl a s ma crea ti ni ne cl ea ra nces fa l l
b. Amount of dos a ge reducti on needed i n the pres ence of l i ver dys functi on
c. Feta l ri s k when gi ven to pregna nt women
d. Rel a ti ve ma rgi ns of s a fety (or thera peuti c i ndex)
e. The number of unl a bel ed us es for a drug
3. You ora l l y a dmi ni s ter a wea k a ci d drug (A) wi th a pKa of 3.4. Gut pH i s 1.4 a nd bl ood pH i s 7.4. As s ume the drug cros s es membra nes by s i mpl e
pa s s i ve di ffus i on (eg, no tra ns porters a re i nvol ved). Whi ch obs erva ti on woul d be true?
a . Onl y the i oni zed form of the drug, A, wi l l be a bs orbed from the gut
b. The concentra ti on ra ti o of tota l drug (A + HA) woul d be 10,000:1 (gut:pl a s ma )
c. The drug wi l l be hydrol yzed by rea cti on wi th HCl , a nd s o ca nnot be a bs orbed
d. The drug wi l l not be a bs orbed unl es s we ra i s e ga s tri c pH to equa l pKa, a s mi ght be done wi th a n a nta ci d
e. The drug woul d be a bs orbed, a nd a t equi l i bri um the pl a s ma concentra ti on of the noni oni zed moi ety (HA) woul d be 104 ti mes hi gher tha n the
pl a s ma concentra ti on of A.
4. Experi ments s how tha t 95% of a n ora l 80-mg dos e of vera pa mi l i s a bs orbed i n a 70-kg tes t s ubject. However, beca us e of extens i ve
bi otra ns forma ti on duri ng i ts fi rs t pa s s through the hepa ti c porta l ci rcul a ti on, the bi oa va i l a bi l i ty wa s onl y 0.25 (25%). As s umi ng a l i ver bl ood fl ow
of 1500 mL/mi n, wha t i s the hepa ti c cl ea ra nce of vera pa mi l i n thi s s i tua ti on?
a . 60 mL/mi n
b. 375 mL/mi n
c. 740 mL/mi n
d. 1110 mL/mi n
e. 1425 mL/mi n
5. Such s ubs ta nces a s i nos i tol tri s phos pha te (IP3 ), di a cetyl gl ycerol (DAG), cycl i c AMP (cAMP), cAMP-dependent protei n ki na s es , a nd cha nges i n s uch
functi ons a s membra ne i on conducta nce (eg, of gK+ a nd gCa 2+) a re i mporta nt wi th res pect to the effects of l i ga nds on cel l res pons es . Whi ch bes t
s umma ri zes where they a re found or wha t they do?
a . Are pres ent i n nerve cel l s , but not the va ri ous types of mus cl es or gl a nds
b. Are the receptors for va ri ous a goni s ts a nd a nta goni s t drugs
c. Intera ct wi th neurotra ns mi tters or hormones (endogenous l i ga nds ), but not to chemi ca l s tha t a re not found na tura l l y i n the body
d. Medi a te exci ta tory, but not i nhi bi tory, res pons es i n va ri ous ta rget s tructures
e. Tra ns duce a chemi ca l s i gna l from a l i ga nd i nto the fi na l cel l res pons e(s )
6. Azi thromyci n, a n a nti bi oti c, ha s a n a ppa rent vol ume of di s tri buti on (Vd) of a pproxi ma tel y 30 L/kg. Wha t i s the ma i n i nterpreta ti on of thi s
i nforma ti on?
a . Effecti ve onl y when gi ven i ntra venous l y
b. El i mi na ted ma i nl y by rena l excreti on, wi thout pri or meta bol i s m
c. Extens i vel y di s tri buted to s i tes outs i de the va s cul a r a nd i nters ti ti a l s pa ces
d. Not extens i vel y bound to pl a s ma protei ns
e. Una bl e to cros s the bl ood-bra i n or pl a centa l ba rri ers

7. A ca rdi ova s cul a r pha rma col ogi s t i s a s s es s i ng the i notropi c (contra cti l e) res pons es of ca rdi a c mus cl e to a va ri ety of drugs . She us es a s ma l l
a ni ma l i s ol a ted pa pi l l a ry mus cl e prepa ra ti on to ga i n her da ta . The experi menta l s etup i s s hown here:

The pa pi l l a ry mus cl e ha s been exci s ed from the a ni ma l s hea rt a nd put i nto a phys i ol ogi c s ol uti on tha t wi l l keep the mus cl e a l i ve a nd ful l y
functi ona l for s evera l hours . The mus cl e i s el ectri ca l l y s ti mul a ted a t a cons ta nt ra te s o tha t there a re no us ua l ra te-dependent effects on
contra cti l e force devel opment, a nd a l l neura l i nfl uences on pa pi l l a ry mus cl e functi on or drug res pons es a re a bs ent.
A reference s ta nda rd pos i ti ve i notropi c drug i s a dmi ni s tered, i n va ryi ng concentra ti ons , to determi ne the ma xi mum i ncrea s e of contra cti l e force
(the i notropi c res pons e; ma xi mum i s s et a t 100% a s ca us ed by the s ta nda rd drug). Therea fter, three other drugs X, Y, a nd Za re tes ted a nd thei r
a bi l i ty to i ncrea s e contra cti l e force devel opment (compa red wi th the s ta nda rd or reference drug) i s mea s ured. The dos e-res pons e curves to X, Y,
a nd Z a re s hown here:

Whi ch s ta tement des cri bes the fi ndi ngs of thi s experi menta l s tudy i nvol vi ng drugs X, Y, a nd Z?
a . Drug X i s the mos t effi ca ci ous beca us e i ts ED 50 i s l owes t
b. Drug Y i s the l ea s t potent drug a mong the three drugs s hown
c. Drug Z i s the mos t potent ca rdi a c i notrope
d. Drug Y i s more potent tha n drug Z, a nd more effi ca ci ous tha n drug X
e. Drug X i s more potent tha n drug Y, a nd more effi ca ci ous tha n drug Z
8. A pa ti ent needs a drug tha t ha s a n a ppa rent vol ume of di s tri buti on of 20 L. The pl a n i s to a dmi ni s ter a l oa di ng dos e to rea ch a ta rget pl a s ma
l evel of 5 mcg/mL. Thi s pl a s ma concentra ti on i s the ta rget s tea dy-s ta te concentra ti on (CSS), a nd i t wi l l be ma i nta i ned by s ubs equent ora l
ma i ntena nce dos es . Wha t IV l oa di ng dos e woul d be needed to yi el d tha t 5 mcg/mL ta rget?
a . 1 mg
b. 5 mg
c. 10 mg
d. 20 mg
e. 100 mg
9. We a re repea tedl y a dmi ni s teri ng a drug ora l l y. Every dos e i s 50 mg; the i nterva l between dos es i s 8 h, whi ch i s i denti ca l to the drugs pl a s ma
(overa l l el i mi na ti on) ha l f-l i fe. The bi oa va i l a bi l i ty i s 0.5. For a s l ong a s the drug i s a dmi ni s tered no i ntera cti ng drugs a re a dded or s topped, a nd
there a re no a ppl i ca bl e fa ctors a ffecti ng s uch thi ngs a s a bs orpti on or el i mi na ti on tha t mi ght cha nge the drugs pha rma coki neti cs .
Whi ch formul a gi ves the bes t es ti ma te of how l ong i t wi l l ta ke for the drug to rea ch s tea dy-s ta te pl a s ma concentra ti ons (CSS)?
Abbreviations:
Cl = cl ea ra nce (mL/mi n)
D = dos e (mg)
F = bi oa va i l a bi l i ty
ke = el i mi na ti on ra te cons ta nt

t1/2 = ha l f-l i fe (h)

Vd = vol ume of di s tri buti on
a . (0.693 Vd)/Cl
b. 1/ke
c. 4.5 t1/2
d. (t1/2 ) (ke)
e. D/(F t1/2 )
10. A cl a s s ma te i s doi ng s ummer res ea rch, i n your s chool s cl i ni ca l pha rma col ogy di vi s i on, between her fi rs t a nd s econd yea rs of medi ca l s chool .
Her topi c i nvol ves new i nves ti ga ti ons i nto the rol es of P-gl ycoprotei n. Whi ch s ta tement a ccura tel y s umma ri zes the bi ol ogi c rol e of P-gl ycoprotei ns ,
pa rti cul a rl y a s i t a ffects drugs a nd thei r a cti ons ?
a . Conjuga tes a va ri ety of drugs , or thei r meta bol i tes , to fa ci l i ta te thei r ul ti ma te rena l el i mi na ti on from the body
b. Ma i nta i ns s tructura l i ntegri ty of cel l membra nes a nd the s urfa ce receptors found on them
c. Phos phoryl a tes certa i n s ubs ta nces , s uch a s i n the convers i on of a denos i ne monophos pha te (AMP) i nto the di phos pha te a nd tri phos pha te forms
(ADP, ATP)
d. Tra ns ports certa i n drugs a nd xenobi oti cs a cros s cel l membra nes
e. Works , i n conjuncti on wi th va ri ous G-protei ns , to tra ns duce (convert) i ntera cti ons between drugs a nd thei r receptors i nto bi ol ogi c res pons es
11. You a re conducti ng pha rma coki neti c s tudi es on a new drug tha t we hope wi l l be a pproved for cl i ni ca l us e. We i ns ert a venous ca theter to
s a mpl e bl ood a t va ri ous ti mes a fter drug a dmi ni s tra ti on, a nd a l s o ta ke a s a mpl e for the i mmedi a te pre-drug bl ood concentra ti ons of the drug
(whi ch s houl d be zero). After a s s a yi ng the bl ood s a mpl es for the drug we ma ke a gra ph tha t pl ots pl a s ma drug concentra ti ons over ti me,
conti nui ng unti l tes ts revea l undetecta bl e bl ood l evel s . Wha t ca n you ca l cul a te or es ti ma te ba s ed on the ra ti o of the a rea under the curve (AUC)
obta i ned by ora l a dmi ni s tra ti on vers us the AUC for i ntra venous a dmi ni s tra ti on of the s a me drug?
a . Abs orpti on
b. Bi oa va i l a bi l i ty
c. Cl ea ra nce
d. El i mi na ti on ra te cons ta nt
e. Extra cti on ra ti o
f. Vol ume of di s tri buti on
12. Identi ca l dos es of a drug a re gi ven ora l l y a nd i ntra venous l y. We s a mpl e bl ood a t va ri ous ti mes , mea s ure bl ood concentra ti ons of the drug, a nd
pl ot the da ta (s hown bel ow).

Further a na l ys i s of onl y thes e da ta wi l l a l l ow you to determi ne whi ch of the fol l owi ng?
a . El i mi na ti on route(s )
b. Extent of pl a s ma protei n bi ndi ng
c. Ora l bi oa va i l a bi l i ty
d. Potency
e. Thera peuti c effecti venes s
13. Duri ng your ca reer you ma y ha ve pa ti ents i n a ge ra nges from very young to very ol d, a nd a djus tments i n drug dos a ges or i nterva l s between
repea ted dos es ma y be requi red ba s ed on a ge. As s ume you cons i der onl y the effects of one drug; no i ntera cti ng drugs or comorbi di ti es a re
i nvol ved. Wha t s ta tement bes t des cri bes the general rel a ti ons hi p between chronol ogi c a ge a nd the overa l l el i mi na ti on pl a s ma ha l f-l i ves of drugs ?
a . Depends on chemi ca l cl a s s of drug (eg, benzodi a zepi ne, ca techol a mi ne, a nd di hydropyri di ne)
b. Depends on rena l functi on (eg, crea ti ni ne cl ea ra nce), not a ge per s e
c. Li nea r: ha l f-l i fe l engthens i n di rect proporti on to a ge
d. No genera l l y a ppl i ca bl e rel a ti ons hi p beca us e el i mi na ti on ha l f-l i fe depends on the drug, not i ts cl a s s
e. Pea ks a t a round a ge 18 to 20 yea rs , wi th ha l f-l i ves bei ng much l onger a t younger or ol der a ges
14. The el i mi na ti on of a drug a nd i ts numerous meta bol i tes i s des cri bed a s bei ng hea vi l y dependent on Pha s e II meta bol i c rea cti ons . Whi ch of
the fol l owi ng i s a Pha s e II rea cti on?

a . Gl ucuroni da ti on
b. Deca rboxyl a ti on
c. Es ter hydrol ys i s
d. Ni tro reducti on
e. Sul foxi de forma ti on
15. The hos pi ta l pha rma cy s ends up a s ol uti on of a drug tha t i s to be i nfus ed i ntra venous l y a t a cons ta nt, s peci fi ed ra te. It ha s been di l uted to the
proper concentra ti on i n a s ui ta bl e IV a dmi ni s tra ti on fl ui d. As s umi ng tha t no pa ti ent- or drug-rel a ted va ri a bl es cha nge duri ng the a dmi ni s tra ti on
peri od, whi ch one of the fol l owi ng wi l l be the ma i n determi na nt of how l ong i t wi l l ta ke for bl ood concentra ti ons of thi s drug to rea ch s tea dy s ta te
(pl a tea u; no cha nge of mea n bl ood l evel s over ti me)?
a . Bi oa va i l a bi l i ty of the drug
b. Concentra ti on of the drug i n the s ol uti on tha t wi l l be i nfus ed
c. Ha l f-l i fe of the drug
d. Pres ence or a bs ence of ca rdi ova s cul a r or rena l di s ea s e
e. Pl a s ma crea ti ni ne concentra ti on (or crea ti ni ne cl ea ra nce)
f. Tota l dos e per 24 hours
g. Vol ume of drug a dmi ni s tered per mi nute
16. Yee et a l . (Effect of gra pefrui t jui ce on bl ood cycl os pori ne concentra ti on. Lancet 1995;345:955956) exa mi ned s evera l pha rma coki neti c va ri a bl es
rel a ted to ora l cycl os pori ne a dmi ni s tra ti on wi th wa ter, gra pefrui t jui ce, a nd ora nge jui ce:

The numbers l i s ted a re a ri thmeti c mea ns one s ta nda rd devi a ti on of the mea n. Cmax i s the pea k bl ood concentra ti on, a nd Tmax i s the ti me a fter
a dmi ni s tra ti on a t whi ch pea k pl a s ma concentra ti ons of the drug a re rea ched. The p va l ues a re ba s ed on a na l ys i s of va ri a nce (ANOVA) corrected for
repea ted mea s ures .
Thes e da ta , a nd wha t you s houl d ha ve l ea rned from your ba s i c pha rma col ogy s tudi es , a re mos t cons i s tent wi th a n hypothes i s tha t gra pefrui t
jui ce does whi ch of the fol l owi ng?
a . Aci di fi es the uri ne, fa vori ng cycl os pori nes tubul a r rea bs orpti on vi a a pH-dependent effect
b. Acti va tes a n i ntes ti na l wa l l tra ns porter for cycl os pori ne
c. Al ters the route(s ) of el i mi na ti on for cycl os pori ne
d. Inhi bi ts meta bol i s m of cycl os pori ne
e. Reduces bi ndi ng of cycl os pori ne to pl a s ma protei ns , thereby ra i s i ng free (a cti ve) drug l evel s i n the ci rcul a ti on
17. A 60-yea r-ol d ma n wi th rheuma toi d a rthri ti s wi l l be s ta rted on a nons teroi da l a nti -i nfl a mma tory drug (NSAID) to s uppres s the joi nt
i nfl a mma ti on. Publ i s hed pha rma coki neti c da ta for thi s drug i ncl ude:
Bi oa va i l a bi l i ty (F): 1.0 (100%)
Pl a s ma ha l f-l i fe (t1/2 ) = 0.5 hour
Appa rent vol ume of di s tri buti on (Vd): 45 L
For thi s drug i t i s i mporta nt to ma i nta i n a n a vera ge s tea dy-s ta te concentra ti on of 2.0 mcg/mL i n order to ens ure a dequa te a nd conti nued a nti i nfl a mma tory a cti vi ty.
The drug wi l l be gi ven (ta ken) every 4 hours .
Wha t dos e wi l l be needed to obta i n thi s 2 mcg/mL a vera ge s tea dy-s ta te drug concentra ti on?
a . 5 mg

b. 100 mg
c. 325 mg
d. 500 mg
e. 625 mg
18. We ta ke a bl ood s a mpl e from a pa ti ent (ba s el i ne mea s urement) a nd then a dmi ni s ter drug A i ntra venous l y. We ta ke a ddi ti ona l bl ood s a mpl es
peri odi ca l l y therea fter a nd mea s ure drug concentra ti on i n ea ch s a mpl e. We repea t the experi ment, thi s ti me gi vi ng the s a me drug ora l l y. Then we
pl ot the l oga ri thm of drug concentra ti on vers us ti me wi th da ta from both a dmi ni s tra ti on routes to fi nd compa ra bl e el i mi na ti on curves i ndi ca ti ve
of fi rs t-order el i mi na ti on. Wha t do the s l opes of the res ul ti ng concentra ti on vers us ti me curves i ndi ca te a bout the pha rma coki neti cs of drug A?
a . Area under the curve (AUC)
b. Bi oa va i l a bi l i ty
c. El i mi na ti on ra te cons ta nt
d. Extra cti on ra ti o
e. Vol ume of di s tri buti on
19. The offi ci a l pa cka ge i ns ert for pres cri pti on drugs i denti fi es (a mong ma ny other thi ngs ) the s peci fi c us e(s ) or i ndi ca ti on(s ) for the drug
a pproved by the FDA. It i s a l s o l i kel y to note one or s evera l more s o-ca l l ed off-l a bel us es : us es tha t ha ve not been s a ncti oned offi ci a l l y by the
FDA, but for whi ch there i s rea s ona bl e evi dence tha t the drug i s both s a fe a nd effecti ve. For whi ch other us es ca n you, a s a l i cens ed phys i ci a n,
a dmi ni s ter or pres cri be thes e FDA-a pproved drugs ?
a . Anythi ng you wi s h, provi ded no s peci fi c l a ws (eg, control l ed-s ubs ta nce l a ws ) prohi bi t i t
b. Noneonl y FDA a pproved a nd wri tten off-l a bel us es
c. Onl y a pproved a nd off-l a bel us es for ol der drugs i n the s a me chemi ca l class (eg, a nother thi a zi de di ureti c, benzodi a zepi ne, etc)
d. Onl y a pproved a nd off-l a bel us es of ol der drugs us ed for the s a me purpose (eg, a nother a nti hypertens i ve, a nti depres s a nt, or ca ncer
chemothera peuti c a gent, etc)
e. Onl y us es for whi ch there i s s ome evi dence of drug effi ca cy a nd s a fety i n the experi menta l l i tera ture
20. When new drugs undergo precl i ni ca l tes ti ng, one of ma ny thi ngs to know i s whether i ts l a rgel y confi ned to the va s cul a r compa rtment or
di s tri buted more wi del y, perha ps to s peci fi c ti s s ues s uch a s the l i pi d-ri ch CNS. Thi s i s , of cours e, ul ti ma tel y cl i ni ca l l y i mporta nt i f the drug
eventua l l y gets FDA a pprova l . One wa y to get a ha ndl e on tha t i s to ca l cul a te the a ppa rent vol ume of di s tri buti on (Vd).
The ta bl e a nd gra ph bel ow s how s ome da ta concerni ng a new a mi no-gl ycos i de a nti bi oti c. We gi ve a n IV dos e (5 mg/kg) of the drug to a 70-kg 21yea r-ol d vol unteer, who i s hea l thy a nd ta ki ng no other drugs . After a l l owi ng ti me for redi s tri buti on a nd equi l i bra ti on of the drug i n va ri ous body
compa rtments , we mea s ure pl a s ma concentra ti ons a t va ri ous ti mes .

Whi ch va l ue comes cl os es t to the a ppa rent Vd for thi s drug? (By a l l mea ns , feel free to us e your fa vori te ca l cul a tor.)
a . 0.62 L
b. 19 L
c. 50 L
d. 110 L
e. 350 L
21. You a re revi ewi ng the da ta from s evera l meta -a na l ys es tha t a ddres s ed the mos t common ca us es of a dvers e or otherwi s e exces s i ve effects of
pres cri pti on drugs i n young a dul ts a nd i n the el derl y (>60 yea rs of a ge). Intera cti ons between mul ti pl e drugs were not cons i dered. Whi ch va ri a bl e
woul d you fi nd to be decreased, a nd be the mos t common genera l ca us e of thes e probl ems , i n the el ders ?
a . Body fa t content
b. Lea n body ma s s

c. Li ver functi on
d. Rena l functi on/cl ea ra nce
e. Pl a s ma a l bumi n l evel s
22. Some texts s ta te tha t the a bi l i ty of one drug (s ometi mes ca l l ed the object drug) to di s pl a ce mol ecul es of a nother drug (the ta rget drug) from
pl a s ma protei n bi ndi ng s i tes , thereby ra i s i ng the concentra ti on a nd a cti vi ty of free ta rget drug i n the bl ood, i s not cl i ni ca l l y rel eva nt. The cl a i med
rea s on? Drug mol ecul es tha t a re di s pl a ced a re ra pi dl y el i mi na ted a nd the equi l i bri um between bound a nd free drug i s ra pi dl y rees ta bl i s hed.
Thi s i nterpreta ti on ma y be correct for s ome drugs , but not for others .
Cons i deri ng onl y the pha rma coki neti cs or other rel eva nt properti es of the target drug, upon whi ch drug-rel a ted va ri a bl e does the s peed of
el i mi na ti on a nd rees ta bl i s hment of the bound vers us free equi l i bri umi ndeed, whether the i ntera cti on i s a pt to be cl i ni ca l l y rel eva ntdepend
the mos t?
a . Bi oa va i l a bi l i ty
b. Overa l l el i mi na ti on t1/2
c. pK (a ci d or ba s e)
d. Rena l cl ea ra nce
e. Whether the drug i s meta bol i zed, or excreted wi thout pri or meta bol i s m
23. Upon eva l ua ti ng the effects of certa i n s ympa thomi meti c drugs i n a va ri ety of i n vi tro a nd i n vi vo model s , you fi nd tha t the res pons es exhi bi t the
phenomenon of tachyphylaxis. Wha t does the term ta chyphyl a xi s mea n?
a . An i ncrea s e i n the ra te of the res pons e, for exa mpl e, a n i ncrea s e of the ra te of mus cl e contra cti on
b. Immedi a te hypers ens i ti vi ty rea cti ons (i e, a na phyl a xi s )
c. Prompt conforma ti ona l cha nges of the receptor s uch tha t a goni s ts , but not a nta goni s ts , a re a bl e to bi nd a nd ca us e a res pons e
d. Qui ck a nd progres s i ve ri s es i n the i ntens i ty of drug res pons e, wi th repea ted a dmi ni s tra ti on, even when the dos es a re uncha nged
e. Ra pi d devel opment of tol era nce to the drugs effects
24. A pos topera ti ve pa ti ent wi l l requi re prol onged a na l ges i a . We choos e a drug tha t ha s the fol l owi ng pha rma coki neti c properti es :
Ha l f-l i fe: 12 hours
Cl ea ra nce: 0.08 L/mi n
Vol ume of di s tri buti on: 60 L
The pa ti ent ha s a n i ndwel l i ng venous ca theter wi th a s l ow dri p of 0.9% Na Cl , a nd we wi l l us e thi s to a dmi ni s ter i ntermi ttent i njecti ons of the
drug every 4 hours . The ta rget bl ood l evel of the drug, fol l owi ng ea ch i njecti on, i s 8 mcg/mL.
Wi th thi s pl a n i n mi nd, a nd us i ng no l oa di ng dos e of the drug, whi ch one of the fol l owi ng comes cl os es t to the dos e tha t s houl d be
a dmi ni s tered every 4 hours ?
a . 0.960 mg (or 1 mg)
b. 6.4 mg (or 6 mg)
c. 25.6 mg (or 25 mg)
d. 150 mg
e. 550 mg
25. A pa ti ent i s experi enci ng s evere pos topera ti ve pa i n, a nd we need to gi ve a l oa di ng dos e of a n a na l ges i c drug for prompt rel i ef of di s comfort.
The drug we choos e ha s the s a me pha rma coki neti c properti es a s the one des cri bed i n Ques ti on 24:
Ha l f-l i fe: 12 hours
Cl ea ra nce: 0.08 L/mi n
Vol ume of di s tri buti on: 60 L
Our ta rget pl a s ma concentra ti on for the drug i s 8 mcg/mL. Wha t number comes cl os es t to the correct l oa di ng dos e?
a . 0.48 mg (rounded to 0.5 mg)
b. 150 mg
c. 320 mg
d. 480 mg
e. 640 mg
26. We a dmi ni s ter a hi ghl y l i pi d-s ol ubl e drug a nd moni tor i ts el i mi na ti on i n vi vo a nd i n vi tro. Al l the da ta i ndi ca te tha t i t i s tra ns formed to a
va ri ety of more pol a r a nd oxi di zed meta bol i tes by a group of heme protei ns tha t a cti va te mol ecul a r oxygen to a form tha t i s ca pa bl e of i ntera cti ng
wi th orga ni c s ubs tra tes s uch a s our tes t drug. Wha t enzyme or enzyme s ys tem i s mos t l i kel y i nvol ved i n the i ni ti a l meta bol i s m of thi s drug?
a . Cycl ooxygena s e
b. Cytochrome P450s (CYP s ys tem, mi xed-functi on oxi da s es )
c. Monoa mi ne oxi da s e (MAO)
d. Ni coti na mi de a deni ne di nucl eoti de phos pha te (NADPH)
e. UDP-gl ucuronos yl tra ns fera s e
27. We mea s ure the hea rt ra te of a hea l thy s ubject under the condi ti ons noted bel ow, a l l owi ng a mpl e ti me for return to ba s el i ne condi ti ons a nd
ful l el i mi na ti on of drugs between ea ch s tep:
1. At res t

2. Duri ng trea dmi l l exerci s e s uffi ci ent to a cti va te the s ympa theti c nervous s ys tem a t a ti me when ma xi mum hea rt ra te i s rea ched
3. After a dmi ni s tra ti on of a cebutol ol , a drug wi th a ffi ni ty for -a drenergi c receptors
4. After gi vi ng a cebutol ol , fol l owed by exerci s e a t the s a me l evel us ed i n condi ti on 2
Acebutol ol gi ven a t res t ca us es a s l i ght but cons i s tent i ncrea s e i n hea rt ra te. Gi ve a bi gger dos e a t res t a nd hea rt ra te ri s es a bi t more.
When the pa ti ent exerci s es a fter recei vi ng a l ow-dos e a cebutol ol , hea rt ra te ri s es s i gni fi ca ntl y l es s tha n i t di d i n the a bs ence of a cebutol ol .
Wi th exerci s e a fter the hi gher dos e of a cebutol ol , the ta chyca rdi a i s bl unted even more.
The fi gure bel ow s umma ri zes the ma i n fi ndi ngs .

Whi ch s ta tement bes t s umma ri zes the a cti ons of a cebutol ol ?

a . Ha s hi gher a ffi ni ty for a drenergi c receptors tha n the endogenous a goni s ts , epi nephri ne, a nd norepi nephri ne
b. Is a pa rti a l a goni s t for -a drenergi c receptors
c. Is a cti va ti ng s pa re receptors on myoca rdi a l cel l s
d. Is a n i rrevers i bl e or noncompeti ti ve -bl ocker
e. Is cha ngi ng conforma ti on of the a drenergi c receptors
28. We a re pl a nni ng to i nfus e a drug i ntra venous l y a t a cons ta nt a mount per uni t ti me (ra te). It ha s a fi rs t-order el i mi na ti on ra te cons ta nt (kel) of
0.35/h. No l oa di ng dos e wi l l be gi ven. Approxi ma tel y how l ong wi l l i t ta ke for bl ood l evel s to rea ch s tea dy s ta te a fter the i nfus i on begi ns ?
a . 0.7 hour
b. 1.2 hours
c. 3.5 hours
d. 9 hours

e. 24 hours
29. A pa ti ent who i s s uppos ed to be ta ki ng a drug once a da y gets confus ed a nd for a coupl e of da ys ta kes exces s i ve da i l y dos es , l ea di ng to
toxi ci ty. The drug ha s a mea n pl a s ma ha l f-l i fe of 40 hours .
Ri ght now the pa ti ents pl a s ma concentra ti on of the drug i s 6 mcg/mL. Al though wha t to do next wi l l depend on a ctua l bl ood tes ts for drug
l evel s , the us ua l pl a n i n thi s ca s e i s to ha ve the pa ti ent s ki p one or s evera l da i l y dos es of the drug unti l bl ood l evel s fi rs t enter the thera peuti c
a nd nontoxi c ra nge, whi ch i n thi s ca s e i s 0.8 mcg/mL. As s ume the drug i s el i mi na ted by fi rs t-order ki neti cs . How ma ny da i l y dos es s houl d be
wi thhel d?
a. 1
b. 2
c. 3
d. 4
e. 5
30. We wa nt to ca l cul a te the a ppa rent vol ume of di s tri buti on (Vd) for a hypotheti ca l drug (drug A) tha t ha s a ha l f-l i fe of 4 hours . Al l (100%) of a n
a bs orbed dos e of thi s drug undergoes Pha s e I oxi da ti on, fol l owed by conjuga ti on (Pha s e II rea cti on) a nd then rena l excreti on.
We ra pi dl y i nject a known dos e, a nd 30 mi nutes l a ter begi n ta ki ng s eri a l bl ood s a mpl es (30 mi n a pa rt) a nd qua nti fyi ng drug concentra ti on i n
ea ch s a mpl e. Wha t one other pi ece of i nforma ti on mus t be mea s ured or otherwi s e determi ned to ca l cul a te Vd i n the ea s i es t wa y?
a . Area under the drug concentra ti on-ti me curve (AUC)
b. Bi oa va i l a bi l i ty (F)
c. Cl ea ra nce (Cl )
d. El i mi na ti on ra te cons ta nt (kel)
e. Ma xi mum bl ood concentra ti on a fter the bol us i njecti on (C0 )
31. A pa ti ent wi th a ba cteri a l i nfecti on requi res i ntra venous a nti bi oti c thera py. The chos en drug ha s a cl ea ra nce (Cl ) of 70 mL/mi n. The a ppa rent
vol ume of di s tri buti on (Vd) i s 50 L. The pl a n i s to a dmi ni s ter the drug i ntra venous l y every 6 hours a nd a chi eve a 4 mg/L s tea dy-s ta te bl ood l evel of
the drug. No l oa di ng dos e s tra tegy i s to be us ed. Wha t ma i ntena nce dos e i s needed to a chi eve thi s ?
a . 14 mg
b. 24 mg
c. 100 mg
d. 300 mg
e. 1200 mg
32. A pha rma col ogi ca l l y i nert but ea s i l y mea s ured s ubs ta nce, X, i s el i mi na ted i n a ma nner tha t fol l ows l i nea r ki neti cs (fi rs t-order pl ot of l og drug
concentra ti on vs ti me duri ng el i mi na ti on i s a s tra i ght l i ne). The pl a s ma ha l f-l i fe i s 30 mi nutes . Bol us IV dos es wel l i n exces s of 100 mg mus t be
gi ven i n order to s a tura te the enzymes res pons i bl e for meta bol i zi ng the drug, whi ch wi l l then l ea d to zero-order el i mi na ti on ki neti cs .
We i nfus e a s ol uti on of X i ntra venous l y. The concentra ti on of the s ol uti on i s 2 mg/mL; the i nfus i on ra te i s 1 mL/mi n a nd i s kept cons ta nt a t tha t.
We conti nue the i nfus i on for 24 hours .
After a l l owi ng a mpl e ti me for the drug to be el i mi na ted compl etel y, we repea t the a dmi ni s tra ti on. Thi s ti me the concentra ti on of the s ol uti on
of X i s 4 mg/mL, a nd we i nfus e i t a t a ra te of 2 mL/mi n.
Whi ch other va ri a bl e wi l l a l s o be cha nged a s a res ul t of the s ta ted cha nges to the i nfus i on protocol ?
a . El i mi na ti on ra te cons ta nt
b. Ha l f-l i fe
c. Pl a s ma concentra ti on when CSS i s rea ched
d. Ti me to rea ch s tea dy-s ta te concentra ti on (CSS)
e. Tota l body cl ea ra nce
f. Vol ume of di s tri buti on
33. A new drug, drug A, undergoes a s eri es of Pha s e I meta bol i c rea cti ons before i ts meta bol i tes ul ti ma tel y a re el i mi na ted. Whi ch s ta tement bes t
des cri bes the cha ra cteri s ti cs of drug A, or the rol e of Pha s e I rea cti ons i n i ts meta bol i s m or a cti ons ?
a . Compl ete meta bol i s m of drug A by Pha s e I rea cti ons wi l l yi el d products tha t a re l es s l i kel y to undergo rena l tubul a r rea bs orpti on
b. Drug A i s a very pol a r s ubs ta nce
c. Drug A wi l l be bi ol ogi ca l l y i na cti ve unti l i t i s meta bol i zed
d. Pha s e I meta bol i s m of drug A i nvol ves conjuga ti on, a s wi th gl ucuroni c a ci d or s ul fa te
e. Pha s e I meta bol i s m of drug A wi l l i ncrea s e i ts i ntra cel l ul a r a cces s a nd a cti ons
34. Dopa mi ne, epi nephri ne (or norepi nephri ne), a nd hi s ta mi ne a re i mporta nt neurotra ns mi tter a goni s ts . When thes e l i ga nds i ntera ct wi th thei r
cel l ul a r receptors , how do they ma i nl y el i ci t thei r res pons es ?
a . Acti va ti ng a denyl yl cycl a s e, l ea di ng to i ncrea s ed i ntra cel l ul a r cAMP l evel s
b. Acti va ti ng phos phol i pa s e C
c. Induci ng or i nhi bi ti ng s ynthes i s of l i ga nd-s peci fi c i ntra cel l ul a r protei ns
d. Openi ng or cl os i ng l i ga nd-ga ted i on cha nnel s
e. Regul a ti ng i ntra cel l ul a r s econd mes s engers through G protei n-coupl ed receptors

35. You ha ve jus t eva l ua ted a nd s ta rted trea tment on a 40-yea r-ol d woma n i n whom you ha ve di a gnos ed malignant hypertens i on, ba s ed on her
hi s tory, her cl i ni ca l pres enta ti on, a nd the bl ood pres s ure cha nges you mea s ured over the rel a ti vel y s hort ti me youve been a t the beds i de. You
now go to the fa mi l y, i n the wa i ti ng room, a nd expl a i n your di a gnos i s . You expl a i n tha t hypertens i on mea ns hi gh bl ood pres s ure. But when they
hea rd the word ma l i gna nt one of the fa mi l y members s a ys Oh, her bl ood pres s ure i s hi gh beca us e s he ha s ca ncer? How s houl d you bes t expl a i n
the term to the fa mi l y?
a . Bl ood pres s ure i s ri s i ng very qui ckl y a nd da ngerous l y
b. Ca ncer i s pres ent, but i t i s not the ca us e of the hi gh bl ood pres s ure
c. Her hi gh bl ood pres s ure i s , i ndeed, ca us ed by a ca ncer (ma l i gna ncyi n thi s ca s e proba bl y a n a drena l corti ca l tumora pheochromocytoma )
d. Her hi gh bl ood pres s ure di d not fa l l i n res pons e to a bl ood pres s ure medi ca ti on tha t i s effecti ve for mos t pa ti ents
e. The hypertens i on i s l i kel y to prove fa ta l (eg, from a ruptured a neurys m i n the bra i n or el s ewhere)
36. The Food a nd Drug Admi ni s tra ti on ha s broa d regul a tory a uthori ty over pres cri pti on drugs , over-the-counter (OTC) drugs , a nd nutri ti ona l
s uppl ements (herba l s a nd other s o-ca l l ed nutri ceuti ca l s ). Thi s a uthori ty i ncl udes a pprova l , ma rketi ng (a dverti s i ng), a nd wi thdra wa l of drugs from
the ma rket. Whi ch s ta tement s umma ri zes a n el ement of FDA rul es or gui del i nes ?
a . Drugs a pproved for s a l e OTC fi rs t recei ved FDA a pprova l for s a l e a nd ma rketi ng by pres cri pti on onl y
b. If a pha rma ceuti ca l ma nufa cturer provi des da ta s uffi ci ent to obta i n FDA a pprova l for s a l e by pres cri pti on, the ma nufa cturer i s then a l l owed to
s el l the drug over-the-counter (OTC)
c. If the FDA a pproves a pres cri pti on drug for s a l e (pres cri bi ng), the phys i ci a n ca n pres cri be the drug onl y for the FDA-a pproved i ndi ca ti on (us e)
d. Nutri ti ona l s uppl ements ca n be ma rketed wi thout provi di ng proof of effi ca cy or s a fety to the FDA
e. Pha s e III tes ti ng of pres cri pti on drugs tha t ha ve been a pproved by the FDA gi ves compl ete i nforma ti on a bout a dvers e res pons es a nd perti nent
drug-drug i ntera cti ons

General Principles of Pharmacology

Answers
1. The answer is a. (Brunton, pp 32, 36-39; Katzung, pp 43-44). We obta i n the AUC ora l l y, by mea s uri ng drug concentra ti ons mea s ured i n s equenti a l
bl ood s a mpl es . However, we mus t compa re thos e da ta to mea s urements of AUC obta i ned wi th gi vi ng the s a me drug i ntra venous l y (where
bi oa va i l a bi l i ty i s , by defi ni ti on, 1.0). The fra cti on of a drug dos e a bs orbed a fter ora l a dmi ni s tra ti on i s a ffected by a va ri ety of fa ctors tha t ca n
s trongl y i nfl uence the pea k bl ood l evel s a nd the ti me-to-pea k bl ood concentra ti on. The Vd a nd the tota l body cl ea ra nce a l s o a re i mporta nt i n
determi ni ng the a mount of drug tha t rea ches a ta rget ti s s ue. Onl y the a rea under the bl ood concentra ti on-ti me curve, however, refl ects a bs orpti on,
di s tri buti on, meta bol i s m, a nd excreti on fa ctors , a nd thei r i ntera cti ons ; i t i s the mos t rel i a bl e method of eva l ua ti ng bi oa va i l a bi l i ty overa l l .
2. The answer is c. (Brunton, p 1846; Katzung, pp 1039-1043.) Thes e a re FDA pregna ncy ca tegori es . The s hort ta bl e pres ented bel ow s umma ri zes wha t
ea ch of the fi ve FDA pregna ncy cl a s s es mea ns . The a ctua l a dvers e feta l effect(s ), a nd the tri mes ter(s ) of pregna ncy a t whi ch thei r ri s ks a re
grea tes t, depend on the drug cl a s s or, i n ma ny i ns ta nces , on the a ctua l drug. The a dvers e effects ma y i ncl ude tera togenes i s , feta l dea th, or s uch
other res pons es a s endocri ne i mba l a nces (eg, neona ta l hypothyroi di s mcreti ni s mi f mother recei ved certa i n a nti thyroi d drugs ). You ca n l ook up
i nforma ti on for s peci fi c drugs , a nd the tri mes ter(s ) duri ng whi ch the feta l ri s k i s grea tes t or a ppl i ca bl e (for exa mpl e, the ma i n ri s ks of
embryopa thy from wa rfa ri n, a wi del y us ed ora l a nti coa gul a nt, a ppl y to the fi rs t 12 or s o weeks of ges ta ti on), a s the need a ri s es (eg, duri ng your obgyn a nd perha ps other cl erks hi ps ).

Notes : Some drugs , a nd/or thei r a cti ve meta bol i te(s ), a re excreted i n ma terna l mi l k a nd ma y a dvers el y a ffect the nurs i ng chi l d. If the mother
requi res one or more of thos e drugs , s he s houl d be i ns tructed not to brea s t-feed or a s ui ta bl e a l terna ti ve drug tha t i s not excreted i n ma terna l
mi l k (i f one i s a va i l a bl e) mi ght be pres cri bed i ns tea d. Provi di ng a l i s t of s uch drugs i s beyond the s cope of thi s revi ew book; ma ny profes s i ona l
texts a nd on-l i ne res ources a re a va i l a bl e for you to get more i nforma ti on. Drugs tha t pos e or ha ve feta l ri s ks (from ma terna l us e) a re not
neces s a ri l y ones tha t s houl d be a voi ded by brea s t-feedi ng women; the convers e a l s o a ppl i es .
3. The answer is e. (Brunton, pp 17-19; Katzung, pp 10-12.) Reca l l the two Henders on-Ha s s el ba ch equa ti ons , whi ch a ppl y to how l oca l pH a ffects the
i oni za ti on of mol ecul es (eg, of a drug) i n a n a queous envi ronment. As s ume tha t membra nes a re permea bl e onl y to noni oni zed (a nd more l i pi ds ol ubl e) forms of a drug. Thus , we a re ma ki ng the a s s umpti on tha t i oni zed drugs tend to s ta y, or concentra te, i n a n envi ronment tha t fa vors tha t
pH-dependent i oni za ti on; convers el y, i n a n envi ronment tha t fa vors forma ti on of noni oni zed drug mol ecul es , a concentra ti on gra di ent wi l l fa vor
pa s s i ve di ffus i on of noni oni zed mol ecul es to a nother l oca l e.

Our drug wa s a n a ci d wi th pKa = 3.4. In the s toma ch (a s s ume pH = 1.4 a s noted) the ra ti o of noni oni zed to i oni zed mol ecul es wi l l be a bout 1:0.01.
The noni oni zed mol ecul es wi l l di ffus e a cros s the membra ne. Once i n the pl a s ma , pH 7.4, the ra ti o of HA:A wi l l become 1:10,000. And the
concentra ti on ra ti o of tota l drug a cros s the membra ne wi l l be 10,000:1, but wi th the l a rger a mount bei ng i n the pl a s ma , not the gut.

You mi ght a l s o wa nt to l ook a t the fi gure, bel ow, to get a bi g pi cture of how cha ngi ng pH cha nges the i oni za ti on of a ci di c a nd ba s i c drugs .

4. The answer is d. (Brunton, pp 28-30; Katzung, p 43.) Bi oa va i l a bi l i ty i s defi ned a s the fra cti on or percenta ge of a drug tha t becomes a va i l a bl e to the
s ys temi c ci rcul a ti on fol l owi ng a dmi ni s tra ti on by a ny route, compa red wi th bi oa va i l a bi l i ty when the drug i s gi ven IV (s i nce IV bi oa va i l a bi l i ty i s
defi ned a s 1.0, or 10%). Thi s ta kes i nto cons i dera ti on tha t not a l l of a n ora l l y a dmi ni s tered drug i s a bs orbed, a nd tha t a drug ca n be removed from
the pl a s ma a nd meta bol i zed by the l i ver duri ng i ts i ni ti a l pa s s a ge through the porta l ci rcul a ti on (i e, a fi rs t-pa s s effect). An ora l bi oa va i l a bi l i ty of
0.25 (25%) i ndi ca tes tha t onl y 20 mg of the 80-mg dos e (i e, 80 mg 0.25 = 20 mg) rea ched the s ys temi c ci rcul a ti on. Orga n cl ea ra nce ca n be
determi ned by knowi ng the bl ood fl ow through the orga n (Q, expres s ed a s a vol ume per uni t ti me, eg, mL/mi n) a nd the extra cti on ra ti o (ER) for the
drug by the orga n, a ccordi ng to the equa ti on:

The extra cti on ra ti o i s a functi on of the a mounts of drug enteri ng the orga n (a rteri a l s i de; CA) a nd l ea vi ng i t on the venous s i de (CV), a nd the
ra ti o i s ca l cul a ted a s :

In thi s probl em, the a mount of vera pa mi l enteri ng the l i ver per uni t ti me wa s 76 mg (80 mg 0.95) a nd the a mount l ea vi ng wa s 20 mg. Therefore,

5. The answer is e. (Brunton, pp 51-52; Katzung, pp 21-30.) The s ubs ta nces a nd functi ons l i s ted a bove provi de s i gna l tra ns ducti on between l i ga nd
i ntera cti ons wi th s peci fi c receptors , a nd res pons es tha t a re cha ra cteri s ti c of the a goni s t a nd the ta rget cel l (s ). Sui ta bl e l i ga nds i ncl ude
neurotra ns mi tters (ACh, ca techol a mi nes , va ri ous a mi no a ci ds [-a mi nobutyri c a ci d, gl yci ne, gl uta ma te, a s pa rta te] opi oi ds , s erotoni n, a nd
hi s ta mi ne to na me a few) a nd hormones (i ns ul i n, gl uca gon, thyroi d hormones , etc)or drugs wi th s ui ta bl e s tructures . They a re not, however, the
a ctua l receptors (b) for a goni s ts or a nta goni s ts . Thes e s ubs ta nces wi l l a l s o pa rti ci pa te i n l i ga nd bi ndi ng-res pons e coupl i ng to s ui ta bl e forei gn
s ubs ta nces drugs (c). Aga i n, dependi ng on the l i ga nd a nd the type of cel l , res pons es ca n be ei ther exci ta tory or i nhi bi tory (d), a nd they occur i n
va ri ous neura l , mus cl e, a nd gl a nd cel l s (a ).
6. The answer is c. (Brunton, pp 28, 30-32; Katzung, p 38.) For a 70-kg i ndi vi dua l , tota l body wa ter i s a bout 40 L (0.6 L/kg); i nters ti ti a l pl us pl a s ma wa ter
occupi es a bout 12 L (0.17 L/kg).
Azi thromyci n, wi th a Vd of 30 L/kg, woul d be di s tri buted i n a n a ppa rent vol ume of a bout 2100 L i n a typi ca l 70-kg pers on.
Us e s i mpl e l ogi c to a ns wer thi s ques ti on, but l ook a t the a ns wer to Ques ti on 20 i f you wi s h. Even i f you dont remember wha t tota l body wa ter i s
(a bout 40 L or 0.6 L/kg), or the a pproxi ma te va l ue for i nters ti ti a l pl us pl a s ma wa ter (a bout 12 L or 0.17 L/kg), do the qui ck ma th. If you ta ke the
s ta ted 30 L/kg a nd compute the tota l (a nd very hypotheti ca l ) a ppa rent vol ume for a 70-kg i ndi vi dua l , you woul d a rri ve a t 2100 L. Tha t number not
onl y refl ects di s tri buti on i nto a hypotheti ca l vol ume fa r i n exces s of va s cul a r a nd i nters ti ti a l vol umes , but i s a l s o fa r beyond wha t coul d be
phys i ca l l y rea l . After a l l , 2100 L of wa ter equa l 2100 kg; you wont fi nd huma n bei ngs wei ghi ng tha t much!
Wi thout more i nforma ti on, you ca nnot ma ke defi ni ti ve concl us i ons a bout the other properti es l i s ted a s a ns wer choi ces .
7. The answer is d. (Brunton, pp 44-45, 73-74; Katzung, pp 30-32.) Our product i s the mos t potent pa i n rel i ever (or wha tever) you ca n buy wi thout a
pres cri pti on, the TV a ds s a y fa r too often for me. Wha t thos e cl a i ms dont s a y i s how effi ca ci ous a pa rti cul a r drug i s , pa rti cul a rl y compa red wi th
a nother (eg, a competi ng product). So, l ets a ddres s s ome funda menta l s .
The mos t ba s i c defi ni ti on of effi ca cy i s s i mpl y the a bi l i ty to ca us e a n effect. More i mporta nt i s the ques ti on how bi g a n effect? As pi ri n, for
exa mpl e, wi l l a l l evi a te hea da che for ma ny pa ti ents , but i t s i mpl y ca nnot, a t s a fe dos es , a l l evi a te s evere pa i n from, for exa mpl e, a n a bdomi na l
i nci s i on. So, i n the s etti ng of s evere pa i n, a s pi ri n i s l es s effi ca ci ous tha n, s a y, morphi ne.
If rel i ef of s i mpl e hea da che i s the goa l , then s uch drugs a s a s pi ri n, a ceta mi nophen, a nd i buprofen, a re equa l l y effi ca ci ous . Wha t di ffers i s how
ma ny mi l l i gra ms of ea ch a re neces s a ry to do tha t. Ibuprofen i s more potent tha n a ceta mi nophen, whi ch i s s l i ghtl y more potent tha n a s pi ri n: 400
mg of i buprofen, 600 mg of a ceta mi nophen, a nd 650 mg of a s pi ri n a re rea s ona bl e numbers .
In the ques ti on provi ded here, drugs X, Y, a nd Z a l l ha ve effi ca cy: they a l l i ncrea s e contra cti l e force devel opment by the i s ol a ted ca rdi a c mus cl e
prepa ra ti on s hown a nd des cri bed i n the ques ti on. However, i t s houl d be obvi ous tha t drugs Y a nd Z a re more effi ca ci ous tha n drug X. The ED 50 of
drug X i s l ower tha n tha t of the other drugs (a ), but tha t does nt mea n tha t i t i s more effi ca ci ous : i ndeed, i ts ma xi ma l effect on the tes t mus cl es
force of contra cti on i s a bout l es s tha n ha l f of tha t for drugs Y a nd Z.
Ans wer b i s i ncorrect: Drug Y i s more potent tha n drug Z: i ts ED 50 i s l ower tha n tha t of drug Z, but Y a nd Z a re equa l l y effi ca ci ous s i nce thei r pea k
effects a re i denti ca l . Thi s a l s o el i mi na tes a ns wer c a s a correct a ns wer: a ga i n, the ED 50 for drug Z i s hi gher tha n tha t of drug Y, a nd s o Z i s l es s
potent. Ans wer e ca nnot be correct: a l though the ED 50 of drug X i s l ower tha n the ED 50 s of Y a nd Z, the ma xi mum i ntens i ty of drug Xs res pons e i s
much l ower tha n thos e of Y a nd Z.
8. The answer is e. (Brunton, pp 28-37, 1894-1898; Katzung, pp 38, 41-49.) Si nce the vol ume of di s tri buti on i s expres s ed i n the vol ume uni t of l i ters , a nd
the ta rget concentra ti on i s per mL, convert one of the vol ume uni ts to be the s a me a s the other. For exa mpl e, the ta rget concentra ti on of 5 mcg/mL
equa l s 5 mg/L. We ca n fi nd the a ns wer by us i ng fol l owi ng s i mpl e equa ti ons :

9. The answer is c. (Brunton, pp 17-20, 27-30, 33-34, 1802-1804; Katzung, pp 41-47.) Thi s ques ti on, wi th i ts ma ny va ri a bl es a nd equa ti ons , wa s wri tten
i ntenti ona l l y to s ee whether you woul d ta ke a needl es s l y compl i ca ted a pproa ch to a concept tha t i s , when reduced to i ts es s enti a l poi nt,
rel a ti vel y s tra i ghtforwa rd. If you gi ve dos es of a drug repea tedl y a t i nterva l s tha t a re equa l to or l es s tha n the drugs overa l l el i mi na ti on ha l f-l i fe,
a nd keep every other perti nent va ri a bl e cons ta nt (dos e, route, el i mi na ti on s ta tus , etc), you s i mpl y mul ti pl y the ha l f-l i fe by 4 or 5 (hence, my us e of
4.5 to ta ke a mi ddl e ground) to a rri ve a t the a pproxi ma te ti me unti l CSS: the ti me a t whi ch drug i n = drug out i s rea ched.
You ca n s ee i n the fi gure bel ow tha t wi th repea ted a dmi ni s tra ti on of a drug a t i nterva l s equa l to the drugs ha l f-l i fe. Note tha t the average
pl a s ma concentra ti on (Cav) does not a ppea r to fl a tten-out, or rea ch a pl a tea u, unti l a t l ea s t four dos es (= 4 ha l f-l i ves ) ha ve been gi ven. After tha t,
a nd a s s umi ng nothi ng el s e cha nges (dos e, dos e i nterva l , route of a dmi ni s tra ti on, el i mi na ti on ki neti cs , s ta rti ng, or s toppi ng other drugs ), a l though
there wi l l s ti l l be fl uctua ti ons i n pea k a nd trough drug l evel s a round the mea n (ri ght a fter ea ch dos e, ri ght before the next), the a vera ge bl ood
concentra ti on wi l l not cha nge.

Note: The equa ti on (0.693 Vd)/Cl (a ns wer a ) i s the equa ti on for ca l cul a ti ng the ha l f-l i fe.
10. The answer is d. (Brunton, pp 97, 148; Katzung, pp 9, 10t.) P-gl ycoprotei n (PGP; the P s ta nds for permea bi l i ty) i s pa rt of a s uper-fa mi l y of
tra ns membra ne tra ns porter protei ns , s ubs tra tes for whi ch i ncl ude ma ny xenobi oti cs (chemi ca l s not found na tura l l y i n the body), i ncl udi ng ma ny
thera peuti c a gents . An i mporta nt member of the P-gl ycoprotei n fa mi l y i s i nvol ved i n a n ATP-dependent (i e, a cti ve tra ns port; thi s i s pa rt of the ABC
ATP-bi ndi ng ca s s ettefa mi l y) mecha ni s m tha t pumps drugs a nd other chemi ca l l y di vers e xenobi oti cs out of certa i n cel l s , a ga i ns t the us ua l
concentra ti on gra di ent. Tha t i s , PGP s erves a n ATP-dri ven effl ux pump. PGP does not form drug conjuga tes (a ) or pa rti ci pa te i n other Pha s e II
rea cti ons ; ma i nta i n membra ne/receptor s tructure a nd functi on (b); phos phoryl a te a ny s ubs tra tes (c); or pl a y a rol e i n s i gna l tra ns ducti on (e).
Here a re s ome of the s i tes where PGP i s a bunda nt a nd i mporta nt, a nd s ome i mporta nt effects a t thos e s i tes :

i n hepa tocytes (where i t tra ns ports s ubs tra tes i nto the bi l e);
i n the i ntes ti na l epi thel i um (i mporta nt for tra ns porti ng a va ri ety of drugs a cros s membra nes duri ng a bs orpti on);
i n the ki dneys (certa i n proxi ma l tubul e cel l s , where s ubs tra tes a re tra ns ported i nto the uri ne for eventua l el i mi na ti on); a nd
i n ca pi l l a ry endothel i a l cel l s of the bl ood-bra i n ba rri er, where certa i n drugs tha t ma y ha ve di ffus ed a cros s the ba rri er, i nto the CNS, a re
tra ns ported ba ck out to the s ys temi c ci rcul a ti on. Thi s reduces expos ure of the bra i n to the drugs .
Wha t a re s ome cl i ni ca l l y rel eva nt phenomena rel a ted to PGP a cti vi ty? For s ta rters , PGP a cti vi ty i s i mporta nt i n the devel opment of mul ti drug
res i s ta nce (MRPmul ti -drug res i s ta nce-a s s oci a ted protei n), pa rti cul a rl y cel l ul a r res i s ta nce to certa i n chemothera peuti c a gents a nd
a nti vi ra l /a nti retrovi ra l drugs . PGP promptl y tra ns ports thos e cel l ul a r toxi ns out of the cel l s the drugs a re mea nt to ki l l .
There i s broa der i mporta nce. Cons i der, for exa mpl e, PGP a cti vi ty i n the i ntes ti na l epi thel i a . Ma ny drugs tha t a re s ubs tra tes for PGP di ffus e from
the i ntes ti na l l umen i nto the epi thel i a l cel l s duri ng a bs orpti on, but PGP pumps a porti on of thos e drug mol ecul es ri ght ba ck i nto the l umen, from

whi ch they ma y not be rea bs orbed to ga i n a cces s to the ci rcul a ti on. Thus , PGP ha s a n i mporta nt rol e i n a bs orpti on a nd bi oa va i l a bi l i ty of ma ny
ora l l y a dmi ni s tered drugs .
Jus t a s there a re s ubs tra tes , i nducers , a nd i nhi bi tors for the cytochrome P450 s ys tem, s o there a re s ubs tra tes , i nducers , a nd i nhi bi tors for PGP. If
PGP a cti vi ty i s i ncrea s ed by a n i nducer, the ora l bi oa va i l a bi l i ty of PGP s ubs tra tes wi l l be reduced (by vi rtue of grea ter tra ns port ba ck i nto the
l umen), pl a s ma l evel s i n res pons e to a dos e (or dos es ) wi l l be reduced (a bs ol ute decrea s es of pl a s ma l evel s a nd of the a rea under the [ti meconcentra ti on] curve), a nd the i ntens i ty of drug res pons es wi l l be reduced. Convers el y, PGP i nhi bi tors ca n i ncrea s e ora l bi oa va i l a bi l i ty, pl a s ma
l evel s (AUC), a nd res pons e i ntens i ty of PGP s ubs tra tes . Thus , there a re both pha rma coki neti c a nd pha rma codyna mi c cons equences of PGP a cti vi ty.
In s ome ca s es the cl i ni ca l s i gni fi ca nce of a n i ntera cti on i nvol vi ng PGP i s wea k or otherwi s e i ncons equenti a l ; however, wi th ma ny other drugs ,
i nducers or i nhi bi tors ma y ca us e cl i ni ca l l y s i gni fi ca nt di fferences i n bi oa va i l a bi l i ty, drug bl ood l evel s , a nd the ma gni tude of drug res pons es .
The s hort ta bl e tha t fol l ows l i s ts s ome of the drugs , menti oned i n thi s book, tha t a re PGP s ubs tra tes , i nducers , or i nhi bi tors .

11. The answer is b. (Brunton, pp 20-24; Katzung, pp 43-44.) Among other thi ngs , knowi ng the AUC of a drug gi ven i ntra venous l y (whi ch, by defi ni ti on, i s
a s s oci a ted wi th a bi oa va i l a bi l i ty of 1.0, or 100%) i s a prerequi s i te for determi ni ng the bi oa va i l a bi l i ty of the s a me drug gi ven by a ny other route;
bi oa va i l a bi l i ty i s ca l cul a ted a s the ra ti o of AUC for a ny non-IV route a nd the AUCIV.
12. The answer is c. (Brunton, pp 20-24; Katzung, pp 39-44.) We a re ma ki ng thes e da ta compa ri s on to determi ne the drugs bi oa va i l a bi l i ty. We defi ne
the bi oa va i l a bi l i ty of a drug gi ven i ntra venous l y a s 1.0 (100%), s i nce wi th IV a dmi ni s tra ti on we a voi d a l l the a ppl i ca bl e ba rri ers to drug a bs orpti on.
But, of cours e, i ts i mporta nt to know how much tota l drug, over a peri od of ti me, gets i nto the bl oods trea m wi th other a dmi ni s tra ti on routes tha t
we mi ght wa nt to us e cl i ni ca l l y. Drugs gi ven by routes other tha n IV mus t be a bs orbed (a nd be expos ed to a l l the ba rri ers tha t l i mi t or s l ow or
otherwi s e a ffect a bs orpti on); a nd beca us e they mi ght not be a bs orbed from thei r a dmi ni s tra ti on s i te, or mi ght be s us cepti bl e to s uch proces s es
a s hepa ti c fi rs t-pa s s meta bol i s m, they us ua l l y ha ve a bi oa va i l a bi l i ty <1.0.
The ca l cul a ti on of bi oa va i l a bi l i ty i s ba s ed on the ra ti o of the a rea under the concentra ti on-ti me curve (AUC) for the a dmi ni s tra ti on route bei ng
cons i dered (ora l , IM, etc) a nd the AUC obta i ned wi th IV a dmi ni s tra ti on.
Mea s urement of bl ood l evel s of a drug a t a s i ngl e ti me poi nt wi l l not gi ve us the i nforma ti on we need to determi ne bi oa va i l a bi l i ty.
Note tha t wi th ora l a bs orpti on there i s a del a y unti l there i s s ome detecta bl e drug i n the bl ood; tha t refl ects both the ti me needed for
a bs orpti on of the drug a nd, i n mos t ca s es , the s ens i ti vi ty of the a s s a y to mea s ure the drug (whi ch ma y be pres ent, but a t undetecta bl e l evel s ).
Wi th IV a dmi ni s tra ti on bl ood l evel s ri s e i ns ta nta neous l y. Wi th ora l a dmi ni s tra ti on you s houl d a l s o note tha t a s bl ood l evel s of the drug ri s e
towa rd the pea k the ra tes of drug entry i nto the bl ood exceed ra tes of el i mi na ti on (whether by meta bol i s m, excreti on, or both, dependi ng on wha t
the drug i s ) beca us e bl ood l evel s a re ri s i ng. Once bl ood concentra ti ons s ta rt to fa l l , the a mount of drug enteri ng the s ys tem becomes l es s tha n the
a mount bei ng el i mi na ted, per uni t ti me. Tha t i s , a mount i n = a mount out.
Fi na l l ya nd a l though you ca nt tel l preci s el y from the gra phthe ha l f-l i ves for the drug, mea s ured under di fferent experi menta l condi ti ons , a re
i denti ca l : i n genera l (a nd i t depends on the drug a nd i ts bl ood l evel ), the drug wi l l be el i mi na ted a t the s a me ra te (ba s ed on us ua l ki neti c
i nfl uences , s uch a s fi rs t-order ki neti cs ) rega rdl es s of a dmi ni s tra ti on route.
None of the other choi ces i n the ques ti on (i e, potency, effecti venes s , or pl a s ma protei n bi ndi ng) ca n be eva l ua ted us i ng thi s type of
compa ri s on.
13. The answer is d. (Brunton, pp 29-38; Katzung, pp 66, 1047, 1049.) How (or even whether) a ge or extremes of a ge a ffect the overa l l el i mi na ti on ha l fl i fe of a drug (a nd thus the ri ght dos e a nd dos i ng i nterva l ) depends on wha t the drug i s . Whi l e rena l functi on, s uch a s tha t refl ected by the
crea ti ni ne cl ea ra nce (b), wi l l cha nge over certa i n a ge ra nges , rena l functi on per s e i s not uni vers a l l y i mporta nt to the el i mi na ti on or el i mi na ti on
ra tes of a l l drugs . Remember tha t ma ny drugs a re compl etel y meta bol i zed to i na cti ve s ubs ta nces , a nd s o cha nges of rena l functi on a re l a rgel y
uni mporta nt i n thei r el i mi na ti on (a nd pl a s ma ha l f-l i ves ). Us ua l l y, too, there a re expected a ge-rel a ted cha nges i n s uch va ri a bl es a s body wa ter or
fa t content. They a l s o a ffect pha rma coki neti cs , but there i s no overa rchi ng rel a ti ons hi p tha t a ppl i es to a l l drugs .
Cons i der s ome exa mpl es .
Theophyl l i nes ha l f-l i fe i s s hortes t between the a ges of 6 months to a bout 9 yea rs , bei ng much l onger a t younger or ol der a ges . Tha t i s beca us e
of di fferences i n the ra te of the drugs meta bol i s m. Thus , the dos e of thi s ol d bronchodi l a tor, norma l i zed to body wei ght, i s much hi gher for tha t
a ge ra nge; i ndeed, i t i s l i kel y to be exces s i ve for a nd toxi c to younger or ol der i ndi vi dua l s . Thi s ra ther odd rel a ti ons hi p certa i nl y does not a ppl y
to a l l (or even ma ny) drugs , a nd s o a ns wer e i s not correct for mos t drugs .
When compa ri ng the ha l f-l i fe of peni ci l l i n G i n a dul ts >60 yea rs ol d to a dul ts i n the 20- to 30-yea r ra nge, the ha l f-l i fe i s twi ce a s l ong i n the ol der
pa ti ents ; i ts nea rl y twi ce a s l ong wi th l i doca i ne, too; 50% l onger wi th di goxi n; a nd vi rtua l l y not di fferent, a ge-wi s e wi th wa rfa ri n.
Other drugs for whi ch there a re s i gni fi ca nt di fferences (here, i n terms of hepa ti c cl ea ra nce): mos t ba rbi tura tes ; i mi pra mi ne; meperi di ne;
propra nol ol ; a nd qui ni di ne. And no s i gni fi ca nt a ge-rel a ted cha nges ? Exa mpl es a re a s pi ri n, etha nol , pra zos i n, a nd a s noted a bove, wa rfa ri n.
The chemi ca l class to whi ch a drug bel ongs (a ) a l s o does not i nva ri a bl y predi ct a ge-rel a ted cha nges . Cons i der the benzodi a zepi nes . There a re
s i gni fi ca nt a ge-rel a ted pha rma coki neti c cha nges wi th di a zepa m (i ts ha l f-l i fe i s more or l es s di recti ona l l y proporti ona l to a ge). In contra s t, there
a re no s i gni fi ca nt a ge-rel a ted di fferences i n the ha l f-l i ves of l ora zepa m or ni tra zepa m.
14. The answer is a. (Brunton, pp 131-138; Katzung, pp 59-60.) Bi otra ns forma ti on rea cti ons i nvol vi ng the oxi da ti on, reducti on, or hydrol ys i s of a drug a re
cl a s s i fi ed a s Pha s e I (or nons yntheti c) rea cti ons ; thes e rea cti ons ma y res ul t i n ei ther the a cti va ti on or i na cti va ti on of a pha rma col ogi c a gent. There
a re ma ny types of thes e rea cti ons ; oxi da ti ons a re the mos t numerous . Pha s e II (occa s i ona l l y ca l l ed s yntheti c) rea cti ons , whi ch a l mos t a l wa ys
res ul t i n the forma ti on of a n i na cti ve product, i nvol ve conjuga ti on of the drug (or i ts deri va ti ve) wi th a n a mi no a ci d, ca rbohydra te, a ceta te, s ul fa te
or gl ucuroni c a ci d a s noted i n the ques ti on. The conjuga ted form(s ) of the drug or i ts deri va ti ves ma y be more ea s i l y excreted tha n the pa rent
compound.
15. The answer is c. (Brunton, pp 32-33, 1804, 1807-1808; Katzung, pp 42, 44-47.) Wi th i ntra venous i nfus i ons of a drug, onl y the drugs ha l fl i fe determi nes
how l ong i t wi l l ta ke for bl ood l evel s to rea ch a s tea dy s ta te (on a vera ge, nei ther ri s i ng nor fa l l i ng therea fter) s o l ong a s the i nfus i on ra te i s not
cha nged. By defi ni ti on, when s tea dy s ta te i s rea ched, the a mount of drug enteri ng the bl ood per uni t ti me i s equa l to the ra te a t whi ch drug i s
bei ng el i mi na ted, whether by excreti on, meta bol i s m, or a combi na ti on of both (dependi ng on the drug).
The a ppa rent vol ume of di s tri buti on ha s no i mpa ct on ti me to CSS. Bi oa va i l a bi l i ty does not, ei ther, beca us e wi th i ntra venous drug
a dmi ni s tra ti on the bi oa va i l a bi l i ty i s 1.0 (100%). Cl ea ra nce, a pa ra meter tha t rel a tes el i mi na ti on ra te of a drug to the drugs concentra ti on [Cl = ra te
of el i mi na ti on (mg/h)/drug concentra ti on (mg/mL)]. Beca us e cl ea ra nce cons i ders a ra te of drug el i mi na ti on, i t a ffects the CSS, but i t i s not a
determi na nt of i t.
The i nfus i on ra te cl ea rl y a ffects the bl ood concentra ti on rea ched a t s tea dy s ta te, but i t does not a ffect the ti me needed to rea ch i t. For exa mpl e,
i f we ha d a drug wi th a ha l f-l i fe of 4 hours , i nfus ed i t a t a ra te of x mg/mi n, a nd then repea ted the experi ment wi th the s a me drug a t a n i nfus i on
ra te of 2x mg/mi n, bl ood concentra ti ons a t s tea dy s ta te woul d cl ea rl y be di fferent. However, i t woul d s ti l l ta ke the s a me a mount of ti me (roughl y
four to fi ve ha l f-l i ves ), to rea ch s tea dy s ta te. (See the a ns wer to Ques ti on 9 for rel a ted i nforma ti on.)
16. The answer is d. (Brunton, pp 139, 1012; Katzung, pp 57-59.) Gra pefrui t jui ce (but not mos t other ci trus jui ces ) a nd jui ce from Sevi l l e ora nges (not
others ; s ee notes a t end of the a ns wer) conta i n compounds (eg, na ri ngi n, fura nocouma ri ns ) tha t ca n i nhi bi t the meta bol i s m of s evera l drugs , one
of whi ch i s cycl os pori ne, vi a i nhi bi tory effects on CYP3A4). The route (pa thwa y) of el i mi na ti on (c) i s not cha nged, however. (Other drugs i nvol ved i n
thi s i ntera cti on i ncl ude vera pa mi l , s ome of the s ta ti n-type chol es terol -l oweri ng medi ca ti ons ; mos t of the s econd-genera ti on a nti hi s ta mi nes ,
i ncl udi ng fexofena di ne; a nd s evera l a nti depres s a nts a nd a nti hypertens i ves .) The res ul t i s i ncrea s ed bi oa va i l a bi l i ty of a n ora l l y a dmi ni s tered
dos e a nd i ncrea s ed a rea under the curve i n a concentra ti on vers us ti me pl ot. The potenti a l outcome i s exces s i ve (a nd, occa s i ona l l y, trul y toxi c)

effects .
The gra pefrui t jui ce effect nei ther a l ters the ma i n route(s ) of drug a bs orpti on or el i mi na ti on, nor a ffects pl a s ma protei n bi ndi ng ca pa ci ty,
beca us e thos e a re properti es rel a ted to the drug, not howor how wel l or qui ckl yi t enters the ci rcul a ti on. Note tha t thes e da ta a re cons i s tent
wi th the hypothes i s tha t gra pefrui t jui ce does not s ta ti s ti ca l l y s i gni fi ca ntl y a ccel era te or s l ow entry of cycl os pori ne i nto the bl ood, s uch a s by
a ffecti ng i ntes ti na l tra ns porters (b).
Cha nges of uri ne pH (a ) or effects tha t i nvol ve drug bi ndi ng to pl a s ma protei ns (e) a re not a ppl i ca bl e, nor ca n s uch cha nges be gl ea ned from the
da ta pres ented i n the ques ti on.
Notes : (1) The frui t-deri ved i ntera cta nts a re found i n the fl es hy ma teri a l under the s ki n a nd between frui t s egments . (2) Sevi l l e ora nges (a l s o
known a s bl ood ora nge) a re ra rel y us ed a s jui ce ora nges beca us e of thei r very bi tter ta s te (a nd s o they a re a l s o ca l l ed bi tter ora nges ). However,
Sevi l l e/bl ood ora nge jui ce i s now a ppea ri ng more a nd more i n hea l th food s tores a nd other reta i l grocery s tores tha t s el l orga ni c or other
na tura l foods . (3) There a re s evera l books , a nd ma ny web s i tes , tha t s ta te dogma ti ca l l y tha t ordi na ry ora nges or ora nge jui ces i ntera ct wi th
ma ny medi ca ti ons jus t a s gra pefrui t jui ce does . Thi s ha s , na tura l l y, a l a rmed ma ny i ndi vi dua l s . So fa r, s ol i d res ea rch evi dence poi nts to no drug
i ntera cti ons i nvol vi ng ora nges other tha n Sevi l l e. (4) Dont be s urpri s ed to s ee fura nocouma ri n-free gra pefrui t jui ce on the ma rket s oon.
17. The answer is d. (Brunton, pp 28-38; Katzung, pp 37-51.) Here i s how you s ol ve the probl em. Note: Its ea s y to be mi s l ed by i ncons i s tent us e of uni ts
of mea s urement (mcg vs . mg, mL vs . L), s o be s ure you fi rs t convert uni ts a s neces s a ry for cons i s tency.
Ca l cul a te the drugs el i mi na ti on ra te cons ta nt:

Then ca l cul a te the cl ea ra nce:

Reca l l tha t Cave = (F/Cl ) (Dos e/t), where F i s the bi oa va i l a bi l i ty (between 0 a nd 1.0) a nd t i s the dos i ng i nterva l (gi ven a s 4 hours ).
Rea rra nge to s ol ve for the dos e.

Thus , Dos e = 499,000 mcg, or 499 mg (cl os e enough to 500 mg).

18. The answer is c. (Brunton, pp 26-38; Katzung, p 41.) Rega rdl es s of whi ch a dmi ni s tra ti on route ha s been us ed, i f we pl ot the l og of pl a s ma
concentra ti on of a drug vers us ti me (a nd a s s umi ng fi rs t-order ki neti cs , whi ch a ppl i es to the el i mi na ti on of mos t drugs when bl ood l evel s a re
thera peuti c a fter i ni ti a l redi s tri buti on), we get a s tra i ght l i ne. It i s des cri bed by the equa ti on:

The s l ope of thi s l i ne, k, i s the el i mi na ti on ra te cons ta nt.

An a rgua bl y more us eful (a nd fa mi l i a r) mea s ure of the ra te a t whi ch a drug i s el i mi na ted i s the ha l f-l i fe (t1/2 ). It i s equa l to 0.693/k, a nd i s
defi ned a s the ti me i t ta kes for the concentra ti on of a drug i n the bl ood to fa l l to preci s el y one-ha l f of wha t i t i s now (or a t a ny s peci fi ed ti me).
The a rea under the curve (AUC) i s the i ntegra ti on of a ti me vers us concentra ti on pl ot for a drug. It i s a l i nea rnot a l oga ri thmi c or s emi l ogpl ot.
One us e for pl ots of AUC i s to es ti ma te ones tota l expos ure to a drug, us ua l l y from ti me zero (i ns ta nta neous l y upon a dmi ni s tra ti on) unti l
bl ood concentra ti ons of drug a re no l onger rel i a bl y detecta bl e or further mea s urements a re i mpra cti ca l . The AUC ca n be us ed to es ti ma te tota l
body cl ea ra nce of a drug, wi thout the need to know the drugs vol ume of di s tri buti on or i ts ha l f-l i fe, s i nce

Determi ni ng AUC a l s o ena bl es us to ca l cul a te a drugs bi oa va i l a bi l i ty. Bi oa va i l a bi l i ty (F) i s a mea s ure of the fra cti on of a n a dmi ni s tered dos e
tha t i s a bs orbed s ys temi ca l l y a nd i s detecta bl e i n the pl a s ma . Note tha t when a drug i s gi ven i ntra venous l y, bi oa va i l a bi l i ty i s , by defi ni ti on, 1.0
(100%), s i nce there a re no ba rri ers tha t mi ght prevent the a bs orpti on of drug from the a dmi ni s tra ti on s i te. So by a dmi ni s teri ng a drug
i ntra venous l y, a nd a l s o gi vi ng i t by a nother route, we ca n ca l cul a te bi oa va i l a bi l i ty. For exa mpl e, a s s ume the other route we us e i s ora l (PO).

If we do our bi oa va i l a bi l i ty determi na ti ons by gi vi ng the s a me dos e of the drug, the dos a ge uni ts i n the a bove equa ti on ca ncel out, a nd s o

The extra cti on ra ti o (ER) i s a mea s ure of a drugs remova l from the bl ood a s i t pa s s es through a n orga n (eg, the l i ver) tha t ca n meta bol i ze (or
otherwi s e extra ct) i t, for exa mpl e, from the a rteri a l to the venous s i de of tha t orga n.
The ra te of drug entry to a n orga n i s the product of bl ood fl ow (Q) a nd the a rteri a l concentra ti on of the drug (CA). The ra te a t whi ch the drug
l ea ves i s fl ow the venous concentra ti on (CV). If fl ow i nto a nd out of a n orga n a re i denti ca l (a s i t often i s ), then the extra cti on ra ti o ca n be
expres s ed a s

We ca n a l s o us e the extra cti on ra ti o to ca l cul a te the orga n cl ea ra nce of a drugtha t i s , the vol ume per uni t ti me from whi ch a n orga n removes a
drug

The vol ume of di s tri buti on (Vd) rel a tes the a mount of drug i n the body to i ts concentra ti on i n the bl ood (or pl a s ma ). It i s typi ca l l y ca l cul a ted a s
the a dmi ni s tered dos e di vi ded by the concentra ti on of drug i n the bl ood

To s i mpl i fy the a s s es s ment of the ki neti cs we typi ca l l y gi ve the drug i ntra venous l y (s o we know how much drug enters the s ys temthe enti re
dos e, s i nce bi oa va i l a bi l i ty = 1.0) a nd mea s ure the concentra ti on i mmedi a tel y therea fter (or us e a pl ot of the l og of drug concentra ti on vs . ti me),
then extra pol a te to fi nd drug concentra ti on a t ti me zero (the y-a xi s i ntercept).
19. The answer is a. (Brunton, pp 7-10; Katzung, pp 72-76, 1146.) Once the FDA a pproves a drug, you, a s a l i cens ed phys i ci a n, ca n pres cri be i t for a nythi ng
you des i re. Of cours e, there s houl d be s ome s ci enti fi c ba s i s for your new-found or hypothes i zed us e, hopeful l y s upporti ng or other ra ti ona l
evi dence i n s ol i d peer-revi ewed cl i ni ca l l i tera ture. (You proba bl y wont, for exa mpl e, s ee a -bl ocker bei ng us ed for trea ti ng a na l wa rts , but i f you
wa nted to us e one tha t wa y you a re not vi ol a ti ng a ny federa l l a ws . Jus t be s ure you ha ve a good rea s on to do s o, a nd a good a ttorney s houl d
s omethi ng ba d ha ppen a nd you get s ued.) And i f you a re conducti ng a cl i ni ca l tri a l a t your i ns ti tuti on to determi ne new i nforma ti on a bout future
cl i ni ca l effi ca cy of a drug for whi ch there a re other a pproved us es , a nd even pri nted off-l a bel us es , youl l proba bl y need Ins ti tuti ona l Revi ew
Boa rd a pprova l a nd wi l l ha ve to provi de wri tten i nformed cons ent to your s tudy s ubjects .
Note: Lets cons i der jus t one drug i n one drug cl a s s : fl uoxeti ne, the prototype of the SSRI cl a s s of a nti depres s a nts . Wha t i s i t a pproved for? Wel l ,
depres s i on, of cours e. But other a pproved or off-l a bel us es for thi s a nti depres s a nt (a nd the i denti ca l chemi ca l enti ty, s a me dos e a s us ed for
depres s i on but a pproved under a di fferent tra de na me for premens trua l dys phori c di s order) i ncl ude the fol l owi ng: obs es s i ve-compul s i ve
di s order; bul i mi a nervos a ; a l cohol i s m; a norexi a nervos a ; ADHD; bi pol a r II a ffecti ve di s order; borderl i ne pers ona l i ty di s order; na rcol eps y;
kl eptoma ni a ; mi gra i ne; chroni c da i l y hea da ches a nd tens i on-type hea da che; pos t-tra uma ti c s tres s di s order; s chi zophreni a ; l evodopa -i nduced
dys ki nes i a ; s oci a l phobi a ; chroni c rheuma toi d pa i n; pa ni c di s order; a nd di a beti c peri phera l neuropa thy. Oh, one more: tri choti l l oma ni a but dont
s ta rt pul l i ng out your own ha i r, or get depres s ed, tryi ng to memori ze thi s i ncompl ete l i s t of s ometi mes -odd us es .
20. The answer is c. (Brunton, pp 24-26; Katzung, pp 41-51.) The a ppa rent Vd i s defi ned a s the vol ume of fl ui d i nto whi ch a drug a ppea rs to di s tri bute
wi th a concentra ti on equa l to tha t of pl a s ma , or the vol ume of fl ui d neces s a ry to di s s ol ve the drug a nd yi el d the s a me concentra ti on a s tha t found
i n pl a s ma . By conventi on, we us e the va l ue of the pl a s ma concentra ti on, ba s ed on da ta s uch a s thos e s hown here, tha t ha s been extra pol a ted
ba ck to ti me zero. Pl otti ng the drug concentra ti on (y-a xi s ) on a l oga ri thmi c s ca l e, a s s hown here, a l l ows us to do the extra pol a ti on ea s i l y. In thi s
exa mpl e, tha t i s a bout 7 mcg/mL. Therefore, the a ppa rent Vd i s ca l cul a ted a s :

The tota l a mount of drug i n the body i ni ti a l l y i s the dos e we ga ve (100% bi oa va i l a bi l i ty, s i nce we ga ve i t IV), 350 mg (i e, 5 mg/kg 70 kg). The
es ti ma ted pl a s ma concentra ti on a t zero ti me i s 7 mcg/mL (0.007 mg/mL). Putti ng thes e numbers i n the equa ti on yi el ds the a ppa rent Vd:

21. The answer is d. (Brunton, pp 24-27; Katzung, pp 1057-1058.) Mos t exces s i ve a nd a dvers e effects from a s i ngl e drug occur beca us e of decl i nes i n
rena l excretory functi on. It a ffects drugs tha t a re el i mi na ted wi thout pri or meta bol i s m, thos e for whi ch meta bol i c i na cti va ti on pl a ys a rel a ti vel y
s ma l l rol e i n el i mi na ti on, a nd thos e drugs tha t form one or more a cti ve meta bol i tes . Decl i nes of hepa ti c functi on cl ea rl y occur i n a dva nced a ge,
whether i n the pres ence or a bs ence of other fa ctors tha t mi ght i mpa i r hepa ti c drug meta bol i s m, but tha t does not s eem to a ccount for the ma jori ty
of ca s es of exces s i ve drug effects . Body fa t content tends to ri s e, not decrea s e, wi th a ge (a ).
22. The answer is b. (Brunton, p 24; Katzung, pp 38-41, 50, 1044, 1052, 1149.) The s peed of a ny redi s tri buti on or re-equi l i bra ti on of bound/free
concentra ti ons of the ta rget drug depends on the drugs overa l l el i mi na ti on ha l f-l i fe (whi ch, i n turn, i s a compos i te of ei ther or both excreti on a nd
meta bol i s m, dependi ng on the drug). If a drug ha s a n overa l l s hort el i mi na ti on ha l f-l i fe, rel a ti vel y s pea ki ng, the re-equi l i bri um between bound
a nd free mol ecul es wi l l , i ndeed, be rea ched qui ckl y. If the drug ha s a rel a ti vel y l ong ha l f-l i fe (a nd es peci a l l y i f rel a ti vel y l a rge a mounts of the
i ntera cti ng drug a re pres ent a nd/or the i ntera cta nt bi nds a vi dl y to pl a s ma protei ns ), then i t wi l l ta ke l onger for equi l i bri um to be es ta bl i s hed
once a ga i n (i f i t occurs a t a l l ). If the drugs a re i n the ci rcul a ti on l a rgel y unbound, the cons equences a re l es s . However, cons i der wa rfa ri n: norma l l y
99% of a l l wa rfa ri n mol ecul es a t a ny gi ven ti me a re bound to pl a s ma protei ns . Di s pl a cement of even a s ma l l fra cti on of thos e bound mol ecul es
wi l l ha ve a l a rge i mpa ct on the number of free (a cti ve) mol ecul es , a nd wa rfa ri ns norma l a vera ge ha l f-l i fe i s a bout 2.5 da ys .
Bi oa va i l a bi l i ty of the drug (a ) i s not i mporta nt or rel eva nt. No ma tter whether bi oa va i l a bi l i ty i s grea t (a t or nea r 1.0) or s ma l l , once the drug i s i n
the ci rcul a tory s ys tem the i ntera cti on wi l l occur, a nd reequi l i bri um wi l l be rees ta bl i s hed nei ther s l ower nor fa s ter tha n under a ny other
ci rcums ta nces . Li kewi s e, unl es s bl ood pH cha nges (I di d not s a y i t di d, a nd there i s no rea s on to s pecul a te tha t i t woul d), the pK of the drugs (c) i s
l a rgel y i rrel eva nt. Rena l cl ea ra nce (d) ma y be i mporta nt, but reca l l tha t ma ny drugs a re el i mi na ted ma i nl y or compl etel y by meta bol i s m, s o
whether cl ea ra nce i s i mporta nt depends on the drug(s ). The s a me rea s oni ng a ppl i es to a ns wer e: i t i s not i mporta nt how the drug i s el i mi na ted, i t
i s the ra te a t whi ch overa l l el i mi na ti on occurs .
23. The answer is e. (Brunton, pp 199, 1806; Katzung, p 66.) Ta chyphyl a xi s i s defi ned a s ra pi dl y devel opi ng tol era nce to the effects of a n a goni s t tha t i s
a dmi ni s tered repea tedl y, even i f the dos a ges gi ven a fter the fi rs t one a re not cha ngedor even progres s i vel y i ncrea s ed to overcome the

phenomenon. It i s s ometi mes a l s o ca l l ed des ens i ti za ti on or downregul a ti on of the receptor(s ), but thos e phenomena do not expl a i n a l l the
mecha ni s ms by whi ch ta chyphyl a xi s (or tol era nce i n genera l ) occurs . The mecha ni s m behi nd the devel opment of ta chyphyl a xi s or s l owerdevel opi ng drug tol era nce i n genera l va ri es dependi ng on whi ch drug i s bei ng us ed, the bi ochemi ca l proces s es by whi ch the drug exerts i ts
effects , a nd wha t the effector a nd the res pons e(s ) a re. For exa mpl e, cons i der the ra pi dl y di mi ni s hed res pons e of a va ri ety of cel l s /ti s s ues to
repea ted a dmi ni s tra ti on of a mpheta mi ne, whi ch a cts by rel ea s i ng neurona l norepi nephri ne. Cha l l enge the s ys tem repea tedl y a nd the a mount of
i ntra neurona l NE a va i l a bl e to be rel ea s edwhi ch i s es s enti a l for ca us i ng the ul ti ma te res pons egoes down. Another exa mpl e, wi th more
cl i ni ca l rel eva nce, i s the s omewha t s l ower devel opment of tol era nce of a i rwa y s mooth mus cl es , a nd thei r a bi l i ty to rel a x (i e, ca us e
bronchodi l a ti on) i n res pons e to repea ted a dmi ni s tra ti on of -a drenergi c a goni s ts , s uch a s a l buterol , a rgua bl y the mos t wi del y us ed a drenergi c
bronchodi l a tor for a s thma . [Note: There i s no ma gi ca l numberhours or da ys , for exa mpl etha t di s ti ngui s hes between ta chyphyl a xi s a nd
regul a r tol era nce. The brevi ty wi th whi ch the tol era nce devel ops i s the key poi nt.]
24. The answer is d. (Brunton, pp 28-38; Katzung, pp 46-49.) The dos e (D) to gi ve equa l s the product of the ta rget bl ood concentra ti on a nd the drugs
cl ea ra nce.

To s i mpl i fy thi ngs , l ets get the uni ts of vol ume the s a me for both cl ea ra nce a nd concentra ti on. The cl ea ra nce of 0.08 L/mi n = 80 mL/mi n.
Therefore

The s ta ted dos i ng i nterva l i s 4 hours , s o

whi ch (rounded) i s cl os es t to 150 mg.

25. The answer is d. (Brunton, pp 36-37; Katzung, pp 41-47.) Here the l oa di ng dos e (D) equa l s the product of the ta rget bl ood concentra ti on (Cdesired) a nd
the vol ume of di s tri buti on (Vd).

As a l wa ys , convert uni ts to ma ke thi ngs cons i s tent. The vol ume of di s tri buti on, 60 L, i s , of cours e, 60,000 mL

26. The answer is b. (Brunton, pp 127-131; Katzung, pp 54-59.) There a re four ma jor components to thi s mixed-function oxidase s ys tem: (1) cytochrome P450,
(2) NADPH, or reduced ni coti na mi de a deni ne di nucl eoti de phos pha te, (3) NADPH-cytochrome P450 reducta s e, a nd (4) mol ecul a r oxygen.

The fi gure s hows the ca ta l yti c cycl e for the genera l rea cti ons dependent on cytochrome P450s . (Not a l l rea cti on s teps or i ntermedi a tes a re
s hown.) In s i mpl e terms , the s ys tem a cts a s a monooxygena s e, converti ng a reduced form of a drug (RH) to a n oxi di zed form (ROH). For s ome drugs ,
thos e meta bol i c s teps a re fol l owed by Pha s e II rea cti ons , s uch a s conjuga ti on (wi th gl ucuroni c a ci d, s ul fa te, etc) tha t further enha nce the
el i mi na ti on of drug meta bol i tes .
Cytochrome P450s ca ta l yze di vers e oxi da ti ve rea cti ons i nvol ved i n drug bi otra ns forma ti on; they undergo reducti on a nd oxi da ti on duri ng the
ca ta l yti c cycl e. A pros theti c group compos ed of Fe a nd protoporphyri n IX (formi ng heme) bi nds mol ecul a r oxygen a nd converts i t to a n a cti va ted
form for i ntera cti on wi th the drug s ubs tra te.
NADPH gi ves up protons to the fl a voprotei n (FP) NADPH-cytochrome P450 reducta s e. The reduced fl a voprotei n tra ns fers thes e reduci ng
equi va l ents to cytochrome P450. The reduci ng equi va l ents a re us ed to a cti va te mol ecul a r oxygen for i ncorpora ti on i nto the s ubs tra te, a s des cri bed
a bove. Thus , NADPH provi des reduci ng equi va l ents , a nd NADPH-cytochrome P450 reducta s e pa s s es them on to the ca ta l yti c enzymes tha t compri s e
cytochrome P450.
Cycl ooxygena s e (COX; a ns wer a ) i s a genera l term for two ma i n enzymes , COX-1 a nd 2, tha t meta bol i ze endogenous a ra chi doni c a ci d to
pros ta gl a ndi ns , pros ta cycl i ns , a nd other ei cos a noi ds . Its s ubs tra te s peci fi ci ty i s l a rgel y l i mi ted to the endogenous mol ecul es deri ved from
a ra chi doni c a ci d, not xenobi oti cs . A good exa mpl e of COX-1 a nd COX-2 i s a s pi ri n. Mos t other nons teroi da l a nti -i nfl a mma tory drugs a re a l s o COX-1
a nd COX-2 i nhi bi tors . The exempl a r of a s el ecti ve COX-2 i nhi bi tor i s cel ecoxi b.
Monoa mi ne oxi da s e (MAO; c) i s a fl a voprotei n enzyme tha t i s found on the outer membra ne of mi tochondri a i n certa i n neurons , a nd a l s o i n
hepa tocytes . It oxi da ti vel y dea mi na tes s hort-cha i n monoa mi nes onl y, a nd i t i s not pa rt of the drug-meta bol i zi ng mi cros oma l s ys tem. ATP i s
i nvol ved i n the tra ns fer of reduci ng equi va l ents through the mi tochondri a l res pi ra tory cha i n, not the mi cros oma l s ys tem. There a re va ri ous forms
of MAO, di s ti ngui s hed ma i nl y by thei r cel l ul a r l oca ti ons , thei r s ubs tra tes , a nd thei r i nhi bi tors . MAO-A, for exa mpl e, i s found i n ra ther di vers e
l oca ti ons , s uch a s i n the l i ver a nd other cel l s . MAO-B i s the predomi na nt form i n certa i n pa rts of the bra i n (hence, B).
UDP-gl ucuronos yl tra ns fera s e, a l ong wi th s uch enzymes a s gl uta thi one-S-tra ns fera s e, methyl tra ns fera s es , a nd N-a cetyl tra ns fera s es , a re
i mporta nt i n Pha s e II meta bol i s m of va ri ous drugs . Subs tra tes for thes e enzymes genera l l y a re drugs or xenobi oti cs tha t were previ ous l y
tra ns formed by Pha s e I rea cti ons , s uch a s the a cti ons of the CYP450 mi xed-functi on oxi da s es . Thes e enzymes a dd a functi ona l group to a s ubs tra te,
ra ther tha n chemi ca l l y modi fyi ng the ori gi na l s ubs tra te vi a oxi da ti on, reducti on, dea mi na ti on, a nd the l i kea l l of whi ch a re res pons i bi l i ti es of
the mi xed-functi on oxi da s e s ys tems .
Note: How di d the cytochrome P450 s ys tem get the 450 des i gna ti on? Si mi l a r to hemogl obi n, cytochrome P450 i s i nhi bi ted by ca rbon monoxi de.
Thi s i ntera cti on res ul ts i n mol ecul es wi th a s pectrophotometri c a bs orba nce s pectrum pea k a t 450 nm, hence the des i gna ti on 450.
27. The answer is b. (Brunton, pp 44-50; Katzung, pp 1821.) Pa rti a l a goni s ts ha ve both the a bi l i ty to bi nd to receptors (a ffi ni ty) a nd the a bi l i ty to evoke
a res pons e by a cti va ti ng thos e receptors (effi ca cy), a l bei t wea kl y, under ba s a l condi ti ons . Thus , when a cebutol ol i s a dmi ni s tered a t res t (a
condi ti on under whi ch endogenous ca techol a mi ne l evel s a re l ow), hea rt ra te ri s es s l i ghtl y due to -1 receptor a cti va ti on vi a wea k a goni s t a cti vi ty.

However, the occupa ti on of a drenergi c receptors by thi s wea k a goni s t reduces the number of receptors a va i l a bl e to bi nd a nd res pond to s tronger
a goni s ts (epi nephri ne, norepi nephri ne). As a res ul t, the ma gni tude of the res pons e to s tronger a goni s ts i n the pres ence of the pa rti a l a goni s t i s
l ower tha n i n the a bs ence of i t (a l l other thi ngs bei ng equa l ).
28. The answer is d. (Brunton, pp 34-38; Katzung, pp 37-45.) Wi th fi rs t-order el i mi na ti on of a drug, we get a s tra i ght l i ne i f we pl ot the l og of drug
concentra ti on i n the bl ood vers us ti me once dos i ng ha s s topped. The s l ope of the l i ne i s the el i mi na ti on ra te cons ta nt (kel). The drugs ha l f-l i fea
va l ue we wi l l need to us e momenta ri l yi s rel a ted to kel a s fol l ows : t1/2 (kel)/0.693. So, for the drug noted i n the ques ti on, t1/2 = 0.693/0.35, or
a pproxi ma tel y 2 hours . It ta kes a pproxi ma tel y four to fi ve ha l f-l i ves to rea ch a s tea dy-s ta te bl ood concentra ti on. Do the ma th a nd youl l s ee tha t
the ti me for thi s drug to rea ch s tea dy s ta te i s a pproxi ma tel y 8 to 10 hours .
29. The answer is e. (Brunton, pp 32-33, 1804, 1807-1808; Katzung, pp 42-44.) After a 40-hour (a bout 1.67 da ys ) drug-free i nterva l pa s s es the concentra ti on
of the drug wi l l fa l l , a s predi cted by the ha l f-l i fe, to 3 mcg/mL; to 1.5 mcg/mL 40 hours a fter tha t; a nd to 0.75 mcg (now i n the nontoxi c ra nge) a fter
yet a nother 40 hours pa s s es . Thus we ha ve to wa i t 120 hours , or fi ve da i l y dos es s ki pped, to a chi eve the goa l .
30. The answer is e. (Brunton, pp 30-38; Katzung, pp 47-48.) You s houl d reca l l tha t Vd = Dos e/C0 . We know wha t the dos e i s . Wha t we mus t ca l cul a te i s
the i ni ti a l drug concentra ti on (C0 )the pea k drug concentra ti on tha t i s rea ched i ns ta nta neous l y a fter gi vi ng the IV bol us dos e. Unfortuna tel y,
weve wa i ted 30 mi nutes before ta ki ng our fi rs t bl ood s a mpl e, but tha t i s not a s i gni fi ca nt probl em: pl ot the l og of drug concentra ti on vers us ti me
a nd extra pol a te to where the l i ne i ntercepts the l og-concentra ti on a xi s (t0 ). Thi s gi ves us a good es ti ma te of C0 . Pl ug the extra pol a ted C0 i nto the
equa ti on a nd you ha ve your a ns wer.
Note tha t bi oa va i l a bi l i ty i s not a fa ctor i n thi s i ns ta nce, beca us e wi th IV a dmi ni s tra ti on bi oa va i l a bi l i ty i s , by defi ni ti on, 1.0 (100%). Knowi ng or
ca l cul a ti ng the el i mi na ti on ra te cons ta nt wont hel p ei ther, beca us e i t i s i nextri ca bl y l i nked to the ha l f-l i fe, whi ch we a l rea dy know a s kel =
0.693/t1/2 (a nd you ca n rea rra nge the equa ti on ea s i l y.)
Ca l cul a ti ng the AUC (concentra ti on vs . ti me i ntegra l ) wi th a bol us i njecti on wi l l gi ve us no i nforma ti on more us eful tha n wha t we a l rea dy ha ve.
Cl ea ra nce (genera l l y referri ng to rena l cl ea ra nce) i s i rrel eva nt i n thi s s i tua ti on: Ive s ta ted tha t the drug i s compl etel y meta bol i zed to other
products ; thus , there i s no drug A to mea s ure i n the uri ne.
31. The answer is c. (Brunton, pp 35-36; Katzung, pp 37-46.) The s cena ri o a bove ma kes ca l cul a ti ons rel a ti vel y s tra i ghtforwa rd, pa rti cul a rl y beca us e no
l oa di ng dos e thera py wi l l be us ed.
Stea dy-s ta te bl ood l evel s occur when the ra te of drug i n equa l s the ra te of drug out. The vol ume of di s tri buti on, gi ven i n the ques ti on, i s
i rrel eva nt for the ca l cul a ti ons .
The ra te of drug out i s gi ven a s a Cl = 70 mL/mi n
Reca l l tha t the dos e (D) = Cl CSS
Therefore, wi th a l i ttl e rea rra ngi ng, the dos e ca n be computed a s :

Convert the uni ts s o theyre cons i s tent for both va ri a bl es , a nd dont forget to ca l cul a te how ma ny mi nutes there a re i n the dos i ng i nterva l , 6
hours . Now, the res t of the ma th:
The ta rget bl ood l evel of 4 mg/L i s the s a me a s 4 mcg/mL, a nd thi s i s a rea s ona bl e cha nge of vol ume uni ts to ma ke for s ubs equent ca l cul a ti ons ,
s i nce cl ea ra nce i s gi ven i n uni ts of mL/mi n.

And s i nce the drug wi l l be gi ven every 6 hours :

32. The answer is c. (Brunton, pp 28-38; Katzung, pp 37-45.) Onl y the drug concentra ti on a t s tea dy s ta te wi l l cha nge: i t wi l l be grea ter wi th thi s a l tered
protocol . Do not be mi s l ed by the numbers . The ti me to rea ch CSS wi th a cons ta nt drug i nfus i on i s a functi on of ha l f-l i fe (or the el i mi na ti on ra te
cons ta nt, whi ch i s rel a ted to i t: kel = 0.693/t1/2 ), a nd tha t wi l l not cha nge under the condi ti ons s ta ted. Li kewi s e, wi th the va s t ma jori ty of drugs
el i mi na ted by fi rs t-order ki neti cs , there wi l l be no cha nge of tota l body cl ea ra nce or of vol ume of di s tri buti on. (Note: I des cri bed s ubs ta nce X a s
bei ng pha rma col ogi ca l l y i nert s i mpl y s o you di dnt conjure up confoundi ng but l a rgel y i rrel eva nt i s s ues , s uch a s a n a cti ve drug tha t i s a bl e to
ca us e res i dua l or l ong-l a s ti ng effects on i ts el i mi na ti on or el i mi na ti on ra te, for exa mpl e, a drug tha t ca us ed l ong-l a s ti ng i nducti on of hepa ti c
drug-meta bol i zi ng enzymes .)
33. The answer is a. (Brunton, pp 27-28, 127-138; Katzung, pp 54-59.) Pha s e I meta bol i c rea cti ons genera l l y convert (vi a a ddi ti on or unma s ki ng of s uch
pol a r functi ona l groups a s NH 2 or OH through, s a y, oxi da ti ons , reducti ons , or dea mi na ti on) very nonpol a r (i e, very l i pi d-s ol ubl e) drugs i nto more
pol a r (more wa ter-s ol ubl e) meta bol i tes . Among other thi ngs , pol a r meta bol i tes of drugs i n genera l a re l es s l i kel y to undergo tubul a r
rea bs orpti on. We ca n genera l i ze by s a yi ng tha t Pha s e I rea cti ons pl a y a rol e i n formi ng meta bol i tes tha t a re more ea s i l y excreted. If drug A, the
pa rent drug, wa s a l rea dy very pol a r (a ns wer b), there woul d be l i ttl e need for Pha s e I meta bol i s m. There i s no rea s on to a s s ume tha t drug A wi l l
l a ck i ntri ns i c bi ol ogi ca l a cti vi ty (a ns wer c); a nd beca us e i t i s qui te l i pi d-s ol ubl e to begi n wi th, once i n the ci rcul a ti on i t s houl d ha ve good a bi l i ty to
di ffus e a cros s membra nes a nd rea ch i ntra cel l ul a r s i tes (hence, e i s i ncorrect). Fi na l l y, note tha t thos e rea cti ons des cri bed a s Pha s e II a re the
ones tha t further i ncrea s e pol a ri ty (wa ter-s ol ubi l i ty) of s ome drugs vi a formi ng conjuga tes wi th gl ucuroni c a ci d or s ul fa te.
34. The answer is e. (Brunton, pp 51-52, 55-58; Katzung, pp 21-29.) The genera l i s s ue of l i ga nd-receptor-res pons e coupl i ng i nvol ves s i gna l tra ns ducti on,
a nd i s a ddres s ed i n Ques ti on 5. The s peci fi c a goni s ts noted i n the ques ti on tra ns duce thei r s i gna l s a nd eventua l l y ca us e a res pons e by proces s es
i nvol vi ng G protei ns a fa mi l y of gua ni ne nucl eoti de-bi ndi ng protei ns . Thes e l i ga nds bi nd to the extra cel l ul a r fa ce of the tra ns membra ne protei n.
The va ri ous G protei ns (eg, G i, G q, a nd G s ) bi nd to i ntra cel l ul a r porti ons of the receptor. They then coupl e the i ni ti a l l i ga nd i ntera cti on to the

eventua l res pons e through a s eri es of effector enzymes or enzyme s ys tems tha t a re G protei n-regul a ted.
For exa mpl e, a denyl yl cycl a s e ca n be a cti va ted, ca ta l yzi ng the forma ti on of cAMP tha t then a cti va tes a pa rti cul a r ki na s e tha t phos phoryl a tes
s peci fi c i ntra cel l ul a r protei ns . However, the a ctua l s teps tha t occur a fter l i ga nd bi ndi ng depend on wha t the l i ga nd i s , wha t s peci fi c G protei n i s
i nvol ved, whi ch ki na s es a re a cti va ted, a nd wha t protei ns they phos phory-l a te. And wha t ha ppens (i e, wha t the res pons e i s ) depends on a l l of the
a bove a nd, of cours e, whi ch cel l type i s bei ng a ffected.
Acti va ti on of a denyl yl cycl a s e a nd i ncrea s ed cAMP l evel s ma y occur i n one s ys tem, but the oppos i te ma y occur i n a nother. Some s i gna l
tra ns ducti on pa thwa ys i nvol ve phos phol i pa s e C, others do not. A ca l ci um cha nnel ma y be a ffected i n one s ys tem a nd a pota s s i um cha nnel (or no
i on cha nnel ) i n others .
By wa y of revi ew, reca l l tha t there a re three other ma i n mecha ni s ms or pa thwa ys for s i gna l tra ns ducti on a bout whi ch we ha ve rea s ona bl e
knowl edge.
One us es a receptor protei n tha t s pa ns the cel l membra ne, but G protei ns a re not i nvol ved. On the i nner membra ne fa ce the protei n pos s es s es
enzyma ti c a cti vi ty tha t i s regul a ted by the pres ence or a bs ence of l i ga nd bound to the extra cel l ul a r fa ce. The tyros i ne ki na s e pa thwa y i s a n
exa mpl e, a nd the overa l l pa thwa y i s res pons i bl e for the a cti vi ty of va ri ous growth fa ctors a nd i ns ul i n (whi ch i s a l s o a growth-regul a ti ng hormone).
Another mecha ni s m i s us ed by very l i pi d-s ol ubl e l i ga nds tha t cros s cel l membra nes ea s i l y a nd a ct on s ome i ntra cel l ul a r receptor. For exa mpl e,
gl ucocorti cos teroi ds ul ti ma tel y a ct i n the nucl eus a nd, through i ntera cti on wi th hea t-s hock protei n (hs p90), eventua l l y a l ter tra ns cri pti on of
s peci fi c genes .
The thi rd i nvol ves tra ns membra ne i on cha nnel s , the open or cl os ed s ta tes of whi ch a re control l ed by l i ga nd bi ndi ng to the cha nnel . Thi s
proces s a ppl i es to s ome of the i mporta nt neurotra ns mi tters , es peci a l l y thos e i n the bra i n (GABA, the ma i n i nhi bi tory neurotra ns mi tter) a nd s uch
a mi no a ci ds a s gl yci ne, whi ch exert exci ta tory a cti ons . The ni coti ni c receptor for ACh fi ts i n thi s ca tegory too.
35. The answer is a. You ma y not fi nd the defi ni ti on of malignant i n a pha rma col ogy book, but you ought to know wha t i t i s . Ma ny peopl e thi nk
ma l i gna nt i nva ri a bl y mea ns ca ncer, but tha t i s nt true. Remember ma l i gna nt hypertens i on, ma l i gna nt hyperthermi a , neurol epti c ma l i gna nt
s yndrome? The term s i mpl y mea ns a condi ti on i s ra pi dl y getti ng wors e. Nothi ng neces s a ri l y l i nked to ca ncer; no i mpl i ca ti on tha t the condi ti on wi l l
not res pond to us ua l l y effecti ve (or even s econd- or thi rd-l i ne) thera pi es a nd medi ca ti ons (refra ctory i s the term for res i s ta nce to i nterventi on); no
gua ra ntee, or even a l i kel i hood, tha t the condi ti on wi l l be fa ta l i f i t i s trea ted properl y.
36. The answer is d. (Brunton, pp 7-11; Katzung, pp 73-76, 1134-1136.) One of the mos t controvers i a l a s pects of ma rketi ng herba l s , nutri ti ona l
s uppl ements , a nd other nutri ceuti ca l s i s tha t ma nufa cturers a nd s el l ers ha ve to provi de no pri or or s ci enti fi c proof of s a fety or effi ca cy to the
FDAs omethi ng tha t mus t be provi ded, a nd wi th a bunda nt a nd s ci enti fi ca l l y s ound da ta , before the FDA wi l l a pprove a drug for s a l e by
prescription. Herba l s , for exa mpl e, ca me under the umbrel l a of the Di eta ry Suppl ement Hea l th a nd Educa ti on Act (DSHEA) of 1994.
Such products , you ma y ha ve noted, come wi th l a bel s tha t s ta te s ervi ng s i ze, ra ther tha n dos e, a s i f we a re goi ng to be i nges ti ng s ome ca rrots
i ns tea d of a potenti a l l y a cti ve a nd da ngerous drug.
Sel l ers of s uch products a s herba l s ca nnot ma ke expl i ci t cl a i ms tha t thei r products wi l l prevent, di a gnos e, trea t, or cure a ny di s ea s e. DSHEA
a l l ows a s el l er of a nutri ti ona l s uppl ement to s a y s uch obtus e thi ngs a s boos ts your memory, or i mproves uri na ry tra ct hea l th, but they ca nnot
s ta te hel ps prevent or trea t Al zhei mer di s ea s e or reduces uri na ry frequency a nd nocturi a i f you ha ve beni gn pros ta ti c hypertrophy. In fa ct,
DSHEA s i mpl y requi res tha t the l a bel on the product s ta tes , i n es s ence, tha t the FDA ha s nt eva l ua ted a ny of the cl a i ms the ma nufa cturer ha s
ma de, pl a i nl y or i mpl i ci tl y, on the l a bel .
Moreover, whi l e a drug compa ny mus t provi de a nd pa y for the obl i ga tory precl i ni ca l a nd cl i ni ca l s tudi es before a pres cri pti on drug gets the OK,
i f there i s a rea s on or a ttempt to pul l a nutri ceuti ca l from the ma rket the FDA mus t do the work a nd pa y the cos ts to prove tha t the product i s
uns a fe or i neffecti ve.
Drugs neednt be a pproved by the FDA a s pres cri pti on drugs (a ns wer a ) before they ca n be s ol d OTC. Whi l e s uch pri or a pprova l i s the trend, i f
not the norm (for exa mpl e, cons i der ma ny a nti hi s ta mi nes for a l l ergy or i ns omni a ; or drugs tha t i nhi bi t ga s tri c a ci d s ecreti on bei ng ma rketed for
hea rtburn or a ci d i ndi ges ti on), cons i der a s pi ri n. Its been a va i l a bl e OTC for deca des a nd for i ts common us es (pa i n, fever, i nfl a mma ti on) i t ha s
never gotten a n FDA bl es s i ng a s a pres cri pti on drug. Indeed, s ome s a y tha t i f a s pi ri n were bei ng cons i dered for a pprova l a s a pres cri pti on drug
toda y, i t mi ght not be a pproved beca us e of the ri s ks of s eri ous a dvers e res pons es (eg, bl eedi ng tendenci es from a nti pl a tel et effects ;
bronchos pa s m i n ma ny a s thma ti cs ) a nd drug-drug i ntera cti ons . Nonethel es s , we ha ve ma ny OTC drugs nowa da ys tha t fi rs t got a pprova l for s a l e by
pres cri pti on onl y, for exa mpl e, a nti hi s ta mi nes , i nhi bi tors of ga s tri c a ci d s ecreti on (noted a bove), a nd others . Approva l for OTC s a l e wa s
peti ti oned by the ma nufa cturer, a nd then a pproved onl y a fter revi ews by a nd recommenda ti ons from FDAs expert a dvi s ory pa nel s .
Ans wer c i s i ncorrect. Once a drug gets a pprova l for s a l e a nd us e a s a pres cri pti on drug, a nd for a gi ven i ndi ca ti on (or more, dependi ng on da ta
s ubmi tted a nd a pproved), the phys i ci a n ca n pres cri be tha t drug for a ny (rea s ona bl e) purpos e tha t he or s he thi nks i s a ppropri a te, s a fe, a nd
effecti ve. Phys i ci a ns a nd s ci enti s ts l ea rn or hypothes i ze a bout new us es for a drug, conduct cl i ni ca l s tudi es , a nd overa l l ca n l ega l l y pres cri be
drugs for the off-l a bel or unl a bel ed us es .
Pha s e III tes ti ng of drugs i s conducted i n us ua l l y no more tha n 5000 pa ti ents wi th a di s ea s e for whi ch the drug i s to be ma rketed. The ma i n goa l
i s to a s s es s effecti venes s for the s ta ted us e, a nd for overa l l s a fety. Thes e a re ra ther ti ghtl y control l ed s tudi es . The number of s ubjects , a nd the
condi ti ons i n whi ch the drug i s gi ven, a re qui te di fferent from wha t ha ppens i n the rea l worl di ncl udi ng Pha s e IV, whi ch i s the pos tma rketi ng
s urvei l l a nce pha s e of drug a pprova l , where tens or hundreds of thous a nds of pa ti ents ma y get the drug i n l a rgel y uncontrol l ed ci rcums ta nces .
Ma ny drugs ha ve come (been FDA-a pproved) a nd gone (pul l ed from the ma rket beca us e of a dvers e rea cti ons or i ntera cti ons , i ncl udi ng thos e
l ea di ng to dea th) beca us e of wha t weve l ea rned after the drug wa s a pproved by the FDA, a nd wa s a pproved for us e by phys i ci a ns i n condi ti ons
tha t werent nea rl y a s wel l control l ed a s thos e i nvol ved i n pre-a pprova l s tudi es .

The Peripheral Nervous Systems: Autonomic and Somatic Nervous System Pharmacology
Acetyl chol i ne s ynthes i s , fa tes , a nd a cti ons
Acetyl chol i nes tera s e a nd i ts i nhi bi tors
Adrenergi c a goni s ts a nd a nta goni s ts
Adrenergi c receptor s ubtypes
Ca techol a mi ne s ynthes i s , fa tes , a nd a cti ons
Chol i nergi c receptor s ubtypes
Chol i nergi c a goni s ts a nd a nta goni s ts
Ga ngl i oni c s ti mul a nts a nd bl ockers
Peri phera l nervous s ys tem s tructure a nd functi on
Skel eta l mus cl e rel a xa nts (centra l l y a cti ng)
Skel eta l neuromus cul a r bl ockers

Questions
Note: The fi rs t s evera l ques ti ons i n thi s cha pter a re ba s ed on a s chema ti c di a gra m of the peri phera l nervous s ys tem. I thi nk thi s i s a s ui ta bl e a nd
effi ci ent wa y to hel p you a s s es s , or cl a ri fy, s ome funda menta l (a nd es s enti a l ) a s pects of peri phera l nervous s ys tem a na tomy, (neuro)phys i ol ogy,
a nd pha rma col ogy ba s ed on a few ma i n rul es a nd key excepti ons to them. I hope thi s a pproa ch wi l l be benefi ci a l .
The di a gra m bel ow s hows the ma i n efferent pa thwa ys i n the peri phera l nervous s ys tems the a utonomi c (pa ra s ympa theti c a nd s ympa theti c;
PNS, SNS, res pecti vel y) a nd s oma ti c nervous s ys tems from the CNS/s pi na l cord (a t the fa r l eft, not l a bel ed) out to the peri phera l ta rget (effectors ).
The s wea t gl a nds s hown i n the fi gure repres ent eccri ne s wea t gl a nds . The i nnerva ti on of a rrector pi l i mus cl es i s ba s i ca l l y the s a me.
Thos e nerves (a nd a ns wer choi ces ) a re:
a . Prega ngl i oni c pa ra s ympa theti c
b. Pos tga ngl i oni c pa ra s ympa theti c
c. Prega ngl i oni c s ympa theti c
d. Pos tga ngl i oni c s ympa theti c to s tructures other tha n s wea t gl a nds
e. Prega ngl i oni c (functi ona l equi va l ence) s ympa theti c to the a drena l (s upra rena l ) medul l a
f. Prega ngl i oni c s ympa theti c, s wea t gl a nd (eccri ne) i nnerva ti on
g. Pos tga ngl i oni c s ympa theti c to eccri ne s wea t gl a nds
h. Motor nerve, s oma ti c nervous s ys tem

37. Ana tomi c, neurochemi ca l , a nd pha rma col ogi c s tudi es of nerves a, c, e, f, a nd h i ndi ca te tha t they s ha re one common property. Whi ch s ta tement
bel ow correctl y s umma ri zes wha t tha t i s ?
a . Are chol i nergi c, a cti va te pos ts yna pti c mus ca ri ni c receptors
b. Are chol i nergi c, a cti va te pos ts yna pti c ni coti ni c receptors
c. Ca nnot rel ea s e thei r neurotra ns mi tter(s ) i n the pres ence of a tropi ne
d. Ha ve the a bi l i ty to a cti va te a l l the a drenergi c a nd a l l the chol i nergi c nerves
e. Recycl e thei r neurotra ns mi tter a fter ea ch a cti on potenti a l , ra ther tha n s ynthes i zi ng new tra ns mi tter de novo
38. Mul ti di s ci pl i na ry a s s es s ments of nerve d, a typi ca l pos tga ngl i oni c s ympa theti c nerve, i ndi ca te tha t i t i s qui te di fferent from a l l the other
nerves s hown i n the peri phera l nervous s ys tem s chema ti c. Whi ch s ta tement des cri bes tha t di fference?
a . Atropi ne s el ecti vel y bl ocks a cti va ti on of receptors by the neurotra ns mi tter rel ea s ed from nerve d
b. It ca us es bronchodi l a ti on (a i rwa y s mooth mus cl e rel a xa ti on) when i t i s a cti va ted
c. It i s a drenergi c (or nora drenergi c i f you wi s h to us e tha t term i ns tea d)
d. The pri ma ry neurotra ns mi tter s ynthes i zed by nerve d i s epi nephri ne
e. When nerve d i s phys i ol ogi ca l l y a cti va ted by a n a cti on potenti a l , a cti ons of i ts rel ea s ed neurotra ns mi tter a re termi na ted ma i nl y by hydrol ys i s i n
the s yna pti c cl eft
39. Reupta ke (i nto the nerve) i s the ma i n phys i ol ogi c proces s for termi na ti ng the pos ts yna pti c a cti vi ty of a peri phera l nervous s ys tem
neurotra ns mi tter. To whi ch nerve does thi s proces s a ppl y?
a . Nerve a
b. Nerve b
c. Nerve c
d. Nerve d
e. Nerve e
f. Nerve f
g. Nerve g
h. Nerve h
40. Nerve d, the more typi ca l pos tga ngl i oni c s ympa theti c nerve, i s a cti va ted by a norma l l y genera ted a cti on potenti a l fol l owed by neurotra ns mi tter
rel ea s e i nto the s yna ps e. On whi ch receptor type does the neurotra ns mi tter i t rel ea s es a ct? Remember: You ca n s el ect onl y one a ns wer.
a . 1 a drenergi c
b. 2 a drenergi c
c. 1 a drenergi c
d. 2 a drenergi c
e. Mus ca ri ni c
f. Ni coti ni c
g. It depends on the ta rget ti s s ue (effector) type
41. Whi ch s ta tement correctl y des cri bes wha t i s ra ther uni que a bout nerve g, the pos tga ngl i oni c fi bers tha t i nnerva te eccri ne s wea t gl a nds ,
compa red wi th vi rtua l l y a l l other pos tga ngl i oni c s ympa theti c nerves ?
a . Coca i ne bl ocks rel ea s e of i ts neurotra ns mi tter
b. Is chol i nergi c
c. Is s ti mul a ted by prega ngl i oni c a drenergi c nerves (nerve f)
d. Its rel ea s ed neurotra ns mi tter a cts on ni coti ni c receptors
e. Us es epi nephri ne a s i ts neurotra ns mi tter
42. Nerve g, the pos tga ngl i oni c nerve i nnerva ti ng eccri ne s wea t gl a nds a nd a rrector pi l i mus cl es , i s a cti va ted by a norma l l y genera ted a cti on
potenti a l a nd s ubs equent rel ea s e of neurotra ns mi tter from nerve f. On whi ch receptor type does the neurotra ns mi tter rel ea s ed by nerve g a ct?
a . 1 a drenergi c
b. 2 a drenergi c
c. Mus ca ri ni c
d. Ni coti ni c
e. 1 a drenergi c
f. 2 a drenergi c
43. As s ume tha t a l l the efferent a utonomi c pa thwa ys i n the s chema ti c a re toni ca l l y a cti ve (a rea s ona bl e a s s umpti on), even i f a t l ow a nd
qua nti ta ti vel y di fferent l evel s . We a dd vecuroni um (or a ny of s evera l rel a ted drugs ) to the s ys tem a nd, a s expected, i t bl ocks neurotra ns mi tter
a cti va ti on of certa i n s tructures . Whi ch nerve i nnerva tes thos e s tructures a nd norma l l y woul d a cti va te them i n the a bs ence of pa ncuroni um or i ts
rel a ted drugs ?
a . Nerve a
b. Nerve b
c. Nerve c
d. Nerve d
e. Nerve e

f. Nerve f
g. Nerve g
h. Nerve h
44. Nea rl y every s tructure tha t i s i nfl uenced by s ympa theti c nervous s ys tem a cti vi ty ha s pos tga ngl i oni c s ympa theti c (a drenergi c) nerves i nnerva ti ng
i t. Whi ch one of the fol l owi ng s tructures i s mos t defi ni tel y a ffected by s ympa theti c nervous s ys tem i nfl uences , a nd res ponds to epi nephri ne, but
l a cks i nnerva ti on by pos tga ngl i oni c a drenergi c fi bers a nd s o i s not a ffected by norepi nephri ne rel ea s ed from a drenergi c nerves ?
a . Ai rwa y (eg, bronchi ol a r) s mooth mus cl e
b. Arteri ol a r s mooth mus cl e
c. Iri s di l a tor mus cl es of the eyes
d. Si noa tri a l cel l s (pa cema ker) of the hea rt
e. Ventri cul a r myocytes
Questions 45 to 49
The fi gure bel ow s hows s ome of the ma i n el ements of norepi nephri ne (NE) s ynthes i s , rel ea s e, a cti ons , a nd other s teps i n a drenergi c
neurotra ns mi s s i on. You do not need the di a gra m to a ns wer thi s s eri es of ques ti ons , but s eei ng i t ma y a i d your a ns weri ng or revi ewi ng. Note tha t
the effector (ta rget) cel l on the fa r ri ght ha s ei ther a n -a drenergi c receptor or a -a drenergi c receptor.

45. Mi tochondri a i n the termi nus of a drenergi c nerve endi ngs conta i n a n a bunda nce of monoa mi ne oxi da s e (MAO). Wha t bes t s umma ri zes the
bi ol ogi ca l rol e of the MAO i n thes e a drenergi c nerves ?
a . Dri ves s tora ge ves i cl es tha t conta i n norepi nephri ne to the nerve endi ng s o tha t exocytoti c norepi nephri ne rel ea s e ca n occur i n res pons e to a n
a cti on potenti a l
b. Meta bol i ca l l y degra des NE tha t i s free (not s tored i n ves i cl es ) i n the nerve termi na l
c. Meta bol i zes dopa mi ne to norepi nephri ne
d. Provi des meta bol i c energy for nonexocytoti c rel ea s e of norepi nephri ne i n res pons e to a mpheta mi nes a nd other ca techol a mi ne-rel ea s i ng drugs
e. Synthes i zes ATP tha t i s requi red to tra ns port free i ntra neurona l norepi nephri ne i nto the s tora ge gra nul es /ves i cl es

46. Ma ny s tudi es ha ve s hown tha t a l a rge fra cti on of norepi nephri ne (NE) i n the norma l res ti ng a drenergi c neuron i s s tored i n membra ne-bound
ves i cl es or gra nul es . We a dmi ni s ter a drug tha t, over ti me, depl etes thi s s uppl y of neurotra ns mi tter a nd decrea s es the i ntens i ty of res pons es to
s ympa theti c nerve a cti va ti on. In vi tro s tudi es revea l tha t the drug a cts by i nhi bi ti ng upta ke of i ntra neurona l NE i nto the ves i cl es ; i t ha s no di rect
effect on ca techol a mi ne s ynthes i s , rel ea s e, or i ntera cti ons wi th i ts receptors . Whi ch drug fi ts thi s des cri pti on bes t?
a . Pa rgyl i ne
b. Pra zos i n
c. Propra nol ol
d. Res erpi ne
e. Tyra mi ne
47. A s ubs ta nce a bus er s el f-a dmi ni s ters coca i ne a nd experi ences a va ri ety of s i gni fi ca nt cha nges i n ca rdi ova s cul a r functi on, i n a ddi ti on to the
CNS-s ti mul a ti ng effects for whi ch the drug wa s us ed. Wha t s ta tement des cri bes the mecha ni s m by whi ch the coca i ne ca us ed i ts ma i n peri phera l
a nd CNS effects ?
a . Acti va tes 2 -a drenergi c receptors l ea di ng to i ncrea s ed NE rel ea s e
b. Bl ocks NE (a nd dopa mi ne, i n the CNS) reupta ke vi a the a mi ne pump
c. Di rectl y a cti va tes pos ts yna pti c - a nd -a drenergi c receptors , l ea di ng to s ym-pa thomi meti c (a drenomi meti c) res pons es
d. Inhi bi ts MAO, l ea di ng to i ncrea s ed i ntra neurona l NE l evel s
e. Prevents NE exocytos i s
48. We a dmi ni s ter a drug tha t i s a s el ecti ve a nta goni s t a t the pres yna pti c -receptors (2 ) i n the peri phera l nervous s ys tems . It ha s no effect on 1
receptors , receptors , or a ny other l i ga nd receptors tha t a re i mporta nt i n peri phera l nervous s ys tem functi on. Wha t i s the ma i n res pons e tha t i s
l i kel y to occur fol l owi ng a dmi ni s tra ti on of the 2 -bl ocker?
a . Acti va ti on of the a mi ne pump, s ti mul a ti on of norepi nephri ne reupta ke
b. Inhi bi ti on of dopa mi ne -hydroxyl a s e, the enzyme tha t converts i ntra neurona l dopa mi ne to norepi nephri ne
c. Increa s ed norepi nephri ne rel ea s e i n res pons e to ea ch a cti on potenti a l
d. Inhi bi ti on of norepi nephri ne exocytos i s
e. Sti mul a ti on of i ntra neurona l monoa mi ne oxi da s e a cti vi ty
49. Not s hown i n the di a gra m i s a n enzyme tha t ha s the a bi l i ty to meta bol i ca l l y i na cti va te NE tha t ha s di ffus ed a wa y from the s yna ps e. It i s a l s o
pres ent i n the l i ver (a s i s MAO) a nd i n the i ntes ti na l wa l l s . Among other thi ngs , the ra pi di ty wi th whi ch thi s enzyme ca ta bol i zes i ts s ubs tra tes
a ccounts for why norepi nephri ne, dopa mi ne, a nd dobuta mi ne ha ve extra ordi na ri l y s hort ha l f-l i ves , mus t be gi ven i ntra venous l y i n order to ca us e
mea ni ngful effects , ha ve negl i gi bl e effects when gi ven by other pa rentera l routes , a nd a re i neffecti ve when gi ven by mouth. An i nhi bi tor of thi s
drug i s us ed thera peuti ca l l y, but not for i ts a utonomi c effects . Wha t i s the na me of thi s enzyme?
a . Aroma ti c L-a mi no a ci d deca rboxyl a s e
b. Ca techol O-methyl tra ns fera s e (COMT)
c. Dopa mi ne -hydroxyl a s e
d. Phenyl etha nol a mi ne N-methyl tra ns fera s e
e. Tyros i ne hydroxyl a s e
50. We a dmi ni s ter a thera peuti c dos e of a drug tha t s el ecti vel y a nd competi ti vel y bl ocks the pos ts yna pti c -a drenergi c (1 ) receptors . It ha s no
effects on pres yna pti c -a drenergi c receptors (2 ) or -a drenergi c receptors found a nywhere i n the peri phery, whether a s a n a goni s t or a nta goni s t.
Wha t i s the mos t l i kel y drug?
a . Cl oni di ne
b. Phentol a mi ne
c. Phenoxybenza mi ne
d. Phenyl ephri ne
e. Pra zos i n
51. Fes toterodi ne i s a rel a ti vel y new drug tha t wa s hea vi l y ma rketed to pres cri bers a nd di rectl y to cons umers . It i s i ndi ca ted for the trea tment of
a n overa cti ve uri na ry bl a dder, reduci ng the s ymptoms of urge i nconti nence, uri na ry urgency, a nd uri na ry frequency. It prevents phys i ol ogi c
a cti va ti on of the bl a dders detrus or a nd s i mul ta neous l y prevents rel a xa ti on of the s phi ncter. Si de effects i ncl ude cons ti pa ti on, dry mouth, bl urred
vi s i on, photophobi a , uri na ry retenti on, a nd s l i ght i ncrea s es i n hea rt ra te. Another a dvi s ory for the drug: Hea t s troke a nd fever due to decrea s ed
s wea ti ng i n hot tempera tures ha ve been reported. Fes toterodi ne ha s no di rect effects on bl ood ves s el s tha t mi ght cha nge bl ood pres s ure. Ba s ed
on thi s i nforma ti on, wha t prototype drug i s mos t l i ke fes toterodi ne?
a . Atropi ne
b. -a drenergi c bl ockers (eg, propra nol ol )
c. Is oproterenol
d. Neos ti gmi ne
e. Phentol a mi ne
52. A morbi dl y obes e pers on vi s i ts the l oca l ba ri a tri c (wei ght l os s ) cl i ni c s eeki ng a pi l l tha t wi l l hel p s hed wei ght. The phys i ci a n pres cri bes
dextroa mpheta mi ne. In a ddi ti on to ca us i ng i ts expected centra l l y medi a ted a norexi geni c (a ppeti te-s uppres s a nt) a nd corti ca l -s ti mul a ti ng effects i t
ca us es a hos t of peri phera l a drenergi c effects tha t, for s ome pa ti ents , ca n prove fa ta l . Wha t bes t s umma ri zes the ma i n mecha ni s m by whi ch
dextroa mpheta mi ne, or a mpheta mi nes i n genera l , ca us e thei r peri phera l a utonomi c effects ?
a . Acti va tes MAO

b. Bl ocks NE reupta ke vi a the a mi ne pump/tra ns porter

c. Di s pl a ces , rel ea s es , i ntra neurona l NE
d. Enha nces NE s ynthes i s , l ea di ng to ma s s i ve neurotra ns mi tter overproducti on
e. Sta bi l i zes the a drenergi c nerve endi ng by di rectl y a cti va ti ng 2 receptors
53. We a dmi ni s ter a pha rma col ogi c dos e of epi nephri ne a nd obs erve (a mong other res pons es ) a di rect i ncrea s e of ca rdi a c ra te, contra cti l i ty, a nd
el ectri ca l i mpul s e conducti on ra tes . Whi ch a drenergi c receptor wa s res pons i bl e for thes e di rect ca rdi a c effects ?
a . 1
b. 2
c. 1
d. 2
e. 3a
54. A pa ti ent wi th a hi s tory of na rrow-a ngl e (a ngl e-cl os ure) gl a ucoma experi ences a s udden ri s e of i ntra ocul a r pres s ure tha t i s s uffi ci entl y s evere.
In a ddi ti on to pa i n there i s a n i mmi nent ri s k of perma nent vi s i on l os s . They requi re i mmedi a te trea tment, one el ement of whi ch i s a dmi ni s tra ti on
of echothi opha te. Wha t enzyme i s a ffected by thi s a utonomi c drug?
a . Tyros i ne hydroxyl a s es ti mul a ted
b. Acetyl chol i nes tera s e (AChE)i nhi bi ted
c. Ca techol -O-methyl tra ns fera s e (COMT)i nhi bi ted
d. Monoa mi ne oxi da s e (MAO)s ti mul a ted
e. DOPA deca rboxyl a s es ti mul a ted
55. A pa ti ent ha s es s enti a l hypertens i on, a nd l a b tes ts woul d s how tha t thei r ci rcul a ti ng ca techol a mi ne a nd pl a s ma reni n l evel s a re unus ua l l y
hi gh. The chos en thera peuti c a pproa ch for thi s pa ti ent i s to gi ve a s i ngl e drug tha t bl ocks both - a nd -a drenergi c receptors , thereby reduci ng
bl ood pres s ure by reduci ng both ca rdi a c output a nd tota l peri phera l res i s ta nce (s ys temi c va s cul a r res i s ta nce). Wha t drug i s mos t ca pa bl e of doi ng
tha t?
a . La beta l ol
b. Metoprol ol
c. Na dol ol
d. Pi ndol ol
e. Ti mol ol
56. A ma n who ha s been s urfi ng the Web i n s ea rch of a n a phrodi s i a c or s ome other a gent to enha nce s exua l prowes s a nd performa nce
di s covers yohi mbi ne. He cons umes the drug i n exces s a nd devel ops s ymptoms of toxi ci ty tha t requi re your i nterventi on. You cons ul t your preferred
drug reference a nd l ea rn tha t yohi mbi ne i s a s el ecti ve 2 -a drenergi c a nta goni s t tha t a cts ma i nl y i n the bra i ns medul l a ry ca rdi ova s cul a r control
center. Wha t woul d you expect a s a res pons e to thi s drug?
a . Bra dyca rdi a
b. Bronchocons tri cti on
c. Exces s i ve s ecreti ons by exocri ne gl a nds (s a l i va ry, l a cri ma l , etc)
d. Reduced ca rdi a c output from reduced l eft ventri cul a r contra cti l i ty
e. Ri s e of bl ood pres s ure
57. You pl a n to pres cri be s copol a mi ne, a s a tra ns derma l drug del i very s ys tem (s ki n pa tch), for a pa ti ent who wi l l be l ea vi ng for a n expens i ve crui s e
a nd i s very s us cepti bl e to moti on s i cknes s . Wha t comorbi di ty woul d wei gh a ga i ns t pres cri bi ng the drug beca us e i t i s mos t l i kel y to pos e a dvers e
effects or be trul y contra i ndi ca ted?
a . Angl e-cl os ure (na rrow-a ngl e) gl a ucoma
b. Bra dyca rdi a
c. Hi s tory of a l l ergi c rea cti ons to uncooked s hel l fi s h
d. Res ti ng bl ood pres s ure of 112/70
e. Hypothyroi di s m, mi l d
f. Pa rki ns on di s ea s e (ea rl y ons et, not currentl y trea ted)
58. A chi l d overdos es on a drug tha t a ffects both the a utonomi c a nd s oma ti c nervous s ys tems . As bl ood l evel s of the drug ri s e he experi ences
hypertens i on a nd ta chyca rdi a , a ccompa ni ed by s kel eta l mus cl e tremor. Further el eva ti ons of bl ood l evel s of the drug ca us e a l l the expected s i gns
a nd s ymptoms of a utonomi c ga ngl i oni c bl ocka de, pl us wea knes s a nd eventua l pa ra l ys i s of s kel eta l mus cl e. Whi ch drug di d the chi l d mos t l i kel y
i nges t?
a . Betha nechol
b. Ni coti ne
c. Pi l oca rpi ne
d. Propra nol ol (or a nother -a drenergi c bl ocker)
e. Scopol a mi ne
59. Ma ny cl i ni ca l s tudi es ha ve s hown tha t propra nol ol wi l l l ower bl ood pres s ure to va ryi ng degrees i n nea rl y every pa ti ent wi th es s enti a l
hypertens i on (i e, hi gh BP of unknown eti ol ogy or i denti fi a bl e ca us es , s uch a s pheochromocytoma or va s opres s or drug overdos e). Wha t i s the most
likely a nd phys i ol ogi ca l l y mos t i mporta nt mecha ni s m for propra nol ol s pres s ure-l oweri ng effect?

a . Induced a ba roreceptor refl ex tha t reduces va s ocons tri cti on us ua l l y ca us ed by a cti va ti on of the s ympa theti c nervous s ys tem
b. Inhi bi ted ca techol a mi ne rel ea s e from a drenergi c nerves a nd the a drena l medul l a (s upra rena l medul l a )
c. Reduced hea rt ra te a nd l eft ventri cul a r contra cti l i ty
d. Reduced tota l peri phera l res i s ta nce vi a di rect va s odi l a tor a cti ons i nvol vi ng ni tri c oxi de s ynthes i s i n endothel i a l cel l s
e. Sti mul a ted reni n rel ea s e, ul ti ma tel y l ea di ng to enha nced s ynthes i s of va s odi l a tor chemi ca l s s uch a s bra dyki ni n
60. A 35-yea r-ol d ma n who wei ghs 150 pounds a nd i s 5 feet 10 i nches ta l l i s tra ns ported to the emergency depa rtment i n s evere di s tres s . He
compl a i ns of epi s odes of s evere, throbbi ng hea da ches , profus e di a phores i s , a nd pa l pi ta ti ons . Ei ghteen months a go hi s phys i ci a n tol d hi m he i s
hea l thy except for es s enti a l hypertens i on, but he refus ed medi ca ti on a nd ha s not s een a hea l th ca re provi der for the l a s t yea r a nd a ha l f. He
deni es us e of a ny drugs , whether pres cri pti on or over-the-counter, l ega l or otherwi s e.
As s es s ment revea l s tha t he i s ta chyca rdi c a nd ha s a n i rregul a r pul s e (occa s i ona l prema ture ventri cul a r bea ts a re noted on hi s ECG). Hea rt ra te
a t res t i s a pproxi ma tel y 130 bea ts /mi n, s ometi mes more. Hi s res ti ng bl ood pres s ure i s 200/140 mm Hg. Thes e ca rdi ova s cul a r fi ndi ngs a re s hown i n
the fi gure bel ow.
The fi rs t yea r hous e offi cer who i s ca ri ng for thi s pa ti ent knows tha t a l l the ora l l y effecti ve -a drenergi c bl ockers a re a pproved for us e to trea t
es s enti a l hypertens i on, a nd concl udes tha t prompt l oweri ng of bl ood pres s ure i s es s enti a l for thi s pa ti ent. Therefore, he orders i ntra venous
a dmi ni s tra ti on of propra nol ol (a t the a rrow, a bove), a nd a l a rge dos e of the drug s i nce the s ymptoms s eem s evere. Unknown to the phys i ci a n i s
the fa ct tha t the pa ti ents s i gns a nd s ymptoms a re due to a pheochromocytoma (epi nephri ne-s ecreti ng tumor of the a drena l /s upra rena l medul l a ).
Wha t i s the mos t l i kel y ul ti ma te outcome of a dmi ni s teri ng thi s -bl ocker (or a ny other -bl ocker tha t l a cks -bl ocki ng or other va s odi l a tor
a cti vi ty), s uppl emented wi th no other medi ca ti on?

a . Hea rt fa i l ure, ca rdi ogeni c s hock, dea th

b. Long-l a s ti ng norma l i za ti on of hea rt ra te, contra cti l i ty, a nd bl ood pres s ure
c. Norma l i za ti on of bl ood pres s ures but pers i s tence of ta chyca rdi a
d. Res tora ti on of norma l s i nus ra te a nd rhythm, but no cha nge of bl ood pres s ure from predrug l evel s
e. Sudden a nd s i gni fi ca nt ri s e of s ys tol i c bl ood pres s ure a nd hea rt ra te

61. A pa ti ent wi th chroni c obs tructi ve pul mona ry di s ea s e (COPD, eg, emphys ema , chroni c bronchi ti s ) i s recei vi ng a n ora l l y i nha l ed mus ca ri ni c
receptor-bl ocki ng drug to ma i nta i n bronchodi l a ti on. Wha t drug bel ongs to tha t cl a s s ?
a . Al buterol
b. Di phenhydra mi ne
c. Ipra tropi um (or ti otropi um)
d. Pi l oca rpi ne
e. Vecuroni um
62. You gi ve a n effecti ve dos e of a tropi ne to a pers on who wa s poi s oned wi th a n AChE i nhi bi tor. Wha t s tructure wi l l conti nue to be overa cti va ted
by the exces s ACh a fter the a tropi ne i s gi ven?
a . Ai rwa y s mooth mus cl e
b. S-A node of the hea rt
c. Sa l i va ry a nd l a cri ma l gl a nds
d. Skel eta l mus cl e
e. Va s cul a r s mooth mus cl e
63. The hous e offi cer cons i ders pres cri bi ng na dol ol for a 53-yea r-ol d pa ti ent. Wha t preexi s ti ng condi ti on (comorbi di ty) woul d mos t l i kel y
contra i ndi ca te s a fe us e of thi s drug?
a . Angi na pectori s , chroni c-s ta bl e (effort-i nduced)
b. As thma
c. Es s enti a l hypertens i on
d. Hea rt fa i l ure, mi l d
e. Si nus ta chyca rdi a
64. A va ri ety of ophtha l mi c drugs , worki ng by s evera l ma i n mecha ni s ms of a cti on, a re us eful for ma na gi ng chroni c open-a ngl e gl a ucoma . Whi ch
one reduces i ntra ocul a r pres s ure by decrea s i ng the forma ti on of a queous humor, ra ther tha n by cha ngi ng the s i ze of the pupi l (s )?
a . Echothi opha te
b. Is ofl uropha te
c. Neos ti gmi ne
d. Pi l oca rpi ne
e. Ti mol ol
65. Its fa i r to s a y tha t epi nephri ne, norepi nephri ne, a nd a cetyl chol i ne pl a y the mos t i mporta nt rol es a s endogenous a goni s ts for the va ri ous
receptors under control of the peri phera l nervous s ys tems . However, dopa mi ne a l s o pl a ys a s ma l l but i mporta nt thera peuti c rol e, pa rti cul a rl y
when a dmi ni s tered IV a t low doses. Wha t other peri phera l effects ca n dopa mi ne ca us e a t us ua l thera peuti c dos es ?
a . Bronchodi l a ti on vi a rel a xa ti on of a i rwa y s mooth mus cl es
b. Di rect a cti va ti on of pres s ure receptors (eg, ba roreceptors ) i n res pons e to bl ood pres s ure cha nges tri ggered by other a goni s ts
c. Di rect a cti va ti on of the juxta gl omerul a r a ppa ra tus , rel ea s e of a l dos terone
d. Inhi bi ti on of epi nephri ne rel ea s e from chroma ffi n cel l s (eg, cel l s of the a drena l /s upra rena l medul l a )
e. Regul a ti on of rena l bl ood fl ow vi a control of rena l a rteri a l tone
66. Gua na drel i s a n a nti hypertens i ve drug: i t reduces a rteri ol a r cons tri cti on, a nd i n doi ng s o l owers BP by reduci ng the a mount of NE i n peri phera l
a drenergi c nerves . Lowered bl ood pres s ure i s not a ccompa ni ed by refl ex ta chyca rdi a , a nd i n fa ct a reducti on of hea rt ra te from predrug l evel s i s
the more common outcome. The ma i n ocul a r effect of gua na drel i s mi os i s . The wi des prea d a bol i ti on of s ympa theti c i nfl uences throughout the
body often ca us es di a rrhea a nd uri na ry frequency. Ba s ed on thi s des cri pti on, to whi ch prototypi c drug i s gua na drel mos t s i mi l a r i n terms of i ts
ul ti ma te qua l i ta ti ve a utonomi c effects , a nd i n terms of overa l l mecha ni s m of a cti on?
a . Acetyl chol i ne
b. Atropi ne
c. Epi nephri ne
d. Is oproterenol
e. Norepi nephri ne
f. Propra nol ol
g. Res erpi ne
67. An effecti ve dos e of a drug i s gi ven a nd the fol l owi ng res pons es occur:
Sti mul a tes hea rt ra te a nd, a ppa rentl y, l eft ventri cul a r s troke vol ume
Di l a tes s ome bl ood ves s el s but cons tri cts none
Di l a tes the bronchi (rel a xes a i rwa y s mooth mus cl es )
Ra i s es bl ood gl ucos e l evel s
Nei ther di l a tes nor cons tri cts the pupi l of the eye
Wha t drug i s ca pa bl e of ca us i ng a l l thes e res pons es ?
a . Atropi ne
b. Epi nephri ne

c. Is oproterenol
d. Norepi nephri ne
e. Phenyl ephri ne
68. It i s common to i ncl ude s ma l l a mounts of epi nephri ne (EPI) i n s ol uti ons of l oca l a nes theti cs tha t wi l l be a dmi ni s tered by i nfi l tra ti on (i njecti on
a round s ens ory nerve endi ngs ), a s when a s ki n l a cera ti on needs s uturi ng. Wha t i s the mos t l i kel y rea s on for, or outcome of, i ncl udi ng the EPI?
a . To a nta goni ze the otherwi s e i ntens e a nd common va s ocons tri ctor a nd hypertens i ve effects of the a nes theti c
b. To countera ct ca rdi a c depres s i on ca us ed by the a nes theti c
c. To prevent a na phyl a xi s i n pa ti ents who a re a l l ergi c to the a nes theti c
d. To reduce the ri s k of toxi ci ty ca us ed by s ys temi c a bs orpti on of the a nes theti c
e. To s horten the dura ti on of a nes theti c a cti on
69. In your thi rd yea r of medi ca l s chool , you a re conducti ng a s tudy on s i mi l a ri ti es a nd di fferences between two prototypi c drugs , phentol a mi ne
a nd pra zos i n, a s they a ffect ca rdi ova s cul a r res pons es . You s el ected two i denti ca l twi ns to ens ure thei r pha rma cogeneti c ma ke-up, a nd s o thei r
res pons es to drugs , i s a s nea rl y i denti ca l a s pos s i bl e. One twi n wi l l get the phentol a mi ne, the other gets pra zos i n.
Thei r ca rdi ova s cul a r pa ra meters a t ba s el i ne (res t) a re i denti ca l a nd norma l , a nd everythi ng el s e tha t mi ght ha ve a n i mpa ct on thei r drug
res pons es i s norma l a nd, wel l , i denti ca l . They a rent ta ki ng a ny other drugs .
One twi n gets a n IV i njecti on of phentolamine. Hi s mea n bl ood pres s ure fa l l s 20 mm Hg i n 20 s econds .
The other gets a n IV i njecti on of prazosin a t a n equa l l y effecti ve dos e i n terms of the bl ood pres s ure res pons e. Hi s mea n BP fa l l s by a n i denti ca l
a mount, 20 mm Hg, over the s a me ti me peri od, 20 s econds .
Which is the most likely difference you wi l l fi nd i n the res pons es of thes e two l a ds , one who got phentol a mi ne a nd the other who got a n
equi va l ent pres s ure-l oweri ng dos e of pra zos i n?
a . Phentol a mi ne wi l l tri gger a grea ter ba roreceptor-medi a ted refl ex i ncrea s e of hea rt ra te a nd contra cti l i ty tha n the pra zos i n wi l l .
b. Pra zos i n wi l l l ea d to a bi gger refl ex pos i ti ve i notropi c a nd chronotropi c res pons e tha n phentol a mi ne.
c. Pra zos i n wi l l bl ock a l l refl ex ca rdi a c res pons es beca us e i t a l s o ha s s trong -bl ocki ng a cti vi ty.
d. Pra zos i n wi l l l ea d to a grea ter ri s e of ca rdi a c output tha n phentol a mi ne by s el ecti vel y bl ocki ng norepi nephri ne-medi a ted va s odi l a ti on.
e. Phentol a mi ne wi l l reduce l eft ventri cul a r a fterl oa d, pra zos i n wi l l ra i s e i t.
70. A 48-yea r-ol d woma n ha s a hi s tory of mya s theni a gra vi s . She ha s been trea ted wi th a n ora l a cetyl chol i nes tera s e (AChE) i nhi bi tor for s evera l
yea rs , a nd ha s done wel l unti l now. Toda y s he pres ents i n your cl i ni c wi th mus cl e wea knes s a nd other s i gns a nd s ymptoms tha t coul d refl ect
ei ther a chol i nergi c cri s i s (exces s dos a ges of her ma i ntena nce drug) or a mya s theni c cri s i s (i ns uffi ci ent trea tment). You wi l l us e a ra pi dl y a cti ng
pa rentera l a cetyl chol i nes tera s e i nhi bi tor to hel p ma ke the di fferenti a l di a gnos i s . Whi ch drug woul d, therefore, be mos t a ppropri a te to us e?
a . Edrophoni um
b. Ma l a thi on
c. Phys os ti gmi ne
d. Pra l i doxi me
e. Pyri dos ti gmi ne
71. A pa ti ent pres ents wi th a n a na phyl a cti c rea cti on fol l owi ng a wa s p s ti ng. Wha t i s the drug of choi ce for trea ti ng the mul ti pl e ca rdi ova s cul a r a nd
pul mona ry probl ems tha t, i f not promptl y corrected, coul d l ea d to the pa ti ents dea th?
a . Atropi ne
b. Di phenhydra mi ne
c. Epi nephri ne
d. Is oproterenol
e. Norepi nephri ne
72. Ca rdi a c output i mproves when dobuta mi ne i s gi ven, by IV i nfus i on, to a 60-yea r-ol d ma n wi th a cute, s ymptoma ti c hea rt fa i l ure. By wha t
a drenergi c receptor-medi a ted a cti ons , a nd through whi ch ul ti ma te effects of i t, do thera peuti c dos es of dobuta mi ne ma i nl y ra i s e ca rdi a c output?
a . -a drenergi c a goni s t
b. -a drenergi c a nta goni s t
c. 1 -a drenergi c a goni s t
d. 1 -a drenergi c a nta goni s t
e. Mi xed a nd a goni s t
f. Mi xed a nd a nta goni s t
73. We a re us i ng novel i n vi tro methods to i nves ti ga te the fa te a nd pos t-s yna pti c a cti ons of norepi nephri ne, rel ea s ed upon a n a cti on potenti a l
genera ted i n a n a drenergi c nerve. An a cti on potenti a l i s genera ted a nd the pos ts yna pti c effector bri efl y res ponds . Al mos t i ns ta nta neous l y the
res pons e i s over. Wha t proces s ma i nl y a ccounted for the brevi ty of the res pons e, a nd termi na ti on of the rel ea s ed NEs a cti ons ?
a . Meta bol i s m by enzyme(s ) l oca ted nea r the pos ts yna pti c receptor(s ) a nd/or i n the s yna pti c cl eft
b. Reupta ke i nto the nerve endi ng
c. Meta bol i s m by ca techol -O-methyl tra ns fera s e (COMT)
d. Degra da ti on by mi tochondri a l monoa mi ne oxi da s e (MAO)
e. Convers i on to a fa l s e neurotra ns mi tter i n the nerve endi ng
74. We a re contempl a ti ng a dmi ni s tra ti on of a nons el ecti ve -a drenergi c bl ocker to a pa ti ent. In whi ch of the fol l owi ng condi ti ons i s thi s

cons i dered genera l l y a ccepta bl e, a ppropri a te, a nd s a fe?

a . Angi na , va s os pa s ti c (va ri a nt; Pri nzmeta l )
b. As thma
c. Bra dyca rdi a
d. Di a betes mel l i tus , i ns ul i n-dependent a nd poorl y control l ed
e. Hea rt bl ock (s econd degree or grea ter)
f. Hyperthyroi di s m, s ymptoma ti c a nd a cute
g. Severe conges ti ve hea rt fa i l ure
75. A pa ti ent pres ents i n the Emergency Depa rtment i n grea t di s tres s a nd wi th the fol l owi ng s i gns a nd s ymptoms :

Whi ch drug mos t l i kel y ca us ed thes e s i gns a nd s ymptoms ?

a . AChE i nhi bi tor
b. -a drenergi c bl ocker
c. Anti mus ca ri ni c
d. -a drenergi c bl ocker
e. Pa ra s ympa thomi meti c (mus ca ri ni c a goni s t)
f. Peri phera l l y a cti ng (neurona l ) ca techol a mi ne depl etor
76. Acebutol ol a nd pi ndol ol a re cl a s s i fi ed a s -a drenergi c bl ockers wi th i ntri ns i c s ympa thomi meti c a cti vi ty (ISA). In a pra cti ca l s ens e, wha t does
ISA mea n a propos the a cti ons of thes e two drugs ?
a . Are pa rti a l a goni s ts (mi xed a goni s t/a nta goni s ts )
b. Ca us e norepi nephri ne a nd epi nephri ne rel ea s e
c. Induce ca techol a mi ne s ynthes i s
d. Potenti a te the a cti ons of norepi nephri ne on -a drenergi c receptors
e. Us eful when ca rdi a c pos i ti ve i notropi c a nd chronotropi c effects a re wa nted
77. A 10-yea r-ol d boy i s di a gnos ed wi th Attenti on Defi ci t/Attenti on Defi ci t-Hypera cti vi ty di s order (ADD/ADHD). Whi ch drug i s mos t l i kel y to prove
effecti ve for rel i evi ng the boys ma i n s ymptoms ?
a . Dobuta mi ne
b. Methyl pheni da te
c. Pa ncuroni um
d. Pra zos i n
e. Scopol a mi ne
f. Terbuta l i ne
Questions 78 to 84
The ta bl e bel ow s hows the peri opera ti ve medi ca ti on a dmi ni s tra ti on record (MAR) for a n otherwi s e hea l thy 50-yea r-ol d woma n. (To ma ke thi ngs
i nteres ti nga nd wri te s ome a ddi ti ona l ques ti ons Il l devi a te from her a ctua l MAR a nd a s k a few ques ti ons a bout rel eva nt but hypotheti ca l
s cena ri os .) She i s a nons moker, cons umes no more tha n four gl a s s es of wi ne per week, a nd ha s no pers ona l or fa mi l i a l ri s k fa ctors for hea rt
di s ea s e or di a betes . She i s ta ki ng no other medi ca ti ons . Thi s pa ti ent ha d two s chedul ed (nonemergent) l a pa ros copi c a bdomi na l s urgeri es done
ba ck-to-ba ck i n the OR. The fi rs t wa s to remove a n a dnexa l (ova ry a nd/or fa l l opi a n tube) ma s s tha t ha d been pres ent for a coupl e of yea rs a nd
grew s l owl y a nd i rregul a rl y over a coupl e of yea rs , a nd to get a pa thol ogy report to s ee whether i t i s ca ncerous . Her pa thol ogy a ffected one ova ry.
Once the ova ry wa s removed a di fferent s urgeon performed a s econd procedure, through the s a me bel l y i nci s i ons , to a l l evi a te s ome i nconveni ent
uri na ry bl a dder probl ems .
Her MAR i s very typi ca l of wha t you woul d fi nd for ma ny otherwi s e hea l thy pa ti ents undergoi ng the s a me or s i mi l a r s urgeri es . The fi rs t drug
l i s ted, mi da zol a m, wa s gi ven i n the preop a rea ri ght before s he wa s tra ns ported to the OR (a nd I wi l l a ddres s i ts us e i n the CNS ques ti ons ; the
a bbrevi a ti on IVP next to mi da zol a m mea ns IV pus h, tha t i s , a bol us i njecti on). Al l the res t were gi ven i n the OR by a CRNA (certi fi ed regi s tered
nurs e a nes theti s t).
Us e the ta bl es da ta , or wha t you s houl d be a bl e to i nfer from i t, to a ns wer the next s even ques ti ons .

78. Ephedri ne wa s the fi rs t drug a dmi ni s tered a fter a nes thes i a premedi ca ti on a nd i nducti on wi th s evera l pa rentera l drugs . Wha t bes t des cri bes
ephedri nes mecha ni s m of a cti on?
a . Di rectl y, s el ecti vel y, s trongl y s ti mul a tes -a drenergi c receptors i n the peri phera l va s cul a ture
b. Enha nces norepi nephri ne rel ea s e by bl ocki ng pres yna pti c -receptors
c. Increa s es norepi nephri ne s ynthes i s
d. Inhi bi ts norepi nephri nes i ntra neurona l meta bol i c i na cti va ti on
e. Rel ea s es i ntra neurona l norepi nephri ne i nto the s yna ps e, a l s o wea kl y but di rectl y a cti va tes a l l a drenergi c receptors
79. Ephedri ne a nd drugs tha t a ct i n s i mi l a r wa ys or ca us e s i mi l a r effects ha ve a va ri ety of thera peuti c us es . Gi ven the ba ckground i nforma ti on
provi ded for thi s pa ti ent, a nd the ti mi ng of ephedri ne a dmi ni s tra ti on on the medi ca ti on a dmi ni s tra ti on record, wha t i s the mos t l i kel y rea s on why
the ephedri ne wa s gi ven?
a . Ca us e bronchodi l a ti on s o mecha ni ca l s upport of venti l a ti on woul d be ea s i er
b. Countera ct CNS depres s i on ca us ed by the i nducti on a gents
c. Inhi bi t s i noa tri a l a nd a tri oventri cul a r noda l a utoma ti ci ty to termi na te or prevent a nes thes i a -rel a ted ca rdi a c a rrhythmi a s
d. Lower hea rt ra te tha t wa s ra i s ed exces s i vel y by the a nes theti c drugs
e. Ra i s e bl ood pres s ure tha t wa s l owered exces s i vel y by the i nducti on a gents
80. As s ume, hypotheti ca l l y, tha t the s urgery ha d to be done emergentl y. The pa ti ent ha d been ta ki ng a nother drugs ti l l i n her ci rcul a ti on a t
us ua l l y effecti ve concentra ti ons tha t wea kened but di d not compl etel y el i mi na te a l l of ephedri nes peri phera l a utonomi c effects . Whi ch drug(s )
woul d be mos t l i kel y to do tha t?
a . Atenol ol (or metoprol ol )
b. Coca i ne or a tri cycl i c a nti depres s a nt (eg, i mi pra mi ne)
c. Tri metha pha n (or hexa methoni um)

d. Pa rgyl i ne (or a s i mi l a r nons el ecti ve MAO i nhi bi tor)

e. Propra nol ol
81. Shortl y a fter the s urgi ca l wounds were cl os ed a nd dres s ed, a nd ri ght before the pa ti ent wa s tra ns ferred to the pos ta nes thes i a ca re uni t (PACU),
s he recei ved neos ti gmi ne. Wha t wa s the rea s on for whi ch i t wa s gi ven?
a . Ra i s e a nd s upport bl ood pres s ure duri ng recovery
b. Ra i s e or otherwi s e control bra dyca rdi a upon recovery from a nes thes i a
c. Res tore norma l neurotra ns mi s s i on i n the bra i n, s i nce i t ha d been s uppres s ed by the i nducti on a nd a nes theti c a gents
d. Revers e s kel eta l neuromus cul a r bl ocka de/pa ra l ys i s
e. Suppres s uri na ry bl a dder functi on to reduce the ri s k of pos topera ti ve bl a dder i nconti nence
82. The pa ti ent got her dos e of gl ycopyrrol a te mere s econds before the neos ti gmi ne wa s i njected. Thi s i s done routi nel y i n thous a nds of s urgeri es
i n whi ch the drugs us ed a re i denti ca l or a t l ea s t very s i mi l a r to thos e us ed here. To whi ch pha rma col ogi c cl a s s does gl ycopyrrol a te mos t l i kel y
bel ong?
a . -Adrenergi c a goni s t
b. Anti mus ca ri ni c (a tropi ne-l i ke)
c. Chol i nes tera s e i nhi bi tor
d. Mus ca ri ni c receptor a goni s t
e. Ni coti ni c receptor (s kel eta l mus cl e; NM) a goni s t
83. The pa ti ent i n the ca s e pres ented here wa s not fa ci ng a ny emergent or i mmi nentl y l i fe-threa teni ng probl ems , s o s kel eta l mus cl e pa ra l ys i s a nd
i ntuba ti on were rel a ti vel y s tra i ghtforwa rd procedures , not a t a l l rus hed. Now a s s ume, hypotheti ca l l y, tha t emergency i ntuba ti on wa s requi red, a nd
s ucci nyl chol i ne (SuCh) wa s us ed beca us e of i ts very ra pi d ons et of a cti on. As s ume further tha t a s l ow i nfus i on of SuCh wa s us ed to ma i nta i n
pa ra l ys i s throughout the procedure; bl ood l evel s of the drug were kept wel l i n the thera peuti c ra nge; no cura re-l i ke (nondepol a ri zi ng) bl ocker wa s
us ed; a nd the pa ti ent ha d no geneti c or other fa ctors tha t woul d a ffect the drugs pha rma coki neti cs or a cti on. When the s urgery i s done, wha t drug
woul d be gi ven to revers e s ucci nyl chol i nes effects ?
a . Atropi ne
b. Betha nechol
c. Neos ti gmi ne
d. Phys os ti gmi ne
e. Nothi ng
84. Now a s s ume thi s pa ti ent recei ved betha nechol s evera l hours a fter her a bdomi na l s urgery, a fter effects of a l l the drugs us ed i ntra opera ti vel y,
except for morphi ne a nd ketorol a c (a na l ges i cs ) ha d worn off. Her hea rt ra te fel l s l i ghtl y a nd s he experi enced s ome wheezi ng. Whi ch word or
phra s e mos t l i kel y a ccounts for or des cri bes thes e ca rdi a c a nd pul mona ry res pons es ?
a . Expected s i de effects
b. Idi os yncra s y
c. Pa ra s ympa theti c ga ngl i oni c a cti va ti on
d. Refl ex (ba roreceptor) s uppres s i on of ca rdi a c ra te
e. Undi a gnos ed a s thma
85. Unti l recentl y the drug ri todri ne ha s been us ed to s uppres s uteri ne contra cti ons i n s ome women who a re i n prema ture l a bor. Si de effects of
the drug i ncl ude ri s es of hea rt ra te a nd i ncrea s es i n the force of contra cti on of the hea rt. Hi gh-output hea rt fa i l ure (ca us ed by exces s i vel y
i ncrea s ed ca rdi a c output) a nd pul mona ry edema ha ve occurred, a nd i n s ome ca s es the outcome ha s been fa ta l . Ri todri ne a l s o ca us es
bronchodi l a ti on. It ha s no va s ocons tri ctor effects , nor a ny effects on the s i ze of the pupi l (s ) of the eye(s ). The des cri pti on mos t cl os el y fi ts the
cha ra cteri s ti cs of wha t cl a s s of drugs ?
a . -Adrenergi c a goni s t
b. Atropi ne-l i ke/a nti mus ca ri ni c drug
c. -Adrenergi c a goni s t
d. -Adrenergi c bl ocker
e. Mus ca ri ni c receptor a goni s t (pa ra s ympa thomi meti c)
86. A pa ti ent wi th a hi s tory of a s thma experi ences s i gni fi ca nt bronchocons tri cti on a nd urti ca ri a , a nd drug-i nduced hi s ta mi ne rel ea s e i s a ma i n
contri butor to thes e res pons es . Whi ch drug i s mos t l i kel y to ha ve ca us ed thes e probl ems not beca us e i t ha s a ny bronchocons tri ctor or hi s ta mi ne
a goni s t effects i n i ts own ri ght, but beca us e i t qui te effecti vel y rel ea s es hi s ta mi ne from ma s t cel l s ?
a . Atropi ne
b. Morphi ne
c. Neos ti gmi ne
d. Pa ncuroni um
e. Propra nol ol
87. Duri ng s urgery the a nes thes i ol ogi s t a dmi ni s ters tri metha pha n, cl a s s i fi ed a s a n a utonomi c ga ngl i oni c bl ocker to a n a nes theti zed pa ti ent. Wha t
woul d you expect i n res pons e to thi s drug?
a . Bra dyca rdi a medi a ted by a cti va ti on of the ba roreceptor refl ex
b. Increa s ed GI tra ct moti l i ty, pos s i bl e s ponta neous defeca ti on
c. Increa s ed s a l i va ry s ecreti ons

d. Mi os i s
e. Va s odi l a ti on
88. Fi rs t-genera ti on (ol der) hi s ta mi ne H 1 bl ockers s uch a s di phenhydra mi ne, phenothi a zi ne a nti ps ychoti c drugs (eg, chl orproma zi ne), a nd tri cycl i c a nti depres s a nts (eg, i mi pra mi ne) ha ve pha rma col ogi c a cti ons , s i de effects , toxi ci ti es , a nd contra i ndi ca ti ons tha t a re very s i mi l a r to thos e of
whi ch other drug?
a . Atropi ne
b. Betha nechol
c. Is oproterenol
d. Neos ti gmi ne
e. Propra nol ol
89. A 6-yea r-ol d i s tra ns ported to the Emergency Depa rtment by a pa rent, who s a ys the boy took a l a rge a mount of a n a l l ergy medi ca ti on. The s ol e
a cti ve i ngredi ent i n the product the pa rent menti ons i s di phenhydra mi ne, a nd i t i s cl ea r the chi l d i s experi enci ng toxi ci ty from a n overdos e. The
i ntern, fres h out of medi ca l s chool , orders pa rentera l a dmi ni s tra ti on of neos ti gmi ne, a nd the medi ca ti on order i s not ques ti oned. Wha t a dvers e
effect of the di phenhydra mi ne wi l l pers i s t fol l owi ng neos ti gmi ne a dmi ni s tra ti on?
a . Bronchocons tri cti on a nd wheezi ng
b. Del i ri um, ha l l uci na ti ons , a nd other CNS ma ni fes ta ti ons of toxi ci ty
c. Profus e s ecreti ons from l a cri ma l , mucus , a nd s wea t gl a nds
d. Skel eta l mus cl e tremor or fa s ci cul a ti ons
e. Ta chyca rdi a
90. In between your M1 a nd M2 yea rs you a re vol unteeri ng i n a hos pi ta l i n a very poor pa rt of the worl d. Thei r drug s el ecti on i s l i mi ted. A pa ti ent
pres ents wi th a cute ca rdi a c fa i l ure, for whi ch your preferred drug i s dobuta mi ne, gi ven i ntra venous l y. However, there i s none a va i l a bl e. Whi ch
other drug, or combi na ti on of drugs , woul d be a s ui ta bl e a l terna ti ve, gi vi ng the pha rma col ogi c equi va l ent of wha t you wa nt the dobuta mi ne to do?
(Al l thes e drugs a re a va i l a bl e i n pa rentera l formul a ti ons .)
a . Dopa mi ne (a t a very hi gh dos e)
b. Ephedri ne
c. Ephedri ne pl us propra nol ol
d. Norepi nephri ne pl us phentol a mi ne
e. Phenyl ephri ne pl us a tropi ne
91. In genera l , s tructures tha t a re a ffected by s ympa theti c i nfl uences res pond to both s ympa theti c neura l a cti va ti on a nd to the hormona l
component, epi nephri ne rel ea s ed from the a drena l medul l a . Whi ch s tructure/functi on i s uni que i n tha t i t res ponds to epi nephri ne, but not
norepi nephri ne, a nd ha s no di rect s ympa theti c neural control ?
a . Ai rwa y (tra chea l , bronchi ol a r) s mooth mus cl e: rel a xa ti on
b. Atri oventri cul a r node: i ncrea s ed a utoma ti ci ty a nd conducti on vel oci ty
c. Corona ry a rteri es : cons tri cti on
d. Iri s of the eye: di l a ti on (mydri a s i s )
e. Rena l juxta gl omerul a r a ppa ra tus : reni n rel ea s e
92. Adrenergi c nerves to the hea rt a re a cti va ted, l ea di ng to a refl ex i ncrea s e of hea rt ra te a nd ca rdi a c contra cti l i ty, i n res pons e to a s udden a nd
s i gni fi ca nt fa l l of bl ood pres s ure. Thos e s ympa theti c nerves rel ea s e norepi nephri ne (NE). Wha t i s the ma i n phys i ol ogi c mecha ni s m by whi ch the
a cti ons of the rel ea s ed NE a re termi na ted?
a . Di ffus i on a wa y from pos ts yna pti c receptors
b. Hydrol ys i s by nons peci fi c dea mi na s es
c. Meta bol i c i na cti va ti on by MAO
d. Meta bol i c i na cti va ti on by ca techol -O-methyl tra ns fera s e
e. Reupta ke i nto the a drenergi c nerve from whi ch the NE wa s rel ea s ed
93. The fi gure bel ow s hows s evera l res pons es mea s ured i n a s ubject (hea l thy; recei vi ng no other drugs ) a t res t (before) a nd a fter recei vi ng a dos e
of a n unknown drug. Note: The bl ood pres s ures s hown ca n be cons i dered mea n bl ood pres s ure; the fa l l ca us ed by the unknown wa s ma i nl y due to
a fa l l of di a s tol i c pres s ure.

Whi ch drug mos t l i kel y ca us ed the obs erved res pons es ?

a . Atropi ne
b. Is oproterenol
c. Neos ti gmi ne
d. Phenyl ephri ne
e. Propra nol ol
94. A 59-yea r-ol d ma n ha s a hi s tory of emphys ema from 40 yea rs of ci ga rette s moki ng; hyperchol es terol emi a tha t i s bei ng ma na ged wi th
a torva s ta ti n; a nd Sta ge 2 es s enti a l hypertens i on for whi ch he i s ta ki ng metol a zone. He pres ents i n cl i ni c toda y wi th hi s ma i n new compl a i nts :
nocturi a , uri na ry frequency, a nd a n i na bi l i ty to uri na te forceful l y a nd empty hi s bl a dder. Fol l owi ng a compl ete work-up, the phys i ci a n a rri ves a t a
di a gnos i s of beni gn pros ta ti c hypertrophy (BPH). We s ta rt da i l y thera py wi th ta ms ul os i n. Wha t i s the mos t l i kel y s i de effect the pa ti ent ma y
experi ence from the ta ms ul os i n, a nd a bout whi ch he s houl d be forewa rned?
a . Bra dyca rdi a
b. Increa s ed ri s k of s ta ti n-i nduced s kel eta l mus cl e pa thol ogy
c. Orthos ta ti c hypotens i on
d. Photophobi a a nd other pa i nful res pons es to bri ght l i ghts
e. Wheezi ng or other exa cerba ti ons of the emphys ema
95. A pa ti ent wa l ks out of the ophtha l mol ogi s ts offi ce a nd i nto bri ght s unl i ght a fter a comprehens i ve eye exa m, for whi ch he recei ved a topi ca l
ophtha l mi c drug. The drug ha s not onl y di l a ted hi s pupi l s , but a l s o i mpa i red hi s a bi l i ty to focus hi s eyes up-cl os e.
The drug thi s pa ti ent recei ved wa s mos t l i kel y cl a s s i fi ed a s , or worked mos t s i mi l a r to, whi ch prototype?
a . Acetyl chol i ne
b. Epi nephri ne
c. Homa tropi ne
d. Is oproterenol

e. Pi l oca rpi ne
f. Propra nol ol
96. Youve recei ved a pprova l from the Ins ti tuti ona l Revi ew Boa rd to s tudy the i n vi tro (ti s s ue ba th) res pons i venes s of i s ol a ted huma n a rteri ol a r
s egments (obta i ned duri ng s urgery) to a va ri ety of pha rma col ogi c a nd other i nterventi ons . The ti s s ue s a mpl es a re 1 cm-l ong cyl i nders of
otherwi s e-norma l (but now denerva ted) a rteri ol es obta i ned from the l ower l egs of pa ti ents undergoi ng a mputa ti on s urgery.
The s etup a l l ows you to perfus e the ves s el s wi th a s ol uti on tha t wi l l keep the ti s s ue functi ona l l y a nd s tructura l l y i nta ct for ma ny hours ; to
moni tor a nd cha nge perfus i on pres s ure (mm Hg; a na l ogous to bl ood pres s ure i n the i nta ct orga ni s m) a nd perfus a te fl ow (mL/mi n); a nd to
a s s es s the effects of va ri ous va s oa cti ve drugs on the s ys tem.
You a dd ACh to the perfus a te to gi ve a concentra ti on i denti ca l to the pl a s ma concentra ti on of ACh tha t ca us es expected res pons es i n a n i nta ct
huma n.
Under thi s experi menta l s etup, a ddi ng ACh ca us es a ri s e of perfus i on pres s ure a nd a decrea s e of fl ow, both of whi ch ba s i ca l l y refl ect
va s ocons tri cti on.
Wha t i s the mos t l i kel y expl a na ti on for thes e fi ndi ngs ?
a . ACh rel ea s ed norepi nephri ne from the endothel i um, whi ch ca us ed va s ocons tri cti on
b. Atropi ne wa s a dded to the ti s s ue ba th before a ddi ng the ACh
c. Botul i num toxi n wa s a dded to the ba th before a ddi ng the ACh
d. The va s cul a r endothel i um ha s been da ma ged or removed (denuded)
e. Thi s res pons e i s preci s el y wha t wed expect wi th i njecti on of ACh i nto the i nta ct huma n
97. A 33-yea r-ol d woma n becomes poi s oned a fter recei vi ng a n i njecti on of i l l i ci tl y prepa red a nd overl y concentra ted botul i num toxi n. Wha t i s the
ma i n neurochemi ca l mecha ni s m by whi ch thi s Clostridium toxi n ca us es i ts effects ?
a . Di rectl y a cti va tes a l l mus ca ri ni c a nd ni coti ni c receptors
b. Inhi bi ts ACh rel ea s e from a l l chol i nergi c nerves
c. Prevents neurona l norepi nephri ne reupta ke
d. Rel ea s es norepi nephri ne vi a a nonexocytoti c proces s
e. Sel ecti vel y a nd competi ti vel y bl ocks ni coti ni c receptors
98. A 43-yea r-ol d woma n wi th di a gnos ed mya s theni a gra vi s , a nd ta ki ng pyri dos ti gmi ne da i l y, pres ents i n the neurol ogy cl i ni c wi th profound
s kel eta l mus cl e wea knes s . You a re uns ure whether s he i s experi enci ng a chol i nergi c cri s i s or a mya s theni c cri s i s , s o you a dmi ni s ter a us ua l l y
a ppropri a te di a gnos ti c dos e of pa rentera l edrophoni um. As s ume the pa ti ent wa s a ctua l l y experi enci ng a chol i nergi c cri s i s . Wha t i s the mos t l i kel y
res pons e to the edrophoni um?
a . Hypertens i ve cri s i s from peri phera l va s ocons tri cti on
b. Myoca rdi a l i s chemi a , a nd a ngi na , from drug-i nduced ta chyca rdi a a nd corona ry va s ocons tri cti on
c. Prema ture ventri cul a r contra cti ons from i ncrea s ed ventri cul a r a utoma ti ci ty
d. Prompt i mprovement of s kel eta l mus cl e tone a nd functi on
e. Venti l a tory di s tres s or fa i l ure
99. A pa ti ent ta kes a ma s s i ve overdos e of di phenhydra mi ne, s ufferi ng not onl y s i gni fi ca nt CNS depres s i on but a l s o numerous a nd s eri ous
peri phera l a utonomi c s i de effects . By wha t mecha ni s m di d di phenhydra mi ne exert i ts untowa rd peri phera l a utonomi c a cti ons ?
a . Acti va ti on of both 1 a nd 2 a drenoceptors
b. Bl ocka de of -a drenergi c receptors
c. Competi ti ve a nta goni s m of ACh a cti ons on mus ca ri ni c receptors
d. Ma s s i ve, di rect overa cti va ti on of ga ngl i oni c ni coti ni c receptors
e. Sudden rel ea s e of epi nephri ne from the a drena l medul l a (s upra rena l medul l a )
100. A pa ti ent wi th a recent drug poi s oni ng i s tra ns ported to the emergency depa rtment. The phys i ci a n correctl y orders a dmi ni s tra ti on of
pra l i doxi me a s pa rt of the comprehens i ve emergency trea tment pl a n. Whi ch bes t des cri bes who the pa ti ent wa s ?
a . A 13-yea r-ol d boy who to took a n overdos e of methyl pheni da te for hi s ADD/ADHD.
b. A 43-yea r-ol d who took a n overdos e of neos ti gmi ne, pres cri bed for her mya s theni a gra vi s , i n a s ui ci de a ttempt.
c. A 6-yea r-ol d who got i nto the fa mi l y medi ci ne ca bi net a nd took 10 a dul t dos es of her da ds pra zos i n.
d. A fa rm/fi el d worker a cci denta l l y dous ed wi th i ns ecti ci de from a n overfl yi ng crop-dus ter pl a ne.
e. An a s thma pa ti ent who a cci denta l l y ga ve hi ms el f a n i ntra venous i njecti on of epi nephri ne i n a n a ttempt to s el f-trea t a devel opi ng a na phyl a cti c
rea cti on.
101. To fa ci l i ta te a certa i n eye exa m you wa nt to ca us e mydri a s i s , but not a l ter norma l control of a ccommoda ti on. Al l of the fol l owi ng drugs a re
a va i l a bl e a s topi ca l ophtha l mi c formul a ti ons . Whi ch one wi l l di l a te the pupi l wi thout a l teri ng a ccommoda ti on?
a . Atropi ne
b. Epi nephri ne
c. Homa tropi ne
d. Is oproterenol
e. Pi l oca rpi ne
f. Ti mol ol
102. A 26-yea r-ol d woma n ha s rhi norrhea , exces s i ve l a cri ma ti on, a nd ocul a r conges ti on from a bout wi th the common col d. Di phenhydra mi ne
provi des s ymptoma ti c rel i ef. Wha t i s the mos t l i kel y mecha ni s m by whi ch thi s drug rel i eved her s ymptoms ?

a . -a drenergi c a cti va ti on (a goni s t, va s ocons tri ctor)

b. -a drenergi c bl ocka de
c. Ca l ci um cha nnel bl ocka de
d. Hi s ta mi ne (H 2 ) receptor bl ocka de
e. Mus ca ri ni c receptor bl ocka de
103. You ha ve trea ted dozens of pa ti ents wi th a cute hypotens i on from va ri ous ca us es , i ncl udi ng overdos es of a nti hypertens i ve drugs , a l l of whi ch
ca n ca us e hypotens i on. Your us ua l a pproa ch to res tori ng bl ood pres s ure, a nd one tha t ha s worked wel l every ti me before, i s to i nject x mg of
phenyl ephri ne i ntra venous l y. Toda y a pa ti ent wi th s evere drug-i nduced hypotens i on pres ents i n the Emergency Depa rtment. He ha s been ta ki ng
thi s drug for ma ny months . He i s not vol ume-depl eted, nor hemorrha gi ng. You gi ve the phenyl ephri ne a t the s a me dos e a nd by the s a me route a s
you a l wa ys ha ve. It ca us es no cha nge of bl ood pres s ure. Whi ch drug di d the pa ti ent mos t l i kel y ta ke a nd overdos e on?
a . Atenol ol
b. Betha nechol
c. Pra zos i n
d. Propra nol ol
e. Res erpi ne
104. Thi s i s a s tra nge da y for you i n the ED. Now you ha ve to trea t a nother normovol emi c pa ti ent wi th a cute drug-i nduced hypotens i on, a nd gi ve the
us ua l l y correct a nd effecti ve dos e of phenyl ephri ne. Thi s ti me the drug ca us es a va s opres s or res pons e tha t i s fa r grea ter tha n youve ever
encountered when gi vi ng the very s a me dos e: s ys tol i c pres s ure ri s es dra ma ti ca l l y, i f not da ngerous l y. Wha t drug di d the pa ti ent mos t l i kel y ta ke?
a . Atenol ol
b. Betha nechol
c. Pra zos i n
d. Propra nol ol
e. Res erpi ne
105. A pa ti ent who wi l l be new to your pra cti ce ma kes a n a ppoi ntment for thei r fi rs t vi s i t. Your nurs e a s ks them to bri ng i n a l l thei r current
pres cri bed medi ca ti ons a nd a ny OTC drugs they ta ke regul a rl y. They compl y. One OTC drug i s a popul a r bra nd-na me product tha t conta i ns
doxyl a mi ne a s i ts s ol e a cti ve i ngredi ent. Whi ch property or cha ra cteri s ti c bes t des cri bes thi s drug?
a . Li kel y to l ower hea rt exces s i vel y
b. Ma y be a ca us e of di a rrhea tha t the pa ti ent s a ys he often gets
c. Shoul d not be us ed by pa ti ents wi th pros ta ti c hypertrophy or a ngl e-cl os ure gl a ucoma
d. Tends to ra i s e bl ood pres s ure through a typi ca l ca techol a mi ne-l i ke va s ocons tri ctor (-a drenergi c) mecha ni s m
e. Us ed duri ng the da y, hel ps them keep a wa ke a nd a l ert vi a a wea k a mpheta mi ne-l i ke a cti on i n the CNS

The Peripheral Nervous Systems: Autonomic and Somatic Nervous System Pharmacology
Answers
Ive reproduced bel ow the fi gure you s a w i n the ques ti ons s ecti on, but modi fi ed i t to s how the nerve types a nd l oca ti ons , a nd the receptors , to
s a ve you a bi t of pa ge-fl i ppi ng when you revi ew your a ns wers .

37. The answer is b. (Brunton, pp 171-177; Katzung, pp 80-87.) Heres a s i mpl e rul e: i n the peri phera l nervous s ys tems tha t i s , the s oma ti c nervous
s ys tem a nd both bra nches of the a utonomi c nervous s ys temthe fi rs t nerve out of the CNS (i n thi s di a gra m, a, c, e, f, a nd h) i s a l wa ys chol i nergi c
a nd the ACh rel ea s ed from thos e nerves a l wa ys a cti va tes the ni coti ni c s ubtype of chol i nergi c receptor on the pos ts yna pti c ta rget cel l (s ).
38. The answer is c. (Brunton, pp 171-177; Katzung, pp 80-87) Another rul e, wi th one i mporta nt excepti on: a l l the efferents i n the peri phera l nervous
s ys tems a re chol i nergi c except pos tga ngl i oni c s ympa theti cs goi ng to s tructures other than sweat glands (a nd the arrector pili mus cl es too). There a re
ei ght nerves i n the s chema ti c. Seven of thema l l except the ma jori ty of pos tga ngl i oni c s ympa theti cs (nerve d)a re chol i nergi c (s ynthes i ze a nd

rel ea s e ACh a s thei r neurotra ns mi tter). The ma i n pos tga ngl i oni c s ympa theti c fi bers (except thos e i nnerva ti ng s wea t gl a nds ) s ynthes i ze a nd
rel ea s e NE (not epi nephri ne; a ns wer d) a s thei r neurotra ns mi tter, a nd s o a re a drenergi c (or nora drenergi c i f you prefer) nerves . Wha t el s e ca n you
ca l l nerve d? A pos tga ngl i oni c s ympa theti c nerve to certa i n s mooth mus cl es , to ca rdi a c mus cl e, a nd certa i n exocri ne gl a nds except s wea t gl a nds .
(Be s ure to s ee the expl a na ti on for Ques ti ons 38 a nd 40.)
Atropi ne (a ) i s i ncorrect. It s el ecti vel y a nd competi ti vel y bl ocks the effects of ACh (a nd other mus ca ri ni c a goni s ts ) on mus ca ri ni c receptors . In the
di a gra m a bove, thos e receptors a re found on s tructures i nnerva ted by nerves b a nd g.
Ans wer b i s i ncorrect. NE, nerve ds neurotra ns mi tter, i s a n effecti ve a goni s t for -a drenergi c receptors (1 a nd 2 ) a nd for 1 receptors .
Bronchodi l a ti on ca us ed by s ympa theti c a cti va ti on requi res a cti va ti on of 2 receptors ; NE ca nnot do tha t but EPI, rel ea s ed from the a drena l
(s upra rena l ) medul l a , certa i nl y ca n. And once NE ha s been rel ea s ed from i ts neurons a nd a cti va tes i ts pos ts yna pti c receptors , i ts a cti ons a re
promptl y termi na ted by reupta ke (vi a a n a mi ne pump tha t ca n be bl ocked by coca i ne or tri cycl i c a nti depres s a nts ). Hydrol ys i s i n the s yna pti c cl eft
(e) i s the mecha ni s m by whi ch the a cti ons of ACh, rel ea s ed from chol i nergi c nerves , i s termi na ted.
39. The answer is d. (Brunton, pp 194-200; Katzung, pp 85-86.) The a cti ons of norepi nephri ne (NE), rel ea s ed from a drenergi c nerves , a re termi na ted by
neurona l reupta ke. (Dont forget tha t thi s reupta ke proces s i s i nhi bi ted by coca i ne a nd tri cycl i c a nti depres s a nts , a nd the outcome i s i ncrea s ed a nd
more prol onged a drenergi c effects of NE beca us e NE l i ngers l onger a nd a ccumul a tes i n the s yna ps e, expos ed to i ts pos ts yna pti c ta rgets .) Al l the
other nerves s hown i n the di a gra m a re chol i nergi c; the a cti ons of the ACh they rel ea s e a re termi na ted promptl y by hydrol ys i s (vi a
a cetyl chol i nes tera s e).
40. The answer is g. (Brunton, pp 119, 196-198, 201, 400-401; Katzung, pp 84-87.) The neurotra ns mi tter rel ea s ed from nerve d, the pos tga ngl i oni c
s ympa theti c fi bers (to s tructures other tha n s wea t gl a nds a nd a rrector pi l i mus cl es ), i s norepi nephri ne. NE ca n a cti va te -a drenergi c receptors
(both 1 a nd 2 ), a nd 1 receptors (not 2 ). Of cours e, di fferent s tructures ha ve di fferent s ubtypes of thes e receptors : s tructures s uch a s a rteri ol es
a nd the i ri s di l a tor mus cl e ha ve 1 receptors ; 1 receptors a re found i n the hea rt a nd i n the juxta gl omerul a r a ppa ra tus (ki dneys ; they hel p regul a te
reni n rel ea s e there), whi l e 2 receptors (not a cti va ted by NE) a re found on va ri ous s mooth mus cl es , ma i nl y i n the a i rwa ys . So, the onl y correct
res pons e to the ques ti on whi ch receptors a re a cti va ted? rea l l y depends on whi ch s tructure i s bei ng i nnerva ted. As a fi na l note, NE ca nnot
a cti va te chol i nergi c receptors , a nd s o a ns wers e a nd f a re defi ni tel y i ncorrect.
41. The answer is b. (Brunton, pp 173-180; Katzung, pp 80f, 90t, 120.) The pos tga ngl i oni c s ympa theti c fi bers i nnerva ti ng s wea t gl a nds a nd a rrector pi l i
mus cl es a re chol i nergi c. Tha t i s the exception to the rul e tha t a l l pos tga ngl i oni c s ympa theti c fi bers a re a drenergi c. How do you know i ts
chol i nergi c? A va ri ety of bi ochemi ca l a nd hi s tochemi ca l methods ca n prove tha t ACh i s the neurotra ns mi tter. They a l s o s how tha t there i s
a bunda nt a cetyl chol i nes tera s e (AChE), whi ch hydrol yzes ACh, i n the s yna pti c cl eft. But were goi ng to ma ke the a s s es s ment pha rma col ogi ca l l y: We
ca n prevent rel ea s e of neurotra ns mi tter from nerve g wi th botul i num toxi n, whi ch a ffects onl y (a nd all) chol i nergi c nerves ; a nd we ca n prevent the
res pons e of the s wea t gl a nds i nnerva ted by nerve g wi th a tropi ne, the prototype mus ca ri ni c receptor a nta goni s ta drug tha t ha s no effects on
ni coti ni c (or other) receptors (eg, a ns wer d) a t us ua l dos es . Li kewi s e, ni coti ni c receptor bl ockers (or ni coti ne i ts el f) ha ve no effect a t thi s s i te
a nother rea s on why a ns wer d i s i ncorrect. And how you do know i ts pa rt of the SNS? Swea t gl a nds a re a cti va ted (s ecreti ons a re i ncrea s ed) a nd
a rrector pi l i mus cl es contra ct (the ha i r on our s ki n s ta nds on end) when the enti re SNS i s a cti va ted, s uch a s i n the fi ght or fl i ght res pons e; a nd
i f you tra ce the ori gi ns of the prega ngl i oni c nerves tha t a cti va te the pos tga ngl i oni c ones , they ema na te from the s a me regi ons of the s pi na l cord
from whi ch a l l other s ympa theti c prega ngl i oni c fi bers a ri s ethe thora ci c a nd l umba r regi ons .
Coca i ne (a ) i s i ncorrect. It, a nd tri cycl i c a nti depres s a nts (eg, a mi tri ptyl i ne, i mi pra mi ne, etc), bl ock neurona l reupta ke of NE. Tha t i s , i ts s i te of
a cti on i s a t the neuroeffector juncti on of pos tga ngl i oni c s ympa theti c neurons (nerve d)a l l of them except thos e tha t i nnerva te mos t s wea t gl a nds
a nd a rrector pi l i mus cl es , of cours e.
42. The answer is c. (Brunton, pp 173-180; Katzung, pp 80f, 90t.) The nerve i s chol i nergi c, s o the neurotra ns mi tter i t a cts on, pos ts yna pti ca l l y, mus t be
ei ther ni coti ni c or mus ca ri ni c. Ni coti ni c receptors a re found on cel l bodi es of a l l pos tga ngl i oni c nerves (i n both SNS a nd PNS; NN receptors ), on the
a drena l medul l a (a l s o NN), a nd on s kel eta l mus cl e (s oma ti c nervous s ys tem, NM)a t the fi rs t s yna ps es out of the CNS. Chol i nergi c receptors a t
a l l other s i tes a re mus ca ri ni c, defi ned by the fa ct tha t thos e receptors a re competi ti vel y bl ocked by a tropi ne. Be s ure to s ee the expl a na ti on for
Ques ti on 37, a bove.
43. The answer is h. (Brunton, pp 177, 258-262; Katzung, pp 80f, 466-479, 474t.) Vecuroni um a nd s evera l rel a ted drugs (a l l of whi ch ha ve curoni um or, a t
l ea s t, cur i n thei r generi c na mes ) a re nondepol a ri zi ng s kel eta l neuromus cul a r bl ockers (qui te di fferent, mecha ni s ti ca l l y, from s ucci nyl cho-l i ne,
the depol a ri zi ng bl ocker). They s peci fi ca l l y a nd competi ti vel y bl ock a cti va ti on of ni coti ni c receptors (NM) on s kel eta l mus cl e by ACh, thereby
preventi ng s kel eta l mus cl e depol a ri za ti on a nd s ubs equent contra cti on; a nd ha ve no effect on mus ca ri ni c receptors or a ny of the a drenergi c
receptor s ubtypes . Remember s omethi ng a bout the na ti ves of the Ama zon obta i ni ng a poi s onous s ubs ta nce from the s ki n of certa i n s peci es of
frogs , putti ng i t on the ti ps of thei r da rts , a nd us i ng tha t to ki l l thei r di nner wi th a bl ow-gun? Tha t wa s cura re, d-tubocura ri ne, the very ol d
prototype nondepol a ri zi ng s kel eta l neuromus cul a r bl ocker, a s weve come to know i t.
44. The answer is a. (Brunton, pp 173f, 194-200; Katzung, pp 80f, 84-87.) The neurotra ns mi tter of pos tga ngl i oni c s ympa theti c nerves i s norepi nephri ne
(unl es s the ta rget cel l s a re s wea t gl a nds or a rrector pi l i mus cl es , i n whi ch ca s e the fi na l neurotra ns mi tter i s a cetyl chol i ne). Norepi nephri ne i s a
good a goni s t for - a nd 1 -a drenergi c receptors , but not for 2 . Ai rwa y s mooth mus cl e cel l s a re not i nnerva ted by the s ympa theti c nervous s ys tem.
In terms of s ympa theti c i nfl uences , bronchodi l a ti on (a i rwa y s mooth mus cl e rel a xa ti on) i s ca us ed onl y by epi nephri ne rel ea s ed from the a drena l
(s upra rena l ) medul l a .
Here a ga i n i s the di a gra m to whi ch Ques ti ons 45 to 49 referred.

45. The answer is b. (Brunton, pp 172, 194-210; Katzung, pp 87, 88f.) Whi l e mi tochondri a i n vi rtua l l y a l l cel l s i n whi ch they a re found a re i mporta nt for
oxi da ti ve phos phoryl a ti on a nd ATP s ynthes i s , I a s ked a bout the mi tochondri a l MAO tha t i s ri ch i n a drenergi c neurons . There MAO wi l l degra de NE
tha t i s free (i e, not s a fel y s tored a wa y) i n the s tora ge ves i cl es . If tha t i ntra ves i cul a r upta ke i s i nhi bi ted, NE s tores wi l l be depl eted.
None of the s tructures or proces s es s hown i n the di a gra m a re res pons i bl e for i ntra neurona l movement of NE-conta i ni ng s tora ge ves i cl es to, a nd
ul ti ma te fus i on wi th, the nerve endi ng (a ). Meta bol i s m of dopa mi ne to NE (c) occurs i n the s tora ge ves i cl es vi a the enzyme, dopa mi ne hydroxyl a s e. MAO does not provi de energy for nonexocytoti c NE rel ea s e (d), a nd pl a ys no rol e i n ATP s ynthes i s (e).
46. The answer is d. (Brunton, pp 211, 400-401, 783; Katzung, pp 83f, 178.) Res erpi ne bl ocks i ntra neurona l s ynthes i s a nd s tora ge of norepi nephri ne (NE),
a nd the a bi l i ty of the reupta ke proces s to re-s tore norepi nephri ne tha t ha s a l rea dy been rel ea s ed from a n a cti va ted a drenergi c nerve (s ee

Ques ti on 39), thereby expos i ng the free i ntra neurona l NE to degra da ti on by i ntra neurona l MAO. Thi s i s i mporta nt for other rea s ons : the fi na l
s ynthes i s of NE from i ts precurs or, dopa mi ne, occurs i n the ves i cl es . If dopa mi ne entry i s bl ocked, a s i t i s by res erpi ne, NE s ynthes i s i s decrea s ed.
Res erpi ne a l s o bl ocks ves i cul a r upta ke of dopa mi ne i n pa rts of the CNS.
Pa rgyl i ne (a ) i s a nons el ecti ve MAO i nhi bi tor. Note tha t unl i ke res erpi ne, MAO i nhi bi tors do not i nhi bi t i ntra neurona l s tora ge of NE. Ra ther, they
i nhi bi t meta bol i c i na cti va ti on of NE i n a drenergi c nerve endi ngs (or, a t other s i tes , other monoa mi nes ). Thi s l ea ds to a bui l d-up of
norepi nephri ne i n a drenergi c nerve endi ngs . Pra zos i n (b) a nd propra nol ol (c) a re a drenergi c receptor bl ockers (1 a nd 1-2 , res pecti vel y) a nd ha ve
no di rect effect on NE s tora ge. Tyra mi ne (e) i s a n i ndi rect-a cti ng s ympa thomi meti c tha t di s pl a ces a nd rel ea s es neurona l NE vi a a proces s tha t does
not i nvol ve exocytos i s .
47. The answer is b. (Brunton, pp 116, 198; Katzung, pp 143, 451t, 460, 463.) Coca i ne (a nd tri cycl i c a nti depres s a nts s uch a s i mi pra mi ne) a re cl a s s i c
exa mpl es of drugs tha t i nhi bi t ca techol a mi ne reupta ke by the a mi ne pump, whi ch i s the ma i n proces s by whi ch rel ea s ed NE (or dopa mi ne) reenters the neuron a nd i ts receptor-medi a ted effects a re termi na ted phys i ol ogi ca l l y. In the pres ence of coca i ne or a tri cycl i c, rel ea s ed
neurotra ns mi tter l i ngers a nd a ccumul a tes i n the s yna ps e (neuroeffector juncti on), a nd s o perti nent a drenergi c res pons es a ppea r hei ghtened or
more i ntens e, a nd prol onged. The pump i s a l s o i mporta nt for the neurona l upta ke, a nd ul ti ma te effects , of s uch ca techol a mi ne-rel ea s i ng drugs a s
ephedri ne, ps eudo-ephedri ne, a mpheta mi nes , methyl pheni da te, a nd tyra mi ne.
As l ong a s a n a drenergi c s yna ps e i s pres ent (a s i t i s i n the di a gra m) a nd expos ed to coca i ne or a tri cycl i c a nti depres s a nt, the drugs effects a re
not dependent on whether the effector (ta rget) i s s mooth mus cl e, ca rdi a c mus cl e, or a n exocri ne gl a nd of a ny s ort.
Coca i ne ha s no di rect effect on 2 -a drenergi c receptors (a ), nor on a ny of the pos ts yna pti c a drenergi c receptors (c). Li kewi s e, the drug ha s no
effect on MAO (d) nor on the exocytoti c rel ea s e of NE i n res pons e to a n a cti on potenti a l (e).
There i s no di rect functi ona l l i nk between the a mi ne pump a nd s uch proces s es a s NE rel ea s e (exocytoti ca l l y or otherwi s e) or a cti va ti on of pres yna pti c (2 ) a drenergi c receptors .
48. The answer is c. (Brunton, pp 201-210, 212; Katzung, pp 84-87.) The a drenergi c neurona l 2 (pres yna pti c) receptor, l i ke a l l other a drenergi c receptors ,
i s G-protei n-coupl ed. When the receptor i s a cti va ted by a s ui ta bl e a goni s t, i t s i gna l s the neuron to s top further NE rel ea s e fol l owi ng a n a cti on
potenti a l . Norepi nephri ne i ts el f i s one s uch a goni s t; i ts a cti va ti on of the pres yna pti c 2 receptor, whi ch occurs concomi ta nt wi th a cti va ti on of
pos ts yna pti c (1 or 1 ) a drenergi c receptors (dependi ng on wha t the di s ta l ta rget cel l i s ), provi des a phys i ol ogi c feedba ck s i gna l tha t ha l ts
further NE rel ea s e. Tha t i s , rel ea s ed NE regul a tes the rel ea s e of more NE from the very neuron from whi ch the neurotra ns mi tter ca me.
Al though a cti va ti on of both the pres yna pti c 2 receptors a nd NE reup-ta ke by the a mi ne pump/tra ns porter occurs a l mos t s i mul ta neous l y, there
i s no di rect functi ona l or bi ochemi ca l l i nka ge between the two. Tha t i s , bl ocki ng (or s ti mul a ti ng) the 2 receptor wi l l not di rectl y a ffect NE reupta ke
(a ), nor wi l l drugs tha t a ffect the a mi ne pump neces s a ri l y ha ve a ny di rect effect on the 2 receptors a nd the functi on they s erve. There i s no effect
on norepi nephri ne s ynthes i s (b, whether by dopa mi ne -hydroxyl a s e or other enzymes i nvol ved i n neurotra ns mi tter s ynthes i s ), nor on MAO (d).
Note: Cl oni di ne, whi ch you typi ca l l y (a nd correctl y) thi nk of a s a centra l l y a cti ng a nti hypertens i ve drug, a cts a s a n 2 a goni s t i n the peri phery. Its
turni ng off of NE rel ea s e, then, ca n contri bute to reduced va s ocons tri cti on (a nd other a drenergi c proces s es medi a ted by NE), whi ch i n turn hel ps
l ower bl ood pres s ure. However, cl oni di ne i s a very l i pophi l i c drug. When i t i s gi ven i n us ua l dos es , by the us ua l route (ora l or tra ns derma l ), the
drug enters the CNS wel l , a nd ra ther promptl y, a nd i t a cts there (i n the ca rdi ova s cul a r control center of the bra i ns medul l a ) to i nhi bi t s ympa theti c
outfl ow. It i s tha t centra l effect tha t a ccounts for the drugs ma i n a nti hypertens i ve mecha ni s m.
49. The answer is b. (Brunton, pp 138, 200; Katzung, pp 87, 88f, 490-491.) Onl y COMT ha s the properti es noted i n the ques ti on. Enta ca pone i s a n exa mpl e
of a COMT i nhi bi tor tha t i s us ed thera peuti ca l l y. It i s gi ven ma i nl y to ma na ge Pa rki ns on di s ea s e, i n conjuncti on wi th l evodopa . It i nhi bi ts the
peri phera l (eg, i ntes ti na l ) convers i on of l evodopa to dopa mi ne (reca l l tha t dopa mi ne i ts el f does not cros s the bl ood-bra i n ba rri er), a nd i s a n
a l terna ti ve to ca rbi dopa (whi ch i nhi bi ts ca rboxyl a s es ). (See Ques ti ons 113, 114, 147, 166, a nd 174-176, i n the CNS cha pter, for more i nforma ti on on
thes e a nd other dopa mi nergi c drugs for pa rki ns oni s m.)
The other enzymes l i s ted i n the ques ti on a re i nvol ved i n ca techol a mi ne s ynthes i s . Aroma ti c L-a mi no a ci d deca rboxyl a s e (a ) converts DOPA to
dopa mi ne, whi ch i s then converted to norepi nephri ne by dopa mi ne -hydroxyl a s e (c). In the a drena l medul l a , phenyl etha nol a mi ne Nmethyl tra ns fera s e (d) converts s ome norepi nephri ne to epi nephri ne. Tyros i ne hydroxyl a s e (e) converts tyros i ne to DOPA.
50. The answer is e. (Brunton, pp 206t, 212, 305-307; Katzung, pp 152f, 154, 167-180, 189.) Pra zos i n s el ecti vel y a nd competi ti vel y bl ocks 1 a drenergi c
receptors a nd, unl i ke ma ny other -bl ockers (phentol a mi ne, phenoxybenza mi ne), ha s vi rtua l l y no pres yna pti c (2 ) effects a t us ua l dos es .
None of the other drugs fi t the bi l l : Cl oni di ne (a ) i s a centra l l y a cti ng -a drenergi c a goni s t us ed ma i nl y a s a n a nti hypertens i ve drug. The ma i n
cons equence of tha t effect i s a reducti on of s ympa theti c outfl ow tha t reduces a l l of the three ma i n determi na nts of bl ood pres s ure: hea rt ra te,
s troke vol ume, a nd tota l peri phera l res i s ta nce. Phentol a mi ne i s a competi ti ve -bl ocker, but i t bl ocks both pres yna pti c (2 ) a nd pos ts yna pti c (1 )
receptors more or l es s equa l l y wel l . Phenoxybenza mi ne (c) i s s i mi l a r to phentol a mi ne i n terms of i ts receptor ta rgets . However,
phenoxybenza mi nes a cti ons l a s t fa r l onger tha n thos e of phentol a mi ne, a nd they a ri s e from noncompetitive/irreversable -bl ocka de. (Ra ther tha n
merel y occupyi ng the receptors , a s i s the ca s e wi th mos t a nta goni s ts , phenoxybenza mi ne a l kyl a tes the receptors , perma nentl y i mpa i ri ng thei r
a bi l i ty to i ntera ct wi th s ui ta bl e a goni s ts ). Phenyl ephri ne (d) i s a s trong a goni s t for a l l the -a drenergi c receptors , ha s no -a nta goni s t a cti vi ty, a nd
exerts no di rect effects of a ny type on -receptors .
51. The answer is a. (Brunton, pp 225-232; Katzung, pp 120-124). You proba bl y never l ea rned or rea d a bout fes toterodi ne (i ts s ti l l rel a ti vel y new), but
tha t ma kes no di fference i n terms of bei ng a bl e to a ns wer thi s ques ti on.
The des cri pti on of thi s drug i s , i n rea l i ty, a l s o a n excel l ent des cri pti on of ma ny of the properti es of a tropi ne, the prototype mus ca ri ni c receptor
bl ocki ng drug, a nd of nea rl y a dozen other a nti mus ca ri ni cs ma rketed for overa cti ve bl a dder. In terms of bl a dder functi on, pa ra s ympa theti c
i nfl uences tend to promote uri ne fl ow; a nti mus ca ri ni cs , then, tend to s uppres s tha t effect. (Convers el y, s ympa theti c i nfl uences , vi a -a drenergi c
receptor a cti va ti on, tend to s uppres s uri ne fl ow a nd -a drenergi c bl ockers ca us e the oppos i te.)
You s houl d be a bl e to el i mi na te i ncorrect a ns wers by a s i mpl e proces s of el i mi na ti on. For exa mpl e, do -bl ockers (b) ca us e the vi s ua l , uri na ry
tra ct, s wea t gl a nd, or ca rdi ova s cul a r res pons es noted i n the ques ti on? Not a t a l l , nor do i s oproterenol (c; 1/2 a goni s t), neos ti gmi ne (d;
chol i nes tera s e i nhi bi tor, whi ch produces preci s el y the oppos i te res pons es tha t a tropi ne, fes toterodi ne, a nd a l l the other a nti mus ca ri ni cs us ed for
bl a dder overa cti vi ty do), or phentol a mi ne (e; nons el ecti ve -bl ocker).
Note: The mecha ni s m of a cti on of fes toterodi ne, i ts i ndi ca ti ons , s i de effects , a nd a dvers e res pons es a nd jus t a bout a ny other rel eva nt
property you ca n i ma gi ne, i ncl udi ng the dos ea re exa ctl y the s a me a s thos e of a n ol der a nd wi del y a dverti s ed bra nd na me drug, i ts s ol e a cti ve
generi c i ngredi ent bei ng tol terodi ne. Coi nci denta l ? Not a t a l l . Both drugs ha ve the s a me a cti ve meta bol i te.

52. The answer is c. (Brunton, pp 116, 206t, 297-299; Katzung, pp 136f, 142.) Ampheta mi nes (dextroa mpheta mi ne, metha mpheta mi ne, a mpheta mi ne, a nd
s evera l rel a ted drugs ) ca n be cl a s s i fi ed a s i ndi rect-a cti ng s ympa thomi meti cs (a drenomi meti cs ). They a re tra ns ported i nto the a drenergi c nerve
endi ng by the a mi ne pump, di s pl a ce NE from i ts s tora ge ves i cl es (vi a proces s es tha t a re not dependent on a n a cti on potenti a l ), a nd ca us e the
s tored neurotra ns mi tter to be rel ea s ed i nto the s yna pti c s pa ce. At tha t poi nt, a l l the expected effects of NE on i ts receptors a nd effectors occur.
Thes e drugs ha ve no di rect effects , whether a s a n a goni s t or a nta goni s t, on the a drenergi c receptors . Thei r a cti ons a re whol l y dependent on
i ntra neurona l ca techol a mi ne s tores .
Ampheta mi nes a nd rel a ted drugs ha ve no a bi l i ty to di rectl y a cti va te (or i nhi bi t) MAO (a ); to a ffect i ntra neurona l NE s tores (c); or s ti mul a te (or
i nhi bi t) i ntra neurona l NE s ynthes i s (d). The a mi ne pump upon whi ch coca i ne a nd rel a ted drugs ma i nl y a ct i s l oca ted on the pres yna pti c a drenergi c
nerve endi ng, a s a re the ma i n popul a ti ons of 2 receptors ; however, thes e drugs do not di rectl y a ffect, ei ther by s ti mul a ti ng or bl ocki ng, thos e 2
receptors (e).
53. The answer is c. (Brunton, pp 177-180, 283-286; Katzung, pp 89t, 90t.) The i notropi c (contra cti l i ty), chronotropi c (ra te), a nd dromotropi c (conducti on
vel oci ty-rel a ted) effects of epi nephri ne on the hea rt a re medi a ted through a cti va ti on of 1 -a drenergi c receptors . Thes e receptor s i tes medi a te a n
epi nephri ne-i nduced i ncrea s ed fi ri ng ra te of the SA node (s ponta neous , or Pha s e 4, depol a ri za ti on), i ncrea s ed conducti on vel oci ty through the AV
node a nd the Hi s -Purki nje s ys tem, a nd i ncrea s ed contra cti l i ty a nd conducti on vel oci ty of a tri a l a nd ventri cul a r mus cl e. Epi nephri ne a cti va ti on of
a drenoceptors does not a ffect ca rdi a c functi on i n a ny phys i ol ogi ca l l y or thera peuti ca l l y i mporta nt wa yexcept for the cruci a l rol e of
a drenoceptors a s medi a tors of corona ry a rtery va s ocons tri cti on (cl ea rl y a va s cul a r s mooth mus cl e, not ca rdi a c mus cl e, phenomenon). The 2 a drenergi c receptors pl a y vi rtua l l y no di rect rol e i n ca rdi a c s ti mul a ti on. They a re more i mporta nt i n the rel a xa ti on of tra cheobronchi a l s mooth
mus cl e, di l a ti on of a rteri ol es tha t s erve s kel eta l mus cl es , i ncrea s ed s ecreti on of i ns ul i n by the pa ncrea s , a nd to a l es s er degree rel a xa ti on of the
detrus or of the uri na ry bl a dder. (Li pol ys i s i n fa t cel l s a nd mel a toni n s ecreti on by the pi nea l gl a nd a ppea r to i nvol ve s ti mul a ti on of 3 -a drenergi c
receptors . However, we do not ha ve a ny cl i ni ca l l y us eful drugs tha t s el ecti vel y a cti va te or bl ock the 3 receptors , a nd s o you mi ght wa nt to ques ti on
how much you l ea rn a bout the 3 s .)
54. The answer is b. (Brunton, pp 239-242, 245, 1785t, 1788; Katzung, pp 105-111.) Echothi opha te i odi de i s a l ong-a cti ng (i rrevers i bl e, whi ch ba s i ca l l y
mea ns very l ong a cti ng i n terms of the dura ti on of effects ) a cetyl chol i nes tera s e i nhi bi tor. It i s us ed topi ca l l y on the eye for the trea tment of
va ri ous types of gl a ucoma . By i ncrea s i ng s yna pti c l evel s of a cetyl chol i ne, i t i ncrea s es contra cti on of the ci rcul a r mus cl es of the eye, ca us i ng the
pupi l s to cons tri ct (mi os i s ). Tha t reduces mecha ni ca l obs tructi on of a queous humor outfl ow vi a the Ca na l of Schl emm a nd the tra becul a r
mes hwork i n the a ngl e of the a nteri or cha mber. (In contra s t, s ympa theti c a cti va ti on ca us es mydri a s i s by a cti va ti ng the ra di a l mus cl es through a goni s t effects , a nd ca n l ea d to i ncrea s ed i ntra ocul a r pres s ure.) Ma xi mum reducti on of i ntra ocul a r pres s ure occurs wi thi n 24 hours , a nd the effect
ma y pers i s t for s evera l da ys . The drug i s wa ter-s ol ubl e, whi ch a ffords a pra cti ca l a dva nta ge over the l i pi d-s ol ubl e i s ofl uropha te (a nother
chol i nes tera s e i nhi bi tor us ed to trea t gl a ucoma ).
Note: Ha d I l i s ted a drug wi th a generi c na me endi ng i n the s uffi x -s ti gmi ne, you no doubt woul d ha ve a ns wered correctl y a nd i mmedi a tel y.
However, echothi opha te i s one of thos e chol i nes tera s e i nhi bi tors tha t i s not a s ti gmi ne. If youre unfa mi l i a r wi th the drugthi s one or a ny one a s
you work your wa y through the ques ti ons by a l l mea ns l ook i t up!
Tyros i ne hydroxyl a s e (a ) i s i nvol ved i n the bi os ynthes i s of ca techol a mi nes . COMT (c) i s i nvol ved i n extra neurona l meta bol i s m of
ca techol a mi nes , whi l e MAO (d) i s the ma jor i ntra neurona l enzyme tha t degra des NE i n a drenergi c nerves . Forms of MAO a re a l s o found i n, a nd
i mporta nt i n, the l i ver a nd pa rts of the CNS. DOPA deca rboxyl a s e (e) ca ta l yzes the meta bol i s m of DOPA (di hydroxyphenyl a l a ni ne) to dopa mi ne a s
pa rt of the ca techol a mi ne bi os yntheti c pa thwa y.
55. The answer is a. (Brunton, pp 328-329, 780-781; Katzung, pp 151-162.) La beta l ol i s a competi ti ve a nta goni s t a t both - a nd -a drenergi c (both 1 a nd
2 ) receptors . [Thi s tri ck mi ght hel p you remember tha t l a beta l ol bl ocks both ma i n types of a drenergi c receptors : ta ke the fi rs t two l etters i n
l a beta l ol a nd revers e themla tra npos es to al, a s i n alphaa nd then a dd the next four l etters beta. Youl l s i mpl y ha ve to memori ze the na me of
a nother i mporta nt -/-bl ocker, ca rvedi l ol .) Note, too, tha t the generi c na mes of a l l the drugs l i s ted end i nolola grea t ti p-off tha t a drug ha s bl ocki ng a cti vi ty. In fa ct, every drug wi th a generi c na me tha t ends i n -olol i s a -bl ocker.
La beta l ol s -bl ocki ng a cti ons a re wea k compa red wi th i ts a cti ons a t the -receptors , but they a re cl i ni ca l l y i mporta nt i n terms of bl ood
pres s ure control nonethel es s . Thi s di fference i s s omewha t concentra ti on-dependent: a t rel a ti vel y l ow bl ood l evel s , a s mi ght be a chi eved wi th
typi ca l ora l dos es , i t i s a bout three ti mes more potent a s a -bl ocker tha n a s a n -bl ocker (do not commi t thi s to memory!). Wi th hi gher
concentra ti ons , s uch a s thos e often a chi eved wi th pa rentera l (eg, IV) dos i ng, the i ntens i ty of -bl ocka de i ncrea s es cons i dera bl y wi th l i ttl e
i ncrea s e i n -bl ocki ng effi ca cy (a nother poi nt tha ts not pri ori ty knowl edge now!). One of l a beta l ol s ma i n us es i s for ma na gi ng es s enti a l
hypertens i on (a l l the ora l l y a dmi ni s tered -bl ockers a re i ndi ca ted for es s enti a l hypertens i on, a nd for chroni c-s ta bl e a ngi na ). It l owers pres s ure i n
three wa ys : reduces hea rt ra te, reduces contra cti l i ty, a nd a l s o reduces reni n rel ea s e, thereby reduci ng the forma ti on of a ngi otens i n II a nd,
i ndi rectl y, rel ea s e of a l dos terone. Al l thes e effects a re medi a ted by 1 bl ocka de. Gi ven pa rentera l l y (IV), l a beta l ol i s often a fi rs t-choi ce a gent for
ma na gi ng urgent hypertens i ve cri s es when more effi ca ci ous (a nd potenti a l l y more da ngerous ) IV drugs a rent i ndi ca ted or ca nnot be gi ven s a fel y.
Metoprol ol (b; a nd a tenol ol a nd a cebutol ol , not l i s ted) ha ve a preferenti a l (but certa i nl y not a bs ol ute!) a nd dos e-dependent effect on 1
receptors (ca rdi os el ecti vi ty) vers us 2 , a nd ha ve no -bl ocki ng a cti ons . Rel a ti vel y hi gh dos es of thos e drugs ca n (a nd often do) bl ock 2 receptors ,
a nd a ny dos e ma y pos e s eri ous ri s ks of bronchocons tri cti on or broncho-s pa s m for pa ti ents wi th a s thma . Na dol ol (c) a nd ti mol ol (d) a re
nons el ecti ve -bl ockers . (One property to remember for na dol ol i s i ts rel a ti vel y l ong ha l f-l i fe; for ti mol ol you mi ght wa nt to reca l l tha t a topi ca l
ophtha l mi c dos a ge form i s often us ed for chroni c opena ngl e gl a ucoma .) Pi ndol ol (d) i s a nons el ecti ve -bl ocker a nd a l s o exerts s trong i ntri ns i c
s ympa thomi meti c a cti vi ty (ISA; i e, pa rti a l a goni s t-a nta goni s t a cti vi ty).
56. The answer is e. (Brunton, pp 207t, 212, 309, 383t; Katzung, p 155.) Whether you memori ze tha t yohi mbi ne i s a s el ecti ve 2 a nta goni s t i s up to you,
but you s houl d know wha t the ma i n effects of a s el ecti ve 2 a nta goni s t a re. Tha t, of cours e, depends on knowi ng wha t 2 receptors a t l ea s t i n
the peri phera l a utonomi c nervous s ys temdo i n the phys i ol ogi ca l s ens e. Reca l l tha t the prepondera nce of phys i ol ogi ca l l y i mporta nt 2 receptors
a re l oca ted on a drenergi c nerve termi na l s (or nerve endi ngs ). When s ti mul a ted by a s ui ta bl e a goni s t, the res pons e i s a turni ng-off of further NE
rel ea s e. Beca us e NE i s the neurotra ns mi tter rel ea s ed from a drenergi c nerves a nd i t i s a n excel l ent a goni s t, the pres yna pti c 2 receptors upon
whi ch NE a cts s erve a s the ma i n phys i ol ogi c mecha ni s m for regul a ti ng neurotra ns mi tter rel ea s e.
So, when we bl ock thos e receptors wi th yohi mbi ne, we enha nce the a ppa rent overa l l a cti vi ty of the s ympa theti c nervous s ys tem on i ts effectors
by i nterferi ng wi th norepi nephri nes a bi l i ty to turn-off i ts own rel ea s e. Of the res pons es l i s ted, onl y hypertens i on (owi ng to the va s ocons tri ctor
effects of NE on pos ts yna pti c -a drenergi c receptors ) occurs a s a res ul t of yohi mbi ne (or of NE exces s ). The other ma i n effects you s houl d
a nti ci pa te woul d be ca rdi a c s ti mul a ti on (ra te, contra cti l i ty, el ectri ca l i mpul s e conducti on ra tes ; a l l 1 -medi a ted effects ) a nd, us ua l l y of l es s
cl i ni ca l cons equence, mydri a s i s ().

In terms of the a phrodi s i a c effects , the drug proba bl y i ncrea s es a rous a l vi a a n a cti on i n the CNS, but the mecha ni s m i s nt known for s ure; a nd i t
i ncrea s es the vi gor of eja cul a ti on, whi ch i s predomi na ntl y a n -medi a ted effect. (Reca l l tha t erecti on pri ma ri l y i nvol ves mus ca ri ni c-chol i nergi c
va s cul a r effects , medi a ted by enha nced producti on of endothel i um-deri ved rel a xi ng fa ctor, i e, ni tri c oxi de.)
57. The answer is a. (Brunton, pp 230-233, 920, 923, 1785t; Katzung, pp 99-105.) Wi th a ny a nti mus ca ri ni c druga nd s copol a mi ne certa i nl y i s one
na rrow-a ngl e gl a ucoma (whi ch a ccounts for a bout 10% of a l l gl a ucoma s ) i s the bi gges t concern (a s s umi ng no other rel eva nt comorbi di ti es ). The
drug mi ght provoke s i gni fi ca nt ri s es of i ntra ocul a r pres s ure a s i t further reduces a queous humor dra i na ge, ca us i ng not onl y pa i n but vi s i on
probl ems tha t mi ght be s evere or perma nent. Bra dyca rdi a (b) i s not a concern; i f a nythi ng, us ua l dos es of s copol a mi ne ma y i ncrea s e hea rt ra te a
bi t. Shoul d the pa ti ent ea t s ome s hel l fi s h or other a l l ergy-provoki ng food (c), the i nci dence or s everi ty di a rrhea mi ght be reduced or prevented
a l together by the s copol a mi ne, due to i ts effects on l ongi tudi na l mus cl es i n the gut (i nhi bi ted) a nd on s phi ncters (a cti va ted). A res ti ng bl ood
pres s ure of 112/70 or therea bouts (d) i s not a t a l l uncommon or worri s ome, a nd not l i kel y to be cha nged a t a l l by the drug. Hypothyroi di s m (e)
typi ca l l y i s a s s oci a ted wi th s l i ght bra dyca rdi a ; a ga i n, no l i kel y probl em wi th s copol a mi ne. And i f our pa ti ent ha d mi l d Pa rki ns on di s ea s e (f), we
mi ght a ctua l l y, eventua l l y, s ee a l i ttl e i mprovement wi th thi s drug. Reca l l , one s tra tegy to ma na ge pa rki ns oni s mwhi ch i s ba s i ca l l y a centra l
i mba l a nce between dopa mi ne a nd ACh, the l a tter a ppea ri ng to be a cti ng i n rel a ti ve exces s i s to bl ock centra l mus ca ri ni c receptors (wi th s uch
drugs a s benztropi ne or tri hexypheni dyl ; s ee CNS cha pter).
58. The answer is b. (Brunton, pp 189, 206t, 255-258, 270-272; Katzung, pp 24, 87-89, 101f, 109-110) Ni coti ne i ni ti a l l y s ti mul a tes a nd then bl ocks ni coti ni cs kel eta l mus cul a r (NM) a nd ni coti ni c-neura l (NN; i n a utonomi c ga ngl i a a nd on a drena l medul l a ry cel l s ) chol i nergi c receptors . (Both effects i nvol ve
depol a ri za ti on of the ta rget cel l s , a nd i n ma ny wa ys i t i s compa ra bl e to the depol a ri zi ng bl ocka de of s kel eta l mus cl e a cti va ti on by s ucci nyl chol i ne
i ni ti a l s ti mul a ti on fol l owed by i nhi bi ti on.) Ini ti a l ga ngl i oni c s ti mul a ti on l ea ds to va s ocons tri cti on a nd hypertens i on, both of whi ch a re
ma ni fes ta ti ons of s ympa theti c a cti va ti on. Bra dyca rdi a ma y or ma y not occur; pa ra s ympa theti c ga ngl i oni c a cti va ti on i s l i kel y to i ncrea s e the
predomi na nt pa ra s ympa theti c (bra dyca rdi c) tone on hea rt ra te, but s ympa theti c a cti va ti on ma y ca us e the oppos i te effect. Ini ti a l s ti mul a ti on of
s kel eta l mus cl e NM receptors woul d a ccount for the tremor. As ni coti nes bl ood l evel s ri s e we get a utonomi c ga ngl i oni c bl ocka de, l ea di ng to
hypotens i on a nd bra dyca rdi a . Subs equent bl ocka de a t the s kel eta l neuromus cul a r juncti on l ea ds to mus cl e wea knes s a nd res pi ra tory depres s i on
ca us ed by i nterference wi th the functi on of the di a phra gm a nd i ntercos ta l s . Betha nechol (a ) a nd pi l oca rpi ne (c) a re chol i nomi meti cs tha t, a t us ua l
bl ood l evel s , exert thei r pri ma ry effects a s di rect a goni s ts on mus ca ri ni c receptors for ACh, not on ni coti ni c receptors . -Bl ockers (d) woul d not
ca us e hypertens i on or ta chyca rdi a . Indeed, overdos es woul d cha nge bl ood pres s ure a nd hea rt ra te i n the other di recti on. Moreover, propra nol ol
i ts el f i s s ometi mes us e to ma na ge s kel eta l mus cl e tremor of certa i n eti ol ogi es . Scopol a mi ne (e) i s a mus ca ri ni c bl ocker wi th vi rtua l l y no effects
on s kel eta l mus cl e (ni coti ni c res pons es ).
59. The answer is c. (Brunton, pp 313-319, 774t; Katzung, pp 161-164, 178-179.) Reca l l tha t the ba s i c equa ti on for bl ood pres s ure i s :

a nd s i nce CO = hea rt ra te s troke vol ume (HR SV), then

Propra nol ol i s , of cours e, a nons el ecti ve (1 a nd 2 ) -a drenergi c bl ocker tha t l a cks a ny -bl ocki ng or other va s odi l a tor effects (eg, due to ni tri c
oxi de genera ti on), rega rdl es s of the dos e. So to a ns wer the ques ti on, gi ven the a bove equa ti on, you s i mpl y a s k whi ch one or more of the va ri a bl es
HR, SV, or TPRi s reduced by a nons el ecti ve -bl ocker. The a ns wer, of cours e, i s both HR a nd SV.
Ra pi d pa rentera l a dmi ni s tra ti on of propra nol ol or a nother -bl ocker i n the s a me cl a s s wi l l l ower bl ood pres s ure, a nd i f tha t occurs qui ckl y
enough (eg, wi th ra pi d- a nd bri ef-a cti ng -bl ocker es mol ol ) a nd bl ood pres s ure fa l l s by a s uffi ci ent ma gni tude, a ba roreceptor refl ex (a ns wer a )
wi l l be a cti va ted. Thi s refl ex s ympa theti c a cti va ti on wi l l l ea d to i ncrea s ed peri phera l va s ocons tri cti on, s i nce -a drenergi c receptors a re not
bl ocked by propra nol ol or a ny other -bl ockers except for l a beta l ol or ca rvedi l ol (therefore a ns wer a i s i ncorrect), but thi s wi l l not l ea d to refl exmedi a ted i ncrea s es of ei ther HR or SV. No -bl ocker ha s the a bi l i ty to i nhi bi t ca techol a mi ne rel ea s e, whether from a drenergi c nerves or from the
a drena l (s upra rena l ) medul l a (b). As noted a bove, there i s no mecha ni s m by whi ch a -bl ocker s uch a s propra nol ol wi l l l ower TPR (d). (La beta l ol
a nd ca rvedi l ol ca n, by a -bl ocka de; a nd nebi vol ol does by a ni tri c-oxi de medi a ted mecha ni s m.) Fi na l l y, -bl ockers reduce reni n rel ea s e (a 1 medi a ted effect) from the ki dneys juxta gl omerul a r a ppa ra tus , a nd s o a ns wer e i s i ncorrect.
60. The answer is a. (Brunton, p 744t; Katzung, pp 155-156.) The fi gure, bel ow, a pproxi ma tes wha t i s l i kel y to ha ppen fol l owi ng a dmi ni s tra ti on of a bl ocker to a pa ti ent wi th a pheochromocytoma .

To a ns wer thi s ques ti on correctl y you mus t i ntegra te your ba s i c knowl edge of both a utonomi c pha rma col ogy a nd ca rdi ova s cul a r phys i ol ogy. Wi th
a pheochromocytoma we ha ve wha t mi ght be des cri bed a s ma s s i ve a mounts of ca techol a mi nes ma i nl y epi nephri nebei ng rel ea s ed from the
tumor i nto the bl oods trea m. Germa ne to our probl em, then, i s exces s i ve s ti mul a ti on of ca rdi a c ra te, contra cti l i ty, i mpul s e conducti on, a nd
a utoma ti ci ty (1 ); i ntens e va s ocons tri cti on (); a nd va s odi l a ti on i n s ome va s cul a r beds (2 ).
Nonethel es s , whi l e the pa ti ent Ive des cri bed i s not a t a l l hea l thy, he i s s ti l l a l i ve before we gi ve the -bl ocker. But wha t ha ppens a fter we gi ve
the -bl ocker i s cri ti ca l . The -bl ocker does nothi ng to bl ock the -medi a ted va s ocons tri cti on, s o i n terms of onl y va s cul a r effects BP wi l l rema i n
very hi gh. If you wi s h to opi ne tha t bl ocki ng 2 -medi a ted va s odi l a ti on wi l l ra i s e BP a bi t, tha ts fi ne; Ive s hown tha t i n the fi gure a bove.
(Remember: Us ua l l y effecti ve dos es of a -bl ocker wi l l ei ther l ower BP [mos t common res pons e], or not a ffect i t a t a l l , i n pa ti ents wi th es s enti a l
hypertens i on. If pres s ure ri s es i n res pons e to a -bl ocker, suspect pheochromocytoma.)
Nonethel es s , there wi l l not be a s udden a nd s i gni fi ca nt ri s e or norma l i za ti on of BP a nd/or ca rdi a c functi on (b, c, d). Li kewi s e, hea rt ra te wi l l not
ri s e s i gni fi ca ntl y (e); i t ca nt: the 1 receptors neces s a ry for tha t to occur a re bl ocked.
Next you mus t reca l l tha t the i notropi c s ta te of the hea rt (i e, of the l eft ventri cl e, LV) i s cri ti ca l . Thi s i s cri ti ca l beca us e LV pea k s ys tol i c pres s ure
mus t exceed a orti c pres s ure i n order to es ta bl i s h the LV-a orti c pres s ure gra di ent to expel bl ood i nto the a orta , a nd propel bl ood throughout the
ci rcul a ti on. If a orti c di a s tol i c pres s ure exceeds LV pea k s ys tol i c pres s ure, bl ood wi l l not fl ow out of the hea rt. But unti l we gi ve the -bl ocker, the
hea rt ca n ma i nta i n (for a whi l e) i ts functi on tha nks to ca techol a mi ne-medi a ted s ti mul a ti on.
But when we gi ve jus t a -bl ocker to the pheochromocytoma pa ti ent we ha ve done l i ttl e i f a nythi ng to l ower the a l rea dy hi gh a orti c pres s ure,
a nd s i mul ta neous l y ha ve i nhi bi ted ca rdi a c contra cti l i ty, ra te, a nd other key pa ra meters . The functi on of the hea rt a s a pump i s s uppres s ed. It now
fa ces a very hi gh a orti c pres s ure, a nd ul ti ma tel y i t fa i l s . Ca rdi a c output fa l l s , the pa ti ent devel ops ca rdi ogeni c s hock, a nd i s then l i kel y to di e.
Thi s i s why, when trea ti ng hypertens i on a s s oci a ted wi th a pheochromocytoma , we gi ve a n -bl ocker fi rs t. Bl ood pres s ure wi l l fa l l . We then dea l
wi th the exces s i ve ca rdi a c s ti mul a ti on (whi ch ma y be i ntens i fi ed, vi a the ba roreceptor refl ex, i n res pons e to a s udden a nd s i gni fi ca nt BP fa l l ) by
gi vi ng a s ui ta bl e -bl ocker i mmedi a tel y therea fter.
61. The answer is c. (Brunton, pp 226-227, 230-231; Katzung, pp 120, 127t, 339-357.) Ipra tropi um, a qua terna ry (a nd s o poorl y a bs orbed) a nti mus ca ri ni c
drug, i s FDA-a pproved for us e a s a n i nha l ed bronchodi l a tor for COPD. Its a cti on i nvol ves bl ocka de/a nta goni s m of ACh-medi a ted
bronchocons tri cti on, a nd i t i s often us ed a djuncti vel y wi th a l buterol or other 2 a goni s t bronchodi l a tors . A rel a ted drug i s ti otropi um.
Al buterol (a ) i s a n i nha l ed bronchodi l a tor for a s thma or COPD, but i t works , of cours e, a s a 2 -a drenergi c a goni s t. Di phenhydra mi ne (b) ha s

bronchodi l a tor a cti vi ty (by bl ocki ng both hi s ta mi ne H 1 a nd mus ca ri ni c receptors ), but i t i s not gi ven by i nha l a ti on; moreover, for a mbul a tory
pa ti ents wi th a s thma the mucus -thi ckeni ng effects of mus ca ri ni c receptor bl ocka de ca n do more ha rm tha n good. Vecuroni um (e) i s a cura re-l i ke
s kel eta l neuromus cul a r bl ocker (competi ti ve a nta goni s t of ACh a t NM receptors ) a nd i s us ed ma i nl y for ca us i ng i ntenti ona l s kel eta l mus cl e
pa ra l ys i s duri ng s urgry to s uppres s s ponta neous venti l a ti on i n s ome ICU pa ti ents on a venti l a tor. Pi l oca rpi ne (d) i s a mus ca ri ni c a goni s t, us ed
ma i nl y for ca us i ng mi os i s (cons tri cti ng the pupi l [s ] of the eye[s ]) i n s ome pa ti ents wi th a ngl e-cl os ure gl a ucoma . Pi l oca rpi ne wi l l ca us e
bronchocons tri cti ona n effect tha t ma y be ha rmful , i f not fa ta l , for pa ti ents wi th COPD or a s thma .
62. The answer is d. (Brunton, pp 189-194, 225-230; Katzung, pp 80f, 105-1111, 1034-1036.) In chol i nes tera s e poi s i oni ng we a re dea l i ng wi th
overs ti mul a ti on (from a ccumul a ted ACh) of both peri phera l mus ca ri ni c a nd ni coti ni c receptors . Reca l l tha t a tropi ne i s a s peci fi c mus ca ri ni c
receptor bl ocker, a nd the mus ca ri ni c receptors a re the ones found on s uch s tructures a s s mooth mus cl e, ca rdi a c noda l ti s s ue, a nd exocri ne gl a nds .
In contra s t, the chol i nergi c receptor on s kel eta l mus cl e i s ni coti ni c, s o s kel eta l mus cl e i s nt a ffected by a tropi ne. If one recei ves a l etha l dos e of a
chol i nes tera s e i nhi bi tor, he or s he ma y be a l i ttl e more comforta bl e (l es s defeca ti on, uri na ti on, res pi ra tory tra ct mucus hypers ecreti on a nd
bronchocons tri cti on, a nd a l l tha t, a fter the a tropi ne i s gi ven), but they a re s ti l l l i kel y to di e from s kel eta l mus cl e (NM ni coti ni c) overs ti mul a ti on
a nd then pa ra l ys i s . Pa ra l ys i s of the di a phra gm a nd i ntercos ta l s mus cl es a re the mos t l etha l cons equences .
63. The answer is b. (Brunton, pp 316-317; Katzung, pp 157-165.) You proba bl y l ea rned tha t na dol ol i s a -bl ocker, a nd perha ps tha t i ts a nons el ecti ve
(1 /2 ) bl ocker wi th a ra ther l ong dura ti on of a cti on a nd ha l f-l i fe. If not, you s houl d ha ve been a bl e to recogni ze tha t s i nce the generi c na me ends
i n -ol ol i t i s , i ndeed, s ome ki nd of -bl ocker. You s houl d a l s o know tha t a s thma i s one of the ma i n contra i ndi ca ti ons for -bl ocker
a dmi ni s tra ti on. -Adrenergi c bl ocka de res ul ts i n a n i ncrea s e i n a i rwa y res i s ta nce (by a nta goni s m of bronchodi l a ti on medi a ted by epi nephri ne)
tha t ca n be fa ta l i n s ome a s thma ti c pa ti ents . Na dol ol , a nd a l l the other ora l l y effecti ve -bl ockers , a re a pproved for trea ti ng chroni c-s ta bl e a ngi na
(a ) a nd es s enti a l hypertens i on (c). They a re cri ti ca l el ements i n contempora ry thera py of hea rt fa i l ure (d; except when i t i s s evere a nd ca rdi a c
output i s profoundl y depres s ed); a nd ha ve benefi ci a l effects to control hea rt ra te i n s uch condi ti ons a s s i nus ta chyca rdi a (e).
64. The answer is e. (Brunton, pp 318, 1787; Katzung, pp 160, 163-164.) When a ppl i ed topi ca l l y to the eye, both the di rect-a cti ng chol i nomi meti c a gents
(eg, pi l oca rpi ne) a nd thos e tha t a ct by i nhi bi ti on of AChE (eg, echothi opha te, i s ofl uropha te, a nd phys os ti gmi ne) ca us e mi os i s by cons tri cti ng the
pupi l . In pa ti ents wi th na rrow-a ngl e (a ngl e cl os ure) gl a ucoma , thi s effect provi des grea ter dra i na ge of the a queous humor through the tra becul a r
mes hwork a nd the ca na l of Schl emm a nd a reducti on i n res i s ta nce to outfl ow of the a queous humor. Certa i n -a drenergi c bl ocki ng a gents (eg,
ti mol ol a nd l evobunol ol ), a ppl i ed to the eye(s ), a re a l s o very us eful i n trea ti ng chroni c wi de-a ngl e gl a ucoma . Thes e drugs a ppea r to a ct by
decrea s i ng the s ecreti on (or forma ti on) of a queous humor by a nta goni zi ng the effect of ci rcul a ti ng ca techol a mi nes on -a drenergi c receptors i n
the ci l i a ry epi thel i um. Echothi opha te (a ), i s ofl uropha te (b), a nd neos ti gmi ne (e) a re a cetyl chol i nes tera s e i nhi bi tors a nd a l l cons tri ct the pupi l .
Pi l oca rpi ne (d) i s mus ca ri ni c receptor a goni s t; i t, too, ca us es mi os i s .
65. The answer is e. (Brunton, pp 288, 351-359; Katzung, pp 84t, 136f, 138t, 141, 148, 225.) Infus i ng l ow dos es of dopa mi ne ra ther preferenti a l l y a cti va tes
D 1 receptors , ra i s es va s cul a r s mooth mus cl e cAMP l evel s , a nd ca us es va s odi l a ti on i n the ki dneys a nd mes entery. (Cl i ni ci a ns often refer to thes e a s
rena l dos es beca us e, i n s uch condi ti ons a s l ow ca rdi a c output the drug i s gi ven not onl y a s a ca rdi a c s ti mul a nt but a l s o to i ncrea s e rena l bl ood
fl ow a nd uri ne output.) The outcome of the i ncrea s ed rena l bl ood fl ow i s i ncrea s ed gl omerul a r fi l tra ti on a nd s odi um excreti on. A s i mi l a r D 1 /cAMPmedi a ted effect a l s o occurs i n the rena l tubul es (pa rti cul a rl y the proxi ma l tubul es a nd the medul l a ry regi on of the thi ck a s cendi ng l i mb i n the
Loop of Henl e). Thi s i nhi bi ts a Na + -K+ -ATPa s e, whi ch further i ncrea s es rena l s odi um l os s by i nhi bi ti ng s odi um rea bs orpti on.
66. The answer is g. (Brunton, pp 206t, 210, 782-783; Katzung, pp 84-87, 178, 189.) The qua l i ta ti ve a nd mecha ni s ti c effects of gua na drel a re very s i mi l a r to
thos e of res erpi ne. Both drugs ca us e wha t ha s been des cri bed a s a chemi ca l s ympa thectomy, gra dua l l y but eventua l l y ma rkedl y reduci ng
s ympa theti c (a drenergi c) i nfl uences on a l l the us ua l ta rget s tructures a nd thereby expos i ng or unma s ki ng oppos i ng pa ra s ympa theti c i nfl uences .
(The res ul ti ng s yndrome ha s been ca l l ed pa ra s ympa theti c predomi na nce s i nce a drenergi c i nfl uences a re removed, l ea vi ng PNS tone on a hos t of
s tructures unoppos ed a nd now expos ed.) For exa mpl e, i n the pres ence of gua na drel mi os i s , di a rrhea a nd uri na ti on devel op; a nd a rteri ol es di l a te
a nd bl ood pres s ure fa l l s (beca us e theres l i ttl e/no norepi nephri ne to be rel ea s ed, s i nce i t ha s been depl eted from a drenergi c nerve endi ngs ).
Hea rt ra te does not i ncrea s e refl exl y (vi a the ba roreceptor refl ex mecha ni s m) for two ma i n rea s ons . Fi rs t, hea rt ra te ca nnot ri s e beca us e a fter a
s uffi ci ent dura ti on of trea tment there i s l i ttl e or no NE to be rel ea s ed. The s econd rea s on for no ba roreceptor refl ex i s tha t gua na drel (a nd
res erpi ne) ca us e BP to fa l l s o s l owl y tha t the ba roreceptors s i mpl y do not res pond to a ny BP cha nges . Indeed, hea rt ra te fa l l s ma rkedl y duri ng
trea tment. Res erpi ne ca us es i ts effects ma i nl y by i nterferi ng wi th i ntra neurona l s tora ge of NE, expos i ng the neurotra ns mi tter to meta bol i c
i na cti va ti on by MAO a nd ul ti ma tel y depl eti ng the NE. Gua na drel rel ea s es NE di rectl y, a nd gra dua l l y, eventua l l y l ea di ng to a s ta te of i ntra neurona l
NE depl eti on wi th s i gns a nd s ymptoms very s i mi l a r to thos e ca us ed by res erpi ne.
None of the other drugs l i s ted wi l l ha ve a ny effects on the l evel s of NE i n a drenergi c nerves . Acetyl chol i ne (a ), the phys i ol ogi c a goni s t for both
mus ca ri ni c a nd ni coti ni c receptors , wi l l ca us e ma ny of the res pons es des cri bed for gua na drel , but, a ga i n, does not do s o by reduci ng
ca techol a mi ne l evel s i n a drenergi c neurons . Its a l s o worth noti ng tha t ACh i s not cl a s s i fi eda nd certa i nl y not us eda s a n a nti hypertens i ve drug.
The peri phera l a utonomi c effects of a tropi ne (b) a dmi ni s tra ti on woul d be the oppos i te of thos e des cri bed for gua na drel . Us ua l pa rentera l dos es
of epi nephri ne (c; a nd 1 a nd 2 a goni s t) or norepi nephri ne (e; a nd 1 a goni s t) tend to ra i s e bl ood pres s ure a nd peri phera l res i s ta nce (the
effects cl ea rl y a re dos e-dependent), a nd i f there were a ny cha nges i n pupi l s i ze i t woul d be ma ni fes t a s mydri a s i s due to a cti va ti on of -receptors
on i ri s di l a tor mus cl e cel l s . Is oproterenol (d; 1 a nd 2 a goni s t wi th no di rect effects on receptors ) ma y ra i s e BP by i ncrea s i ng ca rdi a c output (vi a
i ncrea s ed hea rt ra te a nd s troke vol ume). Propra nol ol (f), the prototypi c 1 a nd 2 a nta goni s t, certa i nl y i s a n a nti hypertens i ve drug, but i t a nd other
-bl ockers do not a ffect i ntra neurona l NE l evel s ; do not ca us e a ny cha nge i n pupi l s i ze (i e, nei ther mydri a s i s nor mi os i s ); a nd do not typi ca l l y
unma s k pa ra s ympa theti c i nfl uences on s uch s tructures a s the gut a nd uri na ry tra ct mus cul a ture.
67. The answer is c. (Brunton, pp 283f, 289-290; Katzung, pp 136-139, 141-142, 148, 343.) Pi ece thi ngs together. Some ti p-offs to hel p a rri ve a t the correct
a ns wer: no effect on the s i ze of the pupi l , s o rul e out a ny drug tha t ha s effects on the pa ra s ympa theti c s i de, whether a s a n a goni s t or a nta goni s t
(here, a tropi ne), a nd rul e out a ny drug wi th effects . (As noted a bove, no -receptors control the s i ze of the pupi l of the eye.)
Does i s oproterenol fi t a l l the other cri teri a /properti es ? Yes . And none of the other choi ces ha ve a l l the s ta ted properti es , onl y s ome of them.
68. The answer is d. (Brunton, pp 575-576; Katzung, p 457.) There a re s evera l rea s ons for a nd outcomes of a ddi ng a va s ocons tri ctor (us ua l l y
epi nephri ne) to s ome l oca l a nes theti cs gi ven by i nfi l tra ti on. The va s ocons tri ctor confi nes the l oca l a nes theti c to the des i red s i te of a cti on
(ba s i ca l l y the s i te of a dmi ni s tra ti on) by reduci ng l oca l bl ood fl ow a nd the ra te of a nes theti c entry i nto the bl oods trea m. It i s the bl oods trea m (or,
more preci s el y, i t i s the pres ence of a nes theti c i n the s ys temi c ci rcul a ti on) tha t del i vers the drug to s i tes where s i gns a nd s ymptoms of toxi ci ty
occur. Sl ow down a nes theti c a bs orpti on ra tes a nd the drug wi l l enter the ci rcul a ti on s l owl y enough tha t i t ca n be meta bol i zed (i na cti va ted) fa s t

enough to prevent a ccumul a ti on to toxi c l evel s . Tha t i s , we reduce the ri s k of s ys temi c toxi ci ty wi th a dded va s ocons tri ctor.
Another outcome of i ncl udi ng a va s ocons tri ctor i s to prol ong (a nd certa i nl y not s horten) the dura ti on of l oca l a nes theti c effect. Tha t occurs a l s o
beca us e reduced l oca l bl ood fl ow keeps the a nes theti c i n the vi ci ni ty of s ens ory nerves l onger (s i nce the a nes theti c i s not bei ng removed a s
qui ckl y by bl ood fl ow).
More on thi s i s s ue wi l l be pres ented i n the CNS ques ti ons . But for now: Loca l a nes theti cs (except coca i ne) ca n ca us e va s odi l a ti on (not
va s ocons tri cti on; a ), but unl es s the l oca l a nes theti c dos a ges a re qui te hi gh (toxi c), the va s odi l a ti on i s not i ntens e; hypotens i on i s uncommon wi th
us ua l dos a ges . Li kewi s e, ca rdi a c depres s i on ca n occur, but a ga i n tha t i s a ma ni fes ta ti on of overdos e. We dont routi nel y i ncl ude epi nephri ne i n a
l oca l a nes theti c to comba t or prevent thes e ca rdi a c-depres s a nt probl ems (b), a nd the a mount of epi nephri ne found i n thes e prepa ra ti ons i s fa r
too l ow to do a nythi ng mea ni ngful to remedy thes e a dvers e res pons es s houl d they occur. Li kewi s e, the a mounts of va s ocons tri ctor a re fa r too l ow
to prevent (or trea t) a nes theti c-i nduced a na phyl a xi s (c)a rea cti on tha t requi res onl y a few mol ecul es of a nti gen to occur.
So wha t the va s ocons tri ctor does i s es s enti a l l y ca us e a pha rma col ogi c tourni quet, reduci ng regi ona l bl ood fl ow tha t otherwi s e woul d qui ckl y
wa s h a wa y the a nes theti c. Thi s es s enti a l l y confi nes the a nes theti c to the des i red s i te l onger (not s horter; e) tha n otherwi s e, a nd decrea s es the
potenti a l s ys temi c rea cti ons (d). Some l oca l a nes theti cs ca us e va s odi l a ti on, whi ch a l l ows more compound to es ca pe the ti s s ue a nd enter the
bl ood.
Two fi na l notes : In pl a s ti c s urgery, otol a ryngol ogi c s urgery (nos e, throa t) a nd ma ny other types of s urgery, the di rect va s ocons tri ctor effects of
EPI, a dmi ni s tered a s pa rt of a mi xture of the a nes theti c a nd epi nephri ne, not onl y a nta goni ze the l oca l va s odi l a tor effects of a l oca l a nes theti c,
but a l s o ca us e di rect va s ocons tri cti on i n the regi ona l oca l hemos ta ti c effect tha t l i mi ts bl ood l os s i n yet a nother wa y. It i s a l s o i mporta nt to
note tha t epi nephri ne (or other va s ocons tri ctors ) s houl d not be us ed i n or a s a s uppl ement to pa rentera l l oca l a nes theti cs bei ng us ed to rel i eve
or prevent pa i n i n end orga ns fi ngers , toes , peni s , ti p of the nos e, ea rl obes , etc. Such s tructures ha ve rel a ti vel y di s crete bl ood s uppl i es , a nd
bl ocki ng bl ood fl ow to di s ta l ti s s ues ca n l ea d to i s chemi a a nd ti s s ue da ma ge.
69. The answer is a. (Brunton, pp 305-307, 309, 774t, 779-780, 793; Katzung, pp 152-154, 167, 180, 189.) Fi rs t you need to know tha t pra zos i n a nd
phentol a mi ne a re -a drenergi c bl ockers . Then you need to know upon whi ch -a drenergi c receptors they a ct, a nd wha t res pons es they el i ci t.
Phentol a mi ne i s a nons el ecti ve -a drenergi c bl ocker, a cti ng a t both 1 (pos ts yna pti c) a nd 2 (pres yna pti c) receptors . Pra zos i n s el ecti vel y bl ocks 1
receptors . Acti va ti ng the pos ts yna pti c receptors , on va s cul a r s mooth mus cl e cel l s , ca us es contra cti on (va s ocons tri cti on); bl ock thos e receptors a nd
va s odi l a ti on (i e, the fa l l of bl ood pres s ure we noted) occurs . Both phentol a mi ne a nd pra zos i n do thi s .
The bl ood pres s ure fa l l upon drug a dmi ni s tra ti on i s of a s uffi ci ent ma gni tude (20 mm Hg), a nd occurs s uffi ci entl y qui ckl y (20 s econds or l es s ),
tha t the ba roreceptor refl ex i s a cti va ted. Thi s l ea ds to i ncrea s ed s ympa theti c outfl ow to the peri phery a s pa rt of the bodys a ttempt to ma i nta i n
the ca rdi ova s cul a r s ta tus quo. Sympa theti c s ti mul a ti on of va s cul a r s mooth mus cl e norma l l y wi l l ca us e va s ocons tri cti on, but s i nce the -a drenergi c
receptors tha t mus t be a cti va ted to ca us e i t a re bl ocked (by phentol a mi ne or pra zos i n), va s ocons tri cti on wi l l not occur (or be very much reduced).
Increa s ed ba roreceptor-medi a ted s ympa theti c s ti mul a ti on of the hea rt a l s o occurs , a nd nei ther phentol a mi ne nor pra zos i n bl ocks the 1
receptors on whi ch rel ea s ed NE exerts i ts ca rdi a c-s ti mul a ti ng effects .
But wha t el s e occurs a t the a drenergi c neuroeffector juncti ons , s uch a s a t the hea rt? Norma l l y, s ome of the rel ea s ed NE a cts on the pres yna pti c
-receptors . The res ul t of tha t i ntera cti on i s a phys i ol ogi c turni ng off or feedba ck-i nhi bi ti on of further NE rel ea s e i n res pons e to ea ch a cti on
potenti a l . Phentol a mi ne bl ocks the pres yna pti c -receptors , thereby bl ocki ng wha t a mounts to the a bi l i ty of rel ea s ed NE to s uppres s further NE
rel ea s e. The cons equence of thi s ? Si gni fi ca nt i ncrea s es i n the a mount of NE rel ea s ed i nto the s yna ps e, a nd prol onged pres ence of NE i n the
s yna ps e, a nd s i gni fi ca ntl y i ncrea s ed ca rdi a c s ti mul a ti on. Pra zos i n, however, does not bl ock the pres yna pti c -receptors , a nd i n doi ng s o does not
i nterfere wi th the norma l feedba ck-i nhi bi tory effects of rel ea s ed NE. And the obvi ous di fference? Much l es s i ntens e refl ex ca rdi a c s ti mul a ti on
wi th pra zos i n tha n tha t wi th phentol a mi nenot the oppos i te (b).
Pra zos i n a nd phentol a mi ne ha ve no -bl ocki ng a cti vi ty (c). Nei ther drug bl ocks NE-medi a ted va s odi l a ti on (d). And nei ther wi l l reduce LV
a fterl oa d (e): a s noted i n the ques ti on, both drugs l owered a rteri a l pres s ure a nd s o a fterl oa d i s obvi ous l y decrea s ed too.
70. The answer is a. (Brunton, pp 234, 251-252; Katzung, pp 105-112.) Al though s evera l of the l i s ted drugs i nhi bi t the a cti vi ty of AChE, onl y edrophoni um
i s us ed i n the di a gnos i s of mya s theni a gra vi s . The drug ha s a more ra pi d ons et of a cti on (1 to 3 mi nutes fol l owi ng i ntra venous a dmi ni s tra ti on)
a nd a s horter dura ti on of a cti on (a pproxi ma tel y 5 to 10 mi nutes ) tha n pyri dos ti gmi ne. Thi s fa s t a cti ng/s hort dura ti on profi l e i s preci s el y wha t we
wa nt i n thi s s i tua ti on. We ca n qui ckl y get our di a gnos ti c a ns wer, yet not ha ve to dea l too l ong wi th a dvers e res pons es (s uch a s venti l a tory
pa ra l ys i s ) i f the pa ti ent wa s experi enci ng a chol i nergi c cri s i s (exces s i ve dos es of thei r ora l chol i nes tera s e i nhi bi tor) a nd weve now wors ened the
s i tua ti on by i nhi bi ti ng the meta bol i c i na cti va ti on of ACh even more wi th our di a gnos ti c medi ca ti on. (The s hort dura ti on a nd the need for
pa rentera l a dmi ni s tra ti on precl ude us e of edrophoni um a s a pra cti ca l drug for l ong-term trea tment of mya s theni a gra vi s .)
Ma l a thi on (b) i s us ed topi ca l l y to trea t hea d l i ce a nd i s never us ed i nterna l l y (i ntenti ona l l y). Pyri dos ti gmi ne (e) i s us ed ora l l y for ma i ntena nce
thera py of mya s theni a gra vi s . Phys os ti gmi ne (c) i s i ndi ca ted for trea tment of gl a ucoma (gi ven topi ca l l y), a nd i s a l s o a va l ua bl e pa rentera l drug for
trea ti ng toxi ci ty of a nti chol i nergi c drugs s uch a s a tropi ne. They a re a l l chol i nes tera s e i nhi bi tors . Pra l i doxi me (d) i s a chol i nes tera s e rea cti va tor
a nd i s us ed a djuncti vel y (wi th a tropi ne) i n the trea tment of poi s oni ngs ca us ed by i rrevers i bl e chol i nes tera s e i nhi bi tors , s uch a s the nerve
ga s es us ed a s bi owea pons a nd s ome commerci a l i ns ecti ci des .
71. The answer is c. (Brunton, pp 282-287, 302; Katzung, p 145.) Epi -nephri ne, a n excel l ent a goni s t for a l l the a drenergi c receptors , i s the drug of choi ce
for ma na gi ng the s ymptoms of a n a cute, s ys temi c, i mmedi a te hypers ens i ti vi ty rea cti on to a n a l l ergen (a na phyl a cti c s hock), a l l of whi ch res ul t from
the rel ea s e or producti on of va ri ous s ubs ta nces (eg, hi s ta mi ne, ki ni ns ) tha t contri bute to ca rdi a c, va s cul a r, a nd pul mona ry dys functi on. Dea th ca n
occur beca us e of s evera l ma i n a dvers e res pons es : profound hypotens i on a nd a ngi oedema (whi ch ca n be revers ed by epi nephri nes a goni s t/va s ocons tri ctor effects ); ca rdi a c depres s i on (revers ed by epi nephri nes 1 a cti ons ); a nd l a ryngos pa s m a nd bronchos pa s m (revers ed by the
2 effects of epi nephri ne).
Atropi ne (a ), the prototype mus ca ri ni c receptor bl ocker, wi l l ha ve modes t effects to countera ct a i rwa y s mooth mus cl e contra cti on ca us ed by
a cetyl chol i ne, but no effect on the s trong a dvers e ca rdi ova s cul a r or a i rwa y effects of hi s ta mi ne, ki ni ns , a nd other medi a tors tha t pl a y a cri ti ca l rol e
i n a na phyl a xi s . Di phenhydra mi ne (b) ha s s trong hi s ta mi ne H 1 a nd mus ca ri ni c receptor bl ocki ng a cti ons , but i t, too, ca nnot bl ock a l l the a dvers e
a nd potenti a l l y l etha l ca rdi ova s cul a r a nd pul mona ry effects of a na phyl a xi s -a s s oci a ted medi a tors . (Di phenhydra mi ne cl ea rl y ca n a l l evi a te
bothers ome urti ca ri a a nd other cuta neous ma ni fes ta ti ons of a l l ergi c or a na phyl a cti c rea cti ons , but thos e a cti ons a re ra ther tri vi a l compa red wi th
other l i fe-threa teni ng res pons es tha t i t ca nnot benefi ci a l l y a ffect.) No a nti hi s ta mi ne ca n be cons i dered a l i fe-s a vi ng s ubs ti tute for epi nephri ne.
Is oproterenol (d), the prototype 1 a nd 2 a goni s t, wi l l countera ct a i rwa y s mooth mus cl e contra cti on a nd hel p res tore ca rdi a c functi on, but beca us e
i t l a cks a ny va s ocons tri ctor (i e, -a goni s t) a cti vi ty i t wi l l not countera ct wi des prea d va s odi l a ti on a nd the hemodyna mi c cons equences of i t.
Norepi nephri ne (e) ha s benefi ci a l ca rdi a c a nd peri phera l va s ocons tri ctor a cti vi ty, but s i nce i t l a cks 2 -bronchodi l a tor a cti vi ty i t i s not a n
a ccepta bl e a l terna ti ve to epi nephri ne. Its bronchodi l a tor effects a re rel a ti vel y wea k, a nd i t l a cks a ny va s opres s or effects tha t a re needed to hel p
res tore bl ood pres s ure.

72. The answer is c. (Brunton, pp 206t, 290; Katzung, pp 141-142, 148, 225.) Dobuta mi ne i s ma i nl y a 1 -s el ecti ve a goni s t tha t ca us es a pos i ti ve i notropi c
effect a nd i n turn ra i s es s troke vol ume, l ea di ng to i ncrea s ed ca rdi a c output. Dobuta mi ne ha s s ome pos i ti ve chronotropi c a cti vi ty (a l s o 1 medi a ted) tha t a l s o contri butes to a ri s e of ca rdi a c output, but the drugs effects on the hea rts i notropi c s ta te predomi na te.
Note: The bes t wa y to cha ra cteri ze the receptor-medi a ted effects of dobuta mi ne i s a s a s el ecti ve 1 a goni s t, but dobuta mi nes a cti ons (i n the
form a va i l a bl e for thera peuti c us e) a re a bi t more compl ex. It i s a ctua l l y a ra cemi c mi xture of two i s omers : the (+) i s omer i s the potent 1 a goni s t
tha t ca us es the predomi na nt ca rdi a c a nd hemodyna mi c effects , but i t a l s o ha s s ome wea k 1 a nta goni s t (va s odi l a tor) effects ; the () i s omer i s a n
effi ca ci ous a nd potent 1 a goni s t (va s ocons tri ctor). The oppos i ng va s ocons tri ctor effects of one i s omer es s enti a l l y ca ncel -out the va s odi l a tor
effects of the other. Rega rdl es s , i t woul d not be correct to cha ra cteri ze the drugs predominant ca rdi ova s cul a r a cti ons a s i nvol vi ng -a goni s t or
a nta goni s t effects (a , b, e, f), a nd the drug certa i nl y ha s no -bl ocki ng a cti ons (d).
73. The answer is b. (Brunton, pp 116, 196-198; Katzung, pp 85-87, 134.) Norepi nephri ne (a nd other monoa mi ne neurotra ns mi tters s uch a s dopa -mi ne) i s
removed from i ts receptors by a n a mi ne pump l oca ted i n the neurona l membra ne. Reca l l tha t thi s reupta ke proces s ca n be bl ocked by (a mong
other drugs ) coca i ne a nd tri cycl i c a nti depres s a nts . (You mi ght a s k wha t a bout s ti mul a ti on of pres yna pti c 2 receptors ? Wel l , tha t a ns wer mi ght
work, but i t wa s nt one of the choi ces here. Moreover, pres yna pti c 2 receptor a cti va ti on onl y i nhi bi ts rel ea s e of a ddi ti ona l NE; i t does not s top the
effects of NE tha t ha s a l rea dy been rel ea s ed.)
Monoa mi ne oxi da s e (MAO; a ns wer d), a nd to a l es s er degree ca techol -O-methyl tra ns fera s e (COMT; a ns wer c), a re enzymes res pons i bl e for
meta bol i c degra da ti on of NE (the former i ntra neurona l l y a s fa r a s monoa mi nergi c nerves go, the other extra neurona l ). However, they a re not
i mporta nt i n termi na ti ng the i mmedi a te a cti ons of rel ea s ed NE, whi ch i s a proces s dependent ma i nl y on neurona l reupta ke fol l owi ng ea ch a cti on
potenti a l a nd whi ch i s not a ffected by MAO or COMT i nhi bi tors .
Ans wer a , whi ch ci tes meta bol i c i na cti va ti on of neurotra ns mi tter i n the s yna pti c cl eft, i s a good des cri pti on of wha t ha ppens to neurona l l y
rel ea s ed ACh. Ans wer e, whi ch menti ons forma ti on of a fa l s e neurotra ns mi tter, does not expl a i n the phys i ol ogi c termi na ti on of rel ea s ed
norepi nephri nes a cti ons . Tha t concept, however, ha s been menti oned a s a potenti a l mecha ni s m by whi ch monoa mi ne oxi da s e i nhi bi tors a l ter
the a drenergi c res pons es when MAO i nhi bi tors a re a dmi ni s tered.
74. The answer is f. (Brunton, pp 316-317; Katzung, pp 162-165, 691-694.) The ta chyca rdi a a s s oci a ted wi th s ymptoma ti c hyperthyroi di s m refl ects , to a
grea t degree, thyroi d hormone-rel a ted hyperrea cti vi ty of -a drenergi c receptors to drugs tha t ha ve -a goni s t a cti vi ty. Of mos t concern i n thi s
s i tua ti on i s hyperrea cti vi ty of 1 receptors , whi ch a ccounts for the untowa rd a nd potenti a l l y da ngerous ca rdi a c res pons es tha t us ua l l y occur. Thes e
ca n be ma na ged, s ymptoma ti ca l l y, wi th a -bl ocker. Indeed, duri ng a n a cute a nd l i fe-threa teni ng epi s ode of hyperthyroi di s m (thyrotoxi cos i s , or
thyroi d s torm) a -bl ocker i s not onl y i ndi ca ted but a l s o ma y be l i fes a vi ng. Of a l l the condi ti ons l i s ted, thi s i s the onl y i ndi ca ti on for propra nol ol
or vi rtua l l y a ny other -bl ocker; a nd the onl y one tha t i s not l i kel y to wors en s ome a s pect of the current cl i ni ca l pres enta ti on.
-Bl ockers a re genera l l y s a fe a nd effecti ve for chroni c-s ta bl e a ngi na (chroni c-s ta bl e or s tres s -i nduced a ngi na ), a nd they a re often us ed
prophyl a cti ca l l y i n tha t condi ti on. However they ma y wors en, a nd s o a re genera l l y contra i ndi ca ted i n pa ti ents wi th va s os pa s ti c (va ri a nt, or
Pri nzmeta l ) a ngi na (a ). In s i tua ti ons of corona ry va s os pa s m, -medi a ted va s ocons tri ctor/s pa s m-provoki ng i nfl uences tend to be oppos ed by 2 medi a ted va s odi l a tor i nfl uences . Bl ock the 2 effects a nd the cons tri ctor or s pa s m-fa vori ng -i nfl uences a re unma s ked, l ea di ng to i ncrea s ed
frequency a nd s everi ty of a ngi na a nd myoca rdi a l i s chemi a .
As thma (b) i s a n i mporta nt a nd common condi ti on tha t rel a ti vel y or a bs ol utel y contra i ndi ca tes the us e of a -bl ocker, rega rdl es s of i ts s pectrum
of a cti vi ty or a dmi ni s tra ti on route. Even very s ma l l dos es of a -bl ockereven a topi ca l -bl ocker tha t mi ght be us ed for gl a ucoma , a nd even the
s o-ca l l ed s el ecti ve 1 -bl ockers s uch a s a tenol ol or metoprol ol ca n prove l etha l for s ome a s thma ti cs . Tha t i s beca us e the a i rwa ys of a s thma ti c
i ndi vi dua l s depend grea tl y on 2 a cti va ti on (a nd other i nfl uences ) to prevent bronchocons tri cti on or bronchos pa s m. Bl ock thos e effects , a nd
s eri ous or even fa ta l cons equences ma y a ri s e.
-Adrenergi c bl ockers l ower hea rt ra te a nd s l ow A-V noda l conducti on vel oci ty. Thus , pre-exi s ti ng bra dyca rdi a (c) or hea rt (A-V noda l ) bl ock (e)
tends to wei gh a ga i ns t, i f not contra i ndi ca te, s a fe us e of a ny -bl ocker. A worki ng defi ni ti on of hea rt bl ock i s , of cours e, a n a bnorma l l y prol onged
P-R i nterva l , whi ch ca n be detected ea s i l y on a n el ectroca rdi ogra m. If the pa ti ent ha s fi rs t-degree hea rt bl ock (P-R i nterva l s a re prol onged, but a l l
s upra ventri cul a r el ectri ca l a cti vi ty pa s s es through the A-V node to a cti va te the ventri cl es ), a -bl ocker ma y ca us e s econd-degree hea rt bl ock (s ome
s upra ventri cul a r i mpul s es a re not conducted through the A-V node). If the pa ti ent ha s s econd-degree hea rt bl ock, a -bl ocker ma y ca us e compl ete
(thi rd degree) bl ock, whi ch ca n ha ve di re cons equences beca us e the ventri cul a r myoca rdi um l os es a l l control by i mpul s es pa s s i ng through the A-V
node, a nd s o ventri cul a r a cti vi ty i s l i kel y to fa l l to da ngerous l evel s .
-Bl ockers ma y pos e s i gni fi ca nt probl ems for s ome pa ti ents wi th s evere, poorl y control l ed di a betes mel l i tus (d). Thes e drugs ca n, for exa mpl e,
prevent ta chyca rdi a tha t i s one s i gna l to the pa ti ent tha t bl ood gl ucos e l evel s a re too l ow, a nd they ca n del a y the recovery of bl ood gl ucos e l evel s
fol l owi ng a n epi s ode of hypogl ycemi a . However, for ma ny pa ti ents wi th mi l d a nd wel l -control l ed di a betes (es peci a l l y type 2), i n s uch condi ti ons
a s mi l d-to-modera te hea rt fa i l ure (a nd others ), the judi ci ous us e of a -bl ocker proba bl y provi des more benefi t tha n ha rm.
75. The answer is c. (Brunton, pp 234-235; Katzung, pp 116-124, 1034.) Thes e a re a mong the cl a s s i c s i gns a nd s ymptoms of a tropi ne poi s oni ng, whi ch i s
a l s o more genera l l y known a s the a nti mus ca ri ni c or a nti chol i nergi c s yndrome. The a nti mus ca ri ni c drug-poi s oned pa ti ent often ca n be des cri bed
as:
red a s a beet (cha ra cteri s ti c fa ci a l fl us hi ng; a s o-ca l l ed a tropi ne fl us h);
dry a s a bone (no exocri ne gl a nd s ecreti ons , no feca l or uri na ry output beca us e bowel a nd bl a dder moti l i ty a re i nhi bi ted);
hot a s a furna ce (profound fever; a CNS probl em compounded by a l a ck of body hea t l os s norma l l y a fforded by s wea ti ng);
bl i nd a s a ba t (pa ra l ys i s of a ccommoda ti on a nd di l a ted pupi l s do not res pond to even very bri ght l i ght);
ma d a s a ha tter (a s i n the Ma d Ha tter from Lewi s Ca rrol l s Alice in Wonderland: CNS probl ems , i ncl udi ng del i ri um a nd ha l l uci na ti ons ).
You ma y never s ee true a tropi ne poi s oni ng. As you know, tha t prototype a nti mus ca ri ni c drug i s not us ed cl i ni ca l l y a l l tha t often, except i n s ome
pa rti cul a r s peci a l ti es or s i tua ti ons . However, you s houl d rea l i ze tha t ma ny common groups of drugs (s ee Ques ti on 88), s ome of whi ch a re
a va i l a bl e over-the-counter (s peci fi ca l l y, di phenhydra mi ne), exert s trong a nti mus ca ri ni c effects . The s i gns a nd s ymptoms of a tropi ne poi s oni ng
a re a n i mporta nt component of thei r overdos e s yndromes , a nd you s houl d be a bl e to recogni ze them.
76. The answer is a. (Brunton, pp 310-316; Katzung, pp 151-152.) The -bl ockers wi th i ntri ns i c s ympa thomi meti c a cti vi ty (ISA) a re pa rti a l a goni s ts they
a ct s i mul ta neous l y a s both -a goni s ts a nd competi ti ve -bl ockers . How ca n tha t be? At us ua l dos es , a nd i n the pres ence of l ow (eg, res ti ng)
s ympa theti c tone, they a ct a s wea k a goni s ts for -a drenergi c receptors . Under thes e condi ti ons , then, they ma y a ctua l l y but s l i ghtl y i ncrea s e s uch
-medi a ted res pons es a s hea rt ra te. However, whi l e thes e drugs a re occupyi ng the -a drenergi c receptors , they s i mul ta neous l y bl ock (a nta goni ze)

the effects of more effi ca ci ous (s tronger) a goni s ts , eg, epi nephri ne a nd norepi nephri ne, or s uch exogenous a gents (drugs ) a s i s oproterenol .
Thus , a l though they wea kl y i ncrea s e res ti ng hea rt ra te, when ca techol a mi ne l evel s a re hi gh (a s wi th s tres s , or exerci s e), s uch -medi a ted
res pons es a s a ccel era ti on of hea rt ra te a nd contra cti l i ty a re l es s i ntens e tha n they woul d be ha d thes e drugs wi th ISA not been pres ent. See
Ques ti on 27 (i n the Genera l Pri nci pl es cha pter) for more i nforma ti on, beca us e i t wa s ba s ed on the effects of a -bl ocker wi th ISA/pa rti a l a goni s t
a cti vi ty.
Acebutol ol a nd pi ndol ol i ndeed, a l l drugs cl a s s i fi ed a s -bl ockers ha ve no a bi l i ty to ca us e rel ea s e of norepi nephri ne (from a drenergi c
nerves ) or epi nephri ne (from the a drena l medul l a ), a nd s o a ns wer b i s i ncorrect. Li kewi s e, thes e drugs do not i nduce (s ti mul a te; nor i nhi bi t)
ca techol a mi ne s ynthes i s (c); do not potenti a te the a cti ons of norepi nephri ne on - (or on -) a drenergi c receptors (d); a nd ca us e nega ti ve i notropi c
a nd chronotropi c effects (not pos i ti ve; a ns wer e).
77. The answer is b. (Brunton, pp 299-300, 303; Katzung, pp 136f, 142, 703t, 1032-1034.) Methyl pheni da te i s pha rma col ogi ca l l y s i mi l a r to a mpheta mi ne. In
the context of ADD/ADHD thera py i t works a s a CNS s ti mul a nt, wi th more pronounced effects on menta l tha n on motor a cti vi ti es . It does s o by
rel ea s i ng neurona l norepi nephri ne a nd dopa mi ne vi a a nonexocytoti c (not dependent on a cti on potenti a l s ) mecha ni s m. It i s a l s o us ed to trea t
na rcol eps y. Dobuta mi ne (a ) i s a 1 -a drenergi c a goni s t. Pa ncuroni um (c) i s a nondepol a ri zi ng s kel eta l neuromus cul a r bl ocker (ni coti ni c receptor
competi ti ve a nta goni s t). Pra zos i n (d) i s a competi ti ve a nd s el ecti ve 1 -a drenergi c bl ocker. Scopol a mi ne (e) i s a n a nti mus ca ri ni c (a tropi ne-l i ke)
drug wi th grea ter effi ca cy for ca us i ng s eda ti on a nd a nti moti on s i cknes s effects . Terbuta l i ne (f) i s a n a goni s t predomi na ntl y s el ecti ve for 2 a drenergi c receptors a t l ow dos es , but i t ca n exert nons el ecti ve (i s oproterenol -l i ke) 1 - a nd 2 -a goni s t effects a t hi gh dos es , i ncl udi ng dos es
tha t ma y commonl y be gi ven thera peuti ca l l y.
78. The answer is e. (Brunton, pp 198, 300, 323t; Katzung, pp 136f, 141-142.) Ephedri ne (a nd ps eudoephedri ne) a re cl a s s i fi ed a s mi xed-a cti ng
s ympa thomi meti cs , mea ni ng tha t thei r overa l l a cti ons a re a mi xture or combi na ti on of two mecha ni s ms . They ma i nl y rel ea s e i ntra neurona l
norepi nephri ne, a nd s o the predomi na nt effects you s ee i n the peri phery a re qui te s i mi l a r to thos e of NE i ts el f (- a nd 1 a cti va ti on) beca us e they
a re ca us ed by NE. They a l s o di rectl y, but rel a ti vel y very wea kl y, a cti va te a l l the a drenergi c receptors a l pha s a nd the beta s . Ephedri ne a nd
ps eudoephedri ne a l s o exert s i mi l a r effects i n the CNS, l ea di ng to s uch effects a s grea ter a l ertnes s (a nd di ffi cul ty fa l l i ng a s l eep) a nd a ppeti tes uppres s i on (a norexi geni c effect). The i ntens i ty of thes e effects i s grea ter tha n thos e of typi ca l di rect-a cti ng a drenergi c a goni s ts (EPI, NE, etc) but
much wea ker tha n thos e of i ndi rect-a cti ng s ympa thomi meti cs s uch a s the a mpheta mi nes .
Ephedri nes a cti ons a re not a t a l l s el ecti ve for -receptors on va s cul a r s mooth mus cl e, or a nywhere el s e. So, a ns wer a i s i ncorrect. The mi xeda cti ng (a nd i ndi rect-a cti ng) s ympa thomi meti cs ha ve no - (or - or chol i nergi c) bl ocki ng a cti vi ty (b); do not enha nce NE s ynthes i s (c); a nd do not
i nhi bi t NEs meta bol i s m i n a ny other wa y (d).
Note: Some texts a nd l ecturers downpl a y di s cus s i ons of ephedri ne. After a l l , i t wa s commonl y a bus ed a s a genera l CNS s ti mul a nt (to keep one
a wa ke) a nd a s a n a norexi geni c (a ppeti te s uppres s i ng/wei ght l os s ) drug. Such us es ha ve l a rgel y been reduced by FDA ma nda te. It i s a l s o a n
outmoded drug for a s thma , beca us e i t ha s bronchodi l a tor a cti vi ty, but tha t i s very wea k. Al though the drugs va s ocons tri ctor effects a re a l s o
rel a ti vel y wea k (compa red wi th, s a y, epi nephri ne, norepi nephri ne, or phenyl ephri ne), i t i s jus t enough for ma ny cl i ni ca l s i tua ti ons , a nd the drug
i s us ed preci s el y for tha t purpos e qui te frequentl y i ntra opera ti vel y, a s s hown i n thi s pa ti ents opera ti ve drug a dmi ni s tra ti on cha rt.
79. The answer is e. (Brunton, pp 198, 300; Katzung, pp 136f, 141-142.) Ephedri nes mecha ni s ms of a cti on were a ddres s ed i n a previ ous a ns wer. There I
noted tha t ephedri nes di rect va s ocons tri ctor effects a re wea k, a nd they a re not a t a l l l i mi ted to -a drenergi c receptors (va s cul a r or el s ewhere).
Nonethel es s , the wea k di rect va s ocons tri ctor effect combi ned wi th the predomi na nt NE-rel ea s i ng a cti on l ea ds to cl i ni ca l l y us eful va s opres s or
effects . The prea nes theti c a nd i nducti on drugs gi ven to thi s pa ti ent (a nd ma ny others ) a re l i kel y to produce s ome ca rdi odepres s a nt effects
(centra l , ca rdi a c, a nd va s cul a r), one ma ni fes ta ti on of whi ch i s a n exces s i ve fa l l of bl ood pres s ure. Res tori ng bl ood pres s ure i s the ma i n purpos e
for whi ch the ephedri ne i s gi ven here.
Ephedri ne does ca us e CNS-s ti mul a ti ng effects (b), but i t i s genera l l y wea k a nd certa i nl y i ns uffi ci ent to overcome (l et a l one a ffect) the CNS
depres s i on ca us ed by s evera l other drugs the pa ti ent recei ved (mi da zol a m, propofol , a nd morphi ne). Moreover, the pa ti ent i s s uppos ed to be
a nes theti zed; why woul d we wa nt to gi ve a drug to countera ct thi s s o ea rl y i nto s urgery? Ephedri ne does not i nhi bi t SA a nd AV noda l
el ectrophys i ol ogy (c), nor hea rt ra te (d) or contra cti l i ty. If a nythi ng, through i ts i ndi rect a nd NE-rel ea s i ng effects i t woul d be much more l i kel y to
s ti mul a te the hea rt.
Ma ny yea rs a go ephedri ne wa s us ed a s a n ora l bronchodi l a tor, ma i nl y for pa ti ents wi th a s thma . Ha vi ng no ora l or i nha l ed s el ecti ve 2
a goni s ts a s we ha ve toda y, i t wa s ba s i ca l l y the onl y ga me i n town for chroni c ma na gement of a i rwa y s mooth mus cl e cons tri cti on. Its
bronchodi l a tor effects were, a t bes t, wea k. The di rect a cti ons on 2 receptors a re i ntri ns i ca l l y wea k; a nd s i nce NE does not a cti va te 2 receptors , NE
rel ea s e tha t occurs el s ewhere does nothi ng i n the wa y of ca us i ng bronchodi l a ti on. Aga i n, there wa s nothi ng i n the pa ti ents hi s tory of
bronchocons tri cti on, nor di d s he recei ve a ny drugs tha t were l i kel y to ca us e bronchocons tri cti on. (Yes , morphi ne ca n rel ea s e hi s ta mi ne, whi ch ca n
ca us e bronchocons tri cti on, but thi s pa ti ent wa s des cri bed a s otherwi s e hea l thy; a nd s he wa s not a s moker, whi ch mi ght ha ve put her a t s l i ghtl y
grea ter ri s k of bronchocons tri cti on.)
80. The answer is b. (Brunton, p 408; Katzung, pp 84-87, 136f, 148, 355.) In order for ephedri ne to exert i ts predomi na nt NE-rel ea s i ng effects , i t mus t be
ta ken up from the s yna ps e, i nto the a drenergi c nerve endi ng. Coca i ne a nd the tri cycl i c a nti depres s a nts i nhi bi t ephedri ne tra ns port, jus t a s they
i nhi bi t reupta ke of NE tha t ha s been rel ea s ed from a drenergi c nerves i n res pons e to a n a cti on potenti a l (or i n res pons e to other NE-rel ea s i ng
drugs ).
Atenol ol a nd metoprol ol (a ) rel a ti vel y s el ecti vel y bl ock 1 receptors (a t us ua l thera peuti c dos es ; a t hi gh dos es they a l s o bl ock 2 receptors
i mporta nt i f the pa ti ent ha s a s thma , for exa mpl e). They ha ve no -bl ocki ng a cti vi ty a t a l l . Thus , they dont wea ken all the effects of ephedri ne. (If I
ha d l i s ted l a beta l ol or ca rvedi l ol , whi ch bl ock a l l the - a nd a l l the -receptors , Id gi ve you your two poi nts i f you pi cked tha t a ns wer.)
Hexa methoni um a nd tri metha pha n (c) a re a utonomi c (PNS a nd SNS) ga ngl i oni c (NN receptor) bl ocki ng drugs . They ha ve no effect on ephedri nes
di rect receptor-medi a ted a cti ons , nor on ephedri nes NE-rel ea s i ng effects , both of whi ch occur di s ta l to the ga ngl i a . (They woul d, of cours e, reduce
or el i mi na te ba roreceptor refl ex res pons es tha t mi ght a ri s e i f ephedri ne s uddenl y a nd ma rkedl y ra i s ed bl ood pres s ure.) Pa rgyl i ne (d), a rgua bl y
the prototypi c nons el ecti ve monoa mi ne oxi da s e i nhi bi tor, woul d i ntens i fy the res pons es to ephedri ne or other s ympa thomi meti cs tha t work i n
pa rt or i n whol e by rel ea s i ng i ntra neurona l NE. Remember tha t MAO i nhi bi tors ca us e a gra dua l but eventua l l y dra ma ti c ri s e i n i ntra neurona l NE
l evel s by i nhi bi ti ng NE degra da ti on by the enzyme; a nd a l though tha t NE i s not rel ea s ed by a norma l a cti on potenti a l , ca techol a mi ne-rel ea s i ng
s ympa thomi meti cs (ephedri ne, ps eudoephedri ne, a mpheta mi nes , a nd even di eta ry tyra mi ne) certa i nl y, s uddenl y, a nd ma s s i vel y do s o.
Propra nol ol (e), of cours e, bl ocks a l l -a drenergi c receptors , but ha s no -bl ocki ng a cti vi ty a nd s o does not a ffect a ny -medi a ted res pons es to
ephedri ne.
81. The answer is d. (Brunton, pp 241-242, 268; Katzung, pp 106-109.). In the va s t ma jori ty of s i tua ti ons i n whi ch we gi ve a pa ti ent a nondepol a ri zi ng

(cura re-l i ke) neuromus cul a r bl ocki ng drug (vecuroni um i n thi s ca s e), we wi l l a l s o be gi vi ng the pa ti ent two other drugs . One, the focus of thi s
ques ti on, i s a n a cetyl chol i nes tera s e (AChE) i nhi bi tor (neos ti gmi ne, l i s ted here, i s the mos t common one). It i s gi ven to revers e the competi ti ve
s kel eta l neuromus cul a r bl ocka de: ca us e a bui l d-up of ACh a t the s yna ps e by i nhi bi ti ng i ts enzyma ti c hydrol ys i s by AChE), a nd the ACh ca n now
overcome the bl ocka de of the NM receptors on s kel eta l mus cl e.
As expl a i ned more ful l y i n other ques ti ons , the AChE i nhi bi tor wi l l ca us e bui l d-up of ACh a t a l l peri phera l chol i nergi c s yna ps es by i nhi bi ti ng
AChs meta bol i c i na cti va ti on. Thi s l ea ds to a va ri ety of us ua l l y unwa nted mus ca ri ni c effects . [Neos ti gmi ne does not enter the CNS, a s does
phys os ti gmi ne (whi ch i s not a t a l l a ppropri a te for thi s i ndi ca ti on), a nd s o a ns wer c i s i ncorrect.] If the neos ti gmi ne (a l one) does a nythi ng to bl ood
pres s ure i t wi l l ca us e a fa l l (not a ri s e, a ) due to the drugs i ndi rect (vi a i ncrea s ed ACh) nega ti ve chronotropi c effect on the hea rt (thus , b i s a l s o
i ncorrect). The s econda ry ri s e of ACh wi l l a l s o s ti mul a te the bl a dders detrus or a nd tri gone, a nd rel a x the s phi ncter, a nd s o there wi l l be no
reduced ri s k or s everi ty of uri na ry i nconti nence (e).
82. The answer is b. (Brunton, pp 265-268; Katzung, pp 106-109.) The pa ti ent wi l l recei ve neos ti gmi ne, a nd a s expl a i ned i n the previ ous ques ti on i t wi l l
a ct a t a l l chol i nergi c s yna ps es i n the peri phera l nervous s ys temthe NM receptors on s kel eta l mus cl e tha t we wa nt to rea cti va te, a nd the
mus ca ri ni c receptors tha t we dont. If we di dnt bl ock the mus ca ri ni c res pons es fi rs t, the pa ti ent i s l i kel y to experi ence ACh-medi a ted s uppres s i on
of hea rt ra te a nd noda l a utoma ti ci ty a nd conducti on; s ti mul a ti on of va ri ous gut a nd uri na ry tra ct mus cl es a nd rel a xa ti on of s phi ncters ;
bronchocons tri cti on; a nd i ncrea s es i n the s ecretory a cti vi ty of a hos t of exocri ne gl a nds (s a l i va ry, l a cri ma l , mucous , ga s tri c a ci d/pa ri eta l cel l ). As a
res ul t, a nd routinely, we gi ve a n a nti mus ca ri ni c drug ri ght before gi vi ng the s ti gmi ne, a nd tha t i s wha t you need to know (a nd s houl d ha ve been
a bl e to deduce, even though you mi ght not be fa mi l i a r a t a l l wi th gl ycopyrrol a te.)
Note: Gl ycopyrrol a te i s yet a nother drug tha t s eems to get rel ega ted to mi s cel l a neous or uni mporta nt s ta tus i n texts a nd l ectures (i n whi ch i t
mi ght not be menti oned a t a l l ). However, i t i s us ed routi nel y i n ma ny hos pi ta l s a s the go-to a nti mus ca ri ni c i n s i tua ti ons s uch a s des cri bed here.
Why not a tropi ne, whi ch you obvi ous l y know a bout? The effects of a tropi ne tend to l a s t much l onger tha n wha t i s needed here. Gl ycopyrrol a tes
ons et a nd dura ti on of a cti on a re s horter tha n a tropi nes i ndeed, a ra ther cl os e ma tch to the pha rma coki neti cs of neos ti gmi ne, a nd s o i t i s a n
excel l ent choi ce for thi s us e.
83. The answer is e. (Brunton, pp 263-268; Katzung, pp 466-467, 475-476, 481.) At us ua l thera peuti c (i e, nontoxi c) dos es s ucci nyl chol i ne (SuCh) ca us es
ra pi d, bri ef (wi th a s i ngl e dos e), a nd noncompeti ti ve depol a ri zi ng bl ocka de of NM receptors on s kel eta l mus cl e. Even i f s kel eta l mus cl e pa ra l ys i s
i s ma i nta i ned l onger by conti nuous i nfus i on of the drug (i t i s s ometi mes done), s kel eta l mus cl e functi on wi l l return s ponta neous l ydue to ra pi d
meta bol i c i na cti va ti on of the drug by chol i nes tera s es wi thout the need to a dmi ni s ter a ny revers a l drug. Indeed, for a l l pra cti ca l purpos es there
i s no cl i ni ca l l y us eful SuCh revers a l drug (but s ee the note bel ow). Succi nyl chol i ne ha s no effect on mus ca ri ni c receptors , a nd s o a tropi ne (a ) or
a ny other a nti mus ca ri ni c drug wi l l do nothi ng i n terms of s kel eta l mus cl e functi on. Betha nechol (b) a cti va tes onl y mus ca ri ni c receptors (a t a l l but
extra ordi na ri l y hi gh dos es ). Sti gmi nes (neos ti gmi ne, phys os ti gmi ne, or a ny other AChE i nhi bi tors ) wi l l theoreti ca l l y a dd to s kel eta l mus cl e
pa ra l ys i s , not revers e i t. (I s a y theoreti ca l l y beca us e i f s kel eta l mus cl e i s now pa ra l yzed by SuCh, i ts not l i kel y tha t ma ki ng more ACh a va i l a bl e a t
the s kel eta l neuromus cul a r juncti on wi l l i ntens i fy a n a l rea dy ma xi mum res pons e.)
Note: You ma y ha ve l ea rned a bout s o-ca l l ed Pha s e-2 neuromus cul a r bl ocka de ca us ed by SuCh, a nd tha t i t ca n be revers ed wi th s uch drugs a s
a tropi ne. Thi s Pha s e 2 bl ock i s not a pa rt of the norma l pha rma col ogy of SuCh unl es s a fra nk overdos e occurs a nd toxi ci ty devel ops . Pha s e 2
bl ock can be pa rti a l l y revers ed by a dmi ni s tra ti on of a n a nti chol i nergi c drug (eg, gl ycopyrrol a te or a tropi ne i ts el f), but a ddi ng yet a nother drug to a
drug-overdos ed pa ti ent i s nt the wa y to go. If Pha s e 2 bl ock from s ucci nyl chol i ne does occur a l l one needs to do i s keep the pa ti ent on mecha ni ca l
venti l a ti on for a s l ong a s neces s a ry, s i mpl y wa i t for the drug to be el i mi na ted (yes , i t ma y ta ke a whi l e), a nd be a s s ure a s pos s i bl e before
extuba ti ng the pa ti ent a nd/or s toppi ng mecha ni ca l venti l a ti on tha t s ponta neous res pi ra ti on i s a dequa te a nd not l i kel y to be compromi s ed a ga i n.
84. The answer is a. (Brunton, pp 227-234; Katzung, pp 99-104.) Thes e a re expected s i de effects (not a t a l l i di os yncra ti c, b) from betha nechol , a
mus ca ri ni c a goni s t (pa ra s ympa thomi meti c drug). They occur even though the effects of the drugthe ones for whi ch i t i s gi vena re
predomi na tel y on the bl a dder mus cul a ture: contra cti on of the detrus or a nd rel a xa ti on of the s phi ncter to ena bl e (i f not ca us e) uri na ti on. The
s i de effects noted i n the ques ti on nonethel es s a re common a nd dos e- (a nd pa ti ent-) dependent, a nd not a t a l l i di os yncra ti c rea cti ons . Moreover,
a l though we coul d i nhi bi t thos e s i de effects wi th a n a tropi ne-l i ke (a nti mus ca ri ni c) drug, doi ng s o woul d s i mul ta neous l y i nhi bi t the drugs
i ntended effects on the bl a dder. Betha nechol ha s no s ympa theti c (or pa ra s ympa theti c) ga ngl i oni c a cti va ti ng (c) or bl ocki ng a cti ons a t us ua l dos es .
The potenti a l ca rdi a c/ca rdi ova s cul a r effects of betha nechol us ed a t us ua l dos es a re not s o s i mpl e to expl a i n, but certa i nl y woul d not i nvol ve
ba roreceptor refl ex-medi a ted s uppres s i on of ca rdi a c ra te (d). In order for the ba roreceptors to refl exl y s uppres s hea rt ra te, bl ood pres s ure woul d
ha ve to go up qui te a bi t, a nd qui te qui ckl y. Betha nechol i s a va s odi l a tor, a nd s o woul d l ower BP (qui ckl y, i f i njected too fa s t). The expected ba roreceptor res pons e to tha t woul d be i ncrea s ed s ympa theti c outfl ow from the CNS to the peri phery, a nd tha t i n turn woul d fa vor refl ex ta chyca rdi a .
However, betha nechol s i mul ta neous l y wi l l di rectl y s uppres s s ponta neous depol a ri za ti on (Pha s e 4 of the a cti on potenti a l ) of the S-A node,
a ttempti ng to s l ow hea rt ra te vi a di rect mus ca ri ni c receptor a goni s t a cti vi ty. So, wha t ha ppens to hea rt ra te? So the chronotropi c effects depend on
whether the di rect bra dyca rdi c effect wi ns out or the refl ex ta chyca rdi c i nfl uences do.
If the pa ti ent ha d undi a gnos ed a s thma (e; the pres ence of a s thma woul d contra i ndi ca te us e of the drug), the pul mona ry res pons e woul d be
much more s i gni fi ca nt tha n s ome wheezi ng. Potenti a l l y fa ta l broncho-s pa s m coul d occur beca us e the a i rwa y s mooth mus cl es of a s thma ti c
i ndi vi dua l s a re exqui s i tel y (hyper)s ens i ti ve to mus ca ri ni c a goni s ts , wi th even s ma l l dos es of thos e drugs ca pa bl e of ca us i ng a l etha l outcome.
85. The answer is c. (Brunton, pp 178-180t, 290; Katzung, pp 90t, 131-132, 136-140, 145-147.) Ri todri ne ma y no l onger be us ed for s uppres s i ng prema ture
uteri ne contra cti ons (a tocol yti c effect), but the des cri pti on of thi s drugs a cti ons , I thi nk, hel ps you work through your unders ta ndi ng of ba s i c
a utonomi c functi on a nd drugs . Ri todri ne i s a rel a ti vel y s el ecti ve 2 -a drenergi c a goni s t tha t rel a xes uteri ne s mooth mus cl e. Note the word
rel a ti vel y; the preferenti a l 2 effects (vs 1 ) a re not a bs ol ute, a nd they a re dos e-dependent. Yes , ri todri ne, the uteri ne-rel a xi ng drug i s cl a s s i fi ed
mecha ni s ti ca l l y the s a me a s , for exa mpl e, a l buterol , s a l meterol , or terbuta l i ne, a nd s evera l other drugs typi ca l l y us ed a s a drenergi c
bronchodi l a tors for a s thma . Wi l l , or ca n, ri todri ne ca us e bronchodi l a ti on? Abs ol utel y, even a t the rel a ti vel y l ow dos es us ed for uteri ne-rel a xi ng
effects ! And when bl ood l evel s become s uffi ci entl y hi gh (a nd perha ps even s ti l l i n the thera peuti c ra nge for uteri ne effects ) the preferenti a l
a cti va ti on of 2 receptors i s l os t, a nd the drug beha ves jus t l i ke i s oproterenol , the prototype 1 /2 a goni s t, to ca us e not onl y bronchodi l a ti on but
a l s o ca rdi a c s ti mul a ti on, enha nced reni n s ecreti on, hypergl ycemi a , a nd more. Thi s dos e-dependent l os s of 2 -a drenergi c a goni s t s el ecti vi ty i s a
property of a l l the drugs cl a s s i fi ed, qui te i mpreci s el y, a s s el ecti ve 2 a goni s ts or (even l es s preci s el y) a s s el ecti ve a drenergi c bronchodi l a tors .
86. The answer is b. (Brunton, pp 154-158, 172t, 220-226; Katzung, p 460.) Morphi ne i s one of s evera l drugs tha t ca n ca us e a di rect degra nul a ti ng effect
on ma s t cel l s , ca us i ng the rel ea s e of not onl y hi s ta mi ne but a l s o of ma ny other ma s t cel l -deri ved medi a tors . The hi s ta mi ne-rel ea s i ng effect i s not
cl i ni ca l l y s i gni fi ca nt for pa ti ents who do not ha ve a s thma , but for ma ny who do the bronchocons tri cti on ca n be i ntens e a nd probl ema ti c. Youl l
proba bl y s ee the ma ni fes ta ti ons of thi s , even i f the res pons e i s mi l d. They typi ca l l y a ppea r i n the form of cuta neous fl us hi ng (l a rgel y hi s ta mi ne-

medi a ted), pa rti cul a rl y i n the neck a nd fa ce regi ons .

Atropi ne (a ) ca us es bronchodi l a ti on by bl ocki ng mus ca ri ni c receptors on a i rwa y s mooth mus cl e cel l s . Pa ncuroni um (d) does not ca us e
s i gni fi ca nt hi s ta mi ne rel ea s e, nor do i ts rel a ted nondepol a ri zi ng s kel eta l neuromus cul a r bl ockers (eg, vecuroni um). (D-tubocura ri ne, whi ch us ed
to be the prototype of thi s cl a s s of neuromus cul a r bl ockers , di d ca us e a ppreci a bl e hi s ta mi ne rel ea s e, but i t i s no l onger us ed.) Neos ti gmi ne (c)
ca n ca us e s i gni fi ca nt bronchocons tri cti on i n a s thma ti cs , but tha t occurs beca us e the drug i nhi bi ts meta bol i c i na cti va ti on (by AChE) of a cetyl chol i ne
a nother bronchocons tri ctor a goni s t to whi ch the a i rwa ys of a s thma ti cs a re exqui s i tel y s ens i ti ve. Propra nol ol (e) ca n provoke s evere a nd
s ometi mes fa ta l a i rwa y s mooth mus cl e contra cti on i n a s thma ti cs , but tha t i s due to bl ocka de of epi nephri nes a goni s t (bronchodi l a tor) a cti ons on
2 receptors . It does not i nvol ve hi s ta mi ne rel ea s e from ma s t cel l s .
87. The answer is e. (Brunton, pp 142-145, 233-235; Katzung, pp 122-123, 174.) Ans weri ng thi s ques ti on requi res your knowl edge of two thi ngs : how
tri metha pha n i s cl a s s i fi ed (wha t i t does ); a nd whi ch bra nch of the a utonomi c nervous s ys tem, pa ra s ympa theti c or s ympa theti c, exerts
predomi na nt res ti ng tone over va ri ous s tructures a nd thei r functi ons . Tri metha pha n i s a n a utonomi c ga ngl i oni c bl ocki ng drug, preventi ng
a cti va ti on of NN receptors found on a l l pos tga ngl i oni c nerves (a nd on the a drena l /s upra rena l medul l a ). Upon gi vi ng thi s drug we es s enti a l l y
denerva te di s ta l s tructures by a pha rma col ogi c mea ns . (If you ha ve not s peci fi ca l l y l ea rned or rea d a bout tri metha pha n, perha ps you know a bout
other a nd very ol d ga ngl i oni c bl ocki ng drugs s uch a s hexa methoni um. Its OK to cons i der thes e ga ngl i oni c bl ockers equi va l ent for the purpos e of
a ns weri ng thi s ques ti on.) Now, we obs erve how thi ngs cha nge.
For a l l the s tructures a nd functi ons l i s ted (a nd s evera l others tha t werent), with the exception of controlling vascular smooth muscle and peripheral
resistance (vasomotor tone), i t i s the pa ra s ympa theti c nervous s ys tem tha t exerts the predomi na nt res ti ng tone. In contra s t, control of va s cul a r
s mooth mus cl e tone (a nd, therefore, of peri phera l res i s ta nce a nd bl ood pres s ure) i s pri ma ri l y regul a ted by the s ympa theti c nervous s ys tem. Bl ock
a l l ga ngl i oni c tra ns mi s s i on a nd va s odi l a ti on wi l l occur a s predomi na nt SNS i nfl uences on the ves s el s a re removed.
As fa r a s the other s tructures goa l l of whi ch, I s a i d, ha ve predomi na nt PNS tone a t res tyou woul d obs erve a ri s e of hea rt ra te (not
bra dyca rdi a , a ); decrea s es of bl a dder a nd gut tone (eg, reduced tone of the bl a dder detrus or a nd l ongi tudi na l mus cl es of the gut), not i ncrea s es
(b); contra cti on of s phi ncters i n the GI a nd uri na ry tra cts ; mydri a s i s ; a nd reduced s a l i va ry s ecreti ons (xeros tomi a ), not i ncrea s es (c). Eccri ne s wea t
gl a nd s ecreti ons , whi ch a re ma i nl y under s ympa theti c-chol i nergi c i nfl uences , woul d decrea s e too. In terms of pupi l s i ze, ga ngl i oni c bl ocka de
woul d l ea d to mydri a s i s , not mi os i s (d).
Fi na l l y, rea l i ze tha t i n the pres ence of a n a utonomi c ga ngl i oni c bl ocki ng drug no a utonomi c refl exes (eg, ba roreceptor refl exes ; pupi l l a ry
cons tri cti on i n res pons e to bri ght l i ght) ca n occur. Al though the a fferent pa thwa ys tha t a re i mporta nt i n el i ci ti ng thos e refl exes a re uni mpa i red,
res pons es s uch a s cha nges i n hea rt ra te or pupi l s i ze depend on i nta ct efferent pa thwa ys , a nd ga ngl i oni c bl ocka de i nterrupts thos e pa thwa ys a nd
the refl ex res pons es tha t otherwi s e mi ght occur.
88. The answer is a. (Brunton, pp 918-926, 1313-1314; Katzung, pp 115-124, 278f, 292, 518, 525-528, 534-536.) Thes e drugs a l l pos s es s a nti mus ca ri ni c
(a tropi ne-l i ke) a cti ons tha t often a re s uffi ci entl y s trong to ca us e a l l the s i de effects a nd a dvers e res pons es a s s oci a ted wi th a tropi ne i ts el f.
Li kewi s e, i t i s prudent to a s s ume they s ha re a l l the contra i ndi ca ti ons a nd preca uti ons a s s oci a ted wi th a tropi ne a nd tha t ma na gi ng s evere
overdos es of thos e drugs or drug groups wi l l res embl e (a nd need to be trea ted) i n qui te the s a me wa y a s thos e of the prototype a nti mus ca ri ni c.
Tha t woul d i ncl ude the potenti a l need to a dmi ni s ter phys os ti gmi ne, the a cetyl chol i nes tera s e i nhi bi tor tha t pl a ys a n i mporta nt rol e i n ma na gi ng
a tropi ne poi s oni ng.
Note tha t of a l l the drugs wi th a tropi ne-l i ke a cti ons , di phenhydra mi ne (a nd, to a s omewha t l es s er extent the other fi rs t-genera ti on
a nti hi s ta mi nes ) a re a va i l a bl e over-the-counter. Al though you ma y do your bes t to a voi d pres cri bi ng drugs wi th a tropi ne-l i ke a cti ons for pa ti ents
who s houl d not recei ve them, a tropi ne-l i ke probl ems ca n a ri s e i n pa ti ents who s el f-pres cri be thes e nonpres cri pti on medi ca ti ons .
Cl ea rl y, the effects of betha nechol (mus ca ri ni c a goni s t) a nd neos ti gmi ne (a cetyl chol i nes tera s e i nhi bi tor) a re the oppos i te of thos e youd expect
to s ee wi th a tropi ne (mus ca ri ni c receptor bl ocker). You mi ght a rgue tha t i s oproterenol (1 a nd 2 a goni s t) ca us es s ome effects (eg, ta chyca rdi a )
tha t you woul d expect wi th a tropi ne. True. However, des pi te a ny s i mi l a ri ti es i n a ppea ra nce, the mecha ni s m i s qui te di fferent, the s pectrum of a l l
effects ca us ed by the drug i s di fferent, a nd certa i nl y mos t contra i ndi ca ti ons a nd toxi c ma ni fes ta ti ons a re very di fferent. Propra nol ol (prototype
nons el ecti ve -bl ocker) i s ra di ca l l y di fferent from a tropi ne i n nea rl y every i mporta nt wa y.
89. The answer is b. (Brunton, pp 86t, 250, 918-924, 1313-1314, 1851-1816; Katzung, pp 122-125, 1034.) The ma jor s i gns a nd s ymptoms of di phenhydra mi ne
toxi ci ty a re a ttri buta bl e to i ts s trong a nti mus ca ri ni c (a tropi ne-l i ke) effects i n both the peri phera l a nd centra l nervous s ys tems . Neos ti gmi ne
unl i ke the preferred a nti dote, phys os ti gmi nei s a qua terna ry compound a nd does not enter the CNS. Thus , del i ri um, ha l l uci na ti ons , a nd other
CNS ma ni fes ta ti ons of di phenhydra mi ne poi s oni ng wi l l pers i s t. Phys os ti gmi ne i s the preferred a nti dote s peci fi ca l l y beca us e i t i s not a qua terna ry
(i oni zed) a t phys i ol ogi c pH, a nd wi l l rea di l y ca us e des i red a nti dota l effects i n the CNS a s wel l a s i n the peri phery.
Bronchocons tri cti on a nd wheezi ng (a ) a re not expected outcomes of di phenhydra mi ne toxi ci ty; the a nti mus ca ri ni c effects of the drug wi l l ca us e
bronchodi l a ti on by bl ocki ng the bronchocons tri ctor i nfl uences of endogenous ACh. Li kewi s e, toxi c (or even thera peuti c) bl ood l evel s of
di phenhydra mi ne wi l l i nhi bi tnot s ti mul a teexocri ne gl a nd s ecreti ons (c). Exces s es of di phenhydra mi ne (or a tropi ne i ts el f) wi l l ha ve no
s i gni fi ca nt effects on s kel eta l mus cl e a cti va ti on (d) beca us e thes e drugs onl y a ffect mus ca ri ni c receptors ; s kel eta l mus cl e a cti va ti on by ACh
i nvol ves ni coti ni c receptors . Overdos es of di phenhydra mi ne or a ny other drugs wi th s trong peri phera l mus ca ri ni c receptor-bl ocki ng effects
certa i nl y wi l l ca us e ta chyca rdi a by bl ocki ng mus ca ri ni c receptor a cti va ti on of the s i no-a tri a l node. Tha t effect ca n be revers ed by
a cetyl chol i nes tera s e i nhi bi tors , even thos e tha t work onl y i n the peri phera l nervous s ys tems , s uch a s neos ti gmi ne.
You wont encounter too ma ny pa ti ents overdos ed on a tropi ne i ts el f, but youl l s ee ma ny peopl e s ufferi ng toxi ci ty from ol der a nti hi s ta mi nes
(eg, di phenhydra mi ne), ol der (tri cycl i c or tetra cycl i c) a nti depres s a nts (eg, i mi pra mi ne), s ome of the centra l l y a cti ng a nti mus ca ri ni cs tha t a re us ed
for pa rki ns oni s m (eg, benztropi ne a nd tri hexypheni dyl ); s copol a mi ne (us ed for moti on s i cknes s ), a nd mos t of the phenothi a zi ne a nti ps ychoti cs
(eg, chl orproma zi ne). Owi ng to the often s trong a nti mus ca ri ni c s i de effects of thes e drugs , trea ti ng overdos es of a ny of them proba bl y wi l l i nvol ve
ma na gi ng wha t a mounts to a tropi ne poi s oni nga nd ma ny other probl ems too.
(You ma y not know thi s , but perha ps i t wi l l ha ve s ome mea ni ng or hel p jog your memory: the tra de na me for phys os ti gmi ne i s Anti l i ri um. Reca l l
tha t one of the ha l l ma rk CNS s i gns of a tropi ne/a nti mus ca ri ni c poi s oni ng i s del i ri um. Hence, anti-lirium ma kes s ens e.)
90. The answer is d. (Brunton, pp 206t, 290, 301, 321t, 804-805; Katzung, pp 141-142, 144, 148, 225.) Dobuta mi ne beha ves , for a l l pra cti ca l purpos es , a s a
s el ecti ve 1 a goni s t. Norepi nephri ne i s a 1 a goni s t tha t a l s o a cti va tes -a drenergi c receptors effecti vel y. However, when i t i s a dmi ni s tered wi th
phentol a mi ne (prototype -bl ocker) i ts s pectrum of a cti vi ty i s , qua l i ta ti vel y, i denti ca l to tha t of dobuta mi ne.
Hi gh dos es of dopa mi ne (a ) ca us e pos i ti ve i notropi c a nd chronotropi c effects , but a l s o rel ea s e neurona l norepi nephri ne a nd proba bl y a cti va te
-a drenergi c receptors di rectl y (ca us i ng unwa nted va s ocons tri cti on). Thes e va s ocons tri ctor effects woul d nega te va s odi l a tor effects due to
s ti mul a ti on of dopa mi ne D 1 receptors found i n s ome a rteri ol es ; a nd of D 2 receptors found on s ome ga ngl i a , a nd i n the ca rdi ova s cul a r control
center of the CNS.

Ephedri ne (b) wea kl y a cti va tes a l l a drenergi c receptors a nd a l s o l ea ds to norepi nephri ne rel ea s e. Overa l l , i ts effects a re qui te s i mi l a r to thos e
produced by norepi nephri ne i ts el f. Rega rdl es s , the i ntens i ty peri phera l a drenergi c res pons es for a us ua l thera peuti c dos e of ephedri ne us ua l l y
a re l es s i ntens e tha n thos e norepi nephri ne. And i f one a dmi ni s ters ephedri ne wi th propra nol ol (c), the prototypi c nons el ecti ve (1 a nd 2 )
bl ocker, ephedri nes rema i ni ng a cti ons a mount to s el ecti ve -a drenergi c a cti va ti on (i e, phenyl ephri ne-l i ke)not a t a l l l i ke dobuta mi ne, a nd not
a t a l l wha t we wa nt i n thi s s i tua ti on.
Phenyl ephri ne (-a goni s t) pl us a tropi ne (mus ca ri ni c a nta goni s t) (e) ca us es effects tha t i n no wa y res embl e thos e of dobuta mi ne or the
norepi nephri ne-phentol a mi ne combi na ti on. From a ca rdi ova s cul a r pers pecti ve, thi s combi na ti on woul d gi ve us a ri s e of bl ood pres s ure due to
peri phera l va s ocons tri cti on. The va s ocons tri cti on woul d el i ci t a ba roreceptor refl ex ta nta mount to wi thdra wi ng s ympa theti c tone a nd i ncrea s i ng
oppos i ng pa ra s ympa theti c tone. However, the pres ence of a tropi ne woul d bl unt pa ra s ympa theti c-medi a ted ca rdi a c s l owi ng. The overa l l a nd
combi ned effect on hea rt ra te of reduced s ympa theti c tone to the SA node, a nd concomi ta nt bl ocka de of ACh-medi a ted ca rdi a c s l owi ng (a l s o a n
effect on the SA node) ca n va ry. However, i t woul d be rea s ona bl e to predi ct a s l i ght i ncrea s e of ra te over predrug ra tes . Nonethel es s , there woul d
not be a pos i ti ve i notropi c res pons e, whi ch i s wha t woul d occur wi th ei ther dobuta mi ne or a norepi nephri ne-phentol a mi ne combi na ti on.
91. The answer is a. (Brunton, pp 178-179; Katzung, pp 88-90, 138-145.) Wi th onl y one ma jor excepti on (eccri ne s wea t gl a nds ), the neurotra ns mi tter
rel ea s ed by pos tga ngl i oni c s ympa theti c nerves (a drenergi c nerves ) to a cti va te thei r ta rgets i s norepi nephri ne (NE). NE i s a good a goni s t for onl y
- a nd 1 -a drenergi c receptors , but not 2 . In contra s t, epi nephri ne (EPI; from the a drena l medul l a ) i s a very effi ca ci ous a goni s t for both cl a s s es of
a drenergi c receptors a nd thei r ma i n s ubtypes , i ncl udi ng 2 . Of the res pons es l i s ted i n the ques ti on, onl y a i rwa y s mooth-mus cl e rel a xa ti on i s a
proces s tha t i nvol ves (depends on) a utonomi c a cti va ti on of 2 -a drenergi c receptors . There i s no i nnerva ti on of thes e mus cl es , a nd s o no NE to be
rel ea s ed. Even i f NE were i njected, i ts l a ck of 2 -a goni s t a cti vi ty woul d render i t i neffecti ve a s a bronchodi l a tor.
A-V noda l a utoma ti ci ty a nd conducti on (b) a re i ncrea s ed, i n terms of s ympa theti c i nfl uences , by 1 receptors , whi ch ca n be a cti va ted by ei ther or
both NE a nd EPI. The s a me a ppl i es to the corona ry va s cul a ture, whi ch cons tri cts i n res pons e to -a drenergi c receptor a cti va ti on by ei ther or both NE
or EPI. (If the a ns wer choi ce were corona ry va s odi l a ti on i nvol vi ng s ympa theti c i nfl uences , then onl y EPI woul d be a correct a ns wer, s i nce
s ympa theti c corona ry va s odi l a ti on i nvol ves 2 receptors .) Ei ther NE or EPI wi l l ca us e mydri a s i s (d), whi ch i s a n -medi a ted res pons e. Fi na l l y,
s ympa theti ca l l y i nfl uenced reni n rel ea s e from the juxta gl omerul a r a ppa ra tus i nvol ves 1 a cti va ti on, whi ch ca n be ca us ed by ei ther NE or EPI.
Note: You ma y ha ve l ea rned s omethi ng l i ke i f i ts a s ympa theti c res pons e i nvol vi ng the hea rt, the receptor i nvol ved i s 1 . Wel l , tha ts us ua l l y
true, but now you s ee tha t s ympa theti c medi a ted corona ry vascular smooth muscle rel a xa ti ona res pons e tha t occurs i n the hea rti nvol ves 2
receptors . (-Adrenergi c receptor a cti va ti on i n the corona ri es ca us es va s ocons tri cti on, jus t a s occurs i n the peri phery.) You ma y ha ve a l s o l ea rned
i f a 1 receptor i s i nvol ved, the res pons e i s occurri ng (onl y) i n the hea rt. Aga i n, the s ta tement i s us ua l l y true, but juxta gl omerul a r cel l reni n
rel ea s e i s obvi ous l y occurri ng outs i de the hea rt, but i t i s a 1 -medi a ted res pons e nonethel es s .
92. The answer is e. (Brunton, pp 200-201; Katzung, pp 84-86.) In s hort, the a ns wer i s reupta ke. A norepi nephri ne tra ns porter pl a ys the ma i n rol e i n
termi na ti ng the a cti vi ty of neurona l l y (phys i ol ogi ca l l y) rel ea s ed NE. Thi s tra ns porter i s bl ocked by coca i ne a nd tri cycl i c a nti depres s a nts (eg,
i mi pra -mi ne). Di ffus i on of rel ea s ed NE from the s yna pti c s pa ce, l ea di ng to meta bol i s m by s uch enzymes a s COMT (d), i s overa l l a mi nor proces s i n
terms of the phys i ol ogi c i na cti va ti on of the effects of NE. Meta bol i c i na cti va ti on by MAO (c) requi res reupta ke of the ca techol a mi nes i nto the
neuron, s i nce the MAO tha t degra des ca techol a mi nes i s l oca ted i ntra neurona l l y (a nd i ntra mi tochondri a l l y).
93. The answer is b. (Brunton, pp 289-290; Katzung, pp 90t, 108, 118, 136-145.) To me, the ti p-off tha t hel ps get to the correct a ns wer, i s oproterenol , i s to
focus (no pun i ntended) on the fa ct tha t the unknown drug di d not cha nge the s i ze of the pupi l of the eye. Of a l l the ma i n a utonomi c receptor
types , a drenergi c a nd chol i nergi c, onl y the -receptors pl a y no rol e i n regul a ti ng the s i ze of the pupi l . Tha t na rrows thi ngs down to i s oproterenol or
propra nol ol . Propra nol ol mi ght l ower BP (pa rti cul a rl y i n a hypertens i ve pa ti ent), but i t woul d not ra i s e hea rt ra te or di l a te the bronchi . Onl y
i s oproterenol fi ts the bi l l .
And the other a ns wers ? Atropi ne (a ) mi ght ra i s e hea rt ra te, i t i s not l i kel y to l ower BP, a nd i t wi l l rel a x a i rwa y s mooth mus cl e cel l s a nd i ncrea s e
bronchi ol a r di a meter, but i t woul d ca us e mydri a s i s , whi ch we dont s ee i n the res ul ts pres ented i n the di a gra m. Neos ti gmi ne (c) woul d s l ow hea rt
ra te, perha ps l ower BP (proba bl y not), a nd cons tri ct the a i rwa ys a nd pupi l s . Phenyl ephri ne (d) woul d ra i s e BP, a nd i f the BP ri s e i s s uffi ci entl y hi gh
a nd qui ck, refl exl y l ower hea rt ra te (ba roreceptors ). It woul d do nothi ng to a i rwa y di a meter, but woul d ca us e mydri a s i s .
94. The answer is c. (Brunton, pp 206t, 212, 305-307; Katzung, pp 151-156.) Ta ms ul os i n i s a s el ecti ve 1 -a drenergi c bl ocker, much l i ke pra zos i n (note the
-os i n a t the end of the generi c na mes tha ts a certa i n ti p-off to the drugs genera l cl a s s ), a nd pres uma bl y i ts a ffi ni ty i s grea ter for -receptors
on s mooth mus cl es i n the pros ta te (hence, i ts us e for BPH, due to rel a xa ti on of s mooth mus cl es there) tha n for thos e i n the peri phera l
va s cul a ture. Nonethel es s , i ts pha rma col ogi c profi l e i s mos t s i mi l a r to tha t of pra zos i n, whi ch ca n be cons i dered the prototypi c 1 -s el ecti ve
a drenergi c bl ocker tha t i s ma i nl y us ed to trea t hypertens i on beca us e i t competi ti vel y bl ocks va s ocons tri cti on ca us ed by -a goni s ts s uch a s
epi nephri ne a nd norepi nephri ne. (Remember: Drugs wi th a generi c na me tha t ends i n -os i n or -zos i n a re s el ecti ve 1 -a drenergi c bl ockers : eg,
ta ms ul os i n, pra zos i n, tera zos i n, doxa zos i n.)
So, of the a ns wers l i s ted a bove, orthos ta ti c hypotens i on i s the mos t l i kel y s i de effect. Among the ma ny cl a s s es of a drenergi c drugs , bra dyca rdi a
(a ) woul d mos t l i kel y be ca us ed by a -bl ocker (or l es s er pres cri bed drugs s uch a s res erpi ne, a ca techol a mi ne depl etor), or a mus ca ri ni c a goni s t or
chol i nes tera s e i nhi bi tor, a nd certa i nl y not by a drug tha t ha s no di rect ca rdi a c effects a nd i s more l i kel y to el i ci t refl ex ca rdi a c s ti mul a ti on
s econda ry to reduced bl ood pres s ure. There a re no known i ntera cti ons between -bl ockers a nd a torva s ta ti n or rel a ted drugs , whether i nvol vi ng
s kel eta l mus cl e pa thol ogy a nd dys functi on (b) or other a dvers e res pons es tha t a s ta ti n mi ght ca us e. Photophobi a (d) i s a n exceedi ngl y unl i kel y
probl em: i t i s us ua l l y ca us ed by drugs tha t ca us e mydri a s i s (eg, -a drenergi c a goni s ts or a nti mus ca ri ni cs ), a nd i f a nythi ng ta ms ul os i n i s l i kel y to
prevent the mydri a s i s tha t i s a common ca us e of photophobi a . Exa cerba ti ons of emphys ema (e), whether due to bronchocons tri cti on or other
ca us es , i s unl i kel y too. From a n a utonomi c pers pecti ve, epi nephri ne i s the ma i n bronchodi l a tor s ubs ta nce (vi a 2 a cti va ti on), ACh i s the ma i n
a utonomi c bronchocons tri ctor (vi a mus ca ri ni c a cti va ti on). Ta ms ul os i n a ffects nei ther.
95. The answer is c. (Brunton, pp 226-227, 234-237; Katzung, p 118.) There a re a coupl e of wa ys you coul d ha ve a rri ved a t thi s a ns wer, even i f you di d not
l ea rn s peci fi ca l l y a bout homa tropi ne bei ng a s horter-a cti ng, s emi s yntheti c deri va ti ve of a tropi ne, the prototypi c a nti mus ca ri ni c drug. For one
thi ng, the drugs generi c na me, homa tropi ne, s houl d i mmedi a tel y l ea d you to thi nki ng a bout a n a nti mus ca ri ni c drug.
Now, cons i der ma jor a utonomi c i nnerva ti on of the eye. The s ympa theti c nervous s ys tem, vi a -a drenergi c receptors , control s ma i nl y the s i ze of
the pupi l of the eye; there i s very l i ttl e i nfl uence on the ci l i a ry mus cl e or other s tructures tha t control a ccommoda ti on. (-Adrenergi c i nfl uences
pl a y no rol e i n control l i ng pupi l s i ze or tone of the ci l i a ry mus cl e.) The pa ra s ympa theti c bra nch of the ANS, a nd i ts i nfl uences on mus ca ri ni c
receptors , ca n a l ter both pupi l s i ze a nd a ccommoda ti onpreci s el y wha t we ha ve here. So, we ca n rul e out a ny s ympa theti c drug, a goni s t or
a nta goni s t, a s a correct a ns wer. Thus , we reject epi nephri ne (b), a n - a nd -a goni s t tha t woul d ca us e mydri a s i s ; i s oproterenol (d), the 1/2 a goni s t

a nd propra nol ol (f), the 1/2 bl ocker, tha t a ffect nei ther pupi l s i ze nor a ccommoda ti on. We reject ACh (a ); thi s mus ca ri ni c a goni s t woul d ca us e
mi os i s a nd fa ci l i ta tes a ccommoda ti on. The s a me a ppl i es to pi l oca rpi ne (e). Thi s l ea ves us wi th homa tropi ne (c). So you coul d a rri ve a t thi s correct
a ns wer ei ther by the proces s of el i mi na ti on, or by ma ki ng a n educa ted gues s (correctl y, of cours e) tha t homa tropi ne i s a n a tropi ne-l i ke
(a nti mus ca ri ni c) drug.
96. The answer is d. (Brunton, pp 178-179, 214; Katzung, pp 102-103, 331-337.) ACh, i n vi vo or i n vi tro, ca us es i ts va s odi l a tor res pons e vi a a n a cti on on the
endothel i um, where the mus ca ri ni c receptors a re l oca ted. The va s odi l a tor res pons e ul ti ma tel y depends on endothel i a l cel l forma ti on of ni tri c
oxi de (NO), whi ch i n the ca s e of ACh i s a proces s tha t requi res endothel i a l cel l i ntegri ty. When the endothel i um i s da ma ged or removed (d; the
mos t l i kel y ca s e des cri bed here), the di rect effect of ACh on va s cul a r s mooth mus cl e i s contra cti on (cons tri cti on of a rteri ol es ). Atropi ne, the
prototype mus ca ri ni c a nta goni s t, wi l l prevent ACh-medi a ted va s odi l a ti on of i nta ct a rteri ol es (b), wi th i nta ct endothel i um, by bl ocki ng the
i ntera cti on between ACh a nd endothel i a l cel l mus ca ri ni c receptors , but i t wi l l not ca us e va s ocons tri cti on when the endothel i um i s i nta ct (i t i s
i mporta nt here to di s ti ngui s h between preventi ng va s odi l a ti on a nd ca us i ng va s ocons tri cti on). Botul i num toxi n (c) prevents ACh rel ea s e from
chol i nergi c nerves , but i n our experi menta l s etup tha t i s i rrel eva nt beca us e the i n vi tro prepa ra ti on i s devoi d of i nnerva ti on, a nd ACh i s a dded
di rectl y to the ti s s ue ba th. Moreover, even i f the s mooth mus cl e prepa ra ti on were i nnerva ted, botul i num toxi n woul d not convert the us ua l
va s odi l a tor res pons e to ACh i nto a va s ocons tri ctor one.
97. The answer is b. (Brunton, pp 186f, 206t, 1792; Katzung, pp 84, 479, 481.) Botul i num toxi n, the ca us e of botul i s m, i nhi bi ts rel ea s e of ACh from a l l
chol i nergi c nerves , pa rti cul a rl y thos e i n the a utonomi c a nd s oma ti c/motor nervous s ys tems . (Ta ke a l ook a t the s chema ti c of the peri phera l
nervous s ys tems on pa ges 50 a nd 81 to refres h your memory a bout where thes e s i tes a re.) It ha s no a goni s t (a ) a cti vi ty on a ny chol i nergi c
receptors , nor a n a bi l i ty to bl ock ni coti ni c (e) or mus ca ri ni c receptors . The toxi n ha s no di rect effects on a drenergi c nerves (other tha n preventi ng
thei r phys i ol ogi c a cti va ti on by ACh, norma l l y rel ea s ed by prega ngl i oni c s ympa theti c nerves . Thus , NE reupta ke i s not a ffected (c; reca l l tha t coca i ne
a nd tri cycl i c a nti depres s a nts do i nhi bi t NE reupta ke); nor i s NE rel ea s ed (d) a s occurs wi th, s a y, a mpheta mi nes .
98. The answer is e. (Brunton, pp 207t, 234, 242-243f, 251-252; Katzung, pp 105-107, 112.) Edrophoni um i s a fa s t- a nd s hort-a cti ng pa rentera l
a cetyl chol i nes tera s e i nhi bi torone of the rel a ti vel y few thera peuti c AChE i nhi bi tors wi th a generi c na me tha t does nt end i n -s ti gmi ne.
The ques ti on s ta tes tha t we a re dea l i ng wi th a pa ti ent experi enci ng a chol i nergi c cri s i s . Tha t mea ns , of cours e, tha t s he ha s recei ved ei ther
rel a ti vel y or a bs ol utel y exces s i ve dos es of the ora l chol i nes tera s e i nhi bi tor (eg, pyri dos ti gmi ne, neos ti gmi ne, etc) us ed to ma na ge her mya s theni a
gra vi s . Beca us e of the dos a ge exces s , a nd the exces s ACh a ccumul a ti ng a t the s kel eta l neuromus cul a r juncti ons (owi ng to reduced meta bol i c
i na cti va ti on of the neurotra ns mi tter), her s kel eta l mus cl es a re wea kened a nd fa ti gued from wha t a mounts to overs ti mul a ti on of ni coti ni c
receptors by the ACh. Thi s s kel eta l mus cl e hypofuncti on i nvol ves not onl y mus cl es i n the extremi ti es , but a l s o the di a phra gm a nd i ntercos ta l s tha t
mus t functi on norma l l y for a dequa te venti l a ti on. So, when we gi ve a chol i nes tera s e i nhi bi tor to pa ti ents l i ke the one des cri bed a bove, who i s
a l rea dy experi enci ng exces s i ve chol i nergi c effects , further (over)a cti va ti on of the di a phra gm a nd i ntercos ta l s ma y be s uffi ci ent to ca us e venti l a tory
di s tres s or tota l venti l a tory fa i l ure. Thi s i s a ma i n rea s on why the edrophoni um tes t i s s o da ngerous s houl d the underl yi ng probl em a ctua l l y be
the chol i nergi c cri s i s , a nd why edrophoni um i s preferred to other ACh es tera s e i nhi bi tors beca us e i t ha s a very s hort dura ti on of a cti on (hi ghl y
des i ra bl e s houl d a dvers e effects occur).
Edrophoni um i s not a t a l l l i kel y to tri gger a hypertens i ve cri s i s (a ). It a nd other drugs i n i ts cl a s s , or di rect mus ca ri ni c a goni s ts (eg, betha nechol )
for tha t ma tter, ha ve no va s ocons tri ctor a cti vi ty (when va s cul a r endothel i a l cel l s a re i nta ct). Chol i nes tera s e i nhi bi tors a re fa r more l i kel y to l ower
hea rt ra te (vi a i ndi rect mus ca ri ni c receptor a cti va ti on s econda ry to i nhi bi ted ACh hydrol ys i s a t the S-A node) tha n s ti mul a te i t (b); a nd jus t a s the
drug ca us es no peri phera l va s ocons tri cti on, i t ca us es no corona ry va s ocons tri cti on. Ventri cul a r a utoma ti ci ty i s l i kel y to decrea s e further, not
i ncrea s e (c), i n res pons e to i ncrea s ed mus ca ri ni c a cti va ti on. Edrophoni um wi l l not i mprove s kel eta l mus cl e tone a nd functi on (d) i f the probl em i s
a chol i nergi c cri s i s ; tha t i s the expected res pons e, however, i f the pa ti ent ha s a mya s theni c cri s i s (refl ecti ng i na dequa te dos a ges of the
chol i nes tera s e i nhi bi tor us ed for ma i ntena nce thera py).
Note: For ma ny pa ti ents wi th mya s theni a gra vi s , a nd who a re bei ng trea ted wi th a n ora l chol i nes tera s e i nhi bi tor, you s houl d be a bl e to
di fferenti a te between a mya s theni c a nd a chol i nergi c cri s i s wi thout res orti ng to the edrophoni um tes t. You s i mpl y need to a s s es s your pa ti ent
ca reful l y, a nd a ppl y s ome ba s i c a utonomi c pha rma col ogy knowl edge. In ei ther cri s i s , the ma i n common fea tures a re s kel eta l mus cl e fa ti ga bi l i ty,
wea knes s , or pa ra l ys i s due to i na dequa te (mya s theni c cri s i s ) or exces s i ve (chol i nergi c cri s i s ) a cti va ti on of ni coti ni c receptors on s kel eta l mus cl e.
Wi th a mya s theni c cri s i s , the pri ma ry probl ems a re confined to skeletal muscle functi on (a nd s econda ry cons equences of tha t, s uch a s i na dequa te
venti l a ti on).
Thi ngs us ua l l y pres ent qui te di fferentl y, however, i f the underl yi ng probl em i s a chol i nergi c cri s i s . Remember tha t chol i nes tera s e i nhi bi tors do
not a ct onl y a t s kel eta l neuromus cul a r juncti ons . They a l s o a ct a t a l l chol i nergi c s yna ps es i n the peri phera l nervous s ys tems : a t a l l the
pos tga ngl i oni c pa ra s ympa theti c nerve endi ngs a nd a t the s yna ps es between pos tga ngl i oni c s ympa theti c fi bers a nd s wea t gl a nds i nhi bi ti ng
ACh meta bol i s m there, a nd l ea di ng to s i gns a nd s ymptoms of mus ca ri ni c a cti va ti on i n a ddi ti on to ni coti ni c/s kel eta l mus cl e effects .
Thus , i n pa ti ents who a re experi enci ng a chol i nergi c cri s i s ma ny or mos t of the s i gns a nd s ymptoms typi ca l l y a s s oci a ted wi th pa ra s ympa theti c
(mus ca ri ni c) a cti va ti on wi l l occur, a nd they wi l l be us eful to you i n ma ki ng the di fferenti a l di a gnos i s i f you l ook a nd l i s ten ca reful l y: mi os i s a nd
exces s i ve l a cri ma ti on; s a l i va ti on; bra dyca rdi a (a nd pos s i bl y A-V bl ock determi ned by a n ECG); wheezi ng or other ma ni fes ta ti ons of
bronchocons tri cti on a nd/or i ncrea s ed a i rwa y mucus s ecreti ons ; gut a nd bl a dder hypermoti l i ty (eg, defeca ti on, uri na ry frequency or i nconti nence,
i ncrea s ed bowel s ounds ); a nd di a phores i s . See s ome of thes e i n a ddi ti on to s kel eta l mus cl e dys functi on a nd you s houl d be thi nki ng chol i nergi c
cri s i s a nd pl a ci ng mya s theni c cri s i s further down on your l i s t of pos s i bl e di a gnos es .
99. The answer is c. (Brunton, pp 225-235, 918-919, 921t, 923, 1816; Katzung, pp 115-122, 124-125, 278f, 292.) The peri phera l a utonomi c a cti ons of
di phenhydra mi ne (a n etha nol a mi ne-type fi rs t-genera ti on hi s ta mi ne H 1 a nta goni s t) a re very s i mi l a r to thos e of a tropi ne, the prototypi c
competi ti ve mus ca ri ni c receptor a nta goni s t. Thes e effects a re s een wi th both thera peuti c dos es (eg, dry mouth, bl urred vi s i on, a nd occa s i ona l l y
uri na ry retenti on or cons ti pa ti on) a nd wi th toxi ci ty. In l i fe-threa teni ng ca s es phys os ti gmi ne, the a nti dote for a tropi ne poi s oni ng, ma y be a
va l ua bl e a djunct.
Di phenhydra mi ne, a nd other H 1 bl ockers for tha t ma tter, ha ve no di rect effects ei ther a s a goni s t (a ) or a nta goni s t (b) on a drenergi c receptors ;
a nd no ni coti ni c receptor-a cti va ti ng a cti vi ty, whether i n a utonomi c ga ngl i a (d) or a t the a drena l medul l a (s upra rena l gl a nd; e).
100. The answer is d. (Brunton, p 250; Katzung, pp 123f, 127, 1033t.) Pra l i doxi me i s cl a s s i fi ed a s a chol i nes tera s e rea cti va tor a nd i s us ed s peci fi ca l l y,
a nd a djuncti vel y, for ma na gi ng poi s oni ng wi th the l ong-a cti ng (i rrevers i bl e) orga nophos pha te chol i nes tera s e i nhi bi tors tha t a re found i n s ome
i ns ecti ci des ; a nd nerve ga s es s uch a s s oma n, s a ri n, a nd VX. Pra l i doxi me, a n oxi me, ha s very hi gh a ffi ni ty for phos phorus i n the orga nophos pha tes . If gi ven ea rl y enough i n the poi s oni ng i t wi l l prevent or revers e the bi ndi ng of the orga nophos pha te to, a nd l ong-term i nhi bi ti on of,
the a cti ve bi ndi ng s i te on the chol i nes tera s e. The need for ea rl y pra l i doxi me a dmi ni s tra ti on i s cri ti ca l : i f i t i s del a yed too l ong the enzyme wi l l
a ge, yi el di ng a l a rgel y perma nent a nd i rrevers i bl e enzyme confi gura ti on.

Methyl pheni da te (a ) i s a n i ndi rect-a cti ng (norepi nephri ne-rel ea s i ng or a mpheta mi ne-l i ke) s ympa thomi meti c; pra l i doxi me ha s no effect on i ts
a cti ons , nor on the a cti ons of epi nephri ne (b) or pra zos i n (e), a s el ecti ve 1 a drenergi c bl ocker. Al though neos ti gmi ne (d) i s a chol i nes tera s e
i nhi bi tor i t i s not a n orga nophos pha te (i t i s a ca rba ma te), a nd i t i s s ponta neous l y a nd rel a ti vel y qui ckl y hydrol yzed l ea di ng to l os s of
chol i nes tera s e-i nhi bi tory a cti vi ty. Thus , us e of pra l i doxi me for exces s es of neos ti gmi ne (or other ca rba ma te) dos es woul d be both i neffecti ve
(mecha ni s ti ca l l y) a nd unneces s a ry.
101. The answer is b. (Brunton, pp 228, 233, 286, 1776, 1785t-1786t; Katzung, pp 88t, 89t, 93.) Sta rt wi th a funda menta l revi ew of a utonomi c i nnerva ti on of
the eye i ns ofa r a s control of pupi l s i ze, a nd effects on the ci l i a ry mus cl e (whi ch a ffects a ccommoda ti onthe a bi l i ty of the l ens of the eye to
thi cken s o we ca n s ee cl os e-up). The s ympa theti c nervous s ys tem, vi a -a drenergi c receptor a cti va ti on, ha s the a bi l i ty to ca us e mydri a s i s . Acti va te
thos e receptors a nd the pupi l di l a tes ; or bl ock the oppos i ng pa ra s ym-pa theti c i nfl uences (vi a mus ca ri ni c receptor bl ocka de) a nd the s a me thi ng
ha ppens , s i nce theres a rel a ti vel y compa ra bl e i nfl uence of both bra nches of the a utonomi c nervous s ys tem on pupi l s i ze. However, there i s l i ttl e
res ti ng i nfl uence of the s ympa theti c nervous s ys tem (or a drenergi c receptors ) on the tone of the ci l i a ry mus cl e. Tha t i s ma i nl y a pa ra s ympa theti cdependent phenomenon tha t i ndi rectl y a ffects the s ha pe of the l ens of the eyes a nd, s o, the poi nt of s ha rp focus . And, for a l l pra cti ca l purpos es ,
-receptor a cti va ti on ha s no i nfl uence on pupi l s i ze or a ccommoda ti on.
Now, cl a s s i fy the drugs by thei r s i tes a nd mecha ni s ms of a cti on.
El i mi na te a tropi ne (a ) a s a pos s i bl e a ns wer choi ce. By bl ocki ng a l l ocul a r effects of norma l pa ra s ympa theti c i nnerva ti on (mus ca ri ni c bl ocka de),
i t wi l l both di l a te the pupi l a nd i mpa i r a ccommoda ti on. The s a me a ppl i es to homa tropi ne (c), a drug tha t i s , for a l l pra cti ca l purpos es , a tropi nel i ke. Pi l oca rpi ne (e), a mus ca ri ni c a goni s t, wi l l constrict the pupi l of the eye a nd i mpa i r chol i nergi c mecha ni s ms i nvol ved i n focus i ng of the l ens .
Is oproterenol (d) a cti va tes a l l -a drenergi c receptors , ti mol ol (f) bl ocks them a l l ; a nd a s I s a i d, -receptors a re not rel eva nt i n terms of pupi l s i ze
or a ccommoda ti on. Thi s l ea ves us wi th epi nephri ne: i t ha s both -a drenergi c a nd -a drenergi c a cti va ti ng a cti vi ty, a nd no chol i nergi c/mus ca ri ni c
a cti vi ty. It wi l l di l a te the pupi l a nd not s i gni fi ca ntl y a ffect a ccommoda ti on.
102. The answer is e. (Brunton, pp 920-922, 1816; Katzung, pp 278f, 292.) You ma y ha ve chos en d (hi s ta mi ne H 2 receptor bl ocker) a s your a ns wer to thi s
ques ti on. However, H 2 receptors a re ma i nl y i nvol ved i n regul a ti ng ga s tri c a ci d s ecreti on, not typi ca l res pons es to s ea s ona l a l l ergi es . Wha t i f I ha d
gi ven Hi s ta mi ne H 1 receptor bl ocka de a s a n a ns wer choi ce? Al though di phenhydra mi ne bl ocks H 1 receptors qui te wel l , hi s ta mi ne pl a ys a
rel a ti vel y mi nor rol e i n the s ymptoms of rhi novi rus i nfecti ons (i n contra s t wi th a much more i mporta nt rol e i n, s a y, s ea s ona l a l l ergi es ). As a res ul t,
bl ocki ng the effects of hi s ta mi ne on H 1 receptors per s e does not a ccount for mos t of the s ymptom rel i ef i n the common col d. The dryi ng up of
na s a l s ecreti ons a fforded by di phenhydra mi ne i n thi s i ns ta nce i s due to the drugs ra ther i ntens e mus ca ri ni c receptor-bl ocki ng (a tropi ne-l i ke)
a cti ons .
The a nti hi s ta mi nes (fi rs t-genera ti on drugs s uch a s di phenhydra mi ne or s econd-genera ti on ones s uch a s l ora ta di ne) l a ck a ny a nta goni s t or
a goni s t a cti vi ty on -a drenergi c receptors (a ) or on -a drenergi c receptors (b); a nd ha ve no di rect or ma jor effect on ca l ci um cha nnel s (d).
103. The answer is c. (Brunton, pp 305-307, 324t, 383t; Katzung, pp 152f, 154, 167, 180, 189.) Phenyl ephri ne ra i s es bl ood pres s ure by a cti va ti ng a drenergi c receptors on va s cul a r s mooth-mus cl e cel l s . Pra zos i n competi ti vel y bl ocks thos e receptors , a nd when pres ent a t s uffi ci entl y hi gh dos es
(a s mi ght occur wi th a n a cute, s evere overdos e) ma y el i mi na te the va s opres s or res pons e to even hi gher tha n us ua l dos es of phenyl ephri ne. Bl ockers (a tenol ol , propra nol ol ) ha ve no -bl ocki ng a cti vi ty a nd s o wont reduce the va s opres s or res pons e to phenyl ephri ne. Nor wi l l betha nechol ,
whi ch ca us es va s odi l a ti on by a cti va ti ng mus ca ri ni c receptors for ACh. And res erpi ne? See the a ns wer to Ques ti on 104.
104. The answer is e. (Brunton, pp 68, 783; Katzung, pp 83f, 178.) Res erpi ne trea tment of s uffi ci ent dura ti on (beca us e i ts effects devel op s l owl y)
depl etes neurona l norepi nephri ne. Thi s a ccounts for the l owered bl ood pres s ure wi th thera peuti c dos es or fra nk hypotens i on wi th overdos es .
One cons equence of thi s , l ong-term, i s devel opment of a drenergi c receptor s upers ens i ti vi ty beca us e the receptors jus t a rent bei ng a cti va ted a s
they s houl d. And a cons equence of tha t, i n turn, there wi l l be hei ghtened (a nd s ometi mes extreme) res pons es to a gi ven dos e of a drenergi c
a goni s ts tha t ca n a cti va te thei r receptors ( or ) di rectl y, i ncl udi ng the phenyl ephri ne you a dmi ni s tered. (Tha t i s , the dos e-res pons e curve for
di rect-a cti ng a drenergi c a goni s ts i s s hi fted to the l eft a fter l ong-term res erpi ne trea tment.)
Atenol ol (a ) a nd propra nol ol (d) a re -bl ockers . Al though a tenol ol preferenti a l l y bl ocks 1 receptors , whi l e propra nol ol (a nd mos t other bl ockers ) a ffect both 1 a nd 2 , nei ther drug wi l l a l ter the expected va s cul a r res pons es to a n -a goni s t s uch a s phenyl ephri ne. Pra zos i n (c)
competi ti vel y a nta goni zes the effects of a n -a goni s t. Betha nechol (b) i s a mus ca ri ni c a goni s t; i f effecti ve concentra ti ons of the drug were i n the
ci rcul a ti on a t the s a me ti me a s phenyl ephri ne wa s gi ven, i ts effects woul d phys i ol ogi ca l l y a nta goni ze the pres s or res pons es to the
va s ocons tri ctor.
105. The answer is c. (Brunton, pp 918-923, 1816; Katzung, pp 278f, 292.) Fi rs t off, I thi nk you s houl d know tha t the ma i n a cti ve i ngredi ent i n OTC s l eep
a i ds (other tha n thos e a dverti s ed a s na tura l s uppl ements s uch a s mel a toni n, vi ta mi ns , etc) i s a s eda ti ng a nti hi s ta mi ne: doxyl a mi ne or, more
l i kel y, di phenhydra mi ne. Doxyl a mi ne i s extremel y s i mi l a r to di phenhydra mi ne, the prototype fi rs t-genera ti on (ol der) a nti hi s ta mi nea
competi ti ve H 1 receptor a nta goni s t. Chemi ca l l y, they a re i n the etha nol a mi ne cl a s s a nd a re us ed not onl y for a l l ergy rel i ef, but a l s o for s eda ti on
a nd s l eep. If one wa nted to s ta y a wa ke a nd a l ert (e) thes e certa i nl y woul d not be drugs tha t a chi eve tha t goa l ; moreover, they dont ha ve a ny
a mpheta mi ne-l i ke ca techol a mi ne-rel ea s i ng a cti vi ty. Thes e drugs a l s o bl ock mus ca ri ni c receptors a nd qui te effecti vel y to boot. So the a ns wer to
thi s ques ti on boi l s -down to Wha t bes t des cri bes the a cti ons or effects of a tropi ne? As you s houl d know, a tropi ne or drugs wi th s i mi l a r
a nti mus ca ri ni c a cti ons s houl d not be us ed by pa ti ents wi th pros ta ti s m or a ngl e-cl os ure (na rrowa ngl e) gl a ucoma .
Gi ven the a nti mus ca ri ni c effects , i f thera peuti c dos es do a nythi ng to hea rt ra te i t wi l l be a n i ncrea s e, not a decrea s e (a ) s i nce chronotropi c
effects of ACh on the S-A node a re i nhi bi ted. ACh norma l l y i ncrea s es gut moti l i ty, fa ci l i ta tes mi cturi ti on by s ti mul a ti ng the bl a dders tri gone a nd
detrus or, a nd rel a xes s phi ncters i n the GI a nd uri na ry tra cts . Bl ocki ng thos e i nfl uences on the gut woul d tend to ca us e cons ti pa ti on, not di a rrhea
(b). Bl ood pres s ure wi l l not ri s e beca us e of ca techol a mi ne-l i ke va s ocons tri cti on; thes e drugs ha ve no -a drenergi c (or a ny other) a goni s t a cti vi ty.
Note: Once a ga i n I wrote a ques ti on a bout a n os tens i bl y mi s cel l a neous drug, s o why di d I a s k a bout doxyl a mi ne? I di d s o not to be pi cky, but
beca us e doxyl a mi ne (a nd more s o di phenhydra mi ne) a re wi del y us ed; ca n ca us e probl ems for certa i n peopl e; a nd a re a va i l a bl e OTC, whi ch mea ns
your pa ti ent ca n ta ke them wi thout your a dvi ce, cons ent, or knowl edge.

Central Nervous System Pharmacology

Al zhei mer drugs
Anti depres s a nts a nd other mood-s ta bi l i zi ng drugs
Anti epi l epti cs /a nti convul s a nts
Anti pa rki ns on drugs
Anti ps ychoti cs
Anxi ol yti cs
Centra l nervous s ys tem s ti mul a nts a nd a norexi geni c a gents
Etha nol
Genera l a nes theti cs
Intra venous a nes theti cs a nd a nes thes i a a djuncts
Loca l a nes theti cs
Opi oi d a na l ges i cs a nd a nta goni s ts
Ps ychotomi meti cs
Seda ti ves , hypnoti cs

Questions
106. Gua nfa ci ne ha s recentl y been FDA-a pproved for ma na gi ng a ttenti on-defi ci t hypera cti vi ty di s order (ADHD) i n pa ti ents between the a ges of 6
a nd 17 yea rs . In a ddi ti on to i ts benefi ts for ADHD, i t a ppea rs to provi de s ymptom rel i ef i n genera l i zed a nxi ety di s order a nd pos t-tra uma ti c s tres s
di s order.
Al though the newl y a pproved i ndi ca ti ons for gua nfa ci ne focus on the centra l nervous s ys tem, the drug ca n ca us e ma ny i mporta nt peri phera l
a utonomi c effects . They a re a s fol l ows :
l owers tota l peri phera l res i s ta nce (s ys temi c va s cul a r res i s ta nce);
a t us ua l dos es i t does not bl ock va s opres s or res pons es to s uch drugs a s phenyl ephri ne;
res ti ng hea rt ra te a nd ventri cul a r s troke vol ume decl i ne a s effects of gua nfa ci ne bui l d duri ng l ong-term thera py;
s ympa theti c-medi a ted i ncrea s es of hea rt ra te a nd s troke vol ume norma l l y a s s oci a ted wi th s uch a cti vi ti es a s exerci s e, or a s a ba roreceptor refl ex
res pons e to a s udden fa l l of bl ood pres s ure, a re bl unted;
mi os i s ma y occur; a nd
gua nfa ci ne ha s no di rect or i ndi rect effects on a i rwa y s mooth mus cl e.
Ba s ed on thi s des cri pti on, whi ch one of the fol l owi ng drugs i s mos t s i mi l a r to gua nfa ci ne?
a . Atropi ne
b. Cl oni di ne
c. Phentol a mi ne
d. Pra zos i n
e. Propra nol ol
Questions 107 to 111
The next fi ve ques ti ons refer to the ta bl e bel ow (s hown ea rl i er for Ques ti ons 78 to 84 i n the cha pter Peri phera l Nervous Sys tems /Autonomi cs ),
whi ch i s the a nes thes i a record from a pa ti ent undergoi ng two opera ti ve procedures duri ng l a pa ros copi c a bdomi na l s urgery. Here I a s k you a bout
s ome drugs not a ddres s ed before. Remember: Thi s medi ca ti on a dmi ni s tra ti on pl a n i s very typi ca l of wha t youl l s ee wi th ma ny s i mi l a r opera ti ve
procedures .

107. You s ee tha t mi da zol a m wa s the fi rs t drug gi ven to the pa ti enta ctua l l y ri ght before s he wa s tra ns ported i nto the OR. (The nota ti on IVP next
to mi da zol a m mea ns IV pus h, i e, a ra pi d bol us i njecti on.) In a ddi ti on to ca us i ng s eda ti on, a nxi ety rel i ef, a nd genera l l y s moothi ng the
i nducti on of a nes thes i a , whi ch of the fol l owi ng i s the mos t l i kel y effect you woul d expect to a chi eve a s a res ul t of premedi ca ti ng wi th mi da zol a m?
a . Potenti a ti ng the a na l ges i c effects of the morphi ne
b. Preventi ng a n i ntra opera ti ve fa l l of bl ood pres s ure
c. Preventi ng s ei zures l i kel y to be ca us ed by the propofol
d. Prophyl a xi s of ca rdi a c a rrhythmi a s
e. Provi di ng a mnes ti c effects (s uppres s i ng reca l l of peri opera ti ve events )
108. The record s hows tha t propofol wa s gi ven for i nducti on. Wha t i s /a re the mos t l i kel y a dvers e res pons e(s ) a s s oci a ted wi th the a dmi ni s tra ti on

of thi s wi del y us ed drug?

a . Hypotens i on a nd res pi ra tory (venti l a tory) depres s i on
b. La ryngos pa s m
c. Long-term memory l os s
d. Ma l i gna nt hyperthermi a
e. Sei zures
f. Uni ntended or exces s i vel y prol onged s kel eta l mus cl e pa ra l ys i s
109. As s ume tha t i ns tea d of i nduci ng a nes thes i a wi th propofol , the nurs e a nes theti s t us ed a pa rentera l ba rbi tura te (eg, methohexi ta l , thi a myl a l ,
a nd thi openta l ) wi th a n extremel y fa s t ons et of a cti on a nd s hort dura ti on (s ometi mes ca l l ed ul tra s hort). Thes e ba rbi tura te i nducti on a gents a re
effecti ve, but a re a s s oci a ted wi th a fa i rl y hi gh i nci dence of a certa i n a nd ra ther uni que a dvers e effect. Wha t bes t des cri bes wha t tha t a dvers e
effect i s ?
a . Hypera l ges i a (hei ghtened percepti on of pa i n)
b. Hypertens i ve cri s i s
c. La ryngos pa s m
d. Ma l i gna nt hyperthermi a
e. Sei zures , typi ca l l y monocl i ni c
110. The pa ti ent recei ved a n i ntra venous dos e of ketorol a c s hortl y before the wounds were cl os ed a nd s urgery wa s done. Wha t i s the mos t l i kel y
purpos e for whi ch i t wa s gi ven?
a . Control of a nti ci pa ted pos topera ti ve na us ea a nd vomi ti ng
b. Pos topera ti ve pa i n control
c. Revers a l of CNS depres s i on ca us ed by mul ti pl e depres s a nt drugs
d. Revers a l of drug-i nduced neuromus cul a r bl ocka de (pa ra l ys i s )
e. Suppres s i on of wound i nfl a mma ti on
111. Onda ns etron wa s a dmi ni s tered a bout a n hour before the a nti ci pa ted end of s urgery. Wha t wa s the mos t l i kel y rea s on for gi vi ng thi s to the
pa ti ent?
a . Ha s ten recovery of cons ci ous nes s whi l e effects of a nes theti cs wea r off
b. Intens i fy pa i n-rel i evi ng effects of other a na l ges i cs gi ven to the pa ti ent
c. Les s en ri s ks of pos top uri na ry retenti on through effects on bl a dder mus cul a ture
d. Prevent or reduce the ri s k of pos topera ti ve pa ra l yti c i l eus
e. Reduce the ri s k of pos topera ti ve na us ea a nd vomi ti ng
112. Two i nha l ed genera l a nes theti cs , A a nd B, ha ve the fol l owi ng MAC va l ues :

Ba s ed onl y on thi s i nforma ti on (note tha t we ha ve not na med a ny drugs ), whi ch s ta tement i s true?
a . Drug A ha s a l onger dura ti on of a cti on tha n Drug B
b. Drug A i s more s ol ubl e i n the bl ood tha n Drug B
c. Drug B ca us es grea ter a na l ges i a a nd s kel eta l mus cl e rel a xa ti on tha n Drug A
d. The concentra ti on of drug i n i ns pi red a i r tha t i s needed to ca us e a dequa te s urgi ca l a nes thes i a i s hi gher for Drug B tha n for Drug A
e. The ti me to ons et of a dequa te genera l a nes thes i a i s 50 ti mes l onger for Drug B tha n for Drug A
113. A pa ti ent wi th Pa rki ns on di s ea s e ha s s i gns a nd s ymptoms tha t ca n be cons i dered modera te now, but they a re wors eni ng a nd not
res pondi ng wel l to current drug thera py. The phys i ci a n deci des to empi ri ca l l y a s s es s a n a nti pa rki ns on drug tha t i s a s el ecti ve i nhi bi tor of
monoa mi ne oxi da s e type B (MAO-B). Wha t drug woul d tha t be?
a . Bromocri pti ne
b. Ca rbi dopa
c. Phenel zi ne
d. Sel egi l i ne
e. Tra nyl cypromi ne
114. A pa ti ent who ha s been trea ted wi th l evodopa i s s wi tched to a regi men wi th a product tha t conta i ns l evodopa pl us ca rbi dopa . Wha t i s the
ma i n a cti on of ca rbi dopa tha t provi des the ra ti ona l e for us i ng i t i n thi s dua l -drug a pproa ch?
a . Bl ocks ACh rel ea s e i n the CNS, thereby fa ci l i ta ti ng l evodopa s a bi l i ty to res tore a dopa mi ne-ACh ba l a nce
b. Hel ps a cti va te di eta ry vi ta mi n B 6 , a defi ci ency of whi ch occurs duri ng l evodopa thera py
c. Increa s es permea bi l i ty of the bl ood-bra i n ba rri er to l evodopa , gi vi ng l evodopa better a cces s to the CNS
d. Inhi bi ts meta bol i c convers i on of l evodopa to dopa mi ne outs i de the CNS
e. Reduces l evodopa -i nduced hypotens i on by bl ocki ng va s cul a r dopa mi ne receptors
115. A 34-yea r-ol d ma n wi th mi l d a nxi ety a nd depres s i on s ymptoms ha s hea rd a bout bus pi rone on TV a nd a s ks whether i t mi ght be s ui ta bl e for

hi m. Accordi ng to the mos t di a gnos ti c a nd trea tment cri teri a , the drug woul d be a ppropri a te, pa rti cul a rl y for s hort-term s ymptom control . Whi ch
phra s e correctl y des cri bes a n i mporta nt property of bus pi rone?
a . As s oci a ted wi th a wi thdra wa l s yndrome tha t, i f uns upervi s ed or control l ed, ma y be fa ta l
b. Ha s a s i gni fi ca nt potenti a l for a bus e
c. Is l i kel y to potenti a te the CNS depres s a nt effects of a l cohol , benzodi a zepi nes , a nd s eda ti ve a nti hi s ta mi nes (eg, di phenhydra mi ne), s o s uch
i ntera cta nts mus t be a voi ded a t a l l cos t
d. Requi res a l mos t da i l y dos a ge ti tra ti ons i n order to opti mi ze the res pons e
e. Sel dom ca us es drows i nes s
116. A phys i ci a n cons i ders pl a ci ng a pa ti ent on l ong-term (months , yea rs ) phenoba rbi ta l for control of a rel a ti vel y common medi ca l condi ti on. For
mos t of thes e i ndi ca ti ons , newer a nd a rgua bl y more effi ca ci ous drugs , whi ch pa rti ci pa te i n fewer drug i ntera cti ons , a re a va i l a bl e a nd preferred.
For whi ch one of the fol l owi ng us es , nonethel es s , i s thi s ba rbi tura te s ti l l cons i dered rea s ona bl e a nd a ppropri a te?
a . Al cohol wi thdra wa l s i gns /s ymptoms
b. Anxi ety ma na gement
c. Certa i n epi l eps i es
d. Endogenous depres s i on (a djunct to SSRIs )
e. Sl eep di s orders s uch a s i ns omni a
117. One rea s on for the decl i ni ng us e of tri cycl i c a nti depres s a nts s uch a s i mi pra mi ne, a nd the growi ng us e of newer cl a s s es , i s the preva l ence of
common tri cycl i c-i nduced s i de effects or a dvers e res pons es . Wha t s i de effect or a dvers e res pons e, l i s ted bel ow, i s mos t l i kel y to occur wi th us ua l
thera peuti c dos es of a tri cycl i c?
a . Anti chol i nergi c (a nti mus ca ri ni c) effects
b. Arrhythmi a s
c. Hepa totoxi ci ty
d. Nephrotoxi ci ty
e. Sei zures
118. A 42-yea r-ol d woma n devel ops a ka thi s i a s , pa rki ns oni a n-l i ke dys ki nes i a s , ga l a ctorrhea , a nd a menorrhea , a s a cons equence of ps ychotropi c
drug thera py. Wha t drug-receptor-ba s ed mecha ni s m, occurri ng i n the centra l nervous s ys tem, mos t l i kel y ca us ed thes e res pons es ?
a . Bl ocka de of -a drenergi c receptors
b. Bl ocka de of dopa mi ne receptors
c. Bl ocka de of mus ca ri ni c receptors
d. Supers ens i ti vi ty of dopa mi ne receptors
e. Sti mul a ti on of ni coti ni c receptors
119. A pa ti ent on the tra uma -burn uni t recei ved a drug to ea s e the pa i n of debri dement a nd dres s i ng cha nges for s evera l s evere burns . He
experi ences good, prompt a na l ges i a , but des pi te the a bs ence of pa i n s ens a ti on duri ng the procedure hi s hea rt ra te a nd bl ood pres s ure ri s e
cons i dera bl y, cons i s tent wi th s ympa theti c nervous s ys tem a cti va ti on by the pa i n a nd not a ffected by the a na l ges i c drug. As the effects of the drug
devel op hi s s kel eta l mus cl e tone progres s i vel y i ncrea s es . He a ppea rs a wa ke a t ti mes beca us e hi s eyes peri odi ca l l y open. As drug effects wea r off
he ha l l uci na tes a nd beha ves i n a very a gi ta ted fa s hi on. Ha l l uci na ti ons , ba d drea ms , a nd peri ods of del i ri um recur over s evera l da ys a fter
recei vi ng the drug. Wha t drug wa s mos t l i kel y gi ven?
a . Fenta nyl
b. Keta mi ne
c. Mi da zol a m
d. Succi nyl chol i ne
e. Thi openta l
120. A 17-yea r-ol d ma l e wa s di a gnos ed wi th epi l eps y a fter devel opi ng repea ted epi s odes of genera l i zed toni c-cl oni c s ei zures fol l owi ng a motor
vehi cl e a cci dent i n whi ch he recei ved a cl os ed-hea d i njury. After trea ti ng a cute s ei zures wi th the proper i njecta bl e drugs , he i s s ta rted on a
regi men of ora l phenytoi n, the da i l y dos e ti tra ted upwa rd unti l s ymptom control a nd a thera peuti c pl a s ma concentra ti on were rea ched. The
el i mi na ti on ha l f-l i fe of the drug duri ng i ni ti a l trea tment wa s mea s ured to be 24 hours , a va l ue tha t i s qui te typi ca l for otherwi s e hea l thy a dul ts
ta ki ng no other drugs .
Toda y he pres ents i n the neurol ogy cl i ni c wi th nys ta gmus , a ta xi a , di pl opi a , cogni ti ve i mpa i rment, a nd other s i gns a nd s ymptoms cons i s tent wi th
phenytoi n toxi ci ty. A bl ood s a mpl e, dra wn a t noon, ha s a pl a s ma phenytoi n concentra ti on of 30 mcg/mL. Tha t va l ue i s 50% hi gher tha n typi ca l pea k
thera peuti c pl a s ma concentra ti ons , a nd twi ce the us ua l mi ni mum effecti ve bl ood l evel . Thes e va l ues a re s umma ri zed i n the fi gure bel ow.

The a ttendi ng orders di s conti nua ti on of further dos es of phenytoi n unti l pl a s ma l evel s fa l l i nto the thera peuti c ra nge, a nd the pa ti ent i s l a rgel y
free of s i gns a nd s ymptoms of phenytoi n toxi ci ty. In the i nteri m, wha t woul d you do or expect to occur next?
a . Admi ni s ter fl uma zeni l , whi ch wi l l qui ckl y revers e s i gns a nd s ymptoms of phenytoi n toxi ci ty but ma y ca us e s ei zures to recur
b. Anti ci pa te tha t el i mi na ti on of phenytoi n from the pl a s ma wi l l fol l ow zero-order ki neti cs for s evera l da ys
c. Gi ve a n a mpheta mi ne or other CNS s ti mul a nt to revers e genera l i zed CNS depres s i on due to the phenytoi n exces s
d. Gi ve phenoba rbi ta l to i nduce the P450 s ys tem, thereby ha s teni ng phenytoi ns meta bol i c el i mi na ti on
e. Pl a s ma phenytoi n concentra ti ons wi l l fa l l to 15 mcg/mL, i n the mi ddl e of the thera peuti c ra nge, by noon tomorrow (24 hours l a ter, per the us ua l
ha l f-l i fe)
121. A 12-yea r-ol d boy ha s been trea ted wi th methyl pheni da te for the l a s t 3 yea rs . Hi s younger s i s ter fi nds the bottl e of pi l l s a nd cons umes
enough to ca us e s i gni fi ca nt toxi ci ty. Whi ch of the fol l owi ng fi ndi ngs woul d you mos t l i kel y expect?
a . Hypertens i on, ta chyca rdi a , s ei zures
b. Hypotens i on, bronchos pa s m
c. Drows i nes s , obtunded refl exes , di a rrhea
d. Mi os i s , bra dyca rdi a , profus e s a l i va ti on, s wea ti ng
e. Hypothermi a , s kel eta l mus cl e wea knes s or pa ra l ys i s , pupi l s tha t a re not res pons i ve to l i ght

122. Meperi di ne i s s i mi l a r to morphi ne i n ma ny wa ys , but ha s s ome deci ded di fferences tha t a re cl i ni ca l l y rel eva nt: wi th very hi gh bl ood l evel s or
wi th true overdos es , meperi di ne ca n ca us e s i gni fi ca nt a dvers e res pons es tha t s i mpl y a rent s een wi th morphi ne or mos t other opi oi d a na l ges i cs .
Wha t i s tha t ra ther unique effect of meperi di ne?
a . Cons ti pa ti on l ea di ng to pa ra l yti c i l eus
b. Hei ghtened res pons e to pa i n (pa ra doxi ca l hypera l ges i a )
c. Intens e bi l i a ry tra ct s pa s m
d. Ps ychos i s -l i ke s ta te, pos s i bl y s ei zures
e. Res pi ra tory depres s i on, a pnea , venti l a tory a rres t
123. Chl orproma zi ne a nd ha l operi dol ca n be cons i dered prototypes of two rel a ti vel y ol d but s ti l l -us ed a nti ps ychoti c drug cl a s s es : the
phenothi a zi nes a nd the butyrophenones , res pecti vel y. Whi l e ma ny of the a cti ons a nd s i de effects of thes e drugs a re qua l i ta ti vel y s i mi l a r, they a re
di fferent qua nti ta ti vel y: tha t i s , i n terms of i nci dence a nd s everi ty. Whi ch effect or s i de effect typi ca l l y occurs more frequentl y, i s us ua l l y more
s evere, a nd ha s a rel a ti vel y ra pi d ons et, wi th ha l operi dol ?
a . Extra pyra mi da l rea cti ons
b. Intens e a tropi ne-l i ke s i de effects
c. Letha l bl ood dys cra s i a s
d. Orthos ta ti c hypotens i on
e. Uri na ry retenti on neces s i ta ti ng bl a dder ca theteri za ti on
124. A pa ti ent i s tra ns ported to the emergency depa rtment. A fri end who a ccompa ni es the pa ti ent s a ys he wa s experi menti ng wi th a ngel dus t.
Wha t bes t des cri bes the a cti ons or other cha ra cteri s ti cs of thi s recrea ti ona l drug, more properl y know a s phencycl i di ne?
a . Ca us es i ts peri phera l a nd centra l effects vi a a nti mus ca ri ni c properti es
b. Ca us es s i gni fi ca nt wi thdra wa l s ymptoms
c. Ha s s trong opi oi d receptor-a cti va ti ng a cti vi ty
d. Ha s a mpheta mi ne-l i ke properti es a nd i s a n ha l l uci nogen
e. Overdos es s houl d be trea ted wi th fl uma zeni l
125. Pa cka ge i ns erts for a drug ca uti on a ga i ns t a dmi ni s teri ng i t concurrent wi th a ny other drug tha t ca n ra i s e or l ower s odi um concentra ti ons . The
ri s ks a re i na dequa te or exces s i ve effects of the drug, dependi ng on the di recti on i n whi ch s odi um concentra ti ons cha nge. Thi s , of cours e, requi res
ca uti ous us e or a voi da nce (i f pos s i bl e) of the common di ureti cs . To whi ch of the fol l owi ng drugs does thi s ca uti on or wa rni ng a ppl y?
a . Chol es tyra mi ne
b. Li thi um (eg, l i thi um ca rbona te)
c. Ni fedi pi ne
d. Phenyl ephri ne
e. Sta ti n-type chol es terol -l oweri ng drugs
126. A 31-yea r-ol d woma n ha s been trea ted wi th fl uoxeti ne for 5 months . She i s di a gnos ed wi th a nother medi ca l probl em a nd recei ves one or
more drugs tha t, otherwi s e, woul d be s ui ta bl e a nd proba bl y probl em-free. She i s rus hed to the ED wi th uns ta bl e vi ta l s i gns , mus cl e ri gi di ty,
myocl onus , CNS i rri ta bi l i ty a nd a l tered cons ci ous nes s , a nd s hi veri ng. Wha t a dd-on drug(s ) mos t l i kel y ca us ed thes e res pons es ?
a . Codei ne for cough
b. Lora ta di ne for s ea s ona l a l l ergi es
c. Mi da zol a m a nd fenta nyl , us ed to ea s e di s comfort from endos copy
d. Suma tri pta n for mi gra i ne
e. Zol pi dem for s hort-term i ns omni a
127. A 72-yea r-ol d woma n wi th a l ong hi s tory of a nxi ety tha t ha s been trea ted wi th di a zepa m deci des to tri pl e her da i l y dos e beca us e of i ncrea s i ng
fea rful nes s a bout envi ronmenta l noi s es . Two da ys a fter her a ttempt a t s el f-pres cri bi ng, s he i s found extremel y l etha rgi c a nd nonres pons i ve,
wi th ma rkedl y obtunded refl exes a nd rea cti ons to pa i nful s ti mul i . Res pi ra ti ons a re 8/mi n a nd s ha l l ow. Wha t drug s houl d be gi ven to revers e
thes e s i gns a nd s ymptoms ?
a . Dextroa mpheta mi ne
b. Fl uma zeni l
c. Na l trexone
d. Phys os ti gmi ne
e. Pra l i doxi me
128. A pa ti ent who ha s been trea ted for Pa rki ns on di s ea s e for a bout a yea r pres ents wi th purpl i s h, mottl ed cha nges to her s ki n. Wha t drug i s the
mos t l i kel y ca us e of thi s cuta neous res pons e?
a . Ama nta di ne
b. Bromocri pti ne
c. Levodopa (a l one)
d. Levodopa combi ned wi th ca rbi dopa
e. Pra mi pexol e
129. A young boy who ha s been trea ted for epi l eps y for a yea r i s referred to a peri odonti s t for eva l ua ti on a nd proba bl e trea tment of ma s s i ve
overgrowth of hi s gi ngi va l ti s s ues . Some teeth a re a l mos t compl etel y covered wi th hyperpl a s ti c ti s s ue. Whi ch drug wa s the mos t l i kel y ca us e of the
ora l pa thol ogy?

a . Ca rba ma zepi ne
b. Lora zepa m
c. Phenoba rbi ta l
d. Phenytoi n
e. Va l proi c a ci d
130. A pa ti ent wi th undi a gnos ed corona ry a rtery di s ea s e i s gi ven a medi ca ti on. Shortl y therea fter s he devel ops i ntens e ti ghtnes s a nd crus hi ng
di s comfort of her ches t. An ECG revea l s ST-s egment cha nges i ndi ca ti ve of a cute myoca rdi a l i s chemi a . Whi ch drug mos t l i kel y ca us ed thi s rea cti on?
a . Cl oza pi ne
b. Penta zoci ne
c. Phenytoi n
d. Suma tri pta n
e. Zol pi dem
131. Ni trous oxi de i s a common component i n the techni que of ba l a nced a nes thes i a . It i s us ed i n conjuncti on wi th s uch other drugs a s a
ha l ogena ted hydroca rbon vol a ti l e l i qui d a nes theti c, a nd us ua l l y i ncl uded a s 80% of the tota l i ns pi red ga s mi xture. Whi ch phra s e bes t s umma ri zes
why ni trous oxi de ca nnot be us ed a l one for genera l a nes thes i a ?
a . Al mos t tota l l a ck of a na l ges i c a cti vi ty, rega rdl es s of concentra ti on
b. Ins pi red concentra ti ons >10% tend to profound ca rdi a c nega ti ve i notropi c effects
c. MAC (mi ni mum a l veol a r concentra ti on) i s >100%
d. Methemogl obi nemi a occurs even wi th l ow i ns pi red concentra ti ons
e. Such grea t s ol ubi l i ty i n bl ood tha t i ts effects ta ke a n extra ordi na ri l y l ong ti me to devel op
f. Very hi gh frequency of bronchos pa s m
132. A pa ti ent devel ops a s evere a nd ra pi dl y wors eni ng a dvers e res pons e to a drug. The phys i ci a n orders prompt a dmi ni s tra ti on of a nti pyreti cs , IV
hydra ti on, a nd bromocri pti ne or da ntrol ene to ma na ge s ymptoms a nd hopeful l y to prevent a fa ta l outcome. Whi ch drug or drug group mos t l i kel y
ca us ed thes e a dvers e res pons es ?
a . Benzodi a zepi nes , es peci a l l y thos e us ed a s hypnoti cs
b. Chl orproma zi ne
c. Levodopa
d. Phenytoi n
e. SSRIs
133. Ropi ni rol e i s a rel a ti vel y new drug tha t recentl y wa s a pproved to trea t wha ts commonl y ca l l ed res tl es s l eg s yndrome (a l s o known a s Ekbom
s yndrome). The drug works a s a dopa mi ne receptor a goni s t i n certa i n pa rts of the bra i n. Gi ven thi s mecha ni s m of a cti on, wha t other di s order i s ,
mos t l i kel y, a nother i ndi ca ti on for thi s drug?
a . Da yti me a nxi ety
b. Hypers omni a (exces s i ve s l eepi nes s )
c. Pa rki ns on di s ea s e
d. Schi zophreni a
e. Sta tus epi l epti cus
f. Trea tment of s evere pa i n
134. A pa ti ent i n the neurol ogy uni t a t your hos pi ta l devel ops s ta tus epi l epti cus , a nd a t the ti me there i s no good i nforma ti on a bout the eti ol ogy.
Wha t drug s houl d be gi ven fi rs t for the fa s tes t s uppres s i on of the s ei zures ?
a . Ca rba ma zepi ne
b. Lora zepa m
c. Phenoba rbi ta l
d. Phenytoi n
e. Va l proi c a ci d
135. A pa ti ent ha s ha d a documented s evere a l l ergi c rea cti on to es ter-type l oca l a nes theti cs . Wha t other drug i s a member of the es ter cl a s s , a nd
s o woul d be the mos t l i kel y to provoke a n a l l ergi c or a na phyl a cti c rea cti on i f thi s pa ti ent recei ved i t?
a . Bupi va ca i ne
b. Li doca i ne
c. Mepi va ca i ne
d. Pri l oca i ne
e. Tetra ca i ne
136. A 66-yea r-ol d woma n i s di a gnos ed wi th Al zhei mer di s ea s e, wi th s ymptoms bei ng des cri bed a s mi l d-to-modera te. Wha t pha rma col ogi c
a pproa ch i s genera l l y cons i dered the mos t frui tful i n terms of a l l evi a ti ng s ymptoms of ea rl y Al zhei mer a nd proba bl y s l owi ng the cours e of the
underl yi ng bra i n pa thol ogy?
a . Acti va te a popul a ti on of s erotoni n receptors
b. Bl ock dopa mi ne rel ea s e or receptor a cti va ti on
c. Inhi bi t a cetyl chol i nes tera s e

d. Inhi bi t MAO
e. Di s s ol ve cerebra l va s cul a r thrombi
137. Tri hexypheni dyl i s pres cri bed a s a n a djunct to other drugs bei ng us ed to ma na ge a pa ti ent wi th Pa rki ns on di s ea s e. Wha t i s the mos t l i kel y
purpos e or a cti on of thi s drug a s pa rt of the overa l l drug trea tment pl a n?
a . To countera ct s eda ti on tha t i s l i kel y to be ca us ed by the other medi ca ti ons
b. To hel p correct further the dopa mi ne-ACh i mba l a nce tha t a ccounts for pa rki ns oni a n s i gns a nd s ymptoms
c. To ma na ge cuta neous a l l ergi c res pons es tha t a re s o common wi th typi ca l a nti -pa rki ns on drugs
d. To prevent the devel opment of ma ni c/hypoma ni c res pons es to other a nti pa rki ns on drugs
e. To revers e ta rdi ve dys ki nes i a s i f the pa rki ns oni s m wa s i nduced by a n a nti ps ychoti c drug
138. A few yea rs a go the FDA gra nted a pprova l to ma rket a new pres cri pti on drug (drug X) tha t wi l l be a dmi ni s tered i n the form of a derma l pa tch
(a ppl y the pa tch to i nta ct s ki n, the drug i s a bs orbed from there).
Drug X bel ongs to a very ol d cl a s s of drugs tha t, when gi ven by i ts us ua l route, ora l l y, ca n i ntera ct wi th foods s uch a s chees e a nd proces s ed
mea ts (a nd certa i n brea ds , other foods , a nd a l cohol i c bevera ges ) l ea di ng to a n i ntera cti on tha t ca n el eva te bl ood pres s ure to s evere a nd
s ometi mes fa ta l l evel s . After more tha n a deca de of tes ti ng, the FDA a pproved i ts us e for a dul ts . In i ts l owes t dos e, no di eta ry res tri cti on(s ) a re
requi red.
Ba s ed on thi s i nforma ti on, how i s drug X mos t l i kel y cl a s s i fi ed a nd wha t i s i ts mos t l i kel y cl i ni ca l us e?
a . Ampheta mi ne-l i ke a gent for ADD/ADHD
b. Ba rbi tura tes us ed for da yti me a nxi ety
c. Benzodi a zepi ne for a nxi ety a nd s l eep
d. MAO i nhi bi tor for depres s i on
e. Morphi ne-l i ke a na l ges i c for s evere/chroni c pa i n
139. The pedi a tri ci a n wri tes a pres cri pti on for a combi na ti on (of s evera l drugs ) product tha t conta i ns dextromethorpha n, whi ch i s a n i s omer of a
codei ne a na l og. The pa ti ent i s a 12-yea r-ol d boy. Wha t i s the mos t l i kel y purpos e for whi ch the drug wa s pres cri bed?
a . Control mi l d-modera te pa i n a fter the l a d broke hi s wri s t pl a yi ng s occer
b. Ma na ge di a rrhea ca us ed by food-borne ba cteri a
c. Provi de s eda ti on beca us e the chi l d ha s ADD/ADHD
d. Suppres s s evere cough a s s oci a ted wi th a bout of i nfl uenza
e. Trea t nocturna l bed-wetti ng
140. Ma ny l ega l juri s di cti ons ha ve i mpos ed va ri ous res tri cti ons on over-the-counter s a l e of products , ma i nl y ora l deconges ta nts , tha t conta i n
ps eudoephedri ne. Tha t i s beca us e ps eudoephedri ne ca n be ra ther ea s i l y us ed to s ynthes i ze whi ch hi ghl y ps ychoa cti ve a nd a bus e-prone drug?
a . Metha mpheta mi ne
b. Morphi ne
c. Oxycodone
d. Penta zoci ne
e. Phencycl i di ne (PCP)
141. The a nes thes i ol ogi s t prepa res to a dmi ni s ter s evera l drugs to a pa ti ent a s pa rt of norma l pre- a nd i ntra opera ti ve ca re. Wha t drug lacks, a s i ts
norma l s pectrum of a cti on, the a bi l i ty to ca us e genera l i zed CNS depres s i on or the pa ti ents l evel of cons ci ous nes s , or l a cks a ny i ntri ns i c a na l ges i c
effects ?
a . Droperi dol
b. Mi da zol a m
c. Vecuroni um
d. Propofol
e. Thi openta l
142. A 26-yea r-ol d woma n ha s been on a nti depres s a nt thera py for s evera l months . Toda y s he compl a i ns of mi s s i ng her peri od a nd ha vi ng ga l a ctorrhea , a nd your ca reful a s s es s ment s ugges ts tha t s he ha s devel oped s ome dys ki nes i a s (mi l d tremors , for exa mpl e) not unl i ke thos e you woul d
typi ca l l y a s s oci a te wi th a phenothi a zi ne or butyrophenone (eg, ha l operi dol ) a nti ps ychoti c drug. Pregna ncy tes ts a re nega ti ve. Wha t drug mos t
l i kel y to ha ve ca us ed thes e fi ndi ngs ?
a . Amoxa pi ne
b. Ci ta l opra m
c. Fl uoxeti ne
d. Sertra l i ne
e. Tra nyl cypromi ne
143. A pa ti ent ha s been ta ki ng a n ora l monoa mi ne oxi da s e i nhi bi tor (MAOI), but tha t fa ct i s unknown to the hea l th tea m who i s now ta ki ng ca re of
her, for unrel a ted medi ca l condi ti ons , i n the hos pi ta l . The pa ti ent recei ves a drug tha t l ea ds to a fa ta l res pons e cha ra cteri zed by profound fever,
del i ri um, ps ychoti c beha vi or, a nd s ta tus epi l epti cus . It wa s found to ha ve occurred beca us e of a n i ntera cti on wi th the MAOI. Whi ch, mos t l i kel y,
wa s thi s s econd drug or the drug cl a s s to whi ch i t bel ongs ?
a . Ba rbi tura te
b. Di a zepa m

c. Meperi di ne
d. Morphi ne
e. Phenytoi n
144. A young woma n i s ta ken to the emergency depa rtment by s ome of her fri ends . It s eems they were out on ba r ni ght a nd s omeone s l i pped
s omethi ng i nto her a l cohol i c bevera ge, the fi rs t a nd onl y one s he cons umed tha t ni ght. She i s now extra ordi na ri l y drows y a nd ha s l i ttl e reca l l of
wha t ha ppened between the ti me s he s i pped her dri nk a nd now. Someone overhea rd a nother ba r pa tron ta l ki ng a bout roofi es . You s us pect her
dri nk wa s s pi ked wi th Rohypnol , the l es s er-known generi c na me of whi ch i s fl uni tra zepa m. A pos i ti ve res pons e (i e, s ymptom i mprovement) to
wha t drug tha t you gi ve woul d confi rm your s us pi ci on?
a . Di a zepa m
b. Fl uma zeni l
c. Keta mi ne
d. Na l trexone
e. Tri a zol a m
145. In deci di ng on pha rma cothera py for ma ny pa ti ents youve di a gnos ed wi th depres s i on, youve us ua l l y cons i dered s ta rti ng wi th a n SSRI or, i n
s ome ca s es , a tri cycl i c. Toda y you a s s es s a pa ti ent a nd s us pect endogenous depres s i on. Whi l e di s cus s i ng trea tment opti ons they refer to a drug
by na me a nd a s k you a bout i t; theyve s een ma ny a dverti s ements for i t i n ma ga zi nes a nd on TV. The drug (generi c na me) i s bupropi on. In wha t
ma i n wa y does bupropi on di ffer from ei ther or both the SSRIs or tri cycl i cs ?
a . Hi gher i nci dence of CNS depres s i on, drows i nes s
b. Hi gher i nci dence of wei ght ga i n
c. Les s drug-i nduced s exua l dys functi on
d. Much more common a nd s evere fa l l s of res ti ng bl ood pres s ure a nd orthos ta ti c hypotens i on
e. More s evere a nd more frequent peri phera l a nti chol i nergi c (a tropi ne-l i ke) s i de effects
f. Stronger i nhi bi ti on of monoa mi ne oxi da s e
146. A 33-yea r-ol d woma n pa ti ent trea ted wi th ha l operi dol i s s een i n the emergency depa rtment (ED). Her hus ba nd des cri bes compl a i nts of ra pi dl y
wors eni ng fever, mus cl e s ti ffnes s , a nd tremor. Her l evel of cons ci ous nes s i s di mi ni s hi ng. Her tempera ture i s 104F, a nd her bl ood crea ti ne ki na s e
(CK) l evel i s el eva ted. Wha t i s the mos t l i kel y expl a na ti on for thes e fi ndi ngs ?
a . Al l ergi c res pons e to her medi ca ti on
b. Neurol epti c ma l i gna nt s yndrome (NMS)
c. Overdos e
d. Pa rki ns oni s m
e. Ta rdi ve dys ki nes i a
147. Nea rl y a l l the drugs us ed a s pri ma ry thera py, or a s a djuncts , for the trea tment of Pa rki ns on di s ea s e or drug-i nduced pa rki ns oni s m exert thei r
des i red effects di rectl y i n the bra i ns s tri a tum. Whi ch one exerts i ts ma i n effects i n the gut, not i n the bra i n?
a . Ama nta di ne
b. Benztropi ne
c. Bromocri pti ne
d. Ca rbi dopa
e. Sel egi l i ne
148. You ha ve a pa ti ent wi th s evere pos topera ti ve pa i n who i s not getti ng a dequa te a na l ges i a from us ua l l y effecti ve dos es of morphi ne. The
phys i ci a n orders a n i mmedi a te s wi tch to penta zoci ne (a t us ua l l y effecti ve a na l ges i c dos es ). Wha t i s the mos t l i kel y outcome of s toppi ng the
morphi ne a nd i mmedi a tel y s ta rti ng the penta zoci ne?
a . Abrupt, a dded res pi ra tory depres s i on
b. Acute devel opment of phys i ca l dependence
c. Coma
d. Sei zures
e. Wors eni ng of pa i n
149. The chos en pha rma col ogi c a pproa ch to ma na gi ng a pa ti ent wi th mi l d a nd recentl y di a gnos ed pa rki ns oni s m wi l l be to enha nce s peci fi ca l l y
the a cti vi ty of endogenous bra i n dopa mi ne by i nhi bi ti ng i ts meta bol i c i na cti va ti on. Wha t drug works pri ma ri l y by tha t mecha ni s m?
a . Benztropi ne
b. Sel egi l i ne
c. Tri hexypheni dyl
d. Bromocri pti ne
e. Chl orproma zi ne
150. Chl orproma zi ne ha s been pres cri bed for a pa ti ent wi th s chi zophreni a , a nd the pa ti ent ha s been ta ki ng the drug, a t us ua l l y effecti ve dos es , for
a bout 6 months . Toda y he comes to the hos pi ta l wi th other medi ca l condi ti ons tha t requi re s urgery a nd the a dmi ni s tra ti on of other drugs , a nd we
deci de i t i s unwi s e to s top the chl orproma zi ne a nd run the ri s k of ps ychoti c beha vi or whi l e we perform other i nterventi ons . Wha t other
s i gns /s ymptoms tha t the pa ti ent ma y a l s o ha ve or a cqui re a s the res ul t of s urgery a nd drug thera py a re mos t l i kel y to be a ffected benefi ci a l l y by
the conti nued us e of chl orproma zi ne?
a . Epi l eps y a nd the ri s k of s ei zures

b. Hypotens i on
c. Na us ea a nd vomi ti ng
d. Uri na ry retenti on ca us ed by a bdomi na l s urgery
e. Xeros tomi a (dry mouth) ca us ed by a nti mus ca ri ni c drugs us ed to prevent i ntra -opera ti ve bra dyca rdi a
151. There a re, ri ghtful l y, concerns a bout coca i ne a bus e, a nd too ma ny dea ths ha ve occurred from s moki ng cra ck coca i ne or i njecti ng or na s a l l y
i nha l i ng the drug. Wha t s ta tement bes t des cri bes the ma i n mecha ni s m by whi ch coca i ne exerts i ts del eteri ous effects i n the centra l nervous
s ys tem or i n the peri phery?
a . Di rectl y a cti va tes , a s a n a goni s t, both - a nd 1 -a drenergi c receptors
b. Enha nces neurona l l y medi a ted a drenergi c receptor a cti va ti on by i nhi bi ti ng neurona l norepi nephri ne reupta ke
c. Inhi bi ts ca techol a mi ne i na cti va ti on by i nhi bi ti ng MAO a nd ca techol -O-methyl tra ns fera s e
d. Produces bra dyca rdi a a nd va s odi l a ti on, l ea di ng to hypotens i on a nd a cute hea rt fa i l ure, by bl ocki ng neurona l NE rel ea s e
e. Sti mul a tes a utonomi c nerve conducti on effecti vel y, l ea di ng to i ncrea s ed neurona l norepi nephri ne rel ea s e
152. One a pproa ch to ma na gi ng hyperprol a cti nemi a i s to a dmi ni s ter a drug tha t ha s rel a ti ve s el ecti vi ty, a s a n a goni s t, for centra l (a s a n a goni s t)
dopa mi ne D 2 receptors . Wha t drug works i n tha t ma nner?
a . Bromocri pti ne
b. Chl orproma zi ne
c. Fl uphena zi ne
d. Ha l operi dol
e. Prometha zi ne
153. We perform a meta -a na l ys i s on the a bi l i ty of va ri ous a nti ps ychoti c drugs to ca us e cons ti pa ti on, uri na ry retenti on, bl urred vi s i on, a nd dry
moutha l l of whi ch refl ect s i gni fi ca nt bl ocka de of mus ca ri ni c receptors i n the peri phera l nervous s ys tems . Wha t drug mos t l i kel y ca us ed thes e
unwa nted effects ?
a . Chl orproma zi ne
b. Cl oza pi ne
c. Ha l operi dol
d. Ol a nza pi ne
e. Sertra l i ne
154. It i s obvi ous tha t morphi ne s houl d a l wa ys be a dmi ni s tered wi th ca re. However, one of i ts expected effects tha t occur onl y whi l e the drug i s
bei ng gi ven ma kes i t pa rti cul a rl y da ngerous to a dmi ni s ter to certa i n pa ti ents unl es s s peci a l mea s ures ca n be ta ken to prevent thi s a dvers e
effect. Whi ch comorbi di ty wei ghs a ga i ns t us i ng morphi ne, unl es s you fi rs t ta ke preca uti ons to prevent a dvers e cons equences from occurri ng?
a . Acute pul mona ry edema
b. Cl os ed-hea d i njury
c. Hi s tory of epi l eps y
d. Hypertens i on
e. Recent/evol vi ng myoca rdi a l i nfa rcti on
155. A 66-yea r-ol d woma n ha s termi na l ca ncer, a nd i s i n hos pi ce. She i s recei vi ng round-the-cl ock opi oi ds , a t ra ther hi gh dos es , but s ti l l reports
wha t s he des cri bes a s s i gni fi ca nt burni ng, s hooti ng pa i n. The phys i ci a n bel i eves i t i s neuropa thi c. Increa s i ng the dos e of opi oi ds ma y be hel pful ,
but tha t opti on i s rul ed-out a t thi s ti me beca us e doi ng s o i s l i kel y to s uppres s venti l a ti on exces s i vel y. In a ddi ti on, the pa ti ent does not wa nt the
exces s i ve groggi nes s tha t i s a pt to occur wi th more opi oi d on boa rd. Al though the pa ti ent i s not a t a l l hypertens i ve, the phys i ci a n pres cri bes a s a n
a na l ges i c a djunct tha t i s fa r more wi del y us ed a s a n a nti hypertens i ve drug. Wha t i s the mos t l i kel y a djuncti ve drug s he pres cri bed?
a . Ca ptopri l
b. Cl oni di ne
c. Hydrochl orothi a zi de
d. La beta l ol
e. Pra zos i n
156. A pa ti ent i s on l ong-term metha done thera py a s pa rt of a hol i s ti c pl a n to curb thei r opi oi d a ddi cti on a nd a bus e. Wha t phra s e bes t des cri bes a
cha ra cteri s ti c of thi s drug?
a . Ca us es penta zoci ne-l i ke a cti va ti on of receptors a nd bl ocka de of receptors
b. Ha s grea ter ora l bi oa va i l a bi l i ty tha n morphi ne, es peci a l l y when ora l a dmi ni s tra ti on i s s ta rted
c. Rema rka bl y devoi d of s uch typi ca l opi oi d a na l ges i c s i de effects a s cons ti pa ti on a nd res pi ra tory depres s i on
d. Us eful for ma i ntena nce thera py i n opi oi d- (eg, heroi n-) dependent i ndi vi dua l s , but l a cks cl i ni ca l l y us eful a na l ges i c effects
e. When a bruptl y s topped a fter l ong-term a dmi ni s tra ti on, ca us es a wi thdra wa l s yndrome tha t i s more i ntens e, but bri efer, tha n tha t a s s oci a ted
wi th morphi ne or heroi n wi thdra wa l
157. A mom gets a note from her 10-yea r-ol d da ughters tea cher tha t the chi l d recentl y s ta rted experi enci ng numerous a l bei t bri ef epi s odes of jus t
s ta ri ng i nto s pa ce throughout the s chool da y. The mother rea l i zes s hes noti ced the s a me i n her gi rl a t home. After a tri p to the pedi a tri ci a n, a nd
referra l to a neurol ogi s t, a di a gnos i s of a bs ence epi l eps y i s ma de. Wha t drug i s genera l l y cons i dered the preferred s ta rti ng drug for thi s type of
epi l eps y i n a n otherwi s e hea l thy chi l d?
a . Di a zepa m

b. Ethos uxi mi de
c. Lora zepa m
d. Methyl pheni da te
e. Phenytoi n
158. A 43-yea r-ol d woma n becomes hypertens i ve a nd s uffers a fa ta l a cute corona ry s yndrome s hortl y a fter s ta rti ng thera py on a drug. Autops y
s hows l i ttl e i n the wa y of corona ry a theros cl eros i s , but ECG cha nges noted jus t before her dea th revea l ed s i gni fi ca nt myoca rdi a l i s chemi a i n the
myoca rdi um s erved by the l eft a nteri or des cendi ng a nd ci rcumfl ex corona ry a rteri es . The ca us e of dea th i s thought to i nvol ve corona ry va s os pa s m.
Wha t drug mos t l i kel y preci pi ta ted thi s event?
a . Bromocri pti ne for Pa rki ns on di s ea s e
b. Ergota mi ne gi ven to a bort a mi gra i ne a tta ck
c. Morphi ne for pos t-tra uma a na l ges i a
d. Phenoxybenza mi ne us ed for ca rci noi d s yndrome
e. Phenytoi n to ma na ge genera l i zed toni c-cl oni c s ei zures
159. Prometha zi ne, a phenothi a zi ne deri va ti ve wi th s ubs ta nti a l a nti -emeti c, a nti tus s i ve, a nd H 1 -hi s ta mi ne receptor bl ocki ng a cti vi ty, ha s a cl i ni ca l
profi l e qui te s i mi l a r to di phenhydra mi ne. Recentl y the FDA ma nda ted a bl a ck box wa rni ng for thi s wi del y us ed drug. The FDA now wa rns a ga i ns t
us e of the drug, i n a l l dos es a nd forms , for chi l dren a ged 2 yea rs or younger. Fa ta l i ti es ha ve occurred i n thes e young pa ti ents , even i n res pons e to
dos a ges tha t previ ous l y were cons i dered thera peuti c a nd s a fe. Wha t i s the mos t l i kel y ca us e of dea th from prometha zi ne i n thes e pa ti ents ?
a . Compl ete (thi rd degree) hea rt bl ock fol l owed by a s ys tol e
b. Hypertens i ve cri s i s , i ntra cra ni a l hemorrha ge
c. Pa rki ns oni a n-l i ke dys ki nes i a s , i ncl udi ng ta rdi ve dys ki nes i a s
d. Severe a nd refra ctory di a rrhea l ea di ng to fl ui d a nd el ectrol yte l os s
e. Venti l a tory depres s i on, a pnea , exces s i ve CNS depres s i on
160. A 55-yea r-ol d undergoes s urgery. She recei ves s evera l drugs for pre-a nes thes i a ca re, i ntuba ti on, a nd i ntra opera ti ve s kel eta l mus cl e pa ra l ys i s ;
a nd a mi xture of i nha l ed a nd pa rentera l a gents to provi de ba l a nced a nes thes i a . Towa rd the end of the procedure s he devel ops a ra pi dl y
progres s i ng fever, hypertens i on, hyperka l emi a , ta chyca rdi a , mus cl e ri gi di ty, a nd meta bol i c a ci dos i s . Whi ch drug combi na ti on i s mos t l i kel y to ha ve
el i ci ted thi s rea cti on?
a . Fenta nyl a nd mi da zol a m
b. Mi da zol a m a nd morphi ne
c. Ni trous oxi de a nd etomi da te
d. Propofol a nd mi da zol a m
e. Succi nyl chol i ne a nd i s ofl ura ne
161. A 30-yea r-ol d woma n wi th pa rti a l s ei zures i s trea ted wi th vi ga ba tri n. Wha t i s the s peci fi c mecha ni s m of a cti on of thi s GABA-rel a ted
a nti convul s a nt?
a . Bl ocked neurona l reupta ke of rel ea s ed GABA
b. Di rectl y a cti va ted pos ts yna pti c GABA receptors
c. Increa s ed neurona l GABA rel ea s e
d. Inhi bi ted ca ta bol i s m of rel ea s ed GABA
e. Sti mul a ted neurona l GABA s ynthes i s by a cti ng a s a meta bol i c precurs or
162. A 24-yea r-ol d woma n ha s a hi s tory of epi l eps y tha t i s bei ng trea ted wi th phenytoi n. She i s hea l thy otherwi s e. She becomes pregna nt. Wha t
woul d you do throughout the rema i nder of her pregna ncy, i n a ddi ti on to provi di ng otherwi s e proper peri na ta l ca re?
a . Add va l proi c a ci d
b. Di s conti nue a l l a nti convul s a nt medi ca ti on
c. Increa s e da i l y di eta ry i ron i nta ke
d. Pres cri be da i l y fol i c a ci d s uppl ements
e. Swi tch from the phenytoi n to phenoba rbi ta l
163. A pa ti ent i s tra ns ported to the emergency depa rtment by a mbul a nce a fter repea ted epi s odes of fa i nti ng. The ca us e wa s a ttri buted to s evere
drug-i nduced orthos ta ti c hypotens i on due to -a drenergi c bl ocka de from one of the drugs ma i n s i de effects . Wha t drug wa s the mos t l i kel y ca us e
of thi s probl em?
a . Bus pi rone
b. Chl orproma zi ne
c. Di phenhydra mi ne
d. Ha l operi dol
e. Zol pi dem
164. Cl oza pi ne, a s a n exa mpl e of the a typi ca l a nti ps ychoti cs , s el dom i s us ed a s fi rs t-l i ne (i ni ti a l ) thera py of s chi zophreni a . Compa red wi th the
ol der tra di ti ona l a nti ps ychoti cs , i t i s a s s oci a ted wi th a much hi gher ri s k of a s eri ous a dvers e res pons e. Wha t i s tha t grea ter ri s k?
a . Agra nul ocytos i s
b. Extra pyra mi da l s i de effects (pa rki ns oni s m)
c. Hypogl ycemi a

d. Hypotens i on, s evere

e. Venti l a tory depres s i on or a rres t
165. Youre a t the end of the fi rs t week of your M3 ob-gyn cl erks hi p. You a re a bout to go i nto the del i very room to s ee your fi rs t chi l dbi rth. Youve
revi ewed her cha rt a nd s ee tha t s he wa s ta ki ng, for the dura ti on of pregna ncy, a drug tha t i s not a bs ol utel y contra i ndi ca ted i n pregna ncy (i e, not
ca tegory X). You note tha t a bout 1 month before s he wa s pres cri bed da i l y ora l vi ta mi n K s uppl ements . The ba by i s born a nd promptl y gets a n
i njecti on of vi ta mi n K. Knowi ng wha t you do a bout vi ta mi n K, you correctl y rea s on tha t thes e mea s ures were ta ken to reduce the ri s ks of exces s i ve
or a bnorma l bl eedi ng, ca us ed by drug-i nduced i mpa i rments of hepa ti c vi ta mi n K-dependent cl otti ng fa ctors , i n the newborn. Wha t drug di d the
mother mos t l i kel y recei ve duri ng pregna ncy, a s s umi ng tha t i t wa s not i n pregna ncy ca tegory X?
a . Bupropi on
b. Di a zepa m
c. Metha done
d. Phenytoi n
e. Wa rfa ri n
166. When ca rbi dopa i s a dmi ni s tered a l ong wi th l evodopa for Pa rki ns on di s ea s e, we i ncrea s e the bi oa va i l a bi l i ty of l evodopa by i nhi bi ti ng the
forma ti on of dopa mi ne i n the gut. However, the ca rbi dopa -i nduced i nhi bi ti on of dopa deca rboxyl a s e fa vors the peri phera l meta bol i s m of
l evodopa to a nother meta bol i te tha t competes wi th l evodopa for tra ns port a cros s the bl ood-bra i n ba rri er. Thi s i s ca ta l yzed by ca techol -Omethyl tra ns fera s e (COMT). If your goa l i s to i nhi bi t COMT, a nd s o i ncrea s e the centra l bi o-a va i l a bi l i ty a nd effects of l evodopa , wha t drug woul d you
choos e?
a . Donepezi l
b. Enta ca pone
c. Sel egi l i ne
d. Ta cri ne
e. Tri hexypheni dyl
167. A pa ti ent ha s a l ong hi s tory of exces s i ve a l cohol cons umpti on. He wa s a rres ted s evera l ti mes for drunk dri vi ng a nd wa s referred to a phys i ci a n
for thera py. The phys i ci a n pres cri bed a drug to s ti fl e further a l cohol i nges ti on, to be us ed a l ong wi th other i nterventi ons . The doctor properl y
i ns tructed the pa ti ent not to cons ume a ny a l cohol , not to us e a l cohol -conta i ni ng mouthwa s hes , nor even a ppl y a l cohol -ba s ed toi l etri es , beca us e
a l cohol ma y ca us e a di s turbi ng, i f not da ngerous , i ntera cti on wi th hi s medi ca ti on. The pa ti ent i gnored the a dvi ce a nd deci ded to ha ve a beer.
Wi thi n mi nutes he devel ops fl us hi ng, a throbbi ng hea da che, na us ea , a nd vomi ti ng. Whi ch drug wa s he mos t l i kel y ta ki ng to curb hi s a l cohol us e?
a . Na l trexone
b. Di a zepa m
c. Di s ul fi ra m
d. Phenoba rbi ta l
e. Tra nyl cypromi ne
168. A pa ti ent wi th endogenous depres s i on i s s ta rted on a drug tha t s el ecti vel y i nhi bi ts neurona l s erotoni n (5-HT) reupta ke a nd ha s mi ni ma l
effect on the reupta ke of norepi nephri ne or dopa mi ne. Wha t drug bes t fi ts thi s des cri pti on?
a . Ami tryptyl i ne
b. Bupropi on
c. Fl uoxeti ne
d. Imi pra mi ne
e. Venl a fa xi ne
169. A 29-yea r-ol d ma n us es a n ora l benzodi a zepi ne a nd a l cohol to s a ti s fy hi s a ddi cti on to CNS depres s a nts . Duri ng the pa s t week, he ha s been
i nca rcera ted a nd i s not a bl e to obta i n the drugs . He i s brought to the medi ca l wa rd beca us e of the ons et of s evere a nxi ety, i ncrea s ed s ens i ti vi ty to
l i ght, di zzi nes s , a nd genera l i zed tremors due to drug wi thdra wa l . On phys i ca l exa mi na ti on, he i s hyperrefl exi c. Whi ch drug woul d be the bes t
choi ce to di mi ni s h hi s wi thdra wa l s ymptoms ?
a . Bus pi rone
b. Chl ora l hydra te
c. Chl orproma zi ne
d. Lora zepa m
e. Tra zodone
170. A 50-yea r-ol d ma n ha s been cons umi ng l a rge a mounts of etha nol on a n a l mos t da i l y ba s i s for ma ny yea rs . One da y, una bl e to fi nd a ny
etha nol , he i nges ts a l a rge a mount of metha nol (wood a l cohol ) tha t he ha d bought for hi s ca mp l a ntern. Wha t drug woul d a dmi ni s ter to bes t trea t
underl yi ng bi ochemi ca l cons equences of the metha nol poi s oni ng?
a . Di a zepa m
b. Etha nol
c. Fl uma zeni l
d. Phenoba rbi ta l
e. Phenytoi n
171. Ma ny news reports ha ve tol d of a l a rge number of dea ths of opi oi d a bus ers who purcha s ed a nd s el f-a dmi ni s tered i l l i ci t drugs tha t conta i ned
l etha l a mounts of fenta nyl . One pa ti ent who recei ved thi s fenta nyl -l a ced drug pres ents i n your emergency depa rtment, ba rel y a l i ve. Wha t drug
woul d you a dmi ni s ter fi rs t, wi th the bes t hope tha t i t ca n promptl y revers e the l etha l effects of the fenta nyl ?

a . Di a zepa m
b. Fl uma zeni l
c. Na l oxone
d. Na l trexone
e. Phenytoi n
172. A 10-yea r-ol d boy ha s nocturna l enures i s . Hi s pa rents ta ke hi m to a cl i ni c tha t s peci a l i zes i n ma na gement of thi s condi ti on. The phys i ci a n
wri tes a n order for a l ow dos e of i mi pra mi ne. After a coupl e of weeks on the drug, the epi s odes of bed-wetti ng decrea s e dra ma ti ca l l y. Wha t i s the
mos t l i kel y mecha ni s m by whi ch the i mi pra mi ne provi ded benefi t?
a . Al l evi a tes depres s i on s i gns a nd s ymptoms by i ncrea s i ng neurona l ca techol a mi ne reupta ke
b. Bl ocks mus ca ri ni c receptors i n the bl a dder mus cul a ture
c. Ca us es s eda ti on s uch tha t the boy s l eeps through the ni ght wi thout voi di ng
d. Reduces rena l bl ood fl ow, gl omerul a r fi l tra ti on, a nd uri ne output
e. Rel ea s es a nti di ureti c hormone (ADH)
173. A pa ti ent i s tra ns ported to your emergency depa rtment beca us e of a s ei zure. A revi ew of hi s hi s tory revea l s tha t he ha s been trea ted by
di fferent phys i ci a ns for di fferent medi ca l condi ti ons , a nd there ha s been no di a l og between them i n terms of wha t theyve pres cri bed. One
phys i ci a n pres cri bed a drug for s hort-term ma na gement of depres s i on. Another pres cri bed the very s a me drug, ma rketed under a di fferent tra de
na me, to hel p the pa ti ent qui t s moki ng ci ga rettes . Wha t drug wa s mos t l i kel y pres cri bed by both doctors , a nd wa s the mos t l i kel y ca us e of the
s ei zures ?
a . Bupropi on
b. Chl ordi a zepoxi de
c. Fl uoxeti ne
d. Imi pra mi ne
e. Li thi um
174. About 1 yea r a go you di a gnos ed s chi zophreni a s i gns a nd s ymptoms i n a 23-yea r-ol d otherwi s e hea l thy ma n. As a res ul t of i ntens i ve
ps ychothera py, ca reful ti tra ti on of chl orproma zi ne dos a ges , a nd rema rka bl y good compl i a nce on the pa ti ents pa rt, he i s wel l enough to return to
work. Severa l months l a ter, a t a s chedul ed vi s i t, you obs erve numerous s i gns a nd s ymptoms of drug-i nduced pa rki ns oni s m, a nd the pa ti ent reports
ra ther di s tres s i ng s ymptoms of a ka thi s i a s (i nner res tl es s nes s , ji tteri nes s , etc). However, typi ca l ma ni fes ta ti ons of s chi zophreni a s eem to be wel l
control l ed. Whi ch a pproa ch i s mos t l i kel y to a l l evi a te the motor a nd s ubjecti ve pa rki ns oni a n res pons es , a nd pos e the l owes t ri s k of ca us i ng
s chi zophreni a s i gns a nd s ymptoms to rea ppea r?
a . Add a ca techol -O-methyl tra ns fera s e i nhi bi tor (eg, tol ca pone)
b. Add a centra l l y a cti ng chol i nes tera s e i nhi bi tor (eg, donepezi l or ta cri ne)
c. Add benztropi ne
d. Add l evodopa or l evodopa pl us ca rbi dopa
e. Swi tch from chl orproma zi ne to ha l operi dol
175. A pa ti ent wi th Pa rki ns on di s ea s e s ta rts thera py wi th a drug tha t a cts i n the CNS a s a n a goni s t for dopa mi ne receptors . It ha s no di rect effects
on dopa mi ne s ynthes i s , neurona l reupta ke, or meta bol i c i na cti va ti on. Wha t drug fi ts thi s des cri pti on the bes t?
a . Ama nta di ne
b. Apomorphi ne
c. Bel l a donna
d. Bromocri pti ne
e. Sel egi l i ne
176. A pa ti ent devel ops profound fever, s kel eta l mus cl e ri gi di ty, a nd a utonomi c a nd s ys temi c el ectrol yte i mba l a nces a s pa rt of a s evere a dvers e
res pons e to a ps ychoa cti ve drug. The worki ng di a gnos i s i s neurol epti c ma l i gna nt s yndrome. In a ddi ti on to a dmi ni s teri ng da ntrol ene i n a n a ttempt
to res tore s ome s embl a nce of norma l s kel eta l mus cl e functi on, wha t other drug i s mos t l i kel y to be gi ven to hel p provi de a ddi ti ona l s ymptom
rel i ef?
a . Benztropi ne
b. Bromocri pti ne
c. Di a zepa m
d. Fl uma zeni l
e. Na l oxone
f. Propra nol ol
177. A pa ti ent di a gnos ed wi th depres s i on ha d been ta ki ng a mi tri ptyl i ne for s evera l months . Duri ng a vi s i t to hi s phys i ci a n he reported di ffi cul ty
s l eepi ng, s o the MD pres cri bed tra zodone, to be ta ken once da i l y, a t bedti me. The dos a ges of both the a mi tri ptyl i ne a nd the tra zodone were
cl ea rl y wi thi n the thera peuti c ra nge. Severa l weeks l a ter the pa ti ent di ed. The a ttorney hi red by the decea s ed ma ns pa ti ent, a s pa rt of a wrongful
dea th s ui t, conta cted s evera l expert wi tnes s es who s ta ted tha t the a mi tri ptyl i netra zodone combi na ti on ca us ed a l etha l s erotoni n s yndrome.
Ba s ed onl y on the i nforma ti on pres ented here, wha t i s your mos t rea s ona bl e concl us i on?
a . An i ntera cti on between tra zodone a nd a n SSRI, ea ch a t proper dos a ges , i s unl i kel y to ca us e the s erotoni n s yndrome.
b. The tra zodone-SSRI combi na ti on i s a bs ol utel y contra i ndi ca ted, a nd s houl d never ha ve been pres cri bed.
c. Tra zodone woul d be a ppropri a te onl y i f the pa ti ent were ta ki ng a monoa mi ne oxi da s e (MAO) i nhi bi tor or for depres s i on.
d. Suma tri pta n s houl d ha ve been pres cri bed to prevent the devel opment of the s erotoni n s yndrome.

e. Tra zodone s houl d never be pres cri bed to hel p pa ti ents go to s l eep, whether or not they a re depres s ed or a re ta ki ng a nti depres s a nts .

Central Nervous System Pharmacology

Answers
106. The answer is b. Apol ogi es for s ta rti ng the cha pter on CNS pha rma col ogy wi th a ques ti on tha t defi ni tel y focus es on the a utonomi c nervous
s ys tem. However, the ques ti on i s hel pful a s yet a nother wa y to recogni ze the connecti ons between os tens i bl y di fferent a rea s of pha rma col ogy a nd
drug thera py. The des cri pti on of gua nfa ci nes a utonomi c effects a re extra ordi na ri l y s i mi l a r to thos e of cl oni di ne, whi ch i s genera l l y cons i dered the
prototype of the centra l l y a cti ng a nti hypertens i ve drugs . Cl oni di ne a nd gua nfa ci ne a ct a s pos ts yna pti c -a drenergi c a goni s ts (s peci fi ca l l y, 2A; i n
the CNS, proba bl y on prefronta l corti ca l neurons i n terms of the effects on ADHD a nd a nxi ety; a nd i n the medul l a ry ca rdi ova s cul a r control center
i n terms of peri phera l a utonomi c effects . Indeed, the overa l l di a l i ng-down of s ympa theti c outfl ow, whi ch a ccounts for gua nfa ci nes ma i n
a utonomi c a cti on, a l s o a ccounts for i ts much ol der us e a s a n a nti hypertens i ve drug.
None of the res pons es des cri bed for gua nfa ci ne a re qua l i ta ti vel y or mecha ni s ti ca l l y s i mi l a r to thos e expected wi th a tropi ne (a ) or a ny other
drug wi th s trong mus ca ri ni c receptor bl ocki ng a cti vi ty. Phentol a mi ne (c), the prototype peri phera l l y a cti ng 1 - a nd 2 -a drenergi c bl ocker, woul d
ca us e mi os i s (by unma s ki ng oppos i ng pa ra s ympa theti c i nfl uences on pupi l s i ze), a l though a s des cri bed i n the ques ti on i t woul d ha ve no effect on
a i rwa y s mooth mus cl e (whi ch i s a ffected by drugs tha t ei ther work di rectl y on 2 a drenergi c, or mus ca ri ni c-chol i nergi c, receptors ). And, unl i ke the
s i tua ti on wi th gua nfa ci ne or cl oni di ne, phentol a mi ne wi l l markedly a nta goni ze va s opres s or effects of -a goni s ts s uch a s phenyl ephri ne. Fi na l l y,
phentol a mi ne woul d not ca us e fa l l s of res ti ng hea rt ra te or s troke vol ume, s i nce both of thos e functi ons a re regul a ted by a cti va ti on of 1 a drenergi c receptors i n va ri ous pa rts of the hea rt.
Pra zos i n (d) i s a peri phera l l y a cti ng a nd s el ecti ve 1 a nta goni s t. Some of the effects of gua nfa ci ne a re s i mi l a r to thos e of pra zos i n, but there a re
three effects tha t were noted a nd tha t woul d a rgue a ga i ns t pra zos i n bei ng the correct a ns wer: (1) pra zos i n will i ndeed bl ock the va s opres s or
res pons es to phenyl ephri ne or a ny other drug tha t a cti va tes -a drenergi c receptors ; (2, 3) i t wi l l not i nterfere wi th -medi a ted i ncrea s es of hea rt
ra te or s troke vol ume, whether medi a ted by the ba roreceptor refl ex or otherwi s e. In contra s t, propra nol ol (d; or a ny other -bl ocker tha t l a cks
va s odi l a tor a cti vi ty) woul d l ower res ti ng hea rt ra te a nd a l s o bl unt ba roreceptor-medi a ted i ncrea s es of hea rt ra te a nd s troke vol ume.
107. The answer is e. (Brunton, pp 466t, 527-560; Katzung, pp 40t, 373-381.) Benzodi a zepi nes a s a cl a s s tend to ca us e s hort-term memory l os s fol l owi ng
a dmi ni s tra ti on. The i ntens i ty of the effect depends on the uni que drug (common a nd i ntens e wi th mi da zol a m, whi ch ha s a fa s t ons et a nd s hort
ha l f-l i fe; a nd fl uni tra zepa m [Rohypnol , known on the s treet ma i nl y a s roofi es ], for exa mpl e), the drugs pha rma coki neti cs , a nd the dos e a nd
a dmi ni s tra ti on route.
The memory l os s does not a ffect reca l l of pri or events but ra ther events occurri ng s hortl y a fter the drug i s gi ven. Thi s antegrade amnesia i s
va l ua bl e i n s etti ngs s uch a s des cri bed i n the s cena ri o, where ma ny unpl ea s a nt a nd a nxi ety-provoki ng events ma y occur between preop
medi ca ti on, the tri p to the opera ti ng room, a nd other unpl ea s a ntri es tha t mi ght occur before the pa ti ent i s a nes theti zed. (The pa ti ent here ha d
a bs ol utel y no reca l l of events occurri ng wi thi n a bout 30 s econds a fter the mi da zol a m wa s gi ven, up to a bout a n hour a fter s he rega i ned
cons ci ous nes s i n the OR. Ma ny pa ti ents who recei ve mi da zol a m for endos copi c procedures s uch a s col onos copy or bronchos copy a l s o l a ck reca l l .)
Mi da zol a m i ntens i fi es the overa l l s eda ti ve a nd menta l cl oudi ng effects of opi oi ds , but does not potenti a te a na l ges i a (a ). It does not prevent or
revers e hypotens i on (b), a nd i f the dos e i s too l a rge or i t i s a dmi ni s tered too qui ckl y, the drug ma y a ctua l l y l ower bl ood pres s ure i n i ts own ri ght.
Mi da zol a m ha s s ome a nti convul s a nt effects but i t i s s el dom us ed for tha t purpos e (l ora zepa m i s one benzodi a zepi ne tha t i s routi nel y us ed for
certa i n s ei zures , pa rti cul a rl y s ta tus epi l epti cus ). More i mporta ntl y the ques ti on s ta ted s ei zures l i kel y to be ca us ed by propofol , but propofol
ra rel y ca us es s ei zures (c). Benzodi a zepi nes a re not a rrhythmogeni c nor do they ha ve a nti a rrhythmi c a cti vi ty (d).
108. The answer is a. (Brunton, pp 538t, 541-542; Katzung, pp 438-441.) Hypotens i on a nd res pi ra tory/venti l a tory depres s i on i s a common s i de effect wi th
propofol a nd, i ndeed, wi th mos t other cl a s s es of CNS depres s a nts i njected for ei ther a nes thes i a i nducti on or ma i ntena nce. La ryngos pa s m (b)
s ometi mes a nd ra ther uni quel y a ppl i es to i njecti on of ra pi dl y a cti ng ba rbi tura te i nducti on a gents (s ee the next ques ti on). Memory l os s (c)
s peci fi ca l l y s hort-term a ntegra de a mnes i a i s a s s oci a ted wi th certa i n benzodi a zepi nes (here, the mi da zol a m, previ ous ques ti on).
Propofol does not ca us e ma l i gna nt hyperthermi a (d), or i ntera ct wi th other medi ca ti ons (thos e l i s ted i n the MAR, or others ) to ca us e i t.
Ma l i gna nt hyperthermi a i s ma i nl y l i nked, i n the s urgi ca l s etti ng, to the combi ned us e of a ha l ogena ted hydroca rbon i nha l ed a nes theti c
(pa rti cul a rl y ha l otha ne, the us e of whi ch i s decl i ni ng) a nd a neuromus cul a r bl ocker (typi ca l l y s ucci nyl chol i ne more s o tha n a cura re-l i ke
nondepol a ri zi ng a gents ). Propofol does not ca us e s ei zures (e); of the i njecta bl e i nducti on a gents , s ei zures a re ma i nl y a probl em wi th etomi da te.
Fi na l l y, a s i de from genera l i zed s uppres s i on of the CNS, propofol ca us es no s i gni fi ca nt or cl i ni ca l l y rel eva nt effects on s kel eta l mus cl e, a nd tends
not to ca us e na us ea or emes i s (when us ed a l one) tha t i s common wi th other rea s ona bl e a l terna ti ves .
109. The answer is c. (Brunton, pp 539-540; Katzung, pp 441-442.) La ryngos pa s m i s a s s oci a ted wi th the ba rbi tura te IV i nducti on a gents , whether the drug
i s a n oxyba rbi tura te (methohexi ta l ) or a thi oba rbi tura te (thi a myl a l , thi openta l , others ; thi o refers to a s ul fur a tom repl a ci ng a n oxygen a tom a t a
certa i n poi nt i n the mol ecul e). The mecha ni s m i s not known for s ure, but the phenomenon i s , a nd the l a ryngos pa s m ma y be s uffi ci ent i n a s ma l l
number of ca s es to ma ke a i rwa y i ntuba ti on di ffi cul t. The ba rbi tura tes a l s o ca us e venti l a tory depres s a nt effects (centra l l y medi a ted), but i n the
s i tua ti on des cri bed here tha t i s not worri s ome, beca us e the pa ti ent i s recei vi ng mecha ni ca l venti l a ti on.
Ba rbi tura tes l a ck a na l ges i c effects (a t bl ood l evel s not fa r l ower tha n l etha l ). They ca n a ctua l l y i ncrea s e the s ens a ti on of pa i n (hypera l ges i c
effect, a ) when thera peuti c dos es of ora l a gents (ma i nl y phenoba rbi ta l nowa da ys ) a re gi ven (i na ppropri a tel y) to pa ti ents wi th pa i n a nd who a re
not bei ng trea ted wi th true a na l ges i c drugs s ui ta bl e for the degree of pa i n the pa ti ent ha s . Thi s i s one of the rea s ons why ba rbi tura tes a nd
benzodi a zepi nes for tha t ma tters houl d never be us ed a s a na l ges i cs . Note, however, tha t when the fa s t-a cti ng i njecta bl e ba rbi tura tes a re gi ven
a t us ua l i nducti on/a nes theti c dos es the hypera l ges i c effect does not occur; i n a ddi ti on, thi s pa ti ent got other proper a na l ges i cs (morphi ne,
ketorol a c).
Ba rbi tura tes , whether gi ven pa rentera l l y or ora l l y, a nd rega rdl es s of thei r pha rma coki neti cs , tend to l ower bl ood pres s ure (not ra i s e i t, a ns wer
b; the proba bl e s i tes of a cti on a re both centra l a nd di rectl y on the hea rt). Ba rbi tura tes us ed a s IV i nducti on a gents tend to l ower bl ood pres s ure
s i gni fi ca ntl y a nd s ometi mes exces s i vel y. Ma l i gna nt hyperthermi a (d) i s a s eri ous a dvers e peri opera ti ve res pons e tha t i s a s s oci a ted wi th the
combi ned a dmi ni s tra ti on of s kel eta l neuromus cul a r bl ockers (typi ca l l y s ucci nyl cho-l i ne) a nd certa i n i nha l ed ha l ogena ted hydroca rbon
a nes theti cs (eg, ha l otha ne). Ba rbi tura tes do not i ntera ct or ca us e ma l i gna nt hyperthermi a i n thei r own ri ght. Al l the ba rbi tura tes ha ve
a nti convul s a nt a cti vi ty (dos e-dependent a nd a l s o dependent on whi ch ba rbi tura te i s bei ng us ed), a nd they do not ca us e myocl onus or other types
of s ei zures (e). The hi gher ri s k of myocl oni c s ei zures i s ma i nl y a s s oci a ted wi th etomi da te, whi ch i s a nother IV i nducti on a gent. (Etomi da tei nduced s ei zure ri s k ca n be reduced by premedi ca ti on wi th a n opi oi d or a benzodi a zepi ne.)

110. The answer is b. (Brunton, pp 529, 967t, 986; Katzung, pp 638t, 642, 655.) Al though ketorol a c i s us ua l l y pres ented i n a cha pter on NSAIDs , i t ha s very
wea k (a nd not cl i ni ca l l y us eful ) a nti -i nfl a mma tory a cti vi ty. However, i t provi des excel l ent a na l ges i a tha t ha s been des cri bed a s equi va l ent to tha t
provi ded by us ua l s ta rti ng dos es of a n opi oi d (eg, morphi ne) when pa i n i s modera te a nd rel a ti vel y s hort l i ved. The mecha ni s m proba bl y i nvol ves
i nhi bi ted pros ta gl a ndi n s ynthes i s (a s wi th a l l NSAIDs ) a nd does not i nvol ve a cti va ti on of a ny opi oi d receptors . The drug ha s no a nti emeti c effects
(a ); does not a ffect venti l a tory ra te or depth (c); ha s no effect on s kel eta l neuromus cul a r tra ns mi s s i on or the effects of neuromus cul a r bl ockers (d).
Unl i ke mos t opi oi ds , ketorol a c a l s o l a cks a dvers e effects on the bi l i a ry tra ct, us ua l l y ma ki ng i t a good choi ce for pa ti ents wi th nephrol i thi a s i s or
other condi ti ons tha t tri gger ga l l bl a dder/bi l e duct s pa s m a nd pa i n.
Ketorol a c i s not s ui ta bl e, a l one, for s evere pa i n (when a n opi oi d trul y i s i ndi ca ted) nor for chroni c pa i n. In s urgi ca l s etti ngs s uch a s the one
des cri bed here i t i s us ed a s a s uppl ement to a n opi oi d. Wha t a re the a dva nta ges of ketorol a c, whether us ed a l one or a s a s uppl ement, compa red
wi th a n opi oi d? Ketorol a cs a na l ges i a i s not a ccompa ni ed by typi ca l opi oi d-l i ke venti l a tory depres s i on; hypotens i on; s eda ti on, menta l cl oudi ng or
euphori a ; nor a potenti a l for dependence or a bus e. It i s often us ed a s a n opi oi d s uppl ement preci s el y beca us e the ma i n a l terna ti ve a pproa ch
s i mpl y gi vi ng a hi gher dos e of morphi necoul d l ea d to exces s i ve venti l a tory depres s i on a nd hypotens i on.
Des pi te the rel a ti ve l a ck of a nti -i nfl a mma tory a cti vi ty, the ma i n a dvers e res pons es to ketorol a c a re s i mi l a r to thos e of tra di ti ona l NSAIDs on the
GI tra ct: the potenti a l for ga s tri c ul cera ti on, potenti a l l y wi th GI bl eedi ng or hemorrha ge; for rena l i mpa i rment; a nd for prol onged bl eedi ng due to
a nti pl a tel et effects (wea k a nd not thera peuti ca l l y us eful ). Thes e a dvers e effects a re mos t l i kel y to occur wi th l ong-term us e, whi ch i s why
ketorol a c s houl d be us ed onl y for s hort-term pa i n control (no more tha n 5 da ys ). Mos t of the contra i ndi ca ti ons tha t a ppl y to tra di ti ona l NSAIDs
a ppl y to ketorol a c, for exa mpl e, pepti c ul cer di s ea s e (a cti ve or a ri s k thereof); rena l dys functi on; a cti ve bl eedi ng (es peci a l l y i ntra cra ni a l );
pregna ncy; a nd pri or hypers ens i ti vi ty.
Notes : You s houl d know a bout ketorol a c beca us e i t i s us ed wi del y i n genera l s urgi ca l s etti ngs s uch a s des cri bed i n the ques ti on; i n
orthopedi cs ; a nd i n ora l s urgery a nd other s etti ngs where good s hort-term a na l ges i a i s needed a nd i t i s bes t to mi ni mi ze or a voi d other
unwa nted effects of opi oi ds .
When ketorol a c wa s fi rs t a pproved, ma ny pra cti ti oners us ed i t frequentl y a nd pres cri bed i t for chroni c pa i n control . (Some des cri bed pres cri bi ng
the drug l i ke ca ndy. After a l l , i t provi ded excel l ent pa i n control wi th no opi oi d-l i ke probl ems .) Not l ong therea fter pres cri bers rea l i zed the s trong
ul cerogeni c a cti ons of the drug, a nd s o new gui del i nes a nd wa rni ngs were ma de to res tri ct us e of the drug to no more tha n s evera l da ys i n a row.
111. The answer is e. (Brunton, pp 1341-1343; Katzung, pp 287, 1098-1099.) Onda ns etron, l i ke a rel a ted drug, drona bi nol , i s us ed to ma na ge drugi nduced na us ea a nd vomi ti ng tha t ca n occur pos topera ti vel y or i n res pons e to emetogeni c drugs (eg, ma ny a nti ca ncer drugs ). It i s a s erotoni n
receptor (5-HT3 ) bl ocker tha t a cts ma i nl y i n the medul l a ry chemoreceptor tri gger zone a nd on va ga l a fferents (i nhi bi ted) to pa rts of the upper GI
tra ct.
Onda ns etron ha s no genera l CNS or corti ca l s ti mul a ti ng effects tha t woul d hel p res tore cons ci ous nes s , a l ertnes s , or a wa renes s of ti me a nd
pl a ce (a ); no a na l ges i c-i ntens i fyi ng effects (b); no s i gni fi ca nt effects on the bl a dder (c); a nd does not reduce the ri s k of pa ra l yti c i l eus (d) beca us e
va ga l tone to i ntes ti na l s mooth mus cl es i s s uppres s ed.
112. The answer is d. (Brunton, pp 540-542, 546-547; Katzung, pp 431-436.) MAC (mi ni mum a l veol a r concentra ti on) i s a n expres s i on of i nha l ed a nes theti c
potency. It i s defi ned a s the mi ni mum i ns pi red concentra ti on needed to a bol i s h a s peci fi ed pa i nful res pons e i n 50% of trea ted pa ti ents . (Thus ,
i t i s much l i ke the ED 50 , mea s ured i n a popul a ti on dos e-res pons e curve, for mos t other drugs .) Obvi ous l y, gi vi ng a drug a t a dos e tha t s uppres s es a
res pons e i n onl y ha l f the trea ted pa ti ents i s not des i ra bl e, s o i nha l ed a nes theti cs a re typi ca l l y gi ven a t a dos e more tha n the MAC. (Reca l l , too,
tha t MAC i s not a bs ol ute: i t ca n cha nge dependi ng on the us e of other a nes thes i a a djuncts a nd s uch other fa ctors a s body tempera ture, venti l a tory
ra te, pres ence of other di s ea s es , etc.)
A drugs MAC gi ves us no us eful a nd i nva ri a bl e i nforma ti on a bout ons ets or dura ti ons of a cti on (a , e). You ca nnot s ta te correctl y tha t drug Y (MAC
100%) ca us es grea ter a na l ges i a a nd/or s kel eta l mus cl e rel a xa ti on tha n a nother drug a ny more tha n we ca n s a y tha t a drug wi th a n ED 50 of 5 mg
ca us es a grea ter res pons e tha n one wi th a n ED 50 of 1 mg. It a l l depends on the dos e gi ven, not the MAC or ED 50 .
113. The answer is d. (Brunton, pp 398, 408, 614t, 618; Katzung, pp 488f, 490, 499.) Two of the i mporta nt types of MAO a re: (1) MAO-A, whi ch meta bol i zes
norepi nephri ne a nd s erotoni n a nd other bi ogeni c a mi nes , a nd i s the predomi na nt hepa ti c form of the enzyme; a nd (2) MAO-B, whi ch meta bol i zes
dopa mi ne a nd other monoa mi nes i n the bra i n. Sel egi l i ne i s a s el ecti ve i nhi bi tor of MAO-B. It therefore i nhi bi ts the brea kdown of dopa -mi ne a nd
prol ongs the thera peuti c effecti venes s of l evodopa (endogenous or tha t provi ded pha rma col ogi ca l l y) i n pa rki ns oni s m. The ri s ks of s eri ous drug
i ntera cti ons i n pa ti ents ta ki ng nons el ecti ve MAO i nhi bi tors (eg, phenel zi ne, tra nyl cypromi ne), s uch a s hypertens i ve cri s i s i n res pons e to mi xeda nd i ndi rect-a cti ng s ympa thomi meti cs (tyra mi ne, ps eudoephedri ne, a nd a mpheta mi nes ) a re much l es s (but s ti l l pos s i bl e) wi th s el egi l i ne.
Bromocri pti ne (a ) i s a dopa mi ne receptor a goni s t. Ca rbi dopa (b) i nhi bi ts the peri phera l meta bol i s m of l evodopa by DOPA deca rboxyl a s e. Both
a re us eful i n the trea tment of s ome ca s es of i di opa thi c (but not a nti ps ychoti c drug-i nduced) pa rki ns oni s m. Phenel zi ne (c) a nd tra nyl cypromi ne (e)
a re nons el ecti ve MAOIs . Combi ni ng them wi th L-dopa ma y l ea d to a potenti a l l y fa ta l hypertens i ve cri s i s , a nd thus they a re not us ed i n the thera py
of pa rki ns oni s m. A s i mi l a r i ntera cti on ma y occur wi th tyra mi ne-ri ch foods a nd bevera ges ; a nd wi th ca techol a mi ne-rel ea s i ng s ympa thomi meti cs
(ephedri ne, ps eudoephedri ne, a mpheta mi nes , a nd a mpheta mi ne-l i ke drugs ). As a res ul t of thes e common a nd potenti a l l y l etha l i ntera cti ons ,
non-selective MAO i nhi bi tors a re ra rel y us ed for a nythi ng unl es s no other us ua l l y effecti ve thera pi es work a dequa tel y or a re otherwi s e
contra i ndi ca ted.
114. The answer is d. (Brunton, pp 536-537, 614t; Katzung, pp 485, 499.) When l evodopa i s a dmi ni s tered ora l l y, the va s t ma jori ty of the a dmi ni s tered
dos e (a bout 90%) i s meta bol i zed i n the gut to dopa mi ne by DOPA deca rboxyl a s e. However dopa mi ne ca nnot cros s the bl ood-bra i n ba rri er, a nd s o
onl y a fra cti on of the pa rent drug gets i nto the CNS, to be meta bol i zed a nd ca us e i ts des i red effects there. Ca rbi dopa i nhi bi ts DOPA deca rboxyl a s e
i n the peri phery, reduci ng peri phera l meta bol i s m of l evodopa to dopa mi ne a nd s pa ri ng a bi gger fra cti on of the a dmi ni s tered l evodopa dos e s o
i t ca n be meta bol i zed i n the ni gros tri a tum. By reduci ng peri phera l convers i on of l evodopa to dopa mi ne, the a djuncti ve us e of ca rbi dopa often
ena bl es ma na gement of pa rki ns oni a n s i gns a nd s ymptoms wi th dos es of l evodopa much l ower tha n woul d be needed i n the a bs ence of
ca rbi dopa . One a ddi ti ona l benefi t of tha t i s a reducti on i n the number a nd s everi ty of peri phera l s i de effects of the l evodopa (or, more preci s el y,
i ts meta bol i te, dopa mi ne).
Addi ng ca rbi dopa to a regi men i nvol vi ng l evodopa onl y ma y a l s o hel p (a t l ea s t tra ns i entl y) comba t s uch probl ems a s dopa mi nes on-off
phenomenon a nd end-of-dosefailure. The on-off phenomenon i s cha ra cteri zed by frequent, a brupt, a nd dra ma ti c cha nges between wha t a ppea rs to
be good s ymptom control to epi s odes tha t l ook l i ke pa rki ns oni a n s i gns a nd s ymptoms werent i mproved a t a l l (much l i ke wha t ha ppens when
s wi tchi ng the l i ghts on a nd off). Wi th end-of-dos e fa i l ure, s ymptom control between dos es gets progres s i vel y l es s progres s i vel y s ooner. For
exa mpl e, a pa ti ent who ha d good s ymptom control up to a n hour or s o before the next s chedul ed l evodopa dos e ma y gra dua l l y experi ence l os s of
tha t control 2 hours , 3 hours , or even much more, before they were to ta ke thei r next dos e.
Ca rbi dopa , whether cons i dered i n i ts own ri ght or i n the context of coa dmi ni s tra ti on wi th l evodopa ha s no effects (i nhi bi tory or s ti mul a tory) on

ACh rel ea s e (a ). Vi ta mi n B 6 defi ci enci es of the vi ta mi n do not occur i n res pons e to thera py wi th ei ther or both drugs (b); a nd i t i s i mporta nt to note
tha t i nges ti ng l a rge a mounts of tha t vi ta mi n, whether a s pa rt of the di et or i n the form of s uppl ements , wi l l a nta goni ze the des i red effects of
l evodopa wi th or wi thout a dded ca rbi dopa . Ca rbi dopa does gi ve better a cces s of l evodopa to the CNS, but tha t effect ha s nothi ng to do wi th
i ncrea s i ng bl ood-bra i n ba rri er permea bi l i ty to dopa mi ne (c). It i s due, a s noted, to i ncrea s ed concentra ti ons of l evodopa i n the ci rcul a ti on due to
i nhi bi ted peri phera l convers i on to dopa mi ne. Ca rbi dopa ha s no benefi ci a l effects on dopa mi ne-i nduced bl ood pres s ure cha nges , a nd ha s no
a bi l i ty to bl ock dopa mi ne receptors i n the va s cul a ture (e) or a nywhere el s e.
115. The answer is e. (Brunton, p 349; Katzung, pp 283-285, 374, 376, 387.) Bus pi rone i s a n a ttra cti ve drug for ma na gi ng mi l d s hort-term a nxi ety. Among
the rea s ons (a nd es peci a l l y when compa red wi th more tra di ti ona l a nxi ol yti cs , s uch a s benzodi a zepi nes ) a re a l a ck of s eda ti on (bus pi rone i s not a
CNS depres s a nt); very l i ttl e (i f a ny) potenti a ti on of the effects of other CNS depres s a nts , i ncl udi ng a l cohol ; no known a bus e potenti a l (i t i s not
regul a ted by the Control l ed Subs ta nces Act) or tendency for devel opment of tol era nce; a nd no ma jor wi thdra wa l s yndrome. One ma jor dra wba ck i s
a s l ow ons et of s ymptom rel i ef (a week or two), a nd typi ca l l y i t ta kes a bout a month from the ons et of thera py for a nti a nxi ety effects to s ta bi l i ze.
(Knowi ng thi s s l ow ons et, one s houl d res i s t the tempta ti on to ti tra te the dos a ge upwa rd, to ha s ten or i ncrea s e the drugs effects , prema turel y.)
You s houl d reca l l tha t l ong-term benzodi a zepi ne a dmi ni s tra ti on i s a s s oci a ted wi th wi thdra wa l phenomena (a nd, dependi ng on the us e, dos e,
exa ct drug, a nd other pa ti ent-rel a ted fa ctors , the s yndrome ca n be s evere). Thus , one ca n envi s a ge a s wi tch from a benzodi a zepi ne to bus pi rone.
Beca us e bus pi rone l a cks CNS depres s a nt effects a nd i ts effects ta ke s ome ti me to devel op, one s houl d s ta rt the bus pi rone s evera l weeks before
s toppi ng the benzodi a zepi ne a nd then ta per the benzodi a zepi ne dos e once i ts ti me to s top the drug.
116. The answer is c. (Brunton, pp 593-594; Katzung, p 411.) Phenoba rbi ta l s rol e i n the pri ma ry ma na gement of a l l of the na med condi ti ons ha s wa ned
dra ma ti ca l l y, a nd a ppropri a tel y, a s newer drugs , wi th fewer ri s ks of drug i ntera cti ons a nd tol era nce devel opment, ha ve come on the ma rket. The
onl y us e i n the opti ons provi ded i n the ques ti on, for whi ch phenoba rbi ta l i s s ti l l cons i dered rea s ona bl e for l ong-term thera py i n s ome pa ti ents , i s
for ma na gi ng certa i n epi l eps i es (ma i nl y a s a n a l terna ti ve to phenytoi n). The s ei zure types i ncl ude, ma i nl y, pa rti a l s ei zures a nd genera l i zed toni ccl oni c s ei zures . Benzodi a zepi nes a re a l mos t a l wa ys preferred, a nd us ed, for ma na gi ng a l cohol wi thdra wa l (a ) a nd thera py of a nxi ety (b).
Benzodi a zepi nes , or the benzodi a zepi ne-l i ke a gents za l epl on or zol pi dem, a re a l mos t a l wa ys turned to for i ns omni a (e). Phenoba rbi ta l a nd
other ba rbi tura tes for tha t ma tterha ve no benefi ci a l effects on depres s i on s i gns a nd s ymptoms (d), a nd they a re not properl y us ed a l one or i n
combi na ti on wi th a n SSRI (or tri cycl i c or a typi ca l a nti depres s a nt).
Ma jor rea s ons for s el ecti ng a benzodi a zepi ne over a ba rbi tura te i ncl ude fewer drug-drug i ntera cti ons (phenoba rbi ta l i s a cl a s s i c P450 i nducer
tha t ha s tens the el i mi na ti on of ma ny other drugs tha t a re meta bol i zed by the P450 s ys tem); a l es s er ri s k of genera l i zed ri s k of CNS depres s i on
(s omnol ence, etc); l ower ri s k of dependence; wi thdra wa l s yndromes tha t a re typi ca l l y l es s s evere or da ngerous ; l ower ri s k of fa ta l venti l a tory
depres s i on wi th ora l overdos es (a nd the a va i l a bi l i ty of fl uma zeni l , the s peci fi c benzodi a ze-pi ne a nta goni s t, to trea t them); a nd l es s na rrowi ng
between l etha l a nd effecti ve dos es (better thera peuti c i ndex or ma rgi n of s a fety) a s us e conti nues .
Note tha t even though benzodi a zepi nes ma y be preferred, trea tment for s uch probl ems a s a nxi ety a nd i ns omni a s houl d be kept a s s hort a s
pos s i bl e.
117. The answer is a. (Brunton, pp 225-235, 400-403; Katzung, pp 526-527, 531-534, 536-537.) The mos t common s i de effects a s s oci a ted wi th tri -cycl i c
a nti depres s a nts a re thei r a nti mus ca ri ni c effects , whi ch ma y occur a nd often be promi nent i n over 50% of pa ti ents . Cl i ni ca l l y, thes e effects ma y
ma ni fes t a s dry mouth, bl urred vi s i on, cons ti pa ti on, ta chyca rdi a , di zzi nes s , a nd uri na ry retenti on. Thes e a re, of cours e, s ome of the typi ca l a nd
common s i de effects a s s oci a ted wi th a tropi ne or a ny other drug wi th s ubs ta nti a l a nti mus ca ri ni c effects . At thera peuti c pl a s ma concentra ti ons
thes e drugs us ua l l y do not ca us e cha nges i n the ECG (b)but wi th s evere overdos es l etha l a rrhythmi a s often do occur. Thes e drugs a re not
pa rti cul a rl y hepa totoxi c or nephrotoxi c (c, d); s ei zures a re not l i kel y to occur unl es s the pa ti ent ha s a hi s tory of s ei zure di s orders or ma s s i ve
overdos es ha ve been ta ken.
Note: In terms of tri cycl i c toxi ci ty, i e, wi th overdos es , you mi ght wa nt to reca l l wha t s ome s tudents l ea rn a s the Three Cs : coma , ca rdi otoxi ci ty
(ma i nl y a rrhythmi a s tha t a re often di ffi cul t to trea t), a nd convul s i ons . In a ddi ti on, a l l the other ma ni fes ta ti ons of a tropi ne poi s oni ng wi l l
devel op a nd us ua l l y be s evere. Thi s i s a n extremel y di ffi cul t s i tua ti on to trea t, a nd to trea t s ucces s ful l y, when the ca us e i s a tri cycl i c
a nti depres s a nt.
118. The answer is b. (Brunton, pp 356-357, 611, 614t; Katzung, pp 501-520.) Unwa nted extra pyra mi da l s i de effects produced by a nti ps ychoti c drugs (eg,
chl orproma zi ne, a s the exempl a r of the phenothi a zi nes ; a nd, more s o, by ha l operi dol a s the prototype of the butyrophenones ) i ncl ude Pa rki ns onl i ke s yndrome, a ka thi s i a , dys toni a s , ga l a ctorrhea , a menorrhea , a nd i nferti l i ty. Thes e s i de effects a re due to the a bi l i ty of thes e a gents to bl ock
dopa mi ne receptors . The phenothi a zi nes a l s o bl ock mus ca ri ni c a nd -a drenergi c receptors , whi ch a re res pons i bl e for other effects i n both the CNS
a nd (es peci a l l y) i n the peri phery. The i nci dence a nd s everi ty of thes e a utonomi c s i de effects i s much grea ter wi th l ow-potency a nti ps ychoti cs (eg,
chl orproma zi ne a nd other phenothi a zi nes ) tha n wi th the hi gh-potency butyrophenones (eg, ha l operi dol ).
119. The answer is b. (Brunton, pp 542-544; Katzung, pp 444-446, 550.) The s cena ri o des cri bes mos t of the cl a s s i c res pons es to keta mi ne, a di s s oci a ti ve
a nes theti c: a na l ges i a ; a n os tens i bl y l i ght s l eep-l i ke s ta te; a tra ncel i ke a nd ca ta pl ecti c s ta te (i ncl udi ng i ncrea s ed mus cl e tone); a nd a cti va ti on of
mos t ca rdi ova s cul a r/hemodyna mi c pa ra meters . The va ri ous ps ychos i s -l i ke emergence rea cti ons a re the ma i n di s a dva nta ges to us i ng a drug tha t,
otherwi s e, ca us es ma ny of the des i red el ements of ba l a nced a nes thes i a , us ua l l y wi thout the need for compl i ca ted a nd expens i ve a nes thes i a
a dmi ni s tra ti on devi ces or pers onnel . Keta mi ne undergoes s i gni fi ca nt meta bol i s m i n huma ns , wi th a bout 20% of the a bs orbed dos e recovered a s
meta bol i tes . The onl y other drug l i s ted tha t provi des a dequa te a na l ges i a i s fenta nyl (a ). Mi da zol a m (c; benzodi a zepi ne), s ucci nyl chol i ne (d;
depol a ri zi ng neuro-mus cul a r bl ocker), a nd thi openta l (e; thi oba rbi tura te) l a ck a na l ges i c a cti vi ty; moreover, i f a ny ca rdi ova s cul a r or a utonomi c
cha nges were to occur i n res pons e to a ny of thos e drugs , they woul d be better cha ra cteri zed a s depres s i on, not a cti va ti on.
120. The answer is b. (Brunton, pp 591-593, 845, 1012, 1524, 1528, 1873t; Katzung, pp 40t, 407-409, 427.) The hepa ti c enzymes res pons i bl e for phenytoi n
meta bol i s m (ma i nl y CYP2C9) become s a tura ted a t pl a s ma drug concentra ti ons a bove a pproxi ma tel y 10 to 15 mcg/mL, whi ch a re cl ea rl y wi thi n the
typi ca l thera peuti c ra nge yet wel l bel ow ma xi mum or pea k thera peuti c l evel s . At da i l y dos a ges a s s oci a ted wi th or bel ow thos e 10 to 15 mcg/mL
va l ues , dos e i ncrea s es gi ve rel a ti vel y proporti ona l i ncrea s es i n pl a s ma drug concentra ti ons , a nd phenytoi n el i mi na ti on fol l ows us ua l fi rs t-order
ki neti cs (a cons ta nt fra cti on of drug i s el i mi na ted wi th the pa s s i ng of ea ch ha l f-l i fe). Once the meta bol i c ca pa ci ty i s exceeded (a s i t ha s i n our
pa ti ent, whi ch ma y a ri s e wi th i ntenti ona l or i na dvertent i ncrea s es i n the da i l y dos e), s ma l l i ncrea s es i n dos a ge l ea d to di s proporti ona tel y l a rge
i ncrea s es of pl a s ma concentra ti ons (a nd effects ) beca us e, i n es s ence, drug i n grea tl y exceeds drug out: zero-order ki neti cs now des cri bes the
drugs el i mi na ti on, s uch tha t a cons ta nt a mount (not fra cti on) of drug i s el i mi na ted per uni t ti me. Therefore, the fi rs t-order ha l f-l i fe does not
a ppl y; el i mi na ti on i s s l ower, a nd the pl a s ma concentra ti on wi l l be much grea ter tha n 15 mcg/mL (ha l f of 30 mcg/mL; a ns . e) 24 hours a fter the
i ni ti a l bl ood s a mpl e i s ta ken.
The fi gure bel ow s hows a n approximation of the rel a ti ons hi p between pl a s ma phenytoi n l evel s a nd da i l y dos es (the pl a cement of the curve ca n

va ry from pa ti ent to pa ti ent a l ong the x-a xi s ). From the ra pi d ri s e i n the curve a t dos a ges a bove a bout 300 mg/da y you ca n deduce a s i gni fi ca nt
reducti on of cl ea ra nce ra tes owi ng to s l owed meta bol i s m (s i nce meta bol i s m i s the ma i n pa thwa y for phenytoi ns el i mi na ti on).

Ans wer a i s i ncorrect; fl uma zeni l i s a benzodi a zepi ne receptor a nta goni s t (competi ti ve bl ocker) tha t ha s no effects (benefi ci a l l y or not;
pha rma coki neti c or otherwi s e) on the el i mi na ti on or effects of phenytoi n. It woul d be i na ppropri a tea nd da ngerous to gi ve a n a mpheta mi ne or
a ny other CNS s ti mul a nt to countera ct the exces s CNS depres s i on. Ti tra ti ng upwa rd the dos e of a CNS s ti mul a nt to comba t CNS depres s i on (whether
ca us ed by a drug or from a nother ca us e) i s a ri s ky endea vor, due to the cha nce of i nduci ng s ei zures from exces s i ve CNS s ti mul a ti on, a nd the ri s ks
a re fa r grea ter i n a pers on wi th a hi s tory of s ei zure di s orders .
Phenoba rbi ta l (d) i s a cl a s s i c exa mpl e of a P450 i nducer, a nd i ndeed i t i s meta bol i zed ma i nl y by CYP2C9, on whi ch phenytoi ns el i mi na ti on i s
ma i nl y dependent. In theory, gi vi ng phenoba rbi ta l mi ght i ncrea s e phenytoi ns meta bol i s m vi a P450 i nducti on. In rea l i ty, the pha rma coki neti c
outcomes of a phenoba rbi ta l -phenytoi n i ntera cti on a re qui te va ri a bl e (a nd dependent on bl ood l evel s of ea ch drug), but the more l i kel y
cons equence i s i nhi bi ted phenytoi n el i mi na ti on a s the ba rbi tura te competes wi th i t for convers i on by the s a me cytochromes . Rega rdl es s , a ddi ng
phenoba rbi ta l i s l i kel y to a dd to the genera l i zed CNS depres s i on ca us ed by the phenytoi n, a nd compl i ca te both the cl i ni ca l pi cture a nd i ts
ma na gement. Therefore, thi s a pproa ch, too, woul d be i na ppropri a te.
121. The answer is a. (Brunton, pp 299-300; Katzung, pp 142, 146, 1032-1034.) Methyl pheni da te, whi ch i s wi del y us ed to ma na ge ADHD, ha s
a mpheta mi ne-l i ke s ympa theti c a nd CNS-s ti mul a ti ng effects . Indeed, a mpheta mi ne i ts el f (a nd deri va ti ves or mi xtures of a mpheta mi ne) i s us ed for
trea tment of ADHD.
Peri phera l s ympa theti c (a drenergi c) effects a ri s e from the drugs a bi l i ty to rel ea s e neurona l norepi nephri ne. Rel a ted fi ndi ngs woul d i ncl ude
i ncrea s ed va s ocons tri cti on (grea ter 1 -receptor a cti va ti on of va s cul a r s mooth mus cl e), a nd therefore i ncrea s ed bl ood pres s ure; a nd ta chyca rdi a
(pl us i ncrea s ed ca rdi a c contra cti l i ty a nd el ectri ca l i mpul s e conducti on ra tes , proba bl y a ccompa ni ed by ta chya rrhythmi a s , from 1 a cti va ti on).
At toxi c dos es , the CNS effect of the drug i s l i kel y to ca us e s ei zures .
There i s no mecha ni s m by whi ch di rect effects of methyl pheni da te or a mpheta mi ne (whether a t norma l or toxi c dos es ) woul d ca us e
bronchos pa s m, bronchocons tri cti on, or even bronchodi l a ti on (beca us e norepi nephri ne tha t i s rel ea s ed by thos e drugs ha s no a bi l i ty to a cti va te or
bl ock 2 receptors on a i rwa y s mooth mus cl e). Mi os i s (whi ch occurs wi th ei ther mus ca ri ni c a cti va ti on or bl ocka de) woul d be the oppos i te of wha t

you woul d predi ct i n terms of ocul a r effects .

In terms of a utonomi c effects , s kel eta l mus cl e wea knes s or pa ra l ys i s a re fi ndi ngs you woul d expect from drugs tha t ei ther bl ocked ni coti ni c
chol i nergi c receptors (eg, tubocura ri ne [no l onger on the ma rket i n the Uni ted Sta tes ], but rel a ted a gents s uch a s vecuroni um a re) or s ti mul a ted
them i n a n exces s i ve a nd prol onged fa s hi on (eg, s ucci nyl chol i ne).
122. The answer is d. (Brunton, pp 503-506; Katzung, pp 551-552, 557, 562.) Hi gh or fra nkl y toxi c pl a s ma l evel s of meperi di ne ca n ca us e s ei zures ,
hypertens i on, a nd a ps ychos i s -l i ke s ta te, i n a ddi ti on to typi ca l morphi ne-l i ke effects (eg, a na l ges i a a nd venti l a tory depres s i on). Interes ti ngl y, i t
a ppea rs tha t a dmi ni s tra ti on of na l oxone to comba t exces s i ve effects of meperi di ne ma y i ncrea s e the ri s k of s ei zures . Thi s i s s omethi ng tha t i s
extra ordi na ri l y ra re when na l oxone i s a dmi ni s tered to countera ct exces s i ve effects of morphi ne a nd mos t other opi oi ds .
The ra ther uni que a dvers e effects a s s oci a ted wi th meperi di ne a re proba bl y due to a ma jor meta bol i te, normeperi di ne. A wea k opi oi d
a na l ges i c, propoxyphene (s tructura l l y rel a ted to metha done), ca n produce toxi c rea cti ons s i mi l a r to thos e of meperi di ne. It i s off the Uni ted Sta tes
ma rket now, l a rgel y beca us e of the ri s ks a nd the drugs overa l l poor effi ca cy. Nonethel es s , the ri s ks des cri bed here a ccount for why meperi di ne
dos es s houl d be kept a s l ow a s pos s i bl e, a nd the dura ti on of trea tment wi th i t s houl d be kept s hort (us ua l l y no more tha n a da y or two).
Meperi di ne, l i ke other opi oi ds , ca n ca us e cons ti pa ti on (a ) through i ts a cti ons on l ongi tudi na l mus cl es a nd s phi ncters i n the GI tra ct. Hypera l ges i a (b), a n i ncrea s ed percepti on of pa i n, does not occur. Bi l i a ry tra ct/s phi ncter of Oddi s pa s m (c) i s much l es s l i kel y to occur wi th meperi di ne
tha n wi th mos t other opi oi ds (s a y, the prototype, morphi ne). Indeed, the ri s ks of bi l i a ry tra ct/ga l l bl a dder probl ems a re s a i d to be l es s wi th
meperi di ne tha n a ny other opi oi d a na l ges i c. And s o, meperi di ne ca n be cons i dered a preferred opi oi d (for s hort-term us e) for pa ti ents wi th
modera te-to-s evere pa i n a nd ga l l bl a dder di s ea s e.
Res pi ra tory depres s i on (e), pos s i bl y l ea di ng to venti l a tory a rres t, i s a property s ha red by a l l the opi oi d a na l ges i cs , but of cours e to va ryi ng
degrees ba s ed on thei r effi ca cy a nd dos e.
Note: Before the unus ua l ri s ks of meperi di ne were ful l y a ppreci a ted, the drug wa s often pres cri bed for da ys or weeks on end. Tha t s houl d never
be done a nymore.
123. The answer is a. (Brunton, pp 359, 422, 424t, 436-442, 920, 924; Katzung, pp 504-509, 511-512.) In genera l , a utonomi c s i de effects a re fa i rl y common
wi th phenothi a zi nes s uch a s chl orproma zi ne. Thes e i ncl ude mus ca ri ni c receptor bl ocka de l ea di ng to dry mouth, bl urred vi s i on; a nd a l l the res t of
the unwa nted effects ca us ed by a tropi ne, or a drug wi th s trong a tropi ne-l i ke a cti ons . Ha l operi dol , the butyrophenone a nti ps ychoti c drug, tends to
ca us e extra pyra mi da l s i de effects more often, more s trongl y, tha n a utonomi c s i de effects noted a bove. As a res ul t, extra pyra mi da l (pa rki ns oni a n)
s i de effects a re more common. Indeed, when ha l operi dol i s gi ven by i njecti on to hel p trea t a cute ps ychos i s ma ny trea ted pa ti ents devel op
(tempora ri l y) mus cl e tremors a nd other ma ni fes ta ti ons of Pa rki ns on di s ea s e.
124. The answer is d. (Brunton, pp 664-665; Katzung, pp 569t, 575-577.) Angel dus t i s phencycl i di ne (PCP), a n ha l l uci nogen or ps ychotomi meti c wi th a n
a mpheta mi ne-l i ke mecha ni s m of a cti on. Thus , the probl ems tha t a ri s e a re due to bl ocka de of neurona l reupta ke of s uch monoa mi nes a s
dopa mi ne, norepi nephri ne, a nd s erotoni n. The drug does not ha ve centra l or peri phera l mus ca ri ni c receptor a nta goni s t a cti vi ty (a ), nor opi oi d
a goni s t a cti ons (c). A phencycl i di ne wi thdra wa l s yndrome (b) ha s not been documented cons i s tentl y huma ns , l a rgel y beca us e i t i s us ed
epi s odi ca l l y a nd not chroni ca l l y pres ent i n the ci rcul a ti on. In overdos e, the trea tment of choi ce for ma ni fes ta ti ons of drug-i nduced ps ychos i s i s
ha l operi dol , a l though ra pi dl y a cti ng a nd hi ghl y s eda ti ng benzodi a zepi nes ma y be us ed i ns tea d. Fl uma zeni l (e) i s a benzodi a zepi ne receptor
a nta goni s t wi th no us e or effi ca cy i n phencycl i di ne toxi ci ty.
125. The answer is b. (Brunton, pp 446-447, 448-450, 976; Katzung, pp 514-517.) In es s ence, the i ntens i ty of effects from a ny gi ven pl a s ma concentra ti on
of l i thi um i s i nvers el y rel a ted to s odi um concentra ti ons . When s odi um concentra ti on fa l l s , the effects of l i thi um ca n be i ntens i fi ed to the poi nt of
ca us i ng toxi ci ty. By wa y of thei r a cti ons to i ncrea s e rena l s odi um l os s , vi rtua l l y a l l the common di ureti cs a l s o reduce rena l l i thi um excreti on. It i s
proba bl y of grea tes t concern wi th thi a zi des or thi a zi de-l i ke di ureti cs , whi ch ha ve the grea tes t potenti a l of a l l the common di ureti cs to ca us e
hypona tremi a . Chol es tyra mi ne (a ) i s a chol es terol -bi ndi ng res i n. Gi ven concomi ta ntl y wi th a n ora l di ureti c, the mos t l i kel y outcome woul d be
reduced bi oa va i l a bi l i ty of the di ureti c, not i ncrea s ed or decrea s ed chol es tyra mi ne effects . Ni fedi pi ne (c), a di hydropyri di ne ca l ci um cha nnel
bl ocker, ma y ca us e exces s i ve a nti hypertens i ve effects when a dmi ni s tered wi th a ny di ureti c (a l though combi ned a dmi ni s tra ti on i s common a nd
us ua l l y probl em-free). If exces s i ve effects of ni fedi pi ne occur i n conjuncti on wi th a di ureti c, they a re mos t l i kel y bl ood vol ume-rel a ted, not
s peci fi ca l l y due to cha nges of s odi um concentra ti ons . Phenyl ephri nes (d) va s ocons tri ctor effects a re not l i kel y to be a l tered a ppreci a bl y i n the
pres ence of a di ureti c. The s a me l a ck of a cl i ni ca l l y s i gni fi ca nt i ntera cti on a ppl i es to the s ta ti ns (e; HMG Co-A reducta s e i nhi bi tors , eg,
a torva s ta ti n).
126. The answer is d. (Brunton, pp 405, 408, 412, 1538; Katzung, pp 285-286, 1162t.) Thi s pa ti ent proba bl y ha s the s erotoni n s yndrome. Serotoni n i s
a l rea dy pres ent i n i ncrea s ed a mounts i n s yna ps es beca us e of bl ocka de of i ts reupta ke by the SSRIs . When s uma tri pta n (or other tri pta ns us ed for
mi gra i ne thera py; they a re 5-HT1B/2D a goni s ts ) i s a dded, ra pi d a ccumul a ti on of s erotoni n a nd/or the tri pta n i n the bra i n ca n occur.
The ri s k of the s erotoni n s yndrome i n SSRI-trea ted pa ti ents i s much hi gher when MAO i nhi bi tors a re us ed concomi ta ntl y. Nonethel es s , s uch
s evere rea cti ons from a n SSRI-tri pta n i ntera cti on ha ve been reported. In a ddi ti on, do not forget tha t MAO i nhi bi tors ca n a l s o ca us e a n a cute a nd
potenti a l l y fa ta l hypertens i ve cri s i s when co-a dmi ni s tered wi th tri cycl i c/tetra cycl i c a nti depres s a nts (eg, i mi pra mi ne); s uch combi ned us e s houl d
be a voi ded.
None of the other drugs l i s ted (codei ne, a ; l ora ta di ne or a nother s econd-genera ti on a nti hi s ta mi ne, b; mi da zol a m or fenta nyl or other
benzodi a zepi nes or opi oi ds c; or zol pi dem or the rel a ted drug za l epl on, e) i ntera ct wi th fl uoxeti ne or other SSRIs i n terms of s peci fi ca l l y ra i s i ng
s ys temi c or s yna pti c s erotoni n l evel s .
127. The answer is b. (Brunton, pp 86t, 468-469, 1059; Katzung, pp 381-382, 1033t, 1037.) Fl uma zeni l i s a competi ti ve a nta goni s t of benzodi a zepi nes a t
the GABA receptor. Repea ted a dmi ni s tra ti on i s neces s a ry beca us e of i ts s hort ha l f-l i fe rel a ti ve to tha t of mos t benzodi a zepi nes es peci a l l y
di a zepa m, whi ch forms ma ny l ong-l a s ti ng a cti ve meta bol i tes .
Dextroa mpheta mi ne (a ) i s a CNS s ti mul a nt tha t wi l l i ncrea s e the pa ti ents l evel of cons ci ous nes s , but i t i s not i ndi ca ted for thi s us e. Hi gh dos es
proba bl y be needed to overcome the i ntens e benzodi a zepi ne effects , a nd they ma y ca us e da ngerous CNS a nd ca rdi ova s cul a r res pons es ra ther
tha n s i mpl y norma l i zi ng va ri a bl es depres s ed by the di a zepa m. Na l trexone (c) s peci fi ca l l y a nta goni zes the effects of opi oi d a goni s ts on a nd
receptors a nd i s us ed to di a gnos e or trea t opi oi d overdos es ; i t ha s no benzodi a zepi ne receptor-bl ocki ng a cti vi ty. Phys os ti gmi ne (d) i s a l i pophi l i c
a cetyl chol i nes tera s e i nhi bi tor tha t ma y be a l i fe-s a vi ng i nterventi on for s evere poi s oni ng wi th ma ny drugs (a key excepti on bei ng tri cycl i c
a nti depres s a nts ) ha vi ng s i gni fi ca nt a nti mus ca ri ni c (a tropi ne-l i ke) a cti ons . Pra l i doxi me (e) i s a chol i nes tera s e rea cti va tor us ed i n the a djuncti ve
ma na gement of poi s oni ng wi th s uch i rrevers i bl e chol i nes tera s e i nhi bi tors a s the orga no-phos pha te i ns ecti ci des a nd ma ny nerve ga s es
(s oma n, s a ri n, VX).

128. The answer is a. (Brunton, pp 438, 614t, 619; Katzung, p 491.) Thi s cuta neous res pons e, ca l l ed l i vedo reti cul a ri s , i s cha ra cteri s ti ca l l y a s s oci a ted
wi th a ma nta di ne. Reca l l tha t thi s s el dom-us ed a nti pa rki ns on drug proba bl y works by rel ea s i ng endogenous dopa mi ne a nd bl ocki ng i ts neurona l
reupta ke. Li vedo reti cul a ri s i s not a s s oci a ted wi th l evodopa (us ed a l one or wi th ca rbi dopa ; c or d), nor wi th the dopa mi ne a goni s ts bromocri pti ne
(d) or pra mi pexol e (e; a newer a nd genera l l y preferred drug for s ta rti ng trea tment of mi l d pa rki ns oni a n s i gns a nd s ymptoms ). (You mi ght a l s o
reca l l tha t a ma nta di ne i s a l s o us ed for prophyl a xi s of s ome s tra i ns of i nfl uenza vi rus i nfecti ons . The mecha ni s m of a cti on i n thi s s etti ng i s not
wel l unders tood.)
129. The answer is d. (Brunton, pp 591-593; Katzung, pp 407-409.) For ma ny yea rs , phenytoi n ha s been ci ted a s a cl a s s i c exa mpl e of a drug tha t ca n
ca us e gi ngi va l hyperpl a s i a . (Among ora l s urgeons a nd denti s ts , i t i s often referred to a s Di l a nti n hyperpl a s i a , i n recogni ti on of phenytoi ns
common propri eta ry na me.) The mecha ni s m i s unknown, but we s us pect the drug a l ters col l a gen meta bol i s m i n the gi ngi va l ti s s ues . Al though
phenytoi n i s nt the onl y drug a s s oci a ted wi th potenti a l gi ngi va l hyperpl a s i a (vera pa mi l i s a nother common one), i t i s the onl y one l i s ted a s a
choi ce. Note tha t phenoba rbi ta l , whi ch i s s ti l l us ed a s a n a l terna ti ve to phenytoi n for s ei zures , does not ca us e gi ngi va l hyperpl a s i a . It i s preci s el y
beca us e of the l ow gi ngi va l hyperpl a s i a ri s k tha t phenoba rbi ta l i s s ometi mes pres cri bed for chi l dren wi th res pons i ve s ei zure di s orders i n l i eu of
phenytoi n.
130. The answer is d. (Brunton, pp 344-347, 832; Katzung, pp 285, 292.) The s erotoni n receptor a goni s t a cti ons of the tri pta ns , i ncl udi ng the prototype,
s uma tri pta n, ca n tri gger i ntens e va s ocons tri cti on i n va ri ous va s cul a r beds . The cerebra l va s ocons tri ctor effects of thes e drugs contri bute
i mporta ntl y to the rel i ef they a fford i n mi gra i ne hea da ches . However, corona ry va s os pa s m ca n occur a l s o; i t ma y be pa rti cul a rl y i ntens e a nd
potenti a l l y l i fe-threa teni ng i n pa ti ents wi th corona ry va s os pa s ti c di s ea s e (i e, va ri a nt or Pri nzmeta l a ngi na ), for whom the tri pta ns a re
contra i ndi ca ted.
None of the other drugs l i s ted ha ve a ny s i gni fi ca nt corona ry (or other) va s ocons tri ctor effects . Indeed, s ome s uch a s phenytoi n a nd zol pi dem (a
benzodi a zepi ne-l i ke hypnoti c) ma y ca us e s l i ght ca rdi ova s cul a r cha nges (eg, a fterl oa d reducti on) tha t woul d a ctua l l y reduce the degree of myoca rdi a l i s chemi a a nd the ri s k of a ngi na .
131. The answer is c. (Brunton, pp 551-552; Katzung, pp 430-438.) Reca l l tha t ni trous oxi de ha s a MAC (mi ni mum a l veol a r concentra ti on) of a bout 105%.
Achi evi ng tha t concentra ti on i n a n i ns pi red ga s mi xture i s phys i ca l l y i mpos s i bl e a t norma l a tmos pheri c pres s ure. Even i f we coul d s a fel y gi ve pure
ni trous oxi de (we obvi ous l y ca nnot), a nd we rounded-off the MAC to 100%, the drug woul d (1) ca us e a bol i ti on of a pa i nful res pons e i n onl y 50% of
s ubjects (thi s i s one el ement of the defi ni ti on of MAC), a nd (2) be l etha l , s i nce 100% ni trous oxi de mea ns no (0%) oxygen a t norma l a tmos pheri c
pres s ures . Thi s very effecti ve a na l ges i c ga s i s poorl y s ol ubl e i n the bl ood, s o equi l i bra ti on between a l veol a r a nd bl ood concentra ti on a nd the
ons et of i ts centra l effects a re qui te ra pi d.
Even a t the us ua l concentra ti ons (typi ca l l y 80% of the i ns pi red ga s mi xture), a nd whether us ed onl y wi th a i r (a s i n ma ny a s pects of denta l
pra cti ce) or wi th other i nha l ed a gents (common i n s urgery), ni trous oxi de ca us es l i ttl e or no bronchos pa s m nor s i gni fi ca nt ca rdi a c depres s i on.
132. The answer is b. (Brunton, pp 86t, 437t; Katzung, pp 503-512.) The ques ti on des cri bed common a nd neces s a ry i nterventi ons for ma na gi ng
neurol epti c ma l i gna nt s yndrome, whi ch i s cha ra cteri s ti ca l l y a s s oci a ted wi th ol der a nti ps ychoti cs chl orproma zi ne a nd other l ow potency a nti ps ychoti cs to a degree, but occurs more s o wi th ha l operi dol (butyrophe-none). Si gns a nd s ymptoms i ncl ude mus cl e teta ny/ri gi di ty, profound fever,
ra pi d s wi ngs of hea rt ra te, rhythm, bl ood pres s ure (a utonomi c i ns ta bi l i ty), el ectrol yte a bnorma l i ti es , a nd dehydra ti on. None of the other a gents
a re a s s oci a ted wi th thi s s yndrome, whether a cutel y or wi th l ong-term thera py or a t thera peuti c or toxi c pl a s ma l evel s , nor woul d the i nterventi ons
des cri bed be i ndi ca ted.
133. The answer is c. (Brunton, pp 356-357, 614; Katzung, pp 487, 489f, 496, 499.) Thi s i s a ques ti on a bout a drug you ma y not ha ve l ea rned a bout
expl i ci tl y, but gi ven the des cri pti on of i ts mecha ni s m, whi ch s houl d be qui te fa mi l i a r, you s houl d ha ve no probl em a rri vi ng a t the ri ght a ns wer.
Ropi ni rol e (a rel a ted drug i s pra mi pexol e) di rectl y a cti va tes s tri a ta l dopa mi ne receptors . It i s one of s evera l dopa mi nergi c drugs tha t ca n be
us ed to i ni ti a te thera py of ea rl y Pa rki ns on di s ea s e. (Wi th the a va i l a bi l i ty of ropi ni rol e, pra mi pexol e, a nd s ome rel a ted drugs , we now hol d-off on
pres cri bi ng s uch ol der drugs a s l evodopa when pa rki ns oni a n s i gns a nd s ymptoms a re i n the ea rl y s ta ges ). Dys ki nes i a s a nd hypotens i on a re
rel a ti vel y common s i de effects , a s a l s o a ppl i es to a l terna ti ves s uch a s l evodopa a nd bromocri pti ne. Ropi ni rol e a l s o ca us es drows i nes s or
s l eepi nes s ; ei ther woul d render the drug not i dea l for ma na gi ng da yti me a nxi ety (a ), but a nxi ety ma na gement i s not a n i ndi ca ti on for the drug, nor
i s hypers omni a (b). Ropi ni rol es dopa mi nergi c a cti on ma y exa cerba te s i gns a nd s ymptoms of s chi zophreni a (d); l i ke ma ny other a nti pa rki ns on
drugs i t ma y l ower the s ei zure thres hol d i n pa ti ents wi th epi l eps y, a nd s o woul d be i rra ti ona l for ma na gi ng s ta tus epi l epti cus (e). It ha s no
cl i ni ca l l y us eful a na l ges i c a cti vi ty (f).
134. The answer is b. (Brunton, pp 583-606, 1859t; Katzung, pp 377t, 420, 423, 439t.) Intra venous l ora zepa m i s genera l l y rega rded a s the drug of choi ce for
i ni ti a l trea tment of s ta tus epi l epti cus . (It ha s s urpa s s ed di a zepa m beca us e of a fa s ter ons et of a cti on a nd l es s venous i rri ta ti on, a mong other
thi ngs .) Lora zepa m, l i ke the benzodi a zepi nes i n genera l , i ncrea s es the a ppa rent a ffi ni ty of the i nhi bi tory neurotra ns mi tter GABA for bi ndi ng s i tes
on bra i n cel l membra nes . Thi s i ncrea s es the frequency of chl ori de cha nnel openi ng, whi ch then l ea ds to i nhi bi ted ta rget nerve a cti vi ty.
It i s es s enti a l to note tha t IV l ora zepa ms a nti convul s a nt effects a re rel a ti vel y s hort l i ved; i f onl y l ora zepa m wa s gi ven for s ta tus the s ei zures
woul d s top qui ckl y (a l mos t i mmedi a te ons et of a cti on), but there i s a grea t ri s k of s ei zure rea ppea ra nce a s the drug i s el i mi na ted qui ckl y a nd
bl ood concentra ti ons fa l l (too s hort a dura ti on of a cti on). Therefore, i mmedi a tel y a fter gi vi ng the l ora zepa m ei ther phenytoi n or fos phenytoi n
s houl d be gi ven to provi de l onger s ei zure s uppres s i on a nd covera ge beca us e l ora zepa ms effect wa nes s o qui ckl y. Compa red wi th l ora zepa m,
phenytoi ns ons et of a cti on i s too s l ow, but the dura ti on of a cti on i s much l onger.
Why not jus t gi ve phenytoi n or fos phenytoi n a nd s ki p the l ora zepa m? Reca l l tha t the l onger s ta tus epi l epti cus pers i s ts , the grea ter the ri s k of
bra i n da ma ge or dea th. Our goa l i s to termi na te the s ei zures a s fa s t a s pos s i bl e. As noted a bove, phenytoi n or fos phenytoi n ha ve ons ets of a cti on
tha t a rent fa s t enough to a chi eve the goa l of prompt s ei zure s uppres s i on. Lora zepa m works qui ckl y, a nd tha ts why we gi ve i t fi rs t.
None of the other drugs l i s ted i n the ques ti on a re a ppropri a te for i ni ti a l thera py of s ta tus epi l epti cus , des pi te thei r wi des prea d us e for ora l
thera py of s ei zure di s orders l ong-term.
135. The answer is e. (Brunton, pp 564-565, 571, 574; Katzung, pp 449-464.) Fi rs t, a l ea rni ng tri ck for how to tel l whether a l oca l a nes theti c (one youve
l ea rned a bout, or not) i s a n es ter or a mi de. Look a t the drugs generic na me; i f there a re two occurrences of the l etter i i n i t, i ts a n a mi de; i f not,
i ts a n es ter. Thus , we ha ve s uch es ters a s coca i ne, chl or(o)proca i ne, proca i ne i ts el f, a nd tetra ca i ne, whi ch i s the correct a ns wer for thi s ques ti on.
The others I l i s ted a re a mi des .
Thi s ma y s eem l i ke a pi cky ques ti on, or perha ps a tri cky one, i f youve been ta ught the ma i n properti es of onl y one or two prototypi c l oca l
a nes theti cs eg, l i doca i ne a s the prototype a mi de a nd prototype l oca l a nes theti c overa l l , proca i ne a s the prototype of the es ter cl a s s a nd
perha ps a thi rd drug, benzoca i ne, a n es ter tha t i s s ui ta bl e onl y for topi ca l a dmi ni s tra ti on beca us e i t i s l a rgel y i ns ol ubl e a nd ca nt be gi ven s a fel y

or effecti vel y by other routes . Nonethel es s , there a re a coupl e of i mporta nt poi nts here, a nd they revol ve a round a funda menta l di fference
between a mi des a nd es ters , a nd s o knowi ng the cl a s s to whi ch a pa rti cul a r l oca l a nes theti c bel ongs : (1) a l l ergi c rea cti ons of va ri ous s everi ti es
a re more common wi th es ters tha n wi th a mi des ; (2) there i s cl a s s e-ba s ed cros s -rea cti vi ty, mea ni ng tha t i f a pa ti ent ha s ha d a true i mmunol ogi c
rea cti on to a ny es ter, he or s he i s a t ri s k for a s i mi l a r rea cti on from s ubs equent expos ure to a ny es ter; a nd (3) there i s no cros s -rea cti vi ty between
es ters a nd a mi des , s uch tha t us e of a n a mi de i n a n es ter-s ens i ti ve pa ti ent i s not l i kel y to pos e probl ems of a l l ergeni ci ty.
As a fi na l a s i de, i f you a s k a group of peopl e how ma ny of you ha ve recei ved Novoca i n before? youl l get a l ot yes res pons es . And mos t of
them wi l l be i ncorrect. Novoca i n i s the mos t wi del y known bra nd na me for the generi c drug, proca i ne. Truth i s , proca i ne i s s uch a poor l oca l
a nes theti c (l ow potency, s hort dura ti on, a l l ergeni ci ty, etc) i n compa ri s on wi th drugs l i ke l i doca i ne tha t i ts a l mos t never us ed nowa da ys (not
a va i l a bl e i n the Uni ted Sta tes ), i n fa ct ha s nt s een much us e for deca des . Before then, however, i t wa s ba s i ca l l y the onl y choi ce when a n
i njecta bl e l oca l a nes theti c wa s needed, a nd the na me Novoca i n pers i s ted a s a ubi qui tous (but i ncorrectl y a ppl i ed) na me for ma ny l oca l
a nes theti cs tha t ca me out l a ter. If a pa ti ent younger tha n a bout 40 yea rs ol d reports a Novoca i n a l l ergy, be ca reful how you i nterpret tha t
i nforma ti on. Cha nces a re good tha t s omeone i na ppropri a tel y tol d them they were getti ng Novoca i n when the drug wa s a ctua l l y s omethi ng el s e.
And be s ure tha t i f youre goi ng to gi ve s omeone a dos e of a l oca l a nes theti c you dont ca l l i t Novoca i n when, i n fa ct, i tl l s urel y be s omethi ng el s e.
Na mes ma tter.
136. The answer is c. (Brunton, pp 252-253, 621-622; Katzung, pp 509, 1054-1055.) Ini ti a l recommended thera py i ncl udes us e of a cetyl chol i nes tera s e
i nhi bi tors (donepezi l , ta cri ne, ga l a nta mi ne, ri va s ti gmi ne; a l l a re revers i bl e chol i nes tera s e i nhi bi tors ). Thes e drugs a re not cures , but they a ppea r
to s l ow s ymptoms of bra i n neurodegenera ti on i n s ome pa ti ents . None a ppea rs to be i nva ri a bl y s uperi or to a ny other. Thei r a cti ons a l mos t
certa i nl y i nvol ve a cti va ti on of centra l mus ca ri ni c receptors i ndi rectl y, by i nhi bi ti ng meta bol i s m of ACh rel ea s ed from vi a bl e nerves , of cours ei n
pa rt beca us e drugs wi th centra l a nti mus ca ri ni c a cti ons reduce thei r effi ca cy. Ta cri ne i s noteworthy, compa red wi th the other drugs noted i n the
a ns wer, beca us e i t ca us es a hi gher i nci dence of chol i nes tera s e i nhi bi ti on i n the peri phery: more a nd more di s turbi ng s ymptoms typi ca l
cha ra cteri s ti c of i ncrea s ed (a nd i ndi rect, due to chol i nes tera s e i nhi bi ti on) mus ca ri ni c effects on the gut, bl a dder, a i rwa ys , etc.
Acti va ti ng s erotoni n receptors (a ) or bl ocki ng dopa mi nergi c effects (b) a re not s ui ta bl e or effecti ve thera pi es for Al zhei mer. Sel egi l i ne (MAO-B
i nhi bi tor, d) a nd hi gh dos es of vi ta mi n E (a nti oxi da nt) a ppa rentl y s l ow neurodegenera ti ve proces s es , but s o fa r there a re no convi nci ng da ta tha t
they s l ow cogni ti ve decl i ne, a nd they a re not fi rs t-l i ne thera pi es . Thrombol yti c drugs (e) a re not i ndi ca ted, a s the s i gns a nd s ymptoms of Al zhei mer
a re not due to cl ots or other va s o-obs tructi ve ca us es .
137. The answer is b. (Brunton, p 234; Katzung, pp 492t, 499.) Reca l l tha t i n i di opa thi c pa rki ns oni s m the s i gns a nd s ymptoms genera l l y refl ect a n
i mba l a nce between the oppos i ng effects of dopa mi ne a nd of ACh i n the bra i ns s tri a tum. More s peci fi ca l l y, dopa mi nergi c i nfl uences a re, or a t
l ea s t a ppea r to be, outwei ghi ng the effects of mus ca ri ni c chol i nergi c a cti vi ty. There a re two ba s i c wa ys to ma na ge thi s : (1) enha nce dopa mi nergi c
a cti vi ty; a nd/or (2) di mi ni s h the centra l mus ca ri ni c i nfl uences . Tri hexypheni dyl (a nd the rel a ted drug benztropi ne) do the l a tter. They ca us e
s i gni fi ca nt a nti mus ca ri ni c (a tropi nel i ke) a cti ons i n the CNShence, thes e drugs ha ve been cl a s s i fi ed a s centra l l y a cti ng a nti mus ca ri ni cs . Thes e
drugs a re qui te l i pophi l i c a nd enter the CNS wel l (thi s a ccounts for the drugs ma rked s eda ti ve effects , too) to bl ock mus ca ri ni c receptors there.
Tha t hel ps a djus t the dopa mi ne-ACh i mba l a nce tha t a ppea rs to be a ma i n bi ochemi ca l underpi nni ng of pa rki ns oni s m. Di phenhydra mi ne ca n be
us ed i ns tea d of tri hexypheni dyl or benztropi ne, but i t ca us es more drows i nes s i n mos t pa ti ents . Nonethel es s , none of thes e drugs i s us ed to
countera ct CNS depres s i on ca us ed by other a nti pa rki ns on drugs .
Di phenhydra mi ne does hel p a l l evi a te cuta neous a l l ergy s ymptoms (eg, urti ca ri a ; d), but thos e a re ra re wi th a ny of the common a nti pa rki ns on
drugs (I di d not s peci fy whi ch other drug wa s gi ven). None of thes e drugs a ffect ma ni c/hypoma ni c epi s odes tha t mi ght occur wi th, s a y, hi gh dos es
of l evodopa . They do not revers e a nti ps ychoti c-i nduced ta rdi ve dys ki nes i a s (e); no drug does tha t effecti vel y.
138. The answer is d. (Brunton, pp 404, 411-412; Katzung, pp 490, 527-528, 1034.) Ma ny drugs (but not a mpheta mi nes , a ; ba rbi tura tes , b;
benzodi a zepi nes , c; or morphi ne or rel a ted opi oi d a na l ges i cs , e) pa rti ci pa te i n s i gni fi ca nt i ntera cti ons wi th certa i n foods or bevera ges . However,
when you rea d phra s es a l ong the l i nes of thos e noted i n the ques ti ons evere a nd s ometi mes fa ta l hypertens i on from cons umi ng s uch foods a s
chees es a nd proces s ed mea ts you s houl d a utoma ti ca l l y be thi nki ng of the ol der, nons el ecti ve (MAO A/B) monoa mi ne oxi da s e i nhi bi tors . Thes e
drugs ha ve been us ed for s evere hypertens i on or depres s i on, but due to the potenti a l l y l etha l i ntera cti ons wi th tyra mi ne-conta i ni ng foods or
bevera ges , thei r us e ha s dwi ndl ed beca us e the ri s ks were too grea t. (Nonethel es s , you need to know your pha rma col ogy for s uch drugs a s
pa rgyl i ne, phenel zi ne, a nd tra nyl cypromi ne.) Reca l l tha t tyra mi ne i s a ca techol a mi ne-rel ea s i ng drug wi th s ympa thomi meti c a cti ons i n i ts own
ri ght. When we cons ume tyra mi ne-ri ch foods or bevera ges much of tha t s ympa thomi meti c i s meta bol i zed by hepa ti c MAO before i t rea ches the
s ys temi c ci rcul a ti on (fi rs t-pa s s meta bol i s m), a nd s o i ts effects a re s l i ght. In the pres ence of a nons el ecti ve MAO i nhi bi tor, however, the meta bol i c
i na cti va ti on does not occur a nd s i gni fi ca nt a mounts of the drug rea ch the ci rcul a ti on to ca us e more i ntens e a nd potenti a l l y very i ntens e effects
tha t i nvol ve a drenergi c receptor a cti va ti on. In a ddi ti on, ca techol a mi nergi c (eg, a drenergi c) nerves i n the MAO-trea ted pa ti ent ca n be cons i dered
l oa ded wi th a n a bunda nce of the neurotra ns mi tter due to i nhi bi ted i ntra neurona l meta bol i s m of the neurotra ns mi tter. Al though the
neurotra ns mi tter ma y not be rel ea s ed phys i ol ogi ca l l y, i n res pons e to a n a cti on potenti a l (a t l ea s t i n the peri phera l s ympa theti c nervous s ys tem),
i t ca n be rel ea s ed by s uch drugs a s tyra mi ne or by s uch drugs a s ps eudoephedri ne a nd ephedri ne (mi xed-a cti ng s ympa thomi meti cs ) or
a mpheta mi nes (i ndi rect-a cti ng s ympa thomi meti cs ), whi ch ca n then tri gger pos s i bl y fa ta l hypertens i ve cri s i s , profound ca rdi a c s ti mul a ti on, a nd the
cons equences thereof. Thes e probl ems l ed to the devel opment of MAO i nhi bi tors (eg, s el egi l i ne) tha t ha ve preferenti a l effects on MAO i n the
bra i n (MAO-B) a nd fa r l es s a n effect on MAO forms i n the l i ver a nd peri phera l nervous s ys tem (MAO-A). Nonethel es s , a s s ta ted i n the ques ti on,
there i s a new nons el ecti ve MAO i nhi bi tor tha t ha s jus t been a pproved for us e, for depres s i on, i n the form of a tra ns derma l del i very s ys tem (s ki n
pa tch).
139. The answer is d. (Brunton, p 516; Katzung, p 559.) Dextromethorpha n i s , i ndeed, chemi ca l l y rel a ted to codei ne, but i t l a cks ma ny effects you
proba bl y a s s oci a te wi th codei ne or other opi oi ds , except one: i t ha s excel l ent a nti tus s i ve a cti vi ty. Thi s cough-s uppres s a nt effect pres uma bl y
occurs vi a s ome i l l -defi ned centra l mecha ni s m, but does not i nvol ve a goni s t a cti ons on opi oi d receptors . (Some ha ve s pecul a ted tha t the
mecha ni s m i nvol ves s uppres s i on of the a fferent l i mb of the 10th cra ni a l nerve, but dont memori ze tha t!)
Dextromethorpha n does not ha ve a na l ges i c effects (a ); a l ter gut moti l i ty (b); or ha ve effects on the bl a dder mus cul a ture tha t mi ght rel i eve
nocturi a . Very hi gh dos es of dextromethorpha n ca n ca us e CNS depres s i on, but rega rdl es s of the dos e i t i s not us ed a s a s eda ti ve or other a gent for
control l i ng s ymptoms of ADD/ADHD. Fi na l l y, unl i ke codei ne a nd mos t other opi oi ds , dextromethorpha n l a cks s i gni fi ca nt a ddi cti ve properti es or
potenti a l .
140. The answer is a. (Brunton, pp 297t, 299, 302; Katzung, pp 142, 148.) Whether you ha ve l ea rned or rea d a bout thi s s peci fi ca l l y i n a pha rma col ogy
cl a s s or text, for medi col ega l a nd s oci eta l (a nd boa rd-rel a ted?) rea s ons you s houl d be a wa re of the growi ng probl em of i l l i ci t meth l a bs tha t us e
ps eudoephedri ne (ps eudo) a s the s ta rti ng poi nt for a ra ther ea s y chemi ca l s ynthes i s of thi s hi ghl y a ddi cti ve a nd da ngerous CNS s ti mul a nt. None
of the other drugs l i s ted ca n be s ynthes i zed us i ng thi s common i ndi rect-a cti ng s ympa thomi meti c a s a s ta rti ng poi nt.

141. The answer is c. (Brunton, pp 191t, 206t, 262-263; Katzung, pp 470-474.) Vecuroni um i s a cura re-l i ke nondepol a ri zi ng neuromus cul a r bl ocker tha t i s
us ed to i nduce or ma i nta i n s kel eta l mus cl e pa ra l ys i s for s urgery. (Your l ea rni ng ma y ha ve focus ed on vecuroni um; the two drugs , a nd i ndeed a l l
other drugs wi th curoni um or curi ne i n the generi c na me a re s i mi l a r.) It ha s no effects on bra i n functi ons s uch a s l evel s of cons ci ous nes s or
s ens a ti ons s uch a s of pa i n. The drug prevents a cti va ti on of ni coti ni c receptors on s kel eta l mus cl e (i t i s a competi ti ve a nta goni s t), thereby
preventi ng myocyte depol a ri za ti on a nd other el ements of norma l s kel eta l mus cl e a cti va ti on a nd ul ti ma tel y ca us i ng fl a cci d pa ra l ys i s . The ons et
a nd dura ti on of thi s effect depends on the a ctua l drug bei ng a dmi ni s tered.
Droperi dol (a ) i s a ha l operi dol -l i ke neurol epti c drug. It ca us es drows i nes s a nd s eda ti on i n i ts own ri ght. In s ome i ns ta nces i t i s a dmi ni s tered
wi th fenta nyl to ca us e neurol ept a na l ges i a (a ca l mi ng effect, i ndi fference to pa i n a nd s urroundi ngs ); or wi th fenta nyl a nd ni trous oxi de for grea ter
pa i n control (neurol ept a nes thes i a ). However, droperi dol does not ha ve a ny cl i ni ca l l y us eful i ntri ns i c a na l ges i c effects . A l i mi ta ti on to us i ng
droperi dol for a ny purpos e i s i ts tendency to prol ong ventri cul a r repol a ri za ti on, whi ch renders pa ti ents wi th l ong QT s yndrome) a t ri s k of s eri ous
a rrhythmi a s (es peci a l l y tors a des ).
Mi da zol a m (b), propofol (d), a nd thi openta l (e), when gi ven i ntra venous l y, ca us e prompt s eda ti on or l os s of cons ci ous nes s (dos e-dependent)
a nd ca n be us ed for s uch purpos es a s i nducti on of a nes thes i a or s eda ti on; s ome a re us ed for a va ri ety of purpos es (pa ti ents on venti l a tors , thos e
undergoi ng endos copy, or other noni nva s i ve procedures ). Thes e drugs l a ck i ntri ns i c a na l ges i c effects , a nd s houl d not be us ed a l one for pa i n
control .
142. The answer is a. (Brunton, pp 398-400, 406t, 409t; Katzung, pp 527-530, 539.) The menti on of mens trua l i rregul a ri ti es , ga l a ctorrhea , a nd wha t
a ppea rs to be extra pyra mi da l s i de effects s houl d be a ti p-off tha t we a re dea l i ng wi th a drug tha t i ntera cts wi th dopa mi ne receptors s peci fi ca l l y
D 2 by bl ocki ng them. Amoxa pi ne, the correct a ns wer, i s a tri cycl i c a nti -depres s a nt (s econda ry a mi ne). It i s ra ther uni que a mong a l l the tri cycl i cs
(other s econda ry a mi nes , a nd terti a ry a mi nes s uch a s the more fa mi l i a r a mi tri ptyl i ne a nd i mi pra mi ne) i n s evera l res pects . For one thi ng i t i nhi bi ts
neurona l dopa mi ne a nd norepi nephri ne reupta ke (the others a ffect ma i nl y norepi nephri ne a nd s erotoni n). Tha t, however, does not rea di l y
expl a i n the a menorrhea -ga l a ctorrhea , a nd extra pyra mi da l s i de effects . Wha t provi des the expl a na ti on or mecha ni s m rel a tes to a nother ra ther
uni que property of a moxa pi ne: one of i ts meta bol i tes i s a s trong dopa mi ne receptor a nta goni s t, a n a cti on not s ha red by a ny of the other tri cycl i cs ;
the SSRIs (eg, ci ta l opra m, fl uoxeti ne, s ertra l i ne; a ns wers b, c, a nd d); a nd the monoa mi ne oxi da s e i nhi bi tors (eg, tra nyl cypromi ne, e; or
phenel zi ne).
You s houl d reca l l tha t s uch a nti ps ychoti c drugs a s the phenothi a zi nes a nd ha l operi dol ma y a l s o ca us e a menorrhea -ga l a ctorrhea , a nd
extra pyra mi da l s i de effects , by the s a me dopa mi nergi c receptor-bl ocki ng mecha ni s m. Convers el y, drugs tha t a cti va te dopa mi ne receptors i n one
wa y or a nother (eg, bromocri pti ne) ca n be us ed to ma na ge thes e endocri ne dys functi on. Amoxa pi nes dopa mi ne receptor bl ocka de a l s o s eems to
a ccount for why the drug exerts s ome a nti ps ychoti c properti es , theoreti ca l l y ma ki ng i t us eful for pa ti ents wi th both ps ychos i s a nd depres s i on.
143. The answer is c. (Brunton, pp 404, 412, 913; Katzung, pp 551-552, 557, 562.) Meperi di ne a ppea rs to be ra ther unus ua l a mong the common opi oi d
a na l ges i cs i n terms of i ts a bi l i ty to i nhi bi t neurona l reupta ke of s erotoni n. The MAO i nhi bi tor ha s i ncrea s ed s yna pti c l evel s of s erotoni n (a nd
other endogenous monoa mi nes ) i n the centra l s yna ps es , a nd s o the pres ence of the opi oi d ha s ena bl ed ma s s i ve overs ti mul a ti on of s erotoni n
receptors . We ha ve ca us ed the s erotoni n s yndrome. None of the other drugs l i s ted pa rti ci pa te i n s uch a n i ntera cti on. However, other i mporta nt
drugs not l i s ted i n the ques ti on certa i nl y do. They i ncl ude, es peci a l l y, both tri cycl i c a nd SSRI-type a nti depres s a nts ; a nd the s erotoni n a goni s ts
commonl y referred to a s tri pta ns (eg, s uma tri pta n).
Note: Compa red wi th other opi oi d a na l ges i cs , meperi di ne ca us es s trong a nti mus ca ri ni c s i de effects , whi ch ma y be probl ema ti c or da ngerous
for s ome pa ti ents . The concerns over i ntera cti ons wi th MAOIs , the s trong a nti mus ca ri ni c a cti vi ty, a nd the genera l preva l ence of toxi ci ty owi ng to
rea dy a ccumul a ti on of the drugs toxi c meta bol i te (normeperi di ne; es peci a l l y when the drug i s us ed for l ong-term pa i n ma na gement) ha ve l ed
s ome to s ta te tha t i ts us e a s a fi rs t-l i ne a na l ges i c i s (becomi ng) i ncrea s i ngl y ra re. Tha t ma y be true for l ong-term pa i n control , but for s i ngl e
dos e or other s hort-term ma na gement of modera te-to-s evere pa i n, meperi di ne i s s ti l l us ed often. See the expl a na ti on for the a ns wer to Ques ti on
122 for more i nforma ti on.
144. The answer is b. (Brunton, pp 86t, 468-469, 1059; Katzung, pp 379, 381-382, 1033.) The generi c na me for Rohypnol (roofi es , on the s treet) i s
fl uni tra zepa m, a very l i pophi l i c a nd potent benzodi a zepi ne tha t ma ni fes ts a typi ca l but unus ua l l y s trong benzodi a zepi ne-etha nol i ntera cti on.
Gi ven the unfortuna te frequency wi th whi ch thi s drug i s us ed i l l ega l l y (there a re s ome l ega l us es outs i de the Uni ted Sta tes ), you need to know
a bout i t, a nd we s us pect you know tha t fl uma zeni l i s a competi ti ve benzodi a zepi ne receptor a nta goni s t us ed to revers e (or di a gnos e)
benzodi a zepi ne overdos es . If you s a i d tha t fl uma zeni l ha s no effect on etha nol -i nduced CNS depres s i on you woul d be correct, but our pa ti ent ha s
cons umed l i ttl e a l cohol ; her probl ems a re due to the exces s i ve benzodi a zepi ne effects a nd the i ntera cti on wi th the a l cohol . Di a zepa m (a ) a nd
tri a zol a m (e) bei ng i n the s a me cl a s s a s the offendi ng drug i n thi s s i tua ti on, a re l i kel y to exa cerba te the cl i ni ca l probl ems . Keta mi ne, a
di s s oci a ti ve a nes theti c (b; s ee Ques ti on 119 for more i nforma ti on) woul d be i na ppropri a te. Na l trexone (d) i s a n opi oi d a nta goni s t, much l i ke
na l oxone, but i s us ed ora l l y for us es s omewha t di fferent tha n thos e for na l oxone. Na l oxones s peci fi ci ty i s for opi oi d receptors , a nd s o i t woul d
ha ve no good or ba d i mpa ct on our pa ti ents s ymptoms or vi ta l s i gns .
145. The answer is c. (Brunton, pp 404, 407, 411; Katzung, pp 527-531, 539, 575.) One of the mos t noteworthy a cti ons of bupropi on, compa red wi th
tri cycl i cs or other common a nti depres s a nts , i s a rgua bl y the l owes t i nci dence of s exua l dys functi on. In ma l es there i s no a nti mus ca ri ni c a cti on (e)
tha t mi ght i nterfere wi th erecti on, a nd no peri phera l -a drenergi c bl ocka de (d) tha t mi ght i nterfere wi th eja cul a ti on or ca us e orthos ta ti c
hypotens i on. In fa ct, the drug s eems to enha nce s exua l dri ve a nd performa nce. Thi s l a tter effect ha s been cl i ni ca l l y us eful when the drug ha s
been us ed to countera ct the s uppres s ed s exua l des i re ca us ed by ma ny of the SSRI a nti depres s a nts , a nd mos t of the tri cycl i cs . Women wi th
depres s i on who report a decrea s ed i nteres t i n i ntercours e a l s o s eem to benefi t from thi s drug more tha n others . Bupropi on ha s s tructura l
s i mi l a ri ti es wi th a mpheta mi ne a nd s o i s l a rgel y nons eda ti ng (a nd s o a i s i ncorrect); a nd tends to s uppres s , ra ther tha n i ncrea s e, a ppeti te (b). The
drug l a cks a ny effects on monoa mi ne oxi da s e (f). However, bupropi ons meta bol i s m i s dependent on MAO, a nd i t s houl d not be gi ven wi thi n a bout
2 to 3 weeks of s toppi ng MAO i nhi bi tor thera py to mi ni mi ze ri s ks of toxi ci tythe ma i n a nd mos t s eri ous of whi ch i s a predi s pos i ti on to s ei zures .
You ma y a l s o remember tha t bupropi on i s ma rketed a s a s moki ng ces s a ti on a i d, under a di fferent tra de na me tha n the one l a bel ed for us e for
depres s i on. It i s i n s i tua ti ons s uch a s thi s , where the s a me a cti ve i ngredi ent i s s ol d under two di fferent tra de na mes for deci dedl y di fferent us es ,
tha t a cci denta l overdos es ca n occur i f both products a re i na dvertentl y pres cri bed for the s a me pa ti ents .
146. The answer is b. (Brunton, pp 86t, 359, 423-424, 437t; Katzung, pp 504-512.) Neurol epti c ma l i gna nt s yndrome i s thought to be a s evere form of a n
extra pyra mi da l s yndrome tha t ca n occur a t a ny ti me wi th a ny dos e of a neurol epti c a gent. However, the ri s k i s hi gher when s o-ca l l ed hi gh-potency
a nti ps ychoti cs a re us ed i n hi gh dos es , es peci a l l y i f gi ven pa rentera l l y (Youl l fi nd more i nforma ti on on thi s i n Ques ti ons 118, 132, a nd 153).
Morta l i ty from NMS i s grea ter tha n 10%. Al l ergi c rea cti ons (a ) to ha l operi dol a re ra re. Whi l e ha l operi dol overdos es (c) ma y tri gger NMS, tha t i s not
a prerequi s i te for the devel opment of the s yndrome. Ha l operi dol cl ea rl y ca us es a pa rki ns oni a n-l i ke cl i ni ca l pres enta ti on (d) a nd ta rdi ve
dys ki nes i a s (e); but the fever, el eva ti ons of CK, a nd di mi ni s hi ng l evel of cons ci ous nes s woul d be i ncons i s tent wi th s uch fi ndi ngs .

147. The answer is d. (Brunton, pp 234, 614; Katzung, pp 485-486.) Ca rbi dopa i s us ed a s a n a djunct to l evodopa . It works by i nhi bi ti ng dopa mi ne
deca rboxyl a ti on, a nd s ubs equent meta bol i s m of l evodopa to dopa mi ne, i n the gut. Thi s i s i mporta nt beca us e the ma jori ty of a n ora l l y
a dmi ni s tered dos e of l evodopa i s meta bol i zed to dopa mi ne i n the gut, a nd dopa mi ne i n the s ys temi c ci rcul a ti on does not cros s the bl ood-bra i n
ba rri er (a nd s o never rea ches the s tri a tum to ca us e des i red a nti pa rki ns on effects ). Ama nta di ne (a ) works i n the CNS to promote dopa mi ne rel ea s e
from functi ona l dopa mi nergi c nerves . Benztropi ne (b) works centra l l y to bl ock mus ca ri ni c receptors , thereby hel pi ng to norma l i ze a dopa mi ne-ACh
i mba l a nce tha t s eems to be i mporta nt i n pa rki ns oni s m. Bromocri pti ne (c) works centra l l y a s a di rect dopa mi ne receptor a goni s t. Sel egi l i ne (e) i s
a centra l l y a cti ng MAO-B i nhi bi tor tha t works by reduci ng meta bol i c i na cti va ti on of dopa mi ne.
148. The answer is e. (Brunton, pp 491-493, 521-522; Katzung, pp 545t, 559.) Penta zoci ne i s a pa rti a l a goni s t: i t a cts a s a n a goni s t on receptors , a nd
bl ocks receptors . Addi ng i t to a n a na l ges i c regi men i nvol vi ng morphi ne or a nother pure opi oi d a goni s t wi l l countera ct key effects of morphi ne.
In thi s ca s e, the pa ti ents pa i n wi l l grow wors e, not become l es s ; a nd s uch other effects a s venti l a tory depres s i on wi l l be countera cted a l s o.
Under the ci rcums ta nces des cri bed i n the ques ti on, the wors eni ng of pa i n i s fa r more l i kel y to occur tha n s ei zures , whi ch ha ve been reported
occa s i ona l l y.
To a ns wer thi s ques ti on you need to remember tha t penta zoci ne i s cl a s s i fi ed a s a pa rti a l a goni s t (or mi xed a goni s t-a nta goni s t); a nd tha t
morphi ne ca us es the fol l owi ng effects by a cti ng a s a n a goni s t on receptors : a na l ges i a , res pi ra tory depres s i on, euphori a , s eda ti on, phys i ca l
dependence, a nd decrea s ed gut moti l i ty. Penta zoci ne, gi ven a l one, ca us es a na l ges i a , s eda ti on, a nd decrea s ed gut moti l i ty by a cti ng a s a n a goni s t
on receptors . However, i t i s a wea k a goni s t, yet i t i s ful l y ca pa bl e of a nta goni zi ng the a cti ons of morphi ne on receptors i n a concentra ti ondependent fa s hi on, a nd s o pa i n returns i n thi s pa ti ent.
Concomi ta nt wi th a nta goni s m of a s trong opi oi d a nta goni s ts a na l ges i c effects , a dmi ni s tra ti on of penta zoci ne wi l l a nta goni ze (not i ntens i fy, a )
res pi ra tory depres s i on. It wi l l not promote, a ccel era te, or i ntens i fy s trong opi oi d-rel a ted phys i ca l dependence (b); i nduce coma (c), nor i nduce
s ei zures (d).
149. The answer is b. (Brunton, pp 356-357, 614t; Katzung, pp 488f, 490, 499.) Sel egi l i ne i nhi bi ts MAO-B, thus i nhi bi ti ng the meta bol i c brea kdown of
dopa mi ne a nd ma ki ng more neurona l l y rel ea s ed dopa mi ne a va i l a bl e for i ts pos ts yna pti c receptor a cti va ti on. It i ncrea s es the effecti venes s of
both endogenous a nd pha rma col ogi ca l l y a dmi ni s tered L-dopa . Benztropi ne (a ) a nd tri hexypheni dyl (c) a re chol i nergi c mus ca ri ni c a nta goni s ts tha t
ma i nl y a ct i n the CNS. They ha ve no effect on dopa mi ne meta bol i s m, rel ea s e, or di rect receptor-medi a ted a goni s t a cti ons . Bromocri pti ne (d) i s a
dopa mi ne receptor a goni s t. Chl orproma zi ne (e) i s a n a nti ps ychoti c drug wi th a nti -a drenergi c properti es , a nd i t a l s o competi ti vel y bl ocks
dopa mi ne receptors i n both the CNS a nd i n the peri phery.
150. The answer is c. (Brunton, pp 436, 1344t; Katzung, pp 508-510.) Chl orproma zi ne, the prototype phenothi a zi ne a nti ps ychoti c drug, i s a l s o i ndi ca ted
for ma na gi ng na us ea a nd vomi ti ng, i n both a dul ts a nd chi l dren, from a number of ca us es . The drug ca n be a dmi ni s tered ora l l y, recta l l y, or
i ntra mus cul a rl y for thi s very purpos e. (Some phenothi a zi nes wi th better a nti emeti c a cti vi ty, s uch a s prochl orpera zi ne or prometha zi ne, a re us ua l l y
us ed i ns tea d.) Rega rdl es s , the a nti emeti c mecha ni s m a ppea rs to i nvol ve bl ocka de of dopa mi nergi c receptors i n the chemoreceptor tri gger zone of
the bra i ns medul l a .
Chl orproma zi ne (a nd mos t other a nti ps ychoti cs ) ca n l ower the bra i ns s ei zure thres hol d, thereby potenti a l l y i ncrea s i ng the ri s k of s ei zures (a )
i n s us cepti bl e pa ti ents . (Cons i der the s ei zure thres hol d to be the poi nt a t whi ch further CNS s ti mul a ti on l ea ds to s ei zures ; the l ower i t i s , the
grea ter the l i kel i hood tha t a drug s uch a s a phenothi a zi ne, a dopa mi nergi c drug, etc, ca n ca us e epi l epti form bra i n cha nges .) Chl orproma zi ne, a nd
mos t phenothi a zi nes , tend to l ower bl ood pres s ure (b; by bl ocki ng -a drenergi c receptors i n the va s cul a ture) a nd s o proba bl y woul d a ggra va te
preexi s ti ng hypotens i on. Mos t of the phenothi a zi nes a l s o ca us e s i gni fi ca nt a nti mus ca ri ni c effects , whi ch woul d a ggra va te bl a dder hypomoti l i ty
(d) a nd xeros tomi a (e; a nd other condi ti ons i nvol vi ng reduced exocri ne gl a nd s ecreti ons ). The a nti mus ca ri ni c effects woul d i nhi bi t a cti va ti on of
the bl a dders detrus or mus cl e a nd i nhi bi t rel a xa ti on of the s phi ncter, thereby a ggra va ti ng probl ems wi th mi cturi ti on i n s uch pa ti ents a s the
el derl y ma n wi th a n enl a rged pros ta te.
Note: In genera l , phenothi a zi nes a re not us ed often for ma na gi ng emes i s or na us ea . Tha t i s , i n pa rt, beca us e of the ri s k of exces s i ve s eda ti on,
extra pyra mi da l rea cti ons , orthos ta ti c hypotens i on, a nd occa s i ona l chol es ta ti c ja undi ce (hepa ti ti s ) or bl ood dys cra s i a s . Nowa da ys we tend to turn
to other dopa mi ne a nta goni s ts (eg, metocl opra mi de), a ca nna bi noi d (drona bi nol ), or a s erotoni n receptor bl ocker (onda ns etron; a 5-HT3 -s el ecti ve
bl ocker).
151. The answer is b. (Brunton, pp 198t, 661-663; Katzung, pp 143, 451t, 460.) Coca i ne, a n es ter of benzoi c a ci d, ha s l oca l a nes theti c properti es ; i t ca n
bl ock the i ni ti a ti on or conducti on of a nerve i mpul s e. It i s meta bol i zed by pl a s ma es tera s es to i na cti ve products . Mos t i mporta nt, coca i ne (a nd
tri cycl i c a nti depres s a nts ) bl ocks the neurona l reupta ke of norepi nephri ne a nd other monoa mi nes (eg, dopa mi ne). Thi s a cti on produces CNS
s ti mul a nt effects i ncl udi ng euphori a , exci tement, a nd res tl es s nes s . Peri phera l l y, the bl ocked norepi nephri ne reupta ke ca us e s ympa thomi meti c
effects i ncl udi ng ta chyca rdi a a nd va s ocons tri cti on. Dea th from a cute overdos e ca n be from ca rdi a c fa i l ure, a cute corona ry va s os pa s m, s troke
(hypertens i ve cri s i s ), s ei zures , or a pnea duri ng the s ei zures . Coca i ne does not di rectl y a cti va te a drenergi c (a ) or chol i nergi c receptors ; i t ha s no
effect on ca techol a mi ne meta bol i s m (c); ta chyca rdi a a nd va s ocons tri cti on, not the oppos i te (d) a re expected res pons es ; a nd coca i ne ha s l oca l
a nes theti c a cti vi ty a nd s o a ctua l l y s uppres s es the conducti on of a va ri ety of neuron types .
152. The answer is a. (Brunton, pp 357, 641, 1114.) The ma i n s ubcl a s s es of dopa mi ne receptors i n the CNS a re D 1 a nd D 2 receptors . Bromocri pti ne i s a
s el ecti ve D 2 a goni s t, a nd i s us eful to trea t pa rki ns oni s m or hyperprol a cti nemi a . Chl orproma zi ne (b), fl uphena zi ne (c), ha l operi dol (d), a nd
prometha zi ne (e) a re competi ti ve D 2 receptor a nta goni s ts , a nd a re us ed ma i nl y a s a nti ps ychoti c drugs .
153. The answer is a. (Brunton, pp 424t, 427t; Katzung, pp 507-508, 511-512.) Of a l l the a nti ps ychoti cs , the i nci dence a nd s everi ty of thes e a nti -mus ca ri ni c
(a nd other peri phera l a utonomi c) s i de effects a re hi ghes t wi th the phenothi a zi nes , of whi ch chl orproma zi ne ca n be cons i dered the prototype.
Cl oza pi ne (b) bl ocks -a drenergi c, hi s ta mi ne (H 1 ), ACh (mus ca ri ni c) receptors , but the a ffi ni ty for thos e receptors i s very l ow i n compa ri s on wi th
dopa mi ne a nd s erotoni n receptor bl ocka de. Ha l operi dol ha s cons i dera bl e dopa mi ne receptor-bl ocki ng a cti vi ty, a nd l i ttl e effect on mus ca ri ni c
receptors tha t mi ght a ccount for the s i de effects des cri bed here. (See Ques ti ons 118, 123, a nd 132 for more on funda menta l di fferences between
hi gh potency a nd l ow potency a nti ps ychoti cs , es peci a l l y a s they predi ct the rel a ti ve i nci dence of peri phera l a utonomi c a nd centra l
(extra pyra mi da l ) s i de effects .) Ol a nza pi ne (d) i s pha rma col ogi ca l l y mos t s i mi l a r to cl oza pi ne, except for the fa ct tha t the ri s k of a gra nul ocytos i s i s
qui te l ow. Sertra l i ne (e) i s a n SSRI, a nd you s houl d reca l l tha t SSRIs (eg, the prototype, fl uoxeti ne) l a ck cl i ni ca l l y s i gni fi ca nt a nti mus ca ri ni c effects .
154. The answer is b. (Brunton, pp 502-503; Katzung, pp 549-552.) Morphi ne a nd other s trong opi oi ds ca us e venti l a tory depres s i on. Tha t, i n turn, ra i s es
bl ood p CO2 (mos t i mporta ntl y) a nd l owers p O2 a l s o. Cerebra l bl ood ves s el s res pond by a utoregul a ti ng (di l a ti ng) to i ncrea s e cerebra l perfus i on.
Thi s , i n turn, i ncrea s es i ntra cra ni a l pres s ure (ICP)whi ch i s a l rea dy l i kel y to be hi gh wi th a cl os ed-hea d i njury. If ICP ri s es s uffi ci entl y hi gh from
bra i n s wel l i ng (the combi ned effects of drug-i nduced cerebra l va s odi l a ti on a nd tra uma -i nduced edema ), then cerebra l bl ood fl ow ca n be reduced

to da ngerous or even fa ta l l evel s (i e, i s chemi c s troke).

Now l ets cons i der a s cena ri o tha ts germa ne to the ques ti on. As s ume tha t the pa ti ent s uffered the CHI i n a motor vehi cl e a cci dent, a l ong wi th
numerous a nd s evere l a cera ti ons , fra ctures , a nd i nterna l i njuri es . They hurt. Wi l l we l et them hurt by a voi di ng us e of morphi ne or a ny other s trong
opi oi d a na l ges i cwhi ch a l s o s uppres s es venti l a ti on a nd ra i s es ICP? Of cours e not, s o wha t ca n we do? (1) Mecha ni ca l l y venti l a te the pa ti ent to
control a nd ma i nta i n rea s ona bl y norma l bl ood ga s es ; (2) a dmi ni s ter ma nni tol , the os moti c di ureti c, to hel p countera ct bra i n s wel l i ng; (3) perha ps
gi ve a corti cos teroi d wi th s trong a nti -i nfl a mma tory a cti vi ty, s uch a s dexa metha s one; (4) dri l l a burr hol e i n the s kul l to hel p reduce pres s ure; a nd
s o on.
And the other a ns wer choi ces ? Morphi ne i s i ndi ca ted a s a djuncti ve thera py for a cute pul mona ry edema (a ; i mproves pul mona ry hemodyna mi cs ,
hel ps norma l i ze venti l a ti on, hel ps a l l a y a nxi ety); a nd a l s o does s i mi l a r thi ngs for a recent or evol vi ng MI or a cute corona ry s yndrome (e). A hi s tory
of epi l eps y (c) or hypertens i on (d) does not pos e a ny cl i ni ca l l y rel eva nt probl ems i n terms of morphi ne a dmi ni s tra ti on.
155. The answer is b. (Brunton, pp 295-297; Katzung, pp 146, 176-177, 189.) In a ddi ti on to bei ng a pproved (a nd wi del y us ed) a s a n a nti hypertens i ve drug,
cl oni di ne i s a l s o a pproved for ma na gi ng s evere pa i n i n s i tua ti ons s uch a s the one des cri bed i n the ques ti on. For a na l ges i a i t i s ma i nl y us ed a s
a n a djunct to a n opi oi d, a nd i t s eems to provi de s i gni fi ca nt a dded rel i ef from pa i n or other unpl ea s a nt s ens a ti ons tha t a re neuropa thi c i n ori gi n.
The drug i s gi ven by conti nuous epi dura l i nfus i on a t ra tes a nd dos a ges l ower tha n thos e rea ched when the drug i s gi ven ora l l y or tra ns derma l l y
for bl ood pres s ure control . The receptor-ba s ed a na l ges i c mecha ni s m of thi s very l i pophi l i c drug i s proba bl y s i mi l a r to i ts centra l a nti hypertens i ve
effects . Wherea s a nti hypertens i ve dos es a ct a s a n a goni s t for a popul a ti on of 2 -a drenergi c receptors i n the ca rdi ova s cul a r control center of the
bra i n (medul l a ), a na l ges i c dos es of cl oni di ne pri ma ri l y a ct i n pa rts of the s pi na l cord. Once thos e a drenergi c receptors a re a cti va ted
neurotra ns mi s s i on by a fferent s ens ory nerves i s i nhi bi ted. (The drug a cts onl y i n thos e pa rts of the s pi na l cord tha t ha ve s ens ory a fferent pa i n
pa thwa ys from peri phera l s tructures .) Cl oni di ne-medi a ted a na l ges i a i s not s uppres s ed or a bol i s hed by tra di ti ona l opi oi d receptor a nta goni s ts
(na l oxone, na l trexone). Nonethel es s , when cl oni di ne i s us ed for pa i n (or to ma na ge drug wi thdra wa l s i gns a nd s ymptoms ), you s ti l l s houl d
a nti ci pa te a l l the drugs expected s i de effects , i ncl udi ng a fa l l of bl ood pres s ure (reduced s ympa theti c va s ocons tri cti on) a nd of hea rt ra te a nd
s troke vol ume (reduced 1 a cti va ti on). Al s o, even when us ed a s a n a na l ges i c, when the drug i s to be s topped the da i l y dos es need to be ta pered
gra dua l l y to reduce the ri s k of rebound hypertens i ve epi s odes .
None of the other drugs l i s ted a s pos s i bl e a ns wers , or members of thei r cl a s s ACE i nhi bi tors , di ureti cs , -bl ockers (of a ny s ort or s el ecti vi ty), or
peri phera l l y a cti ng -bl ockers s ha re cl oni di nes a na l ges i c a cti ons or us e. Indeed, of a l l the a nti hypertens i ve drugs cl oni di ne i s the onl y one wi th
thi s a pproved a na l ges i c us e.
156. The answer is b. (Brunton, pp 508-509; Katzung, pp 557, 562.) Metha done i s a s l ow-ons et, l ong-a cti ng, opi oi d receptor ( a nd ) a goni s t. It i s us ed
a s a n a na l ges i c (for l ong-term pa i n control when a n opi oi d i s i ndi ca ted) a nd for ma i ntena nce thera py of i ndi vi dua l s dependent on opi oi ds . It ha s
grea ter ora l bi oa va i l a bi l i ty tha n morphi ne, es peci a l l y when ora l thera py i s s ta rted. (Reca l l tha t morphi ne i s s ubject to extens i ve fi rs t-pa s s hepa ti c
meta bol i s m, a nd onl y wi th repea ted ora l a dmi ni s tra ti on ca n we s a tura te i ts drug-meta bol i zi ng enzymes s uch tha t bi oa va i l a bi l i ty i s i mproved
enough to get good a na l ges i a . Tha ts why i f our a na l ges i c of choi ce i s morphi ne, we s ta rt trea tment wi th pa rentera l a dmi ni s tra ti on.) Metha dones
l ong bi ol ogi c ha l f-l i fe a ccounts for the mi l der but more protra cted a bs ti nence s yndrome when the drug i s s topped. Metha done does not pos s es s
opi oi d a nta goni s t properti es (whether or ) a nd, thus , woul d not preci pi ta te wi thdra wa l s ymptoms i n a heroi n a ddi ct, a s woul d na l oxone or
na l trexone, s o l ong a s we a dmi ni s ter s uffi ci ent dos es of the metha done, a nd tha t i s preci s el y wha t we do wi th metha done ma i ntena nce thera py
or when we s wi tch a pa ti ent to i t from a nother opi oi d. Exces s i ve dos es of metha done ca n ca us e typi ca l opi oi d-rel a ted venti l a tory depres s i on.
157. The answer is b. (Brunton, pp 584t, 596; Katzung, pp 417-418, 422-423.) Ethos uxi mi de i s very effecti ve (a nd, a ccordi ng to ma ny, the drug of choi ce) for
a bs ence s ei zures . Phenytoi n (e) ma y a ggra va te a bs ence s ei zures , des pi te i ts effi ca cy a nd proven tra ck record for other chroni c s ei zure types . None
of the other drugs l i s ted (a , di a zepa m; c, l ora zepa m; d, methyl pheni da te; e, phenytoi n) a re effecti ve or i ndi ca ted for l ong-term thera py of epi l eps y.
Severa l other thi ngs to reca l l : Di a zepa m us ed to be the drug of choi ce for i ni ti a l thera py of s ta tus epi l epti cus . No l onger. For s ta tus epi l epti cus
we gi ve IV l ora zepa m fi rs t, for prompt s ei zure control ; fol l owed i mmedi a tel y by IV phenytoi n (or fos phenytoi n) for a s l ower-ons et but l ongerl a s ti ng control of the s ei zures . Methyl pheni da te, a n a mpheta mi ne-l i ke drug, i s one of s evera l s i mi l a r a gents i ndi ca ted for ma na gi ng ADD-ADHD. It
wi l l not hel p a bs ence s ei zures , a nd owi ng to i ts CNS-s ti mul a ti ng effects ma y a ggra va te other s ei zure types .
158. The answer is b. (Brunton, pp 310, 347-349; Katzung, pp 155, 287-290.) Ergota mi ne ha s for yea rs been cons i dered a ma i ns ta y of a borti ng mi gra i ne
hea da ches , a l though nowa da ys for effi ca ci ous a nd a rgua bl y s a fer drugs s uch a s s uma tri pta n a re us ed. Whether the drug i s a n ergot a l ka l oi d or a
tri pta n, the l i kel y mi gra i ne-a borti ng mecha ni s m i nvol ves a nta goni zi ng cerebra l va s odi l a ti on. It a cti va tes 5-HT3 receptors , whi ch i n turn ca us es
cerebra l va s ocons tri cti on. Ergota mi ne i n pa rti cul a r a l s o ca n ca us e s i gni fi ca nt a nd l ong-l a s ti ng s ys temi c va s ocons tri cti on vi a -a drenergi c receptor
a cti va ti on. Whi l e norma l corona ry ves s el s a rent uni quel y s ens i ti ve to thi s effect, thos e of pa ti ents who a re prone to devel opi ng corona ry
va s os pa s m (Pri nzmeta l or va ri a nt a ngi na ) a re a t grea ter ri s k, a nd tha t i s l i kel y wha t thi s pa ti ent ha d. [Perha ps youve hea rd of St. Anthony Fi re
wha t we now ca l l ergoti s mtha t occurred i n the Mi ddl e Ages . It wa s cha ra cteri zed by ga ngrene a nd bl oodl es s l os s of the fi ngers a nd toes
(a mong other probl ems ), a nd wa s due to i ntens e va s ocons tri cti on ca us ed by ea ti ng s poi l ed gra i ns l a den wi th a fungus tha t produced l a rge
a mounts of ergot a l ka l oi ds .]
Bromocri pti ne (a ), a nother ergot a l ka l oi d, ha s l i ttl e effect on 5-HT or a drenergi c receptors . However i t i s a n effi ca ci ous dopa mi ne D 2 a goni s t,
a nd tha t provi des the ba s i s for i ts us e for pa rki ns oni s m, hyperprol a cti nemi a , a nd trea tment of s ome prol a cti n-s ecreti ng pi tui ta ry tumors .
Morphi ne (c) i s not l i kel y to ca us e hypertens i on, a nd woul d produce myoca rdi a l i s chemi a (of a gl oba l na ture) onl y when s uch hi gh dos es a re gi ven
tha t hypotens i on (a nd venti l a tory depres s i on) ens ue.
Phenoxybenza mi ne (d) bl ocks 5-HT receptors (a nd ACh a nd hi s ta mi ne receptors too), whi ch expl a i ns i ts us e (i nfrequentl y, nowa da ys ) for
ca rci noi d s yndromea tumor tha t s ecretes l a rge a mounts of s erotoni n a nd pepti des tha t s ti mul a te s mooth mus cl es (pri ma ri l y i n the a i rwa ys a nd
GI tra ct). However, phenoxybenza mi nes ma i n pha rma col ogi c effect i s l ong-l a s ti ng a nd noncompeti ti ve bl ocka de of -a drenergi c receptors , a nd the
rel a ted us e i s a djuncti ve ma na gement of ca techol a mi ne-s ecreti ng tumors (i e, pheochromocytoma ). Thus , i t l owers bl ood pres s ure a nd a l s o woul d
bl ock corona ry va s ocons tri cti on or s pa s m medi a ted by -a drenergi c a cti va ti on. Dos a ges needed to bl ock 5-HT receptors a re much hi gher tha n thos e
needed to bl ock s erotoni n receptors .
Phenytoi n (e), a n i mporta nt a nti convul s a nt, ha s no a bi l i ty to ca us e hypertens i on (nor a ny other s i gni fi ca nt i ncrea s e of bl ood pres s ure), nor to
ca us e or exa cerba te corona ry va s os pa s m.
159. The answer is e. (Brunton, pp 920-921; Katzung, pp 279, 1100.) Prometha zi ne, l i ke mos t other phenothi a zi nes , tends to ca us e dos e-dependent CNS
depres s i on. Of the a ns wers gi ven here, the mos t l i kel y outcome of tha t effect i s venti l a tory depres s i on a nd a pnea , a nd tha t i s preci s el y the rea s on
why the FDA bol s tered the wa rni ngs for chi l dren. Li ke mos t other phenothi a zi nes , prometha zi ne ha s s i gni fi ca nt a nti mus ca ri ni c a cti vi ty, a nd tha t
woul d not ca us e hea rt bl ock (a ) or di a rrhea (d). It ha s -a drenergi c bl ocki ng a cti vi ty, whi ch woul d l ower, ra ther tha n ra i s e, bl ood pres s ure (b).
Prometha zi ne ma y, i ndeed, ca us e pa rki ns oni a n-l i ke s i de effects (c), but they a re not l i kel y to be a ca us e of dea th unl es s the pa ti ent devel ops

neurol epti c ma l i gna nt s yndrome tha t goes undi a gnos ed a nd i mproperl y trea ted unti l i t i s too l a te.
160. The answer is e. (Brunton, pp 86t, 268; Katzung, pp 284, 437, 475, 479.) The s yndrome I des cri bed i s tha t of ma l i gna nt hyperthermi a (MH). (Some
fol ks l i ke to us e the mnemoni c FEVERfever, encepha l opa thy, vi ta l s uns ta bl e, el eva ted enzymes s uch a s crea ti ne ki na s e, a nd ri gi di ty of mus cl es .)
For deca des i t ha s been a ttri buted to a n i ntera cti on between ha l ogena ted hydroca rbon vol a ti l e l i qui d a nes theti cs pri ma ri l y ha l otha ne, but s ti l l
a pos s i bi l i ty wi th others , i ncl udi ng i s ofl ura ne; a nd s kel eta l neuro-mus cul a r bl ockers , pa rti cul a rl y s ucci nyl chol i ne. It ca n occur i ntra opera ti vel y or
i n the i mmedi a te pos topera ti ve peri od. The overa l l i nci dence i s a bout 1 i n 50,000 a nes thes i a s , a nd 1 i n a bout 15,000 pedi a tri c a nes thes i a s .
Worl dwi de, MH i s fa ta l a bout 80% of the ti me, but onl y a bout 10% to 15% of the ti me i n the Uni ted Sta tes . There i s a l mos t certa i nl y a geneti c ba s i s
for MH, i nvol vi ng a n a utos oma l domi na nt tra i t tha t a ccounts for a bout ha l f of a l l MH ca s es . On a mol ecul a r ba s i s i t i s cha ra cteri zed by a berra nt
functi on of the s o-ca l l ed rya nodi ne-s ens i ti ve ca l ci um cha nnel i n the s a rcopl a s mi c reti cul um. In es s ence, i t i mpa i rs the a bi l i ty of the s a rcopl a s mi c
reti cul um to ta ke up (vi a a n ATPa s e) a nd reta i n Ca 2+ a s i s neces s a ry for s kel eta l mus cl e to rel a x, a l bei t bri efl y, between contra cti ons . The res ul ti ng
a nd more or l es s perpetua l ri s e of free i ntra cel l ul a r Ca 2+ l ea ds to toni c s kel eta l mus cl e a cti va ti on (hence, ri gi di ty). The hei ghtened ATP
cons umpti on tha t occurs to ma i nta i n cros s -bri dge forma ti on us es a n a bunda nt a mount of oxygen, a nd hea t i s genera ted (the fever). As mus cl e
functi on deteri ora tes a nd ATP i s depl eted, meta bol i s m s wi tches to gl ycol ys i s a nd l a cti c a ci d a ccumul a ti on (a ci dos i s ). Da ma ged mus cl e cel l s l ea k
K+ tha t i n turn ca us es hyperka l emi a , ta chyca rdi a , a nd ca rdi a c a rrhythmi a s . Myogl obi n a nd l a rge i ntra cel l ul a r enzymes s uch a s crea ti ne ki na s e a l s o
l ea k out of da ma ged myocytes . Unl es s trea ted promptl y (da ntrol ene, phys i ca l mea ns to cool the body, a ttempts to correct bl ood pH a nd el ectrol yte
profi l es ), the cons equences ca n be fa ta l . See Ques ti ons 132, 146, 159, a nd 176 for more i nforma ti on on the i s s ue of neurol epti c ma l i gna nt
s yndrome or the s omewha t rel a ted s yndrome, ma l i gna nt hyperthermi a .
None of the other drugs , i ndi vi dua l l y or i n the combi na ti ons gi ven, a re a s s oci a ted wi th ma l i gna nt hyperthermi a .
161. The answer is c. (Brunton, pp 583-606, 1792; Katzung, pp 416-417.) Vi ga ba tri n (-vi nyl GABA) i s , i ndeed, us eful i n pa rti a l s ei zures . Before a ddres s i ng
the s peci fi c mecha ni s m: If you encounter a ques ti on a bout vi ga ba tri n, you s houl d i mmedi a tel y s ee tha t the drug works , i n one wa y or a nother,
beca us e the l etters gaba a re i n the drugs generi c na me. And the s peci fi c mecha ni s m? Vi ga ba tri n i s a n i rrevers i bl e i nhi bi tor of GABA
a mi notra ns fera s e, a n enzyme res pons i bl e for the termi na ti on of GABA a cti on once the neurotra ns mi tter ha s been rel ea s ed i nto the s yna ps e. Thi s
res ul ts i n a ccumul a ti on of GABA a t s yna pti c s i tes , thereby enha nci ng i ts effect. (Note the ma ny pa ra l l el s between pha rma col ogi c modi fi ca ti on of
GAB-Aergi c neurotra ns mi s s i on a nd thos e tha t ca n be us ed to modi fy chol i nergi c a nd a drenergi c neurotra ns mi s s i on. For exa mpl e, jus t a s
vi ga ba tri n i mpa i rs i na cti va ti on of rel ea s ed GABA, thereby boos ti ng GABAs pos ts yna pti c effects , s o do a cetyl chol i nes tera s e i nhi bi tors (eg,
neos ti gmi ne) wi th res pect to the a cti ons of rel ea s ed ACh.
162. The answer is d. (Brunton, pp 509-510; Katzung, pp 407-408, 423-424.) Fol i c a ci d s uppl ementa ti on duri ng pregna ncy i s recommended duri ng norma l
uncompl i ca ted pregna ncy, a nd i t i s cri ti ca l when the mother i s recei vi ng a nti convul s a nt drugs (AEDs ) duri ng ges ta ti on. The purpos e i s to reduce the
ri s k of s pi na bi fi da a nd other neura l tube defects (a nd s ome other tera togeni c cons equences ). The condi ti on i s known a s the feta l hyda ntoi n
s yndrome. The ques ti ons s cena ri o des cri bes no rea s on to a dd va l proi c a ci d (or a dd or s wi tch to a ny other AED, i ncl udi ng phenoba rbi ta l ) i f the
mother i s kept s ei zure-free duri ng pregna ncy a nd gets proper peri na ta l ca re. Va l proi c a ci d i s i n pregna ncy cl a s s D; mos t others a re C, a nd s o i t
a ppea rs to ca rry the hi ghes t ri s k of tera togeni c effects of a l l the common AEDs . Di s conti nui ng a ny or a l l AEDs duri ng pregna ncy (b) i s ri s ky i n thi s
a nd mos t ci rcums ta nces , a s i t ca rri es the ri s k of s ei zure recurrence tha t ca n be more da ngerous to the mother a nd the fetus tha n conti nui ng
effecti ve thera py a nd provi di ng good prena ta l ca rea nd fol i c a ci d s uppl ementa ti on.
Notes : Current recommenda ti ons (Fol i c a ci d for the preventi on of neura l tube defects : US Preventi ve Servi ces Ta s k Force recommenda ti on
s ta tement. Ann. Intern. Med. 2009;150:626) a re tha t women (even) pl a nni ng or ca pa bl e of pregna ncy s houl d ta ke a da i l y s uppl ement (i n a ddi ti on to
a ny fol a te i n the di et) conta i ni ng between 0.4 a nd 0.8 mg of fol i c a ci d. Thes e recommenda ti ons a ppl y even to women who a re otherwi s e hea l thy
a nd ta ki ng no tera togeni c drugs , AEDs , or a ny others . As a n a s i de, the overa l l ri s k of ha vi ng a chi l d born wi th neura l tube defects or other
a noma l i es i s a bout 1%. Wi th s i ngl e-dos e AED thera py throughout pregna ncy, a nd wi th proper peri na ta l ca re, the ri s k (overa l l ) ri s es to a bout 2%.
The ri s k goes up cons i dera bl y, however, when the mother i s ta ki ng more tha n one AED duri ng pregna ncy, whether tha t drug i s va l proi c a ci d (a ) or
a ny other a gent.
Fi na l l y, judi ci ous s uppl ementa ti on of the mothers di et wi th i ron (c) i s often recommended. Tha t i s to reduce the ri s k or s everi ty of hema tol ogi c
a bnorma l i ti es , a nd ha s nothi ng to do wi th preventi on of tera togenes i s or other s i mi l a r AED-rel a ted probl ems .
163. The answer is b. (Brunton, pp 436-443, 920; Katzung, pp 506-508, 511-512.) Chl orproma zi ne, of a l l the drugs l i s ted, ha s s trong -a drenergi c receptorbl ocki ng a cti vi ty. Thi s a ccounts for a rel a ti vel y hi gh i nci dence of orthos ta ti c hypotens i on, a nd expl a i ns why mea s uri ng the pa ti ents bl ood pres s ure
i n both the s upi ne a nd s ta ndi ng pos i ti ons i s i mporta nt. At cl i ni ca l l y rel eva nt dos a ges , bus pi rone (a ) ha s no s i gni fi ca nt a utonomi c or
ca rdi ova s cul a r effects . Di phenhydra mi ne s trongl y bl ocks both mus ca ri ni c a nd H 1 hi s ta mi ne receptors , a nd nei ther a cti on woul d l i kel y ca us e
hypotens i on. Ha l operi dol (d), a butyrophenone a nti ps ychoti c, ca us es few peri phera l a utonomi c s i de effects , i ncl udi ng thos e noted i n the
ques ti on. Zol pi dem (e) i s a benzodi a zepi ne-l i ke hypnoti c tha t l a cks a ppreci a bl e peri phera l a utonomi c s i de effects .
164. The answer is a. (Brunton, pp 350-351, 359; Katzung, pp 504f, 509t, 519.) Cl oza pi ne ca us es a gra nul ocytos i s i n 1% to 2% of trea ted pa ti ents , whi ch i s
fa r more common a nd potenti a l l y s eri ous tha n wi th other, a nd ol der, a nti ps ychoti cs tha t mi ght be us ed i n l i eu of i t. Thi s potenti a l l y l etha l bl ood
dys cra s i a i s genera l l y revers i bl e on di s conti nua ti on of the drug, but thi s of cours e depends on frequent bl ood tes ts to detect the probl em ea rl y on.
Moni tori ng for thi s a dvers e res pons e i s s o cri ti ca l tha t the i ni ti a l pres cri pti on for the drug, a nd refi l l s for conti nued thera py, ca nnot be fi l l ed
wi thout proof of bl ood counts tha t a re wi thi n a ccepta bl e l evel s . (The i nci dence of bl ood dys cra s i a s wi th the cl oza pi ne-l i ke a typi ca l a nti ps ychoti c
ol a nza pi ne i s l ower tha n tha t wi th cl oza pi ne, but nonethel es s hi gher tha n wi th a ny of the ol der a gents .) Other concerns wi th cl oza pi ne, for whi ch
moni tori ng i s i mporta nt, i ncl ude the devel opment of s ei zures ; wei ght ga i n (i t i s common a nd the pa ti ent ma y put on a n extra 10 or 20 pounds );
ri s es of bl ood gl ucos e l evel s (perha ps wi th the devel opment of new-ons et di a betes , a nd s o a ns wer c i s i ncorrect); a nd myoca rdi ti s . Hypotens i on
(d) a nd venti l a tory depres s i on (e) a re not a t a l l common wi th the a typi ca l a nti ps ychoti cs .
Another cri ti ca l di fference between a ny of the a typi ca l a nti ps ychoti cs a nd a ny of the ol der a gents i s thi s : Extra pyra mi da l s i de effects (EPS; b) a re
ra re wi th a ny of the a typi ca l a gents , i n a bs ol ute numbers a nd i n compa ri s on wi th the ol der a gents phenothi a zi nes or, es peci a l l y, ha l operi dol .
The ri s k of EPS wi th cl oza pi ne or rel a ted drugs i s l ow beca us e of the drugs l ow a ffi ni ti es for bl ocki ng dopa mi ne D 2 receptors , a property tha t i s
proba bl y the key fa ctor i n drug-i nduced EPS. Gi ven the s heer number of pa ti ents who a re trea ted wi th a phenothi a zi ne a nti ps ychoti c, or
ha l operi dol , a nd the a s s oci a ted ri s ks of pa rki ns oni s m or ta rdi ve dys ki nes i a s , why i s nt a drug l i ke cl oza pi ne or cl oza pi ne i ts el f us ed more often?
One rea s on i s cos t, but the others i ncl ude the s i de effects ca us ed by the a typi ca l a nti ps ychoti cs , es peci a l l y the ri s k of bl ood dys cra s i a s tha t ca n be
fa ta l i f not detected ea rl y, a nd ma na ged properl y a nd promptl y.
165. The answer is d. (Brunton, pp 591-593, 845, 1012, 1524, 1529; Katzung, pp 409, 425t.) Phenytoi n, gi ven throughout pregna ncy, ca n i nhi bi t hepa ti c
s ynthes i s (a cti va ti on) of vi ta mi n K-dependent cl otti ng fa ctors i n utero. (Phenoba rbi ta l a nd s evera l other a nti convul s a nts ca n do the s a me, a nd s o

vi ta mi n K prophyl a xi s a ppl i es to thei r us e a s wel l .) None of the other drugs l i s ted i s a s s oci a ted wi th s uch a n effect. Wa rfa ri n (e), a rgua bl y the
mos t wi del y us ed ora l a nti coa gul a nt i n the worl d i s a bs ol utel y contra i ndi ca ted (ca tegory X) duri ng pregna ncy beca us e of the ri s ks of s o-ca l l ed
wa rfa ri n embryopa thy. See the expl a na ti on for a ns wers to Ques ti on 199 for more i nforma ti on.
Notes : Bupropi on i s pregna ncy ca tegory B (l ow ri s k i n huma ns ). Mos t of the benzodi a zepi nes , i ncl udi ng di a zepa m, a re i n pregna ncy ca tegory D
(defi ni te ri s ks , not a bs ol utel y contra i ndi ca ted, but bes t a voi ded). Es ta zol a m, fl ura zepa m, qua zepa m, tema zepa m, a nd tri a zol a m a re ca tegory X.
Opi oi ds a re genera l l y ca tegory B or C (metha done, a ns wer c).
166. The answer is b. (Brunton, pp 138, 207t, 212, 617-618; Katzung, pp 488f, 490, 499) Enta ca pone i s a ca techol O-methyl tra ns fera s e (COMT) i nhi bi tor.
COMT norma l l y i s a mi nor pl a yer i n the meta bol i s m of l evodopa , but when the ma jor pa thwa y for l evodopa meta bol i s m to dopa mi ne (vi a dopa
deca rboxyl a s e) i s i nhi bi ted, a s i t i s wi th a dmi ni s tra ti on of ca rbi dopa , COMT pl a ys a more i mporta nt rol e. It hel ps form 3-O-methyl dopa , whi ch
competes wi th l evodopa for upta ke i nto the bra i n. So, when we ha ve poor res pons es to l evodopa (a l one or i n combi na ti on wi th ca rbi dopa ), or
when l evodopa thera py ha s been ongoi ng for s o l ong tha t the pa ti ent devel ops a cute or chroni c refra ctori nes s to i ts effects (eg, the on-off or the
wea ri ng-off phenomena ), a ddi ng enta ca pone (or a s i mi l a r drug, tol ca pone) mi ght be rea s ona bl e.
Donepezi l (a ) a nd ta cri ne (d) a re centra l l y a cti ng chol i nes tera s e i nhi bi tors wi th no effect on dopa mi ne meta bol i s m. Sel egi l i ne (c) i s a s el ecti ve
i nhi bi tor of dopa mi ne meta bol i s m by MAO i n the bra i n (MAO-B). Tri hexypheni dyl (e) i s a centra l l y a cti ng mus ca ri ni c receptor bl ocki ng drug, ma i nl y
us ed for pa rki ns oni s m. Rel a ted a nti mus ca ri ni c drugs for pa rki ns oni s m a re benztropi ne a nd di phenhydra mi ne (the l a tter of whi ch a l s o exerts
s trong peri phera l mus ca ri ni c-bl ocki ng effects ).
167. The answer is c. (Brunton, pp 643-644; Katzung, pp 379, 400, 610t, 1156t.) Thi s i s a cl a s s i c des cri pti on of a n a l cohol -di s ul fi ra m i ntera cti on.
Di s ul fi ra m i s s ometi mes us ed i n control l i ng a l cohol a bus e. It a cts by i nhi bi ti on of a l dehyde dehydrogena s e, res ul ti ng i n the a ccumul a ti on of
a ceta l dehyde. Thi s a ceta l dehyde s yndrome i s cha ra cteri zed by the s i gns a nd s ymptoms des cri bed i n the ques ti on. The ons et of s ymptoms i s
a l mos t i mmedi a tel y fol l owi ng i nges ti on of a l cohol a nd ma y l a s t for s evera l hours i n s ome pa ti ents . None of the other drugs l i s ted i n the a ns wers
ca n ca us e thes e outcomes . Na l trexone (a ), a n opi oi d a nta goni s t, woul d ha ve no effect on the res pons es to etha nol . Di a zepa m (b) a nd
phenoba rbi ta l (d), both CNS depres s a nts tha t cl ea rl y ha ve thei r depres s a nt effects potenti a ted by a l cohol , woul d not l ea d to the des cri bed effects .
Tra nyl cypromi ne (e) i s a n ol der nons el ecti ve MAO i nhi bi tor. MAO pl a ys no rol e i n the meta bol i s m or res pons es to a l cohol .
Note: Severa l other drugs or drug cl a s s es ca n ca us e cl i ni ca l l y s i gni fi ca nt di s ul fi ra m-l i ke rea cti ons . They i ncl ude the ol der s ul fonyl urea s
(tol buta mi de, chl orpropa mi de) us ed for ora l thera py of type 2 di a betes mel l i tus ; a nd s ome of the cepha l os pori n a nti bi oti cs .
168. The answer is c. (Brunton, pp 398-413; Katzung, pp 528-529, 539.) Fl uoxeti nea nd rel a ted SSRI a nti depres s a nts s uch a s s ertra l i ne, fl uvoxa mi ne,
ci ta l opra m, a nd es ci ta l opra ms el ecti vel y i nhi bi t neurona l s erotoni n upta ke, wi th mi ni ma l effects on other monoa mi nes . The tri cycl i cs
(i mi pra mi ne) a nd venl a fa xi ne i nhi bi t s erotoni n a nd norepi nephri ne reupta ke (a nd, a ppa rentl y to a s ma l l degree, dopa mi ne). Bupropi on a ffects
reupta ke of both norepi nephri ne a nd dopa mi ne.
169. The answer is d. (Brunton, pp 458-468, 642-644; Katzung, pp 377t, 420, 439t.) Benzodi a zepi nes (pa rti cul a rl y thos e wi th prompt a nd s i gni fi ca nt
s eda ti ng a cti vi ty) a re cons i dered good choi ces for a l l evi a ti ng benzodi a zepi ne a nd a l cohol wi thdra wa l s ymptoms . The a nxi ol yti c effects of
bus pi rone (a ) ta ke s evera l da ys to devel op, renderi ng i t uns ui ta bl e for a cute, s evere wi thdra wa l s i gns a nd s ymptoms . In a ddi ti on, i t ca us es l i ttl e
or no CNS depres s i on i n mos t pa ti ents . Chl ora l hydra te (b) a nd etha nol i ntera ct by i nhi bi ti ng the meta bol i s m of ea ch other, wi th the ma i n res ul t
bei ng profound CNS depres s i on. We woul d not wa nt to gi ve chl ora l hydra te to a ny pa ti ent who s ti l l ma y ha ve a l cohol i n the ci rcul a ti on.
Chl orproma zi ne (c) i s us ed ma i nl y for ps ychos i s , a nd i s not l i kel y to benefi ci a l l y a ffect the s i gns a nd s ymptoms tha t our pa ti ent ha s . Tra zodone (e)
i s a n a typi ca l a nti depres s a nt wi th a fa i r a mount of genera l i zed CNS-depres s a nt effects , whi ch ma kes i t often pres cri bed for pa ti ents who ha ve
i ns omni a a s a ma jor depres s i on s ymptom. It wea kl y i nhi bi ts neurona l s erotoni n reupta ke a nd s eems to i ncrea s e s erotoni n rel ea s e from
s erotoni nergi c nerves . It woul d not be s ui ta bl e for the i mmedi a te ma na gement of thi s pa ti ent.
170. The answer is b. (Brunton, pp 86t, 631-632; Katzung, pp 397-398, 1037.) Metha nol i s meta bol i zed by the s a me enzymes tha t meta bol i ze etha nol , but
the products a re di fferent: forma l dehyde a nd formi c a ci d i n the ca s e of metha nol . Hea da che, verti go, vomi ti ng, a bdomi na l pa i n, dys pnea , a nd
bl urred vi s i on ca n occur from a ccumul a ti on of thes e meta bol i c i ntermedi a tes . However, the mos t da ngerous (or a t l ea s t perma nentl y di s a bl i ng)
cons equence i n s evere ca s es i s hyperemi a of the opti c di s c, whi ch ca n l ea d to bl i ndnes s . The ra ti ona l e for a dmi ni s teri ng etha nol to trea t
metha nol poi s oni ng i s fa i rl y s i mpl e. Etha nol ha s a hi gh a ffi ni ty for a l cohol a nd a l dehyde dehydrogena s es a nd competes wi th metha nol a s a
s ubs tra te for thos e enzymes , reduci ng meta bol i s m of metha nol to i ts more toxi c products . Importa nt a djuncti ve trea tments i ncl ude hemodi a l ys i s
to enha nce remova l of metha nol a nd i ts products ; a nd a dmi ni s tra ti on of s ys temi c a l ka l i ni zi ng s a l ts (eg, s odi um bi ca rbona te) to countera ct
meta bol i c a ci dos i s . None of the other drugs l i s ted woul d be a ppropri a te. They ma y a l l evi a te s ome of the s i gns a nd s ymptoms res ul ti ng from
metha nol poi s oni ng, but they woul d ha ve no benefi ci a l effects on the crux of the probl emthe meta bol i s m of the metha nol .
171. The answer is c. (Brunton, p 484t; Katzung, pp 559-560, 572, 1033t.) Na l oxone i s gi ven pa rentera l l y. It s peci fi ca l l y bl ocks opi oi d receptors tha t a re
a cti va ted by s uch a goni s ts a s morphi ne, heroi n, a nd fenta nyl (a mong ma ny others ). Di a zepa m (a ) a nd other benzodi a zepi nes (eg, l ora zepa m) ha ve
no effects on opi oi d receptors . Fl uma zeni l (b) i s a s peci fi c benzodi a zepi ne a nta goni s t. It ma y be l i fe-s a vi ng i n ca s es of benzodi a zepi ne
overdos es , but ha s no effects on the res pons es to opi oi ds . Na l trexone (d) i s a n opi oi d receptor a nta goni s t (a s i s na l oxone), but i t i s gi ven ora l l y,
ha s a s l ower ons et of a cti on, a nd s o wi l l be of l i ttl e benefi t i n thi s a cute, l i fe-threa teni ng s i tua ti on. Fenta nyl i s unl i kel y to ca us e s ei zures .
Phenytoi n (e) i s , of cours e, a n a nti convul s a nt; i t woul d be i na ppropri a te to a dmi ni s ter, a nd i f the a dmi ni s tered dos e wa s s uffi ci entl y hi gh i t coul d
contri bute to the CNS a nd venti l a tory depres s i on ca us ed by the fenta nyl .
172. The answer is b. (Brunton, pp 404-405, 411, 923; Katzung, pp 525-530.) Imi pra mi ne, a tri cycl i c a nti depres s a nts , ca us es s trong peri phera l
a nti mus ca ri ni c effects . In the context of our pa ti ent, reca l l tha t mus ca ri ni c receptor a cti va ti on contra cts the detrus or mus cl e of the bl a dder, a nd
rel a xes the bl a dder s phi ncter. Imi pra mi ne bl ocks thos e effects , a nd tha t s eems to expl a i n i ts effects i n ma na gi ng nocturna l enures i s es peci a l l y
i n chi l dren. The drug a nd other members of i ts cl a s s do rel i eve depres s i on s i gns a nd s ymptoms . However, they a re due to i nhi bi ti on, not i ncrea s es
of (a ) monoa mi ne neurotra ns mi tter reupta ke vi a the s o-ca l l ed norepi nephri ne tra ns porter a t the endi ngs of ca techol a mi nergi c neurons .
Imi pra mi ne a nd i ts group members tend to ca us e s eda ti on (c), but tha t i s not l i kel y to reduce the frequency of enures i s . Thes e drugs a l s o ha ve a drenergi c bl ocki ng a cti vi ty, a nd one cons equence of tha t woul d mos t l i kel y be a n i ncrea s e, not a decrea s e, of rena l bl ood fl ow a nd GFR. Tri cycl i c
a nti depres s a nts , nor other ma jor cl a s s es of a nti depres s a nts , ha ve a ny i mporta nt effects on the rel ea s e of a nti di ureti c hormone or the res pons es
of the rena l tubul es to ADH.
173. The answer is a. (Brunton, pp 404, 407, 411; Katzung, pp 527-531, 1034.) Bupropi on i s ma rketed, under di fferent tra de na mes , for two ma i n purpos es :
a nxi ety rel i ef a nd s uppres s i on of the cra vi ngs for ni coti ne. Si nce too ma ny phys i ci a ns pres cri be by bra nd-na me products , a nd i gnore the a cti ve
generi c drug, s uch probl ems a s the one I des cri bed i n our s cena ri o, due to a cci denta l dupl i ca ti on a nd overdos es of a drug, a re more common tha n

youd l i ke to bel i eve. One of the ma i n cons equences of bupropi on overdos e (or even s udden di s conti nua ti on of the drug, es peci a l l y i n pa ti ents
wi th epi l eps y) i s s ei zures . Chl ordi a zepoxi de (b) i s a benzodi a zepi ne tha t i s not i ndi ca ted for depres s i on or a s a s top-s moki ng a i d. If a nythi ng, the
drug wi l l s uppres s , ra ther tha n ca us e, s ei zures . Fl uoxeti ne (c) a nd i mi pra mi ne (d) a re a nti depres s a nts , but they a re not pres cri bed a s s moki ngces s a ti on a i ds , nor a re they ma rketed i n products a pproved for tha t us e. Li thi um (e) i s a mood-s ta bi l i zi ng drug us ed i n bi pol a r i l l nes s . It i s not
us ed for ma na gi ng depres s i on or for s moki ng ces s a ti on.
174. The answer is c. (Brunton, p 234; Katzung, pp 117f, 492t, 499) At fi rs t bl us h i t woul d s eem tha t choos i ng a ny a nti pa rki ns on drug woul d be
a ppropri a te for thi s ma n. However, i f you thi nk a bout the eti ol ogy of s chi zophreni a a nd of pa rki ns oni s m (es peci a l l y drug-i nduced), a nd the
mecha ni s ms of a cti on of the drugs l i s ted, you woul d s el ect benztropi ne (or a rel a ted drug, tri hexypheni dyl )or di phenhydra mi ne, a -bl ocker, or a
benzodi a zepi ne, none of whi ch wa s l i s ted a s a choi ce).
Phenothi a zi nes (chl orproma zi ne), a nd es peci a l l y butyrophenones (ha l operi dol , e), rel i eve s chi zophreni a s i gns a nd s ymptoms l a rgel y by
bl ocka de of centra l dopa mi ne (D 2 ) receptors , pa rti cul a rl y i n the mes ol i mbi c-mes ocorti ca l s ys tem. Si mul ta neous l y, D 2 bl ocka de i n the
ni gros tri a tum, a nd concomi ta nt unma s ki ng of oppos i ng mus ca ri ni c-chol i nergi c effects , s eems to a ccount for the extra pyra mi da l /pa rki ns oni a n s i de
effects tha t ha ve s urfa ced i n pa ti ents l i ke the one I des cri be. Reca l l tha t des pi te the i mpreci s i on of the termi nol ogy, hi gh potency a nti ps ychoti cs
s uch a s ha l operi dol a re a s s oci a ted wi th a much hi gher i nci dence of extra pyra mi da l s i de effects tha n a re the l ow potency a nti ps ychoti cs (i e, the
phenothi a zi nes ), due to thei r s tronger centra l D 2 bl ocka de, a nd s o s wi tchi ng from chl orproma zi ne to ha l operi dol woul d not a t a l l a l l evi a te thi s
pa ti ents pa rki ns oni a n s i de effects : i t woul d l i kel y wors en them.
In i di opa thi c Pa rki ns on di s ea s e there i s deteri ora ti on of dopa mi nergi c neurons a nd, i nferenti a l l y, a decrea s e of centra l dopa mi ne content or
rel ea s e. Tha t pa thophys i ol ogy provi des a ra ti ona l e for pha rma col ogi ca l l y boos ti ng dopa mi nergi c i nfl uences : i ncrea s i ng centra l dopa mi ne
s ynthes i s (l evodopa , a l one or wi th ca rbi dopa ; d); i nhi bi ti ng dopa mi nes meta bol i c i na cti va ti on wi th ei ther a COMT i nhi bi tor (tol ca pone, a ; or
enta ca pone) or a n MAO i nhi bi tor (eg, s el egi l i ne, not l i s ted); or us i ng s uch other s tra tegi es a s dopa mi ne-rel ea s i ng or -mi meti c a gents
(a ma nta di ne, bromocri pti ne).
In thi s s i tua ti on of drug-i nduced pa rki ns oni s m, however, dopa mi ne receptors a re bl ocked by the a nti ps ychoti c. Whi l e we coul d try to overcome
tha t bl ocka de (s i nce i t i s s urmounta bl e a nd competi ti ve a nta goni s m we a re dea l i ng wi th), tha t a pproa ch i s not l i kel y to be effecti ve nor tol era bl e
to the pa ti ent, s i nce we woul d ha ve to try very l a rge dos es of a dopa mi nergi c drugdos es s uffi ci ent to ca us e, i n a l l l i kel i hood, s i gni fi ca nt s i de
effects .
So wha t we do, therefore, i s a tta ck the dopa mi ne-ACh i mba l a nce from the other s i dea dmi ni s ter a centra l l y a cti ng a nti mus ca ri ni c drug. Note
tha t s i nce we a re dea l i ng wi th s ymptoms a ri s i ng from a rel a ti ve exces s of chol i nergi c i nfl uences , a centra l l y a cti ng chol i nes tera s e i nhi bi tor
(donepezi l or ta cri ne, b) woul d wors en the probl ems by ma ki ng even more ACh a va i l a bl e a t centra l mus ca ri ni c s yna ps es .
175. The answer is d. (Brunton, p 357; Katzung, pp 489, 499, 672.) Bromocri pti ne mi mi cs the a cti on of dopa mi ne i n the bra i n, but i s not a s rea di l y
meta bol i zed a nd i na cti va ted a s the endogenous neurotra ns mi tter. It i s es peci a l l y us eful i n pa rki ns oni s m tha t i s unres pons i ve to L-dopa .
Apomorphi ne (b) i s a l s o a dopa mi ne receptor a goni s t, but i ts s i de effects (ma i nl y emes i s ) precl ude i ts us e for pa rki ns oni s m. Sel egi l i ne (e) i s a n
MAO-B i nhi bi tor. Bel l a donna prepa ra ti ons (c) a re a tropi ne a nd a tropi ne-l i ke a nti mus ca ri ncs . Centra l l y a cti ng a nti mus ca ri ni cs s uch a s benztropi ne
a nd tri hexypheni dyl a re i mporta nt drugs for ma na gi ng s ome pa ti ents wi th pa rki ns oni s m, but they work not by enha nci ng the effects of dopa mi ne
but ra ther by bl ocki ng the centra l effects of ACh. Ama nta di ne (a ) i s a n a nti vi ra l a gent tha t a l s o i s us eful i n s ome ca s es of pa rki ns oni s m. It ei ther
(or both) enha nces the s ynthes i s or i nhi bi ts neurona l reupta ke of dopa mi ne. It i s not a dopa mi ne receptor a goni s t.
176. The answer is b. (Brunton, p 357; Katzung, pp 489, 499, 672.) Bromocri pti ne, a n ergot deri va ti ve, i s a di rect-a cti ng dopa mi ne receptor a goni s t. Its
ma i n us es a re for a djuncti ve ma na gement of Pa rki ns on di s ea s e, a nd for ma na gement of a menorrhea a nd i nferti l i ty (a nd, i f pres ent, ga l a ctorrhea )
due to hyperprol a cti nemi a . It i s a l s o us ed, l ong-term, for ma na gement of s ome pi tui ta ry a denoma s . However, i t ha s ga i ned a ccepta nce a s a n
i mporta nt a djunct (us ua l l y a l ong wi th da ntrol ene, a s noted i n the ques ti on) for ma na gement of neurol epti c ma l i gna nt s yndrome (NMS). Reca l l
tha t NMS i s a ra re but potenti a l l y fa ta l res pons e to tra di ti ona l neurol epti c/a nti ps ychoti c drugs (phenothi a zi nes s uch a s chl orproma zi ne, a nd
butyrophenones s uch a s ha l operi dol ). The newer, a typi ca l a nti ps ychoti cs (cl oza pi ne, ol a nza pi ne, a nd ri s peri done) ma y a l s o ca us e NMS, but the
cl i ni ca l pres enta ti on s eems not to i ncl ude mus cl e ri gi di ty tha t i s us ua l l y a n a ccompa ni ment of NMS ca us ed by phenothi a zi nes or butyrophenones .
177. The answer is d. (Brunton, pp 344-350, 403t, 406t, 410t; Katzung, pp 155, 284-285, 529, 536-537, 1034.) Ma ny pa ti ents , pa rti cul a rl y thos e wi th s i gns a nd
s ymptoms of depres s i on, a nd whether or not they a re trea ted wi th a tri cycl i c a nti depres s a nt (or, for tha t ma tter, a n SSRI), a re pres cri bed tra zodone
to hel p them go to s l eep a t ni ght. Tra zodone ha s not onl y genera l CNS depres s a nt effects (hel pi ng to i nduce s l eep), but a l s o i ntri ns i c
a nti depres s a nt properti es . It i s a common a nd l a rgel y s a fe drug for pa ti ents s uch a s the one des cri bed here.
Tra zodone ha s ma ny effects , one of whi ch i s potenti a ti ng the pos ts yna pti c effects of s erotoni n. As s uch, i t s houl d not be pres cri bed for pa ti ents
ta ki ng a nons el ecti ve monoa mi ne oxi da s e (MAO) i nhi bi tor for depres s i on. (Thus , a ns wer a i s i ncorrect. And, beca us e of a hos t of a dvers e effects
a nd drug-drug i ntera cti ons tha t ma y prove fa ta l , nons el ecti ve MAO i nhi bi tors a re, a t bes t, ra rel y pres cri bed for a nyone.) Suma tri pta n (c), whi ch
a dds s erotoni n to s yna ps es a nd i s often pres cri bed to a bort mi gra i ne hea da ches , i s contra i ndi ca ted for pa ti ents ta ki ng a nti depres s a nts
pa rti cul a rl y s el ecti ve s erotoni n reupta ke i nhi bi tors (SSRIs , eg, fl uoxeti ne, s ertra l i ne, es ci ta l opra m, s evera l others ) or MAO i nhi bi tors . Us e of
tra zodone a nd a n SSRI ca rri es a s l i ghtl y i ncrea s ed ri s k of s erotoni n s yndrome. Gi vi ng both tra zo-done a nd a nons el ecti ve MAO i nhi bi tor to a
pa ti ent i s a s s oci a ted wi th a grea tl y i ncrea s ed ri s k of s erotoni n s yndrome.

Cardiovascular Pharmacology
Anti a ngi na l s
Anti a rrhythmi cs
Anti coa gul a nts
Anti hyperl i pi demi cs
Anti hypertens i ves
Anti pl a tel et drugs
Hea rt fa i l ure thera py
Thrombol yti cs (fi bri nol yti cs )
Va s odi l a tors

Questions
178. Your pa ti ent i s a 50-yea r-ol d ma n wi th Type 1 (i ns ul i n-requi ri ng) di a betes , norma l rena l functi on, a nd no mi croa l bumi nuri a . Al though hi s
Hb A1c l evel s a re a ccepta bl e, beca us e of hi s l i fes tyl e a nd ea ti ng ha bi ts he ha s experi enced more tha n a few epi s odes of s ymptoma ti c
hypogl ycemi a fol l owi ng i ns ul i n i njecti ons . He currentl y ha s a s ymptoma ti c hyperuri cemi a , but he ha s ha d s evera l a tta cks of a cute gout over the l a s t
5 yea rs . Toda y you di a gnos e hypertens i on tha t mus t be trea ted. Whi ch a nti hypertens i ve drug woul d be the mos t ra ti ona l fi rs t choi ce for s ta rti ng
hi s a nti hypertens i ve thera py?
a . Angi otens i n-converti ng enzyme (ACE) i nhi bi tor or a ngi otens i n receptor bl ocker
b. -a drenergi c bl ocker
c. Ni fedi pi ne
d. Thi a zi de di ureti c
e. Vera pa mi l or di l ti a zem
179. A pa ti ent i s hos pi ta l i zed a nd wa i ti ng for corona ry a ngi ogra phy. Hi s hi s tory i ncl udes a ngi na pectori s tha t i s brought on by modes t exerci s e,
a nd i s a ccompa ni ed by tra ns i ent el ectroca rdi ogra phi c cha nges cons i s tent wi th myoca rdi a l i s chemi a . There i s no evi dence of corona ry va s os pa s m.
In the hos pi ta l , he i s recei vi ng ni trogl yceri n a nd morphi ne (both by s l ow IV i nfus i on), pl us oxygen vi a na s a l ca nnul a .
He s uddenl y devel ops epi s odes of ches t di s comfort. Hea rt ra te duri ng thes e epi s odes ri s es to 170 to 190 bea ts /mi n; bl ood pres s ure rea ches 180
to 200/110 to 120 mm Hg, a nd promi nent fi ndi ngs on the ECG a re runs of ventri cul a r ectopi c bea ts tha t termi na te s ponta neous l y, pl us ST-s egment
el eva ti on.
Al though there a re s evera l thi ngs tha t need to be done for i mmedi a te ca re, wha t drug woul d you a dmi ni s ter to remedy (a t l ea s t tempora ri l y) the
ma jori ty of thes e s i gns a nd s ymptoms a nd pos e the l owes t ri s k of doi ng further ha rm?
a . As pi ri n
b. Ca ptopri l
c. Furos emi de
d. La beta l ol
e. Li doca i ne
f. Ni trogl yceri n (i ncrea s ed dos e a s a bol us )
g. Pra zos i n
180. A 55-yea r-ol d woma n ha s jus t been di a gnos ed wi th Sta ge 2 es s enti a l /pri ma ry hypertens i on, a nd you concl ude tha t i t i s ti me to s ta rt drug
thera py for i t. She a l s o tends to be ta chyca rdi c. Notes wri tten by her ophtha l mol ogi s t i ndi ca te tha t s he ha s chroni c open-a ngl e gl a ucoma . Whi ch
one of the fol l owi ng drugs woul d be the mos t ra ti ona l choi ce for thi s woma n, gi ven onl y the i nforma ti on pres ented i n thi s ques ti on, beca us e i t
mi ght hel p control both the hypertens i on a nd the i ncrea s ed i ntra ocul a r pres s ure?
a . Ca ptopri l
b. Di l ti a zem
c. Hydrochl orothi a zi de
d. Ti mol ol
e. Vera pa mi l
181. Nebi vol ol i s a fa i rl y new a nd ra ther s el ecti ve 1 -a drenergi c bl ocker tha t i s i ndi ca ted for ma na gi ng es s enti a l hypertens i on. The drug a l l egedl y
ca us es fewer s i de effects tha n mos t other -bl ockers , a nd orthos ta ti c hypotens i on does not occur even wi th ful l thera peuti c dos es . The drug ha s
no effects on cha nges of tota l peri phera l res i s ta nce i nduced by i nfus i on of phenyl ephri ne or a dmi ni s tra ti on a n a mpheta mi ne. Nebi vol ol s
a nti hypertens i ve mecha ni s m of a cti on cl ea rl y i nvol ves thos e common to a l l -bl ockers , but a nother mecha ni s m contri butes to the overa l l effect.
Gi ven your genera l knowl edge of bl ood pres s ure control a nd of a uto-nomi c/ca rdi ova s cul a r pha rma col ogy, whi ch one of the fol l owi ng i s the other
mos t l i kel y mecha ni s m by whi ch nebi vol ol hel ps l ower TPR a nd bl ood pres s ure?
a . Competi ti vel y bl ocks pos ts yna pti c (1 ) a drenergi c receptors
b. Competi ti vel y bl ocks pres yna pti c (2 ) a drenergi c receptors
c. Increa s es ni tri c oxi de forma ti on
d. Increa s es s ynthes i s of thromboxa ne A2
e. Inhi bi ts ca techol O-methyl tra ns fera s e (COMT)
182. A 44-yea r-ol d woma n i s tra ns ported to the emergency depa rtment a fter cons umi ng wha t mi ght be a l etha l dos e of a -a drenergi c bl ocker tha t
ha s no i ntri ns i c va s odi l a tor a cti vi ty. Des pi te a dmi ni s tra ti on of l a rge dos es of i s oproterenol to overcome the bl ocka de, her ca rdi a c output i s

da ngerous l y l ow beca us e hea rt ra te a nd s troke vol ume a re profoundl y depres s ed. Whi ch one of the fol l owi ng a pproa ches i s mos t l i kel y to prove
benefi ci a l , i f not l i fes a vi ng?
a . Admi ni s ter gl uca gon
b. Admi ni s ter phenyl ephri ne
c. Admi ni s ter phentol a mi ne
d. Swi tch from i s oproterenol to ephedri ne
e. Swi tch from i s oproterenol to epi nephri ne
183. At hi gh (but not neces s a ri l y toxi c) bl ood l evel s , a ca rdi ova s cul a r drug ca us es ma ny s i gns a nd s ymptoms tha t res embl e wha t you s ee wi th l owgra de a s pi ri n toxi ci ty (s a l i cyl i s m): l i ght-hea dednes s , ti nni tus , a nd vi s ua l di s turba nces s uch a s di pl opi a . Wha t drug mos t l i kel y ca us ed thes e
res pons es ?
a . Atropi ne
b. Ca ptopri l
c. Dobuta mi ne
d. Propra nol ol
e. Qui ni di ne
184. A pa ti ent ha s peri odi c epi s odes of pa roxys ma l s upra ventri cul a r ta chyca rdi a (PSVT). Wha t drug woul d be mos t s ui ta bl e for outpatient prophylaxis
of thes e worri s ome el ectrophys i ol ogi c events ?
a . Adenos i ne
b. Li doca i ne
c. Ni fedi pi ne
d. Ni trogl yceri n
e. Vera pa mi l
185. You a nd a col l ea gue a re di s cus s i ng whi ch -bl ocker to us e, a djuncti vel y, to control bl ood pres s ure i n a pheochromocytoma pa ti ent before
s urgery for a n a drena l ectomy ca n be performed. Your col l ea gue correctl y s ta tes tha t phenoxybenza mi ne i s the preferred drug. You s ta te tha t
pra zos i n woul d be a better choi ce. Whi ch s ta tement a bout pra zos i n i s correct i n compa ri s on wi th phenoxybenza mi ne, a nd mi ght a ctua l l y s upport
your propos a l tha t i t woul d be a better choi ce?
a . Ca us es not onl y peri phera l -bl ocka de but a l s o s uppres s es a drena l epi nephri ne rel ea s e
b. Ha s a l onger dura ti on of a cti on, whi ch ena bl es l es s frequent dos i ng
c. Ha s good i ntri ns i c -bl ocki ng a cti vi ty, phenoxybenza mi ne does not
d. Overdos es , a nd the hypotens i on i t ma y ca us e, a re ea s i er to ma na ge pha rma col ogi ca l l y
e. Wi l l not ca us e orthos ta ti c hypotens i on, whi ch i s a common cons equence of phenoxybenza mi ne
186. A pa ti ent wi th a hi s tory of a tri a l fi bri l l a ti on devel ops a cute corona ry s yndrome a nd i s a dmi tted to the hos pi ta l s corona ry ca re uni t. As of
toda y, he ha s been recei vi ng otherwi s e proper dos es of a drug for 5 da ys s tra i ght. Dos i ng wa s done correctl y, s ta rti ng wi th us ua l ma i ntena nce
dos es ; no l oa di ng dos e s tra tegy wa s us ed. Then, a nd ra ther preci pi tous l y, the pa ti ent devel ops s i gns a nd s ymptoms of wi des prea d thromboti c
events , a nd pl a tel et counts decl i ne s i gni fi ca ntl y concomi ta nt wi th the thrombos i s . The pa ti ent di es wi thi n 24 hours of the ons et of s i gns a nd
s ymptoms . Wha t drug mos t l i kel y ca us ed thes e ul ti ma tel y fa ta l res pons es ?
a . Abci xi ma b
b. Cl opi dogrel
c. Hepa ri n (unfra cti ona ted)
d. Ni fedi pi ne
e. Wa rfa ri n
187. A 65-yea r-ol d ma n wi th hea rt fa i l ure i s una bl e to cl i mb a fl i ght of s ta i rs wi thout experi enci ng dys pnea . After s evera l yea rs of thera py wi th
ca rvedi l ol , ca ptopri l , l ow dos es of l a beta l ol , a nd furos emi de, the thera peuti c pl a n proba bl y needs to cha nge now. You empi ri ca l l y a dd di goxi n to
i mprove ca rdi a c mus cl e contra cti l i ty. Wi thi n 4 weeks , he ha s a ma rked i mprovement i n hi s s ymptoms . Wha t bes t des cri bes the ma i n cel l ul a r a cti on
of di goxi n tha t a ccounts for i ts a bi l i ty to i mprove hi s ca rdi ova s cul a r functi on a nd overa l l hemodyna mi c s ta tus ?
a . Acti va tes 1 -a drenergi c receptors
b. Fa ci l i ta tes GTP bi ndi ng to s peci fi c G protei ns
c. Increa s es mi tochondri a l ca l ci um (Ca 2+) rel ea s e
d. Inhi bi ts s a rcol emma l Na +-K+-ATPa s e
e. Sti mul a tes cycl i c a denos i ne 5-monophos pha te (cAMP) s ynthes i s
188. A pa ti ent wi th newl y di a gnos ed es s enti a l (pri ma ry) hypertens i on s ta rts trea tment wi th a commonl y us ed a nti hypertens i ve drug a t a dos e tha t
i s cons i dered to be thera peuti c for the va s t ma jori ty of pa ti ents . Soon a fter s ta rti ng thera py the pa ti ent experi ences crus hi ng ches t di s comfort. ECG
cha nges s how myoca rdi a l i s chemi a . Studi es i n the ca rdi a c ca th l a b s how epi s odes of corona ry va s os pa s m, a nd i t i s l i kel y the a nti hypertens i ve
drug provoked the va s os pa s m. Whi ch a nti hypertens i ve drug or drug cl a s s mos t l i kel y ca us ed the i s chemi a a nd the a ngi na ?
a . Atenol ol
b. Di l ti a zem
c. Hydrochl orothi a zi de
d. Los a rta n
e. Metol a zone

189. A pa ti ent wi th chroni c-s ta bl e (effort-i nduced) a ngi na i s on prophyl a cti c -bl ocker (propra nol ol ) thera py, wi th s ubl i ngua l ni trogl yceri n (NTG)
us ed a s needed for ma na gi ng a cute a ngi na . One da y he experi ences pa rti cul a rl y s evere a ngi na a nd ta kes the us ua l l y recommended dos e of
s ubl i ngua l NTG. Hi s di s comfort i s not reduced a t a l l . Seeki ng rel i ef, he repea ts the us ua l recommended NTG dos e frequentl y over a peri od of
a bout 10 mi nutes , a nd now ha s ta ken fa r too much of the ni trova s odi l a tor. An el ectroca rdi ogra m ta ken by the pa ra medi cs , who were ca l l ed for the
pa ti ents emergency, s hows cha nges cons i s tent wi th s evere myoca rdi a l i s chemi a . The pa ti ent goes i nto ca rdi a c a rres t a nd ca nnot be res us ci ta ted.
Wha t i s the mos t l i kel y ca us e of or contri buti ng fa ctor to the pa ti ents res pons es to the exces s i ve dos a ge of NTG?
a . Cya ni de, a toxi c meta bol i te of NTG, a ccumul a ted
b. Ni trogl yceri n di rectl y i nduced corona ry va s ocons tri cti on
c. The NTG l owered a rteri a l pres s ure exces s i vel y
d. The pa ti ent ha s va s os pa s ti c (va ri a nt or Pri nzmeta l ) a ngi na , not chroni c-s ta bl e
e. The -bl ockers i ntri ns i c va s odi l a tor a cti vi ty potenti a ted tha t of the NTG
190. A 50-yea r-ol d ma n ha s a l ong hi s tory of a s ymptoma ti c hyperuri cemi a (el eva ted uri c a ci d l evel s ), a nd you a re a bout to s ta rt thera py for newl y
di a gnos ed es s enti a l hypertens i on (BP 136/90 mm Hg, ba s ed on repea ted mea s urements wi th the pa ti ent s upi ne a nd a t res t). Whi ch
a nti hypertens i ve drug i s mos t l i kel y to i ncrea s e hi s uri c a ci d l evel s further, a nd i n doi ng s o, be mos t l i kel y to ca us e the mos t common cl i ni ca l
pres enta ti on of the hyperuri cemi a gout?
a . Hydrochl orothi a zi de
b. La beta l ol
c. Los a rta n
d. Ra mi pri l
e. Vera pa mi l
191. We conduct a n experi ment to a s s es s the effects of other drugs on the a nti -pl a tel et a ggrega tory effects of a s pi ri n. In ea ch ca s e we s a mpl e
venous bl ood from a n otherwi s e hea l thy pa ti ent, centri fuge the bl ood to obta i n a pl a tel et-ri ch fra cti on, a nd put s a mpl es of the pl a tel ets i nto a n
i ns trument tha t a ccura tel y mea s ures pl a tel et a ggrega ti on in vitro. We then a cti va te the pl a tel ets by a ddi ng ADP (or col l a gen; ma kes no di fference).
Res ul ts a re gra phed bel ow.
The control (top l i ne) condi ti on refl ects res ul ts from the pa ti ents who ha s been ta ki ng no drugs a t a l l . The bottom tra ce s hows a ggrega ti on of
pl a tel ets i s ol a ted from the pa ti ent a fter they ha ve ta ken a s pi ri n (ASA; 81 mg/da y) for 14 da ys i n a row. We s top a s pi ri n for 2 weeks to ens ure tha t
the pa ti ent ha s no a s pi ri n i n thei r bl ood. Then we res ta rt 81 mg/da y aspirin plus an unknown drug ta ken wi th ea ch a s pi ri n ta bl et for fi na l 2 weeks .
The pl a tel ets ta ken a t the end of the 14 da ys s how onl y s l i ght i nhi bi ti on of pl a tel et a ggrega ti onres ul ts not s i gni fi ca ntl y from control .
The res ul ts a re s hown here:

Whi ch drug wa s ta ken wi th the a s pi ri n a nd i nhi bi ted i ts a ggrega tory effects i n res pons e to ADP or col l a gen?
a . Aceta mi nophen
b. Cl opi dogrel
c. Da bi ga tra n
d. Ibuprofen
e. Wa rfa ri n
192. A 57-yea r-ol d pa ti ent compl a i ns of mus cl e a ches , pa i n, a nd tendernes s . Thes e a ffect the l egs a nd trunk. There i s no fever, brui s i ng, or a ny
recent hi s tory of mus cl e tra uma or s tra i ns (a s from exces s i ve exerci s e). He ha s myogl obi nuri a , a cl i ni ca l l y s i gni fi ca nt fa l l of crea ti ni ne cl ea ra nce,
a nd a ri s e of pl a s ma crea ti ne ki na s e (CK) to l evel s nea rl y ten ti mes the upper l i mi t of norma l . Whi ch drug i s the mos t l i kel y ca us e of thes e
fi ndi ngs ?
a . As pi ri n (l ow dos e) for i ts ca rdi oprotecti ve/a nti pl a tel et effects
b. Ca ptopri l for hypertens i on a nd hea rt fa i l ure
c. Ca rvedi l ol for hypertens i on, hea rt fa i l ure, a nd a ngi na prophyl a xi s
d. Furos emi de a s a djuncti ve ma na gement of hi s hea rt fa i l ure
e. Ros uva s ta ti n to control hi s hyperchol es terol emi a a nd the a s s oci a ted ri s ks
193. A corona ry a rtery s a mpl e wa s removed from a hea l thy a ni ma l , put i ns i de a s ui ta bl e oxygena ted s a l t a nd nutri ent s ol uti on, a nd connected to a
tra ns ducer tha t mea s ured i ncrea s es (contra cti on) or decrea s es (rel a xa ti on) of s mooth mus cl e tens i on (force). ACh wa s then a dded to gi ve the
cumul a ti ve concentra ti ons s hown bel ow.
As expected, i n the control s etti ng (l eft) ACh ca us ed concentra ti on-dependent va s orel a xa ti on (equi va l ent to va s odi l a ti on i n the i nta ct a ni ma l ).
The ACh wa s wa s hed out s evera l ti mes , control condi ti ons returned. The condi ti ons were ma ni pul a ted, a nd then the ACh dos e-res pons e
experi ment wa s repea ted (ri ght). Now the da ta s how i ncrea s ed tens i on devel oped by the mus cl e s a mpl e (va s ocons tri cti on i n vi vo) i n res pons e to
ACh a nd i ncrementa l i ncrea s es of i ts concentra ti on.

Whi ch one of the fol l owi ng s umma ri zes wha t wa s mos t l i kel y done to the ves s el under the experi menta l condi ti ons , before retes ti ng the
res pons es to a dded ACh? As s ume tha t the va s cul a r res pons es i n thi s a ni ma l model a re i denti ca l to thos e tha t woul d occur i n a huma n.
a . Endothel i um wa s removed mecha ni ca l l y
b. Is oproterenol wa s a dded ri ght before ACh
c. Mus ca ri ni c receptors were bl ocked wi th a tropi ne
d. Sa mpl e wa s pretrea ted wi th pra zos i n
e. Ti s s ue wa s pretrea ted wi th botul i num toxi n
194. A 28-yea r-ol d woma n i s recei vi ng drug thera py for es s enti a l (pri ma ry) hypertens i on. She s ubs equentl y becomes pregna nt. You rea l i ze tha t the
drug s hes been ta ki ng for her hi gh bl ood pres s ure ca n ha ve s eri ous , i f not fa ta l , effects on the fetus (i t i s i n pregna ncy ca tegory X). As a res ul t, you
s top the current a nti hypertens i ve drug a nd s ubs ti tute a nother tha t i s deemed to be equi effi ca ci ous i n terms of her bl ood pres s ure, a nd s a fer for
the fetus . Whi ch drug wa s s he mos t l i kel y ta ki ng before s he beca me pregna nt?
a . -Methyl dopa
b. Ca ptopri l

c. Furos emi de
d. La beta l ol
e. Vera pa mi l
195. We trea t a pa ti ent wi th a drug tha t a ffects the cl otti ng-thrombol yti c s ys tems for a ti me s uffi ci ent to l et the drugs effects a nd bl ood l evel s
s ta bi l i ze a t a thera peuti c l evel . We then i s ol a te pl a tel ets from a bl ood s a mpl e a nd tes t thei r i n vi tro a ggrega tory res pons es to ADP, col l a gen, PAF,
a nd thromboxa ne A2 . Aggrega tory res pons es to ADP a re i nhi bi ted; res pons es to the other pl a tel et proa ggrega tory a goni s ts a re una ffected. Whi ch
drug exhi bi ts thes e properti es ?
a . As pi ri n
b. Bi va l i rudi n
c. Cl opi dogrel
d. Hepa ri n
e. Wa rfa ri n
196. Your newl y di a gnos ed hypertens i ve pa ti ent ha s va s os pa s ti c a ngi na . Whi ch drug or drug cl a s s woul d be the mos t ra ti ona l for s ta rti ng a nti hypertens i ve thera py beca us e i t exerts not onl y a nti hypertens i ve effects , but a l s o di rectl y l owers myoca rdi a l oxygen dema nd a nd cons umpti on a nd
tends to i nhi bi t cel l ul a r proces s es tha t otherwi s e fa vor corona ry va s o-s pa s m? As s ume there a re no other s peci fi c contra i ndi ca ti ons to the drug you
choos e.
a . Angi otens i n-converti ng enzyme (ACE) i nhi bi tor or a ngi otens i n receptor bl ocker
b. -Adrenergi c bl ocker
c. Ni fedi pi ne
d. Thi a zi de di ureti c
e. Vera pa mi l (or di l ti a zem)
197. You a re revi ewi ng the medi ca ti on hi s tory of a 59-yea r-ol d ma n. He ha s been ta ki ng ra mi pri l a nd pra va s ta ti n for the l a s t 5 yea rs . Other
medi ca ti ons i ncl ude metformi n for type 2 di a betes mel l i tus , a nd es ci ta l opra m to hel p ma na ge hi s depres s i on. At hi s l a s t cl i ni c vi s i t, a yea r a go,
he wa s tol d to conti nue hi s current medi ca ti ons but he wa s a l s o s ta rted on s l ow-rel ea s e ni a ci n beca us e di et, exerci s e a nd other l i fes tyl e
modi fi ca ti ons , a nd hi s current medi ca ti ons were not a dequa te. Wha t wa s the mos t l i kel y rea s on for a ddi ng the ni a ci n?
a . Countera ct defi ci enci es of B-vi ta mi n a bs orpti on ca us ed by the a nti depres s a nt
b. Countera ct pol ypha gi a , a nd over-ea ti ng, ca us ed by the metformi n.
c. Lower HDL a nd tri gl yceri de l evel s tha t di d not res pond a dequa tel y to the s ta ti n
d. Prevent s ta ti n-i nduced neuropa thy
e. Sl ow the progres s i on of di a beti c nephropa thy ca us ed by the ACE i nhi bi tor
198. Qui ni di ne i s ordered for a pa ti ent wi th recurrent a tri a l fi bri l l a ti on a nd who refus es a ny i nterventi ons other tha n drugs i n a n a ttempt to
termi na te a nd control the a rrhythmi a . He ha s s ome pul mona ry fi bros i s a nd a thyroi d di s orderboth l ea di ng you to concl ude tha t a mi oda rone
thera py mi ght not be the bes t a pproa ch. Whi ch s ta tement a ppl i es to the qui ni di ne?
a . Decrea s es SA noda l a utoma ti ci ty due to a s trong a nti chol i nergi c/va gol yti c effect
b. Is l i kel y to i ncrea s e bl ood pres s ure vi a a di rect va s ocons tri ctor effect
c. Is contra i ndi ca ted i f the pa ti ent a l s o requi res a nti coa gul a nt thera py
d. Tends to i ncrea s e el ectri ca l i mpul s e conducti on vel oci ty through the AV node
e. Wi l l i ncrea s e ca rdi a c contra cti l i ty (pos i ti ve i notropi c effect) i ndependent of i ts a nti a rrhythmi c effects
199. A woma n ha s recei ved a ca rdi ova s cul a r drug tha t i s a bs ol utel y contra i ndi ca ted (ca tegory X) i n pregna ncy, but i n the a bs ence of pregna ncy
woul d ha ve been deemed benefi ci a l beca us e of a pa rti cul a r ca rdi ova s cul a r di s order s he ha s . Unfortuna tel y, nei ther s he nor her phys i ci a n (whom
s he ra rel y vi s i ted) knew s he wa s pregna nt unti l s he ha d jus t s ta rted the s econd tri mes ter. The drug i s s topped (a nd a s ui ta bl e a nd s a fer
a l terna ti ve i s s ta rted), but i t i s too l a te. Her ba by i s del i vered prema turel y, a nd s ti l l born. It i s obvi ous from exa mi na ti on of the ba by tha t there i s a
na s a l deformi ty: the nos e i s fl a ttened i nto the fa ce, wi th no a ppa rent bri dge. Sta nda rd x-ra ys revea l s ti ppl i ng of a l l the epi phys es . Thes e
res pons es a re cha ra cteri s ti c of whi ch drug?
a . Cl oni di ne
b. Hepa ri n, l ow mol ecul a r wei ght (eg, enoxa pa ri n)
c. Hydrochl orothi a zi de
d. Ni trogl yceri n
e. Wa rfa ri n
200. A pa ti ent who ha s been ta ki ng a n ora l a nti hypertens i ve drug for a bout a yea r devel ops a pos i ti ve Coombs tes t, a nd now you a re worri ed
a bout the pos s i bi l i ty (a l though l ow) tha t hemol yti c a nemi a ma y devel op i f the drug i s conti nued. Whi ch drug wa s the mos t l i kel y ca us e?
a . Ca ptopri l
b. Cl oni di ne
c. La beta l ol
d. Methyl dopa
e. Pra zos i n
201. A pa ti ent pres ents wi th s evere hypertens i on a nd ta chyca rdi a . Bl ood chemi s try res ul ts , ra di ol ogi c s tudi es , a nd the overa l l cl i ni ca l pres enta ti on
poi nt to pheochromocytoma . The tumor a ppea rs opera bl e, but the pa ti ent wi l l ha ve to wa i t a coupl e of weeks for the a drena l ectomy. We pres cri be
phenoxybenza mi ne i n the i nteri m, wi th the goa l of s uppres s i ng s ome of the ma jor s i gns a nd s ymptoms ca us ed by the tumor a nd the ma s s i ve

a mounts of epi nephri ne i t i s rel ea s i ng. Whi ch of the fol l owi ng bes t s umma ri zes wha t phenoxybenza mi ne does , or how i t a cts ?
a . Control s bl ood pres s ure by bl ocki ng -a drenergi c receptors i n the peri phera l va s cul a ture
b. Control s hea rt ra te by s el ecti vel y bl ocki ng 1 -a drenergi c receptors
c. Inhi bi ts ca techol a mi ne s ynthes i s i n the a drena l (s upra rena l ) medul l a
d. Lowers bl ood pres s ure by i nhi bi ti ng a ngi otens i n converti ng enzyme
e. Sti mul a tes ca techol -O-methyl tra ns fera s e, thereby fa ci l i ta ti ng epi nephri nes meta bol i c i na cti va ti on
202. A 30-yea r-ol d ma n who ha s a hi s tory of a s thma ha s jus t been di a gnos ed Sta ge 1 es s enti a l hypertens i on. He regul a rl y us es a n i nha l ed
corti cos teroi d, whi ch s eems to work wel l a s a control medi ca ti on, but a l s o needs to us e a n a l buterol i nha l er a bout once every 3 weeks for
s uppres s i on of a s thma a tta cks (res cue thera py). Whi ch a nti hypertens i ve drug or drug cl a s s pos es the grea tes t ri s k of exa cerba ti ng the pa ti ents
a s thma a nd countera cti ng the des i red pul mona ry effects of the a l buterol , even though i t mi ght control hi s bl ood pres s ure wel l ?
a . Di l ti a zem
b. Hydrochl orothi a zi de
c. La beta l ol
d. Ra mi pri l
e. Vera pa mi l
203. Di goxi n a ffects a hos t of ca rdi a c el ectrophys i ol ogi c properti es . Some of i ts effects a re ca us ed di rectl y by the drug. Others a re i ndi rect: they ma y
i nvol ve i ncrea s i ng va ga l tone to the hea rt or other compens a ti ons tha t a ri s e when ca rdi a c output i s i mproved i n a pa ti ent wi th hea rt fa i l ure. For
s ome pa ra meters the di rect a nd i ndi rect effects ma y be qua l i ta ti vel y (but not qua nti ta ti vel y) oppos i ng, but one wi l l predomi na te over the other.
Wha t i s a n expected a nd us ua l l y predomi na nt effect of the drug?
a . Increa s ed ra te of SA noda l depol a ri za ti on
b. Reduced a tri a l a utoma ti ci ty
c. Reduced ventri cul a r a utoma ti ci ty
d. Sl owed AV noda l conducti on vel oci ty
e. Sl owed conducti on vel oci ty through the a tri a l myoca rdi um a nd Hi s -Purki nje s ys tem
204. A pa ti ent ha s Sta ge 2 es s enti a l hypertens i on a nd hea rt fa i l ure. After eva l ua ti ng the res pons es to ma ny other a nti hypertens i ve drugs , a l one
a nd i n combi na ti on, the phys i ci a n concl udes tha t i t woul d be rea s ona bl e to try hydra l a zi ne. Whi ch drug(s ) i s /a re l i kel y to be needed, a s a dd-ons
(a djuncts ), to ma na ge the expected a nd unwa nted ca rdi ova s cul a r a nd rena l s i de effects of the hydra l a zi ne?
a . Ca ptopri l pl us ni fedi pi ne
b. Di goxi n pl us s pi ronol a ctone
c. Di goxi n pl us vi ta mi n K
d. Hydrochl orothi a zi de a nd a -bl ocker
e. Ni trogl yceri n
f. Tri a mterene pl us a mi l ori de
205. A hea l thy a dul t s ubject pa rti ci pa ti ng i n a cl i ni ca l tri a l i s gi ven a n i ntra venous i njecti on of a tes t drug. Both bl ood pres s ure a nd tota l
peri phera l res i s ta nce ri s e promptl y. Thi s i s fol l owed i mmedi a tel y by a reducti on of hea rt ra te. In repea ted experi ments we fi nd tha t the
va s opres s or res pons e i s not a ffected by pretrea tment wi th pra zos i n. However, pretrea tment wi th a tropi ne prevents the ca rdi a c chronotropi c
res pons e. The tes t drug wa s mos t l i kel y whi ch of the fol l owi ng?
a . Angi otens i n II
b. Dobuta mi ne
c. Is oproterenol
d. Norepi nephri ne
e. Phenyl ephri ne
206. We a re a dmi ni s teri ng ni troprus s i de i ntra venous l y for control of s evere hypertens i on duri ng s urgery. The dos e ha s gotten too hi gh, a nd the
drug ha s been a dmi ni s tered too l ong. Refra ctori nes s to the a nti hypertens i ve effects ha s occurred. Bl ood pres s ure i s ri s i ng, a nd other s i gns a nd
s ymptoms of potenti a l l y s evere toxi ci ty devel op. Wha t ni troprus s i de meta bol i te a ccounts for or a t l ea s t contri butes to thes e probl ems ?
a . A hi ghl y effi ca ci ous -a drenergi c a goni s t
b. An extra ordi na ri l y potent a nd i rrevers i bl e Na -K-ATPa s e i nhi bi tor
c. An i rrevers i bl e a nta goni s t for a ngi otens i n a t the A-II receptors
d. Cya ni de
e. Ni tri c oxi de
207. A 66-yea r-ol d ma n who l i ves i n a s ma l l rura l town, a nd who ha s been trea ted by hi s fa mi l y doctor for deca des , pres ents a t your medi ca l center.
He ha s corona ry a theros cl eros i s a nd mi l d hea rt fa i l ure tha t ha s been trea ted for the l a s t 10 yea rs wi th di goxi n a nd s evera l other drugs . Hi s chi ef
compl a i nts a re na us ea , vomi ti ng, a nd di a rrhea , whi ch ha ve not res ol ved des pi te a recommenda ti on from hi s phys i ci a n to ta ke pres cri pti on
medi ca ti ons for thos e condi ti ons . Hi s ECG revea l s a bi gemi na l rhythm a nd s econd-degree hea rt bl ock. A drug-drug i ntera cti on i s s us pected. Wha t
coa dmi ni s tered drug mos t l i kel y provoked the probl em?
a . Ca ptopri l
b. Chol es tyra mi ne
c. Furos emi de
d. Lova s ta ti n

e. Ni trogl yceri n
208. We ha ve a pa ti ent who i s di a gnos ed wi th va ri a nt (va s os pa s ti c) a ngi na . Whi ch drug woul d be mos t a ppropri a te, a nd genera l l y rega rded a s
mos t effecti ve, for l ong-term thera py a i med a t reduci ng the i nci dence or s everi ty of the corona ry va s os pa s m?
a . As pi ri n
b. Atorva s ta ti n
c. Di l ti a zem
d. Ni trogl yceri n
e. Propra nol ol
209. A 56-yea r-ol d ma n ha s hea rt fa i l ure. Hi s fa mi l y doctor, who ha s been trea ti ng hi m s i nce he wa s a young l a d, ha s been trea ti ng hi m wi th
di goxi n, furos emi de, a nd tri a mterene for s evera l yea rs . The pa ti ent now devel ops a tri a l fi bri l l a ti on, a nd s o hi s doctor s ta rts qui ni di ne a nd
cl opi dogrel . Wha t i s the mos t l i kel y outcome of a ddi ng the qui ni di ne?
a . Devel opment of s i gns a nd s ymptoms of qui ni di ne toxi ci ty (ci nchoni s m)
b. Hypona tremi a due to qui ni di nes a bi l i ty to enha nce di ureti c-i nduced s odi um l os s
c. Ons et of s i gns a nd s ymptoms of di goxi n toxi ci ty
d. Preci pi tous devel opment of hypoka l emi a
e. Prompt s uppres s i on of ca rdi a c contra cti l i ty, ons et of a cute hea rt fa i l ure
210. Fl eca i ni de a nd propa fenone a re i n Va ugha n-Wi l l i a ms (a nti a rrhythmi c) Cl a s s I-C. Wha t i s the cl i ni ca l l y rel eva nt ta ke home mes s a ge a bout
thi s cl a s s of drugs ?
a . Are onl y gi ven for a rrhythmi a s duri ng a cute myoca rdi a l i nfa rcti on
b. Are pa rti cul a rl y s ui ted for pa ti ents wi th l ow ejecti on fra cti ons or ca rdi a c output
c. Are preferred drugs (drugs of choi ce) for rel a ti vel y i nnocuous ventri cul a r a rrhythmi a s
d. Ca us e pul mona ry fi bros i s a nd a hypothyroi d-l i ke s yndrome when gi ven l ong term
e. Ha ve a s i gni fi ca nt pro-a rrhythmi c effect (i nducti on of l etha l a rrhythmi a s )
211. You wa nt to compa re a nd contra s t the ca rdi a c a nd hemodyna mi c profi l es of i mmedi a te-a cti ng di hydropyri di ne-type ca l ci um cha nnel bl ockers
(CCBs ) a nd the nondi hydropyri di ne, vera pa mi l (or di l ti a zem). Whi ch of the fol l owi ng bes t s umma ri zes how, i n genera l , a nondi hydropyri di ne CCB
di ffers from ni fedi pi ne?
a . Ca us es a much hi gher i nci dence of refl ex ta chyca rdi a
b. Ca us es s i gni fi ca nt dos e-dependent s l owi ng of AV noda l conducti on vel oci ty
c. Ca us es s i gni fi ca nt venodi l a ti on, l ea di ng to profound orthos ta ti c hypotens i on
d. Ha s s i gni fi ca nt a nd di rect pos i ti ve i notropi c effects
e. Is bes t us ed i n conjuncti on wi th a -bl ocker or di goxi n
212. A pa ti ent ha s recei ved exces s i ve dos es of ni troprus s i de, a nd toxi c ma ni fes ta ti ons a re devel opi ng i n res pons e to a meta bol i te. Whi ch of the
fol l owi ng drugs or drug groups woul d be mos t effecti ve i n l i mi ti ng a nd ul ti ma tel y countera cti ng the effects of the toxi c product?
a . Ami noca proi c a ci d
b. Hydroxycoba l a mi n
c. Prota mi ne s ul fa te
d. Thrombi n
e. Vi ta mi n K
213. A pa ti ent wi th Sta ge 2 es s enti a l hypertens i on i s trea ted wi th us ua l l y effecti ve dos es of a n ACE i nhi bi tor. After a s ui ta bl e peri od of ti me, bl ood
pres s ure ha s not been l owered s a ti s fa ctori l y. The pa ti ent ha s been compl i a nt wi th drug thera py a nd other recommenda ti ons (eg, wei ght
reducti on, exerci s e). A thi a zi de i s a dded to the ACE i nhi bi tor regi men. Wha t i s the mos t l i kel y a nd ea rl i es t (a nd proba bl y tra ns i ent) untowa rd
outcome of thi s drug a dd-on, for whi ch you s houl d moni tor cl os el y?
a . Fa l l of bl ood pres s ure s uffi ci ent to ca us e s yncope
b. Hypoka l emi a due to s ynergi s ti c effects of the ACE i nhi bi tor a nd the thi a zi de on rena l pota s s i um excreti on
c. Ons et of a cute hea rt fa i l ure from depres s i on of ventri cul a r contra cti l i ty
d. Pa ra doxi ca l hypertens i ve cri s i s
e. Sudden prol onga ti on of the P-R i nterva l a nd i ncrea s i ng degrees of hea rt bl ock
214. A 45-yea r-ol d ma n pos tmyoca rdi a l i nfa rcti on (MI) i s bei ng trea ted wi th s evera l drugs , i ncl udi ng i ntra venous unfra cti ona ted hepa ri n. Stool
gua i a c on a dmi s s i on wa s nega ti ve, but i s now 4+, a nd he ha s ha d a n epi s ode of hema temes i s . Wha t woul d be the bes t drug to a dmi ni s ter to
countera ct the effects of exces s i ve hepa ri n rema i ni ng i n the ci rcul a ti on?
a . Ami noca proi c a ci d
b. Di pyri da mol e
c. Fa ctor IX
d. Prota mi ne s ul fa te
e. Vi ta mi n K
215. A 45-yea r-ol d ma n a s ks hi s phys i ci a n for a pres cri pti on for s i l dena fi l to i mprove hi s s exua l performa nce. Beca us e of ri s ks from a s eri ous drug
i ntera cti on, thi s drug s houl d not be pres cri bed, a nd the pa ti ent s houl d be urged not to try to obta i n i t from other s ources , i f he i s a l s o ta ki ng whi ch
of the fol l owi ng drugs ?

a . Angi otens i n-converti ng enzyme i nhi bi tor

b. -Adrenergi c bl ocker
c. Ni trova s odi l a tor (eg, ni trogl yceri n)
d. Sta ti n-type a nti hyperchol es terol emi c drug
e. Thi a zi de or l oop di ureti c
216. A phys i ci a n i s prepa ri ng to a dmi ni s ter a drug for whi ch there i s a l a bel wa rni ng: do not a dmi ni s ter thi s drug to pa ti ents wi th s econd-degree
or grea ter hea rt bl ock, or gi ve wi th other drugs tha t ma y ca us e hea rt bl ock. Whi ch fi ndi ng woul d be s peci fi ca l l y i ndi ca ti ve of hea rt bl ock, a nd
s econd-degree hea rt bl ock i n pa rti cul a r?
a . Aus cul ta ti on of the precordi um revea l s a n i rregul a r rhythm
b. Bl ood pres s ure i s l ow
c. Hea rt ra te i s a bnorma l l y l ow (bra dyca rdi a ), but there i s norma l s i nus rhythm
d. ECG revea l s ventri cul a r ectopi c bea ts
e. ECG s hows a n exces s i vel y prol onged PR i nterva l , a nd s ome P wa ves a re not fol l owed by a norma l QRS compl ex
f. ECG s hows a bnorma l l y wi dened QRS compl exes
217. A 52-yea r-ol d woma n wi th es s enti a l hypertens i on, hyperchol es terol emi a , a nd chroni c-s ta bl e a ngi na devel ops s evere cons ti pa ti on. It i s
a ttri buted to one of her medi ca ti ons . Wha t wa s the mos t l i kel y ca us e?
a . Atorva s ta ti n
b. Ca ptopri l
c. La beta l ol
d. Ni trogl yceri n
e. Vera pa mi l
218. We us e s ta nda rd i nva s i ve hemodyna mi c techni ques to mea s ure or ca l cul a te the effects of va ri ous drugs on s uch pa ra meters a s a rteri a l
pres s ure, tota l peri phera l res i s ta nce, a nd centra l venous (ri ght a tri a l ) pres s ures . Our goa l i s to eva l ua te whether the drug pri ma ri l y ca us es
a rteri ol a r or venul a r di l a ti on, or a ffects both s i des of the ci rcul a ti on. Whi ch drug exerts va s odi l a tor effects onl y i n the a rteri a l s i de of the
ci rcul a ti on?
a . Hydra l a zi ne
b. Los a rta n
c. Ni fedi pi ne
d. Ni trogl yceri n
e. Pra zos i n
219. A 20-yea r-ol d col l egi a te va rs i ty hockey pl a yer i s referred to you by hi s coa ch. The young a thl ete ha s exces s i ve brui s i ng a fter a very phys i ca l
ma tch 2 da ys before. Hi s knee ha d been botheri ng hi m, s o he took two 325 mg a s pi ri n ta bl ets s evera l hours before the contes t. He got checked
ha rd i nto the boa rds ma ny ti mes duri ng the ga me, but deni es a ny exces s i ve or unus ua l tra uma . As you ponder the s i tua ti on you order s evera l
bl ood tes ts . Whi ch tes t or fi ndi ng do you mos t l i kel y expect to be a bnorma l a s a res ul t of the pri or a s pi ri n us e?
a . Acti va ted pa rti a l thrombopl a s ti n ti me (APTT)
b. Bl eedi ng ti me
c. INR (Interna ti ona l Norma l i zed Ra ti o)
d. Pl a tel et count
e. Prothrombi n ti me
220. A pa ti ent i n the corona ry ca re uni t devel ops epi s odes of pa roxys ma l AV noda l reentra nt ta chyca rdi a (PSVT). Wha t drug woul d genera l l y be
cons i dered fi rs t-l i ne for promptl y s toppi ng the a rrhythmi a ?
a . Adenos i ne
b. Di goxi n
c. Edrophoni um
d. Phenyl ephri ne
e. Propra nol ol
221. A 60-yea r-ol d ma n, hos pi ta l i zed for a n a cute myoca rdi a l i nfa rcti on, i s trea ted wi th wa rfa ri n (a mong other drugs ). Wha t i s the ma i n mecha ni s m
by whi ch wa rfa ri n i s ca us i ng the effects for whi ch i t i s gi ven?
a . Increa s e i n the pl a s ma l evel of Fa ctor IX
b. Inhi bi ti on of thrombi n a nd ea rl y coa gul a ti on s teps
c. Inhi bi ti on of s ynthes i s /a cti va ti on of prothrombi n a nd Fa ctors VII, IX, a nd X
d. Inhi bi ti on of pl a tel et a ggrega ti on
e. Acti va ti on of pl a s mi nogen
f. Bi ndi ng of Ca 2+ i on cofa ctor i n s ome coa gul a ti on s teps
222. A 42-yea r-ol d ma n wi th a n a cute MI i s trea ted wi th a l tepl a s e, a nd el ectroca rdi ogra phi c a nd hemodyna mi c s ta tus i mprove qui ckl y. By wha t
mecha ni s m di d the a l tepl a s e ca us e i ts benefi ci a l effects ?
a . Bl ocked pl a tel et ADP receptors
b. Inhi bi ted pl a tel et thromboxa ne producti on

c. Inhi bi ted s ynthes i s of vi ta mi n K-dependent coa gul a ti on fa ctors

d. Prevented a ggrega ti on of a dja cent pl a tel ets by bl ocki ng gl ycoprotei n IIb/IIIa receptors
e. Promoted convers i on of pl a s mi nogen to pl a s mi n
223. A pa ti ent wi th a tri a l fi bri l l a ti on i s pl a ced on l ong-term a rrhythmi a control wi th a mi oda rone. In a ddi ti on to s ta nda rd moni tori ng, wha t
s houl d be a s s es s ed peri odi ca l l y i n order to detect a dvers e effects tha t a re ra ther uni que to thi s drug a mong vi rtua l l y a l l the a nti a rrhythmi cs ?
a . Bl ood gl ucos e, tri gl yceri de, chol es terol , a nd s odi um concentra ti ons
b. Hea ri ng thres hol ds (a udi ometry) a nd pl a s ma a l bumi n concentra ti on
c. Prothrombi n ti me a nd a nti nucl ea r a nti body (ANA) ti ters
d. Pul mona ry functi on a nd thyroi d hormone s ta tus
e. Whi te cel l counts a nd bl ood ura te concentra ti on
224. A 64-yea r-ol d woma n ha s ha d s evera l epi s odes of tra ns i ent i s chemi c a tta cks (TIAs ). As pi ri n woul d be a preferred trea tment for preventi on of
thrombos i s , but s he ha s a hi s tory of s evere a s pi ri n s ens i ti vi ty ma ni fes t a s i ntens e bronchocons tri cti on a nd urti ca ri a . Wha t woul d you cons i der to
be the bes t a l terna ti ve to the a s pi ri n?
a . Aceta mi nophen
b. Ami noca proi c a ci d
c. Cl opi dogrel
d. Di pyri da mol e
e. Streptoki na s e
225. A pa ti ent who ha s exces s i vel y s l ow AV noda l conducti on ra tes , tha t unfortuna tel y ha vent been recogni zed, i s s ta rted on a drug. As s oon a s
bl ood l evel s cl i mb towa rd the us ua l thera peuti c ra nge the pa ti ent goes i nto compl ete hea rt bl ock. Whi ch drug mos t l i kel y provoked thi s further
prol onga ti on of the P-R i nterva l , ul ti ma tel y l ea di ng to the ces s a ti on of a l l AV noda l conducti on?
a . Ca ptopri l
b. Los a rta n
c. Ni fedi pi ne
d. Ni trogl yceri n
e. Pra zos i n
f. Vera pa mi l
226. A pa ti ent wi th hea rt fa i l ure, Sta ge 1 es s enti a l hypertens i on, a nd hyperl i pi demi a (el eva ted LDL chol es terol a nd a bnorma l l y l ow HDL-C) i s
ta ki ng furos emi de, ca ptopri l , a tenol ol , a nd s i mva s ta ti n (a n HMG-CoA reducta s e i nhi bi tor).
Duri ng a s chedul ed phys i ca l exa m, a bout a month a fter s ta rti ng a l l the a bove drugs , the pa ti ent reports a s evere, ha cki ng, a nd rel entl es s cough.
Other vi ta l s i gns , a nd the overa l l phys i ca l a s s es s ment, a re cons i s tent wi th good control of both the hea rt fa i l ure a nd bl ood pres s ure a nd i ndi ca te
no other underl yi ng di s ea s e or a bnorma l i ti es . Res ul ts of bl ood tes ts a re not yet a va i l a bl e.
Whi ch of the fol l owi ng i s the mos t l i kel y ca us e of the cough?
a . An expected s i de effect of the ca ptopri l
b. An a l l ergi c rea cti on to the s ta ti n
c. Dys pnea due to ca ptopri l s known a nd powerful bronchocons tri ctor a cti on
d. Exces s i ve dos es of the bumeta ni de, whi ch l ed to hypovol emi a
e. Hyperka l emi a ca us ed by a n i ntera cti on between bumeta ni de a nd ca ptopri l
f. Pul mona ry edema from the bumeta ni de
227. A pa ti ent wi th a hi s tory of hypertens i on, hea rt fa i l ure, a nd peri phera l va s cul a r di s ea s e ha s been on ora l thera py, wi th drugs s ui ta bl e for ea ch,
for a bout 3 months . He runs out of the medi ca ti on a nd pl a ns to ha ve the pres cri pti ons refi l l ed i n a week or s o.
Wi thi n a da y or two a fter s toppi ng hi s medi ca ti ons he experi ences a n epi s ode of s evere ta chyca rdi a a ccompa ni ed by ta chya rrhythmi a s , a nd a n
a brupt ri s e of bl ood pres s ure to 240/140 mm Hgwel l a bove pretrea tment l evel s . He compl a i ns of ches t pa i n, a nxi ety, a nd a poundi ng hea da che.
Soon therea fter he s uffers a hemorrha gi c s troke.
Whi ch drug or drug group tha t the ma n wa s ta ki ng a nd s topped ta ki ng s uddenl y mos t l i kel y ca us ed thes e res pons es ?
a . ACE i nhi bi tor
b. Cl oni di ne
c. Di goxi n
d. Furos emi de
e. Ni fedi pi ne (a l ong-a cti ng formul a ti on)
f. Wa rfa ri n
228. Your cl a s s jus t compl eted a mi ni revi ew of the phys i ol ogy a nd pa thophys i ol ogy of bl ood pres s ure control a nd fi na l l y da wned on a cl a s s ma te:
bra dyki ni n, a n endogenous va s odi l a tor, contri butes to keepi ng bl ood pres s ure l ow; a nd i ts meta bol i te, formed by a n enzyme cl everl y ca l l ed bra dyki ni na s e, l a cks va s odi l a tor a cti vi ty. A col l ea gue s a ys woul dnt i t be grea t i f we ha d a drug tha t coul d i nhi bi t bra dyki ni ns meta bol i c i na cti va ti on?
We coul d proba bl y us e i t a s a n a nti hypertens i ve drug! You repl y tha t we a l rea dy ha ve a drugs evera l , i n fa cttha t does tha t very thi ng. Wha t
drug or drug group woul d tha t be?
a . Atenol ol or metoprol ol
b. Ca ptopri l or other pri l s
c. Hydrochl orothi a zi de or s i mi l a r di ureti c-a nti hypertens i ves

d. La beta l ol or ca rvedi l ol
e. Los a rta n or other s a rta ns
229. A 70-yea r-ol d woma n i s trea ted wi th s ubl i ngua l ni trogl yceri n for occa s i ona l bouts of effort-i nduced a ngi na . Wha t bes t des cri bes pa rt of the
mecha ni s ms by whi ch ni trogl yceri n ca us es i ts des i red a nti a ngi na l effects ?
a . Bl ocks -a drenergi c receptors
b. Forms cya ni de, much l i ke the meta bol i s m of ni troprus s i de does
c. Increa s es l oca l s ynthes i s a nd rel ea s e of a denos i ne
d. Ra i s es i ntra cel l ul a r cGMP l evel s
e. Sel ecti vel y di l a tes /rel a xes corona ry a rteri es
230. Your pa ti ent ha s bi pol a r i l l nes s , hyperchol es terol emi a , chroni c-s ta bl e a ngi na , a nd Sta ge 1 es s enti a l hypertens i on. He ha s been ta ki ng
l i thi um a nd a n SSRI for the bi pol a r i l l nes s . Ca rdi ova s cul a r drugs i ncl ude a torva s ta ti n, di l ti a zem, s ubl i ngua l ni trogl yceri n, ca ptopri l , a nd
hydrochl orothi a zi de. Wha t outcome, due to i ntera cti ons i nvol vi ng thes e drugs , s houl d you mos t l i kel y expect?
a . Devel opment of a cute ps ychos i s from a n ACE i nhi bi tor-a nti ps ychoti c i ntera cti on
b. Devel opment of a hypoma ni c s ta te from a nta goni s m of l i thi ums a cti on by the ni trogl yceri n
c. Li thi um toxi ci ty beca us e of hypona tremi a ca us ed by the hydrochl orothi a zi de
d. Los s of chol es terol control from a nta goni s m of the HMG Co-A reducta s e i nhi bi tor by the a nti ps ychoti c
e. Wors eni ng of a ngi na beca us e the a nti ps ychoti c countera cts the effects of the ca l ci um cha nnel bl ocker
f. Wors eni ng of a ngi na beca us e the l i thi um a nta goni zes the effects of the ni trogl yceri n
231. A fi rs t-yea r hous e offi cer noti ces tha t a pa ti ent i s experi enci ng s i gni fi ca nt a nd ra pi dl y ri s i ng bl ood pres s ure (currentl y 180/120 mm Hg). One of
the medi ca ti ons the pa ti ent ha d been ta ki ng i s i mmedi a te-a cti ng ni fedi pi ne ora l ca ps ul es . There i s a dos e of thi s ni fedi pi ne formul a ti on a t the
beds i de, s o the phys i ci a n pri cks the ca ps ul e open a nd s qui rts the contents i nto the pa ti ents mouth. Thi s techni que a voi ds fi rs t-pa s s
meta bol i s m of the drug a nd ca us es ra pi d a bs orpti on a nd a l l the effects a s s oci a ted wi th thi s ca l ci um cha nnel bl ocker. Wha t i s the mos t l i kel y
outcome of gi vi ng ni fedi pi ne a s des cri bed here?
a . AV noda l bl ock
b. Further ri s e of hea rt ra te, wors eni ng of the ventri cul a r a rrhythmi a
c. Hypotens i on a nd bra dyca rdi a
d. Norma l i za ti on of bl ood pres s ure a nd hea rt ra te
e. Return of bl ood pres s ure towa rd norma l , no s i gni fi ca nt effect on hea rt ra te or the ECG
232. A 55-yea r-ol d pa ti ent wi th mul ti pl e ca rdi ova s cul a r di s ea s es i s bei ng trea ted wi th di goxi n, furos emi de, tri a mterene, a torva s ta ti n, a nd
ni trogl yceri na l l pres cri bed by the fa mi l y phys i ci a n hes ha d for deca des . The pa ti ent now experi ences na us ea , vomi ti ng, a nd a norexi a , a nd
des cri bes a yel l owi s h-greeni s h ti nt to whi te objects a nd bri ght l i ghts . Thes e s i gns a nd s ymptoms a re mos t cha ra cteri s ti c of toxi ci ty due to whi ch
drug?
a . Atorva s ta ti n
b. Di goxi n
c. Furos emi de
d. Ni trogl yceri n
e. Tri a mterene
233. A 28-yea r-ol d fema l e pa ti ent ha s Sta ge 1 es s enti a l hypertens i on (res ti ng BP 144/98), ta chyca rdi a , a nd occa s i ona l pa l pi ta ti ons (ventri cul a r
ectopi c bea ts ). Norma l l y we mi ght cons i der pres cri bi ng a -bl ocker to control the bl ood pres s ure a nd ca rdi a c res pons es , but our pa ti ent a l s o ha s
a s thma , a nd s he i s tryi ng to get pregna nt. Whi ch drug woul d be the bes t a l terna ti ve to the -bl ocker i n terms of l i kel y effi ca cy on pres s ure a nd
hea rt ra te, a nd i n terms of rel a ti ve s a fety?
a . Di l ti a zem
b. Ena l a pri l
c. Furos emi de
d. Phentol a mi ne
e. Pra zos i n
234. A pa ti ent pres ents wi th hypertens i on. The underl yi ng ca us ea pheochromocytoma i s not l ooked-for or detected i n the i ni ti a l work-up. An
ora l a nti hypertens i ve drug i s pres cri bed. We s oon fi nd tha t the pa ti ents bl ood pres s ure ha s ri s en to l evel s a bove pretrea tment l evel s s o much
s o tha t we a re worri ed a bout i mmi nentl y da ngerous effects from the drug-i nduced wors eni ng of hypertens i oni n res pons e to a drug. Concomi ta nt
wi th the drug-i nduced ri s e of bl ood pres s ure the pa ti ent devel ops s i gns a nd s ymptoms of hea rt fa i l ure. Whi ch drug wa s mos t l i kel y a dmi ni s tered?
a . Ca ptopri l
b. Hydrochl orothi a zi de
c. La beta l ol
d. Los a rta n
e. Propra nol ol
f. Vera pa mi l
235. A pa ti ent on l ong-term wa rfa ri n thera py ha s a n INR tha t i s exces s i ve (4.5; norma l , not a nti coa gul a ted i s 1.0; the ta rget for thi s pa ti ent wa s 2.5).
She reports epi s odes of epi s ta xi s over the l a s t 2 da ys a nd now there i s a grea t ri s k of s eri ous bl eedi ng epi s odes . In a ddi ti on to s toppi ng wa rfa ri n
a dmi ni s tra ti on for a da y or more, whi ch drug woul d you wa nt to a dmi ni s ter to countera ct wa rfa ri ns exces s i ve effects tha t l ed to s ponta neous

bl eedi ng?
a . Ami noca proi c a ci d
b. Epoeti n a l fa
c. Ferrous s ul fa te
d. Phytona di one (vi ta mi n K)
e. Prota mi ne s ul fa te
236. A pa ti ent wi th hypertens i on a nd hea rt fa i l ure ha s been trea ted for 2 yea rs wi th ca rvedi l ol a nd l i s i nopri l . He ha s jus t ha d hi p repl a cement
s urgery, but beca us e he i s not a mbul a ti ng he i s s ta rted on unfra cti ona ted hepa ri n, pos topera ti vel y, for prophyl a xi s of deep venous thrombos i s .
Ora l a nta ci ds a nd es omepra zol e (ga s tri c pa ri eta l cel l proton pump i nhi bi tor) ha ve been a dded for prophyl a xi s of a cute s tres s ul cers . Fi ve da ys
pos top, he experi ences s udden ons et dys pnea a nd el ectroca rdi ogra phi c a nd other i ndi ca ti ons of a n a cute MI. The pa ti ents pl a tel et counts a re
da ngerous l y l ow. Wha t i s the mos t l i kel y underl yi ng probl em?
a . Acci denta l s ubs ti tuti on of l ow-mol ecul a r-wei ght hepa ri ns (LMWH) for unfra cti ona ted hepa ri n
b. Acci denta l /i na dvertent a s pi ri n a dmi ni s tra ti on
c. Hemol yti c a nemi a from a ca rvedi l ol -ACE i nhi bi tor i ntera cti on
d. Hepa ri n-i nduced thrombocytopeni a
e. Reduced hepa ri n effects by i ncrea s ed meta bol i c cl ea ra nce (ca us ed by ra ni ti di ne)
237. A pa ti ent wi th a ngi na pectori s i s s ta rted on a ni trogl yceri n tra ns derma l del i very s ys tem (s ki n pa tch) for prophyl a xi s of hi s a ngi na . He wea rs
the pa tch 24 hours a da y, 7 da ys a week, except for the few mi nutes when he s howers ea ch da y. Wha t i s the ma i n concern wi th a round-the-cl ock
a dmi ni s tra ti on of thi s or other l ong-a cti ng formul a ti ons of ni trova s odi l a tors ?
a . Cya ni de poi s oni ng
b. Devel opment of tol era nce to thei r va s odi l a tor a cti ons
c. Gra dua l devel opment of refl ex bra dyca rdi a i n res pons e to s ucces s i ve dos es
d. Ons et of del a yed, cha ra cteri s ti c a dvers e res pons es i ncl udi ng thrombos i s a nd thrombocytopeni a
e. Pa ra doxi ca l va s ocons tri cti on l ea di ng to hypertens i on
238. For ma ny hypertens i ve pa ti ents we ca n pres cri be ei ther l i s i nopri l (or a n a l terna ti ve i n the s a me cl a s s ) or l os a rta n. Wha t s ta tement correctl y
s umma ri zes how l os a rta n di ffers from l i s i nopri l other l i s i nopri l -l i ke drugs ?
a . Li s i nopri l competi ti vel y bl ocks ca techol a mi ne-medi a ted va s ocons tri cti on, l os a rta n does not
b. Li s i nopri l effecti vel y i nhi bi ts s ynthes i s of a ngi otens i n II, l os a rta n does not
c. Los a rta n ca us es a hi gher i nci dence of bronchos pa s m a nd hyperuri cemi a
d. Los a rta n i s preferred for ma na gi ng hypertens i on duri ng pregna ncy, wherea s ca ptopri l i s contra i ndi ca ted
e. Los a rta n i s s ui ta bl e for a dmi ni s tra ti on to pa ti ents wi th hea rt fa i l ure, wherea s ca ptopri l a nd rel a ted drugs s houl d be a voi ded.
239. A 46-yea r-ol d ma n ha s Sta ge 1 es s enti a l hypertens i on (res ti ng BP 150/98), pri ma ry hyperchol es terol emi a , a nd modes tl y el eva ted fa s ti ng
gl ucos e l evel s (130 mg/dL) mea s ured on s evera l occa s i ons . Hi s chol es terol l evel s (tota l , HDL, LDL) ha ve not been a ccepta bl y modi fi ed by di eta ry
cha nges a nd da i l y us e of a s ta ti n. The phys i ci a n a dds ezeti mi be to the regi men. Whi ch s ta tement s umma ri zes ezeti mi bes a cti ons , or wha t
woul d be expected i n res pons e to i ts us e?
a . Exerts profound ca rdi a c nega ti ve i notropi c effects tha t pos es a ri s k of hea rt bl ock
b. Frequentl y ca us es orthos ta ti c hypotens i on tha t i n turn tri ggers refl ex ca rdi a c s ti mul a ti on
c. More l i kel y tha n other drugs to i ncrea s e the ri s k of s evere s ta ti n-i nduced myopa thy
d. Reduces i ntes ti na l chol es terol upta ke, ha s no di rect hepa ti c effect to i nhi bi t chol es terol s ynthes i s
e. Si gni fi ca ntl y i ncrea s es ri s k of a theros cl eroti c pl a que rupture
240. A 58-yea r-ol d ma n pres ents i n the emergency depa rtment wi th hi s fi rs t epi s ode of a cute corona ry s yndrome (ACS) a nd a l l evi dence poi nts to a
myoca rdi a l i nfa rcti on. Angi opl a s ty a nd s tenti ng a re not pos s i bl e beca us e the ca rdi a c ca th l a b i s bus y wi th other hi gher-pri ori ty pa ti ents , s o
a dmi ni s tra ti on of a thrombol yti c drug i s the onl y opti on. Wha t i s the mos t i mporta nt determi na nt, overa l l , of the s ucces s of thrombol yti c thera py i n
terms of s a l va gi ng vi a bl e ca rdi a c mus cl e (or other i s chemi c ti s s ues )?
a . Choos i ng a huma n (cl oned) pl a s mi nogen a cti va tor (eg, t-PA), ra ther tha n one tha t i s ba cteri a l -deri ved (eg, s treptoki na s e)
b. Infa rct l oca ti on (i e, a nteri or wa l l of l eft ventri cul a r vs a nother s i te/wa l l )
c. Pres ence of col l a tera l bl ood ves s el s to the i nfa rct-rel a ted corona ry a rtery
d. Sys tol i c bl ood pres s ure a t the ti me the MI i s di a gnos ed
e. Ti me from ons et of i nfa rcti on to a dmi ni s tra ti on of the thrombol yti c a gent
241. A pa ti ent wi th a n a cute corona ry s yndrome i s gi ven a va ri ety of ca rdi ova s cul a r drugs a s he i s bei ng rea di ed for tra ns port to the ca th l a b for
pos s i bl e pl a cement of a s tent. One of the meds i s a bci xi ma b. Wha t bes t des cri bes the mecha ni s m of a cti on of thi s drug?
a . Bl ocks thrombi n receptors s el ecti vel y
b. Bl ocks ADP receptors
c. Bl ocks gl ycoprotei n IIb/IIIa receptors
d. Inhi bi ts cycl ooxygena s e
e. Inhi bi ts pros ta cycl i n producti on
242. A pa ti ent pres ents i n the emergency depa rtment wi th a cute hypotens i on tha t requi res trea tment. Hypovol emi a i s rul ed-out a s a ca us e or
contri butor, a nd i nforma ti on ga thered from the pa ti ent a nd fa mi l y i ndi ca tes tha t the ca us e i s overdos e of a n a nti hypertens i ve drug.

One a pproa ch to trea tment i s to a dmi ni s ter a pha rma col ogi c (ordi na ri l y effecti ve) dos e of phenyl ephri ne, a n -a drenergi c a goni s t. You do jus t
tha t, a nd bl ood pres s ure fa i l s to ri s e a t a l l a nd a s econd dos e does nt work ei ther. On whi ch a nti hypertens i ve drug di d the pa ti ent mos t l i kel y
overdos e?
a . Ca ptopri l or a nother ACE i nhi bi tor
b. Hydra l a zi ne
c. Pra zos i n
d. Thi a zi de di ureti c (eg, hydrochl orothi a zi de)
e. Vera pa mi l
243. An el derl y ma n who ha s jus t been referred to your pra cti ce ha s been ta ki ng a drug for s ymptoma ti c rel i ef of beni gn pros ta ti c hypertrophy. In
a ddi ti on to i ts effects on s mooth mus cl es of the pros ta te a nd urethra , thi s drug ca n l ower bl ood pres s ure i n s uch a wa y tha t i t refl exl y tri ggers
ta chyca rdi a , pos i ti ve i notropy, a nd i ncrea s ed AV noda l conducti on. The drug nei ther di l a tes nor cons tri cts the bronchi . It ca us es the pupi l s of the
eyes to cons tri ct a nd i nterferes wi th mydri a s i s i n di m l i ght. Ini ti a l ora l dos a ges of thi s drug ha ve been a s s oci a ted wi th a hi gh i nci dence of
s yncope.
Whi ch prototype i s mos t s i mi l a r to thi s unna med drug i n terms of the pha rma col ogi c profi l e?
a . Ca ptopri l
b. Hydrochl orothi a zi de (prototype thi a zi de di ureti c)
c. La beta l ol
d. Ni fedi pi ne
e. Pra zos i n
f. Propra nol ol
g. Vera pa mi l
244. You a re contempl a ti ng s ta rti ng ACE i nhi bi tor thera py for a pa ti ent wi th es s enti a l hypertens i on. Whi ch one of the fol l owi ng pa ti ent-rel a ted
condi ti on(s ) contra i ndi ca tes us e of a ny ACE i nhi bi tor a nd s o s houl d be ruled out before you pres cri be thi s drug?
a . As thma
b. Hea rt fa i l ure
c. Hyperl i pi demi a , corona ry a rtery di s ea s e
d. Hypoka l emi a
e. Is a woma n who i s pregna nt or ma y become pregna nt
245. A pa ti ent devel ops s i nus bra dyca rdi a . Hea rt ra te i s da ngerous l y l ow, a nd a n effecti ve a nd s a fe drug needs to be gi ven ri ght a wa y. Whi ch drug
woul d be the bes t choi ce for norma l i zi ng hea rt ra te wi thout i ni ti a ti ng a ny other a rrhythmi a s ?
a . Atropi ne
b. Ami oda rone
c. Edrophoni um
d. Li doca i ne
e. Phentol a mi ne
246. A pa ti ent pres ents i n the emergency depa rtment (ED) wi th s evere a ngi na pectori s , a nd a cute myoca rdi a l i s chemi a i s confi rmed by
el ectroca rdi ogra phi c a nd other cl i ni ca l i ndi ca tors . Unknown to the ED tea m i s the fa ct tha t the i s chemi a i s due to corona ry va s os pa s m, not to
corona ry occl us i on wi th thrombi . Gi ven thi s eti ol ogy, whi ch drug, a dmi ni s tered i n us ua l l y effecti ve dos es , ma y a ctua l l y ma ke the va s os pa s m, a nd
the res ul ti ng i s chemi a , wors e?
a . Al tepl a s e (t-PA)
b. As pi ri n
c. Ca ptopri l
d. Ni trogl yceri n
e. Propra nol ol
f. Vera pa mi l
247. Ma ny cl i ni ca l s tudi es ha ve i nves ti ga ted the benefi ts of da i l y a s pi ri n us e i n the pri ma ry preventi on of corona ry hea rt di s ea s e a nd s udden
dea th i n a dul ts . The res ul ts ha ve been s omewha t i ncons i s tent, i n pa rt beca us e di fferent dos a ges were s tudi ed, a nd there were i mporta nt
di fferences i n the popul a ti ons tha t were s tudi ed. Nonethel es s , ma ny (i f not mos t) of the s tudi es ha ve revea l ed tha t for s ome pa ti ents a s pi ri n
i ncrea s ed the i nci dence of a pa rti cul a rl y unwa nted a dvers e res pons e, even when dos a ges were kept wi thi n the ra nge typi ca l l y recommended for
ca rdi oprotecti on (eg, 81-162 mg/da y). Wha t i s the mos t l i kel y a dvers e res pons e a s s oci a ted wi th a s pi ri n prophyl a xi s , pa rti cul a rl y i n pa ti ents who
ha ve a l ow ri s k of a n a cute corona ry s yndrome or ca rdi ova s cul a r di s ea s e i n genera l ?
a . Centrol obul a r hepa ti c necros i s
b. Hemorrha gi c s troke
c. Nephropa thy
d. Ta chyca rdi a a nd hypotens i on l ea di ng to a cute myoca rdi a l i s chemi a
e. Va s os pa s ti c a ngi na
248. A pa ti ent wi th es s enti a l hypertens i on ha s been trea ted wi th a fi xed-dos e combi na ti on product tha t conta i ns hydrochl orothi a zi de a nd
tri a mterene. Bl ood pres s ure a nd el ectrol yte profi l es ha ve been kept wi thi n a ccepta bl e l i mi ts for the l a s t 18 months . Now, however, bl ood pres s ure
ha s ri s en to the poi nt where the phys i ci a n wa nts to a dd a nother a nti hypertens i ve drug. The drug i s s ta rted; a fter s evera l weeks bl ood pres s ure
fa l l s i nto a n a ccepta bl e ra nge, but the pa ti ent ha s become hyperka l emi c. Wha t drug wa s a dded a nd wa s mos t l i kel y res pons i bl e for the des i red

bl ood pres s ure fa l l a nd the unwa nted ri s e of pota s s i um l evel s .

a . Di l ti a zem
b. Pra zos i n
c. Propra nol ol
d. Ra mi pri l
e. Vera pa mi l
249. A pa ti ent ha s a s upra ventri cul a r ta chyca rdi a . We i nject a drug a nd hea rt ra te fa l l s to a norma l (or a t l ea s t more a ccepta bl e) l evel . Al though
thi s drug ca us ed the des i red res pons e, i t di d s o wi thout a ny di rect effect i n or on the hea rt. Whi ch drug wa s mos t l i kel y us ed?
a . Edrophoni um
b. Es mol ol
c. Phenyl ephri ne
d. Propra nol ol
e. Vera pa mi l
250. A 69-yea r-ol d ma n pres ents wi th NYHA Sta ge II (mi l d) hea rt fa i l ure. Hi s s ymptoms fa i l ed to i mprove a dequa tel y i n res pons e to ca ptopri l a nd
ca rvedi l ol s o the phys i ci a n s tops the ca rvedi l ol a nd a dds us ua l thera peuti c dos es of di goxi n a nd furos emi de. At a fol l ow-up exa m 3 months l a ter
we fi nd good s ymptoma ti c rel i ef of the hea rt fa i l ure. Bl ood el ectrol ytes a nd a l l other l a b tes ts a re wi thi n norma l l i mi ts . At thi s ti me, whi ch
el ectroca rdi ogra phi c cha nge woul d you expect to s ee i n res pons e to the di goxi n, compa red wi th a ba s el i ne (pretrea tment) ECG?
a . P wa ves wi dened, a mpl i tude i ncrea s ed
b. PR i nterva l s prol onged
c. QRS compl exes wi dened
d. RR i nterva l s s hortened
e. ST s egments el eva ted
251. A pa ti ent pres ents wi th a bl ood pres s ure of 220/120 a nd a hea rt ra te of 90 bea ts per mi nute des pi te us ua l l y effecti ve a nti hypertens i ve drug
thera py. Further work-up i ndi ca tes the pa ti ent ha s a ra re ca us e of thes e a nd other s i gns a nd s ymptoms : pheochromocytoma . You rea l i ze tha t a drenergi c bl ockers a re us eful a s a nti hypertens i ve drugs , a nd for hel pi ng to norma l i ze hea rt ra te i n pa ti ents wi th s upra ventri cul a r ta chyca rdi a . As
a res ul t of the di a gnos i s , a nd your knowl edge, you a dmi ni s ter a us ua l l y effecti ve dos e of propra nol ol . Wha t i s the mos t l i kel y outcome of doi ng
thi s ?
a . Bl ood pres s ure fa l l s promptl y, fol l owed by refl ex ta chyca rdi a
b. Epi nephri ne rel ea s e from the tumor i s s uppres s ed, hemodyna mi cs norma l i ze
c. Hea rt ra te a nd ca rdi a c functi on ri s e qui ckl y beca us e the -bl ocker ha s tri ggered a ddi ti ona l epi nephri ne rel ea s e from the tumor.
d. Left ventri cul a r a fterl oa d i s decrea s ed, ca rdi a c output ri s es vi a i ncrea s es of both l eft ventri cul a r s troke vol ume a nd hea rt ra te
e. Tota l peri phera l res i s ta nce ri s es , ca rdi a c output fa l l s , the pa ti ent goes i nto ca rdi ogeni c s hock
252. A 59-yea r-ol d ma n pres ents i n the emergency depa rtment wi th crus hi ng ches t di s comfort. An ECG i ndi ca tes a s ma l l tra ns mura l l eft ventri cul a r
i nfa rcti on, a nd prompt ca rdi a c ca theteri za ti on a nd a s s es s ment of pri or l a b res ul ts i ndi ca te s i gni fi ca nt hyperchol es terol emi a . The pa ti ent i s gi ven
a l l the drugs l i s ted bel ow, for both i mmedi a te ma na gement of the i s chemi a a nd i ts s ymptoms a nd for l ong-term preventi on of a s ubs equent, a nd
potenti a l l y fa ta l , MI. Whi ch drug woul d provi de i mmedi a te rel i ef of the cons equences of myoca rdi a l i s chemi a , but ha s no l ong-term effects to
reduce the ri s k of s udden dea th or ventri cul a r dys functi on from a nother MI?
a . As pi ri n
b. Atorva s ta ti n
c. Ca ptopri l
d. Ni trogl yceri n
e. Propra nol ol
253. A 65-yea r-ol d woma n i s tra ns ferred to the thora ci c s urgery ICU a fter ca rdi a c s urgery. She ha s di ffus e ra l es bi l a tera l l y, a pul s e of 90/mi n, a n
el eva ted centra l venous pres s ure, a nd a bl ood pres s ure of 160/98 mm Hg. The s urgery res i dent wa nts to i nject a n otherwi s e-correct dos e of a n IV
drug to control hea rt ra te a nd bl ood pres s ure, but gra bs a s yri nge tha t conta i ns a nother drug. The pa ti ents hea rt ra te i ncrea s es to 150/mi n a nd her
bl ood pres s ure ri s es to 180/106. Whi ch drug di d thi s pa ti ent mos t l i kel y recei ve i n error?
a . Dobuta mi ne
b. Es mol ol
c. Neos ti gmi ne
d. Propra nol ol
e. Vera pa mi l
254. A pa ti ent wi th chroni c-s ta bl e (effort-i nduced) a ngi na begi ns ta ki ng metoprol ol , a nd once bl ood l evel s a pproa ch the thera peuti c ra nge the
frequency a nd s everi ty of a ngi na a tta cks , a nd the need for s ubl i ngua l ni trogl yceri n, were reduced. Whi ch of the fol l owi ng s ta tes the di rect
pha rma col ogi c a cti on by whi ch the -bl ocker provi ded the des i red effects ?
a . Decrea s ed myoca rdi a l oxygen dema nd
b. Di l a ted the corona ry va s cul a ture
c. Di rectl y i nhi bi ted a ngi otens i n II s ynthes i s
d. Reduced tota l peri phera l res i s ta nce
e. Sl owed AV noda l conducti on vel oci ty

255. A 50-yea r-ol d ma n i s a wa re of the benefi ts of a s pi ri n i n terms of reduci ng the ri s k of dea th from a n a cute myoca rdi a l i nfa rcti on, ma i nl y
beca us e he ha s s een ma ny of the a ds a nd i nternet pos ts a bout thi s . He noti ces tha t the us ua l recommended dos e of a s pi ri n for ca rdi oprotecti on
i s 81 mg/da y, but rea s ons tha t the bi gger the dos e, the bi gger a nd better the protecti ve effect. He ha s ta ken a t l ea s t 1,000 mg of a s pi ri n (3
regul a r s trength a s pi ri n ta bl ets ) twi ce a da y for the l a s t 6 months . Whi l e he i s fortuna te i n terms of ha vi ng no a ppa rent ga s troi ntes ti na l a dvers e
effects tha t a re a s s oci a ted wi th l ong-term, hi gh-dos e a s pi ri n us e, he s uffers a n MI. Autops y res ul ts s how cons i dera bl e pl a tel et occl us i on of
s evera l corona ry ves s el s . Wha t expl a i ns the mos t l i kel y mecha ni s m by whi ch hi gh dos e a s pi ri n us e thes e adverse events ?
a . Inhi bi ted thromboxa ne A2 s ynthes i s i n pl a tel ets
b. Fa vored a dhes i on of pl a tel ets to the va s cul a r (corona ry) endothel i um
c. Ruptured a theros cl eroti c pl a que i n the corona ri es , expos i ng pl a tel ets to col l a gen
d. Suppres s ed hepa ti c s ynthes i s of vi ta mi n K-dependent cl otti ng fa ctors
e. Tri ggered exces s i ve a cti va ti on of pl a tel ets by ADP
256. In cl i ni c you meet a 55-yea r-ol d ma n who i s des cri bed by the a ttendi ng a s ha vi ng meta bol i c s yndrome, i ncl udi ng hi gh LDL a nd l ow HDL
chol es terol l evel s , es s enti a l hypertens i on, type 2 di a betes mel l i tus , a nd a ngi na l a tta cks upon s tres s a bout once every 2 months . He currentl y ha s
a s ymptoma ti c hyperuri cemi a , but ha s a gout a tta ck a bout once a yea r. The pa ti ent i s obes e (92 kg), 6 feet ta l l , a nd ha s a body ma s s i ndex
(kg/s qua re meter of body s urfa ce a rea ) of 40 (norma l or des i ra bl e no more tha n 24.9 kg/m 2 ). He ha s a 20 yea r hi s tory of s moki ng a ha l f pa ck of
ci ga rettes a da y, a nd both pa rents di ed i n thei r l a te 50s the fa ther from a n a cute MI, the mother from hemorrha gi c s troke. The gentl ema n i s
ta ki ng medi ca ti ons deemed a ppropri a te for ea ch of the condi ti ons noted a bove. One i s col es evel a m. Wha t i s the proba bl y rea s on why the
col es evel a m wa s gi ven?
a . Countera cts hypoka l emi a ca us ed by a thi a zi de di ureti c
b. Lowers LDL-chol es terol l evel s
c. Lowers pl a s ma ura te l evel s , prophyl a xi s of gout
d. Prevents myoca rdi a l i s chemi a , a ngi na , by reduci ng myoca rdi a l oxygen dema nd
e. Provi des a nti hypertens i ve a nd na tri ureti c effects
257. A ma n ha s a n a neurys m i n the a orti c root, a cons equence of Ma rfa n s yndrome. He experi ences a hypertens i ve cri s i s tha t requi res prompt
bl ood pres s ure control . Ni troprus s i de wi l l be i nfus ed for i ts i mmedi a te a nti hypertens i ve effects . Wha t drug woul d we a dmi ni s ter a l ong wi th the
ni troprus s i de to mi ni mi ze the ri s k of a neurys m rupture due to i ncrea s es of l eft ventri cul a r dP/dt (P/t; cha nge i n pres s ure/cha nge i n ti me) a s
bl ood pres s ure fa l l s ?
a . Atropi ne
b. Di a zoxi de
c. Furos emi de
d. Phentol a mi ne
e. Propra nol ol
258. Ni coti ni c a ci d (ni a ci n), i n the rel a ti vel y l a rge dos es tha t a re us ed to trea t certa i n a nd common hyperl i pi demi a s , often ca us es a cuta neous
fl us h a nd pruri tus . Thes e ca n be a ccompa ni ed by wi del y di s tri buted a nd s ha rp pi ns a nd needl es or burni ng s ens a ti on on the s ki n. The res pons e
ca n be a ttenua ted by s evera l mea ns , one of whi ch i nvol ves pretrea tment wi th a s pi ri n. Wha t mecha ni s m or a cti on mos t l i kel y contri butes to the
va s odi l a tory res pons e a nd the fl us hi ng?
a . Acti va ti on of -a drenergi c receptors on va s cul a r s mooth mus cl e
b. Ca l ci um cha nnel bl ocka de i n va s cul a r s mooth mus cl e
c. Loca l producti on of pros ta gl a ndi ns
d. Rel ea s e of a ngi otens i n II
e. Rel ea s e of hi s ta mi ne
259. The fi gure bel ow s hows typi ca l ca rdi ova s cul a r res pons es to the s l ow IV i njecti on of four a drenergi c drugs i nto a norma l , res ti ng s ubject.
As s ume the dos es of ea ch a re s uffi ci ent to ca us e the effects s een here, but not s o hi gh tha t toxi c effects occur. No other drugs a re pres ent, a nd
s uffi ci ent ti me ha s been a l l owed to ena bl e compl ete di s s i pa ti on of the effects of a ny pri or drugs . The da s hed l i ne between the s ys tol i c a nd
di a s tol i c pres s ure tra ces a pproxi ma tes mea n a rteri a l pres s ure.

Abbrevi a ti ons us ed, a nd a ns wer choi ces , a re

EPI, epi nephri ne
ISO, i s oproterenol
NE, norepi nephri ne
PHE, phenyl ephri ne
PHN, phentol a mi ne
PRO, propra nol ol
Sel ect the l etter tha t i ndi ca tes the drugs tha t a re ordered i n the s equence s hown (1, 2, 3, 4).
a . EPI, NE, PHE, ISO
b. ISO, EPI, NE, PHE
c. ISO, PHE, EPI, NE
d. NE, ISO, PHE, EPI
e. PHE, EPI, NE, PRO
f. PHE, ISO, NE, EPI
g. PRO, PHN, PHE, ISO
Questions 260 to 262
Look a t the ECG bel ow a nd a ns wer the fol l owi ng three ques ti ons .

Here you s ee a conti nuous (uni nterrupted) tra ci ng of l ea d V1, before a nd a fter ca roti d s i nus ma s s a ge (a t a rrow).
260. Wha t i s the mecha ni s m by whi ch ca roti d ma s s a ge exerted i ts effect?
a . Acti va ted wha t i s ta nta mount to the ba roreceptor refl ex, i ncrea s i ng va ga l tone a nd a cetyl chol i ne rel ea s e cons i dera bl y
b. Ca us ed ca techol a mi ne rel ea s e
c. Induced a tri a l fi bri l l a ti on (a tri a l ra te >> 300/mi n)
d. Occl uded venous return to the hea rt, thereby i nterferi ng wi th fi l l i ng a nd contra cti on of a l l hea rt cha mbers downs trea m of the ri ght a tri um
261. Ba s ed on the outcome of ca roti d s i nus ma s s a ge, wha t ca n you s a y a bout the origin of the a berra nt el ectri ca l a cti vi ty tha t l ea ds to the
ta chyca rdi a you s ee before the ma s s a ge?
a . Bundl e of Kent (i e, a noma l ous or a cces s ory pa thwa y for AV conducti on) wi th retrogra de a nd a ntegra de conducti on
b. Left bundl e bra nch
c. Mul ti pl e ectopi c ventri cul a r foci
d. Supra ventri cul a r
262. Wha t drug, gi ven a s a n i ntra venous bol us , mi ght be us ed a s a n a l terna ti ve to ca roti d ma s s a ge, ca us i ng es s enti a l l y the s a me outcome a nd,
therefore, the s a me i nterpreta ti on of the ori gi n of the ventri cul a r ta chyca rdi a ?
a . Adenos i ne
b. Atropi ne
c. Epi nephri ne
d. Is oproterenol
e. Li doca i ne
263. A 23-yea r-ol d nonpregna nt woma n ha s been us i ng a prepa ra ti on of ora l ergota mi ne to ma na ge her frequent mi gra i ne hea da ches . She
cons umes a n exces s i ve dos e of the drug whi l e tryi ng to a bort a pa rti cul a rl y s evere a nd refra ctory a tta ck. Wha t a dvers e ca rdi a c or ca rdi ova s cul a r
cons equences a re mos t l i kel y to occur a s a res ul t of the ergot overdos e?
a . Myoca rdi a l a nd peri phera l (eg, l i mb) i s chemi a due to i ntens e va s ocons tri cti on
b. Rena l fa i l ure s econda ry to rha bdomyol ys i s
c. Sponta neous bl eedi ng due to di rect i nhi bi ti on of pl a tel et a cti va ti on/a ggrega ti on
d. Syncope s econda ry to a cute hypotens i on
e. Ta chyca rdi a , ta chya rrhythmi a s from -1 a drenergi c receptor a cti va ti on

Cardiovascular Pharmacology
Answers
178. The answer is a. (Brunton, pp 730-736; Katzung, pp 184-185, 219-220, 295-300.) ACE i nhi bi tors a re often s el ected fi rs t for hypertens i ve pa ti ents who
a l s o ha ve di a betes mel l i tus (type 1 or type 2)provi ded thei r rena l functi on i s s a ti s fa ctory (s peci fi ca l l y, no s evere bi l a tera l rena l a rteri a l s tenos i s ,
or no i na dequa te bl ood fl ow to one ki dney i f the other wa s removed; no a l bumi nuri a ). Reca l l tha t a ngi otens i n II cons tri cts the efferent a rteri ol es
i n the ki dneys , whi ch i ncrea s es gl omerul a r fi l tra ti on. So, by reduci ng a ngi otens i n II s ynthes i s a n ACE i nhi bi tor wi l l bl ock thi s effect a nd reduce
fi l tra ti on even further. Angi otens i n receptor bl ockers (ARBs , eg, l os a rta n) wi l l do the s a me but by bl ocki ng a ngi otens i n receptors ra ther tha n by
i nhi bi ti ng a ngi otens i n s ynthes i s .
ACE i nhi bi tors (a nd ARBs ) do not ca us e a ny probl ems wi th gl ycemi c control or the res pons es to a nti di a beti c drugs , a nd they s eem to exert s ome
protecti ve effect tha t s l ows or del a ys di a betes -rel a ted nephropa thy. Note tha t ei ther cl a s s of a ngi otens i n modi fi er i s contra i ndi ca ted for pa ti ents
wi th s evere bi l a tera l rena l a rteri a l s tenos i s , i ncl udi ng tha t whi ch mi ght occur wi th l ong-s ta ndi ng a nd s evere di a betes mel l i tus . In s uch pa ti ents ,
ma i ntena nce on s ome rea s ona bl e degree of rena l perfus i on a nd rena l functi on overa l l depends on the renova s cul a r/pos tgl omerul a r
va s ocons tri ctor effects of a ngi otens i n. Bl ock a ngi otens i n s ynthes i s (ACE i nhi bi tors ) or a ngi otens i ns a bi l i ty to a cti va te i ts receptors (ARBs ), a nd
a cute rena l fa i l ure ma y ens ue.
-Adrenergi c bl ockers woul d not be a good choi ce i f hypertens i on i s a ccompa ni ed by di a betes mel l i tus , pa rti cul a rl y when i ns ul i n i s us ed for
gl ycemi c control . Shoul d the di a beti c pa ti ent experi ence a n epi s ode of hypogl ycemi a , a -bl ocker ma y del a y recovery of bl ood gl ucos e l evel s , ma s k
ta chyca rdi a tha t i s one s ymptom of hypogl ycemi a devel opment, a nd i ntera ct wi th s ome a nti di a beti c drugs (even thos e us ed for type 2; to ca us e
exces s i ve bl ood gl ucos e-l oweri ng). (If the di a betes i s wel l control l ed, a nd i f the pa ti ent ha s other di s orders for whi ch benefi ts of -bl ocka de ma y
outwei gh potenti a l probl ems , s uch a s mi l d-modera te hea rt fa i l ure or recent myoca rdi a l i nfa rcti on, then a -bl ocker ma y be cons i dered.)
Thi a zi des ca n el eva te bl ood gl ucos e l evel s a nd a nta goni ze the des i red effects of a nti di a beti c drugs (proba bl y by reduci ng the res pons i venes s
of s kel eta l mus cl e cel l s a nd a di pocytes to i ns ul i n). Nonethel es s , they mi ght not be a fi rs t-choi ce i n the s etti ng of di a betes a t l ea s t not for the
pa ti ent des cri bed i n the s cena ri o. (Some cl i ni ci a ns ma y di s a gree, a nd cons i der a thi a zi de or thi a zi de-l i ke di ureti c (eg, metol a zone) a fi rs t-choi ce
drug for es s enti a l hypertens i on i n mos t pa ti ents .)
Vera pa mi l , di l ti a zem, a nd ni fedi pi ne s eem not to compl i ca te bl ood gl ucos e regul a ti on or i ntera ct wi th a nti di a beti c drug thera py. Nonethel es s ,
they l a ck other benefi ts offered by ACE i nhi bi tors (es peci a l l y the rena l -protecti ve effects ) i n the s etti ng of di a betes a nd s o woul d not be a fi rs t
choi ce or of s peci a l va l ue.
179. The answer is d. (Brunton, pp 774t, 780-781; Katzung, pp 155-162, 167, 179.) La beta l ol i s the bes t choi ce, a s s umi ng no contra i ndi ca ti ons to bl ocka de, s uch a s a s thma or s econd degree or compl ete hea rt bl ock. Gi ven i ts combi na ti on of both -a nd -a drenergi c (1 a nd 2 ) bl ocki ng effect, i t
offers the bes t a pproa ch for ma na gi ng the hypertens i on, the ta chyca rdi a , the res ul ti ng oxygen s uppl y-dema nd i mba l a nce tha t l ea ds to both ches t
di s comfort a nd the i s chemi c ST-cha nges , a nd the ventri cul a r ectopy (whi ch i s proba bl y a refl ecti on of exces s i ve ca techol a mi ne s ti mul a ti on of 1 receptors ). If the pa ti ent i s ha vi ng a n a cute myoca rdi a l i nfa rcti on, s ta rti ng -bl ocker thera py ea rl y i s a l s o deci dedl y benefi ci a l s hort term a nd for
the l ong run. (Mos t a ny other -bl ocker mi ght be a s ui ta bl e a l terna ti ve, but l a beta l ol ha s the combi ned /-bl ocki ng a cti ons tha t a re l i kel y to be of
grea tes t benefi t. Ca rvedi l ol ha s the s a me profi l e, but i t i s gi ven ora l l y a nd i n thi s s etti ng tha t woul d not be i dea l beca us e of s l ow ons et of a cti on.)
As pi ri n wi l l do no ha rm i n thi s s i tua ti on, but i t wi l l a l s o do no good a cutel y unl es s there i s ongoi ng pl a tel et a ggrega ti on a nd corona ry
occl us i on. Even i f there were, the a s pi ri n woul d do l i ttl e to control hea rt ra te, bl ood pres s ure, or the ECG cha nges .
Nothi ng i n the s cena ri o s ugges ts tha t thi s pa ti ent i s vol ume-overl oa ded or s ufferi ng a cute pul mona ry edema . Therefore, a dmi ni s teri ng the
furos emi de (c) i n s uch a s i tua ti on i s not a ppropri a te. Moreover, gi vi ng i t i s l i kel y to ca us e prompt reducti ons of bl ood vol ume a nd, a l ong wi th i t, of
bl ood pres s ure. The l a tter effect i s l i kel y to l ea d to furthera nd unwa ntedrefl ex s ympa theti c a cti va ti on tha t woul d ma ke ma tters wors e.
Li doca i ne (e) mi ght be s ui ta bl e for the ventri cul a r ectopy. However, I ha ve i denti fi ed s evera l other i mporta nt s i gns a nd s ymptoms tha t woul d
not be rel i eved by thi s a nti a rrhythmi c drug. As noted a bove, the profi l e of l a beta l ol offers the grea tes t l i kel i hood of ma na gi ng mul ti pl e probl ems
wi th one drug.
Increa s i ng the dos e of ni trogl yceri n (f; a nd es peci a l l y gi vi ng i t a s a bol us ) i s l i kel y to drop bl ood pres s ure a cutel y, tri ggeri ng refl ex
(ba roreceptor) s ti mul a ti on of the hea rt. The us ua l a nti -i s chemi c effects of the drug woul d be countera cted by s uch pro-i s chemi c cha nges a s
further ri s es of hea rt ra te a nd a proba bl e wors eni ng of the prema ture ventri cul a r bea ts .
Pra zos i n (g) woul d l ower bl ood pres s ure ni cel y. However, once a ga i n we ha ve to worry a bout exces s i ve pres s ure l oweri ng, tri ggeri ng the
ba roreceptor refl ex, a nd wors eni ng ma ny of the a l rea dy worri s ome fi ndi ngs (eg, hea rt ra te, PVCs ).
180. The answer is d. (Brunton, pp 313t, 326, 767, 774t, 831; Katzung, pp 159t, 161, 167, 189.) Ti mol ol i s a nons el ecti ve -a drenergi c bl ocker. Ora l dos a ge
forms a re a pproved for ma na gi ng es s enti a l hypertens i on (a nd a ngi na ). A topi ca l ophtha l mi c dos a ge form i s i ndi ca ted for ma na gi ng s ome ca s es of
chroni c open-a ngl e gl a ucoma . -Bl ockers a re not onl y l i kel y to control bl ood pres s ure, a nd hel p l ower i ntra ocul a r pres s ure, but a l s o to reduce
ca techol a mi ne-i nduced ca rdi a c s ti mul a ti on (the ta chyca rdi a ).
Vera pa mi l or di l ti a zem (b, e), both ca l ci um cha nnel bl ockers (CCBs ) of the nondi hydropyri di ne cl a s s , wi l l not onl y l ower bl ood pres s ure but a l s o
tend to modul a te the ta chyca rdi a (through di rect a nd -receptor-i ndependent proces s es ). However, they dont l ower i ntra ocul a r pres s ure. Al l other
thi ngs bei ng equa l , then, the -bl ocker woul d s ti l l be a better choi ce for the hypertens i ve, ta chyca rdi c, gl a ucoma tous pa ti ent. Thus , we get three
potenti a l benefi ts from -bl ocka de a nd onl y two wi th vera pa mi l or di l ti a zem.
ACE i nhi bi tors , s uch a s ca ptopri l (a ) a nd thi a zi de di ureti cs (c), ha ve no a cti ons tha t woul d ma ke them pa rti cul a rl y s ui ta bl e for hypertens i ve
pa ti ents who a re ta chyca rdi c, ha ve gl a ucoma , or both.
181. The answer is c. (Brunton, pp 330, 780-781; Katzung, pp 159t, 161, 179-180.) Even i f you know nothi ng s peci fi ca l l y a bout nebi vol ol you s houl d be a bl e
to concl ude tha t i ncrea s ed forma ti on or a cti vi ty of ni tri c oxi de (a va s odi l a tor, a mong other thi ngs ) i s the onl y rea s ona bl e a ns wer. A drug tha t
competi ti vel y bl ocks 1 receptors (a ; for exa mpl e phentol a mi ne or pra zos i n) woul d, i ndeed, l ower bl ood pres s ure (BP). However, the ques ti on
s ta ted tha t nebi vol ol ha d no effect on the va s ocons tri ctor effects of ei ther phenyl ephri ne (di rect -a goni s t) or a mpheta mi nes (i ndi rect-a cti ng
s ympa thomi meti cs ; rel ea s e neurona l norepi nephri ne). (Reca l l tha t l a beta l ol a nd ca rvedi l ol a re the -bl ockers tha t a l s o bl ock 1 a drenergi c
receptors .) Competi ti ve bl ocka de of 2 receptors (b) ca nnot be correct. Bl ocki ng the pres yna pti c -receptors woul d i nhi bi t rel ea s ed
norepi nephri nes us ua l a bi l i ty to feedba ck i nhi bi t further NE rel ea s e upon a n a cti on potenti a l . Ha d nebi vol ol bl ocked the 2 receptors , then, the
mos t l i kel y res pons e woul d be a ri s e, not a fa l l , of peri phera l res i s ta nce a nd BP. Thromboxa ne A2 (d) i s a va s ocons tri ctor (a mong other thi ngs ).

Increa s i ng i ts s ynthes i s woul d tend to ra i s e BP/peri phera l res i s ta nce a l s o. COMT (e) i nhi bi ts the meta bol i c i na cti va ti on of ca techol a mi nes i n the
GI tra ct, l i ver, a nd el s ewhere. In theory, COMT i nhi bi tors a l s o woul d ra i s e BP ca us ed by i ts s ubs tra tes . Fi na l l y, -bl ockers a re not ca techol a mi nes ,
a nd s o a re not s ubs tra tes for COMT.
182. The answer is a. (Brunton, pp 86t, 1271-1272; Katzung, 743, 762-763, 1033t.) 1 a cti va ti on, whether i n contra cti l e, noda l , or conducti ng ti s s ues of the
hea rt, l ea ds to a nd requi res i ncrea s ed producti on of cycl i c AMP. Thos e res pons es wi l l be i nhi bi ted i n the pres ence of exces s i ve dos es of a bl ocker. Gl uca gon, a pa rentera l drug norma l l y us ed for ma na gi ng s evere a nd a cute hypogl ycemi a , ca n di rectl y i ncrea s e c-AMP l evel s i n the hea rt,
even i n the pres ence of -bl ocka de. It ha s the bes t cha nce of hel pi ng to res tore (or a t l ea s t i mprove) ca rdi a c functi oneven i n the pres ence of
profound -bl ocka de.
Phenyl ephri ne (b), the prototype -a goni s t, woul d ei ther not a ffect the a l rea dy hi gh TPR, or mi ght i ncrea s e i t further. Gi vi ng i t i n thi s ca s e woul d
not onl y be i rra ti ona l , but a l s o da ngerous . Phentol a mi ne (c), the prototype -a nta goni s t, woul d l ower TPR, but i t i s s ti l l unl i kel y tha t the hea rt ca n
genera te s uffi ci ent CO to perfus e the ti s s ues a dequa tel y. Ephedri ne (d), a drug tha t works i n pa rt by rel ea s i ng norepi nephri ne, woul d be of l i ttl e i f
a ny benefi t. If i t were gi ven CO woul d s ti l l be depres s ed owi ng to the -bl ocka de, a nd -receptor a cti va ti on woul d ca us e phenyl ephri ne-l i ke
effects on the peri phera l va s cul a ture. As noted a bove, thos e peri phera l va s ocons tri ctor effects a re preci s el y wha t we dont need or wa nt to ca us e.
Epi nephri ne (e) woul d a l s o ca us e not-needed/unwa nted peri phera l va s ocons tri cti on; i t i s not l i kel y to do better a t a cti va ti ng ca rdi a c -receptors ,
a nd i mprovi ng CO, tha n i s oproterenol a l rea dy ha s .
183. The answer is e. (Brunton, pp 844, 1405-1407; Katzung, pp 238, 921-922.) Ma ny of the s i gns a nd s ymptoms of s a l i cyl i s m a re s i mi l a r to thos e ca us ed
by hi gh bl ood l evel s of qui ni di ne (a nti a rrhythmi c, no l onger a fi rs t-l i ne a nti a rrhythmi c) or qui ni ne (ma i nl y us ed a s a n a nti ma l a ri a l ). Qui ni -di ne,
qui ni ne, a nd rel a ted drugs a re ca l l ed ci nchona a l ka l oi ds , a nd the l ow gra de toxi ci ty s yndrome ca us ed by thes e drugs i s ca l l ed ci nchoni s m. (Thes e
drugs were ori gi na l l y obta i ned from a pl a nt known, generi ca l l y, a s Cinchona.) As pi ri n a nd the ci nchona a l ka l oi ds a re chemi ca l l y s i mi l a r i n s ome
i mporta nt chemi ca l a nd pha rma col ogi c wa ys . The common s i gns a nd s ymptoms i ncl ude l i ght-hea dednes s , ti nni tus , a nd vi s ua l di s turba nces s uch
a s di pl opi a .
184. The answer is e. (Brunton, pp 761, 765-767, 829-831; Katzung, pp 201-205, 245.) Vera pa mi l , a nondi hydropyri di ne ca l ci um cha nnel bl ocker (CCB),
depres s es both the SA node a nd the AV node a nd woul d be effecti ve for prophyl a xi s of pa roxys ma l a tri a l or s upra ventri cul a r ta chyca rdi a .
Ni fedi pi ne (c), the prototypi c di hydropyri di ne CCB, ha s l i ttl e effect on SVT beca us e i t a nd the other di hydropyri di nes l a ck ca rdi a c depres s a nt
effects . Moreover, i f we chos e a fa s t-/i mmedi a te-a cti ng dos a ge form of ni fedi pi ne, we woul d proba bl y tri gger s ubs ta nti a l refl ex ca rdi a c
s ti mul a ti on. The i ncrea s ed s ympa theti c tone to the hea rt coul d wors en the PSVT. Ni trogl yceri n (d) i s ma i nl y a venodi l a tor, but i t ca n ca us e fa l l s of
a rteri a l bl ood pres s ure s uffi ci ent to tri gger refl ex ca rdi a c a cti va ti on tha t woul d exa cerba te the ta chyca rdi a . Adenos i ne (a ) ma y be us eful i n
di a gnos i ng whether ventri cul a r ta chyca rdi a i s of s upra ventri cul a r or ventri cul a r ori gi n, beca us e i t effecti vel y s l ows AV noda l conducti on. It i s a l s o
us ed a s a cute thera py for PSVT. However, i t i s a fa s t- a nd s hort-a cti ng pa rentera l drug, whi ch renders i t uns ui ta bl e for the condi ti on I s ta ted:
outpa ti ent prophyl a xi s . Li doca i ne (b) i s ma i nl y us ed for ventri cul a r ta chya rrhythmi a s , not thos e of s upra ventri cul a r ori gi n. Both a denos i ne a nd
l i doca i ne a re pa rentera l drugs wi th s hort ha l f-l i ves ; nei ther property ma kes them s ui ta bl e for outpa ti ent prophyl a cti c us e.
185. The answer is d. (Brunton, pp 206t, 212, 305-307, 309; Katzung, pp 151-152, 154, 167, 180, 189.) Pra zos i n ca us es competi ti ve -bl ocka de. Thi s i s i n
s ta rk contra s t wi th phenoxybenza mi ne, whi ch ca us es i ns urmounta bl e (noncompeti ti ve) a nd l ong-l a s ti ng bl ocka de of -receptors by a l kyl a ti ng
them. Phenoxybenza mi ne i s cl a s s i fi ed a s a ha l oa l kyl a mi ne. You proba bl y dont need to remember tha t, but perha ps i t wi l l hel p you rea l i ze tha t
the drug a l kyl a tes the -a drenergi c receptors . Thi s cova l ent i ntera cti on, i n compa ri s on wi th typi ca l wea k i oni c i ntera cti ons between mos t drugs
a nd thei r receptors , a ccounts for phenoxybenza mi nes l ong-l a s ti ng (not s horter-a cti ng; a ) a nd noncompeti ti ve bl ocka de. As a res ul t of a l teri ng
receptor confi rma ti on, not merel y occupyi ng them a s pra zos i n a nd mos t other -bl ockers do, phenoxybenza mi ne renders l a rgel y i neffecti ve a goni s ts tha t ordi na ri l y woul d be us ed to countera ct effects of exces s i ve receptor bl ocka de. Thus , i f the pa ti ent beca me hypotens i ve i n res pons e
to phenoxybenza mi ne, ra i s i ng pres s ure wi th typi ca l a nd us ua l l y effecti ve drugs ma y not s ucceed. Nei ther drug ha s i ntri ns i c -bl ocki ng a cti vi ty (b),
a nd s o rega rdl es s of whi ch of thes e drugs we us e for the pheochromocytoma pa ti ent, a -bl ocker wi l l need to be us ed a djuncti vel y to control
(pri ma ri l y) hea rt ra te a nd contra cti l i ty. Nei ther drug s uppres s es epi nephri ne rel ea s e from the a drena l /s upra rena l medul l a (c); both tend to ca us e
orthos ta ti c hypotens i on by bl ocki ng peri phera l -medi a ted va s ocons tri cti on tha t occurs upon s ta ndi ng up s uddenl y.
186. The answer is c. (Brunton, pp 859, 864-865; Katzung, pp 604-607.) Thi s bri ef s cena ri o des cri bes hepa ri n-i nduced thrombocytopeni a (HIT). It i s a n
i mmune-medi a ted thrombocytopeni a tha t i s a ccompa ni ed by a pa ra doxi ca l increase i n thromboti c events (eg, i n l i mbs , bra i n, l ungs , a nd hea rt). It
a ffects a bout 1% to 3% of pa ti ents recei vi ng hepa ri n for more tha n a bout 4 da ys i n a row. The ca us e a ppea rs to i nvol ve forma ti on of a nti bodi es
tha t devel op to hepa ri n-pl a tel et compl exes . Thi s l ea ds to s ubs ta nti a l i ncrea s es of pl a tel et a cti va ti on tha t, i n turn, l ea ds to thrombos i s , va s cul a r
da ma ge, a nd eventua l l y s i gni fi ca nt decl i nes i n the number of functi ona l ci rcul a ti ng pl a tel ets (s i nce pl a tel ets ha ve been cons umed i n wi des prea d
thromboti c events ). Thi s phenomenon i s not a s s oci a ted wi th a ny of the other drugs l i s ted i n the ques ti on.
Importa nt note: Wa rfa ri n ca n a l s o ca us e a pa ra doxi ca l prothromboti c s ta te, proba bl y due to s uppres s ed protei n C a cti vi ty. It i s mos t l i kel y to
occur i f l oa di ng dos es a re us ed, ra ther tha n s ta rti ng wi th the a nti ci pa ted ma i ntena nce dos e. If you do s ome checki ng on the web or i n medi ci ne
texts , you wi l l proba bl y fi nd s evera l a l gori thms for ca l cul a ti ng wa rfa ri n l oa di ng dos es . The s a fes t a dvi ce i s not to us e a ny l oa di ng dos es : a l wa ys
get the i ni ti a l a nti coa gul a ti on wi th a hepa ri n, s ta rt wa rfa ri n s i mul ta neous l y, then conti nue the hepa ri n for a t l ea s t 5 da ys a nd unti l the INR
rea ches the des i red ra nge. Us i ng wa rfa ri n l oa di ng dos e s tra tegi es does not ha s ten wa rfa ri ns a nti thromboti c effect.
187. The answer is d. (Brunton, pp 801-804, 837-839; Katzung, pp 215-218, 220.) Di goxi n i nhi bi ts the s a rcol emma l Na +, K+-ATPa s e (s odi um pump). Thi s
reduces the a cti ve (ATP-dependent) extrus i on of i ntra cel l ul a r Na +. The rel a ti ve exces s of i ntra cel l ul a r Na + competes wi th i ntra cel l ul a r Ca 2+ for s i tes
on a s a rcol emma l 2Na -Ca excha nge di ffus i on ca rri er, s uch tha t l es s Ca 2 + i s extruded from the cel l s . The net res ul ts i ncl ude a ri s e of free [Ca 2+]i a nd
grea ter a cti n-myos i n i ntera cti ons (i e, a pos i ti ve i notropi c effect tha t i ncrea s es ca rdi a c output through a n i ncrea s e of s troke vol ume).
188. The answer is a. (Brunton, pp 752, 767-768; Katzung, pp 205-207.) -Bl ockers (repres ented i n thi s ques ti on by a tenol ol ) s houl d not be a dmi ni s tered
(es peci a l l y by a s ys temi c route) to pa ti ents wi th va s os pa s ti c a ngi na unl es s for a medi ca l emergency tha t requi res -bl ocka de a s a l i fe-s a vi ng
mea s ure. Reca l l the dua l rol es of a drenergi c receptors i n the corona ry va s cul a ture. Acti va ti on of 2 -a drenergi c receptors ca us es va s odi l a ti on.
Acti va ti on of -a drenergi c receptors i n the corona ry (a nd other) va s cul a ture fa vors va s ocons tri cti on ori n the s etti ng of va ri a nt a ngi na
va s os pa s m. Norma l l y thes e receptors a re expos ed to ci rcul a ti ng epi nephri ne, whi ch ca us es the oppos i ng va s odi l a tor (2 ) a nd va s ocons tri ctor ()
effects . Norepi nephri ne i s a l s o a cti va ti ng -a drenergi c receptors . Bl ock onl y the 2 (va s odi l a tor) effects i n the corona ri es a nd the cons tri ctor (a nd
s pa s m-fa vori ng) effects of the receptors a re l eft unoppos ed.
Di l ti a zem (b), a nondi hydropyri di ne ca l ci um cha nnel bl ocker, woul d not onl y l ower bl ood pres s ure but a l s o s uppres s the tendency for corona ry
va s ocons tri cti on or s pa s m by bl ocki ng va s cul a r s mooth mus cl e ca l ci um i nfl ux. Hydrochl orothi a zi de (c) i s the prototype thi a zi de di ureti c, a nd

metol a zone (e) i s thi a zi de-l i ke i n terms of mos t of i ts pha rma col ogi c profi l es . Nei ther i s a t a l l l i kel y to ca us e or fa vor va s ocons tri cti on i n the
corona ry ves s el s or el s ewhere. Los a rta n (d) i s a n a ngi otens i n receptor bl ocker. It not onl y ha s good a nti hypertens i ve a cti vi ty, but a l s o i s a pt to
s uppres s a ny corona ry va s ocons tri ctor i nfl uences of ci rcul a ti ng a ngi otens i n.
189. The answer is c. (Brunton, pp 753-755, 760; Katzung, pp 195-201.) At us ua l thera peuti c dos es , ni trogl yceri n (NTG) a cts pri ma ri l y a s a peri phera l
venodi l a tor. At hi gher dos es a rteri a l di l a ti on a l s o occurs . The net effect i s tha t, pa rti cul a rl y wi th exces s i ve dos es , peri phera l va s odi l a ti on occurs
a nd bl ood pres s ure (BP) fa l l s . Cri ti ca l a mong thes e pres s ure cha nges i s a fa l l of di a s tol i c BP. I s a y cri ti ca l beca us e DBP i s the ma i n dri vi ng force for
bl ood fl ow through the corona ry va s cul a ture. Up to a poi nt a utoregul a ti on of corona ry fl ow ma y hel p ma i nta i n ca rdi a c perfus i on, but once DBP
rea ches a certa i n l ower l evel corona ry bl ood fl ow i s i na dequa te to meet the oxygen dema nds of the myoca rdi um (i e, i s chemi a ha s devel oped).
Add to the underperfus i on of the hea rt by reduced DBP the fa ct tha t i f BP fa l l s by a s uffi ci ent a mount, a nd s uffi ci entl y fa s t, the ba roreceptor refl ex
i s a cti va ted. Tha t, i n turn, i ncrea s es hea rt ra te a nd contra cti l i tya n i ncrea s e of myoca r-di a l oxygen dema nd s i mul ta neous wi th reduced oxygen
s uppl y due to the decrea s ed corona ry perfus i on.
Ni trogl yceri n i s not meta bol i zed to cya ni de (a ). If you s el ected tha t pos s i bi l i ty a s your preferred a ns wer you a re confus i ng NTG wi th a nother
ni trova s odi l a tor tha t cl ea rl y does form cya ni de: ni troprus s i de. NTG does not, ca nnot, i nduce corona ry va s ocons tri cti on or s pa s m di rectl y (b). NTG i s
often us ed, wi th s ucces s a nd no extra ri s k, for pa ti ents wi th corona ry va s os pa s m (d). For s uch i ndi vi dua l s NTG i s ma i nl y us ed for a cute
ma na gement of a n ongoi ng a tta ck (a s a ppl i es to vi rtua l l y a l l a ngi na pa ti ents who ta ke the drug), wi th l ong-term s uppres s i on of va s os pa s m
provi ded by a ca l ci um cha nnel bl ocker. Fi na l l y, for pa ti ents wi th a ngi na tha t does not i nvol ve va s os pa s m, NTG i s frequentl y pres cri bed wi th a a drenergi c bl ocker (e). Here a ga i n, the NTG i s us ed ma i nl y for a cute s ymptom control a nd the -bl ocker for prophyl a xi s .
As a n a s i de, i f you i ndeed chos e a ns wer e, tha t the -bl ockers i ntri ns i c va s odi l a tor a cti vi ty potenti a ted tha t of the NTG, I thi nk you s houl d be
prepa red to ci te a s peci fi c -bl ocker wi th tha t property. The -bl ocker na med i n the ques ti on, propra nol ol , ha s a bs ol utel y no i ntri ns i c va s odi l a tor
a cti vi ty. Indeed, of the l ong l i s t of -bl ockers on the ma rket, onl y three ha ve the a bi l i ty to ca us e va s odi l a ti on. La beta l ol a nd ca rvedi l ol ha ve s ome
-bl ocki ng a cti vi ty tha t ca us es va s odi l a ti on, but the effect i s wea k. Then there i s nebi vol ol , whi ch ca us es s ome va s odi l a ti on through i ts
meta bol i s m to ni tri c oxi de.
Note: There i s a n i nteres ti ng a nd s omewha t controvers i a l phenomenon a s cri bed to NTG a nd s ome other va s odi l a tor drugs : corona ry s tea l . In
es s ence, va s odi l a ti on s hunts or di verts (s tea l s ) bl ood fl ow from a rea s of l ow perfus i on (eg, a s tenoti c corona ry ves s el ) to a rea s of hi gh perfus i on.
The pos tul a ted outcome i s tha t poorl y perfus ed ves s el s (a nd the ti s s ues s erved by them) become even l es s wel l perfus ed, thereby ca us i ng or
wors eni ng di s ta l ti s s ue i s chemi a .
190. The answer is a. (Brunton, pp 688t, 774-775, 791; Katzung, pp 260-262, 270.) Thi a zi de di ureti cs tend to ra i s e uri c a ci d concentra ti on i n the bl ood,
proba bl y by i nhi bi ti ng tubul a r s ecreti on of ura te. The el eva ti ons of ura te ma y be of l i ttl e concern for pa ti ents wi th no hi s tory of hyperuri cemi a or
gout, but for thos e wi th s uch a hi s tory i t ca n be a probl em tha t i s not a s s oci a ted wi th a ny of the other a ns wer choi ces gi ven. Thi a zi des ca n be
a dmi ni s tered to hyperuri cemi c/gouty pa ti ents , but tha t ma y requi re a nother drug (a l l opuri nol or febuxos ta t, whi ch a re xa nthi ne oxi da s e i nhi bi tors )
to countera ct di ureti ci nduced ri s es of ura te l evel s . If one ca n a voi d the probl ems by a voi di ng the thi a zi de, a nd the pos s i bl e need for a ddi ng a
s econd drug to countera ct the hyperuri cemi a , why not do jus t tha t? Tha t i s one of ma ny rea s ons why we mi ght us e a nother cl a s s of
a nti hypertens i ve drugs (eg, a ngi otens i n modi fi ers , ca l ci um cha nnel bl ockers , ma ny more) tha t dont ha ve nega ti ve effects on ura te l evel s .
None of the other a ns wer choi ces ha ve a ny a ppreci a bl e des i red or untowa rd effects on ura te l evel s , rena l ha ndl i ng of ura te, or the i nci dence or
s everi ty of gout.
191. The answer is d. (Brunton, pp 849, 946, 949, 977-982; Katzung, pp 320, 612.) Thes e i n vi tro res pons es , s howi ng tha t i buprofen (or a nother NSAID,
na proxen) ca n s i gni fi ca ntl y a nta goni ze the a nti pl a tel et effects of a s pi ri n, a re cl i ni ca l l y rel eva nt. Both i buprofen a nd a s pi ri n compete for the s a me
bi ndi ng s i tes on both COX-1 a nd COX-2. As pi ri ns i ntera cti on i s cova l ent, a nd i rrevers i bl e. Ibuprofen, however, bi nds to the s a me COX s i tes a s
a s pi ri n. Its a nti pl a tel et effects a re compa ra ti vel y wea k a nd revers i bl e. More i mporta ntl y, the bound i buprofen prevents the a bi l i ty of a s pi ri n to
bi nd to s a me cri ti ca l enzyme s i te. If a s pi ri n thera py i s s topped, COX-1 a cti vi ty wi l l i ncrea s e by a bout 10% per da y, a nd jus t 20% of ba s el i ne COX
a cti vi tytha t i s , s ki ppi ng a s pi ri n for more tha n 2 to 3 da ys ma y be enough to ena bl e s uffi ci ent COX a cti vi ty to be res tored a nd the protecti ve
a nti pl a tel et effects l os t. Us i ng i buprofen for more tha n a few da ys i n a row i s l i kel y to do the s a me. In s hort, the i ntera cti on s houl d be a voi ded.
And remember: i buprofen (a nd na proxen) i s a va i l a bl e OTC, a nd unl es s you expl i ci tl y tel l your pa ti ents to a voi d i t, your pha rma col ogi c efforts to
a fford ca rdi oprotecti on ma y be for na ught. Such NSAIDs a s di cl ofena c, a nd ma ny others , do not i nterfere wi th a s pi ri ns a nti pl a tel et effects .
Aceta mi nophen (a ), i n dos a ges of a bout 1 g/da y or more, ta ken for more tha n 7 da ys i n a row, ma y potenti a te wa rfa ri ns a nti coa gul a nt effects .
However, i t does not i nterfere wi th a s pi ri ns a nti pl a tel et effects ; a nd i t ha s no a nti coa gul a nt or a nti thromboti c effects i n i ts own ri ght. Cl opi dogrel
(b), a pl a tel et ADP receptor bl ocker tha t i s us ed a s a n a nti pl a tel et drug i n l i eu of a s pi ri n (for s ome pa ti ents ), does not bl ock a s pi ri ns a nti pl a tel et
effects , beca us e the mecha ni s ms of a cti on of cl opi dogrel a nd a s pi ri n a re s ynergi s ti c a nd di fferent. Da bi ga tra n (c) i s a n ora l a nti coa gul a nt,
s ometi mes us ed a s a n a l terna ti ve to wa rfa ri n (e). It i s cl a s s i fi ed a s a di rect-a cti ng thrombi n i nhi bi tor. Nei ther da bi ga tra n nor wa rfa ri n countera cts
a s pi ri ns a nti pl a tel et effects .
192. The answer is e. (Brunton, pp 752-753, 885, 892-898; Katzung, pp 625-627.) The fi ndi ngs a re cons i s tent wi th s ta ti n-i nduced myos i ti s a nd myopa thy,
whi ch s eem to ha ve progres s ed to rha bdomyol ys i s a nd rena l fa i l ureboth potenti a l l y fa ta l . Thi s s yndrome (a nd hepa totoxi ci ty) i s the mos t
s eri ous a dvers e res pons e to the s ta ti ns . It i s more preva l ent i n ol der pa ti ents , thos e wi th mul ti pl e i l l nes s es , a nd es peci a l l y thos e wi th rena l or
l i ver di s ea s e. Coa dmi ni s tra ti on of mos t other l i pi d-l oweri ng drugs (none of whi ch a re i n the a bove l i s t) i ncrea s es the ri s k of rha bdomyol ys i s ,
hepa totoxi ci ty, or both. As a n a s i de, the ri s k of rha bdomyol ys i s (or l es s er s kel eta l mus cl e cha nges ) i s not too much di fferent between the currentl y
a va i l a bl e s ta ti ns . However, i t wa s (a l l egedl y) s uch a probl em wi th one rel a ti vel y recent drug, ceri va s ta ti n, tha t the drug wa s pul l ed from the
ma rket.
Note: Never been ta ught s peci fi ca l l y a bout ros uva s ta ti n? Wel l , the drug na me ends i n -s ta ti n s o you s houl d a utoma ti ca l l y know qui te a bi t
a bout i t.
193. The answer is a. (Brunton, pp 178-179, 214t; Katzung, pp 98, 103, 331.) ACh ca us es va s odi l a ti on onl y when the va s cul a r endothel i um i s i nta ct
functi ona l l y a nd a na tomi ca l l y. The norma l res pons e, i ni ti a ted by ACh a cti ng a s a n a goni s t on mus ca ri ni c receptors , i nvol ves endothel i um-deri ved
rel a xi ng fa ctor/ni tri c oxi de (EDRF/NO) tha t i s genera ted i n a nd rel ea s ed from the endothel i um (tha t i s why i ts ca l l ed endothel i um-deri ved). The
NO di ffus es i nto the a dja cent va s cul a r s mooth mus cl e cel l s a nd i ncrea s es cGMP forma ti on. Tha t, i n turn, ca us es extrus i on of Ca 2+ a nd rel a xa ti on of
the mus cl e (va s odi l a ti on i n the i nta ct a ni ma l ). When the endothel i um i s removed (a ctua l l y qui te ea s y to do experi menta l l y) or da ma ged, ACh
ca us es concentra ti on-dependent i ncrea s es of s mooth mus cl e tens i on.
Is oproterenol (b) i s a 1 /2 a goni s t. Added to a n i n vi tro prepa ra ti on s uch a s the one us ed here, i t woul d onl y ca us e s mooth mus cl e rel a xa ti on
(2 effect) unl es s the -receptors were bl ocked; i t does not a l ter the contra cti l e res pons es to a dded ACh. Bl ocka de of mus ca ri ni c receptors (c)
ca nnot be correct. If tha t were the ca s e, pa rti cul a rl y under control condi ti ons , contra cti l e res pons e to ACh woul d be di mi ni s hed or a bol i s hed, a nd

contra cti on s hown under the experi menta l condi ti ons woul d not be cha nged from wha t i s s hown i n the fi gure. Pra zos i n (d) ca nnot be correct. It i s
a n 1 receptor bl ocker, a nd pretrea ti ng wi th i t woul d not ca us e va s ocons tri cti on wi th or wi thout a dded ACh. Botul i num toxi n (e) bl ocks ACh rel ea s e
from chol i nergi c nerves . Al though there ma y be s ome pos tga ngl i oni c pa ra -s ympa theti c (a nd s ympa theti c) nerve endi ngs i n the ti s s ue s a mpl e,
the res pons es s hown a bove were ca us ed by a ddi ng ACh di rectl y to the ti s s ue ba th a nd s o they a re i ndependent of a ny res i dua l a utonomi c neura l
i nfl uences .
194. The answer is b. (Brunton, pp 732-733; Katzung, pp 183-185, 219-220, 299, 1042t.) ACE i nhi bi tors (a nd a ngi otens i n receptor bl ockers , ARBs , eg,
l os a rta n) a re contra i ndi ca ted i n pregna ncy (ca tegory X), a nd s houl d not be a dmi ni s tered to women of chi l dbea ri ng potenti a l not jus t women
who a re pregna nti n the fi rs t pl a ce. Norma l i n utero devel opment of the ki dneys a nd other urogeni ta l s tructures s eems to be a ngi otens i ndependent. ACE i nhi bi tors , or ARBs , gi ven duri ng the s econd or thi rd tri mes ters (not the fi rs t) ha ve been a s s oci a ted wi th s evere a nd s ometi mes
fa ta l devel opmenta l a noma l i es of thes e s tructures . Cra ni a l hypopl a s i a , a nd neona ta l hyperka l emi a a nd hypotens i on, ha ve a l s o been reported.
-Methyl dopa (a ) i s cons i dered one of the preferred a nti hypertens i ve drugs for pregna nt women. It not onl y control s ma terna l bl ood pres s ure
wel l , but a l s o i s rema rka bl y free of a dvers e effects on the fetus . (Indeed, i t i s the mos t l i kel y drug tha t we woul d pres cri be for thi s hypertens i ve
a nd now pregna nt woma n.)
-Bl ockers s uch a s l a beta l ol (d) a re s ometi mes us ed duri ng pregna ncy, pos i ng no s peci fi c or s i gni fi ca nt ri s ks to the mother or the fetus ,
provi ded tha t a dequa te peri na ta l ca re i s gi ven a nd bl ood pres s ure does nt fa l l exces s i vel y. None of the ca l ci um cha nnel bl ockers (i ncl udi ng
vera pa mi l , e) s eem to ha ve a ny s i gni fi ca nt benefi ts or ri s ks duri ng pregna ncy, compa red wi th other drugs . (Vera pa mi l , for exa mpl e, i s i n pregna ncy
ca tegory C.) One theoreti ca l concern wi th vera pa mi l a nd di l ti a zem i s a prol onga ti on of l a bor a s pa rturi ti on dra ws nea r, due to s uppres s i on of
uteri ne contra cti l i ty.
There a re concerns wi th us i ng di ureti cs duri ng pregna ncy. Furos emi de (c) or other l oop di ureti cs pos e rel a ti vel y s i gni fi ca nt feta l ri s ks . However,
tha t i s rel a ted to potenti a l ma terna l hypovol emi a a nd hypotens i on tha t ma y l ea d to pl a centa l underperfus i on. There i s no tera togeni c or
embryopa thi c ri s k on pa r wi th tha t a s s oci a ted wi th the a ngi otens i n modi fi ers (ACE i nhi bi tors or ARBs ). Moreover, when the goa l i s trea ti ng
es s enti a l hypertens i on i n the a bs ence of hypervol emi a , edema , a s ci tes , a nd s o on, l oop di ureti cs s el dom a re us ed. Ins tea d, thi a zi de or thi a zi del i ke di ureti cs a re the ones us ua l l y chos en. Neverthel es s , the thi a zi des a l s o pos e a ri s k of pl a centa l underperfus i on, a nd s o they a re not preferred
or i dea l a nti hypertens i ves for the pregna nt woma n.
Note: It i s not neces s a ry (now) for you to memori ze the pregna ncy cl a s s i fi ca ti ons of the nontera togeni c drugs l i s ted a bove. Wha t you need to
know i s tha t ACE i nhi bi tors a nd ARBs a re a bs ol utel y contra i ndi ca ted. So i s wa rfa ri n, a t l ea s t duri ng the fi rs t 12 weeks of ges ta ti on, whi ch i s
a ddres s ed i n Ques ti on 199.
195. The answer is c. (Brunton, pp 868-870; Katzung, pp 613, 617.) Cl opi dogrel (a nd the much l es s er-us ed drug ti cl opi di ne) i s a noncompeti ti ve
a nta goni s t of ADP. Thi s prodrug (i t mus t be meta bol i ca l l y a cti va ted) ca us es l a rgel y i rrevers i bl e (i e, for the l i feti me of the pl a tel et) i nhi bi ti on of
pl a tel et a ggrega ti on by bl ocki ng ADP bi ndi ng to the G i coupl ed P2Y(AC) receptor. It ha s no effect on pl a tel et a cti va ti on a nd a mpl i fi ca ti on ca us ed by
s uch other proa ggrega tory a goni s ts a s col l a gen, thromboxa ne A2 , thrombi n, PAF, s erotoni n, or epi nephri ne.
As pi ri n (a ) i nhi bi ts pl a tel et a ggrega ti on ca us ed by thromboxa ne A2 (TXA2 ) onl y, a nd does s o onl y by i nhi bi ti ng TXA2 s ynthes i s vi a cycl ooxygena s e,
not by bl ocki ng TXA2 receptors .
Bi va l i rudi n (b) i s a s yntheti c hi rudi n deri va ti ve (you ma y reca l l tha t hi rudi n i s produced by the medi ci na l l ea ch, Hirudo medicinalis). It i s cl a s s i fi ed
a s a n a nti coa gul a nt, not a s a n a nti pl a tel et drug. It i s a di rect-a cti ng i nhi bi tor of free a nd cl ot-bound thrombi n, whi ch l ea ds to two ma i n effects : (1)
decrea s ed convers i on of fi bri nogen to fi bri n; a nd (2) reduced a cti va ti on of Fa ctor XIIIa , whi ch i n turn decrea s es convers i on of s ol ubl e fi bri n
monomers to i ns ol ubl e (pol ymeri zed) fi bri n.
Bi va l i rudi n i s gi ven IV a s a n a l terna ti ve to hepa ri n (both drugs bi nd to free thrombi n, but bi va l i rudi n a l s o i ntera cts wi th cl ot-bound thrombi n),
ma i nl y a l ong wi th a s pi ri n for pa ti ents wi th uns ta bl e a ngi na who a re undergoi ng a ngi opl a s ty. It i s a l s o us ed to hel p trea t hepa ri n-i nduced
thrombocytopeni a ; a nd s eems to be more effecti ve tha n hepa ri n when gi ven pos tmyoca rdi a l i nfa rcti on. A rel a ted drug i s a rga troba n.
Hepa ri n a nd wa rfa ri n (d, e) ha ve no di rect effects on pl a tel ets . (You s houl d a l s o reca l l tha t s i nce wa rfa ri ns s i te of a cti on i s the l i ver, i t ha s no
a nti coa gul a nt effects when tes ted i n vi tro (i e, a dded to a tube of whol e bl ood).
Note: I menti oned tha t ti cl opi di ne i s much l es s er-us ed tha n cl opi dogrel . Actua l l y, i ts s el dom us ed. The rea s on? A grea ter ri s k of thromboti c
thrombocytopeni c purpura (TTP) a nd/or neutropeni a .
196. The answer is e. (Brunton, pp 765-767; Katzung, pp 193-208.) The va s cul a r ca l ci um cha nnel -bl ocki ng a cti ons of vera pa mi l or di l ti a zem
(nondi hydropyri di ne cl a s s ) wi l l not onl y l ower s ys temi c bl ood pres s ure, but a l s o tend to counter corona ry a rteri a l ca l ci um i nfl ux tha t fa vors
va s os pa s m. Thus , i n thi s s etti ng we ca n expect both a nti hypertens i ve a nd a nti a ngi na l effects from one drug.
One mi ght a rgue tha t ni fedi pi ne (a ns wer c) woul d be a rea s ona bl e a l terna ti ve. However, reca l l tha t the di hydropyri di nes (whi ch i s the cl a s s to
whi ch ni fedi pi ne bel ongs ) l a ck ca rdi a c depres s a nt a cti ons . Ra pi dl y a cti ng formul a ti ons of a di hydropyri di ne, even i f gi ven ora l l y, a re l i kel y to
l ower bl ood pres s ure (the des i red a nti hypertens i ve effect), but l a cki ng ca rdi a c-depres s a nt a cti ons a re l i a bl e to tri gger refl ex
(s ympa theti c/ba roreceptor) ca rdi a c s ti mul a ti on. The res ul ti ng i ncrea s es of ei ther or both ca rdi a c ra te a nd contra cti l i ty (medi a ted, refl exl y, by
s ympa theti c a cti va ti on) neces s a ri l y ma y ra i s e myoca rdi a l oxygen dema nd s uffi ci ent to ca us e myoca rdi a l i s chemi a , a nd/or ma y tri gger corona ry
va s os pa s m. (The degree to whi ch a di hydropyri di ne wi l l ca us e unwa nted refl ex ca rdi a c s ti mul a ti on depends on the drug, the dos e, a nd even the
dos a ge form [eg, i mmedi a te-a cti ng vs extended-a cti ng].) Nonethel es s , a nondi hydropyri di ne woul d ha ve a much better overa l l profi l e of
ca rdi a c/va s cul a r a cti ons .
ACE i nhi bi tors or a n ARB (a ), or a thi a zi de (d), mi ght ca us e no pa rti cul a r probl ems for a pa ti ent wi th va s os pa s ti c a ngi na , but they a l s o ha ve no
a cti ons tha t woul d hel p tha t comorbi di ty. Why s el ect one of them when a nondi hydropyri di ne ca l ci um cha nnel bl ocker mi ght be benefi ci a l for both
probl ems ?
-Bl ockers (b) woul d be a poor choi ce. Reca l l tha t the corona ry va s cul a ture cons tri cts i n res pons e to -a drenergi c i nfl uences , whi l e va s cul a r 2
receptor a cti va ti on tends to ca us e corona ry va s odi l a ti on. Pa ti ents wi th va s os pa s ti c a ngi na depend on -medi a ted va s odi l a tory i nfl uences , a nd a re
a t grea ter ri s k of i s chemi c events i f the -receptors a re bl ocked.
197. The answer is c. (Brunton, pp 899-901, 972; Katzung, pp 627-628.) Ans weri ng thi s ques ti on correctl y i ndeed depends on your knowl edge of s evera l
drugs , a nd thei r prototype or repres enta ti ve a gents , tha t goes beyond ca rdi ova s cul a r (s i nce I i ncl uded a di a betes drug [metformi n] a nd a n
a nti depres s a nt [es ci ta l opra m] a s pos s i bl e a ns wer choi ces ).
Nonethel es s , ni a ci n (ni coti ni c a ci d; vi ta mi n B 3 ) i s often a dded-oni n dos a ges hi gher tha n thos e recommended for vi ta mi n s uppl ementa ti on
ma i nl y to l ower HDL a nd tri gl yceri de l evel s , pa rti cul a rl y i n pa ti ents wi th the cl a s s i c mi xed hyperl i pi demi a cha ra cteri zed by el eva ted chol es terol
a nd tri gl yceri de l evel s (Type IIb) a nd who a rent a dequa tel y ma na ged wi th a s ta ti n. The pri ma ry effect of ni a ci n i s to decrea s e producti on of VLDLs

(ma i nl y by i nhi bi ti ng l i pol ys i s i n a di pocytes ). Si nce LDLs a re by-products of VLDL degra da ti on, the fa l l i n VLDL l evel s ca us es LDL l evel s to fa l l a s
wel l . La s tl y, reca l l tha t VLDLs del i ver tri gl yceri des to a nd i ncrea s e thei r s tora ge i n a di pos e ti s s ue. By decrea s i ng VLDL producti on, then, ni a ci n
i ndi rectl y counters tri gl yceri de a ccumul a ti on a nd fa vors tri gl yceri de cl ea ra nce (el i mi na ti on). See the a ns wer for Ques ti on 258 for more i nforma ti on
a bout ni a ci ns more common s i de effects .
Pra va s ta ti n a nd other s ta ti ns (HMG CoA reducta s e i nhi bi tors ), whi l e ma i nl y us ed for hyperchol es terol emi a (to l ower LDL-chol es terol l evel s ),
often concomi ta ntl y ra i s e HDL a nd l ower tri gl yceri de l evel s a dequa tel y. When s ta ti ns a nd l i fes tyl e modi fi ca ti ons fa i l to control tri gl yceri de l evel s
a dequa tel y, a ddi ng ni a ci n i s us ua l l y a rea s ona bl e next s tep.
Ci ta l opra m (a ), es ci ta l opra m, a nd other SSRI-a nti depres s a nts ha ve no known effects on a l tered vi ta mi n a bs orpti on or on the ca rdi ova s cul a r
s ys tem. Metformi n (b), the prototype bi gua ni de often us ed for ma na gi ng type 2 di a betes mel l i tus , typi ca l l y s uppres s es (not i ncrea s es ) a ppeti te.
Sta ti ns do not ca us e peri phera l neuropa thy (d); a nd ACE i nhi bi tors (ra mi pri l a nd others ; e) do not ca us e di a beti c nephropa thy, a l though they a re
cl ea rl y contra i ndi ca ted for pa ti ents wi th s evere bi l a tera l rena l a rteri a l s tenos i s , s uch a s tha t a s s oci a ted wi th s evere a nd poorl y control l ed
di a betes mel l i tus .
198. The answer is d. (Brunton, pp 828, 844, 1405-1407; Katzung, pp 238, 921-922.) Qui ni di ne i s becomi ng a n outmoded drug, but i t i s , of cours e, s ti l l
bei ng us ed. It ma y be des cri bed a s a broa d-s pectrum a nti a rrhythmi c (tha t does not mea n i t i s i ndi ca ted or s a fe for a l l a rrhythmi a s a nd a l l
eti ol ogi es ). It i s ma i nl y us ed for l ong-term ma na gement of s upra ventri cul a r a nd ventri cul a r a rrhythmi a s : a tri a l fl utter a nd fi bri l l a ti on; a nd
s us ta i ned ventri cul a r ta chyca rdi a . The drugs effects refl ect di rect i on cha nnel -bl ocki ng a cti ons pl us a va ri ety of receptor-bl ocki ng effects tha t ma y
countera ct the di rect effects .
Di rect bl ocka de of s odi um cha nnel s (a ma jor a cti on of Cl a s s I a nti a rrhythmi cs ) s l ows i mpul s e conducti on i n the a tri a , ventri cl es , a nd Hi s Purki nje s ys tem. Repol a ri za ti on a t thos e s i tes tends to be del a yed, pres uma bl y by bl ocka de of pota s s i um cha nnel s . Among other cha nges , the ECG
s hows wi dened QRS compl exes a nd prol onged QT i nterva l s (whi ch ma y predi s pos e pa ti ents , pa rti cul a rl y thos e wi th l ong QT s yndrome, to s ome
s eri ous a rrhythmi a s , i ncl udi ng tors a des ).
Qui ni di ne ha s s trong a nti chol i nergi c (va gol yti c) effects tha t a re pa rti cul a rl y a ppa rent a t the SA node (i ncrea s ed a utoma ti ci ty, tends to
predomi na te over di rect depres s a nt effects from s odi um cha nnel bl ocka de) a nd the AV node (i ncrea s ed conducti on vel oci ty, correct a ns wer d).
(Reca l l tha t va ga l tone on the SA node s l ows s ponta neous depol a ri za ti on a nd hea rt ra te; the va gol yti c effects of qui ni di ne wi l l therefore do the
oppos i te.) The effects on AV conducti on a re a ma i n rea s on why, when qui ni di ne thera py i s to be s ta rted a nd a tri a l ra tes a re s ti l l hi gh, we pretrea t
the pa ti ent wi th a dos e of a drug tha t bl ocks down the AV node: di goxi n, s ometi mes vera pa mi l , a nd occa s i ona l l y a -bl ocker. The ma i n rea s on
why ventri cul a r ra tes a rent i denti ca l (or cl os e to) a tri a l ra tes duri ng a tri a l fi bri l l a ti on i s beca us e the AV node ca nnot tra ns mi t i mpul s es a t s uch
hi gh ra tes . Thi s protecti ve effect depends on AV noda l refra ctori nes s a nd a rel a ti ve i na bi l i ty to tra ns mi t too ma ny i mpul s es per ti me. If we di d not
s uppres s the AV node before gi vi ng qui ni di ne, the AV noda l conducti on-s ti mul a ti ng effects of the qui ni di ne mi ght i ncrea s e AV noda l
tra ns mi s s i on; ventri cul a r ra tes mi ght ri s e to da ngerous l evel s a s the a tri a l ra te s l ows i n res pons e to the qui ni di ne.
Qui ni di ne i s not l i kel y to i ncrea s e bl ood pres s ure (b), or wors en preexi s ti ng hypertens i on. Qui te the contra ry: the predomi na nt va s cul a r effect of
the drug i s di l a ti on, a nd bl ood pres s ure fa l l s , due to peri phera l va s cul a r -a drenergi c bl ocki ng a cti vi ty. Li kewi s e, qui ni di ne exerts a nega ti ve
i notropi c effectnot a pos i ti ve one (e)on ventri cul a r mus cl e. Tha t, too, ca n contri bute to a fa l l of bl ood pres s ure. For l ong-term ma na gement of a
pa ti ent wi th a tri a l fi bri l l a ti on, a nti coa gul a nts a re i mporta nt (not contra i ndi ca ted, c) for prophyl a xi s of venous thrombos i s ; the us e of qui ni di ne
does not contra i ndi ca te tha t.
199. The answer is e. (Brunton, pp 857, 865; Katzung, pp 608-611, 1043t.) The s cena ri o des cri bes the cl a s s i c fi ndi ngs wi th wa rfa ri n embryopa thy: na s a l
deformi ti es (ma i nl y a fl a tteni ng of the nos e) a nd s ti ppl i ng (ba s ed on s ta nda rd x-ra y i ma ges ) a t the epi phys es of the l ong bones . The drug i s , a s
noted, a bs ol utel y contra i ndi ca ted duri ng pregna ncy. The feta l ri s ks a re grea tes t i f wa rfa ri n i s ta ken a t a ny ti me duri ng the fi rs t 12 or s o weeks of
ges ta ti on, but a dvers e feta l effects ca n occur l a ter. They a re i rrevers i bl e, s ometi mes fa ta l ; there i s no drug or vi ta mi n (eg, vi ta mi n K, fol a te) thera py
tha t wi l l be of benefi t. Al l the other drugs l i s ted pos e s ome pregna ncy-rel a ted ri s ks (but l ower a nd wi th l es s s upporti ng da ta tha n wi th wa rfa ri n),
a nd they do not s ha re the cha ra cteri s ti cs of wa rfa ri n embryopa thy. Cl oni di ne (a ) i s i n pregna ncy ca tegory C. Its a nti hypertens i ve mecha ni s m i s
l a rgel y i denti ca l to tha t of methyl dopa , whi ch i s i n ca tegory B a nd us ua l l y i s a preferred drug for hypertens i on duri ng pregna ncy. Low mol ecul a r
wei ght hepa ri n (b) i s a l s o i n pregna ncy ca tegory B. If a nti coa gul a ti on i s requi red duri ng pregna ncy, i t i s the drug tha t mos t l i kel y wi l l be us ed.
Hydrochl orothi a zi de (or thi a zi de di ureti cs i n genera l ) ha s no known huma n tera togeni c effects (ca tegory B). Ni trogl yceri n i s not contra i ndi ca ted
beca us e of tera togenes i s (ca tegory C).
Note: Il l ki ndl y a s k you to revi ew the a ns wers a nd expl a na ti ons for Ques ti on 194, a nd reca l l tha t even though a ca rdi ova s cul a r drug ma y not be
tera togeni c nor a bs ol utel y contra i ndi ca ted i n pregna ncy, i t ca n ca us e a dvers e (potenti a l l y fa ta l ) feta l effects i f, for exa mpl e, i t ca us es hypotens i on
a nd/or hypovol emi a , whi ch ca n s i gni fi ca ntl y reduce pl a centa l bl ood fl ow. Reca l l tha t wa rfa ri n, ACE i nhi bi tors , a nd a ngi otens i n receptor bl ockers
a re contra i ndi ca ted i n pregna ncy.
200. The answer is d. (Brunton, pp 297, 780-781; Katzung, pp 175-176.) Among a l l the common ora l a nti hypertens i ves , a Coombs -pos i ti ve tes t i s
a s s oci a ted onl y wi th methyl dopa . It occurs i n up to a bout 20% of pa ti ents ta ki ng thi s drug l ong term. It ma y progres s to hemol yti c a nemi a , but tha t
s el dom occurs . The proba bl e ca us e i s a n i mmune rea cti on (IgG a nti bodi es ) di rected a ga i ns t a nd potenti a l l y l ys i ng the red cel l membra ne. Other
drugs wi th the potenti a l to ca us e a n i mmunohemol yti c a nemi a a re peni ci l l i ns , qui ni di ne, proca i na mi de, a nd s ul fona mi des .
201. The answer is a. (Brunton, pp 206t, 306f, 309, 774; Katzung, pp 151-152, 154-156.) Phenoxybenza mi ne i s a l ong-a cti ng a nd noncompetitive -a drenergi c
bl ocker. It works by a l kyl a ti ng (ra ther tha n merel y occupyi ng a nd bl ocki ng) -a drenergi c receptors , thereby renderi ng them i nca pa bl e of
i ntera cti ng wi th -a drenergi c a goni s ts s uch a s epi nephri ne (whi ch i s bei ng rel ea s ed i n a bunda nce by the pheochromocytoma ). The drug ha s no
a bi l i ty to bl ock -a drenergi c receptors (b), i nhi bi t ca techol a mi ne s ynthes i s (c), i nhi bi t a ngi otens i n converti ng enzyme (d), or a ffect a ny of the ma jor
enzymes i nvol ved i n ca techol a mi ne degra da ti on (COMT, a ns wer e; or MAO).
202. The answer is c. (Brunton, pp 328-329; Katzung, pp 157-161, 165-166.) No -bl ocker ordi na ri l y s houl d be a dmi ni s tered to pa ti ents wi th a s thma ,
beca us e of a grea t ri s k of s evere a nd potenti a l l y fa ta l bronchocons tri cti on or bronchos pa s m (unl es s the -bl ocker i s bei ng gi ven for a medi ca l
emergency tha t requi res -bl ocka de, a nd l i kel y benefi ts outwei gh l i kel y ri s ks ). Thi s a ppl i es to a l l cl a s s es of -bl ockers : nons el ecti ve, l i ke
propra nol ol ; 1 s el ecti ve, tha t i s , a tenol ol or metoprol ol ; thos e wi th i ntri ns i c s ympa thomi meti c/pa rti a l a goni s t a cti vi ty, s uch a s pi ndol ol ; a nd
thos e tha t a l s o ha ve -bl ocki ng a cti vi ty, tha t i s , l a beta l ol a nd ca rvedi l ol . The contra i ndi ca ti on a ppl i es to a l l a dmi ni s tra ti on routes , i ncl udi ng
topi ca l (ophtha l mi c); there a re cl i ni ca l reports of fa ta l bronchos pa s m i nduced by topi ca l ophtha l mi c a dmi ni s tra ti on of jus t one drop of bl ockers .
The rea s on? Ai rwa ys of pers ons wi th a s thma a re exqui s i tel y s ens i ti ve to a hos t of bronchocons tri ctor s ti mul i a nd exqui s i tel y dependent on the
bronchodi l a tor effects of ci rcul a ti ng epi nephri ne (2 -receptors ). Bl ock thos e -receptors , a nd tha t s ets the s ta ge for bronchocons tri cti on or
bronchos pa s m. Another i mporta nt fa ctor i s tha t thi s pa ti ent needs a l buterol for occa s i ona l rel i ef of bronchos pa s m. The drug works , of cours e, by

a cti va ti ng 2 a drenergi c receptors i n the a i rwa ys . Any or a l l of the a va i l a bl e -bl ockers wi l l a nta goni ze a l buterol s des i red effects , the s o-ca l l ed
ca rdi os el ecti ve a gents i ncl uded, beca us e thei r s el ecti vi ty for 1 -receptors i s onl y rel a ti ve, not a bs ol ute; a nd i t i s hi ghl y dos e-dependent.
Di l ti a zem (a ) a nd pa rti cul a rl y vera pa mi l (e), both nondi hydropyri di ne ca l ci um cha nnel bl ockers , mi ght be a good choi ce for thi s pa ti ent. They not
onl y l ower bl ood pres s ure by bl ocki ng ca l ci um i nfl ux i nto va s cul a r s mooth mus cl e, but a l s o (theoreti ca l l y, a t l ea s t) do the s a me i n a i rwa y s mooth
mus cl e, thereby preventi ng or a t l ea s t reduci ng bronchocons tri cti on. Hydrochl orothi a zi de pos s i bl y coul d exa cerba te the probl ems by ca us i ng
exces s i ve fl ui d l os s (whi ch coul d fa vor bronchocons tri cti on), but the cha nces of thi s a re l ow. (Loop di ureti cs s uch a s furos emi de woul d be of more
concern, owi ng to thei r grea ter effi ca cy i n terms of ca us i ng l os s of ci rcul a ti ng fl ui d vol ume). There a re no s peci fi c concerns wi th us i ng ra mi pri l , a n
a ngi otens i n converti ng enzyme i nhi bi tor. (Remember: Drugs wi th generi c na mes endi ng i n -pri l a re ACE i nhi bi tors , s o even i f you l ea rned a bout
onl y ca ptopri l a s a n ACE i nhi bi tor, you s houl d ha ve rea l i zed tha t ra mi pri l i s i n the s a me cl a s s .)
Note: Its fa i r to s a y tha t the Bi g 4 cl a s s es of a nti hypertens i ve drugs ca n be s umma ri zed a s A, B, C, D: ACE i nhi bi tors or a ngi otens i n receptor
bl ockers ; Beta -bl ockers ; Ca l ci um cha nnel bl ockers ; a nd Di ureti cs (thi a zi des or thi a zi de-l i ke a gents s uch a s metol a zone). Whi ch i s bes t for a
pa rti cul a r pa ti ent depends on a hos t of pa ti ent-rel a ted fa ctors tha t ma y wei gh i n fa vor of s el ecti ng a drug from a pa rti cul a r cl a s s (A, B, C, D) or
wei gh a ga i ns t a pa rti cul a r cl a s s . There ha s been a res urgence i n the us e a nd recommenda ti on of thi a zi des or thi a zi de-l i ke drugs for i ni ti a ti ng
a nti -hypertens i ve thera py. Li kewi s e, much more recentl y, a nd for a va ri ety of rea s ons , s ome experts a re s ta ti ng tha t -bl ockers s houl d be dropped
from the Bi g 4 l i s t for mos t pa ti ents .
203. The answer is d. (Brunton, pp 801-804, 829t, 835t, 837-839; Katzung, pp 215-218, 221, 1036-1037.) Of the effects l i s ted here, you woul d expect to fi nd
s l owed AV noda l conducti on vel oci ty i n res pons e to di goxi n. Thi s i s a common a nd, i n ma ny s i tua ti ons us eful , effect. For exa mpl e, when we gi ve
the drug a s pa rt of the pha rma col ogi c ma na gement of a tri a l fi bri l l a ti on or fl utter, the ma i n des i red res pons e i s not s uppres s i on of the a rrhythmi a
per s e, but ra ther to bl ock down the AV node s o tha t a s a tri a l ra tes fa l l (but a re s ti l l hi gh), the AV node wi l l be una bl e to tra ns mi t the s a me
frequency of i mpul s es to the ventri cl es . Tha t i s , we protect the ventri cl es from exces s i ve a ccel era ti on by i nduci ng a degree of AV bl ock. In terms
of more s peci fi c effects on the AV node, di goxi n s l ows conducti on vel oci ty a nd i ncrea s es AV noda l refra ctory peri ods .
Other predomi na nt effects on the hea rta l l concentra ti on-dependenti ncl ude i ncrea s es of both a tri a l a nd ventri cul a r a utoma ti ci ty a nd of
conducti on vel oci ty through thos e s tructures a nd the Hi s -Purki nje s ys tem.
204. The answer is d. (Brunton, pp 767t, 779-781; Katzung, pp 181, 189, 220.) Hydra l a zi ne predomi na tel y di l a tes a rteri ol es , wi th negl i gi bl e effects on
venous ca pa ci ta nce. It typi ca l l y l owers bl ood pres s ure s o wel l a nd qui ckl y tha t i t ca n tri gger two unwa nted ca rdi ova s cul a r res pons es tha t us ua l l y
need to be dea l t wi th:
1. Reflex cardiac stimulation (i nvol vi ng the ba roreceptor refl ex) i s common, a nd i t i s typi ca l l y ma na ged wi th a -a drenergi c bl ocker (unl es s i t i s
contra i ndi ca ted). An a l terna ti ve a pproa ch woul d be to us e ei ther vera pa mi l or di l ti a zem (but not a di hydropyri di ne-type ca l ci um cha nnel
bl ocker s uch a s ni fedi pi ne, whi ch woul d not s uppres s a nd, i n fa ct mi ght a ggra va tethe refl ex ca rdi a c s ti mul a ti on).
2. Activation of the renin-angiotensin-aldosterone system to compens a te for wha t the body bel i eves i s a n exces s i ve a nd unwa nted fa l l of bl ood
pres s ure. One cons equence of thi s unwa nted res pons e i s i ncrea s ed rena l s odi um retenti on tha t woul d expa nd ci rcul a ti ng fl ui d vol ume a nd
countera ct hydra l a zi nes pres s ure-l oweri ng effects . Thi s i s typi ca l l y ma na ged wi th a di ureti c. A thi a zi de ma y be s uffi ci ent to comba t the s odi um
retenti on, but a more effi ca ci ous di ureti c (l oop di ureti c) ma y be neces s a ry a nd i s us ua l l y s el ected.
Ca ptopri l (or a nother ACE i nhi bi tor, or a n a ngi otens i n receptor bl ocker s uch a s l os a rta n) mi ght be a s ui ta bl e a dd-on (i t woul d ca us e s ynergi s ti c
a nti hypertens i ve effects a nd prevent a l dos terone-medi a ted rena l effects ). However, combi ni ng i t wi th ni fedi pi ne (di hydropyri di ne ca l ci um
cha nnel bl ocker) i s i rra ti ona l . As noted a bove, gi ven the pure va s odi l a tor a cti ons of ni fedi pi ne a nd the l a ck of ca rdi a c-depres s i ng a cti vi ty (a s
occurs wi th vera pa mi l ), the net effect on hea rt ra te woul d be ei ther no s uppres s i on of the ta chyca rdi a or a wors eni ng of i t.
Di goxi n, a l one or wi th vi rtua l l y a ny other drug (c), i s not ra ti ona l beca us e i t woul d not meet the goa l s of bl unti ng refl ex ca rdi a c s ti mul a ti on a nd
effi ci entl y countera cti ng the cons equences of reni n-a ngi otens i n-a l dos terone s ys tem a cti va ti on. There i s no i ndi ca ti on tha t there i s need for
i notropi c s upport i n thi s pa ti ent.
Spi ronol a ctone, a l one or wi th di goxi n, woul d be of l i ttl e benefi t. One coul d a rgue tha t by vi rtue of the s pi ronol a ctones a bi l i ty to i nduce
di ures i s by bl ocki ng a l dos terones rena l tubul a r effects , i t woul d countera ct hydra l a zi nes a bi l i ty to l ea d to rena l s odi um retenti on. Tha t ma y be
true, but s pi ronol a ctone (wi th or wi thout di goxi n) wi l l do nothi ng des i ra bl e to bl unt the unwa nted refl ex ca rdi a c a cti va ti on.
Ni trogl yceri n (e) woul d a dd to hydra l a zi nes a nti hypertens i ve effects , but i t woul d proba bl y a ggra va te (a nd certa i nl y not countera ct) the refl ex
ca rdi a c s ti mul a ti on, a nd ma y a l s o i ncrea s e the unwa nted rena l res pons e (vi a a hemodyna mi c mecha ni s m).
Both tri a mterene a nd a mi l ori de a re pota s s i um-s pa ri ng di ureti cs . The combi na ti on of two di ureti cs i n thi s cl a s s i s a l mos t a l wa ys i rra ti ona l (i t
ca n l ea d to hyperka l emi a ). Ei ther mi ght benefi ci a l l y comba t a propens i ty for rena l s odi um retenti on i n res pons e to hydra l a zi ne. But, a s wi th a ny
di ureti c a l one, ei ther or both woul d do l i ttl e i f a nythi ng to control the unwa nted ca rdi a c res pons e.
Vi ta mi n K (i ncl uded i n a ns wer c) wa s i ncl uded a s a foi l . If you a re a s s oci a ti ng hydra l a zi ne wi th s ome vi ta mi n-rel a ted probl em, you s houl d be
thi nki ng of vi ta mi n B 6 (pyri doxi ne): hydra l a zi ne ca n i nterfere wi th B 6 meta bol i s m, ca us i ng s uch s ymptoms a s peri phera l neuri ti s , a nd s o
prophyl a cti c B 6 s uppl ementa ti on i s often us ed a l ong wi th l ong-term hydra l a zi ne thera py. Hydra l a zi ne i s a l s o known to ca us e a l upus -l i ke
s yndrome. Whi l e prophyl a xi s wi th pyri doxi ne hel ps wi th the potenti a l neuri ti s i t does nothi ng for the l upus -l i ke s yndrome.
Note: Nowa da ys ma ny phys i ci a ns cons i der hydra l a zi ne to be (a t bes t) a fi fth or s i xth l i ne a gent for chroni c hypertens i on. Rega rdl es s , the drug i s
not a go to drug unl es s , es s enti a l l y, a l l other rea s ona bl e opti ons ha ve been tri ed a nd s hown to be i neffecti ve.
205. The answer is a. (Brunton, p 725; Katzung, pp 295-300.) The bra dyca rdi a ca us ed by the unknown drug i s refl ex-medi a ted by ba roreceptor a cti va ti on
i n res pons e to the ri s e of bl ood pres s ure. Angi otens i n II, by a cti va ti ng va s cul a r A-II receptors , ra i s es bl ood pres s ure a nd peri phera l res i s ta nce,
a nd tha t res pons e woul d not be i nhi bi ted by pretrea tment wi th pra zos i n (s el ecti ve 1 -a drenergi c a nta goni s t), nor a ny other a drenergi c bl ocker
(a nta goni s t) for tha t ma tter.
The bra dyca rdi a , of cours e, i nvol ves refl ex pa ra s ympa theti c a cti va ti on (a nd rel a ti ve a nd s i mul ta neous wi thdra wa l of s ympa theti c tone to the
hea rt), rel ea s e of ACh from the va gus a nd a cti va ti on of mus ca ri ni c receptors on the SA node. Atropi ne pretrea tment i ndeed prevents tha t res pons e,
a s des cri bed i n the ques ti ona nd rega rdl es s of whether the ori gi na l pres s or res pons e wa s ca us ed by A-II, or a ny other va s opres s or drug for tha t
ma tter.
Dobuta mi ne (b) does nt fi t the bi l l ; i t i s l a rgel y a s el ecti ve 1 a goni s t. For a l l pra cti ca l purpos es i t ca us es no va s ocons tri cti on (a n 1 res pons e i f
we l i mi t thi ngs to a drenergi c drugs ), a nd vi a the 1 a cti va ti on wi l l di rectl y i ncrea s e hea rt ra te, contra cti l i ty, a utoma ti ci ty, a nd el ectri ca l i mpul s e
conducti on (eg, through the AV node). No -a cti va ti on occurs (ri s es of bl ood pres s ure, i f they occur i n res pons e to dobuta mi ne, a re due to the
pos i ti ve i notropi c effect), a nd s o pra zos i n woul d ha ve no di rect effect on res pons es to dobuta mi ne. Is oproterenol (c) ca n be rul ed-out for l a rgel y

s i mi l a r rea s ons ; i t a cti va tes both 1 a nd 2 receptors ; a nd l a cks va s ocons tri ctor a cti vi ty, whether due to a cti va ti on of -a drenergi c receptors or by
other mecha ni s ms .
Coul d norepi nephri ne (d) be a rea s ona bl e a ns wer? It certa i nl y ca us es a va s opres s or res pons e a nd refl ex bra dyca rdi a (a t us ua l dos es ).
However, the ques ti on s ta ted tha t the unknown drugs pres s or res pons e i s not i nhi bi ted by -bl ocka de. Si nce a ma jor el ement of NEs pres s or
effect depends on a cti va ti on, i ts not a rea s ona bl e choi ce. The s a me a ppl i es to phenyl ephri ne (e): thi s nons el ecti ve -a goni s t a l s o ca us es a
pres s or res pons e tha t would be reduced or bl ocked a l together by pra zos i n pretrea tment.
206. The answer is d. (Brunton, pp 390, 793; Katzung, pp 182, 189, 334.) Cya ni de i s the ul ti ma te toxi c meta bol i te of ni troprus s i de s odi um. The drug i s
i ni ti a l l y meta bol i ca l l y reduced to ni tri c oxi de, whi ch i s res pons i bl e for the a rteri ol a r a nd venul a r di l a ti on. However, i t i s a nother meta bol i te, CN
(a nd to a l es s er extent the next meta bol i te, thi ocya na te) tha t i s the ma i n ca us e of or contri butor to toxi ci ty.
When CN a ccumul a tes to s uffi ci entl y hi gh l evel s (a s from exces s i ve or exces s i vel y prol onged a dmi ni s tra ti on of the drug), the va s cul a ture
devel ops wha t a mounts to a tol era nce to the drugs va s odi l a tor effects , a nd s o bl ood pres s ure us ua l l y s ta rts to ri s e des pi te the pres ence of hi gh
drug l evel s . Toxi c cya ni de a ccumul a ti on ca n a l s o l ea d to s evere l a cti c a ci dos i s : the CN rea cts wi th Fe 3+ i n mi tochondri a l cytochrome oxi da s e,
i nhi bi ti ng oxi da ti ve phos phoryl a ti on. Other cha ra cteri s ti c s i gns a nd s ymptoms of the toxi c s yndrome i ncl ude a cherry red s ki n (beca us e
mi tochondri a l oxygen cons umpti on i s bl ocked, venous bl ood rema i ns oxygena ted a nd a s bri ght red a s norma l a rteri a l bl ood), hypoxi a , a nd,
ul ti ma tel y, hypoxi c s ei zures a nd venti l a tory a rres t. Note: Ni trogl yceri n a nd other s i mi l a r ni trova s odi l a tors a re not meta bol i zed to CN a nd s o
ma ni fes ta ti ons of CN poi s oni ng a re not el ements of thei r toxi ci ty profi l e.
207. The answer is c. (Brunton, pp 682-684, 777, 790-791; Katzung, pp 189, 201, 334.) Hypoka l emi a due to the effects of pota s s i um-wa s ti ng di ureti cs s uch
a s furos emi de i ncrea s e s us cepti bi l i ty to di goxi n toxi ci ty, a nd they a re proba bl y the mos t common ca us e of i t. How does thi s occur? Di goxi n bi nds
to a K+-bi ndi ng s i te on the s odi um pump (ATPa s e). Tha t i s , there i s competi ti on between di goxi n mol ecul es a nd K+ for the s a me bi ndi ng s i tes .
When pota s s i um l evel s a re l ow (a s ca n occur wi th a ny pota s s i um-wa s ti ng di ureti c, i e, a l oop, thi a zi de, or thi a zi de-l i ke di ureti c), more di goxi n
mol ecul es a re a bl e to bi nd to the ATPa s eeven though the a ctua l di goxi n concentra ti on i n the bl oods trea m ha s nt cha nged. More bi ndi ng l ea ds
to grea ter ATPa s e i nhi bi ti on: a n i ntens i fi ed di goxi n effect tha t, qui te often, ca n l ea d to a dvers e res pons es ra ther tha n better thera peuti c effects .
Ca ptopri l (a ) ha s no di rect effects on di goxi ns a cti ons . (We mi ght a dd tha t a n ACE i nhi bi tor s uch a s ca ptopri l , a l ong wi th a -bl ocker a nd a
di ureti cnot di goxi na re now cons i dered the preferred thera py for mos t pa ti ents wi th recent ons et a nd mi l d hea rt fa i l ure.) Chol es tyra mi ne (b), a
chol es terol -bi ndi ng res i n, i ntera cts wi th concomi ta ntl y a dmi ni s tered (ora l ) di goxi n to reduce di goxi n a bs orpti on. It woul d not i ncrea s e the ri s k of
di goxi n toxi ci ty; qui te the oppos i te, i t woul d reduce di goxi ns thera peuti c effecti venes s . Lova s ta ti n (d; a n HMG-Co-A reducta s e i nhi bi tor/s ta ti n)
a nd ni trogl yceri n (e) a re not l i kel y to ca us e the obs erved toxi ci ty ei ther.
208. The answer is c. (Brunton, pp 830, 831, 764-765; Katzung, pp 202t, 238t.) The eti ol ogy i nvol ves corona ry va s os pa s m, a nd tha t ca n be bl ocked wel l
wi th a ca l ci um cha nnel bl ocker (CCB): di l ti a zem, vera pa mi l , or di hydropyri di nes (eg, ni fedi pi ne, for whi ch s l ow-/extended-a cti ng ora l formul a ti ons
a re us ed). The CCBs bl ock corona ry va s cul a r s mooth mus cl e i nfl ux of ca l ci um, whi ch i s a cri ti ca l proces s i n tri ggeri ng va s os pa s m.
Ni trogl yceri n s eems to be ma rgi na l l y effecti ve i n terms of l ong-term s ymptom rel i ef, a l though i t ma y be the onl y ra pi dl y a cti ng drug tha t wi l l be
effi ca ci ous for a cute a ngi na a nd s el f-medi ca ti on.
As pi ri n, through i ts a nti pl a tel et a ggrega tory effects , woul d be benefi ci a l , prophyl a cti ca l l y, i f corona ry thrombos i s were pa rt of the eti ol ogy of
va ri a nt a ngi na , but thrombos i s i s not the ma i n probl em wi th corona ry va s os pa s m.
Atorva s ta ti n (or other s ta ti ns ) a re us eful for pri ma ry preventi on of corona ry hea rt di s ea s e, but corona ri es tha t undergo s pa s m ma y be
rema rka bl y free of a theros cl eroti c pl a que, a nd the s ta ti ns ha ve no a nti s pa s modi c effects per s e.
The -bl ockers , whi ch a re i mporta nt drugs for ma ny pa ti ents wi th i s chemi c hea rt di s ea s e, ca n do more ha rm tha n good i n va s os pa s ti c a ngi na . In
es s ence, -receptor a cti va ti on i n the corona ri es tends to ca us e va s odi l a ti on, a n effect tha t to a degree countera cts s i mul ta neous -medi a ted
cons tri cti on. Bl ock onl y the -receptors a nd the -medi a ted cons tri ctor effects va s os pa s m-fa vori ng effects a re l eft unoppos ed. Va ri a nt a ngi na ,
then, i s l i kel y to be ma de wors e, not better, wi th -bl ockers . (You mi ght a s k whether a combi ned -/-bl ocker l i ke l a beta l ol or ca rvedi l ol mi ght be
better tha n a nons el ecti ve or ca rdi os el ecti ve -bl ocker. Perha ps i n theory, but not i n pra cti ce. Remember tha t the -bl ocki ng effects of thes e drugs
a re compa ra ti vel y wea k; thei r -bl ocki ng, s pa s m-fa vori ng effects wi l l predomi na te.)
209. The answer is c. (Brunton, pp 821t, 1405-1407; Katzung, pp 238, 921-922, 1160t.) Di goxi n toxi ci ty i s l i kel y to occur wi thi n 24 to 48 hours unl es s the
di goxi n dos e i s a djus ted down. The rea s on i s tha t qui ni di ne wi l l reduce the rena l excreti on of di goxi n (di goxi ns ma i n el i mi na ti on route). Thi s i s
proba bl y due to s ome mecha ni s m by whi ch qui ni di ne i nhi bi ts P-gl ycoprotei n tra ns port of di goxi n i n the ki dneys . (See the a ns wer for ques ti on 10,
on pa ge 28, for a s hort ta bl e l i s ti ng s ome drugs tha t a re s ubs tra tes , i nducers , a nd i nhi bi tors of P-gl ycoprotei n.)
There i s no revers e i ntera cti ontha t i s , a n a bi l i ty of di goxi n to ca us e s i gns a nd s ymptoms of qui ni di ne toxi ci ty (a ). Qui ni di ne ha s no
s i gni fi ca nt i mpa ct on the rena l a cti ons of a ny di ureti cs , whether thes e a cti ons a re expres s ed i n terms of uri ne output (vol ume or concentra ti on) or
rena l ha ndl i ng of s odi um or pota s s i um or other el ectrol ytes or s ol utes (b, d).
Qui ni di ne-i nduced di goxi n toxi ci ty ma y s uppres s ca rdi a c contra cti l i ty, but tha t woul d not neces s a ri l y be a di rect effect of a n i ntera cti on on the
i notropi c s ta te of the myoca rdi um. Ra ther, i t woul d be s econda ry to potenti a l di goxi n-i nduced a rrhythmi a s , a nd i t woul d not occur promptl y.
Qui ni di ne does ca us e s ome drug-drug i ntera cti ons by pha rma coki neti c mecha ni s ms . It i s a potent i nhi bi tor of CYP2D6, a nd ca n (for exa mpl e)
i nhi bi t the a na l ges i c effects of codei ne by i nhi bi ti ng i ts meta bol i s m to morphi ne. However, thi s mecha ni s m does not a ppl y to the
qui ni di nedi goxi n i ntera cti on; di goxi n i s el i mi na ted compl etel y by the ki dneys , wi th no pri or meta bol i s m.
210. The answer is e. (Brunton, pp 828, 835t, 840-841; Katzung, pp 241-242, 246-248.) The cl a s s I-C a nti a rrhythmi cs a re a s s oci a ted wi th a hi gher i nci dence
of s evere proa rrhythmi c events tha n vi rtua l l y a ny other a nti a rrhythmi cs i n other cl a s s es . Thi s ri s k pa rti a l l y expl a i ns why, when thes e drugs were
fi rs t a pproved, they were i ndi ca ted onl y for l i fe-threa teni ng ventri cul a r a rrhythmi a s tha t fa i l ed to res pond to a l l other rea s ona bl e (a nd s a fer)
a l terna ti ves . (Thi s ri s k a l s o contri buted to why a nother I-C a gent, enca i ni de, wa s wi thdra wn from the ma rket.)
Nowa da ys , thes e I-C a gents a re s ti l l us ed for s eri ous (l i fe-threa teni ng) a nd refra ctory ventri cul a r a rrhythmi a s , thei r effi ca cy a ri s i ng from
s i gni fi ca nt s odi um cha nnel bl ocka de. However, they a l s o bl ock s ome pota s s i um cha nnel s , whi ch a ccounts for modes tl y growi ng i nteres t i n a nd
us e of thes e drugs for s ome a tri a l a rrhythmi a s . Rega rdl es s of whether the us e i s for a n a tri a l or ventri cul a r a rrhythmi a , the proa rrhythmi c effects
s houl d be of concern.
Pul mona ry fi bros i s a nd a l tera ti ons of thyroi d hormone s ta tus (typi ca l l y, a hypothyroi d-l i ke s ta te) a re uni quel y a s s oci a ted wi th a mi oda rone
(a mong a l l the a nti a rrhythmi cs ), a nd a mi oda rone wa s not one of the a ns wer choi ces .
Note: Il l opi ne tha t memori zi ng whi ch a nti a rrhythmi c a gents a re i n whi ch Va ughn-Wi l l i a ms cl a s s ma y not be profi ta bl e (except for a ns weri ng
ni t-pi cky a nd cl i ni ca l l y i rrel eva nt exa m ques ti ons ). Among the rea s ons why (1) thi s cl a s s i fi ca ti on i s ba s ed l a rgel y on el ectrophys i ol ogi c effects of
the drugs i n l a rgel y norma l , i s ol a ted ca rdi a c cel l s , not i n di s ea s ed i nta ct huma n hea rts ; (2) s ome a nti a rrhythmi c drugs ha ve

el ectrophys i ol ogi c/i oni c mecha ni s ms of a cti on tha t woul d rea s ona bl y pl a ce them i n more tha n one Va ughn-Wi l l i a ms cl a s s (eg, a mi oda rone); (3)
bel ongi ng to a pa rti cul a r Va ughn-Wi l l i a ms cl a s s does not neces s a ri l y predi ct cl i ni ca l us e of the a nti a rrhythmi c; a nd (4) s i de effects profi l es a nd
toxi ci ti es of drugs i n the s a me Va ughn-Wi l l i a ms cl a s s both ca rdi a c a nd extra ca rdi a cca n di ffer s ubs ta nti a l l y.
211. The answer is b. (Brunton, pp 752, 766-767, 830-831; Katzung, pp 183, 194, 201-205, 245.) In a nuts hel l , thi s ques ti on s umma ri zes s ome of the ma i n
a nd i mporta nt di fferences between the di hydropyri di ne CCBs (eg, ni fedi pi ne, a nd es peci a l l y i n i mmedi a te-rel ea s e formul a ti ons , pl us ma ny
others ) a nd the nondi hydropyri di nes (pa rti cul a rl y vera pa mi l , l es s s o wi th di l ti a zem). The di hydropyri di nes a re qui te s el ecti ve for thei r va s cul a r
effects . They ca us e s i gni fi ca nt a rteri ol a r di l a ti on, whi ch us ua l l y a cti va tes the ba roreceptor refl ex tha t i ncrea s es s ympa theti c i nfl uences on the
hea rt: pos i ti ve i notropy, pos i ti ve chronotropy (refl ex ta chyca rdi a ca n be s evere), a nd i ncrea s ed a utoma ti ci ty a nd conducti on vel oci ty (dromotropi c
effects ).
In contra s t, a nd i mporta ntl y, vera pa mi l a nd di l ti a zem ca us e not onl y a rteri ol a r di l a ti on (vi a ca l ci um cha nnel bl ocka de i n va s cul a r s mooth
mus cl e), but a l s o di rect ca rdi a c depres s a nt effects (due to ca l ci um cha nnel bl ocka de i n ca rdi a c ti s s ues ). Thes e ca rdi a c effects oppos e, or bl unt,
refl ex s ympa theti c ca rdi a c a cti va ti on tha t otherwi s e woul d occur i n res pons e to onl y peri phera l va s odi l a ti on: s uch probl ems a s refl ex ta chyca rdi a
a nd pos i ti ve i notropy a re much l es s often nonexi s tentwi th the nondi hydropyri di nes . In fa ct, when refl ex ca rdi a c s ti mul a ti on ca us ed by other
drugs (eg, ni trogl yceri n) i s probl ema ti c a nd mus t be control l ed, ei ther vera -pa mi l (proba bl y preferred) or di l ti a zem ma y be a rea s ona bl e
a l terna ti ve to the tra di ti ona l a gents for bl ocki ng the unwa nted ca rdi a c res pons es : the -a drenergi c bl ockers . Moreover, a nondi hydropyri di ne CCB
i s us ua l l y the drug of choi ce for control l i ng ca rdi a c s ti mul a tory res pons es when a -bl ocker i s contra i ndi ca ted (eg, i n a s thma ). Be a wa re tha t
combi ned us e of di l ti a zem or vera pa mi l wi th a -bl ocker i s ri s ky due to pos s i bi l i ty of a ddi ti ve or grea ter i nhi bi tory effects on the ca rdi a c ra te,
contra cti l i ty, a nd es peci a l l y AV noda l functi on. And, whether us ed a l one or i n combi na ti on, -bl ockers a nd the nondi hydropyri di ne CCBs
(vera pa mi l , di l ti a zem) s houl d not be a dmi ni s tered to pa ti ents wi th s evere hea rt fa i l ure due to the a dded ri s ks from further s uppres s i on of ca rdi a c
output.
Notes : The va s odi l a tor effects of vera pa mi l a re wea ker tha n thos e of di l ti a zem, but the peri phera l va s cul a r (va s odi l a ti ng) effects of ei ther a re
s ti l l fa r wea ker tha n thos e of a di hydropyri di ne. Di l ti a zem i s cl a s s i fi ed, chemi ca l l y, a s a benzothi a zepi ne (s i mi l a r to but not to be confus ed wi th
benzodi a zepi nes di a zepa m, mi da zol a m, a nd ma ny other drugs us ed for thei r CNS effects .) Vera pa mi l i s , chemi ca l l y, a phenyl a l kyl a mi ne.
However, memori zi ng the na mes of thes e chemi ca l groups i s proba bl y a wa s te of your ti me: thes e drugs a re a l mos t a l wa ys referred to s i mpl y a s
nondi hydropyri di nes .
212. The answer is b. (Brunton, pp 86t, 390, 793; Katzung, pp 182, 189, 334.) Ni troprus s i des ma i n toxi c meta bol i te i s cya ni de. Nowa da ys , a preferred a nd
effecti ve a pproa ch to ma na gi ng cya ni de toxi ci ty from ni troprus -s i de overdos e i s to a dmi ni s ter hydroxycoba l a mi n. It rea cts wi th cya ni de, formi ng
cya nocoba l a mi n, whi ch i s l a rgel y nontoxi c (a nd i s cons i dered a form of vi ta mi n B 12 ).
A more tra di ti ona l (ol der) a pproa ch to ma na gi ng cya ni de toxi ci tyone tha t i s s ti l l occa s i ona l l y us ed, i s ba s ed on the fa ct tha t cya ni de norma l l y
i s meta bol i zed to the l es s toxi c a nd more rea di l y excreted thi ocya na te by a n enzyma ti c proces s (rhoda nes e i s the key enzyme) tha t us es
thi os ul fa te a s a cofa ctor. Endogenous thi os ul fa te s tores a re ra ther l i mi ted, a nd wi th more s eri ous degrees of cya ni de (or ni troprus s i de) toxi ci ty
the thi os ul fa te i s rea di l y depl eted. Other endogenous s ul fur-conta i ni ng s ubs tra tes a re depl eted too. Thi s tra di ti ona l trea tment pl a n, therefore,
i nvol ves a dmi ni s teri ng s odi um thi os ul fa te to res tore thi ocya na te producti on. Ni tri tes (a myl a nd s odi um ni tri tes ) a re a dmi ni s tered to i nduce
methemogl obi nemi a . The methemogl obi n then bi nds free cya ni de, formi ng l es s toxi c cya n(o) methemogl obi n.
None of the other drugs l i s ted pl a y a rol e i n the ma na gement of cya ni de poi s oni ng, whether from ni troprus s i de exces s or from other ca us es (eg,
s ui ci de a ttempts , envi ronmenta l expos ure to cya ni de). Ami noca proi c a ci d (a ) i s a n a nti thrombol yti c (a nti fi bri nol yti c) drug us ed, for exa mpl e, when
s uch drugs a s a l tepl a s e (t-PA; pl a s mi nogen a cti va tors ) ca us e exces s i ve thrombol ys i s tha t needs to be countera cted pha rma col ogi ca l l y. The drug
i nhi bi ts the a cti ons of not onl y thera peuti c pl a s mi nogen a cti va tors , but a l s o thos e of endogenous a cti va tors . It a l s o wea kl y i nhi bi ts pl a s mi n
a cti vi ty. Prota mi ne s ul fa te (c) s houl d be remembered a s the a nti dote for exces s i ve a nti coa gul a ti on ca us ed by hepa ri n (whi ch occurs ma i nl y wi th
unfra cti ona ted, ra ther tha n l ow mol ecul a r wei ght, hepa ri n). Thrombi n (d) i s a prothromboti c a gent tha t pl a ys no rol e i n ni troprus s i de (or cya ni de)
toxi ci ty. Vi ta mi n K (e) i s us ed to a nta goni ze exces s i ve effects of wa rfa ri n.
213. The answer is a. (Brunton, pp 730-736, 753, 784-785; Katzung, pp 170-174, 185-188.) Al though combi ned us e of a n ACE i nhi bi tor (or a ngi otens i n
receptor bl ocker [ARB], eg, l os a rta n) a nd a di ureti c i s qui te common, grea t ca re mus t be ta ken when a ddi ng one of the drugs to thera py tha t ha s
been s ta rted wi th the other. The rea s on i s tha t s ome pa ti ents devel op a s udden fa l l of bl ood pres s ure tha t ma y be s uffi ci ent to ca us e s yncope or
other compl i ca ti ons . Vol ume a nd s odi um depl eti on s eem to be a mong s evera l proba bl e ca us a ti ve fa ctors .
Ans wer b i s i ncorrect. The effects of ACE i nhi bi tors (or ARBs ) a nd thi a zi des on rena l ha ndl i ng of pota s s i um a re the oppos i te of one a nother, not
s ynergi s ti c. ACE i nhi bi tors tend to el eva te pota s s i um l evel s (i n pa rt, by l oweri ng a l dos terone l evel s ); the thi a zi des (a nd l oop di ureti cs , eg,
furos emi de) a re pota s s i um-wa s ti ng.
There i s no evi dence tha t a ddi ng one of thes e drugs to thera py wi th the other ca n ca us e a cute (or chroni c) hea rt fa i l ure (c); i ndeed, s uch a
combi na ti on i s often a n es s enti a l component i n ma na gi ng chroni c hea rt fa i l ure. Bl ood pres s ure wi l l fa l l , not ri s e, a nd certa i nl y not ca us e
hypertens i ve cri s i s (d); a nd s l owed AV noda l conducti on ra tes (e) due to thi s drug combi na ti on do not occur.
214. The answer is d. (Brunton, pp 853-859; Katzung, pp 604-607.) Admi ni s tra ti on of prota mi ne s ul fa te wi l l qui ckl y revers e the bl eedi ng ca us ed by
exces s i ve effects of hepa ri n. Prota mi ne bi nds to hepa ri n, formi ng a s ta bl e compl ex tha t a bol i s hes hepa ri ns a nti coa gul a nt a cti vi ty. It ma y a l s o
ha ve i ts own a nti coa gul a nt effect by bi ndi ng wi th pl a tel ets a nd fi bri nogen. Ami noca proi c a ci d (a ) bi nds a vi dl y to pl a s mi n a nd pl a s mi nogen, a nd
s o i s a n effecti ve i nhi bi tor of fi bri nol ys i s a nd a n a nta goni s t of fi bri nol yti c/thrombol yti c drugs . Di pyri da mol e wea kl y bl ocks pl a tel et ADP receptors ,
a nd ha s a l ong but uni ns pi ri ng hi s tory a s a n a nti pl a tel et drug. Fa ctor IX wi l l not revers e the exces s i ve effects of hepa ri n. Vi ta mi n K i s us ed a s a n
a nti dote for exces s i ve effects of s uch drugs a s wa rfa ri n, a nd does nothi ng for hepa ri n overdos es .
215. The answer is c. (Brunton, pp 758-759; Katzung, p 199.) Ni trogl yceri n ca us es i ts va s odi l a tor effects vi a a ni tri c oxi de (NO)- a nd cycl i c GMP-dependent
mecha ni s m. The NO a cti va tes gua nyl yl cycl a s e whi ch forms cGMP from GMP. The cGMP, i n turn, dephos phoryl a tes myos i n l i ght cha i ns , l ea di ng to
reduced a cti n-myos i n i ntera cti ons a nd rel a xa ti on of the s mooth mus cl e cel l s . Norma l l y, thi s va s cul a r effect i s modul a ted by cGMP degra da ti on (to
GMP) by cGMP-s peci fi c phos phodi es tera s es (PDEs ). Si l dena fi l (a nd the rel a ted drugs ta da l a fi l a nd va rdena fi l ) i nhi bi t the a cti vi ty of thos e PDEs ,
thereby ma i nta i ni ng cGMP l evel s a nd potenti a ti ng the va s odi l a tor effects . Thi s i ntera cti on ma y l ea d to s evere exces s i ve effects , i ncl udi ng l i fethrea teni ng hypotens i on a nd myoca rdi a l a nd cerebra l i s chemi a . Si l dena fi l a nd rel a ted drugs a l s o i ncrea s e the ri s k of s ymptoma ti c hypotens i on i f
ta ken by peopl e who a re a l s o bei ng trea ted wi th -a drenergi c bl ockers , i ncl udi ng thos e tha t s el ecti vel y bl ock 1 receptors (eg, pra zos i n a nd
doxa zos i n) a nd a re us ed for ma na gi ng hypertens i on.
Note the i mporta nt mecha ni s ti c l i nks between va s odi l a ti on/hypotens i on, s exua l i ntercours e, a nd potenti a l l y fa ta l ca rdi a c res pons es . Sexua l
a rous a l a nd, es peci a l l y orga s mca us es a ma s s i ve a cti va ti on of the s ympa theti c nervous s ys tem. One cons equence of tha t, -medi a ted
va s ocons tri cti on tha t tends to keep bl ood pres s ure up, i s too feebl e to overcome the hypotens i ve effects of the s i l dena fi l -ni trogl yceri n

combi na ti on. Al ong wi th a fa l l of bl ood pres s ure i s a fa l l of corona ry perfus i on pres s ure (di a s tol i c bl ood pres s ure), tha t i s , reduced myoca rdi a l
bl ood fl ow/oxygen s uppl y. Yet the s ympa theti c a cti va ti on concomi ta ntl y ca us es s i gni fi ca nt i ncrea s es of ca rdi a c ra te a nd contra cti l i ty, tha t i s ,
i ncrea s ed myoca rdi a l oxygen dema nd. Oxygen dema nd ri s es , s uppl y fa l l s , a nd the s ta ge i s s et for a cute myoca rdi a l i s chemi a .
A fi na l poi nt to cons i der. It i s rea s ona bl e to a s s ume tha t i f the pa ti ent i s ta ki ng any or even s evera l of the drugs l i s ted i n the ques ti on, he ha s
underl yi ng ca rdi a c di s ea s e. However, a nd i n contra s t wi th wha t s ome s tudents ha ve s ugges ted, underl yi ng ca rdi a c di s ea s e per se does not
a utoma ti ca l l y contra i ndi ca te or even exces s i vel y i ncrea s e the ri s ks from s exua l i ntercours e a nd orga s m. (How s evere i s the pa ti ents
ca rdi ova s cul a r di s ea s e? It i s wel l control l ed? Wha t are the s peci fi c di s ea s es a nd ri s ks he ha s ?) Si mi l a rl y, none of the drugs l i s ted other tha n the
ni trova s odi l a tors (a nd s ome -bl ockers menti oned i n the previ ous pa ra gra ph) contra i ndi ca te the us e of a ny of the ED drugs .
216. The answer is e. (Brunton, pp 818-819, 823; Katzung, pp 233-235.) Al though you ma y not cons i der thi s ques ti on a pha rma col ogy ques ti on, bei ng a bl e
to a ns wer i t correctl y i s i mporta nt to the ra ti ona l a nd s a fe us e of ma ny drugs .
In genera l , hea rt bl ock refers to exces s i vel y s l owed AV noda l conducti on, whi ch you a s s es s by mea s uri ng the PR i nterva l on the ECG. Reca l l tha t
thi s i nterva l gi ves i nforma ti on on how l ong i t ta kes for el ectri ca l i mpul s es tha t ori gi na te wi th SA noda l depol a ri za ti on to pa s s through the a tri a l
myoca rdi a a nd the AV node, ul ti ma tel y l ea di ng to ventri cul a r a cti va ti on (ma ni fes t a s the QRS compl ex). Impul s e conducti on through the a tri a i s
norma l l y qui ck; i t i s the AV node tha t ha s the s l owes t i ntri ns i c i mpul s e conducti on ra te a nywhere i n the hea rt, a nd i t i s a rgua bl y the s tructure tha t
i s mos t s us cepti bl e to drug- (or di s ea s e-) i nduced cha nges of s upra ventri cul a r conducti on tha t l ea d to the di a gnos i s of AV bl ock.
In fi rs t-degree hea rt bl ock, the ma i n ma ni fes ta ti on i s a prol onged PR i nterva l , but ea ch P wa ve i s fol l owed by a norma l l y genera ted QRS
compl ex. In s econd-degree hea rt bl ock, the PR i nterva l i s prol onged a nd s ome P wa ves a re not conducted through the AV node, a nd s o a re not
fol l owed by a QRS tri ggered by the pri or a tri a l a cti va ti on (eg, 2:1 bl ock). In thi rd-degree (compl ete) hea rt bl ock, no P wa ves a re conducted norma l l y
through the AV node, a nd ventri cul a r a cti va ti on i s s ol el y dependent on i ntri ns i c a utoma ti ci ty of the ventri cl es (or conducti ng ti s s ue therei n).
Aus cul ta ti on of the hea rt, the pres ence of bl ood pres s ures tha t a re a bove or bel ow wha t i s genera l l y rega rded a s norma l , or the pres ence of a
s l ow s i nus rhythm, a re not rel i a bl e i ndi ca tors of hea rt bl ock.
217. The answer is e. (Brunton, pp 83t, 765-767; Katzung, pp 201-205, 245.) Cons ti pa ti on i s a fa i rl y common, s ometi mes very bothers ome, a nd
occa s i ona l l y da ngerous res pons e to vera pa mi l (more s o tha n wi th a ny other ca l ci um cha nnel bl ocker). It i s a wi del y us ed drug. The mecha ni s m
underl yi ng thi s s i de effect i s nt known for s ure, but proba bl y l i es i n vera -pa mi l s ra ther uni que a bi l i ty to bl ock ca l ci um cha nnel s on l ongi tudi na l
a nd s phi ncter s mooth mus cl e cel l s i n the GI tra ct. Rega rdl es s of whether we know the mecha ni s m for s ure, i t i s i mporta nt to know tha t vera pa mi l
tends to ca us e cons ti pa ti on i n more tha n a ha ndful of pa ti ents . Sta ti ns (a ), ACE i nhi bi tors (b), -bl ockers of a ny cl a s s or orga ni c ni trova s odi l a tors
s uch a s ni trogl yceri n (d) do not ca us e cons ti pa ti on a s a s i de effect.
218. The answer is a. (Brunton, pp 779-781; Katzung, pp 181, 220.) Hydra l a zi nes pri ma ry va s odi l a tor a cti ons occur on a rteri ol es , not on venul es . The
others ha ve both a rteri ol a r a nd venul a r di l a tor a cti vi ty, thereby l oweri ng both a fterl oa d a nd centra l venous pres s ure (venous ca pa ci ta nce; ri ght
a tri a l pres s ure). Hydra l a zi nes proba bl e mecha ni s m of a cti on i nvol ves a ni tri c oxi de (NO)-medi a ted proces s . (There i s a l s o s ome evi dence tha t the
drug opens vol ta ge-ga ted pota s s i um cha nnel s on va s cul a r s mooth mus cl e cel l s , ca us i ng mus cl e cel l hyperpol a ri za ti on a nd ul ti ma te va s odi l a ti on.)
The other drugs l i s ted ca us e va s cul a r s mooth mus cl e rel a xa ti on on both a rteri ol es a nd venul es : l os a rta n (b), by bl ocki ng a ngi otens i n II
receptors ; ni fedi pi ne (c) vi a ca l ci um cha nnel bl ocka de; ni trogl yceri n (d) by NO a s a n i ntermedi a te; a nd pra zos i n (e) by s el ecti ve 1 -a drenergi c
bl ocka de. Here i s a s hort ta bl e l i s ti ng the ma i n s i tes where va ri ous drugs or drug cl a s s es exert thei r ma i n or s ol e va s odi l a tor a cti ons .

219. The answer is b. (Brunton, pp 849, 977-982; Katzung, p 320.) As pi ri n i nhi bi ts cycl ooxygena s es I a nd II. In terms of cl otti ng, the ma i n effect wi l l be
i nhi bi ti on of pl a tel et a ggrega ti on by reduced forma ti on of thromboxa ne A2 . Bl eedi ng ti me wi l l be prol onged a nd wi l l rema i n tha t wa y unti l
s uffi ci ent numbers of new pl a tel ets ha ve been s ynthes i zed a nd rel ea s ed i nto the bl oods trea m, beca us e a ggrega ti on of thos e pl a tel ets a l rea dy
expos ed to the drug wi l l be i nhi bi ted for thei r l i feti me. The APTT, whi ch s houl d not be a ffected by a s pi ri n, i s us ed to moni tor effects a nd a djus t the
dos e of unfra cti ona ted hepa ri n (s uch moni tori ng i s not requi red wi th l ow mol ecul a r wei ght hepa ri n, eg, enoxa pa ri n). The prothrombi n ti me a nd i ts
norma l i zed va l ue, the INR, a re us ed wi th wa rfa ri n. Pl a tel et counts , a l s o not a ffected by a s pi ri n, a re us ed to a s s es s for the devel opment of
thrombocytopeni c purpura , whi ch ma y ra rel y occur duri ng thera py wi th, for exa mpl e, the cl opi dogrel -l i ke drug ti cl opi di ne, or wi th hepa ri n when
thrombocytopeni a i s a nti ci pa ted or s us pected.
220. The answer is a. (Brunton, pp 824-825, 829t, 834-837; Katzung, pp 238t, 245-246.) Nowa da ys , IV i njecti on of a denos i ne i s genera l l y rega rded a s the
fi rs t choi ce for termi na ti ng PSVT i n whi ch reentry phenomena pl a y a n i mporta nt pa thophys i ol ogi c rol e. (If the ECG s hows a wi de QRS compl ex,

a denos i ne woul d be contra i ndi ca ted.) Among other rea s ons , i t i s preferred over a nother rea s ona bl e a l terna ti ve, vera pa mi l , beca us e of a fa s ter
ons et of a cti on. Adenos i ne i s a l s o a pri ma ry drug for ma na gi ng epi s odes of ventri cul a r ta chyca rdi a , provi ded tha t there a re no ca rdi a c s tructura l
defects (a neurys ms , da ma ge to pa pi l l a ry mus cl es or the chorda e tendi na e, etc).
Di goxi n (b), edrophoni um (c; ra pi dl y a cti ng ACh es tera s e i nhi bi tor), phenyl ephri ne (d; nons el ecti ve -a drenergi c a goni s t), a nd propra nol ol or
other -bl ockers (e) a re ol der thera pi es fa l l i ng i nto rel a ti ve di s us e. In one wa y or a nother thei r effects revol ve a round ca us i ng or unma s ki ng
i ncrea s ed pa ra s ympa theti c i nfl uences on the SA a nd/or AV nodes : di goxi n vi a i ts predomi na nt effects to s l ow AV noda l conducti on; phenyl ephri ne
by i ncrea s i ng bl ood pres s ure, whi ch tri ggers a ba roreceptor refl ex tha t reduces s ympa theti c dri ve a nd es s enti a l l y i ncrea s es or unma s ks
pa ra s ympa theti c tone; propra nol ol , by bl ocki ng 1 -medi a ted s ympa theti c i nfl uences ; a nd edrophoni um, whi ch qui ckl y but bri efl y ra i s es
pa ra s ympa theti c i nfl uences on noda l ti s s ues .
221. The answer is c. (Brunton, pp 857, 861f-862; Katzung, pp 608-611.) Wa rfa ri n i s a couma ri n deri va ti ve tha t i s genera l l y us ed for l ong-term
a nti coa gul a ti on, a nd i s whol l y uns ui ta bl e for i mmedi a te a nti coa gul a ti on beca us e i t ta kes a t l ea s t 5 da ys of a dmi ni s tra ti on for mea ni ngful
i nhi bi ti on of prothrombi n ti me (reported a s the Interna ti ona l Norma l i zed Ra ti o [INR]) to devel op a nd s ta bi l i ze. It a nta goni zes the ga mma
ca rboxyl a ti on of s evera l gl uta ma te res i dues i n prothrombi n a nd the coa gul a ti on fa ctors II, VII, IX, a nd X. Thi s proces s i s coupl ed to the oxi da ti ve
dea cti va ti on of vi ta mi n K. The reduced form of vi ta mi n K i s es s enti a l for s us ta i ned ca rboxyl a ti on a nd s ynthes i s of the coa gul a ti on protei ns . It
a ppea rs tha t wa rfa ri n i nhi bi ts the a cti on of the reducta s e(s ) tha t regenera te the reduced form of vi ta mi n K. The preventi on of the i na cti ve vi ta mi n
K epoxi de from bei ng reduced to the a cti ve form of vi ta mi n K res ul ts i n decrea s ed ca rboxyl a ti on of the protei ns i nvol ved i n the coa gul a ti on
ca s ca de.
222. The answer is e. (Brunton, p 771; Katzung, pp 611-612.) Al tepl a s e, a thrombol yti c drug, i s a n unmodi fi ed ti s s ue pl a s mi nogen a cti va tor (t-PA). It
a cti va tes pl a s mi nogen tha t i s bound to fi bri n (i e, i t i s cl ot-s peci fi c, unl i ke s treptoki na s e whi ch a cts throughout the ci rcul a tory s ys tem). The
pl a s mi n tha t i s formed i n res pons e to the drug a cts di rectl y on fi bri n. Thi s res ul ts i n di s s ol vi ng the fi bri n i nto fi bri n-s pl i t products , fol l owed by
l ys i s of the cl ot. Cl opi dogrel exerts a nti pl a tel et effects by bl ocki ng pl a tel et ADP receptors (a ); a s pi ri n exerts a nti pl a tel et effects by i nhi bi ti ng
thromboxa ne producti on (b) vi a cycl ooxygena s e; a bci xi ma b i s a n exa mpl e of a n a nti pl a tel et drug tha t bl ocks the pl a tel et Gp IIb/IIIa receptors the
fi na l common s tep i n pl a tel et a ggrega ti on, rega rdl es s of whi ch l i ga nd i ni ti a ted pl a tel et a cti va ti on (eg, col l a gen, ADP, TXA2 ). Wa rfa ri n, nei ther a
thrombol yti c nor a n a nti pl a tel et a gent, i nhi bi ts hepa ti c s ynthes i s (a cti va ti on) of vi ta mi n K-dependent cl otti ng fa ctors (c).
223. The answer is d. (Brunton, pp 834-837, 1153t; Katzung, pp 242-243.) Pul mona ry fi bros i s ha s been reported wi th l ong-term a mi oda rone thera py, but
not i n res pons e to other a nti a rrhythmi cs . Pul mona ry functi on tes ts ma y rema i n norma l for months a nd then decl i ne qui ckl y a nd to s i gni fi ca nt
degrees a s i rrevers i bl e fi bros i s devel ops . Cha nges of thyroi d hormone s ta tus occa s i ona l l y refl ecti ng hypothyroi di s m a nd, for more pa ti ents
(a bout 3% of a l l who ta ke a mi oda rone l ong-term), hyperthyroi di s ma re a l s o uni quel y a s s oci a ted wi th a mi oda rone: thi s drug i s s tructura l l y
rel a ted to the thyroi d hormones a nd i s ri ch i n i odi ne. Cha nges of thyroi d hormone s ta tus ma y be s ubcl i ni ca l a nd detecta bl e onl y wi th s ui ta bl e
bl ood tes ts or ma y l ea d to typi ca l s i gns a nd s ymptoms of hyper- or hypothyroi di s m. Note tha t the newer a nti a rrhythmi c s i mi l a r to a mi oda rone,
na mel y droneda rone, does not s ha re the s i de effects profi l e a s s oci a ted wi th a mi oda rone.
Keep i n mi nd tha t s ome a dvers e res pons es tha t a re uni que to other a nti a rrhythmi c drugs were l i s ted a s pos s i bl e a ns wers . For exa mpl e, l owgra de qui ni di ne toxi ci ty (ci nchoni s m) often i ncl udes ti nni tus (but tha t ma ni fes ta ti on of ototoxi ci ty ca nnot be detected wi th a udi ometry), a nd
proca i na mi de commonl y ca us es a l upus -l i ke s yndrome, for whi ch moni tori ng of ANA ti ters i s i mporta nt.
Of cours e, i ts l i kel y tha t a pa ti ent wi th a tri a l fi bri l l a ti on wi l l be pl a ced on wa rfa ri n (a t l ea s t for a whi l e), a nd s o moni tori ng the prothrombi n
ti me (reported a s the INR) woul d be es s enti a l i n tha t ca s e. And, s i nce thi s pa ti ent ma y ha ve mul ti pl e ca rdi ova s cul a r ri s k fa ctors , peri odi c
moni tori ng of l i pi d profi l es woul d be es s enti a l too. Nonethel es s , thes e do not a ppl y s peci fi ca l l y or uni quel y to a mi oda rone.
224. The answer is c. (Brunton, pp 868-870; Katzung, pp 613, 617.) Cl opi dogrel (ti cl opi di ne i s a rel a ted drug) decrea s es pl a tel et a ggrega ti on by bl ocki ng
a popul a ti on of pl a tel et ADP receptors (whi ch di pyri da mol e, d, a l s o s eems to do, but very wea kl y), thereby i nhi bi ti ng ADP-i nduced pl a tel et
a cti va ti on. It ha s no di rect pl a tel et effects i nvol vi ng a cti va ti on by thromboxa ne A2 , col l a gen, or other medi a tors , nor does i t i nhi bi t pl a tel et
a ggrega ti on by a ny a cti ons on the pl a tel et gl ycoprotei n IIb/IIIa receptors . Aceta mi nophen (a ) ha s no a nti pl a tel et effects . Ami noca proi c a ci d (b)
prevents a cti va ti on of pl a s mi nogen a nd i nhi bi ts pl a s mi n di rectl y. It ma y be us ed to countera ct the effects of thrombol yti c drugs gi ven i n rel a ti ve or
a bs ol ute overdos es . Streptoki na s e (e) i s a ba cteri a l deri ved, non-cl ot-s peci fi c thrombol yti c drug.
225. The answer is f. (Brunton, pp 761, 756-767, 830-831; Katzung, pp 201-205, 245.) In es s ence, we a re a s ki ng whi ch drug ca n s uppres s AV noda l
conducti on vel oci ty? Vera pa mi l a nd the very s i mi l a r nondi hydropyri di ne ca l ci um cha nnel bl ocker, di l ti a zem, do tha t. Reca l l the profi l e of
vera pa mi l a nd di l ti a zem: a va s odi l a tor effect pl us a di rect ca rdi a c depres s a nt effect tha t i ncl udes s l owi ng of AV conducti on (a nd potenti a l
depres s i on of other ca rdi a c contra cti l e a nd el ectrophys i ol ogi c phenomena ).
Be s ure you ca n contra s t thi s dua l va s odi l a tor/ca rdi a c depres s a nt profi l e for vera pa mi l a nd di l ti a zem wi th tha t of the di hydropyri di nes (eg,
ni fedi pi ne; a ns wer c). The di hydropyri di nes ca us e va s odi l a ti on, but l a ck a ny ca rdi a c depres s a nt a cti ons . Indeed, wi th di hydropyri di ne dos a ges
s uffi ci ent to l ower bl ood pres s ure enough, a nd qui ck enough, there wi l l be refl ex (ba roreceptor) a cti va ti on of the s ympa theti c nervous s ys tem. One
cons equence of i ncrea s ed norepi nephri ne rel ea s e a t the hea rt woul d be i ncrea s ed (fa s ter) AV noda l conducti on vel oci ty, whi ch coul d be
cons trued a s a n unbl ocki ng of the AV nodepreci s el y the oppos i te of wha t ma y ha ppen wi th vera pa mi l or di l ti a zem.
Ca ptopri l (ACE i nhi bi tor) a nd l os a rta n (a ngi otens i n receptor bl ocker) ha ve no s i gni fi ca nt effects on AV noda l conducti on.
Ni trogl yceri n (ni trova s odi l a tor) a nd pra zos i n (va s odi l a tor tha t a cts by competi ti ve 1 bl ocka de) a l s o ha ve no di rect effect on the AV node, but a re
l i kel y to l ea d to a n i ndi rect qui ckeni ng of AV conducti on vi a ba roreceptor a cti va ti on.
On a fi na l a nd i mporta nt note, be s ure you unders ta nd tha t a l l -a drenergi c bl ockers (i ncl udi ng thos e wi th s ome -bl ocki ng a cti vi ty, eg,
l a beta l ol a nd ca rvedi l ol ) ca n s l ow AV noda l conducti on a nd ca n ca us e or wors en hea rt bl ock.
226. The answer is a. (Brunton, pp 730-736, 798; Katzung, pp 183-185.) Ca ptopri l , a nd s ome of the other ACE i nhi bi tors , ma y ca us e s evere, ha cki ng, a nd
rel entl es s cough i n s ome pa ti ents . One theory i s tha t i t i s due to i ncrea s ed l evel s of bra dyki ni n i n s mooth mus cl es i n the throa t. (Reca l l tha t
a ngi otens i n-converti ng enzyme, whi ch forms a ngi otens i n II, i s the s a me enzyme a s bra dyki ni na s e, whi ch meta bol i ca l l y i na cti va tes bra dyki ni n.)
Ma ny pa ti ents recei vi ng ca ptopri l (or other ACE i nhi bi tors ) experi ence no probl ems of thi s s ort. Sti l l other pa ti ents , ma i nl y ta ki ng other ACE
i nhi bi tors , ma y devel op s wel l i ng of the oropha ryngea l mucos a e, a nd s ome ma y devel op l i fe-threa teni ng a ngi oedema .
There a re no l i kel y a l l ergi c rea cti ons (b) tri ggered by a ny of the drugs , s ta ti ns i ncl uded.
Ca ptopri l i s not a bronchocons tri ctor (c). Hyperka l emi a i s not a l i kel y expl a na ti on. Note tha t by i ndi rectl y l oweri ng a l dos terone l evel s
(a ngi otens i n II i s the ma i n s ti mul us for a l dos terone rel ea s e, a nd we ha ve i nhi bi ted a ngi otens i n II s ynthes i s ), the ma i n rena l effects woul d be
i ncrea s ed s odi um excreti on a nd i ncrea s ed pota s s i um retenti on. However, we a re a dmi ni s teri ng furos emi de (a l oop di ureti c), whi ch ca us es rena l

pota s s i um-wa s ti ng. Thus , we woul d not expect hyperka l emi a from thi s combi na ti on of drugs (a s we woul d i f the di ureti c wa s a pota s s i um-s pa ri ng
one s uch a s a mi l ori de, tri a mterene, or s pi ronol a ctone).
Cough i s not pa rt of the ma i n s i de effect/toxi ci ty profi l e of s i mva s ta ti n or other HMG-CoA reducta s e i nhi bi tors . Reca l l tha t thei r ma i n toxi ci ti es
i ncl ude myos i ti s , myopa thy, rha bdomyol ys i s , rena l da ma ge (from the rha bdomyol ys i s ), a nd hepa totoxi ci ty.
227. The answer is b. (Brunton, pp 296-297, 322t, 782; Katzung, pp 176-177.) Abrupt di s conti nua ti on of cl oni di ne ha s been a s s oci a ted wi th a ra pi dl y
devel opi ng a nd s evere rebound phenomenon tha t i ncl udes exces s i ve ca rdi a c s ti mul a ti on a nd a s pi ke of bl ood pres s ure tha t ma y be s uffi ci entl y
grea t a s to ca us e s troke or other s i mi l a r compl i ca ti ons . Reca l l tha t cl oni di ne i s a centra l l y a cti ng 2 -a drenergi c a goni s t. Through i ts centra l
effects i t reduces s ympa theti c nervous s ys tem tone. Thi s , i n turn, a ppea rs to ca us e s upers ens i ti vi ty of peri phera l a drenergi c receptors to di recta cti ng a drenergi c a goni s ts , i ncl udi ng endogenous norepi nephri ne a nd epi nephri ne. Once, a nd s oon a fter, the drug i s s topped, endogenous
ca techol a mi nes tri gger hyperres pons i venes s of a l l s tructures under s ympa theti c control . When ACE i nhi bi tors (or a ngi otens i n receptor bl ockers ),
furos emi de, or ni fedi pi ne (l ong-a cti ng or otherwi s e) a re a bruptl y s topped, bl ood pres s ure (a nd bl ood vol ume, dependi ng on the drug) wi l l begi n
to ri s e from trea tment l evel s , but there wi l l be no s udden s pi ke of pres s ure nor a n overs hoot of i t.
Di goxi n di s conti nua ti on i s not a s s oci a ted wi th the s ymptoms noted i n the ques ti on. Bes i des , the ha l f-l i fe of di goxi n (a bout 36-40 hours i f rena l
functi on i s norma l ) i s s uch tha t s toppi ng the drug a bruptl y woul d not i n a l l l i kel i hood l ea d to a ny s i gni fi ca nt wi thdra wa l events occurri ng wi thi n
a da y or two of di s conti nua ti on.
There i s no rea s on to predi ct tha t s uddenl y s toppi ng wa rfa ri n woul d ca us e ta chya rrhythmi a s , hypertens i on, or hemorrha gi c s trokea nd
certa i nl y not wi thi n 24 to 48 hours .
Importa nt note: A s i mi l a r, a nd da ngerous , rebound phenomenon occurs when -bl ockers a re s topped a fter conti nuous us e for more tha n a
coupl e of weeks . If the drug bl ocks onl y -receptors , then exces s i ve ca rdi a c s ti mul a ti on wi l l be the ma i n exces s i ve res pons e. If -receptors a re
a l s o bl ocked, rebound va s ocons tri cti on ma y occur too. The ta ke-home mes s a ges : (1) dont s top -bl ockers a bruptl y unl es s you ha ve a rea di l y
a va i l a bl e mea ns to control the potenti a l l y l i fe-threa teni ng res pons es ; (2) ma ke s ure your pa ti ents unders ta nd tha t they mus t not a bruptl y s top bl ockers or cl oni di ne or rel a ted a nti hypertens i ve drugs , wi thout conta cti ng you fi rs t.
228. The answer is b. (Brunton, pp 911, 926-932; Katzung, pp 183-185, 295-300.) Angi otens i n converti ng enzyme (ACE) a nd bra dyki ni na s e (a l s o known a s
ki ni na s e II) a re exa ctl y the s a me enzymes . We us e the former nomencl a ture when the s ubs tra te i s a ngi otens i n I (the product, of cours e, i s
a ngi otens i n II); we us e the na me bra dyki ni na s e when the s ubs tra te i s bra dyki ni n. None of the other drugs l i s ted i nhi bi t the enzyma ti c convers i on
of ei ther A-I to A-II, or of bra dyki ni n to i ts i na cti ve products .
229. The answer is d. (Brunton, pp 752-753; Katzung, pp 195-197.) Ni tri c oxi de i s thought to be enzyma ti ca l l y deri ved from ni trogl yceri n. It then rea cts
wi th a nd a cti va tes gua nyl yl cycl a s e to i ncrea s e GMP, whi ch i n turn dephos phoryl a tes myos i n l i ght cha i n ki na s e, ca us es ca l ci um extrus i on, a nd
s uppres s es s mooth mus cl e tone. Tol era nce ma y devel op i n pa rt from a decrea s e i n a va i l a bl e s ul fhydryl groups . Autonomi c receptors a re not
i nvol ved i n the pri ma ry res pons e of ni trogl yceri n, but compens a tory mecha ni s ms ma y counter the pri ma ry a cti ons .
230. The answer is c. (Brunton, pp 446-450, 976; Katzung, pp 513-517, 1158t.) There i s a cl i ni ca l l y i mporta nt rel a ti ons hi p between bl ood (or extra cel l ul a r)
s odi um concentra ti ons a nd the concentra ti on-dependent effects of l i thi um. In es s ence, Li + a nd Na + compete wi th one a nother, s uch tha t i n the
pres ence of hypona tremi a the effects of the l i thi um ma y be i ncrea s ed to the poi nt of ca us i ng toxi ci ty. (Convers el y, hyperna tremi a ca n countera ct
l i thi ums thera peuti c effects .) Of the drugs l i s ted, hydrochl orothi a zi de (a nd other thi a zi des a nd s uch thi a zi de-l i ke a gents a s metol a zone) pos es
the grea tes t ri s k of ca us i ng hypona tremi a . (And you s houl d cons i der the ul ti ma te rena l effects of ACE i nhi bi ti on to l ower Na + l evel s further when
us ed wi th a di ureti c. ACE i nhi bi tors us ed wi thout a di ureti c a re not a t a l l a s l i kel y to ca us e hypona tremi a .)
There a re no cl i ni ca l l y s i gni fi ca nt pha rma codyna mi c or pha rma coki neti c i ntera cti ons between ni trogl yceri n or HMG CoA reducta s e i nhi bi tors a nd
the SSRIs (fl uoxeti ne, s ertra l i ne, others ) or l i thi um.
231. The answer is b. (Brunton, pp 774t, 784; Katzung, pp 190, 203f, 209.) A good wa y to a rri ve a t the a ns wer i s to remember the ra ther na rrow
ca rdi ova s cul a r profi l e of ni fedi pi ne, the prototype di hydropyri di ne ca l ci um cha nnel bl ocker, a nd perha ps to compa re i t wi th the two ma i n
nondi hydropyri di nes , di l ti a zem a nd vera pa mi l .
The nondi hydropyri di nes bl ock va s cul a r s mooth-mus cl e ca l ci um cha nnel s , a nd s o ca us e va s odi l a ti on. Any of thes e drugs , therefore, woul d hel p
l ower thi s pa ti ents bl ood pres s ure.
However, ni fedi pi ne (a nd other di hydropyri di nes ) l a ck a ny ca rdi a c-depres s a nt effects . The i mpl i ca ti on i s tha t a s the ni fedi pi ne dri ves bl ood
pres s ure down (a nd i t wi l l , qui te promptl y a nd i n a n uncontrol l ed fa s hi on wi th thi s s ometi mes -us ed but whol l y i na ppropri a te a nd uns a fe
a dmi ni s tra ti on method), there wi l l be i ntens e ba roreceptor a cti va ti on a nd res ul ti ng ca rdi a c s ti mul a ti on. There a re no drug-i nduced nega ti ve
i notropi c, chronotropi c, or dromotropi c (conducti on vel oci ty) effects to countera ct the exces s i ve ca rdi a c s ti mul a ti on a s there woul d be i f we ha d
us ed ei ther di l ti a zem or vera pa mi l .
So, i n the pres ence of refl ex-medi a ted i ncrea s es of ca techol a mi nes a ffecti ng the hea rt, AV conducti on woul d i ncrea s e (not be s l owed or
bl ocked); there woul d be further i ncrea s es of hea rt ra te (a t l ea s t; certa i nl y, no fa l l ) to a ccompa ny l oweri ng of bl ood pres s ure (pos s i bl y to
hypotens i ve l evel s ); a nd the current epi s odes of ventri cul a r ectopy mi ght convert to l onger runs , or to ventri cul a r ta chyca rdi a or fi bri l l a ti on.
232. The answer is b. (Brunton, pp 803-804, 834-839, 844; Katzung, pp 215-218, 221.) Thi s col l ecti on of s i gns a nd s ymptoms i s cha ra cteri s ti c (i e, a
s yndrome) of di goxi n toxi ci ty, rega rdl es s of the ca us e (eg, fra nk overdos e or the devel opment of hypoka l emi a , whi ch i ncrea s es the ri s k of di goxi n
toxi ci ty). Al though a proba bl e ca us e of the hypoka l emi a i s the furos emi de, i t i s not correct to s a y tha t furos emi de per se i s the ca us e, beca us e
s i gns a nd s ymptoms of furos emi de toxi ci ty, whether a cute or chroni c, a re not s i mi l a r a t a l l to thos e des cri bed here. Note, too, tha t we ha ve
a dmi ni s tered tri a mterene. The expected effect of tha t pota s s i um-s pa ri ng di ureti c i s to countera ct rena l pota s s i um l os s from the furos emi de
(pota s s i um-wa s ti ng).
Do reca l l tha t the di goxi n-i nduced vi s ua l cha nges des cri bed i n the ques ti on a re ca l l ed chroma tops i a .
233. The answer is a. (Brunton, pp 752, 766-767; Katzung, pp 202t, 245.) The ma i n goa l s a re to s a fel y l ower bl ood pres s ure a nd hel p norma l i ze hea rt
ra te. If we ca nnot us e a -bl ocker for tha t, a nondi hydropyri di ne ca l ci um cha nnel bl ocker, ei ther di l ti a zem or vera pa mi l , woul d be a n excel l ent
choi ce. In a ddi ti on to control l i ng the ca rdi ova s cul a r probl ems they a re unl i kel y to exa cerba te the a s thma .
Ena l a pri l (b), one of ma ny ACE i nhi bi tors , mi ght ni cel y a nd gra dua l l y l ower bl ood pres s ure, a nd s houl d ha ve no a dvers e effects on a i rwa y
functi on. Nonethel es s i t i s unl i kel y tha t i t or a ny other ACE i nhi bi tor woul d ha ve much of a benefi ci a l i mpa ct on the ta chyca rdi a . More i mporta nt i s
the fa ct tha t ACE i nhi bi tors , a nd a ngi otens i n receptor bl ockers s uch a s l os a rta n, s houl d not be a dmi ni s tered to women who a re pregna nt or l i kel y
to become pregna nt. Furos emi de (c) woul d tra ns i entl y l ower bl ood pres s ure, but our pa ti ent ha s es s enti a l hypertens i on: s he i s not vol ume-

overl oa ded, a nd s o thi s di ureti c woul d not be a good choi ce. Moreover, i f ci rcul a ti ng fl ui d vol ume fel l s uffi ci entl y, a nd s uffi ci entl y fa s t, the
ba roreceptor refl ex mi ght be a cti va ted, ca us i ng even further ri s es of hea rt ra te.
Phentol a mi ne (d) a nd pra zos i n (e) a re both -a drenergi c bl ocker. Phentol a mi ne i s ra pi dl y a cti ng, gi ven pa rentera l l y, a nd nons el ecti vel y bl ocks
both 1 a nd 2 (pres yna pti c) receptors . Even wi th s ma l l dos es , the bl ood pres s ure fa l l us ua l l y i s s uffi ci ent to refl exl y i ncrea s e hea rt ra te (a nd
contra cti l i ty) even more. A pa rentera l drug s uch a s thi s s i mpl y i s not a ppropri a te thera py i n thi s s i tua ti on. Pra zos i n i s gi ven ora l l y, works rel a ti vel y
s l owl y, a nd bl ocks onl y 1 receptors . Whi l e i ts effects a re more gra dua l , perha ps s l ow enough tha t the ba roreceptors a re not a cti va ted, thi s drug
wi l l do nothi ng to control the pa ti ents ta chyca rdi a .
234. The answer is e. (Brunton, p 210; Katzung, pp 155-156.) Pheochromocytoma s ra re ca us es of hypertens i ongenera l l y i nvol ve exces s i ve l evel s of
ci rcul a ti ng ca techol a mi nes from tumors of the a drena l (s upra rena l ) medul l a . (In a dul ts , onl y a bout 10% of a l l ca s es of pheochromocytoma a re due
to ca techol a mi nes rel ea s ed from nona drena l s i tes .) Rega rdl es s of the s i te(s ) of the tumor(s ), the ma i n fa ctor i n l ea di ng to a n i ncrea s e of bl ood
pres s ure a nd hea rt ra te i n thi s condi ti on i s -medi a ted va s ocons tri cti on a ri s i ng from exces s i ve l evel s of epi nephri ne, norepi nephri ne, or both.
Epi nephri ne (but not norepi nephri ne) wi l l ca us e 2 -medi a ted di l a ti on of s ome va s cul a r beds . However, tha t va s odi l a tor effect, whi ch mi ght be
cons trued a s a mecha ni s m to keep bl ood pres s ure from ri s i ng too much, i s extra ordi na ri l y s l i ght i n compa ri s on wi th the oppos i ng va s ocons tri ctor
(-medi a ted) i nfl uences of the ca techol a mi nes el s ewhere i n the peri phera l va s cul a ture. Even i f you cons i der the va s odi l a tor i nfl uences to be
s l i ght, they wi l l be bl ocked by propra nol ol or a ny other -a drenergi c bl ocker, s uch tha t di a s tol i c a nd mea n bl ood pres s ures wi l l ri s e further, a t
l ea s t i ni ti a l l y. (The s o-ca l l ed ca rdi os el ecti ve/1 bl ockers s uch a s a tenol ol a nd metoprol ol wi l l bl ock 2 receptors i n the va s cul a ture, a nd
el s ewhere, a t bl ood l evel s tha t a re not too fa r a bove the us ua l thera peuti c ra nge.) In es s ence, bl ocka de of 2 receptors i n the va s cul a ture wi l l
l ea ve -medi a ted cons tri ctor effects unoppos ed, a nd bl ood pres s ure wi l l ri s e (concomi ta nt wi th s uppres s i on of ca rdi a c contra cti l i ty a nd ra te). The
probl em i s not l i kel y to ha ppen wi th l a beta l ol ; i t i s , i ndeed, a -bl ocker, but i t a l s o ha s i ntri ns i c -bl ocki ng a cti vi ty tha t s houl d bl unt to s ome
us eful degree the va s ocons tri ctor i nfl uences of ci rcul a ti ng epi nephri ne a nd neurona l l y rel ea s ed norepi nephri ne. None of the other drug woul d
ra i s e bl ood pres s ure further, a nd whi l e none of them i s i ndi ca ted a s pri ma ry thera py for pheochromocytoma s , ul ti ma tel y a ny of them a re more
l i kel y to l ower bl ood pres s ure.
Ami noca proi c a ci d (a ) i s a ba ckup (to whol e bl ood, pa cked red cel l s , or fres h-frozen pl a s ma ) for ma na gi ng bl eedi ng i n res pons e to exces s i ve
effects of thrombol yti c drugs (eg, a l tepl a s e [tPA]). It i s not i ndi ca ted for wa rfa ri n-rel a ted bl eedi ng. Epoeti n a l fa (b) i s a hema topoi eti c growth
fa ctor tha t s ti mul a tes erythrocyte producti on i n peri tubul a r cel l s i n the proxi ma l tubul es of the ki dney. Its us es i ncl ude ma na gement of a nemi a s
a s s oci a ted wi th chroni c rena l fa i l ure, chemothera py (of nonmyel oi d ma l i gna nci es ), or zi dovudi ne thera py i n pa ti ents wi th a cqui red
i mmunodefi ci ency s yndrome. It i s i na ppropri a te for thi s pa ti ent. Ferrous s ul fa te (b; or fuma ra te or gl ucona te) i s i ndi ca ted for preventi on or
trea tment of i ron-defi ci ency a nemi a s . It wi l l do nothi ng to l ower the pa ti ents INR or a l l evi a te rel a ted s ymptoms . Prota mi ne s ul fa te (e) i s the
a nti dote for hepa ri n overdos es . It a cts el ectros ta ti ca l l y wi th hepa ri n, i n the bl ood, to form a compl ex tha t l a cks a nti coa gul a nt a cti vi ty. It does
nothi ng to the hepa ti c vi ta mi n K-rel a ted probl ems tha t a re a t the root of exces s i ve wa rfa ri n effects .
235. The answer is d. (Brunton, pp 35, 857, 865; Katzung, pp 609f, 614-615.) Phytona di one (vi ta mi n K1 ) i s the a nti dote. It overcomes (revers es ,
a nta goni zes ) wa rfa ri ns hepa ti c a nti coa gul a nt effects , whi ch i nvol ve i nhi bi ted vi ta mi n K-dependent s ynthes i s /a cti va ti on of cl otti ng fa ctors (II, VII,
IX, X, a nd prothrombi n).
236. The answer is d. (Brunton, p 859; Katzung, pp 604-607.) Thi s i s a fa i rl y typi ca l pres enta ti on of hepa ri n-i nduced thrombocytopeni a (HIT) i n terms of
both phys i ca l fi ndi ngs a nd ti me-cours e of ons et. If hepa ri n a dmi ni s tra ti on l a s ts for more tha n a bout a week, pl a tel et counts s houl d be checked
s evera l ti mes a week for the fi rs t month or s o a nd then monthl y therea fter, beca us e thi s i s a potenti a l l y fa ta l res pons e. It i s i mmune-medi a ted:
a nti bodi es form a ga i ns t a hepa ri n-pl a tel et compl ex; pl a tel ets a re a cti va ted (thus , the thrombos i s a nd s uch compl i ca ti ons a s pul mona ry a nd/or
corona ry occl us i on, a s I des cri bed); the va s cul a r endothel i a a re da ma ged; a nd ul ti ma tel y the number of pl a tel ets tha t ca n be detected i n a venous
bl ood s a mpl e decl i nes ma rkedl y (a nd s o, the thrombocytopeni a ). The overa l l i nci dence of HIT i s a bout 10 ti mes hi gher wi th unfra cti ona ted
hepa ri n tha n wi th LMW hepa ri n. Shoul d HIT occur, or be s us pected, the a pproa ch i ncl udes s toppi ng the hepa ri n a nd s ubs ti tuti ng other
a nti coa gul a nts . A good choi ce woul d be a di rect thrombi n i nhi bi tor (eg, bi va l i rudi n).
As pi ri n, by vi rtue of i ts a nti pl a tel et effects , s houl d not i nduce thrombos i s . ACE i nhi bi tors a nd bl ockers (ca rvedi l ol , a ny others ) do not i ntera ct
to ca us e hemol yti c a nemi a or other bl ood dys cra s i a s .
237. The answer is b. (Brunton, pp 757-758, 795; Katzung, pp 195-201.) Us i ng l ong-a cti ng ni trova s odi l a tors 24-7 i s not a t a l l a good i dea , beca us e i t
ul ti ma tel y l ea ds to tol era nce to the des i red va s odi l a tor effects . Thi s i s of concern i n pa rt beca us e, by defi ni ti on, when a s ys tem or functi on
devel ops tol era nce to a drug, we mus t i ncrea s e the dos e i n order to a chi eve effects of the s a me i ntens i ty a s occurred before. Wi th ni trogl yceri n
pa tches , or other l ong-a cti ng ni trova s odi l a tors , i ncrea s i ng the dos e to res tore the res pons e ul ti ma tel y a ccel era tes or otherwi s e i ntens i fi es the
tol era nce, s uch tha t further dos a ge i ncrea s es s eem wa rra nted. More i mporta ntl y, wi th the devel opment of tol era nce, the va s odi l a tor/a nti a ngi na l
effi ca cy of s ubl i ngua l (or tra ns mucos a l ) ni tra te i s di mi ni s hed too. So, s houl d the pa ti ent devel op a ngi na , us ua l dos a ges of i mmedi a te-a cti ng
drugs ma y not provi de rel i ef of ei ther the s ymptoms or the underl yi ng myoca rdi a l i s chemi a .
If you thought cya ni de poi s oni ng (a ) wa s the correct a ns wer you were proba bl y thi nki ng of ni troprus s i de toxi ci ty. Cya ni de i s not a meta bol i te of
ni trogl yceri n or other drugs tra di ti ona l l y us ed for a ngi na . Dos es of ni tra tes tha t a re too hi gh, or tha t otherwi s e l ower peri phera l res i s ta nce too
qui ckl y, ma y tri gger refl ex ta chyca rdi a . Thi s i s , for s ome pa ti ents , a probl em ea rl y-on i n thera py wi th ra pi dl y a cti ng ni tra tes . It us ua l l y becomes l es s
probl ema ti c a s thera py conti nues , of i f the dos a ge i s ti tra ted down a bi t. It i s ra rel y a probl em wi th l ong-a cti ng ni tra tes . We do not s ee
bra dyca rdi a (c), refl ex or otherwi s e, i n res pons e to thes e drugs . Ni trova s odi l a tors , s hort- or l ong-a cti ng, a nd rega rdl es s of the a dmi ni s tra ti on route,
do not ca us e thrombos i s or a ffect a ny other a s pects of the coa gul a ti on-thrombol ys i s proces s es (d). Pa ra doxi ca l va s ocons tri cti on l ea di ng to
hypertens i on (e) does not occur.
238. The answer is b. (Brunton, pp 736-739; Katzung, pp 184-185, 219.) Los a rta n, a n a ngi otens i n receptor bl ocker (ARB), ha s no effect on a ngi otens i n II
s ynthes i s (a s do the ACE i nhi bi tors s uch a s l i s i nopri l , ca ptopri l , a nd others ). Its ma i n a nti hypertens i ve a cti ons , therefore, i ncl ude onl y bl ocka de of
a ngi otens i n II-medi a ted a l dos terone rel ea s e from the a drena l cortex, a nd of a ngi otens i n IIs va s ocons tri ctor effects .
Li s i nopri l a nd the other ACE i nhi bi tors i nhi bi t a ngi otens i n II s ynthes i s , a nd tha t effect a ccounts (i ndi rectl y) for reduced a l dos terone rel ea s e a nd
AII-medi a ted va s ocons tri cti on. They a l s o i nhi bi t meta bol i c i na cti va ti on of bra dyki ni n, a n endogenous va s odi l a tor (bra dyki ni na s e, a ngi otens i nconverti ng enzyme, a nd ki ni na s e II a re s ynonyms for es s enti a l l y the s a me enzyme).
Nei ther a n ACE i nhi bi tor nor a n ARB i s a s s oci a ted wi th a n i ncrea s ed i nci dence of bronchos pa s m (b; a l though s ome ACE i nhi bi tors ma y ca us e
cough, pres uma bl y from l oca l l y i ncrea s ed bra dyki ni n l evel s , a nd a ngi oedema , perha ps by the s a me mecha ni s m). Nei ther el eva tes ura te l evel s .
There i s s ome evi dence tha t a ngi otens i n II enha nces (not i nhi bi ts ) s ympa theti c-medi a ted va s ocons tri cti on (by i ncrea s i ng neurona l
norepi nephri ne rel ea s e a nd/or bl ocki ng neurona l norepi nephri ne reupta ke). Ei ther a n ACE i nhi bi tor or a n ARB s houl d be equi va l ent i n

a ttenua ti ng tha t bl ood pres s ure-el eva ti ng effect.

ACE i nhi bi tors a re cons i dered to be a n es s enti a l pa rt of thera py (a l ong wi th -bl ockers a nd a di ureti c) for mos t pa ti ents wi th hea rt fa i l ure.
Angi otens i n receptor bl ockers s uch a s l os a rta n ma y prove to be equa l l y effecti ve a l terna ti ves .
By the wa y: You di dnt l ea rn expl i ci tl y a bout l i s i nopri l a nd s o di dnt recogni ze i ts cl a s s i fi ca ti on? Remember: drugs wi th generi c na mes tha t end
i n -pri l a re ACE i nhi bi tors .
239. The answer is d. (Brunton, pp 959-960; Katzung, p 616.) Ezeti mi be i nhi bi ts a bs orpti on of di eta ry chol es terol through the gut. It ha s no hepa ti c or
other di rect effects tha t contri bute to i ts cl i ni ca l l y des i red effect. The drug l a cks ca rdi a c effects (a ) or va s cul a r effects (b). There i s no good
evi dence tha t ezeti mi be i ncrea s es the ri s ks of pl a que rupture, a nd the s ubs equent a nd often deva s ta ti ng cons equences of tha t. Other l i pi dl oweri ng drugs , s uch a s ni a ci n, the fi bra tes , a nd perha ps s ome of the chol es terol -bi ndi ng res i ns , s eem to i ncrea s e the ri s ks of s ta ti n-i nduced
myopa thy, rha bdomyol ys i s , or l i ver dys functi on. Such i ncrea s ed ri s ks a re the ma jor probl ems to be fa ced when s ta ti ns a re us ed i n combi na ti on of
other l i pi d-l oweri ng a gents . However, thi s s eems not to be a probl em wi th ezeti mi be. It i s a ra ti ona l drug to combi ne wi th a s ta ti n, a nd one
propri eta ry fi xed-dos e combi na ti on tha t conta i ns ezeti mi be a nd a s ta ti n i s a va i l a bl e a nd qui te wi del y us ed.
240. The answer is e. (Brunton, p 771; Katzung, pp 611-612.) Ti me i s mus cl e, s ome s a y when a ddres s i ng the i s s ue of thrombol ys i s for corona ry
occl us i on. (Thos e who us e a l yti c drug for i s chemi c s troke wi l l s i mpl y s a y ti me i s ti s s ue.) Idea l l y, the door to needl e ti me s houl d be 90 mi nutes
or (prefera bl y) much l es s . It i s true tha t choos i ng a l tepl a s e (a ) or s ome other t-PA va ri a nt ma y be a s s oci a ted wi th a l ower ri s k of bl eedi ng, owi ng to
thei r cl ot-s peci fi c s i te of a cti on; a nd tha t i t i s relatively s a fer to us e them wi th hepa ri n. In contra s t, s treptoki na s e a dmi ni s tra ti on once ma y l ea d to
a nti bodi es tha t, i f the pa ti ent i s retrea ted wi th the s a me drug (wi thi n a bout 5 da ys to 2 yea rs ), ma y ei ther or both neutra l i ze the drug (renderi ng i t
i neffecti ve) or tri gger a n a l l ergi c rea cti on. However, I s ta ted thi s wa s our pa ti ents fi rs t MI. (You coul d a rgue tha t the pa ti ent ma y a l rea dy ha ve a nti SK a nti bodi es from a pri or s treptococca l i nfecti on, but you di dnt thi nk of tha t, di d you?)
The key poi nt, then, i s s ta rti ng thrombol ys i s a s qui ckl y a s pos s i bl e, not whi ch drug i s chos en. There s eems to be ma xi mum benefi t (s a l va gi ng
ti s s ue, reduci ng ul ti ma te i nfa rct s i ze, ma i nta i ni ng rea s ona bl e ca rdi a c functi on, a nd reduci ng morta l i ty) i f a thrombol yti ca ny thrombol yti ci s
a dmi ni s tered wi thi n 1 hour of s ymptom ons et. Accordi ng to ma ny s tudi es , benefi ts of thrombol ys i s become compa ra bl e to pl a cebo i f the drug i s nt
s ta rted unti l a round 6 hours a fter s ymptom ons et, a nd i n terms of morta l i ty thrombol yti cs ma y a ctua l l y i ncrea s e the ri s k of dea th i f not gi ven a fter
a bout 12 hours or s o.
241. The answer is c. (Brunton, pp 752, 868f, 871t; Katzung, pp 613, 617, 994, 999.) Abci xi ma b, a nd s uch rel a ted drugs a s ti rofi ba n a nd epti fi ba ti de, bl ock
the gl ycoprotei n IIb/IIIa receptor on pl a tel ets . Abci xi ma b i s a n a nti body ra i s ed a ga i ns t the IIb/IIIa receptor. It bi nds to the receptor, a nd i n doi ng
s o bl ocks the forma ti on of fi bri nogen bri dges between the IIb/IIIa receptors on a dja cent pl a tel ets . Tha t i s , otherwi s e, the fi na l cri ti ca l s tep i n
ca us i ng pl a tel ets to a ggrega te wi th thei r nei ghbors .
It i s a l s o noteworthy tha t pl a tel et a cti va ti on ca n be tri ggered by thromboxa ne A2 , thrombi n, col l a gen, ADP, a nd pl a tel et-a cti va ti ng fa ctor (PAF)
(a mong other a goni s ts ). Bl ock the a cti va ti ng effects of jus t one of thos e fa ctors (eg, thos e of ADP wi th cl opi dogrel ), a nd the proa ggrega tory effects
of the other a cti va tors a re l eft unchecked. Pl a tel et a cti va ti on ens ues ; s ome pl a tel et-deri ved a cti va tors a re rel ea s ed, thereby recrui ti ng the
a cti va ti on of more pl a tel ets the a mpl i fi ca ti on proces s .
Abci xi ma b, i n contra s t, bl ocks the fi na l s tep i n a ggrega ti on, rega rdl es s of the pres ence or a bs ence of i nfl uences from ups trea m a cti va tors .
242. The answer is c. (Brunton, pp 212, 305-307; Katzung, pp 152f, 154, 167, 180, 189.) Phenyl ephri ne, a s noted, ca us es va s ocons tri cti on through i ts
a goni s t a cti vi ty on -a drenergi c receptors . Pra zos i n competi ti vel y bl ocks thos e receptors , a nd s i nce we ha ve a pa ti ent who ha s ta ken a n exces s i ve
dos e of the a nta goni s t i t s houl d be no s urpri s e tha t us ua l l y effecti ve (or even hi gher) dos es of phenyl ephri ne wi l l not be a bl e to overcome tha t
bl ocka de. None of the other drugs l i s ted ha ve a ny di rect effects on a n -a drenergi c receptors , nor the a bi l i ty of phenyl ephri ne to a cti va te them.
(Thi a zi des proba bl y exert thei r a nti hypertens i ve effects by ca us i ng s ome net s odi um depl eti on, whi ch reduces va s cul a r res pons i venes s to
a drenergi c a goni s ts , a ngi otens i n II, a nd a ny other va s ocons tri ctors you ma y conjure. However, i t i s hi ghl y unl i kel y tha t a thi a zi de woul d compl etel y
el i mi na te a ny va s opres s or effects of a us ua l dos e of phenyl ephri nel et a l one repea ted dos es .)
243. The answer is e. (Brunton, pp 305-307; Katzung, pp 152f, 154, 167, 180, 189.) Thi s i s a n a pt des cri pti on of a n -a drenergi c bl ocker, a nd not a t a l l
des cri pti ve of the a cti ons or effects of a ny other drug l i s ted. Pra zos i n ca n be cons i dered the prototype of the -a drenergi c bl ockers , a t l ea s t thos e
tha t s el ecti vel y bl ock 1 receptors (i n compa ri s on wi th phentol a mi ne a nd s evera l other drugs , whi ch bl ock both 1 a nd 2 receptors ). Its not l i kel y
your pa ti ent wa s ta ki ng pra zos i n i ts el f (or a rel a ted drug l i ke doxa zos i n or tera zos i n). Tha t i s beca us e thos e drugs not onl y exert s i gni fi ca nt
i nhi bi tory effects on s mooth mus cl e of the pros ta te ca ps ul e a nd urethra , but a l s o on the peri phera l va s cul a ture. They coul d be (a nd s ometi mes
a re) us ed for beni gn pros ta ti c hypertrophy. If the pa ti ent i s a l s o hypertens i ve, one drug ma y hel p both condi ti ons . If bl ood pres s ure i s norma l , or
control l ed wel l wi th other a nti hypertens i ves , then pra zos i n or doxa zos i n ma y l ower pres s ure too much (unl es s we cha nge dos a ges or drugs ). More
l i kel y your pa ti ent i s ta ki ng ta ms ul os i n. Its cl ea rl y i n the s a me cl a s s a s pra zos i n, but s eems to ha ve more s el ecti vi ty for s mooth mus cl es i n the
uri na ry tra ct, a nd fewer or mi l der peri phera l va s cul a r a cti ons tha t woul d tend to l ower bl ood pres s ure a nd tri gger the other res pons es I noted.
244. The answer is e. (Brunton, pp 730-736; Katzung, pp 184-185, 1054t.) ACE i nhi bi tors (a nd a ngi otens i n receptor bl ockers , ARBs eg, l os a rta n) a re
contra i ndi ca ted i n women who a re pregna nt or of chi l d-bea ri ng potenti a l . ACE i nhi bi tors a nd ARBs do not exa cerba te a s thma (a ); they a re
cons i dered fi rs t-l i ne a djuncti ve drugs for ma na gi ng mos t pa ti ents wi th hea rt fa i l ure (b), whi ch ma y or ma y not be a n a ccompa ni ment of
hyperl i pi demi a s or corona ry a rtery di s ea s e (c). We woul d wa nt to norma l i ze pota s s i um l evel s i f the pa ti ent were hypoka l emi c (d; but i t depends
on wha t the a bs ol ute pota s s i um l evel s a re, a nd whether the hypoka l emi a i s s ymptoma ti c), before we ga ve a n ACE i nhi bi tor, but one woul d wa nt
to be very ca reful i n terms of how to go a bout doi ng tha t. ACE i nhi bi tors a nd ARBs ul ti ma tel y l ower ci rcul a ti ng a l dos terone l evel s , whi ch i n turn
fa vors more rena l pota s s i um retenti on. One of thes e drugs , a l one, mi ght correct pota s s i um l evel s . Gi vi ng a n ACE i nhi bi tor or ARB a l ong wi th a
pota s s i um-s pa ri ng di ureti c ma y not merel y correct the hypoka l emi a but, eventua l l y a nd more l i kel y, ca us e hyperka l emi a .
245. The answer is a. (Brunton, pp 225-235; Katzung, pp 115-124.) Si nus bra dyca rdi a ca n be conceptua l l y vi ewed a s a n i mba l a nce of two oppos i ng
fa ctors on the SA node: (a ) too grea t a n i nfl uence of the pa ra s ympa theti c nervous s ys tem, s peci fi ca l l y, of ACh a cti ng on mus ca ri ni c receptors ; or (b)
too l i ttl e a cti va ti on of 1 a drenergi c receptors . We ca n a ddres s ei ther, or both, i mba l a nces pha rma col ogi ca l l y. Accordi ng to current ACLS gui del i nes ,
us i ng a tropi ne to bl ock exces s i ve pa ra s ympa theti c i nfl uences , a l l owi ng hea rt ra te to go up, i s the recommended fi rs t a pproa ch.
An a l terna ti ve a pproa ch woul d be to a cti va te 1 a drenergi c receptors , eg, wi th i s oproterenol . Ami oda rone (b) i s nei ther effecti ve nor i ndi ca ted
for s i nus bra dyca rdi a . It i s us ed a s a fi rs t-l i ne drug for ca rdi a c a rres t; i s i ndi ca ted for ma na gi ng s ome s eri ous a nd l i fe-threa teni ng ventri cul a r
a rrhythmi a s ; a nd ha s gotten growi ng a ttenti on for i ts a ppa rent effi ca cy to ma na ge a tri a l fi bri l l a ti ona ra ther unus ua l us e gi ven the s eri ous nes s
of the other a rrhythmi a s for whi ch the drug i s gi ven. Edrophoni um (c) woul d be a mong the wors e drugs you coul d gi ve to thi s bra dyca rdi c pa ti ent.
Thi s ra pi dl y a cti ng ACh es tera s e i nhi bi tor wi l l ca us e a ccumul a ti on of even more ACh a t the SA node (a nd el s ewhere i n the a utonomi c nervous

s ys tem where ACh i s the neurotra ns mi tter a cti va ti ng s mooth mus cl es a nd va ri ous exocri ne gl a nds . If the pa ti ents hea rt does nt s top i n res pons e
to edrophoni um, a s s umi ng we gi ve a us ua l dos e, i t i s mere l uck. Li doca i ne (d) i s effecti ve for a hos t of ventri cul a r a rrhythmi a s , i ncl udi ng thos e
a s s oci a ted wi th a n MI. It wi l l do nothi ng good for the bra dyca rdi a . You mi ght a rgue tha t phentol a mi ne (e), the prototype -a drenergi c bl ocker,
woul d work. It mi ght, but proba bl y a t grea t cos t to thi s pa ti ents hemodyna mi c s ta tus . When we i nject us ua l dos es of phentol a mi ne hea rt ra te
i ndeed goes up. Tha t i s medi a ted by the ba roreceptor refl ex: we ha ve gi ven enough drug to ra pi dl y a nd ma rkedl y drop bl ood pres s ure vi a the
drugs va s odi l a tor a cti ons . Tha t, i n turn, wi thdra ws centra l pa ra s ympa theti c tone a nd ca us es a rel a ti ve i ncrea s e i n s ympa theti c outfl ow. Both
effects woul d i ncrea s e the hea rt ra te. Unfortuna tel y, our bra dyca rdi c pa ti ent proba bl y a l rea dy ha s a bl ood pres s ure a nd ca rdi a c output tha t a re on
the l ow s i de of conduci ve to a l ong a nd ha ppy l i fe. Even i f he di dnt, ca us i ng bl ood pres s ure to promptl y a nd ma rkedl y fa l l often does nt l ea d to a
fa vora bl e outcome.
246. The answer is e. (Brunton, pp 752, 767-768; Katzung, pp 193-208.) In terms of a utonomi c control of corona ry va s cul a r tone, envi s a ge a ba l a nce
between the va s ocons tri ctor i nfl uences of -a drenergi c a cti va ti on a nd the oppos i ng va s odi l a tor i nfl uences of 2 -receptor a cti va ti on. Spa s m-prone
corona ri es a ppea r to be very dependent on the -medi a ted va s odi l a tor i nfl uences to reduce the i nci dence a nd s everi ty of s pa s m. Any -bl ocker
wi l l remove thos e fa vora bl e i nfl uences , a nd tend to provoke (or i ntens i fy or prol ong) s pa s m a nd the res ul ti ng i s chemi a i n di s ta l ti s s ues . Thi s
va s cul a r effect i s l i kel y to overs ha dow a ny benefi ci a l effects a ttri buted to reducti ons of myoca rdi a l oxygen dema nd vi a s uppres s i on of hea rt ra te
a nd contra cti l i ty.
You coul d correctl y a rgue tha t i n the a bs ence of demons tra ted corona ry occl us i on the a dmi ni s tra ti on of t-PA (a ) woul d be i na ppropri a te.
However, tha t drug i s not l i kel y to ma ke ma tters wors e. Ca ptopri l (c), the prototype ACE i nhi bi tor, s houl d ha ve no nega ti ve or pos i ti ve effects on
va s os pa s m. Ni trogl yceri n (d) mi ght reduce the i nci dence or s everi ty of s pa s m through ni tri c-oxi de-medi a ted va s odi l a ti on. Vera pa mi l (f) woul d
proba bl y be one of the mos t ra ti ona l drugs to gi ve, s i nce i ts va s cul a r ca l ci um cha nnel bl ocki ng a cti vi ty woul d hel p s uppres s s pa s m; i ts nega ti ve
i notropi c a nd chrono-tropi c effects woul d, a ddi ti ona l l y, reduce myoca rdi a l oxygen dema nd a nd be benefi ci a l .
247. The answer is b. (Brunton, pp 767, 971-972; Katzung, pp 612, 638-640.) Tha t a s pi ri n mi ght i ncrea s e the ri s k of s troke s houl d not be s urpri s i ng. The
s a me mecha ni s m by whi ch the drug exerts protecti ve effects a ga i ns t MI, by i nhi bi ti ng pl a tel et a ggrega ti on, expl a i ns why s ome pa ti ents who
otherwi s e mi ght devel op a cerebra l bl eed a re a t i ncrea s ed ri s k of doi ng s o. There i s no good evi dence tha t a s pi ri n i nges ti on ca us es hepa totoxi ci ty
of a ny s ort (a ); ta chyca rdi a a nd/or hypotens i on (d; other tha n vi a bl ood l os s a nd hypovol emi a due to exces s i ve bl eedi ng); nor ca us es or provokes
corona ry va s os pa s m (e). Long-term us e of ma ny nons teroi da l a nti -i nfl a mma tory drugs ma y ca us e nephropa thy, but tha t i s typi ca l l y a s s oci a ted wi th
hi gh-dos e us e, a nd ra rel y wi th a s pi ri n i ts el f.
248. The answer is d. (Brunton, pp 113, 732-733, 738-739, 784-785; Katzung, pp 183-185, 219-220.) The pa ti ent ha s been ta ki ng two di ureti cs , one
pota s s i um-wa s ti ng (the thi a zi de), the other pota s s i um-s pa ri ng. Ra mi pri l i s a n ACE i nhi bi tor (reca l l : drugs wi th generi c na mes endi ng i n -pri l a re
members of tha t cl a s s ) tha t ul ti ma tel y wi l l l ower a l dos terone l evel s . Thi s wi l l , i n es s ence, countera ct the s odi um-reta i ni ng effects of a l dos terone,
a nd a l s o i ts pota s s i um-wa s ti ng effects . So by a ddi ng the ACE i nhi bi tor to the regi men we wi l l now be trea ti ng the pa ti ent wi th two drugs tha t tend
to el eva te pota s s i um l evel s to a degree tha t ca nnot be compens a ted for by the thi a zi de.
Addi ng a n ACE i nhi bi tor to your pa ti ents regi men woul d be a good i dea (provi ded there a re no contra i ndi ca ti ons to doi ng s o) i n terms of getti ng
a ddi ti ona l bl ood pres s ure control , but i t woul d proba bl y requi re el i mi na ti ng the tri a mterene a t s ome poi nt (i f not from the s ta rt) to a voi d the
hyperka l emi a .
Pra zos i n (b), a s el ecti ve 1 -a drenergi c bl ocker, i s not a t a l l l i kel y to ha ve el i ci ted the hyperka l emi a . Di l ti a zem (a ) a nd vera pa mi l (e), both nondi hydropyri di ne ca l ci um cha nnel bl ockers , a re not l i kel y to a ffect pota s s i um l evel s i n a mea s ura bl e wa y. -Adrenergi c bl ockers (eg, propra nol ol , c)
ha ve been reported to l ower pota s s i um l evel s , pres uma bl y by enha nci ng K+ upta ke i nto s kel eta l mus cl e. Thes e drugs a re not, therefore, a l i kel y
ca us e of the hypoka l emi a , even when us ed i n combi na ti on wi th the di ureti cs .
249. The answer is c. (Brunton, pp 206t, 211, 302t, 824t; Katzung, pp 136-138, 139f.) Phenyl ephri ne i s the prototypi c -a drenergi c a goni s t. It termi na ted the
a rrhythmi a refl exl y, vi a the ba roreceptors , i n res pons e to a va s opres s or effect. (Ra i s i ng bl ood pres s ure qui ckl y a nd ma rkedl y i s a ri s ky wa y of
termi na ti ng thi s ta chyca rdi a , of cours e, due to s uch ri s ks a s ca us i ng a hemorrha gi c s troke.) Al l the other drugs woul d a l s o termi na te the
a rrhythmi a , but by a cti ons i n the hea rt. Edrophoni um (a ) i s a n a cetyl chol i nes tera s e i nhi bi tor wi th a fa s t ons et of a cti on a nd a bri ef dura ti on. It
woul d s l ow hea rt ra te by i ncrea s i ng the effects of ACh on the SA node, s l owi ng the s ponta neous ra te of pha s e 4 depol a ri za ti on. Es mol ol i s a bl ocker (nons el ecti ve) tha t a l s o ha s a fa s t ons et a nd s hort dura ti on of a cti on. It a nd propra nol ol (d) woul d s l ow hea rt ra te vi a the di rect -bl ocki ng
effects on the SA node. Vera pa mi l (e) wi l l do the s a me by bl ocki ng AV noda l ca l ci um cha nnel s .
250. The answer is b. (Brunton, pp 801-804, 835t; Katzung, pp 216-217.) Ans weri ng thi s ques ti on, of cours e, requi res tha t you not onl y know the expected
effects of di goxi n, but a l s o tha t you ca n tra ns l a te thos e effects i nto i nterpreta ti ons of fi ndi ngs from a mos t us eful di a gnos ti c tool , the
el ectroca rdi ogra m.
An expected a nd i mporta nt effect of di goxi n i s s l owed a tri oventri cul a r noda l conducti on vel oci ty, ma ni fes t a s prol onga ti on of the PR i nterva l .
The effect, whi ch ca n l ea d to i ncrea s i ng degrees of hea rt bl ock, depends on the pl a s ma concentra ti on of di goxi n a nd on the concentra ti ons of
s evera l i ons , pota s s i um a rgua bl y the mos t i mporta nt.
Di goxi n tends to s peed el ectri ca l i mpul s e vel oci ty through the a tri a l myoca rdi um, a nd s o wi deni ng of P wa ves (a ) woul d be the oppos i te of the
expected res pons e. There i s no good rea s on to expect i ncrea s ed P-wa ve a mpl i tude due to the di goxi n. (Atri a l enl a rgement, a res ul t of the hea rt
fa i l ure a nd not the drug, i s l i kel y.)
Di goxi n a l s o s peeds el ectri ca l i mpul s e conducti on vel oci ty through the ventri cl es (eg, the Hi s -Purki nje s ys tem), a nd s o wi dened QRS compl exes ,
compa red wi th ba s el i ne, woul d be counter to the expected effect.
RR i nterva l s es s enti a l l y refl ect ventri cul a r ra te. Before trea tment of hea rt fa i l ure there a re va ryi ng degrees of compens a tory s ympa theti c dri ve
over the hea rt, l ea di ng to ta chyca rdi a a nd s hortened RR i nterva l s (d). Once di goxi n s ta rts i ncrea s i ng ca rdi a c output, there i s a l es s eni ng of
s ympa theti c dri ve (a nd the phys i ol ogi c need for i t). Thus , compa red wi th ba s el i ne hea rt ra te, pos t-trea tment hea rt ra te i s s l ower; thi s i s ma ni fes t
a s a l onger RR i nterva l compa red wi th ba s el i ne.
ST s egment cha nges a re a mong the ma ni fes ta ti ons of a cute corona ry s yndrome a nd regi ona l myoca rdi a l i s chemi a . Ba s ed on the des cri pti on of
the pa ti ent, who a ppea rs to ha ve norma l bl ood profi l es a nd no evi dence of a cute i s chemi a , ST el eva ti on (e) i s not a rea s ona bl e a ns wer.
251. The answer is e. (Brunton, pp 210, 828, 831-832; Katzung, pp 155-156.) Pheochromocytoma s a re epi nephri ne-s ecreti ng tumors , a nd s o the worri s ome
a nd da ngerous cons equences a re due to exces s i ve va s ocons tri cti on (-medi a ted) a nd ca rdi a c chronotropi c a nd i notropi c res pons es (1 ). A a drenergi c bl ocker i s a n es s enti a l component of pha rma cothera py. It mus t be a dmi ni s tered a l ong wi th a nother drug tha t bl ocks -a drenergi c
receptors , but s houl d not be gi ven before the -a drenergi c bl ocker i s gi ven. Acti va ti on of 2 -a drenergi c receptors i n the peri phera l va s cul a ture

pl a ys a s ma l l but i mporta nt rol e i n bl ood pres s ure control (s i nce 2 a cti va ti on i n s ome va s cul a r beds ca us es va s odi l a ti on). Bl ock tha t effect i n a
pa ti ent wi th epi nephri ne exces s a pheochromocytoma a nd a ny potenti a l l y bl ood pres s ure-l oweri ng effects a re l os t. Bl ood pres s ure wi l l ,
therefore, ei ther ri s e or s ta y the s a me i n terms of peri phera l va s cul a r effects .
In the fa ce of thi s s ti l l -hi gh bl ood pres s ure a nd tota l peri phera l res i s ta nce the -bl ocker wi l l reduce both hea rt ra te a nd contra cti l i ty, a nd s o
ca rdi a c output wi l l fa l l (reca l l tha t CO = HR SV). The outcome ma y be not merel y a fa l l of ca rdi a c output, but a cons i dera bl e fa l l i n a very s hort
ti me tha t mi ght wel l put the pa ti ent i nto a cute hea rt fa i l ure.
Bl ood pres s ure i s not a t a l l l i kel y to fa l l promptl y due to a ny peri phera l va s odi l a tor effects ; i f i t di d (a nd i t wont), the -bl ocker woul d prevent
refl ex ta chyca rdi a (a ) vi a di rect a cti ons on ca rdi a c 1 receptors . The -bl ockers do not i nhi bi t ca techol a mi ne rel ea s e (b), whether from a
ca techol a mi ne-s ecreti ng tumor or from a norma l s ympa theti c nervous s ys tem. A -bl ocker wi l l not tri gger ca techol a mi ne rel ea s e from a
pheochromocytoma (c), nor wi l l i t norma l i ze ca rdi ova s cul a r s ta tus i n a ny other wa y i f gi ven wi thout a n -bl ocker. A -bl ocker a l one, i n thi s
s i tua ti on, wi l l ra i s e l eft ventri cul a r a fterl oa d, a nd reduce ca rdi a c output by effects on both hea rt ra te a nd s troke vol ume. Thus , a ns wer e i s wrong.
252. The answer is d. (Brunton, pp 760, 768-771; Katzung, pp 195-201.) Ni trogl yceri n a nd other ni trova s odi l a tors provi de i mmedi a te s ymptom rel i ef i n
mos t pa ti ents wi th a n a cute corona ry s yndrome or MI. However, there i s no evi dence tha t thes e drugs provi de l ong-term preventa ti ve effects
a ga i ns t s udden dea th from a n a cute MI. In contra s t, a s pi ri n (a ; a nti pl a tel et drug), a l i pi d-l oweri ng drug s uch a s a torva s ta ti n (b), ACE i nhi bi tors
s uch a s ca ptopri l (c), a nd -bl ockers s uch a s propra nol ol (e), ha ve documented protecti ve effects to reduce the ri s k of dea th from a s ubs equent MI.
253. The answer is a. (Brunton, pp 206t, 290, 804-805; Katzung, pp 141-142, 144, 148, 218, 225.) Intra venous i nfus i on of dobuta mi ne, a 1 a goni s t, wa s the
mos t l i kel y ca us e of the i ncrea s ed hea rt ra te. Bl ood pres s ure proba bl y ros e s econda ry to a pos i ti ve i notropi c effect of the drug; i t ca nnot be by a ny
di rect effect on tota l peri phera l res i s ta nce, s i nce even a t hi gh dos es dobuta mi ne ha s no va s ocons tri ctor a cti vi ty. Es mol ol (b) i s a nons el ecti ve bl ocker wi th a ra pi d ons et of a cti on, a nd a bri ef dura ti on of a cti on due to ra pi d hydrol ys i s by pl a s ma es tera s es . Bei ng a -bl ocker, nei ther i t nor
propra nol ol (d) woul d ra i s e hea rt ra te or bl ood pres s ure. Neos ti gmi ne (c) i s a n ACh es tera s e i nhi bi tor. It a nd vera pa mi l (e), a nondi hydropyri di ne
ca l ci um cha nnel bl ocker, woul d be expected to reduce hea rt ra te. Vera -pa mi l woul d a l s o tend to l ower, not ra i s e, bl ood pres s ure by vi rtue of i ts
peri phera l va s odi l a tor a cti on.
254. The answer is a. (Brunton, pp 752, 767-768; Katzung, pp 159t, 161, 175t, 179.) Metoprol ol i s pri ma ri l y a 1 -a drenergi c bl ocker a t l ow dos es , but a t
hi gh dos es ca n bl ock 2 receptors a l s o. Thus , i t i s s ometi mes ca l l ed a ca rdi os el ecti ve -bl ocker, much l i ke a tenol ol . Mos t of the -bl ockers ha ve
no va s odi l a ti ng a cti vi ty (noteworthy excepti ons a re l a beta l ol a nd ca rvedi l ol , whi ch ha ve -bl ocki ng a cti vi ty; a nd nebi vol ol , whi ch va s odi l a tes vi a a
ni tri c oxi de-dependent proces s ).
-Adrenergi c receptor bl ockers s l ow res ti ng hea rt ra te a nd reduce contra cti l i ty, both of whi ch reduce myoca rdi a l oxygen dema nd. They a l s o bl unt
ca rdi a c s ti mul a tory res pons es tha t i ncrea s e oxygen dema nd, whenever the s ympa theti c nervous s ys tem i s a cti va ted (eg, i n res pons e to exerci s e or
drugs tha t tend to ca us e refl ex s ympa theti c a cti va ti on). Thes e a l l i nvol ve bl ocka de of 1 receptors .
Metoprol ol does not ca us e corona ry va s odi l a ti on (a nd ma y fa vor cons tri cti on, whi ch ca n become cl i ni ca l l y s i gni fi ca nt i n pa ti ents wi th va ri a nt
a ngi na , by unma s ki ng -medi a ted corona ry va s ocons tri cti on; s ee Ques ti on 188; thus a ns wer b i s i ncorrect); a nd i t ma y i ncrea s e (not decrea s e, d)
tota l peri phera l res i s ta nce by bl ocki ng 2 -medi a ted di l a ti on i n s ome va s cul a r beds . Thi s effect i s us ua l l y s l i ght (s tronger wi th the va s odi l a ti ng bl ocker noted i n the fi rs t pa ra gra ph). Al l the bl ockers s l ow AV noda l conducti on vel oci ty, but tha t effect per se contri butes l i ttl e to the reduced
oxygen dema nd tha t i s ma i nl y deri ved from the drugs effects on overa l l ra te a nd contra cti l i ty. Thus , a ns wer e i s i ncorrect.
Al l the -bl ockers reduce a ngi otens i n II s ynthes i s (c), but i t i s a n i ndi rect effect, i nvol vi ng 1 bl ocka de, due to reduced reni n rel ea s e from the
juxta gl omerul a r a ppa ra tus of the ki dneys . Al though tha t effect cl ea rl y occurs , i t i s not a ma jor mecha ni s m by whi ch -bl ockers exert thei r
a nti a ngi na l effects , nor i s the ma gni tude of the i nhi bi ti on of a ngi otens i n II s ynthes i s on pa r wi th tha t ca us ed by ACE i nhi bi tors .
255. The answer is b. (Brunton, pp 941, 977-982, 849, 964; Katzung, pp 314-316, 323-324, 638-640.) At the us ua l l ow ca rdi oprotecti ve dos es (us ua l l y 81
mg/da y) of a s pi ri n, the ma i n a nd thera peuti ca l l y us eful effect of the drug i s i nhi bi ti on of thromboxa ne A2 (TXA2 ) s ynthes i s vi a the COX-1 pa thwa y.
Reca l l tha t TXA2 i s one i mporta ntbut certa i nl y not the onl ytri gger of pl a tel et a cti va ti on, a mpl i fi ca ti on, a nd a ggrega ti on. However, a t hi gh(er)
dos es , a s pi ri n a l s o i nhi bi ts s ynthes i s of other ei cos a noi ds , of whi ch PGI2 (pros ta cycl i n), s ynthes i zed i n the va s cul a r endothel i um, i s of mos t
i mporta nce here. Endothel i a l pros ta cycl i n s ynthes i s hel ps prevent pl a tel ets from a dheri ng to the va s cul a r wa l l . Suppres s PGI2 i n the endothel i um,
a nd pl a tel et a dherence i s i ncrea s ed, des pi te the fa ct tha t pl a tel et TXA2 s ynthes i s ha s a l rea dy been bl ocked. Its i mporta nt to remember here tha t
a s pi ri n does nothi ng to i nhi bi t pl a tel et a cti va ti on by s uch other a goni s ts a s col l a gen or ADP. By l oweri ng endothel i a l PGI2 l evel s weve i ncrea s ed
the l i kel i hood tha t pl a tel ets a cti va ted by ei cos a noi d-i ndependent a goni s ts wi l l a dhere to the l i ni ng of bl ood ves s el s , a nd potenti a l l y occl ude
them.
As pi ri n ha s no effect on Gp IIb/IIIa receptors (a ); i t does not rupture or otherwi s e da ma ge va s cul a r pl a ques (c) to expos e col l a gen; i nhi bi t
s ynthes i s of a ny l i ver-ba s ed cl otti ng fa ctors (d); or a mpl i fy or otherwi s e enha nce the effects of ADP (e) or of other pl a tel et a cti va tors .
256. The answer is b. (Brunton, pp 898-899; Katzung, pp 629-630, 633, 760.) Col es evel a m i s the newes t bi l e-a ci d s eques tra nt, a nd i s the drug of choi ce
when a bi l e a ci d-s eques tra nt i s i ndi ca ted. The ol der a gents a re chol es tyra mi ne a nd col es ti pol . Thes e drugs , whi ch a re gi ven ora l l y, a re
nona bs orba bl e res i ns tha t bi nd (s eques ters , a ds orbs ) ma ny s ubs ta nces tha t a re pres ent i n the GI tra ct (eg, bi l e s a l ts ) a t the s a me ti me a s the
drug, prevents them from bei ng (re)a bs orbed, a nd fa ci l i ta tes thei r el i mi na ti on i n the feces . None of thes e drugs ha ve a ny effects on rena l
ha ndl i ng of el ectrol ytes , non-el ectrol ytes , or free wa ter (a , e); no effects on ura te l evel s (c); ha ve no di rect a nti a ngi na l effects , a nd certa i nl y no
nega ti ve i notropi c or chronotropi c effects ; a nd a re not a nti hypertens i ve (e).
Col es evel a m ma y be us ed a l one, but us ua l l y i t i s i n combi na ti on wi th a s ta ti n. On a vera ge, col es evel a m a l one ca n l ower LDL chol es terol by
a bout 20% (the typi ca l ra nge i s between 15% a nd 30%). In contra s t, combi ned thera py wi th a s ta ti n ca n reduce LDL chol es terol by up to 50%. Si mi l a r
res ul ts ca n be obta i ned by combi ni ng a s eques tra nt wi th ni a ci n. LDL-l oweri ng effects begi n s oon a fter dos i ng s ta rts , but i t ma y ta ke a month or s o
for effects to pea k.
Al l the bi l e-a ci d s eques tra nts l ower LDL chol es terol through a mecha ni s m tha t ul ti ma tel y depends on i ncrea s i ng LDL receptors on hepa tocytes ,
a nd tha t occurs vi a a s equence of rel a ted s teps . Bi l e s a l ts a nd the chol es terol from whi ch they a re ma de a re excreted i nto the i ntes ti nes .
Norma l l y, therea fter, a good porti on of the excreted bi l e s a l ts a nd chol es terol i s rea bs orbed a nd recycl ed i n a proces s us ua l l y ca l l ed
enterohepa ti c reci rcul a ti on. The bi l e a ci d s eques tra nts i nterrupt the recycl i ng. They a ds orb the chol es terol -ri ch bi l e a ci ds i n the i ntes ti ne a nd
form a n i ns ol ubl e compl ex tha t prevents the bi l e s a l ts a nd chol es terol from bei ng returned to the ci rcul a ti on. As a res ul t, the excreti on of
chol es terol -l a den bi l e s a l ts i ncrea s es . Thi s i ncrea s ed excreti on crea tes a dema nd for i ncrea s ed bi l e a ci d forma ti on i n the l i ver; a nd tha t, i n turn
requi res i ncrea s ed chol es terol s uppl y to the l i ver. Tha t chol es terol comes from LDL. In order to us e more LDL chol es terol the l i ver cel l s i ncrea s e
thei r number of LDL receptors . Tha t i ncrea s es thei r ca pa ci ty for LDL upta ke. The res ul t i s a n i ncrea s e i n LDL upta ke from pl a s ma , a nd a decrea s e of

ci rcul a ti ng LDL l evel s . Wi th conti nued a dmi ni s tra ti on of the s eques tra nt the cycl e repea ts i ts el f a s bi l e s a l t excreti on conti nues to i ncrea s e, a nd
over ti me the eventua l res ul t i s a fa l l of LDL l evel s .
Bi l e-a ci d s eques tra nts ma y i ncrea s e VLDL l evel s i n s ome pa ti ents . In mos t ca s es , the el eva ti on i s tempora ry a nd mi l d. However, i f VLDL l evel s
a re el eva ted before trea tment, the bi l e-a ci d s eques tra nts ma y ca us e further s us ta i ned a nd s ubs ta nti a l VLDL i ncrea s es . Therefore, bi l e-a ci d
s eques tra nts a re not drugs of choi ce for l oweri ng LDL chol es terol i n pa ti ents wi th hi gh VLDL l evel s .
Col es evel a m i s now the preferred bi l e a ci d s eques tra nt beca us e i t di ffers from chol es tyra mi ne a nd col es ti pol i n a t l ea s t four ma i n wa ys : (1)
Col es evel a m i s better tol era ted (l es s cons ti pa ti on, fl a tul ence, bl oa ti ng, a nd cra mpi ng). (2) It does not reduce the a bs orpti on of fa t-s ol ubl e
vi ta mi ns (A, D, E, a nd K), whether from foods , bevera ges , or from vi ta mi n s uppl ements . (3) It does not s i gni fi ca ntl y reduce ora l a bs orpti on of
s ta ti ns , di goxi n, wa rfa ri n, a nd mos t other drugs s tudi ed tha t a re pres ent i n the GI tra ct a t the s a me ti me a s the s eques tra nt. (4) Fi na l l y, i t i s of
cours e very common for pa ti ents wi th CHD ri s k to ha ve hyperchol es terol emi a a nd di a betes . Col es evel a m a l s o ca us es des i ra bl e gl ucos e-control l i ng
effects for ma ny pa ti ents wi th type 2 di a betes (i e, a bout 90% of a l l ca s es of di a betes ) when us ed i n combi na ti on wi th s uch other a nti di a beti c
medi ca ti ons a s metformi n, s ul fonyl urea s , or i ns ul i n. It i s the onl y bi l e a ci d s eques tra nt a pproved for us e a s a n a nti di a beti c a djunct.
257. The answer is e. (Brunton, pp 128t, 320, 831-832, 864; Katzung, pp 157-164.) Ni troprus s i de (or a ny other IV va s odi l a tor, eg, ni trogl yceri n) i s l i kel y to
el i ci t ba roreceptor refl ex-medi a ted ri s es of hea rt ra te a nd contra cti l i ty. It ma y be s i gni fi ca nt a nd da ngerous for a ny pa ti ent, more s o for pa ti ents
wi th i s chemi c hea rt di s ea s e, a nd potenti a l l y dea dl y for pa ti ents wi th a neurys ms , s uch a s our pa ti ent. For a orti c a neurys m pa ti ents , the probl em i s
not the ri s e of hea rt ra te, but ra ther of l eft ventri cul a r contra cti l i ty (l eft ventri cul a r dP/dtthe cha nge of ventri cul a r pres s ure over a s peci fi c cha nge
of ti me). The boundi ng a orti c pres s ure pul s e wi th ea ch s ys tol e fa vors rupture of the a neurys m, a nd us e of a -bl ocker s uch a s propra nol ol i s a n
effecti ve a nd common wa y to mi ni mi ze the ri s k (a nd, of cours e, refl ex ca rdi a c s ti mul a ti on overa l l ).
Atropi ne (a ) i s a n i l l ogi ca l choi ce. It wi l l i ncrea s e hea rt ra te (a nd, i ndi rectl y, contra cti l i ty) further by removi ng pa ra s ympa theti c tone on the SA
node. Di a zoxi de (b) i s a ra pi dl y a cti ng a nti hypertens i ve/va s odi l a tor, gi ven a s a n IV bol us i n s i tua ti ons where s a fe ni troprus s i de us e (a nd the
i nva s i ve moni tori ng i t norma l l y requi res ) i s not pra cti ca l . Di a zoxi de, l i ke ni troprus s i de, tri ggers refl ex ca rdi a c s ti mul a ti on a s bl ood pres s ure fa l l s .
The drug a l s o ha s s ome di rect ca rdi a c-s ti mul a ti ng effects (not i nvol vi ng a nti mus ca ri ni c or a drenergi c-a goni s t effects ). Di a zoxi de a l s o tends to
ca us e hypergl ycemi a (a n ora l dos a ge form of the drug i s s ometi mes pres cri bed to ma na ge bl ood gl ucos e l evel s i n pa ti ents prone to devel opi ng
hypogl ycemi a .) Furos emi de (c) i s a l oop di ureti c tha t i s a n i mporta nt a djunct i n s uch condi ti ons a s hypertens i ve cri s i s , but onl y i f due to or
a ccompa ni ed by vol ume overl oa d, hea rt fa i l ure, a nd a cute pul mona ry edema . However, the vol ume depl eti on a nd hypotens i on i t woul d ca us e
woul d exa cerba te the cl i ni ca l s i tua ti on I ha ve des cri bed. The prompt di ures i s a nd fa l l of bl ood pres s ure ma y a l s o tri gger unwa nted ba roreceptormedi a ted ca rdi a c s ti mul a ti on. Phentol a mi ne (d), a n -a drenergi c bl ocker, woul d be i rra ti ona l . It i s a powerful va s odi l a tor (i ndeed, i t i s often us ed
for va s ocons tri ctor drug-i nduced hypertens i ve emergenci es ) tha t woul d a dd tounfa vora bl yni troprus s i des prompt a nti hypertens i ve effect a nd
the refl ex ca rdi a c s ti mul a ti on tha t i s s o da ngerous for our pa ti ent.
258. The answer is c. (Brunton, p 972; Katzung, pp 627-628.) You ma y a rgue a bout i ncl udi ng thi s ques ti on, but there a re a t l ea s t two ma i n rea s ons for
a s ki ng i t. (1) Ni a ci n i s s ti l l a wi del y us ed drug for ma na gi ng certa i n but common hyperl i pi demi a s , a nd the s i de effects des cri bed a re common. (2)
Al though the mecha ni s ti c expl a na ti on i s ba s ed l a rgel y on empi ri c obs erva ti ons , i t s houl d hel p you unders ta nd funda menta l a cti ons of a l a rge a nd
wi del y us ed group of drugs , the cycl ooxygena s e i nhi bi tors (eg, nons teroi da l a nti -i nfl a mma tory drugs ).
(1) Al though pres cri bi ng ha bi ts ha ve cha nged a bi t over the l a s t yea r or s o, ni a ci n i s the mos t common a dd-on to s ta ti n thera py when a s ta ti n
a l one does not l ower HDL a dequa tel y. We a re ta l ki ng a bout mi l l i ons of pa ti ents ! The cuta neous fl us hi ng a nd pruri tus , a nd the underl yi ng
va s odi l a ti on ca us ed by ni a ci n, a re common (es peci a l l y wi th hi gh dos es of ni a ci n a nd/or certa i n ora l formul a ti ons ). In a ddi ti on, thes e s i de effects
a re qui te di s turbi ng to ma ny pa ti ents who experi ence i t.
(2) The probl ems a l mos t certa i nl y i nvol ve pros ta gl a ndi ns . We ca n rea ch tha t concl us i on ra ther empi ri ca l l y, ba s ed on the fa ct tha t thes e
res pons es ma y be prevented by the pri or a dmi ni s tra ti on of a s pi ri n, whi ch of cours e bl ocks pros ta gl a ndi n s ynthes i s . Al though i ts not true 100% of
the ti me, fa r more l i kel y tha n not, if a response is attenuated or abolished by aspirin (or any other traditional NSAID) the mechanism will involve inhibition of
cyclooxygenase(s) a nd the res ul ti ng i nhi bi ti on of the s ynthes i s of one or more pros ta gl a ndi ns or thromboxa nes (ei cos a noi ds ).
-Adrenergi c receptor a cti va ti on (a ) woul d tend to countera ct, not ca us e or contri bute, to the va s odi l a ti on tha t i s i nvol ved i n the fl us h. Ca l ci um
cha nnel bl ockers ha ve no effect on the phenomenon, s o we ca n rul e out a ns wer b. Si mi l a rl y, drugs tha t i nhi bi t a ngi otens i n s ynthes i s or i ts
receptor a cti va ti on (d), or hi s ta mi ne receptor bl ockers (e; whether H 1 or H 2 ) l a rgel y ha ve no effect on the fl us hi ng a nd pruri tus .
259. The answer is c. (Brunton, pp 274-277, 304-316; Katzung, pp 136-138, 144-145.) ISO, PHE, EPI, NE. Yes , s ome res pons es to thes e drugs a re va ri a bl e,
l a rgel y dependi ng on the dos e a nd the s peed of a dmi ni s tra ti on. Nonethel es s , the res pons es s hown a re typi ca l .
ISO, a 1 /2 a goni s t, l owers peri phera l res i s ta nce (a nd di a s tol i c bl ood pres s ure) vi a 2 -medi a ted peri phera l va s odi l a tor a cti ons . Tha t fa l l of
di a s tol i c pres s ure i s grea ter tha n the ri s e of s ys tol i c pres s ure (whi ch occurs beca us e of a di rect ca rdi a c pos i ti ve i notropi c/1 -a cti va ti ng effect), s o
mea n pres s ure fa l l s a bi t. The combi ned refl ex res pons e to a fa l l of mea n pres s ure (a l bei t s l i ght), pl us the drugs di rect pos i ti ve chronotropi c
effect, l ea ds to s i gni fi ca nt ta chyca rdi a .
PHE, whi ch a cti va tes onl y (a nd a l l ) -a drenergi c receptors , ca us es onl y a va s opres s or res pons e tha t a ccounts for the cha nges of pres s ures a nd
peri phera l res i s ta nce. Thes e cha nges a cti va te the ba roreceptor refl ex, l ea di ng to refl ex bra dyca rdi a . The drug ha s no -a goni s t a cti vi ty.
EPI, i njected i n (rea s ona bl y) l ow dos es i n norma l huma ns , ca n ca us e the effects s hown here (a nd certa i nl y no other drug l i s ted a s a pos s i bl e
a ns wer coul d do the s a me). The fa l l of peri phera l res i s ta nce a nd di a s tol i c pres s ure refl ects predomi na nt 2 -medi a ted va s odi l a ti on; the ri s e of
s ys tol i c pres s ure i s a mel di ng of both peri phera l va s ocons tri cti on () a nd di rect ca rdi a c s ti mul a ti on (1 ). Hea rt ra te a l s o refl ects di rect cha nges
(1 ), a s there i s no a ppreci a bl e ba roreceptor i nfl uence beca us e there i s no s udden or s i gni fi ca nt bl ood pres s ure cha nge. Res pons es to
epi nephri ne a re a rgua bl y more va ri a bl e tha n thos e of a ny other drugs l i s ted. Cl ea rl y, when l a rge dos es a re gi ven to a hypotens i ve pa ti ent (eg, i n
a na phyl a xi s ), the predomi na nt a nd wa nted va s cul a r effect i s a pres s or res pons e, much grea ter tha n wha t we s ee here.
NE, l a cki ng a ny 2 a cti vi ty but bei ng qui te effecti ve a s a n a nd 1 a goni s t, ca us es typi ca l res pons es l i ke thos e s hown here. Peri phera l l y, there i s
no va s odi l a ti on; jus t cons tri cti on. Di a s tol i c, mea n, a nd s ys tol i c pres s ures ri s e. The ri s e i s s uffi ci ent to refl exl y s l ow hea rt ra te; tha t i s , i t i s
s uffi ci ent to overcome NEs di rect pos i ti ve chronotropi c effects .
260. The answer is a. (Brunton, pp 171-175; Katzung, pp 136-141.) You s houl d know the a ns wer to thi s from a ba s i c phys i ol ogy cours e. We ha ve mi mi cked
(but not ca us ed) a s udden ri s e of bl ood pres s ure, s tretchi ng the ba roreceptors a nd a cti va ti ng the ba roreceptor refl ex. Cons equences of thi s
i ncl ude a reducti on i n s ympa theti c outfl ow from the CNS (a nd a reducti on of ca techol a mi ne rel ea s e), a nd a s i mul ta neous unma s ki ng a nd
i ncrea s e of oppos i ng pa ra s ympa theti c i nfl uences . The i ncrea s ed mus ca ri ni c receptor a cti va ti on brea ks the ta chyca rdi a , ma i nl y by s l owi ng
s ponta neous (Pha s e 4) depol a ri za ti on of SA noda l cel l s .
261. The answer is d. (Brunton, pp 815-817; Katzung, pp 231-236, 245.) The ori gi n of the a rrhythmi a i s s upra ventri cul a r (a ny s tructure a bove the AV

node), a nd i n thi s ca s e both the expected effects of ACh a nd of ca roti d ma s s a ge s ugges t the ori gi n i s the SA node i ts el f. If you l ook a t the ECG you
s houl d be a bl e to rul e out the other (a nd i ncorrect) a ns wer choi ces . The ventri cul a r wa ve form s hows no s l urri ng or hump tha t woul d s ugges t
prea cti va ti on of the ventri cl es by a n a cces s ory pa thwa y (a s you mi ght s ee i n Wol ff-Pa rki ns on-Whi te s yndrome). There i s no notchi ng of the QRS tha t
woul d be cons i s tent wi th bundl e bra nch bl ock (ri ght or l eft). And, s i nce ventri cul a r a cti va ti on fol l ows a tri a l a cti va ti on (P wa ves ), we a re not dea l i ng
wi th ventri cul a r ectopy.
262. The answer is a. (Brunton, pp 825, 833t-837; Katzung, pp 245-246.) Adenos i ne i ntera cts wi th G-protei n-coupl ed receptors a nd i ncrea s es ma xi mum
di a s tol i c membra ne potenti a l . When gi ven a s a bol us , whi ch wa s us ed here, the ma i n effects a re a tra ns i ent s l owi ng of s i nus (noda l ) ra te; a n
i ncrea s e of AV noda l refra ctori nes s ; a nd a s l owi ng of AV noda l conducti on vel oci ty. Al s o, wi th thi s a dmi ni s tra ti on route, there i s no effect on the
Hi s -Purki nje s ys tem, nor on ventri cul a r myoca rdi a l cel l s per s e. Gi ven the l a ck of ventri cul a r effects , a denos i ne woul d not ha ve termi na ted the
a rrhythmi a i f the ori gi n wa s i n the ventri cl es . Sta ted otherwi s e, s i nce the drug does a ct on the AV node, a nd i t di d termi na te the ori gi na l
a rrhythmi a , we mus t concl ude tha t the a rrhythmi a ori gi na ted i n the AV node or a nother s upra ventri cul a r s tructure.
Atropi ne, by bl ocki ng the el ectrophys i ol ogi c effects of mus ca ri ni c receptor a cti va ti on (i n the SA node, for exa mpl e), woul d ha ve unma s ked
oppos i ng s ympa theti c (1 ) i nfl uences a nd proba bl y wors ened (but certa i nl y not s topped) the a berra nt el ectri ca l a cti vi ty. Is oproterenol or
epi nephri ne woul d ha ve done the s a me, a l bei t by di rect a cti va ti on of 1 -a drenergi c receptors .
We ca n rul e out l i doca i ne a s a n a ccepta bl e a ns wer i n s evera l wa ys . Fi rs t, we a re dea l i ng wi th a n a rrhythmi a ori gi na ti ng i n a s upra ventri cul a r
s tructure. Li doca i ne ha s no s i gni fi ca nt effect on SA noda l ra te, nor on AV noda l refra ctory peri ods . It a l s o ha s no effects on PR i nterva l s (beca us e i t
l a cks s i gni fi ca nt effects on AV noda l refra ctori nes s or conducti on), QT i nterva l s , or the dura ti on of the QRS. Sta ted more pra gma ti ca l l y, the drug i s
not us eful for s upra ventri cul a r a rrhythmi a s (except, perha ps , di goxi n-a s s oci a ted a tri a l a rrhythmi a s ). It woul d not work i n the s i tua ti on des cri bed
or s hown i n the ECG.
263. The answer is a. (Brunton, pp 310, 347-349; Katzung, pp 155, 287-290, 292.) Al though ergota mi ne, a nd the ergot a l ka l oi ds i n genera l , ma y not be
cons i dered typi ca l ca rdi ova s cul a r drugs , they cl ea rl y ca n ca us e s i gni fi ca nt, cumul a ti ve, a nd s ometi mes da ngerous ca rdi ova s cul a r effects .
Ergota mi ne ca n ca us e i ntens e a nd prol onged va s ocons tri cti on i n both the peri phera l a nd corona ry va s cul a tures . Thus , of the a ns wer choi ces gi ven
myoca rdi a l i s chemi a a nd i s chemi a of (for exa mpl e) one or more extremi ti es a re the mos t l i kel y outcomes . Thes e va s cul a r res pons es pos e
pa rti cul a r probl ems for pa ti ents wi th i s chemi c hea rt di s ea s e, es peci a l l y thos e who ha ve va s os pa s ti c, or va ri a nt, a ngi na , or pa ti ents wi th
peri phera l va s cul a r di s ea s e. (One ergot a l ka l oi d, ergonovi ne, i s s uch a powerful corona ry va s ocons tri ctor tha t i t i s s ometi mes us ed i n
a ngi ogra phi c s tudi es of the hea rt to di a gnos e va s os pa s ti c a ngi na .) The corona ry effects ma y be ra pi dl y fa ta l ; l i mb i s chemi a ma y be s uffi ci entl y
i ntens e a nd prol onged to i nduce ga ngrene a nd requi re a mputa ti on of the a ffected l i mb(s ). Rha bdomyol ys i s , wi th or wi thout rena l fa i l ure (b), i s
unl i kel y, a t l ea s t a s a di rect cons equence of ergota mi ne, a s the ergot compounds i n genera l ha ve no a ppreci a bl e effects on s kel eta l mus cl e
s tructure or functi on. There a re no di rect effects on pl a tel et a cti va ti on or a ggrega ti on tha t woul d l ea d to s ponta neous bl eedi ng (c); however,
pl a tel et a cti va ti on a nd thromboti c events certa i nl y ma y occur s econda ry to s ta s i s i n va s cul a r beds tha t ha ve been i ntens el y cons tri cted by the drug.
Hypertens i on, not hypotens i on wi th or wi thout s yncope (d), i s a l i kel y cons equence of peri phera l va s ocons tri cti on. Sudden ri s es i n bl ood pres s ure
a re l i kel y to ca us e bra dyca rdi a (not ta chyca rdi a , e) via ba roreceptor refl ex a cti va ti on. Members of the ergot a l ka l oi d cl a s s (eg, ergota mi ne,
ergonovi ne) ha ve va ri a bl e a goni s t or a nta goni s t effects (di rect or i ndi rect) on a drenergi c, dopa mi nergi c, a nd s erotoni nergi c receptors ), but not
on -a drenergi c receptors .
[For s tudy purpos es i n other a rea s of pha rma col ogy you ma y wa nt to reca l l the fol l owi ng: (1) Tri pta ns (eg, s uma tri pta n) or methys ergi de tends to
be us ed more tha n ergota mi ne or s i mi l a r drugs for mi gra i ne. (2) Ergo-novi ne i s s ometi mes us ed a s a n a l terna ti ve or ba ckup to oxytoci n for
control l i ng pos tpa rtum uteri ne bl eedi ng or hemorrha ge: i t ca us es i ntens e a nd prol onged uteri ne s mooth mus cl e contra cti on a nd rel a ti vel y s l i ght
ca rdi ova s cul a r effects . (3) Another ergot drug, bromocri pti ne, i s us ed to ma na ge hyperprol a cti nemi a (due to i ts s trong dopa mi nergi c effects ) s uch
a s tha t whi ch ma y occur wi th pi tui ta ry tumors , a nd i s a l s o s ometi mes us ed to ma na ge Pa rki ns on di s ea s e.]

Renal System and Diuretic Pharmacology

Al dos terone a nd i ts a nta goni s ts
Anti di ureti c hormone a nd i ts a nta goni s ts
Ca rboni c a nhydra s e a nd i ts i nhi bi tors
Loop (hi gh cei l i ng or Na -Cl s ymporter i nhi bi tor) di ureti cs
Os moti c di ureti cs
Pota s s i um-s pa ri ng di ureti cs
Thi a zi des (benzothi a di a zi des ) a nd thi a zi de-l i ke di ureti cs

Questions
264. After a few weeks on a drug tha t wa s pres cri bed by a nother phys i ci a n, a pa ti ent reports fi ne tremors of hi s fi ngers , hea da che a nd fa ti gue, a nd
tra ns i ent GI di s tres s . More worri s ome to hi m i s tha t he i s cons ta ntl y thi rs ty a nd uri na tes copi ous l y a nd frequentl y throughout the da y a nd ni ght. A
24-hour uri ne col l ecti on produces nea rl y 5 L of hypotoni c uri ne. Bl ood tes ts s how tha t l evel s of the ca us a ti ve drug a re wi thi n i ts thera peuti c ra nge.
Nonethel es s , the cl i ni ca l pi cture l ea ds you to hypothes i ze tha t the offendi ng drug i s ca us i ng rena l res pons es qui te s i mi l a r to a s yndrome
cha ra cteri zed by reduced producti on or rena l res pons e to ADH. Whi ch drug mos t l i kel y ca us ed or contri buted to thes e s i gns a nd s ymptoms ?
a . Di a zepa m
b. Fl uoxeti ne
c. Ha l operi dol
d. Li thi um
e. Phenytoi n
265. A pa ti ent ta ki ng a n ora l di ureti c for a bout 6 months pres ents wi th el eva ted fa s ti ng a nd pos tpra ndi a l bl ood gl ucos e l evel s . You check the
pa ti ents HbA1c a nd fi nd i t i s el eva ted compa red wi th norma l ba s el i ne va l ues obta i ned 6 months a go. You s us pect the gl ycemi c probl ems a re
di ureti c-i nduced. Wha t wa s the mos t l i kel y ca us e?
a . Aceta zol a mi de
b. Ami l ori de
c. Chl orothi a zi de
d. Spi ronol a ctone
e. Tri a mterene
266. A pa ti ent wi th s evere hea rt fa i l ure i s i n the ICU. Hi s uri ne output i s da ngerous l y l ow. You begi n a n i ntra venous i nfus i on of dopa mi ne a t a
us ua l thera peuti c dos e a nd uri ne output ri s es qui ckl y a nd dra ma ti ca l l y. Wha t i s the mos t l i kel y mecha ni s m by whi ch the dopa mi ne ca us ed thi s
effect?
a . Bl ocked -a drenergi c receptors i n the juxta gl omerul a r a ppa ra tus , thereby i nhi bi ti ng reni n rel ea s e a nd s us equent a ngi otens i n-medi a ted
a l dos terone rel ea s e from the a drena l cortex.
b. Di rectl y i nhi bi ted a rena l Na +, K+, 2Cl - cotra ns porter i n the Loop of Henl e.
c. Improved rena l bl ood fl ow a nd gl omerul a r fi l tra ti on
d. Lowered the medul l a ry-to-corti ca l os moti c gra di ent, s uch tha t norma l uri ne concentra ti ng mecha ni s ms were i mpa i red
e. Reduced the permea bi l i ty of the a s cendi ng l i mb, Loop of Henl e, a nd of the col l ecti ng ducts , to wa ter
267. Us ua l dos es of a thi a zi de di ureti c (eg, hydrochl orothi a zi de) produce a uri ne tha t i s rel a ti vel y ri ch i n s odi um a nd pota s s i um, but conta i ns
rel a ti vel y l i ttl e i ncrea s e i n uri ne vol ume (i e, compa ra ti vel y l i ttl e free wa ter l os s compa red wi th the rel a ti ve l os s of i ons ). An a cti on a t wha t s i te i n
the nephron ma i nl y a ccounts for the a bi l i ty of the thi a zi des to ca us e thes e res pons es ?
a . As cendi ng l i mb of the l oop of Henl e
b. Corti ca l di l uti ng s egment of the proxi ma l nephron
c. Corti ca l -to-medul l a ry countercurrent mul ti pl i er
d. Des cendi ng l i mb of the l oop of Henl e
e. Pri nci pa l cel l s of the nephron
268. A pa ti ent wi th es s enti a l hypertens i on i s bei ng trea ted wi th hydro-chl orothi a zi de a nd a ca l ci um cha nnel bl ocker, a nd i s doi ng wel l . He a l s o
ta kes a torva s ta ti n for hyperchol es terol emi a , a nd a s pi ri n to reduce hi s ri s k of a n a cute corona ry s yndrome. He i s now di a gnos ed wi th a s ei zure
di s order. We begi n thera py wi th one of the s ui ta bl e a nti convul s a nts tha t, fortuna tel y, does not a l ter the meta bol i s m of a ny of the medi ca ti ons
pres cri bed for hi s ca rdi ova s cul a r probl ems . Weve a l s o rea d tha t s ys temi c a dmi ni s tra ti on of a ceta zol a mi de ma y prove to be a us eful a djunct to the
a nti convul s a nt thera py: the meta bol i c a ci dos i s i t ca us es ma y hel p s uppres s s ei zure devel opment or s prea d. So, we s ta rt a ceta zol a mi de thera py
too. Wha t i s the mos t l i kel y outcome of a ddi ng the a ceta zol a mi de?
a . Exces s i ve ri s es of pl a s ma s odi um concentra ti on
b. Hypertens i ve cri s i s (a nta goni s m of both a nti hypertens i ve drugs )
c. Hypoka l emi a vi a s ynergi s ti c a cti ons wi th the thi a zi de
d. Sponta neous bl eedi ng (potenti a ti on of a s pi ri ns a cti ons )
e. Sudden ci rcul a ti ng vol ume expa ns i on, ons et of hea rt fa i l ure
269. A pa ti ent ha s very hi gh pl a s ma uri c a ci d l evel s , ha s ha d two a cute gout a tta cks i n the l a s t 8 months , a nd i s a t i mmi nent ri s k of devel opi ng
a cute uri c a ci d nephropa thy. We wi l l trea t the pa ti ent wi th proper a nti -i nfl a mma tory drugs a nd other a gents , but feel tha t reduci ng s ol ubi l i ty of

uri c a ci d i n the uri ne mi ght hel p wa rd-off the devel opment of rena l probl ems . Wha t drug i s bes t a bl e to produce thi s des i red rena l effect vi s - -vi s
ura te s ol ubi l i ty wi thout a ppreci a bl y i ncrea s i ng s ys temi c ri s ks of the hyperuri cemi a ?
a . Aceta zol a mi de
b. Anti di ureti c hormone (ADH) (va s opres s i n [VP])
c. Etha cryni c a ci d
d. Furos emi de
e. Hydrochl orothi a zi de
270. A pa ti ent wi th hea rt fa i l ure ha s been ma na ged wi th di goxi n a nd furos emi de a nd i s doi ng wel l by a l l mea s ures , for 3 yea rs . He devel ops a cute
rheuma toi d a rthri ti s a nd i s pl a ced on ra ther l a rge dos es of a very effi ca ci ous nons teroi da l a nti -i nfl a mma tory drugone tha t i nhi bi ts both the COX1 a nd -2 cycl ooxygena s e pa thwa ys . Wha t i s the mos t l i kel y outcome of a ddi ng the NSAID?
a . Hyperchl oremi c a ci dos i s i ndi ca ti ve of a cute di ureti c toxi ci ty
b. Dra ma ti c i ncrea s e of furos emi des pota s s i um-s pa ri ng effects
c. Edema , wei ght ga i n, a nd other s i gns /s ymptoms i ndi ca ti ve of reduced di ures i s
d. Increa s ed di goxi n excreti on
e. Reduced di goxi n effects beca us e the NSAID competes wi th di goxi n for myocyte receptor-bi ndi ng s i tes
271. A pa ti ent wa s i n a recumbent pos i ti on for a 45-mi nute ora l s urgery procedure. When the s urgery wa s compl eted the pa ti ent s tood up qui ckl y
a nd promptl y got l i ght-hea ded a nd fa i nted. The ca us e wa s hypotens i on due to hypovol emi a from exces s i ve di ures i s , a ttri buted to a drug
pres cri bed by her phys i ci a n a nd ta ken for s evera l months . Wha t drug wa s the mos t l i kel y ca us e?
a . Aceta zol a mi de
b. Furos emi de
c. Hydrochl orothi a zi de
d. Spi ronol a ctone
e. Tri a mterene
272. One of your cl i ni c pa ti ents i s bei ng trea ted wi th s pi ronol a ctone. Whi ch s ta tement correctl y des cri bes a property of thi s drug?
a . Contra i ndi ca ted i n hea rt fa i l ure, es peci a l l y i f s evere
b. Inhi bi ts Na + rea bs orpti on i n the proxi ma l rena l tubul e of the nephron
c. Interferes wi th a l dos terone s ynthes i s
d. Is a ra ti ona l choi ce for a pa ti ent wi th a n a drena l corti ca l tumor
e. Is genera l l y preferred to a thi a zi de i n mos t pa ti ents wi th es s enti a l hypertens i on
273. Chl ortha l i done a nd tors emi de a re members of di fferent di ureti c cl a s s es , i n terms of mecha ni s ms of a cti on a nd chemi ca l s tructure, but they
s ha re the a bi l i ty to ca us e hypoka l emi a . Whi ch s ta tement bes t des cri bes the genera l a nd common mecha ni s m by whi ch thes e drugs ca us e thei r
effects tha t l ea d to net rena l pota s s i um l os s ?
a . Act a s a l dos terone receptor a goni s ts , thereby fa vori ng K+ l os s
b. Bl ock proxi ma l tubul a r ATP-dependent s ecretory pumps for K+
c. Increa s e del i very of Na + to pri nci pa l cel l s i n the di s ta l nephron, where tubul a r Na + i s tra ns ported i nto the cel l s vi a a s odi um cha nnel i n
excha nge for K+, whi ch gets el i mi na ted i n the uri ne
d. Sti mul a te a proxi ma l tubul a r Na , K-ATPa s e s uch tha t K+ i s a cti vel y pumped i nto the uri ne
e. Lower di s ta l tubul a r uri ne os mol a l i ty, thereby fa vori ng pa s s i ve di ffus i on of K+ i nto the uri ne
274. A 52-yea r-ol d ma n pres ents to your cl i ni c for hi s fi rs t vi s i t wi th you, a fter movi ng from a di s ta nt town. Hi s onl y medi ca ti ons a re a s ta ti n,
a s pi ri n, (81 mg/da y) a nd metol a zone. The pha rma ci s t who fi l l ed hi s pres cri pti ons expl a i ned to the gentl ema n why he wa s ta ki ng the a s pi ri n a nd
the s ta ti n, but merel y referred to the metol a zone a s a wa ter pi l l . Thus , youre a s ked a bout i t. Wha t i s the mos t l i kel y rea s on why the metol a zone
wa s pres cri bed?
a . Adjuncti ve ma na gement of a n a drena l corti ca l tumor
b. Adjuncti ve ma na gement of hepa ti c ci rrhos i s from yea rs of exces s i ve a l cohol cons umpti on
c. Hypertens i on a ccompa ni ed by a hi s tory of gout a nd di a betes
d. Trea tment of es s enti a l hypertens i on
e. Trea tment of edema a nd a s ci tes from hea rt fa i l ure
275. Uri na ry pota s s i um concentra ti ons a re mea s ured before a nd a fter s evera l weeks of a dmi ni s teri ng a l oop di ureti c (eg, furos emi de, a t typi ca l
da i l y dos a ges ). We fi nd tha t pos t-trea tment uri ne K+ concentra ti ons a re s ubs ta nti a l l y lower tha n thos e mea s ured a t ba s el i ne. Wha t i s the mos t
l i kel y expl a na ti on for thi s obs erva ti on?
a . An expected res pons e to the drug
b. Loop di ureti cs ca us e pota s s i um-wa s ti ng onl y i n i n vi tro experi menta l model s
c. Mea s urements of pos t-trea tment uri ne K+ concentra ti ons were erroneous
d. The pa ti ent ha s hypoa l dos teroni s m from bi l a tera l a drena l ectomy
e. Pota s s i um s ecreti on by pri nci pa l cel l s of the nephron a re i nhi bi ted by l oop di ureti cs
276. You ha ve jus t compl eted your thi rd-yea r medi ci ne cl erks hi p, ha vi ng s pent s ome ti me i n genera l i nterna l medi ci ne, ca rdi ol ogy, nephrol ogy, a nd
endocri ne-meta bol i s m cl i ni cs . In ea ch of thos e venues you ha ve revi ewed cha rts of pa ti ents ta ki ng epl erenone. Wha t phra s e bes t des cri bes a
cha ra cteri s ti c or other property of thi s drug?

a . Fa ci l i ta tes rena l s odi um wa ter l os s a nd pota s s i um retenti on

b. Inhi bi ts s teroi dogenes i s (s teroi d hormone producti on)
c. Mi mi cs a nti di ureti c hormone (va s opres s i n)
d. Speci fi ca l l y i nhi bi ts a l dos terone s ynthes i s
e. Us ed to countera ct gl ycos uri a i n pa ti ents wi th type 1 or 2 di a betes mel l i tus
277. A 58-yea r-ol d ma n wi th a hi s tory of hypertens i on a nd hyperchol es terol emi a i s di a gnos ed wi th hea rt fa i l ure. We s ta rt thera py wi th furos emi de
a s one of s evera l medi ca ti ons . Whi ch of the fol l owi ng woul d you expect to occur a l ong wi th the i ncrea s ed uri ne vol ume ca us ed by thi s di ureti c?
a . Di l ute (hypotoni c) uri ne beca us e norma l uri ne concentra ti ng mecha ni s ms a re i mpa i red
b. Hyperca l cemi a due to i mpa i red rena l Ca 2+ excreti on
c. Reduced net excreti on of Cl d. Meta bol i c a ci dos i s due to i ncrea s ed rena l bi ca rbona te excreti on
e. Reduced pl a s ma uri c a ci d (ura te) concentra ti ons beca us e of i ncrea s ed ura te excreti on
278. A pa ti ent pos t-hea d tra uma i s i n the neuros urgery uni t a t your hos pi ta l . He ha s become hypervol emi c a nd hypona tremi c from two ma i n
ca us es : (1) tra uma proba bl y i ncrea s ed va s opres s i n rel ea s e from hi s pos teri or pi tui ta ry gl a nd; a nd (2) the s ta ff wa s not s uffi ci entl y ca reful when
a dmi ni s teri ng IV fl ui ds , whi ch further i ncrea s ed bl ood vol ume a nd l owered bl ood s odi um concentra ti ons . Thi s pa ti ent a l s o ha s s ymptoma ti c hea rt
fa i l ure tha t woul d be further compromi s ed by a ddi ti ona l ri s es of bl ood vol ume, even i f s l i ght or s hort-l i ved. He ha d been on a number of drugs
pri or to a dmi s s i on. One wa s ora l pota s s i um-s uppl ements to countera ct di ureti c-i nduced hypoka l emi a . Unfortuna tel y, the s uppl ement dos e wa s
exces s i ve, a nd the pa ti ent wa s borderl i ne-hyperka l emi c too. Wha t drug woul d be the mos t ra ti ona l to a dmi ni s ter, wi th the goa l of norma l i zi ng or
a t l ea s t i mprovi ng bl ood vol ume a nd el ectrol yte compos i ti on a nd wi thout further compromi s i ng the pa ti ents hemodyna mi c s ta tus ?
a . Coni va pta n
b. Ma nni tol
c. Metol a zone
d. Sodi um chl ori de 0.9% (norma l s a l i ne)
e. Spi ronol a ctone
279. A 60-yea r-ol d ma n ha s mul ti pl e medi ca l probl ems , i ncl udi ng s evere hepa ti c ci rrhos i s from hepa ti ti s a t a ge 40, a nd over 30 yea rs of exces s i ve
a l cohol i nta ke. Three da ys a fter a vi s i t to a phys i ci a n, who pres cri bed a drug for a condi ti on unrel a ted to the l i ver dys functi on, the ma n i s found
coma tos e. He i s tra ns ported to the emergency depa rtment. Wha t drug, pres cri bed 3 da ys before, mos t l i kel y i nduced or contri buted to the ons et
coma i n thi s ma n?
a . Aceta zol a mi de
b. Epl erenone
c. Furos emi de
d. Hydrochl orothi a zi de
e. Tri a mterene
280. Your pa ti ent, who l i ves i n Dea th Va l l ey, Ca l i forni a (240 feet bel ow s ea l evel ) i s pl a nni ng a va ca ti on tha t i ncl udes a s hort hi ke to the top of
Mount Everes t (a pprox. 29,000 feet a bove s ea l evel ). Youre concerned a bout a l ti tude s i cknes s . He ha s no other s i gni fi ca nt medi ca l condi ti ons ,
a nd ta kes no other drugs tha t woul d i ntera ct wi th the drug you wi l l pres cri be for hi s tri p. Whi ch drug woul d you recommend tha t thi s a dventurer
s ta rt ta ki ng before hi s trek, a nd conti nue unti l he returns to a n a l ti tude much cl os er to s ea l evel ?
a . Aceta zol a mi de
b. Ami l ori de
c. Bumeta ni de
d. Furos emi de
e. Spri onol a ctone
f. Tri a mterene
281. A pa ti ent pres ents wi th chroni c open a ngl e gl a ucoma . Wha t rena l drug, or a drug i n the s a me chemi ca l a nd pha rma col ogi c cl a s s , mi ght be
pres cri bed a s a n a djunct to l ower i ntra ocul a r pres s ure a nd hel p ma na ge thi s condi ti on?
a . Aceta zol a mi de
b. Ami l ori de
c. Furos emi de
d. Spri onol a ctone
e. Tri a mterene
282. A pa ti ent ha s una ccepta bl y l ow ca rdi a c output a nd i ntens e refl exmedi a ted s ympa theti c a cti va ti on of the peri phera l va s cul a ture tha t i s
a ttempti ng, uns ucces s ful l y, to keep vi ta l orga n perfus i on pres s ure s uffi ci entl y hi gh. The pa ti ent i s edema tous beca us e of the poor ca rdi a c functi on
a nd rena l compens a ti ons for i t. Whi ch one of the fol l owi ng drugs s houl d be avoided i n thi s pa ti ent beca us e i t i s mos t l i kel y to compromi s e
functi on of the a l rea dy-fa i l i ng hea rt a nd the ci rcul a tory s ys tem overa l l ?
a . Ami l ori de
b. Etha cryni c a ci d
c. Hydrochl orothi a zi de
d. Ma nni tol
e. Spi ronol a ctone

283. A pa ti ent i s recentl y di a gnos ed wi th a drena l corti ca l a denoma . Among the perti nent Cus hi ngoi d s i gns a nd s ymptoms a re hypertens i on a nd
wei ght ga i n from fl ui d retenti on; a nd hyperna tremi a a nd hypoka l emi a . Whi ch drug woul d be the mos t ra ti ona l to pres cri be, a l one or a djuncti vel y,
to s peci fi ca l l y a nta goni ze both the rena l a nd the s ys temi c effects of the hormone exces s ?
a . Aceta zol a mi de
b. Ami l ori de
c. Furos emi de
d. Metol a zone
e. Spi ronol a ctone
284. A pa ti ent ha s been referred to your a ca demi c medi ca l center beca us e of recent-ons et ventri cul a r ectopy, s econd-degree AV noda l bl ock,
chroma tops i a , a nd other extra ca rdi a c s i gns a nd s ymptoms of di goxi n i ntoxi ca ti on. Hi s fa mi l y doctor, who ha s been trea ti ng hi m for a hos t of
common medi ca l probl ems over the l a s t 30 yea rs , ha d pres cri bed furos emi de a nd di goxi n for thi s gentl ema ns hea rt fa i l ure. Bl ood tes ts s how tha t
di goxi n l evel s a re wel l wi thi n a norma l ra nge. We bel i eve the probl ems a re di ureti c-i nduced. Wha t di d the di ureti c mos t l i kel y do to preci pi ta te
the di goxi n toxi ci ty?
a . Ca us ed hyperca l cemi a
b. Ca us ed hypoka l emi a
c. Ca us ed hypona tremi a
d. Di s pl a ced di goxi n from ti s s ue bi ndi ng s i tes
e. Inhi bi ted di goxi ns meta bol i c el i mi na ti on
285. A 48-yea r-ol d ma n wi th bi l a tera l di a beti c nephropa thy devel ops a cute hea rt fa i l ure a nd a ddi ti ona l , a nd s i gni fi ca nt, decl i nes of rena l functi on
(eg, decl i nes of GFR) a s two of s evera l cons equences of s eps i s . You wi l l a dmi ni s ter a ppropri a te a nti bi oti cs , va s odi l a tors , a nd ca rdi a c i notropes ,
but a l s o need to a dmi ni s ter a di ureti c to promptl y reduce ci rcul a ti ng fl ui d vol ume a nd unl oa d the fa i l i ng hea rt. Wha t drug woul d be mos t
a ppropri a te i n terms of ma na gi ng the hemodyna mi c probl ems for thi s pa ti ent?
a . Aceta zol a mi de
b. Hydrochl orothi a zi de
c. Ma nni tol
d. Tors emi de
e. Metol a zone (or chl ortha l i done)
286. A pa ti ent wi th s evere i nfecti ous di s ea s e i s bei ng trea ted wi th a n a mi nogl ycos i de a nti bi oti c. Whi ch di ureti c s houl d be a voi ded, i f pos s i bl e, for
thi s pa ti ent, beca us e of the ri s k of a s eri ous a dvers e effect s ha red by both drugs ?
a . Aceta zol a mi de
b. Furos emi de
c. Metol a zone
d. Spi ronol a ctone
e. Tri a mterene
287. Ami l ori de i s a us eful drug for ma na gi ng hypoka l emi a ca us ed by other drugs . Whi ch phra s e bes t des cri bes the mecha ni s m by whi ch i t ca us es
i ts pota s s i um-s pa ri ng effects ?
a . Bl ocks the a goni s t effects of a l dos terone wi th i ts rena l tubul a r receptors
b. Bl ocks di s ta l tubul a r s odi um cha nnel s a nd, ul ti ma tel y, Na +-K+ excha nge
c. Ha s tens meta bol i c i na cti va ti on of a l dos terone
d. Sti mul a tes a proxi ma l tubul a r Na , K-ATPa s e
e. Suppres s es corti s ol a nd a l dos terone s ynthes i s a nd rel ea s e i n the a drena l cortex
288. A pa ti ent who a dmi ts to dri nki ng ma ny l i ters of wa ter ea ch da y ha s ha d recurrent epi s odes of s ymptoma ti c hypona tremi a , a nd i s a t grea t ri s k
of recurrences . Beca us e of a nother medi ca l probl em he now requi res a dmi ni s tra ti on of a di ureti c. Whi ch drug i s mos t l i kel y to preci pi ta te a nother
recurrence of the hypona tremi a , whether or not the pa ti ents da i l y wa ter i nta ke i s reduced to a more a ccepta bl e l evel ?
a . Bumeta ni de
b. Etha cryni c a ci d
c. Furos emi de
d. Hydrochl orothi a zi de
e. Tors emi de
289. A hypertens i ve pa ti ent ha s been on l ong-term thera py wi th l i s i nopri l , a l ong-a cti ng ACE i nhi bi tor, for hypertens i on. The drug i s nt control l i ng
pres s ure a s wel l a s wa nted, s o the phys i ci a n deci des to a dd a mi l ori de. Wha t i s a potenti a l , i f not l i kel y, outcome of a ddi ng thi s di ureti c to the ACE
i nhi bi tor regi men?
a . Bl ood pres s ure woul d ri s e a bruptl y
b. Bl ood pres s ure woul d fa l l a ga i n once a mi l ori de wa s a dded (better BP control ), but theres a l i kel i hood tha t the pa ti ent woul d become
hyperka l emi c
c. Ca rdi a c depres s i on, beca us e both drugs di rectl y depres s hea rt ra te a nd l eft ventri cul a r contra cti l i ty
d. Di a betes i ns i pi dus -l i ke s yndrome wi th producti on of l a rge vol umes of di l ute uri ne, pl us di l uti ona l hypona tremi a
e. Hypoka l emi a beca us e of the two drugs a ddi ti ve or s ynerges ti c effects on rena l pota s s i um ha ndl i ng
290. Cons i der a ga i n the pa ti ent des cri bed i n the previ ous ques ti on. He now pres ents wi th di ureti c-i nduced hypona tremi a . The condi ti on i s

s ymptoma ti c a nd s evere enough tha t the exces s i vel y l ow Na + concentra ti on needs to be corrected promptl y. In a ddi ti on to ca uti ous i ntra venous
a dmi ni s tra ti on of Na Cl , a djuncti ve drug thera py i s i ndi ca ted. Whi ch drug or drug cl a s s woul d be the mos t ra ti ona l to us e a djuncti vel y, i n a ddi ti on
to IV Na Cl a nd s toppi ng the ca us a ti ve di ureti c a t l ea s t tempora ri l y, to hel p correct s odi um concentra ti on?
a . Ca ptopri l
b. Furos emi de
c. Spi ronol a ctone
d. Thi a zi de-l i ke di ureti c (eg, metol a zone)
e. Tri a mterene
291. The ta bl e bel ow s hows the uri na ry el ectrol yte excreti on pa tterns typi ca l of va ri ous prototype di ureti cs . Thes e a re qua l i ta ti ve cha nges , a nd do
not refl ect the ma gni tude of the cha nges . They show whether excretion of an electrolyte (net amount) is increased or decreased; they do not reflect changes in
urine concentrations of these substances.

Your a ns wer choi ces a re:

a . Aceta zol a mi de
b. Ami l ori de
c. Chl ortha l i done
d. Furos emi de
e. Hydrochl orothi a zi de
Whi ch drug ca us es effects mos t s i mi l a r, i f not i denti ca l , to unknown drug 2, a bove?

Renal System and Diuretic Pharmacology

Answers
264. The answer is d. (Brunton, pp 448-450; Katzung, pp 513-517, 1158t.) Li thi um trea tment (for bi pol a r i l l nes s ) frequentl y ca us es pol yuri a a nd (a s a
cons equence of exces s i ve rena l fl ui d l os s ) pol ydi ps i a (i ncrea s ed thi rs t l ea di ng to i ncrea s ed fl ui d i nta ke). The col l ecti ng ducts of the ki dney l os e
the ca pa ci ty to cons erve wa ter vi a the expected a cti ons a nti di ureti c hormone (a rgi ni ne va s opres s i n). Thi s a mounts to drug-i nduced nephrogeni c
di a betes i ns i pi dus , di l uti ona l hypona tremi a , a nd SIADH: a s yndrome of i na ppropri a te ADH s ecreti on tha t tri es , uns ucces s ful l y, to l i mi t or reduce
free wa ter l os s from the ki dneys . Such fi ndi ngs a re not a s s oci a ted wi th di a zepa m (a ; prototype benzodi a zepi ne a nxi ol yti c); fl uoxeti ne (b; the
prototypi c SSRI a nti depres s a nt); ha l operi dol (c; butyrophenone a nti ps ychoti c); or phenytoi n (e; hyda ntoi n a nti convul s a nt).
265. The answer is c. (Brunton, pp 686-690; Katzung, pp 260-261.) Thi a zi des a nd thi a zi de-l i ke di ureti cs (eg, chl ortha l i done, metol a zone) tend to el eva te
bl ood gl ucos e l evel s , i mpa i r gl ucos e tol era nce, a nd ca us e fra nk hypergl ycemi a .
Severa l mecha ni s ms ha ve been propos ed to expl a i n the effect: decrea s ed rel ea s e of i ns ul i n from the pa ncrea s ; i ncrea s ed gl ycogenol ys i s a nd
decrea s ed gl ycogen s ynthes i s ; a reducti on i n the convers i on of proi ns ul i n to i ns ul i n; a nd reduced res pons i venes s of a di pocyte a nd s kel eta l
myocyte i ns ul i n receptor res pons e to the hormone (i ns ul i n res i s ta ncethe mos t l i kel y mecha ni s m).
(You mi ght reca l l tha t di a zoxi de [ma i nl y us ed a s a pa rentera l drug for prompt l oweri ng of bl ood pres s ure] ca n be us ed i n i ts ora l dos a ge form to
ra i s e bl ood gl ucos e l evel s i n s ome hypogl ycemi c s ta tes . It i s , chemi ca l l y, a thi a zi de, but i s not us ed a s a di ureti c.)
El eva ti ons of bl ood gl ucos e l evel s , or other ma ni fes ta ti ons of gl ycemi c control , a re ra rel y a s s oci a ted wi th trea tment wi th a ceta zol a mi de (a ),
a mi l ori de (b), s pi ronol a ctone (d), or tri a mterene (e).
266. The answer is c. (Brunton, pp 288, 351-359; Katzung, pp 84t, 136f, 138t, 141.) The often dra ma ti c i ncrea s es i n uri ne output ca us ed by thera peuti c
dos es of dopa mi ne (s o-ca l l ed rena l dos es ) i s ma i nl y due to i mproved hemodyna mi cs . The drug, under thes e condi ti ons , not onl y i mproves
ca rdi a c contra cti l i ty a nd ca rdi a c output (whi ch, i n turn, i mproves rena l perfus i on), but a l s o di l a tes the rena l a rteri ol es ; thes e effects l ea d to
i mproved gl omerul a r fi l tra ti on, a nd the i ncrea s ed uri ne vol ume. Improved hemodyna mi cs wi l l s uppres s the reni n-a ngi otens i n-a l dos terone
s ys tem, whi ch wa s a cti va ted i n res pons e to poor rena l perfus i on. Wea k 1 receptor a cti va ti on a l s o contri butes to thi s effect (pa rti cul a rl y wi th s uch
drugs a s dobuta mi ne). However, dopa mi ne does not bl ock (a ) a ny of the a drenergi c receptors .
Dopa mi ne a l s o ha s rena l tubul a r effects , much l i ke tra di ti ona l di ureti cs do, a l though we often overl ook them (perha ps beca us e they a re l es s
i mporta nt tha n the effects des cri bed a bove. The drug, vi a i ts D 1 -receptor a goni s t a cti ons , i ncrea s es c-AMP forma ti on i n the proxi ma l tubul es a nd
a l s o i n the thi ck a s cendi ng l i mb of the Loop of Henl e. At the l a tter s i te, the res ul t i s i nhi bi ti on of both the Na +-H + excha nge mecha ni s m a nd the
Na +, K+-ATPa s e, but not of wa ter (e; reca l l tha t the thi ck a s cendi ng l i mb of the Loop of Henl e i s i mpermea bl e to wa ter.) Ta ken together, the rena l
hemodyna mi c a nd tubul a r a cti ons of dopa mi ne ma ke i t pa rti cul a rl y us eful for ma na gi ng hea rt fa i l ure tha t i s a ccompa ni ed by reduced rena l
functi on.
Hi gher dos es ca us e pos i ti ve i notropy vi a 1 -receptor a cti va ti on, a nd ca us es neurona l NE rel ea s e. Hi gh dos es a cti va te 1 receptors i n va ri ous
va s cul a r beds , i ncl udi ng the rena l , l ea di ng to va s ocons tri cti on tha t ca n ra i s e bl ood pres s ure a nd tota l peri phera l res i s ta nce, a nd ca n reduce rena l
bl ood fl ow, thereby reduci ng rena l excretory functi on.
267. The answer is b. (Brunton, pp 686-690; Katzung, pp 251-255, 260-261.) Thi a zi des typi ca l l y produce a uri ne tha t i s concentra ted (hyper-os mol a l , more
concentra ted tha n norma l ) beca us e the uri ne conta i ns a rel a ti ve exces s of s odi um a nd pota s s i um (a nd s uch a ni ons a s chl ori de a nd, to a l es s er
extent, bi ca rbona te), a nd l i ttl e i n the wa y of extra free wa ter l os s . The ma i n s i te a t whi ch thi a zi des a nd thi a zi de-l i ke di ureti cs (eg, chl ortha l i done,
metol a zone) a ct to ca us e thi s effect i s i n the corti ca l di l uti ng s egment. Contra s t thi s wi th the l oop di ureti cs (furos emi de, tors emi de, bumeta ni de,
a nd etha cryni c a ci d), whi ch ca us e the forma ti on of a di l ute uri ne beca us e they i nhi bi t rea bs orpti on of s odi um i n the des cendi ng l i mb of the Loop
of Henl e (a ), thereby i nhi bi ti ng the forma ti on of the medul l a ry-to-corti ca l os moti c gra di ent (c, d) neces s a ry for the forma ti on of a norma l l y
concentra ted uri ne. None of the common di ureti c drugs a ct on the a s cendi ng l i mb of the Loop of Henl e (a ). Al l the pota s s i um-wa s ti ng di ureti cs ,
tha t i s , the thi a zi des , thi a zi de-l i ke a gents , a nd l oop a gents , s uch a s furos emi de, i ndi rectl y a ct on the pri nci pa l cel l s of the nephron (e). By
i nhi bi ti ng a porti on of s odi um rea bs orpti on more proxi ma l l y they del i ver extra s odi um di s ta l l y to the pri nci pa l cel l s . There, the pri nci pa l cel l s ta ke
up (rea bs orb) a n a ddi ti ona l fra cti on of s odi um i n excha nge for pota s s i um, whi ch i s l os t i nto the uri ne. Thi s a ccounts for the pota s s i um-wa s ti ng
effects of thes e di ureti cs , but does not a ccount for whether they produce a concentra ted or a di l ute uri ne.
268. The answer is c. (Brunton, pp 677-681; Katzung, pp 256-257, 261-262, 265.) We s el dom a dmi ni s ter a ceta zol a mi de as a di ureti c, beca us e i ts effects
a re mi l d; a s s oci a ted wi th s i gni fi ca nt cha nges of both uri ne pH (up) a nd bl ood pH (down; meta bol i c a ci dos i s ); a nd s el f-l i mi ti ng (once s uffi ci ent
bi ca rbona te ha s been l os t from the bl ood, i nto the uri ne, refra ctori nes s to further di ures i s occurs ). More often we a dmi ni s ter a ceta zol a mi de a nd
other ca rboni c a nhydra s e i nhi bi tors for nonrena l /nonca rdi ova s cul a r probl ems , s uch a s to l ower i ntra ocul a r pres s ure i n s ome ca s es of gl a ucoma
(ca rboni c a nhydra s e i nhi bi tors i nhi bi t a queous humor forma ti on) or a s a n a djunct to a nti convul s a nt thera py a s des cri bed here. As a res ul t, we ma y
forget tha t thes e s ys temi ca l l y a dmi ni s tered drugs are di ureti cs , one common property of a l l the di ureti cs bei ng i ncrea s ed rena l s odi um l os s (a
na tri ureti c effect; thus , a ns wer a i s not correct). We ma y even forget tha t ca rboni c a nhydra s e i nhi bi tors , gi ven s ys temi ca l l y, a re pota s s i um-wa s ti ng
di ureti cs : they a ct proxi ma l l y a nd del i ver extra s odi um di s ta l l y where, a t the pri nci pa l cel l s of the nephron, s ome extra Na + i s ta ken up i n excha nge
for a ddi ti ona l K+ tha t gets el i mi na ted i n the uri ne.
In thi s s cena ri o the pa ti ent i s ta ki ng a thi a zi de, whi ch i s obvi ous l y pota s s i um-wa s ti ng a nd ha s the potenti a l i n i ts own ri ght to ca us e
hypoka l emi a . Add a ca rboni c a nhydra s e to the regi men a nd the ri s ks of hypoka l emi a i ncrea s e. Aceta zol a mi de does not a nta goni ze the
a nti hypertens i ve effects of thi a zi des or ca l ci um cha nnel bl ockers , nor provoke hypertens i on or a hypertens i ve cri s i s (b). If there were a ny
i ntera cti ons between the a ceta zol a mi de a nd the a s pi ri n, i t woul d be a nta goni s m, not potenti a ti on (d) of a s pi ri ns a nti pl a tel et effects . As pi ri n
undergoes rena l tubul a r rea bs orpti on, a nd tha t i s a pH-dependent effect. As pi ri ns rea bs orpti on i s reduced (tha t i s , i ts excreti on i ncrea s es ) i n a n
a l ka l i ne uri ne, whi ch i s preci s el y wha t occurs wi th a ceta zol a mi de. (You s houl d reca l l tha t a l ka l i ni zi ng the uri ne i s a n i mporta nt a djuncti ve
mea s ure i n trea ti ng s evere s a l i cyl a te poi s oni ng, i n pa rt beca us e i t reduces tubul a r rea bs orpti on of s a l i cyl a te.) There i s no rea s on to s us pect
s udden ri s es of bl ood vol ume, wi th or wi thout concomi ta nt hea rt fa i l ure from tha t (e). Indeed, the a dded di ures i s from the a ceta zol -a mi de ma y, a t
l ea s t tra ns i entl y, potenti a te the effects of the thi a zi de on uri ne vol ume, bl ood pres s ure, or both.
269. The answer is a. (Brunton, pp 677-681; Katzung, pp 256-257.) Here I a s ked a bout reduci ng the ri s k of ura te nephropa thy a cutel y by i ncrea s i ng uri c
a ci d s ol ubi l i ty, through uri na ry a l ka l i ni za ti on. One key to a ns weri ng thi s ques ti on correctl y i s to rea l i ze tha t uri c a ci d becomes more s ol ubl e (l es s

l i kel y to preci pi ta te or crys ta l l i ze) a s l oca l pH ri s es . Reca l l tha t norma l uri ne i s a ci di c. We wa nt to a l ka l i ni ze the uri ne, a nd tha t i s preci s el y wha t
a ceta zol a mi de does , by i nhi bi ti ng ca rboni c a nhydra s e i n the proxi ma l nephron. Note tha t a ceta zol a mi de i s onl y a n a djunct, a nd i n a ddi ti on to (or
i ns tea d of) us i ng i t, we mi ght a l s o a dmi ni s ter s odi um bi ca rbona te, whi ch wi l l a l ka l i ni ze the uri ne; a nd keep the pa ti ent wel l hydra ted to hel p
form l a rge a mounts of a di l ute uri ne. Aceta zol a mi de does ca us e a meta bol i c a ci dos i s , whi ch woul d s eemi ngl y fa vor reducti ons of uri c a ci d
s ol ubi l i ty i n the bl ood. However, we a re keepi ng our pa ti ent wel l hydra ted (hel ps reduce preci pi ta ti on); a nd the vol ume of bl ood i s fa r grea ter
tha n uri ne vol ume a t a ny gi ven ti me, a nd gi ven the grea t s i ze of the bl ood pool we ha ve l i ttl e to worry a bout i n terms of ura te preci pi ta ti on
s ys temi ca l l y.
Anti di ureti c hormone (b) woul d be i l l ogi ca l . It woul d reduce uri ne vol ume a nd concentra te s ol utes (s uch a s uri c a ci d) i n i t. Etha cryni c a ci d (c)
a nd furos emi de (d) l ea d to the forma ti on of copi ous vol umes of di l ute uri ne. In terms of rena l probl ems , tha t ma y be benefi ci a l . However, the
l oop di ureti cs tend to ca us e s uch l a rge a mounts of fl ui d l os s vi a the uri ne tha t the concentra ti on of s ol utes (i ncl udi ng uri c a ci d) i n the bl ood ma y
go up.
Hydrochl orothi a zi de (e) a nd rel a ted drugs tend to form a very concentra ted uri ne by i nterferi ng wi th norma l uri ne-di l uti ng mecha ni s ms i n the
ki dneys . Whi l e s ome of thes e drugs ha ve ca rboni c a nhydra s e a cti vi ty, a nd a l ka l i ni ze the uri ne, thes e effects a re wea k i n compa ri s on wi th
a ceta zol a mi de. The mos t l i kel y predomi na nt rena l effect i s the unwa nted one: i ncrea s ed ri s k of ura te nephropa thy. In a ddi ti on, thi a zi des tend to
el eva te ura te l evel s (by i nterferi ng wi th tubul a r s ecreti on of ura te), a nd s o thes e drugs a re l i kel y to pos e a ddi ti ona l s ys temi c probl ems .
270. The answer is c. (Brunton, pp 682-684; Katzung, pp 258-260.) An i mporta nt el ement i n the rena l res pons es to furos emi de i s ma i ntena nce of
a dequa te rena l bl ood fl ow. Tha t i s , to a degree, pros ta gl a ndi n-medi a ted. Pros ta gl a ndi ns di l a te the a fferent a rteri ol e (to the gl omerul i ) a nd
i ncrea s e GFR a nd uri ne producti on.
The NSAIDs , s uch a s the hypotheti ca l one des cri bed here, i nhi bi t pros ta gl a ndi n s ynthes i s . Tha t, i n turn, a nta goni zes the des i red effects of the
l oop di ureti c, l ea di ng to l es s fl ui d a nd s a l t el i mi na ti on: edema , wei ght ga i n, a nd other ma rkers of hea rt fa i l ure a re l i kel y to devel op a s a res ul t.
Hyperchl oremi c a l ka l os i s (a ) i s i ncorrect: chroni c or a cute exces s i ve effects of l oop di ureti cs a re cha ra cteri zed by hypochl oremi c meta bol i c
a l ka l os i s . Rega rdl es s , NSAIDs a re not l i kel y to potenti a te the effects of thes e di ureti cs . Dra ma ti c i ncrea s es of furos emi des pota s s i um-s pa ri ng
effects (b) i s i ncorrect. Reca l l tha t l oop di ureti cs a re pota s s i um-wa s ti ng. Di goxi n i s el i mi na ted by rena l excreti on. If we a ccept the noti on tha t
l oop di ureti cs ma y i ncrea s e excreti on of di goxi n, then we s houl d a ccept the l i kel y pos s i bi l i ty tha t NSAID-i nduced reducti ons of di ureti c a cti on
s houl d reduce the gl ycos i des rena l l os s , not i ncrea s e i t (d). The NSAIDs do not bi nd to a nd i nhi bi t the myocyte Na +, K+-ATPa s e, whi ch i s di goxi ns
cel l ul a r receptor (e). Do remember tha t furos emi de (a nd thi a zi des ) a re a pt to i ncrea s e the ri s k or s everi ty of di goxi n toxi ci ty. The mecha ni s m
ma i nl y i nvol ves di ureti c-i nduced hypoka l emi a , not cha nges i n ci rcul a ti ng fl ui d vol ume or uri ne vol ume per s e.
271. The answer is b. (Brunton, pp 682-686; Katzung, pp 258-260.) One wa y to s i mpl i fy a ns weri ng thi s ques ti on i s merel y to a s k whi ch di ureti c ha s the
grea tes t a bi l i ty to ca us e hypovol emi a ? Tha t na rrows the choi ce to furos emi de or the other l oop di ureti cs (bumeta ni de, tors emi de, etha cryni c
a ci d). In terms of extra free wa ter l os s (a nd the concomi ta nt ri s k of hypovol emi a ) the ma xi ma l effi ca cy of a ceta zol a mi de (ca rboni c a nhydra s e
i nhi bi tor; a ) i s modes t a t bes t, a nd s el f-l i mi ti ng to boot. Hydrochl orothi a zi de (c) a nd the two pota s s i um-s pa ri ng di ureti cs l i s ted (s pi ronol a ctone
a nd tri a mterene; d, e) a l s o ha ve modes t effi ca cy i n terms of the pea k di ureti c effect, even i f unus ua l l y l a rge dos es were to be gi ven. Note:
Hypona tremi a reduces the res pons i venes s of the peri phera l va s cul a ture to va s ocons tri ctors (eg, EPI, NE, a nd a ngi otens i n II). If I s ta ted tha t the
pa ti ents hypotens i on were due to di ureti c-i nduced hypona tremi a , then the mos t l i kel y correct a ns wer woul d be hydrochl orothi a zi de or a nother
thi a zi de or thi a zi de-l i ke di ureti c (eg, metol a zone); of a l l the di ureti cs cl a s s es (a nd mos t other cl a s s es of drugs ), they a re the mos t common ca us e
of hypona tremi a .
272. The answer is d. (Brunton, pp 690-693, 1841; Katzung, pp 261-263, 711, 739.) Spi ronol a ctone i s a pota s s i um-s pa ri ng di ureti c. Its a cti ve meta bol i te
bl ocks a l dos terone receptors i n the di s ta l nephron (thus a ns wer b i s i ncorrect). Nei ther s pi ronol a ctone nor i ts a cti ve meta bol i te a l ter a l dos terone
s ynthes i s (c). The drug i s i neffecti ve i n the a bs ence of a l dos terone. Reca l l tha t a l dos terone norma l l y ca us es rena l Na + retenti on a nd K+ l os s . The
effects of a l dos terone a re qua l i ta ti vel y the oppos i te: Na + l os s , K+ retenti on.
Owi ng to the a bi l i ty of s pi ronol a ctone to countera ct the effects of a l dos terone, i t i s pa rti cul a rl y s ui ted for pa ti ents wi th pri ma ry or s econda ry
hypera l dos teroni s m (eg, a drena l corti ca l tumor or hepa ti c dys functi on, a s mi ght occur wi th l ong-term/hi gh-dos e a l cohol cons umpti on,
res pecti vel y). There i s growi ng evi dence tha t the drug i s benefi ci a l i n hea rt fa i l ure a nd proba bl y reduces morbi di ty i n s evere hea rt fa i l ure (a nd s o
a i s i ncorrect). Al though s pi ronol a ctone ha s a nti hypertens i ve effects , i t i s not cons i dered to be a fi rs t-l i ne choi ce (e) for mos t pa ti ents wi th
es s enti a l hypertens i on. For thos e pa ti ents a thi a zi de (mos t often), a n ACE i nhi bi tor, a -bl ocker, or a ca l ci um cha nnel bl ocker i s us ua l l y chos en
fi rs t.
In a ddi ti on to the potenti a l for ca us i ng hyperka l emi a (es peci a l l y i f combi ned wi th ora l pota s s i um s uppl ements , whi ch s houl d not be done) a nd
hypona tremi a (overa l l ri s k i s l ow i f s pi ronol a ctone i s the onl y di ureti c us ed), s pi ronol a ctone ma y ca us e s evera l other s i de effects . CNS s i de effects
i ncl ude l etha rgy, hea da che, drows i nes s , a nd menta l confus i on. Other s i de effects tha t a re fa i rl y common a ri s e from the drugs a ndrogen receptorbl ocki ng a cti ons : gynecoma s ti a (i n men a nd women) a nd erecti l e dys functi on. It ma y a l s o ca us e s eborrhea , a cne, a nd coa rs eni ng of body ha i r.
(Pa ra doxi ca l l y, the drug ca n ca us e hi rs uti s m i n s ome pa ti ents , but i t i s a l s o us ed to ma na ge hi rs uti s m i n others .)
273. The answer is c. (Brunton, pp 676-677, 682-686; Katzung, pp 251-256, 259-261.) Thi a zi des (a nd thi a zi de-l i ke a gents s uch a s chl ortha l i done a nd
metol a zone) a nd l oop di ureti cs (furos emi de, bumeta ni de, tors emi de, a nd etha cryni c a ci d) i ncrea s e del i very of Na + to the di s ta l nephron beca us e
they i nhi bi t rea bs orpti on of Na + a t more proxi ma l s i tes . Thi s extra Na + rea ches the pri nci pa l cel l s i n the di s ta l nephron, a nd s ome of i t i s ta ken
from the tubul a r fl ui d vi a s odi um cha nnel s . Thi s recl a ma ti on of Na + l ea ds to excha nge of K+, whi ch i s l os t i nto the uri ne (i e, pota s s i um wa s ti ng).
In es s ence, the more Na + del i vered (a nd recovered) di s ta l l y, the more K+ tha t i s el i mi na ted i n excha nge.
The proces s es by whi ch thes e pota s s i um-s pa ri ng drugs work do not i nvol ve proxi ma l tubul a r ATP-dependent pota s s i um s ecreti on (b), nor does
i t i nvol ve a ny di rect effect on proxi ma l tubul a r ATPa s e (d). In a ddi ti on, there a re no a goni s t effects on a l dos terone receptors (a )a n a cti on tha t
woul d ca us e a n a nti di ureti c effect a nd rena l pota s s i um loss. Indeed, no di ureti c a cts a s a n a l dos terone receptor a goni s t; s pi ronol a ctone a nd
epl ere-none (not l i s ted here) exert thei r na tri ureti c a nd pota s s i um-sparing effects by blocking a l dos terone receptors . Fi na l l y, l oweri ng di s ta l tubul a r
os mol a l i ty (e) does not occur, nor woul d s uch a n effect (i f i t occurred) fa vor pa s s i ve di ffus i on of K+ i nto the uri ne.
274. The answer is d. (Brunton, pp 688t, 690-692, 776-777; Katzung, pp 260-261, 267.) Metol a zone, a l though not a thi a zi de (benzothi a di a zi de) i n the
chemi ca l s ens e, i s l a rgel y (hydrochl oro)thi a zi de-l i ke i n terms of i ts pha rma col ogi c properti es a nd us es , a l though i t ha s a much l onger dura ti on of
a cti on tha n the prototype, hydrochl orothi a zi de. As fa r a s the ma i n us e of thi a zi des goes , tha t woul d be es s enti a l hypertens i on (a s s umi ng no
contra i ndi ca ti ons ), wi th l es s er us es bei ng mi l d a nd es peci a l l y tra ns i ent edema , ma na gement of i di opa thi c hyperca l ci uri a , a djuncti ve
ma na gement of nephrogeni c di a betes i ns i pi dus , a nd perha ps ma na gement of Meni ere di s ea s e. Thi a zi des (or s uch thi a zi de-l i ke drugs a s
metol a zone) woul d not be ra ti ona l , nor very effi ca ci ous , for drug thera py of a n a drena l corti ca l tumor (a ). In tha t i ns ta nce, i f we a re cons i deri ng
onl y di ureti cs , the proper drug woul d be s pi ronol a ctone, the a l dos terone receptor bl ocker. Li kewi s e, s i nce thi a zi des ca n ra i s e ci rcul a ti ng ura te a nd

gl ucos e l evel s , they woul d not be good choi ces for the pa ti ent wi th hepa ti c ci rrhos i s or other di s ea s es cha ra cteri zed by poor l i ver functi on (b; here
too s pi ronol a ctone woul d be the bes t choi ce) or gout or di a betes (e). If our goa l were to ma na ge s evere edema (e) wi th or wi thout a s ci tes (a s i n a
pa ti ent wi th hea rt fa i l ure), our bes t choi ce woul d be a l oop di ureti c.
275. The answer is a. (Brunton, pp 682-686; Katzung, pp 252f, 252t, 258-260.) One expected res pons e to thera peuti c dos es of l oop di ureti cs , whi ch a re
cl ea rl y a nd correctl y cl a s s i fi ed a s pota s s i um-wa s ti ng, i s a reducti on of uri na ry pota s s i um concentrations. How ca n thi s be? Note tha t the term
concentra ti on refl ects the a mount of a s ubs ta nce (here, pota s s i um) per unit volume; i t i s not equi va l ent to a mount per s e. The l oop di ureti cs do
i ncrea s e K+ excreti on: beca us e they work more proxi ma l l y, they provi de a n a dded l oa d of Na + del i vered to the di s ta l nephron, where s odi um
cha nnel s i n the pri nci pa l cel l s ta ke up the Na + i n excha nge for K+. Pota s s i um s ecreti on by the pri nci pa l cel l s i s not i nhi bi ted (e). Loop di ureti cs
a l s o i mpa i r the a bi l i ty of the ki dneys to form a concentra ted uri ne a nd s o promote forma ti on of a l a rge vol ume of more di l ute (= l es s
concentra ted) uri ne. The net l os s of K+ (s a y, on a 24-h ba s i s ) i s i ncrea s ed, but i ts a ccompa ni ed by a di s proporti ona te i ncrea s e i n free wa ter l os s
s uch tha t uri ne K+ concentra ti on (but not tota l a mount l os t) i s decrea s ed.
276. The answer is a. (Brunton, pp 693t, 695; Katzung, pp 225, 270, 697, 708, 711.) Epl erenone i s a rel a ti vel y new s pi ronol a ctone-l i ke drug. As s uch, i ts
ma i n mecha ni s m of a cti on i nvol ves bl ocka de of a l dos terone receptors (eg, i n the nephron). Its ma i n us es a re a l s o l a rgel y i denti ca l to thos e of
s pi ronol a ctone: hea rt fa i l ure, hypertens i on (ma i nl y a s a pota s s i um-s pa ri ng a djunct, a nd es peci a l l y when pl a s ma reni n l evel s a re el eva ted, a s
tha t l ea ds to i ncrea s ed a ngi otens i n II s ynthes i s whi ch, i n turn, i ncrea s es a l dos terone rel ea s e from the a drena l cortex); a nd i n pa ti ents i n whom
a l dos terone l evel s a re hi gh from other ca us es (eg, a drena l corti ca l tumor, Cus hi ng di s ea s e). The drug ha s no effect on the s ynthes i s of
a l dos terone (d) or other s teroi d hormones (b); i ts ul ti ma te rena l effects a re the oppos i te of thos e of ADH (a t l ea s t i n terms of free wa ter l os s or
cons erva ti on), s o c. i s i ncorrect. Fi na l l y, the drug ha s no di rect or cl i ni ca l l y us eful effects on gl ucos e meta bol i s m or l evel s , nor on gl ycos uri a (e) a nd
other cons equences of hypergl ycemi a .
277. The answer is a. (Brunton, pp 677f, 682-686; Katzung, pp 251-255, 258-260.) Reca l l one of the ma i n mecha ni s ms by whi ch a concentra ted uri ne i s
formed: a hypertoni c mi l i eu i n the rena l medul l a a nd a medul l a ry-to-corti ca l os moti c gra di entos moti ca l l y wi thdra ws wa ter (but not s ol ute)
from the tubul a r fl ui d a s i t pa s s es through the col l ecti ng ducts . Wha t crea tes tha t hypertoni c medul l a ry-to-corti ca l gra di ent? Rea bs orpti on of Na +
a nd Cl - a s tubul a r fl ui d a s cends the l oop of Henl e, whi ch ul ti ma tel y i ncrea s es i nters ti ti a l os mol a l i ty. However, tha t proces s of i on res orpti on i s
i mpa i red by l oop di ureti cs . Tha t reduces os mol a l i ty i n the medul l a ry i nters ti ti um, thereby dra ma ti ca l l y reduci ng the os moti c gra di ent tha t ena bl es
the tubul a r fl ui d to become hypertoni c a s wa ter i s l os t i n the di s ta l nephron. Thus , i n the pres ence of a l oop di ureti c the uri ne rema i ns di l ute a nd
hypotoni c.
Hyperca l cemi a (b) i s not a n expected a ccompa ni ment. Loop di ureti cs (i n contra s t wi th thi a zi des ) i ncrea s e rena l Ca 2+ el i mi na ti on.
Reca l l tha t the ma i n a ni on excreted (a l ong wi th Na +, K+, etc) i n res pons e to a l oop di ureti c i s chl ori de, a nd s o net Cl - excreti on goes up (not
down; c). Meta bol i c a ci dos i s from i ncrea s ed bi ca rbona te excreti on (d) does nt occur. Bi ca rbona te tends to be rea bs orbed, therefore. You s houl d
reca l l tha t hypochl oremi c a l ka l os i s (a l s o ca l l ed contra cti on a l ka l os i s , beca us e bl ood vol ume contra cts a s the res ul t of exces s i ve fl ui d l os s i n the
uri ne) i s one potenti a l a nd qui te da ngerous a dvers e res pons es ca us ed by l oop di ureti cs .
Loop di ureti cs do not l ower ura te concentra ti ons (e). Ra ther, ura te l evel s tend to ri s e, i n pa rt, beca us e of reduced ura te excreti on combi ned wi th
a concentra ti on of ura te i n the bl ood owi ng to i ncrea s ed free wa ter l os s vi a the uri ne. Bl ood uri c a ci d concentra ti on tends to ri s e. The l oop
di ureti cs reduce ura te excreti on through a di rect rena l tubul a r a cti on. More i mporta nt, perha ps , the proporti ona l l y l a rge extra free wa ter l os s
s hri nks bl ood vol ume a nd tends to i ncrea s e s ol ute concentra ti on, i ndependent of a ny rena l tubul a r effects on ura te el i mi na ti on.
278. The answer is a. (Brunton, pp 714, 716t-717; Katzung, pp 264, 270, 675, 678.) Thi s pa ti ent proba bl y ha s SIADHa s yndrome of i na ppropri a te
va s opres s i n (a nti di ureti c hormone; ADH) s ecreti ona nd the s cena ri o des cri bed a bove (hypervol emi a , di l uti ona l hypona tremi a ) i s a fa i rl y common
ca us e or a ccompa ni ment of i t. Coni va pta n, a rel a ti vel y new drug, i s i ndi ca ted for ma na gi ng SIADH. It i s a nonpepti de a nd competi ti ve a nta goni s t of
ADHs wa ter-s pa ri ng effects i n the nephrons col l ecti ng duct.
Why not ma nni tol (b)? Its a na tomi c s i te of rena l a cti on i s the s a me a s coni va pta ns , but i t i ncrea s es free wa ter l os s through a n os moti c, ADHi ndependent, mecha ni s m. (In fa ct, a compens a tory res pons e to countera ct ma nni tol s effects a nd cons erve wa ter i s i ncrea s ed ADH rel ea s e, but
ma nni tol s effects typi ca l l y wi n out a nd di ures i s i ndeed occurs .) Reca l l tha t the os moti c mecha ni s m by whi ch ma nni tol ca us es di ures i s a l s o
contri butes to i ncrea s ed pl a s ma os mol a l i ty a nd bl ood vol umea t l ea s t i ni ti a l l y a nd unti l s uffi ci ent ma nni tol ha s been excreted. Hea rt fa i l ure
(whi ch thi s pa ti ent ha d) i s a contra i ndi ca ti on, or a t l ea s t a n i mporta nt preca uti on, to ma nni tol s us e beca us e even a tra ns i ent i ncrea s e of
ci rcul a ti ng fl ui d vol ume, whi ch tra ns i entl y i ncrea s es bl ood pres s ure, ca n provi de a s i gni fi ca nt a dded hemodyna mi c l oa d on the fa i l i ng hea rt. (The
ri s k woul d be even grea ter i f the pa ti ent ha d poor rena l bl ood fl ow or functi on tha t woul d s l ow ma nni tol s el i mi na ti on a nd keep bl ood os mol a l i ty
hi gh l onger.)
Metol a zone (c) i s a thi a zi de-l i ke di ureti c. Reca l l tha t, a s a cl a s s , thi a zi des or rel a ted a gents ha ve onl y a modes t (a ctua l l y s l i ght) a bi l i ty to
reduce ci rcul a ti ng fl ui d vol ume (whi ch woul d be des i ra bl e i n SIADH). More i mporta ntl y, thi a zi des a nd thi a zi de-l i ke a gents tend to cause
hypona tremi a ; tha ts s omethi ng we dont wa nt to ca us e or, i n thi s ca s e, wors en. Infus i ng 0.9% Na Cl (d) wi l l not correct s odi um concentra ti ons a nd
i f too much i s i nfus ed too qui ckl y ma y put a ddi ti ona l fl ui d-overl oa d-rel a ted hemodyna mi c s tres s es on the fa i l i ng hea rt. Spi ronol a ctone (e) i s
i rra ti ona l . Fi rs t, i t wi l l not correct the exces s i ve free wa ter l os s . More i mporta nt, by a nta goni zi ng the rena l tubul a r effects of a l dos terone i t wi l l
i ncrea s e s odi um l os s a nd i ncrea s e rena l pota s s i um retenti onpreci s el y the oppos i te of wha t we wa nt to do wi th thi s pa ti ent.
279. The answer is a. (Brunton, pp 85, 677-681, 1059; Katzung, pp 251-258.) Aceta zol a mi de, the prototypi c ca rboni c a nhydra s e i nhi bi tor, ca us es meta bol i c
a ci dos i s a s i t i ncrea s es rena l bi ca rbona te excreti on, whi ch i n turn a l ka l i ni zes the uri ne. Al though a ceta zol a mi de i s i nfrequentl y us ed a s a
di ureti c, i t i s us ed more for other condi ti ons i ncl udi ng a l ti tude s i cknes s , a n a djunct to certa i n a nti epi l epti c drugs , a nd (perha ps i n thi s ca s e) for
ma na gement of gl a ucoma .
Pa ti ents wi th s evere l i ver dys functi on ca nnot s ynthes i ze urea a dequa tel y. As a res ul t, el i mi na ti on of a va ri ety of endogenous ni trogen-ba s ed
meta bol i c wa s te products becomes dependent on rena l excreti on of a mmoni um i on. In norma l l y a ci di c uri ne the a mmoni um i ons a re el i mi na ted
ra ther effi ci entl y. However, a nd due to the a ceta zol a mi des uri na ry-a l ka l i ni zi ng effects , a mmoni a ga s forms i n the uri ne. It then rea di l y di ffus es
from the uri ne to the ci rcul a ti on. Thi s ca us es hypera mmonemi a , whi ch i s the mos t l i kel y ca us e of the coma .
Epl erenone (b) a nd the ol der rel a ted drug, s pi ronol a ctone, tend not to a l ter bl ood or uri ne pH. Indeed, s i nce pa ti ents wi th s evere l i ver
dys functi on (s uch a s thi s pa ti ent, wi th hepa ti ti s - a nd a l cohol -i nduced hepa ti c ci rrhos i s ) tend to ha ve hi gh ci rcul a ti ng a l dos terone l evel s , the
bl ocka de of a l dos terone receptors by epl erenone woul d proba bl y be benefi ci a l for thi s pa ti ent, a nd not a t a l l l i kel y to a ccount for the coma a nd
rel a ted neurol ogi c a bnorma l i ti es .
Furos emi de (c) a l s o i s a n unl i kel y expl a na ti on. It i s l i kel y to fa ci l i ta te a mmoni um excreti on, a nd pH-rel a ted cha nges (eg, uri na ry a l ka l i ni za ti on)
a re not a pt to occur. Reca l l tha t one ma ni fes ta ti on of l oop di ureti c exces s i s hypochl oremi c meta bol i c a l ka l os i s (a l s o ca l l ed contra cti on a l ka l os i s

beca us e ci rcul a ti ng fl ui d vol ume s hri nks contra cts ) i n res pons e to the very effi ca ci ous l oop a gents . Beca us e the ki dneys tend to l os e l a rge
a mounts of chl ori de, a nd tend to reta i n bi ca rbona te, uri na ry a l ka l i ni za ti on tha t l ea ds to a mmoni a producti on i n the uri ne i s not l i kel y.
Some of the thi a zi des (eg, hydrochl orothi a zi de, d) a nd thi a zi de-l i ke a gents (eg, chl ortha l i done, metol a zone) ha ve ca rboni c a nhydra s e a cti vi ty
tha t coul d l ea d to a l ka l i ni za ti on of the uri ne. However, thi s property i s genera l l y wea k i n compa ri s on wi th a ceta zol a mi de or rel a ted a gents tha t
a re more a ppropri a tel y cl a s s i fi ed a s ca rboni c a nhydra s e i nhi bi tors . Tri a mterene (e, or the rel a ted drug a mi l ori de), a pota s s i um-s pa ri ng di ureti c
wi th a cti ons tha t a re a l dos terone-i ndependent (contra s t wi th epl erenone, s pi ronol a c-tone), i s not l i kel y to a l ter uri ne pH or ca us e other effects
tha t mi ght preci pi ta te coma i n thi s pa ti ent.
280. The answer is a. (Brunton, pp 677-681, 1059; Katzung, pp 256-258.) The s i gns a nd s ymptoms of a l ti tude s i cknes s a re rel a ted to the devel opment of
res pi ra tory a l ka l os i s : At hi gh a l ti tudes the pa rti a l pres s ure of O2 i n the i ns pi red a i r i s l ow. The hypoxi a tri ggers hyperventi l a ti on, whi ch i ncrea s es
net venti l a tory l os s of CO2 . Bl ood pH ri s es . Aceta zol a mi de effecti vel y i nhi bi ts ca rboni c a nhydra s e a nd s o i ncrea s es bi ca rbona te l os s . Thi s , i n turn,
ca us es a meta bol i c a ci dos i s tha t countera cts the venti l a tory-i nduced ri s e of bl ood pH. It i s the drug of choi ce for prophyl a xi s or ma na gement of
a l ti tude s i cknes s . It i s true tha t s ome of the thi a zi de or thi a zi de-l i ke di ureti cs i nhi bi t ca rboni c a nhydra s e, but the effect i s very wea k i n
compa ri s on to tha t of a ceta zol a mi de. None of the other drugs l i s ted woul d be s ui ta bl e for thi s pa ti ent a nd the a l ti tude s i cknes s he i s l i kel y to
experi ence.
281. The answer is a. (Brunton, pp 680, 1775, 1787; Katzung, p 257.) Aqueous humor forma ti on (a s wel l a s tha t of cerebros pi na l fl ui d) i nvol ves ca rboni c
a nhydra s e a cti vi ty. Reduce a queous humor s ynthes i s a nd, a l l other fa ctors bei ng equa l , i ntra ocul a r pres s ure goes down. Aceta zol a mi de i s , of
cours e, the ca rboni c a nhydra s e-i nhi bi ti ng di ureti c.
Note tha t when a ca rboni c a nhydra s e i nhi bi tor i s us ed to ma na ge gl a ucoma , the drugs rena l /di ureti c effects , whi ch certa i nl y occur i f the drug i s
gi ven s ys temi ca l l y, ha ve nothi ng to do wi th the benefi ci a l effects tha t a re due to a n ocul a r (ci l i a ry body) s i te of a cti on. If fa ct, thos e extra ocul a r
effects a rent needed for gl a ucoma control . Tha t i s why, when we pres cri be a ca rboni c a nhydra s e i nhi bi tor for gl a ucoma , we us ua l l y choos e a
topi ca l ophtha l mi c ca rboni c a nhydra s e i nhi bi tor (eg, dorzol a mi de or metha zol a mi de).
282. The answer is d. (Brunton, pp 681-682; Katzung, pp 251-271.) Ma nni tol i s a n os moti c di ureti c, the prototype of tha t s ma l l cl a s s of drugs
(gl yceri n/gl ycerol i s a nother s omewha t noteworthy member of the group) wi th i ndi ca ti ons a nd potenti a l s i de effects tha t a re qui te di fferent from
thos e of typi ca l di ureti cs l i ke the thi a zi des or l oop a gents . Wha t ha ppens when you i nject (i ntra venous l y) thi s nonmeta bol i za bl e s uga r, whi ch
ha s a s tructure s i mi l a r to tha t of gl ucos e a nd the s a me mol ecul a r wei ght? Ini ti a l l y, a nd unti l i t i s excreted by gl omerul a r fi l tra ti on, ma nni tol
i ncrea s es pl a s ma os mol a l i ty. Tha t, i n turn, os moti ca l l y wi thdra ws wa ter from the extra cel l ul a r s pa ce a nd, ul ti ma tel y, from the pa renchyma l cel l s ,
a nd i nto the bl ood. If the pa ti ent ha s good rena l functi on, rena l bl ood fl ow a nd GFR ri s e, a nd the drug i s eventua l l y excreted. If he or s he ha s
a dequa te ca rdi a c functi on, ci rcul a ti ng tha t extra vol ume (up to a l i mi t) i s not a probl em.
However, i f the pa ti ent ha s a s uffi ci entl y contra cti l i ty or ca rdi a c output to begi n wi th, or rena l perfus i on i s compromi s ed, the i ncrea s ed bl ood
vol ume a nd pres s ure ma y be s uch tha t the hea rt s i mpl y ca nnot ha ndl e the a dded workl oa d. Indeed, i n a futi l e a ttempt to ci rcul a te tha t a ddi ti ona l
vol ume a nd eject i t a ga i ns t a hi gher a fterl oa d, the hea rt ma y fa i l a cutel y.
Ami l ori de (a ), a pota s s i um-wa s ti ng di ureti c wi th rel a ti vel y l ow effi ca cy i n terms of i ts a bi l i ty to i ncrea s e uri ne vol ume, s houl d ha ve no a dvers e
effects i n thi s pa ti ent. The s a me a ppl i es to hydrochl orothi a zi de (c), whi ch i s pota s s i um-wa s ti ng. Etha cryni c a ci d (b) i s a l oop di ureti c. It i s one of
s evera l l oop a gents we mi ght choos e to hel p unl oa d thi s pa ti ents ventri cl es , provi ded the pa ti ent i s nt hypovol emi c a l rea dy. Spi ronol a ctone (e),
a pota s s i um-s pa ri ng a l dos terone a nta goni s t, mi ght ul ti ma tel y be pres cri bed for thi s pa ti ent, pa rti cul a rl y i f hi s hea rt fa i l ure wors ens .
Nonethel es s , a t thi s ti me i t i s not a drug we s houl d a voi d.
283. The answer is e. (Brunton, pp 692-793, 693t, 1841; Katzung, pp 261-263, 711, 739.) The mos t ra ti ona l choi ce for s peci fi ca l l y a nta goni zi ng the
cons equences of hormone exces s a l dos terone bei ng the hormone of mos t i mporta nce i n terms of the rena l , hemodyna mi c, a nd el ectrol yte
probl ems herei s s pi ronol a ctone (or epl erenone). Its pri ma ry mecha ni s m of a cti on i s bl ocka de of a l dos terone receptors . Remember tha t the
ma i n rena l effects of a l dos terone a re s odi um (a nd wa ter) retenti on, a nd i ncrea s ed rena l l os s of pota s s i um.
Aceta zol a mi de (a ), the ca rboni c a nhydra s e i nhi bi tor, exerts wea k a nd s el f-l i mi ti ng di ureti c a nd na tri ureti c effects . It i s a l s o pota s s i um-wa s ti ng,
a nd i ncrea s ed excreti on of pota s s i um i s wha t we do not wa nt to do i n s i tua ti ons of preexi s ti ng hypoka l emi a . Ami l ori de (b) woul d hel p i ncrea s e
s odi um excreti on a nd hel p norma l i ze pota s s i um l evel s too. However, i t does not provi de the ra ti ona l a pproa ch to hypera l dos teroni s m beca us e
i t does not bl ock a l dos terone receptors . Furos emi de (c) or a nother l oop di ureti c mi ght prove effecti ve i n terms of i ncrea s i ng excreti on of s odi um
a nd reduci ng tha t of pota s s i um. Indeed, i f the hypera l dos teroni s m i s s uffi ci entl y grea t to ca us e da ngerous degrees of fl ui d retenti on
(hypervol emi a ) a nd hea rt fa i l ure we ma y need to a dmi ni s ter i t. Nonethel es s , s pi ronol a c-tone woul d be a rea s ona bl e, ra ti ona l , a nd proba bl y
neces s a ry el ement of ma na gement. Metol a zone (d), a thi a zi de-l i ke di ureti c, woul d des i ra bl y hel p i ncrea s e rena l s odi um excreti on a nd l ower
bl ood pres s ure. Ha vi ng rel a ti vel y l ow effi ca cy i n terms of i ncrea s ed uri ne producti on, i t ma y not do much to ma na ge the hypervol emi a a nd the
res ul ti ng wei ght ga i n. More i mporta nt, metol a zone i s l i kel y to a ggra va te the preexi s ti ng hypoka l emi a beca us e i t i s , of cours e, a pota s s i umwa s ti ng di ureti c.
284. The answer is b. (Brunton, pp 801-804, 837-839; Katzung, pp 251-255, 258-260.) Whi l e ma ny i oni c a nd other fa ctors ca n predi s pos e a pa ti ent to
di goxi n toxi ci ty, hypoka l emi a , a s ca n be ca us ed by a l oop di ureti c (us ua l l y us ed for edema a nd/or a s ci tes , i ncl udi ng tha t a s s oci a ted wi th hea rt
fa i l ure) or thi a zi de di ureti c (ma i nl y us ed for trea ti ng es s enti a l hypertens i on), i s a rgua bl y the mos t i mporta nt, i f not the mos t common. There i s a
competi ti on between extra cel l ul a r K+ a nd di goxi n for bi ndi ng to di goxi ns cel l ul a r receptor, the Na +, K+-ATPa s e on the s a rcol emma . When
ci rcul a ti ng (extra cel l ul a r) K+ concentra ti on i s reduced (i e, when hypoka l emi a devel ops ), the bi ndi ng of di goxi n i s enha nced a nd s o i ts effects a re
i ncrea s ed, even wi thout a ri s e of di goxi n concentra ti ons , a nd us ua l l y thos e i ncrea s ed effects a re del eteri ous , a s des cri bed here. Hyperca l cemi a
ca n i ncrea s e the ri s k or s everi ty of di goxi n toxi ci ty. However, l oop di ureti cs i ncrea s e rena l Ca 2+ l os s , a nd s o hyperka l emi a (a ) i s not a l i kel y
expl a na ti on. Hypona tremi a (c) i s not a t a l l l i kel y to ha ve occurred wi th a l oop di ureti c, whi ch tends to i ncrea s e both rena l Na + a nd H 2 O l os s , wi th
the l os s of free wa ter bei ng much grea ter tha n the l os s of Na +. Loop di ureti cs do not di s pl a ce di goxi n from ti s s ue bi ndi ng s i tes (d) or i nhi bi t
di goxi ns el i mi na ti on (whi ch i nvol ves rena l excreti on, not meta bol i s m).
Note tha t i n the s cena ri o I des cri bed the pa ti ent a s ha vi ng been trea ted by hi s fa mi l y doctor who ha s been trea ti ng hi m for the l a s t 30 yea rs .
Thi s i s not a t a l l mea nt to i mpugn fa mi l y doctors or genera l pra cti ti oners . The poi nt i s tha t nowa da ys , a nd for a va ri ety of rea s ons (toxi ci ty bei ng
one), di goxi n i s no l onger cons i dered a n a ppropri a te drug for ma na gi ng hea rt fa i l ure, wi th or wi thout s i gns or s ymptoms of conges ti ve fa i l ure,
unti l a l l other rea s ona bl e a nd more s ui ta bl e opti ons ha ve been tri ed a nd the pa ti ents condi ti on ha s deteri ora ted to the poi nt tha t i notropes
(di goxi n or pa rentera l a gents ) a re wa rra nted. Reca l l tha t our preferred a pproa ch for i ni ti a l thera py of fa i l ure i nvol ves ACE i nhi bi tors , a -bl ocker,
a nd perha ps a l oop di ureti c. Nonethel es s , a nd unfortuna tel y, s ome phys i ci a ns s ti l l us e the ol d wa y, i nvol vi ng di goxi n. It i s thes e pa ti ents who
a re l i kel y to be s een i n the hos pi ta l when the a l mos t i nevi ta bl e probl ems due to di goxi n devel op.

285. The answer is d. (Brunton, pp 682-686; Katzung, pp 258-260.) Thi s pa ti ent needs a di ureti c tha t ha s a fa s t ons et of a cti on the a bi l i ty to ra ther
s i gni fi ca ntl y i ncrea s e rena l excreti on of free wa ter to unl oa d the hea rt. Tors emi de i s very s i mi l a r i n terms of a cti ons a nd us es to the prototype
l oop or hi gh cei l i ng di ureti c, furos emi de, whi ch i nhi bi ts a Na +/K+/2Cl - tra ns porter i n the a s cendi ng l i mb of the Loop of Henl e. (Note tha t both
furos emi de a nd tors emi de end i n -Semi tea ti p for na me recogni ti on.)
Aceta zol a mi de (a ), the prototype ca rboni c a nhydra s e i nhi bi tor, woul d be uns ui ta bl e. Its ons et of a cti on i s s l ow; i ts pea k effects i n terms of
i ncrea s i ng free wa ter el i mi na ti on a re l ow; a nd i ts a bi l i ty to ca us e meta bol i c a ci dos i s (s econda ry to i ncrea s ed rena l bi ca rbona te l os s ) woul d not
onl y compromi s e the pa ti ent des cri bed i n the s cena ri o but a l s o ca us e l os s of the drugs di ureti c effects . Hydrochl orothi a zi de (b) a nd thi a zi de-l i ke
di ureti cs (eg, metol a zone a nd chl ortha l i done, e) woul d not be s ui ta bl e; thei r effi ca ci es a re l ow i n terms of ma na gi ng edema ; thei r effects a re
s l ow to devel op; a nd onl y one thi a zi de, chl orothi a zi de, ca n be gi ven pa rentera l l y (a poi nt I do not thi nk you need to commi t to memory). Ma nni tol
(c), the prototype os moti c di ureti c, i s gi ven pa rentera l l y; i t ha s a rel a ti vel y prompt ons et of a cti on; a nd i t ca n s i gni fi ca ntl y i ncrea s e fl ui d
el i mi na ti on vi a the ki dneys . Ma nni tol s i ntens i ty a nd dura ti on of effects , however, depend on ma ny va ri a bl es , i ncl udi ng ba s el i ne rena l functi on.
Nonethel es s , ma nni tol i ni ti a l l y ra i s es ci rcul a ti ng fl ui d vol umei ncrea s i ng the hemodyna mi c l oa d on the hea rt a nd bei ng pa rti cul a rl y probl ema ti c
i n the fa ce of hea rt fa i l urea nd i ts a dvers e vol ume-rel a ted effects wi l l be prol onged i f GFR i s reduced i n pa ti ents s uch a s the one des cri bed i n
the ques ti on.
286. The answer is b. (Brunton, pp 682-686; Katzung, p 260.) Both the l oop di ureti cs a nd the a mi nogl ycos i des (tobra myci n, s treptomyci n, genta mi ci n,
others ) a re ototoxi cca pa bl e of ca us i ng ves ti bul a r da ma ge (eg, ba l a nce probl ems ), cochl ea r da ma ge (ti nni tus or s ens ori neura l hea ri ng l os s ), or
both. The ototoxi c effects of ea ch drug i s enha nced (often s i gni fi ca ntl y) by the others , a nd s o i t i s bes t to a voi d us e of both thes e drugs (or other
ototoxi ns ) unl es s the benefi ts cl ea rl y outwei gh the ri s k of perha ps perma nent a nd tota l hea ri ng l os s . (Of cours e, there a re i ns ta nces i n whi ch s uch
combi na ti ons a re neces s a ry.) Theres s trong evi dence tha t of a l l the l oop di ureti cs , the ri s k of ototoxi ci ty i s hi ghes t wi th etha cryni c a ci d (a nd i ts
pa rentera l formul a ti on, s odi um etha cryna te). Nonethel es s , a l l the other l oop di ureti cs bumeta ni de, furos emi de, a nd tors emi dea re defi ni tel y
on the s hort l i s t of ototoxi c drugs .
Aceta zol a mi de (a ), metol a zone (c) or other thi a zi de or thi a zi de-l i ke di ureti cs , s pi ronol a ctone (d), a nd tri a mterene (e) a re not ototoxi c, nor do
they potenti a te the a dvers e a udi tory effects of other ototoxi c drugs .
287. The answer is b. (Brunton, pp 690-692; Katzung, pp 261-263.) Ami l ori de a nd tri a mterene bl ock di s ta l tubul a r Na + cha nnel s tha t provi de for Na +
rea bs orpti on i n excha nge for K+, whi ch i s l os t i nto the uri ne. Thi s s odi um cha nnel , whi ch i s the ma i n s i te of a cti on of a mi l ori de, i s on the l umi na l
s i de of the pri nci pa l cel l membra nes . (Pri nci pa l cel l s i n the nephron a re l oca ted i n the l a te di s ta l tubul e a nd col l ecti ng ducts .) There i s a n ATPa s e
on the i nters ti ti a l fa ce of the pri nci pa l cel l s (a ga i n, thes e a re i n the di s ta l nephron, not proxi ma l ; d). The ATPa s e i s res pons i bl e for the extrus i on
of pota s s i um i nto the uri ne i n excha nge for extra s odi um ta ken up by the l umi na l s odi um cha nnel s , a nd s o i t i s es s enti a l i n the overa l l a cti ons of
pota s s i um-s pa ri ng di ureti cs . Nonethel es s , the ATPa s e i s not i nhi bi ted (or s ti mul a ted; d) di rectl y by a mi l ori de.
Ami l ori de ha s no di rect effects on a l dos terone s ynthes i s or meta bol i s m (c), or on a l dos terone receptors (a ; thos e receptors a re bl ocked by
s pi ronol a ctone).
288. The answer is d. (Brunton, pp 686-690; Katzung, pp 252, 260-261, 268.) Thi a zi de a nd thi a zi de-l i ke di ureti cs s houl d be hi gh (hi ghes t!) on your l i s t of
drugs tha t a re l i kel y to ca us e hypona tremi a . Wa s i t ea s y to s el ect hydrochl orothi a zi de a s the correct a ns wer beca us e i t wa s the onl y drug l i s ted
tha t wa s not a l oop di ureti c? Were you puzzl ed beca us e you knew tha t furos emi de i s the prototype l oop a gent, a nd werent s ure a bout the
cl a s s i fi ca ti on bumeta ni de, etha cryni c a ci d, or tors emi de. Or di d you not s el ect the thi a zi de beca us e you cons i dered i ts di ureti c effects to be mi l d,
or modes t, a nd therefore l ea s t l i kel y to ca us e hypona tremi a ?
In a bs ol ute or rel a ti ve terms the na tri ureti c (s odi um-wa s ti ng) effects ca n be cons i dered wea k (es peci a l l y i n compa ri s on wi th l oop di ureti cs ).
They ca us e rel a ti vel y s l i ght i ncrea s es i n free wa ter l os s i n the uri ne (compa red wi th norma l ), i nterfere wi th norma l uri ne-di l uti ng mecha ni s ms ,
a nd l ea d to the forma ti on of a concentra ted (i n terms of s uch s ol utes a s s odi um) uri ne. Tha t i s , the a mount of extra s odi um l os t i s , i n a rel a ti ve
s ens e, much grea ter tha n the extra vol ume l os t. Thi s i s refl ected, i n the bl ood, a s not much extra vol ume l os s coupl ed wi th proporti ona l l y grea ter
decl i nes i n the a mount of s odi um. Remember tha t hypona tremi a mea ns exces s i vel y reduced s odi um concentration, a nd concentra ti on i s a functi on
of a mount per uni t vol ume. The thi a zi des ha ve ca us ed di l uti ona l hypona tremi a .
289. The answer is b. (Brunton, pp 677-701; Katzung, pp 172, 184-185, 219-220, 295-300.) Li s i noprol (a -pri l , a nd therefore a n a ngi otens i n-converti ng
enzyme i nhi bi tor) i ndi rectl y reduces a l dos terone rel ea s e from the a drena l cortex by i nhi bi ti ng a ngi otens i n II s ynthes i s . (Remember: A-II i s the
ma jor phys i ol ogi c s ti mul us for a l dos terone rel ea s e.) Norma l l y a l dos terone ca us es rena l Na + retenti on a nd K+ l os s . When there i s l es s
a l dos terone, the ki dneys wi l l now tend to l os e Na + a nd reta i n K+. Ami l ori de (l i ke tri a mterene) bl ocks s odi um cha nnel s on the l umi na l fa ce of the
pri nci pa l cel l s of the nephron. Thos e s odi um cha nnel s norma l l y a re res pons i bl e for Na + a nd K+ excha nge (s ome extra Na + recl a i med, extra K+ l os t
i nto the uri ne). In the pres ence of a mi l ori de the i on excha nge i s i nhi bi ted a nd thi s cons ti tutes the pota s s i um-s pa ri ng effects tha t we us e to
cl a s s i fy thes e di ureti cs . Al though a l dos terone pl a ys a rol e i n rena l ha ndl i ng of Na + a nd K+, a mi l ori de (l i ke tri a mterene) wi l l work i n the a bs ence of
a l dos teroneunl i ke the pota s s i um-s pa ri ng effects of s pi ronol a ctone or epl erenone, whi ch onl y work i n the pres ence of a l dos terone beca us e
thei r mecha ni s m i nvol ves bl ocka de of a l dos terone receptors , wi th no di rect effects on pri nci pa l cel l i on cha nnel s .
There i s no l ogi ca l mecha ni s m wi th whi ch to envi s a ge a n ACE i nhi bi tor/pota s s i um-s pa ri ng di ureti c ca us i ng hypertens i on (a ). Nei ther a n ACE
i nhi bi tor nor a K+-s pa ri ng di ureti c, a l one or together, ha s di rect ca rdi a c-depres s a nt effects (c; unl es s the drugs were a dmi ni s tered a t s uch toxi c
dos es tha t el ectrol yte l evel s cha nged s o much tha t they a ffected the hea rt). Pol yuri a , a di a betes i ns i pi dus -l i ke s ta te (d) a nd a s yndrome of
i na ppropri a te ADH s ecreti on do not occur wi th ei ther of thes e drugs or wi th the two combi ned. As noted a bove, both drugs exert pota s s i um-s pa ri ng
effects , a nd s o hypoka l emi a (e) wi l l not occur.
290. The answer is b. (Brunton, pp 682-686, 696-701; Katzung, pp 258, 260.) Tha t a l oop di ureti c (furos emi de, bumeta ni de, tors emi de, or perha ps even
etha cryni c a ci d) woul d be a ra ti ona l choi ce for hel pi ng to ma na ge di ureti c-i nduced hypona tremi a s eems i rra ti ona l , i f not pl a i n wrong. After a l l ,
thes e drugs a re cons i dered to be the bi g guns of a l l di ureti cs , ca pa bl e of ca us i ng a l mos t l i mi tl es s dos e-dependent di ures i s l a rge i ncrea s es of
rena l l os s of wa ter, s odi um, pota s s i um, a nd other i ons . So, wha t i s the expl a na ti on?
When I des cri bed the a cti ons of a thi a zi de or thi a zi de-l i ke di ureti c I s a i d tha t they i mpa i r the ki dneys a bi l i ty to form a norma l l y di l ute uri ne: i n
a rel a ti ve s ens e they ca us e the l os s of more Na + tha n of free wa ter, a nd s o Na + concentra ti on i n the bl ood fa l l s (di l uti ona l hypona tremi a ). The
s i tua ti on i s es s enti a l l y the oppos i te wi th l oop di ureti cs . By reduci ng the medul l a ry-to-corti ca l i nters ti ti a l os moti c gra di ent (the countercurrent
mul ti pl i er phenomenon), s econda ry to reduced Na + tra ns port out of the uri ne i n the a s cendi ng l i mb of the Loop of Henl e, they i mpa i r the a bi l i ty of
the ki dneys to form a norma l l y concentra ted uri ne. In a rel a ti ve s ens e, the uri ne formed i n the pres ence of a l oop a gent therefore conta i ns more
wa ter tha n s odi um, a nd s o the concentra ti on of Na + i n the bl ood ri s es . Thi s tends to correct the hypona tremi a .
Ca ptopri l (a ), the prototype ACE i nhi bi tor, tends to l ower or not cha nge bl ood Na + concentra ti ons , but i t does not ra i s e them. ACE i nhi bi tors

reduce the forma ti on of A-II, whi ch norma l l y s ti mul a tes a l dos terone rel ea s e from the a drena l cortex. Al dos terone ca us es the rena l tubul es to
reta i n Na + a nd l os e K+. So when a l dos terone rel ea s e i s reduced (due to l es s A-II a va i l a bl e), the oppos i te occurs : Na + (a nd wa ter) el i mi na ti on ri s es
(but Na + concentra ti on tends not to cha nge), a nd a ddi ti ona l K+ i s l os t. Spi ronol a ctone (c) tends to do ma ny of the s a me thi ngs tha t a n ACE i nhi bi tor
does to the ki dneys , but i t works by bl ocki ng rena l a l dos terone receptors (l ea di ng to i ncrea s ed Na + l os s a nd K+ retenti on) a nd ha s no effects on AIIs s ynthes i s or di rect effects . Thi a zi des or rel a ted a gents (d) a re cl ea rl y the wrong choi ce: to rei tera te a n i mporta nt poi nt, of a l l the di ureti cs the
thi a zi des a nd rel a ted a gents a re the mos t common cause of hypona tremi a . Tri a mterene (a nd the rel a ted drug a mi l ori de) a re K+-s pa ri ng di ureti cs
tha t a ct by bl ocki ng Na + cha nnel s on the l umi na l fa ce of the pri nci pa l cel l s , thereby i nhi bi ti ng Na + for K+ excha nge, i n a ma nner tha t i s not
dependent on a l dos terone. They do not ra i s e pl a s ma Na + concentra ti ons a nd a re not effecti ve or us ed for di l uti ona l hypona tremi a .
291. The answer is d. (Brunton, pp 676-701; Katzung, pp 258-265.) Drug 2 i s furos emi de, a nd there a re s evera l ti p-offs to hel p you pi ck the ri ght a ns wer,
s ome tha t a re a dmi ttedl y l es s hel pful tha n the others . Not a t a l l hel pful i n di s ti ngui s hi ng between di ureti cs i s the i ncrea s ed rena l s odi um l os s .
Al l the common di ureti cs do tha t. Next, note the i ncrea s e i n rena l pota s s i um l os s . Thi s i s a l s o not too hel pful , s i nce a ceta zol a mi de (a ), the
thi a zi de-l i ke di ureti c chl ortha l i done (c), a nd hydrochl orothi a zi de (e) ha ve a pota s s i um-wa s ti ng effect s i mi l a r to tha t of furos emi de.
How do you na rrow thi ngs down from here, then? Fi rs t, the da ta s how tha t Drug 2 ca us es no i ncrea s e i n rena l bi ca rbona te l os s . From tha t you
ca n i nfer no i nhi bi ti on of ca rboni c a nhydra s e a cti vi ty. Tha t rul es out, es peci a l l y, a ceta zol a mi de (a ; i t i s , a fter a l l , a s trong ca rboni c a nhydra s e
i nhi bi tor). But the a bs ence of a ny cha nges i n bi ca rbona te l os s s houl d a l s o l ea d you a wa y from s el ecti ng a thi a zi de (e) or thi a zi de-l i ke (c) a gent,
s i nce mos t of them ha ve a t l ea s t s omebut ra ther wea k i n compa ri s on wi th a ceta zol a mi deca rboni c a nhydra s e i nhi bi tory a cti vi ty.
Perha ps the bes t ti p-off to hel p you di s ti ngui s h between furos emi de a nd a thi a zi de or thi a zi de-l i ke drug? Loop di ureti cs i ncrea s e rena l ca l ci um
l os s ; thi a zi des a nd thi a zi de l i ke a gents do the oppos i te, ca us i ng a ca l ci um-s pa ri ng effect. Cha nges i n rena l ma gnes i um l os s a rent too hel pful ,
s i nce thi a zi des , thi a zi de-l i ke a gents , a nd l oop di ureti cs a l l i ncrea s e ma gnes i um l os s .
So, heres the ful l s et of a ns wers :
Aceta zol a mi de (a ) ha s a profi l e tha t bes t ma tches drug 4 (note the ma rkedl y i ncrea s ed HCO3 - l os s a nd decrea s ed Cl - l os s ). Be a wa re, too, tha t
a ceta zol a mi de i s a l s o a pota s s i um-wa s ti ng di ureti c, a poi nt tha t i s often overl ooked beca us e we tend to ta l k a bout thi a zi des a nd l oop di ureti cs
a s the ma i n pota s s i um-wa s ti ng a gents .
Ami l ori des (b) profi l e fi ts tha t of drug 3. More s o tha n a nythi ng el s e, the gi ve-a wa y i s the reduced rena l K+ l os s not s urpri s i ng s i nce a mi l ori de
i s cl a s s i fi ed a s a pota s s i um-s pa ri ng di ureti c.
Chl ortha l i done (c) a nd hydrochl orothi a zi de (e), whi ch a re thi a zi de-l i ke or true thi a zi de di ureti cs (res pecti vel y), woul d produce profi l es l i ke drug
1: K+ l os s , a decrea s e of Ca 2+ excreti on, a nd va ri a bl e effects on HCO3 - l os s due to va ri a bl e effects (drug- a nd dos e-dependent, but genera l l y wea k)
on ca rboni c a nhydra s e.
Ra ther tha n reha s hi ng the s i tes a nd mecha ni s ms by whi ch the ma i n di ureti cs ca us e thei r effects tha ts l a rgel y been a ddres s ed el s ewhere
a bovewha t fol l ows a re s ome ti ps for a rri vi ng a t a correct a ns wer more ea s i l y. Il l a dd s ome a ddi ti ona l comments tha t ma y not ha ve been
empha s i zed before.
Note tha t a l l the profi l es s how a n i ncrea s ed (qua l i ta ti ve) rena l excreti on of Na +. The es s ence of thi s i s tha t i t refl ects the fa ct tha t a l l the
common di ureti cs do tha t. Indeed, thi s natriuretic effect (s odi um-excreti ng effect) i s pa rt of the worki ng defi ni ti on of di ureti c.
The next s tep i s to i denti fy whi ch a gents i ncrea s e rena l pota s s i um excreti on a nd whi ch do the oppos i te, beca us e the ma i n di ureti cs a re ei ther
pota s s i um-s pa ri ng or pota s s i um-wa s ti ng. Tha t wi l l na rrow your choi ces ni cel y. You s houl d be a bl e to pl a ce a drug i n the proper pota s s i um-rel a ted
cl a s s i ns ta nta neous l y (wi th the pos s i bl e excepti on of a ceta zol a mi de, a pota s s i um-wa s ti ng drug, beca us e we tend to empha s i ze i ts CA-i nhi bi tory
effects a nd overl oa d other i mporta nt properti es ; s ee the a ns wer to Ques ti on 268 a bove).
Fi na l l y, once you s ee tha t a drugs profi l e i nvol ves i ncrea s ed K+ l os s , you ha ve na rrowed your choi ces to a thi a zi de or thi a zi de-l i ke a gent (hydrochl orothi a zi de, chl ortha l i done, metol a zone, ma ny others ), a l oop a gent, or a CA i nhi bi tor.
Look now a t wha t ha ppens to uri na ry Ca 2+ excreti on. If i ts reduced, i ts a thi a zi de or a rel a ted a gent (reca l l we ca n us e thes e drugs for
i di opa thi c hyperca l ci uri a , a n effect tha t ca pi ta l i zes on reduced pres ence of Ca 2+ i n the uri ne due to reduced rena l Ca 2+ l os s ). If Ca 2+ excreti on i s
i ncrea s ed, i ts a l oop di ureti c.
Now, how do you i denti fy whi ch a gent i s a CA i nhi bi tor (i e, a ceta zol -a mi de)? In a ddi ti on to l ooki ng a t Na + a nd K+, note es peci a l l y wha t ha ppens
to HCO3 - a nd Cl -. Aceta zol a mi de ca us es profound uri na ry a l ka l i ni za ti on from the HCO3 - l os s ; s o much s o tha t the bl oods other ma jor a ni on, Cl -, i s
reta i ned. Jus t l ooki ng a t the ta bl e you woul d proba bl y rul e out a thi a zi de (a ) a s bei ng a ceta zol a mi de beca us e I i ndi ca te tha t the effect on tha t
a ni on i s va ri a bl e (+/-).
How coul d you rul e out tri a mterene, s i nce we s howed i ncrea s ed HCO3 - l os s wi th i t? (Its a s l i ght effect, by the wa y, a nd CA i nhi bi ti on i s not i ts
ma i n nor a n i mporta nt mecha ni s m or outcome, but you ca nt tel l from the ta bl e.) Look a t the Cl - profi l e a nd you wi l l s ee tha t a ceta zol a mi de i s the
onl y di ureti c tha t l owers Cl - excreti on. Tha ts beca us e one of the bl oods ma jor a ni ons , HCO3 -, i s l os t to s uch a grea t degree tha t the other ma i n
a ni on, Cl -, i s cons erved.

Respiratory System Pharmacology: Asthma and COPD

Autonomi c control of a i rwa y s mooth mus cl e tone
Corti cos teroi ds a nd control of a i rwa y i nfl a mma ti on i n a s thma
Drugs tha t ca n exa cerba te a s thma
Hi s ta mi ne a nd hi s ta mi ne receptor bl ockers
Immunogl obul i n a nti bodi es for a s thma
Leukotri enes a nd l eukotri ene modi fi ers i n a s thma
Methyl xa nthi ne rol es i n a s thma thera py

Questions
292. A 27-yea r-ol d pa ti ent i s s een i n the outpa ti ent cl i ni c for a routi ne checkup. Shes jus t moved to your town, a nd thi s i s the fi rs t ti me youve met
her. She ha s a s thma a nd s a ys s hes been us i ng her i nha l er (a l buterol ) mos t da ys ea ch week (s ometi mes twi ce a da y) a s her onl y thera py. I
brea the a l ot ea s i er a fter I ta ke s evera l puffs , s he s a ys . She feel s wel l otherwi s e. Whi ch s ta tement a ppl i es to thi s pa ti ent or her trea tment pl a n?
a . Her trea tment pl a n i s i na ppropri a te a nd needs to be modi fi ed
b. If pul mona ry functi on tes ts performed a t your hos pi ta l toda y a re norma l , i t i s l i kel y tha t the di a gnos i s i s i ncorrect: s he does not ha ve a s thma
c. She i s l i kel y to enjoy a cti vi ti es , s uch a s s ki i ng a nd s ka ti ng, i n whi ch s he brea thes col d, cl ea r a i r
d. She i s mos t l i kel y to ha ve troubl e wi th her brea thi ng when i n a wa rm, humi d a tmos phere
e. She i s proba bl y s l i ghtl y bra dyca rdi c a nd hypertens i ve from the drugs expected a cti ons on the hea rt a nd peri phera l va s cul a ture
293. Certa i n a drenergi c a goni s ts cl ea rl y pl a y a rol e i n ma na gi ng s ome pa ti ents wi th a s thma , whether for prophyl a xi s (control medi ca ti on) or for
res cue thera py. Whi ch drug i s cl a s s i fi ed a s a n a drenergi c a goni s t, but ha s no phys i ol ogi ca l l y rel eva nt or cl i ni ca l l y us eful effects on a i rwa y s mooth
mus cl e tone?
a . Al buterol
b. Epi nephri ne
c. Norepi nephri ne
d. Sa l meterol
e. Terbuta l i ne
f. Theophyl l i ne
294. A pa ti ent wi th a s thma ha s modera te bronchos pa s m a nd wheezi ng a bout twi ce a week. Current medi ca ti ons a re i nha l ed a l buterol (ma i nl y for
a cute s ymptom control ) a nd i nha l ed becl ometha s one a s a control medi ca ti on. The pa ti ent conti nues to ha ve occa s i ona l a nd genera l l y mi l d
fl a re-ups of hi s a s thma . If the phys i ci a n wi s hes to ma ke s a l meterol pa rt of the trea tment pl a n, how bes t s houl d i t be us ed for thi s pa ti ent?
a . A repl a cement for the a l buterol
b. A repl a cement for the corti cos teroi d
c. An a dd-on to current medi ca ti ons for a ddi ti ona l prophyl a cti c benefi ts
d. Pri ma ry (s ol e) thera py, repl a ci ng both a l buterol a nd the s teroi d
e. The preferred a gent for a cute s ymptom control (res cue thera py)
295. The a ttendi ng i n the outpa ti ent pul mona ry cl i ni c s ta tes s he i s goi ng to s ta rt oma l i zuma b thera py for a 19-yea r-ol d wi th refra ctory a s thma .
Wha t mos t a ccura tel y des cri bes the a cti ons , us es , or a dvers e effects of thi s drug?
a . Anti body tha t bi nds a nd therefore i na cti va tes endogenous ACh a nd hi s ta mi ne
b. Contra i ndi ca ted i f pa ti ent i s ta ki ng a n ora l or ora l l y i nha l ed corti cos teroi d
c. Good a l terna ti ve to a l buterol or s i mi l a r a drenergi c bronchodi l a tors for res cue thera py
d. Immedi a te- or del a yed-ons et a na phyl a cti c rea cti ons pos e the grea tes t ri s k
e. Novel a gent l i kel y to become fi rs t-l i ne thera py a s a control medi ca ti on for mi l d but recurrent a s thma
296. A 19-yea r-ol d moves from a s ma l l town to your ci ty, a nd i s now your pa ti ent. He ha s a hi s tory of a s thma , a nd hi s previ ous pri ma ry ca re
phys i ci a n wa s ma na gi ng i t wi th ora l theophyl l i ne. Wha t bes t s umma ri zes the effi ca cy or current s ta tus of theophyl l i ne i n pa rti cul a r, or
methyl xa nthi nes i n genera l , i n s uch pa ti ents a s thi s ?
a . Dos i ng i s s i mpl e a nd conveni ent, ra rel y needs to be a djus ted
b. Excel l ent a l terna ti ve to a n i nha l ed s teroi d for res cue thera py
c. Is , a t bes t, a s econd- or thi rd-l i ne a gent for l ong-term a s thma control
d. Pos s es s es s trong a nd cl i ni ca l l y us eful a nti -i nfl a mma tory a cti vi ty
e. Seda ti on i s a ma jor s i de effect, even wi th thera peuti c dos es or bl ood l evel s
297. An el derl y ma n wi th COPD i s bei ng ma na ged wi th s evera l drugs , one of whi ch i s i nha l ed i pra tropi um. Wha t i s the ma i n mecha ni s m tha t
a ccounts for the benefi ci a l effects of thi s drug?
a . Bl ocks receptors upon whi ch a n endogenous bronchocons tri ctor medi a tor a cts
b. Enha nces epi nephri ne rel ea s e from the a drena l medul l a
c. Inhi bi ts cAMP brea kdown vi a phos phodi es tera s e i nhi bi ti on
d. Prevents a nti gen-a nti body rea cti ons tha t l ea d to ma s t cel l medi a tor rel ea s e
e. Sti mul a tes venti l a tory ra tes (CNS effect i n bra i ns medul l a )

f. Suppres s es s ynthes i s a nd rel ea s e of i nfl a mma tory medi a tors

298. A 16-yea r-ol d gi rl trea ted for a s thma devel ops drug-i nduced s kel eta l mus cl e tremors . Wha t wa s the mos t l i kel y ca us e?
a . Al buterol
b. Becl ometha s one
c. Cromol yn
d. Ipra tropi um
e. Montel uka s t
299. A 26-yea r-ol d pa ti ent wi th a s thma i s bei ng trea ted wi th montel uka s t. Wha t i s the ma i n mecha ni s m by whi ch thi s drug works ?
a . Bl ocks receptors for certa i n proi nfl a mma tory a nd bronchocons tri ctor a ra chi doni c a ci d meta bol i tes
b. Enha nces rel ea s e of epi nephri ne from the a drena l (s upra rena l ) medul l a
c. Increa s es a i rwa y -a drenergi c receptor res pons i venes s to endogenous norepi nephri ne
d. Inhi bi ts cAMP brea kdown vi a phos phodi es tera s e i nhi bi ti on
e. Prevents a nti gen-a nti body rea cti ons tha t l ea d to ma s t cel l medi a tor rel ea s e
f. Sti mul a tes venti l a tory ra tes (CNS effect i n bra i ns medul l a )
300. An el derl y ma n, i n obvi ous res pi ra tory di s tres s due to exa cerba ti on of hi s emphys ema a nd chroni c bronchi ti s (COPD), pres ents i n the
emergency depa rtment. One drug ordered by the phys i ci a n, to be a dmi ni s tered by the res pi ra tory thera pi s t, i s N-a cetyl cys tei ne. Wha t i s the ma i n
a cti on or purpos e of thi s drug?
a . Bl ocks receptors for the cys tei nyl l eukotri enes
b. Inhi bi ts meta bol i c i na cti va ti on of epi nephri ne or 2 a goni s ts tha t were a dmi ni s tered
c. Inhi bi ts l eukotri ene s ynthes i s
d. Promptl y s uppres s es a i rwa y i nfl a mma ti on
e. Revers es ACh-medi a ted bronchocons tri cti on
f. Thi ns a i rwa y mucus s ecreti ons for ea s i er remova l by s ucti oni ng or pos tura l dra i na ge
301. A 23-yea r-ol d woma n wi th a s thma ha s wha t i s des cri bed a s a s pi ri n (hyper)s ens i ti vi ty (tri a d a s thma ) a nd experi ences s evere bronchos pa s m
i n res pons e to even s ma l l dos es of the drug. Wha t i s the mos t l i kel y mecha ni s m by whi ch the a s pi ri n provoked her pul mona ry probl ems ?
a . Bl ocked s ynthes i s of endogenous pros ta gl a ndi ns tha t ha ve bronchodi l a tor a cti vi ty
b. Induced forma ti on of a nti bodi es di rected a ga i ns t the s a l i cyl a te on a i rwa y ma s t cel l s
c. Induced hypers ens i ti vi ty of H 1 receptors on a i rwa y s mooth mus cl es
d. Induced hypers ens i ti vi ty of mus ca ri ni c receptors on a i rwa y s mooth mus cl es
e. Prevented epi nephri ne bi ndi ng to 2 -a drenergi c receptors (a i rwa ys a nd el s ewhere)
302. A young boy i s di a gnos ed wi th a s thma . Hi s pri ma ry s ymptom i s frequent cough, not bronchos pa s m or wheezi ng. Other a s thma medi ca ti ons a re
s ta rted, but unti l thei r effects devel op ful l y we wi s h to s uppres s the cough wi thout runni ng a ri s k of s uppres s i ng venti l a tory dri ve or ca us i ng
s eda ti on or other unwa nted effects . Whi ch drug woul d meet thes e needs the bes t?
a . Codei ne
b. Dextromethorpha n
c. Di phenhydra mi ne
d. Hydrocodone
e. Prometha zi ne
303. A mother bri ngs her 10-yea r-ol d s on, who ha s a l ongs ta ndi ng hi s tory of poorl y control l ed a s thma , to the Emergency Depa rtment (ED). He i s i n a
rel a ti vel y ea rl y s ta ge of wha t wi l l prove to be a s evere a s thma a tta ck. Arteri a l bl ood ga s es ha ve not been a na l yzed yet, but i t i s obvi ous tha t the
l a d i s i n grea t di s tres s . He i s pa nti ng wi th grea t effort a t a ra te of a bout 60/mi n.
Gi ven the boys hi s tory a nd the l i kel y di a gnos i s of a cute a s thma , the hea l th ca re tea m a dmi ni s ters a l l the drugs l i s ted bel ow by the s ta ted
routes , a nd wi th the purpos es noted. The chi l ds condi ti on qui ckl y i mproves , a nd the tea m l ea ves the boy wi th hi s mother whi l e they go to ca re for
other ED pa ti ents . Wi thi n a coupl e of mi nutes , the mother comes out of her s ons cubi cl e fra nti ca l l y s crea mi ng hes s topped brea thi ng! Whi ch
drug mos t l i kel y preci pi ta ted the venti l a tory a rres t?
a . Al buterol , i nha l ed, gi ven by nebul i zer for prompt bronchodi l a ti on
b. Atropi ne, nebul i zed a nd i nha l ed
c. Mi da zol a m, IV, to norma l i ze venti l a tory ra te a nd a l l a y a nxi ety
d. Methyl predni s ol one (gl ucocorti cos teroi d), IV, for prompt s uppres s i on of a i rwa y i nfl a mma ti on
e. Norma l s a l i ne, nebul i zed a nd i nha l ed, to hydra te the a i rwa y mucos a e
304. You pres cri be a n ora l l y i nha l ed corti cos teroi d for a pa ti ent wi th a s thma . Previ ous l y s he wa s us i ng onl y a ra pi dl y a cti ng a drenergi c
bronchodi l a tor for both prophyl a xi s a nd trea tment of a cute a tta cks . She us ed the s teroi d a s di rected for 5 da ys , a nd then s topped ta ki ng i t. Wha t i s
the mos t l i kel y rea s on why the pa ti ent qui t us i ng the drug?
a . Di s turbi ng ta chyca rdi a a nd pa l pi ta ti ons occurred
b. Rel entl es s di a rrhea devel oped a fter jus t 1 da y of us i ng the s teroi d
c. She experi enced l i ttl e or no obvi ous i mprovement i n brea thi ng
d. The drug ca us ed extreme drows i nes s tha t i nterfered wi th da yti me a cti vi ti es

e. The drug ca us ed her to reta i n fl ui d a nd ga i n wei ght

305. A pa ti ent cons umes a n exces s i ve dos e of theophyl l i ne a nd devel ops toxi ci ty i n res pons e to the drug. Wha t i s the expected s i gn, s ymptom, or
other cons equence of thi s overdos e?
a . Bra dyca rdi a
b. Drows i nes s progres s i ng to s l eep a nd then coma
c. Hepa totoxi ci ty
d. Pa ra doxi ca l bronchos pa s m
e. Sei zures
306. Acetyl chol i nes tera s e i nhi bi tors , mus ca ri ni c a goni s ts s uch a s pi l oca rpi ne, a nd -bl ockers a re a mong the drugs us ed to ma na ge pa ti ents wi th
gl a ucoma . They a l s o s ha re properti es tha t a re pa rti cul a rl y rel eva nt to pa ti ents wi th a s thma . Whi ch s ta tement s umma ri zes bes t wha t tha t
rel eva nce i s ?
a . Contra i ndi ca ted, or pos e grea t ri s ks , for peopl e wi th a s thma
b. Degra nul a te ma s t cel l s , ca us e bronchocons tri cti on
c. Tend to ra i s e i ntra ocul a r pres s ure i n pa ti ents who ha ve both gl a ucoma a nd a s thma
d. Tri gger bronchocons tri cti on by di rectl y a cti va ti ng H 1 hi s ta mi ne receptors on a i rwa y s mooth mus cl e cel l s
e. Us eful for a cute a s thma , not for a mbul a tory pa ti ents
307. A pa ti ent s ufferi ng s ta tus a s thma ti cus pres ents i n the emergency depa rtment. Bl ood ga s es revea l s evere res pi ra tory a ci dos i s a nd hypoxi a .
Even l a rge pa rentera l dos es of a s el ecti ve 2 a goni s t fa i l to di l a te the a i rwa ys a dequa tel y; ra ther, they ca us e da ngerous degrees of ta chyca rdi a .
Whi ch pha rma col ogi c i nterventi on or a pproa ch i s mos t l i kel y to control the a cute s ymptoms a nd res tore the bronchodi l a tor effi ca cy of the
a drenergi c drug?
a . Gi ve a l i poxygena s e i nhi bi tor (eg, montel uka s t)
b. Gi ve a pa rentera l corti cos teroi d
c. Gi ve pa rentera l di phenhydra mi ne
d. Swi tch to epi nephri ne
e. Swi tch to i s oproterenol (1 /2 a goni s t)
308. The FDA ha s ma nda ted a wa rni ng a bout the i ncrea s ed ri s k of dea th i n a s thma pa ti ents ta ki ng recommended dos es of s a l meterol (or other
s l ow-/l ong-a cti ng a drenergi c a s thma control medi ca ti ons ) for too l ong a peri od of ti me. Wha t i s the mos t l i kel y mecha ni s m or phenomenon by
whi ch thi s fa ta l a dvers e res pons e, or other s evere a i rwa y res pons es , occur?
a . Ana phyl a xi s due to gra dua l forma ti on of a nti bodi es a ga i ns t the drug
b. Hypertens i ve cri s i s
c. Inhi bi ted s ynthes i s , rel ea s e, a nd a nti -i nfl a mma tory a cti ons of endogenous corti s ol
d. Pl uggi ng of the bronchi ol es wi th vi s cous mucus , due to the drugs a nti mus ca ri ni c a cti ons
e. Tol era nce of a i rwa y s mooth mus cl e cel l s to the effects of a drenergi c bronchodi l a tors
309. A hungry 8-yea r-ol d i s vi s i ti ng hi s gra ndpa rents hous e a nd s ees gra ndpa s pri nkl e s ome powder from a s ma l l foi l pa ck onto hi s a ppl es a uce.
Gra ndpa s mi l es a nd s a ys Mmmm, ta s tes good. The pa cket conta i ns a theophyl l i ne s a l t tha t wa s pres cri bed for hi s COPD. Li ki ng a ppl es a uce, a nd
thi nki ng the drug pa ckets conta i n ca ndy, the l a d opens the a ppl es a uce ja r, fi nds gra ndpa s s ta s h of dozens of theophyl l i ne pa ckets , a nd s pri nkl es
on l ots of drug before ea ti ng the whol e thi ng. Toxi ci ty ens ues . Wha t i s thi s chi l d mos t l i kel y to experi ence, a nd do s o before a nythi ng el s e
s i gni fi ca nt a nd untowa rd devel ops ?
a . Acute uri na ry retenti on
b. Bra dyca rdi a a nd hypotens i on
c. Irri ta bi l i ty, other s i gns /s ymptoms of CNS s ti mul a ti on, pos s i bl y s ei zures
d. Is chemi c s troke from drug-i nduced pl a tel et a ggrega ti on
e. Venti l a tory s uppres s i on (centra l l y medi a ted) l ea di ng to res pi ra tory a ci dos i s a nd a pnea

Respiratory System Pharmacology: Asthma and COPD

Answers
292. The answer is a. (Brunton, pp 302, 1035-1040; Katzung, pp 144, 339-357.) Thi s pa ti ent certa i nl y s eems to ha ve recurrent epi s odes of a s thma . Even i f
they a re mi l d a nd os tens i bl y res pons i ve to a n i nha l ed 2 a goni s t, s hes not bei ng trea ted properl y. She or her pri or pres cri ber ha s been overrel i a nt on, a nd overus i ng, a medi ca ti on tha t onl y ma na ges s ymptoms (a nd not wel l i n her ca s e) a nd does not a ddres s the underl yi ng ca us e, whi ch
i s a i rwa y i nfl a mma ti on. (Some phys i ci a ns defi ne overus e of a n i nha l ed a drenergi c bronchodi l a tor more tha n once a da y; the NIH s a ys needi ng to
us e i t more tha n twi ce a week i s overus e.) Rea s ona bl e opti ons for her woul d be to pres cri be a n i nha l ed corti cos teroi d (becl ometha s one, others ),
s i nce s he reports onl y mi l d s ymptoms . (Of cours e, pul mona ry functi on tes ts [PFTs ] s houl d be done.) If her bouts become more s evere or frequent,
then a n ora l s teroi d (eg, predni s one) mi ght be pres cri bed for a whi l e, wi th a proper s wi tch to a n i nha l ed s teroi d.
The PFTs mi ght be rea s ona bl y norma l (b), but tha t depends on s uch fa ctors a s when s he us ed her i nha l er l a s t, a nd whether s he i s s i mpl y ha vi ng
a good da y (eg, no expos ure toda y to a l l ergens , etc). A s i ngl e norma l PFT i n a pa ti ent who des cri bes frequent need for a bronchodi l a tor does not
rul e out a s thma . Lets us e a n a na l ogy tha t a ppl i es to ma ny a s thma pa ti ents . You a re s ta ndi ng ri ght on the edge of a thous a nd-foot drop-off on the
ri m of the Gra nd Ca nyon. Onl y a coupl e of i nches from a ba d tri p down. Ta ke jus t one l i ttl e s tep forwa rd a nd youre a goner. Sa me wi th a s thma : you
ma y be feel i ng good wi th current medi ca ti ons , but jus t a l i ttl e provoca ti on of a i rwa y i nfl a mma ti on a nd bronchocons tri cti on a nd s evere
s ymptoms , pos s i bl y neces s i ta ti ng i ntuba ti on or l ea di ng to a fa ta l a tta ck, ca n put the pa ti ent over the proverbi a l edge.
Pa ti ents wi th a s thma tend not to do wel l i n col d tempera tures (c). Brea thi ng col d a i r often provokes bronchos pa s m (proba bl y medi a ted by
i ncrea s ed pa ra s ympa theti c effects on a i rwa y s mooth mus cl e). (Ha ve you ever ta ken a deep brea th when the tempera tures a re nea r or bel ow zero?)
Convers el y, a s thma ti cs tend to do wel l when i t i s wa rm a nd humi d. (Ever noti ced how ma ny a thl etes wi th a s thma tend to gra vi ta te to s ports tha t
provi de a wa rm, humi d envi ronment, eg, s wi mmi ng?) Fi na l l y, 2 a goni s ts do not ca us e bra dyca rdi a or i ncrea s es of peri phera l res i s ta nce.
Mus ca ri ni c a goni s ts or -bl ockers woul d ca us e the former, a goni s ts the l a tter.
293. The answer is c. (Brunton, pp 173, 196-200, 287-288; Katzung, pp 138-148, 341-344, 352-353.) Reca l l tha t a drenergi c bronchodi l a ti on requi res
a cti va ti on of 2 -a drenergi c receptors on a i rwa y s mooth mus cl e cel l s . Norepi nephri ne i s a n a nd 1 a goni s t, wi th no a bi l i ty to a cti va te 2 receptors ,
a nd s o i t ha s no bronchodi l a tor a cti vi ty. Al buterol (a ), a 2 a goni s t, ca n be cons i dered the prototype of ra pi dl y a cti ng a drenergi c bronchodi l a tors
us ed for a s thma (prophyl a xi s /control , but ma i nl y res cue thera py). Epi nephri ne (b) i s a very effi ca ci ous bronchodi l a tor, but i ts us e for routi ne
ma na gement of a s thma i s cons i dera bl y l i mi ted due to i ts a bi l i ty to ca us e va s ocons tri cti on (-a goni s t a cti vi ty) a nd ca rdi a c s ti mul a ti on (1 a goni s t
a cti vi ty). In terms of pul mona ry probl ems , i t i s res erved ma i nl y for ma na gi ng a na phyl a xi s or s ta tus a s thma ti cus , but i t i ndeed ca us es bronchodi l a ti on wel l a nd promptl y. Sa l meterol (d) i s a a goni s t a l s o. Gi ven by i nha l a ti on, i ts bronchodi l a tor effects a re s l ow i n ons et, but i t ha s a l ong
dura ti on compa red wi th s i mi l a rl y cl a s s i fi ed drugs s uch a s a l buterol . Thus , s a l meterol i s a n effi ca ci ous bronchodi l a tor, but not s ui ta bl e for prompt
effects (res cue thera py). Terbuta l i ne (c) i s cl a s s i fi ed a s a ra pi dl y a cti ng 2 a goni s t, s i mi l a r to a l buterol . However, i t i s s el dom us ed a ny more,
whether a s a n a drenergi c bronchodi l a tor or for i ts other ma i n us e a s a uteri ne rel a xa nt to hel p ma na ge prema ture l a bor. Theophyl l i ne (f) ha s
modes t bronchodi l a tor a cti vi ty, but i t i s not a n a drenergi c a goni s t. It i nhi bi ts phos phodi es tera s e, a nd s o i nhi bi ts meta bol i c i na cti va ti on of c-AMP
(the s econd mes s enger formed by a drenergi c bronchodi l a tors i n a i rwa y s mooth mus cl e).
294. The answer is c. (Brunton, pp 292f, 293, 322t; Katzung, pp 341-344, 352-353.) If you were to deci de to us e s a l meterol i n thi s s i tua ti on, i t woul d be
bes t to cons i der i t a s a n a dd-on. Reca l l tha t s a l meterol , l i ke a l buterol , i s ma i nl y a 2 a goni s t, but s a l meterol s ons et of a cti on i s much s l ower, i ts
dura ti on of a cti on much l onger. The s l ow ons et of s a l meterol ma kes i t a us eful prophyl a cti c a gent for s ome pa ti ents , but renders i t compl etel y
i na ppropri a te for res cue thera py (a , e). It ca n be a dmi ni s tered s epa ra tel y, or the phys i ci a n mi ght pres cri be one of the propri eta ry fi xed-dos e
combi na ti on products tha t conta i n both s a l meterol a nd a s teroi d (gi ven by ora l i nha l a ti on). One coul d rea s ona bl y a rgue tha t s a l meterol i s a l s o
da ngerous i f us ed a s the s ol e i nterventi on for res cue, beca us e s eri ous venti l a tory compromi s e ca n devel op before i ts bronchodi l a tor effects
devel op. The pa ti ent des cri bed needs a corti cos teroi d. You mi ght i ncrea s e the dos e of the i nha l ed s teroi d a s a s ta rt, or perha ps try a burs t of a n
ora l s teroi d (eg, predni s one) for a whi l e. Rega rdl es s , us i ng s a l meterol a s a replacement for a ny corti cos teroi d (b) or for a l l the other current
medi ca ti ons (d) i s l i kel y to provoke more a nd more s evere a s thma a tta cks . Indeed, current gui del i nes a re tha t i f s a l meterol or a nother l ong-a cti ng
a goni s t i s us ed, i t mus t be us ed a s a n a djunct to a corti cos teroi d. Remember: The key to s ucces s i n a s thma thera py l ong-term requi res
control l i ng a i rwa y i nfl a mma ti on, a nd corti cos teroi ds a re the key drugs for doi ng jus t tha t.
295. The answer is d. (Brunton, pp 1054-1055; Katzung, pp 350, 993.) The mos t s eri ous a dvers e res pons e to oma l i zuma b, a monocl ona l a nti body di rected
a ga i ns t IgE, i s a n a na phyl a cti c rea cti on (often s evere, l es s often fa ta l ). Thes e a dvers e rea cti ons us ua l l y (not a l wa ys !) occur a fter the fi rs t dos e, a nd
us ua l l y wi thi n 2 hours of i njecti on. Thi s i s one rea s on why pa ti ents s houl d recei ve the drug onl y i n a control l ed hea l th ca re s etti ng a nd s houl d
be under obs erva ti on for a t l ea s t 2 hours therea fter. Nonethel es s , a na phyl a xi s or l es s s evere untowa rd i mmunol ogi c rea cti ons ha ve been reported
24 hours or l onger, a nd s o the pa ti ent s houl d ha ve a n epi nephri ne a utoi njector (s el f-i njector) (pres cri bed or di s pens ed by the phys i ci a n) ha ndy for
a t l ea s t s evera l da ys a fter a n oma l i zuma b dos e. The ri s k of a na phyl a xi s i s a l s o a ma jor rea s on why the drug s houl d be us ed onl y for pa ti ents who
ha ve s evere a s thma not a dequa tel y control l ed wi th other drugs (a drenergi c bronchodi l a tors , l eukotri ene receptor bl ockers , corti cos teroi ds ).
As noted, the a nti body i s di rected a ga i ns t IgE. The IgE-oma l i zuma b compl ex then prevents IgE from bi ndi ng to ma s t cel l a nd ba s ophi l
membra nes , whi ch otherwi s e woul d tri gger a l l ergen-medi a ted cel l a cti va ti on. Oma l i zuma b does not bi nd other l i ga nds (eg, ACh or hi s ta mi ne; a ),
nor does i t a l ter the effects of thos e bronchocons tri ctor a goni s ts i n a ny other wa y. It a l s o ha s no i ntri ns i c or di rect bronchodi l a tor a cti vi ty.
Owi ng to the a na phyl a xi s ri s k, the drugs s l ow ons et of a cti on, a nd i ts l a ck of bronchodi l a tor a cti vi ty, oma l i zuma b i s not, nor ever wi l l be, fi rs tl i ne thera py for a s thma (e), whether mi l d or s evere, frequent or not. It wi l l never be a s ubs ti tute for a ra pi dl y a cti ng a drenergi c bronchodi l a tor for
res cue thera py (c). And pri or or current us e of a ny of the tra di ti ona l a s thma medi ca ti ons does not contra i ndi ca te (b) a tri a l wi th oma l i zuma b.
Indeed, owi ng to oma l i zuma bs s l ow ons et, conti nued a nd otherwi s e proper corti cos teroi d thera py to s uppres s a i rwa y i nfl a mma ti on i s es s enti a l .
296. The answer is c. (Brunton, pp 821t, 1040-1044, 1534; Katzung, pp 344-346, 1037-1038, 1161t.) Theophyl l i ne, the prototype methyl xa nthi ne, i s a n ora l
bronchodi l a tor tha t ha s s ome benefi ci a l pul mona ry effects i n pa ti ents wi th a s thma or COPD. We dont know preci s el y how i t exerts i ts
bronchodi l a tor a cti vi ty, a t l ea s t a t concentra ti ons found i n huma n bei ngs (i n vi tro i t i nhi bi ts phos phodi es tera s e, pres ervi ng cAMP l evel s ; i t a l s o
bl ocks receptors for a denos i ne, whi ch ha s bronchocons tri ctor a cti vi ty).
However, there a re s eri ous probl ems wi th thi s ol d drug tha t rel ega te i t to s econd or thi rd s ta tus i n thera py; tha t render i t a drug tha t s houl d be
pres cri bed onl y by pul monol ogi s ts who a re qui te fa mi l i a r wi th the l i mi ta ti ons , s i de effects , a nd toxi ci ty; a nd tha t ma ke i ts us e a s pri ma ry thera py
for a s thma us ua l l y i na ppropri a te (a t bes t).

Theophyl l i ne (a nd other methyl xa nthi nes ) ha s a very l ow thera peuti c i ndex: i t i s a l l too ea s y (whether beca us e of drug-drug i ntera cti ons , or
s i mpl y i mproper dos i ng) to ha ve bl ood l evel s ri s e i nto a ra nge tha t ca n ca us e toxi ci ty (ma i nl y exces s i ve ca rdi a c a nd CNS s ti mul a ti on, wi th the
potenti a l for a rrhythmi a s or s ei zures ). Moreover, a nd beca us e of the probl ems s ta ted a bove, frequent bl ood tes ti ng i s neces s a ry i n order to get,
a nd keep, pl a s ma l evel s wi thi n a n a ccepta bl e thera peuti c ra nge a nd hopeful l y a voi d s ubthera peuti c or toxi c bl ood l evel s . The drug depends on
hepa ti c P450 s ta tus for i ts el i mi na ti on, a nd tha t ma kes el i mi na ti on very ea s i l y i nfl uenced by l i ver dys functi on or other i ntera cti ng drugs tha t ca n
ei ther i nduce or i nhi bi t i ts meta bol i s m.
Mos t i mporta nt i s the fa ct tha t theophyl l i ne ha s no a nti -i nfl a mma tory a cti vi ty; a s I s a i d, i f we a re trea ti ng a s thma l ong-term, the s ecret to
s ucces s i s control l i ng a i rwa y i nfl a mma ti on. For our founda ti on we us e corti cos teroi ds to s uppres s i nfl a mma ti on.
If we were dea l i ng wi th COPD a nd the goa l i s bronchodi l a ti on (i t i s ), s uch drugs a s i pra tropi um (i nha l ed a nti mus ca ri ni c) a re not onl y more
effi ca ci ous tha n a methyl xa nthi ne or a n a drenergi c bronchodi l a tor but a l s o a s s oci a ted wi th fewer dos i ng probl ems , moni tori ng needs , a nd s i de
effects . In COPD the pa thophys i ol ogy i nvol ves not onl y bronchocons tri cti on but a l s o gobl et cel l hyperpl a s i a , l ea di ng to i ncrea s ed mucus
producti on. Such drugs a s i pra tropi um a re, therefore, us ua l l y a fi rs t choi ce a nd us ua l l y i mprove s ymptoms a nd pul mona ry functi on tes ts the mos t.
297. The answer is a. (Brunton, pp 231, 1044-1046; Katzung, pp 121, 127, 347, 353, 355.) You s houl d be a bl e to deduce qui ckl y (i f not s i mpl y know outri ght)
tha t i pra tropi um i s a n a tropi ne-l i ke druga n a nti mus ca ri ni c tha t bl ocks the bronchocons tri ctor effect of ACh on a i rwa y s mooth mus cl e. It i s a
qua terna ry, i nha l ed a nti mus ca ri ni c: tha t i s , i t a cts l oca l l y i n the a i rwa ys , a nd very l i ttl e of the a l wa ys cha rged mol ecul e di ffus es i nto the
ci rcul a ti on to ca us e s ys temi c effects . Ipra tropi um ha s no effects on the a drena l medul l a , on ma s t cel l s or other el ements of the i nfl a mma tory
res pons e, or i n the CNS. Ipra tropi um i s a pproved for ma na gi ng COPD, but i s often us ed for s ome a s thma pa ti ents . The drug ha s a ra pi d ons et of
a cti on. However, s ome s tudi es i ndi ca te tha t i t i s not a s effi ca ci ous a bronchodi l a tor a s 2 a goni s ts , a nd s o i t i s not a s ui ta bl e a gent for res cue
thera py. Fi na l l y, the bronchodi l a tor effects of i pra tropi um a nd a goni s ts a re s ynergi s ti c (s a me effect, di fferent mecha ni s ms ), a nd s o theres s ome
l ogi c to us i ng them both.
298. The answer is a. (Brunton, pp 206t, 291, 302, 1035-1040; Katzung, pp 145, 341-344, 355.) Of the drugs l i s ted i n the ques ti on, s kel eta l mus cl e tremor i s
a s i de effect mos t often a s s oci a ted wi th 2 -a drenergi c a goni s ts a l buterol a nd others . It i s a l mos t a l wa ys a dos e-dependent phenomenon. (Note:
Some phys i ci a ns ti tra te the dos e of a drenergi c bronchodi l a tors upwa rd, s toppi ng when tremors devel op a nd equa ti ng the bl ood l evel a s s oci a ted
wi th tha t dos e a s bei ng thera peuti c wi th res pect to control l i ng the pul mona ry di s ea s e. The wi s dom of tha t i s ques ti ona bl e; proper dos a ge
a djus tments or other thera py cha nges s houl d be ba s ed on pul mona ry s ymptom rel i ef [s ubjecti ve a s s es s ment] i n genera l a nd, i dea l l y, qua nti ta ti ve
pul mona ry functi on tes ts .) None of the other drugs l i s ted i s a s s oci a ted wi th s kel eta l mus cl e tremor. Becl ometha s one (b) i s a n i nha l ed
corti cos teroi d; cromol yn (c), a l s o i nha l ed for a s thma , reduces ma s t cel l degra nul a ti on; i pra tropi um (d) i s a n i nha l ed a nti mus ca ri ni c i ndi ca ted for
COPD; montel uka s t (e) i s a l eukotri ene receptor bl ocker tha t i s a l s o i ndi ca ted for a s thma prophyl a xi s .
299. The answer is a. (Brunton, pp 942, 1052-1054; Katzung, pp 328, 339-357.) Montel uka s t (a nd a rel a ted drug, za fi rl uka s t) bl ocks receptors for
l eukotri enes (LTs ). (When you s ee l euk or l uk a s pa rt of thes e drugs generi c na mes , thi nk l eukotri enes or l eukotri ene modi fi ers , a nd thi nk of
drugs for a s thma .)
Reca l l tha t the LTs a re proi nfl a mma tory a nd bronchocons tri ctor medi a tors formed a s pa rt of norma l a ra chi doni c a ci d meta bol i s m vi a the 5l i poxygena s e pa thwa y. LTs a l s o pa rti ci pa te i n recrui ti ng eos i nophi l s to the i nfl a med regi ons (reca l l tha t l oca l eos i nophi l i a i s often a n
a ccompa ni ment of a s thma ), thereby bl unti ng the l oca l i nfl a mma tory proces s es i n yet a nother wa y.
In the context of a s thma thera py l eukotri ene receptor bl ockers a re i ndi ca ted for prophyl a xi s (control thera py) onl y, a nd s houl d not be us ed i n
l i eu of corti cos teroi ds (ora l or ora l l y i nha l ed) when corti cos teroi ds a re s ui ta bl e (whi ch i s mos t of the ti me). They wi l l do vi rtua l l y no good i n a
s hort enough ti me i f they were a dmi ni s tered to s uppres s ongoi ng bronchocons tri cti on (eg, for res cue thera py), ma i nl y beca us e they a re too s l owa cti ng. Its worth noti ng tha t a l though montel uka s t works wel l a s a control medi ca ti on for ma ny a s thma pa ti ents , i t i s not a pa na cea . For a bout
50% of a s thma pa ti ents i ts effi ca cy a ppea rs to be no better tha n pl a cebo.
The l eukotri ene modi fi ers do not enha nce epi nephri ne rel ea s e from the a drena l medul l a (b), i ncrea s e -a drenergi c receptor res pons i venes s (c;
note tha t norepi nephri ne, menti oned i n the ques ti on, ha s no bronchodi l a tor a cti vi ty beca us e i t i s not a 2 a goni s t), i nhi bi t phos phodi es tera s e (d),
or i nterfere wi th ma s t cel l functi on or ma s t cel l res pons i venes s to a nti gens (e).
Note: Remember the two other ma i n cl a s s es of drugs tha t a ffect ei ther the forma ti on or brea kdown of a ra chi doni c a ci d. The cycl ooxygena s e
pa thwa y(s ) meta bol i ze a ra chi doni c a ci d to form va ri ous pros ta gl a ndi ns , pros ta cycl i n (PGI 2 ), a nd thromboxa nes (eg, thromboxa ne A2 ). The
cycl ooxygena s es a re i nhi bi ted by the tra di ti ona l nons teroi da l a nti -i nfl a mma tory drugs , of whi ch a s pi ri n i s a rea s ona bl e a nd common exa mpl e.
The (gl uco) corti cos teroi ds work ups trea m of both l i poxygena s e a nd cycl ooxygena s e. They i nhi bi t the forma ti on of a ra chi doni c a ci d by i nhi bi ti ng
phos phol i pa s e a cti vi ty, whi ch thereby removes s ubs tra te for both l i poxygena s e a nd cycl ooxygena s e meta bol i s m.
300. The answer is f. (Brunton, p 1057; Katzung, p 1033t.) You s houl d know N-a cetyl cys tei ne a s a n a nti dote for a ceta mi nophen poi s oni ng. When us ed
for tha t purpos e, i t i s gi ven ora l l y or i ntra venous l y. The s ul fhydryl groups tha t a re pa rt of the mol ecul e a re i mporta nt, a s they rea ct wi th the toxi c
a ceta mi nophen meta bol i te a nd s pa re gl uta thi one-depl eted hepa tocytes from oxi da ti ve a tta ck. N-Acetyl cys tei ne i s a l s o a mucol yti c (mucus thi nni ng) drug, gi ven by i nha l a ti on i n a nebul i zed s ol uti on or by i ntra tra chea l i ns ti l l a ti on, to reduce the vi s cos i ty of a i rwa y mucus tha t ca n then be
removed ea s i er by coughi ng, pos tura l dra i na ge a nd ches t percus s i on, or a i rwa y s ucti oni ng. Here, too, the mecha ni s m i s ba s ed on i ts -SH-ri ch
compos i ti on. N-Acetyl cys tei ne l a cks other a i rwa y effects s uch a s bronchodi l a ti on or s uppres s i on or i nfl a mma ti on.
301. The answer is a. (Brunton, pp 947, 964; Katzung, pp 339-357.) As pi ri n, the prototype of the nons teroi da l a nti -i nfl a mma tory drugs (NSAIDs ), i nhi bi ts
cycl ooxygena s es (COX-1 a nd -2) a nd the a ra chi doni c a ci d ca s ca de. One outcome of tha t i s i nhi bi ted s ynthes i s of PGE2 . The PGE2 (a l ong wi th
ci rcul a ti ng epi nephri ne) i s a phys i ol ogi ca l l y i mporta nt endogenous bronchodi l a tor tha t i s pa rti cul a rl y i mporta nt to ma i nta i n a i rwa y pa tency
(di l a ti on) for mos t a s thma ti cs . Inhi bi t thi s s ynthes i s , wi th a s pi ri n or a nother nons el ecti ve cycl ooxygena s e i nhi bi tor/NSAID, a nd
bronchocons tri cti on or bronchos pa s m ma y ens ue i n tha t popul a ti on of a s thma ti cs who often a re exqui s i tel y s ens i ti ve to thes e drugs . Thi s a s pi ri n
hypers ens i ti vi ty phenomenon i s rel a ti vel y uncommon i n chi l dren wi th a s thma , but more preva l ent i n a dul ts . Es ti ma tes a re tha t i t a ffects between
10% a nd 25% of a dul t a s thma ti cs wi th s o-ca l l ed tri a d a s thma : a s thma pl us na s a l pol yps , chroni c urti ca ri a , a nd the NSAID s ens i ti vi ty.
Vi rtua l l y a l l other NSAIDs tha t nons el ecti vel y i nhi bi t COX-1 a nd -2 ma y cros s -rea ct, a l though the i nci dence of s evere pul mona ry rea cti ons s eems
the hi ghes t wi th a s pi ri n i ts el f. Sel ecti ve COX-2 i nhi bi tors (i e, cel ecoxi b) pos e l es s of a probl em beca us e they a re l es s l i kel y to i nhi bi t the
bronchodi l a tor pros ta gl a ndi ns tha t a re formed by the COX-1 pa thwa y, but they a re not a bs ol utel y free from the potenti a l probl em. If one needs a
drug to ma na ge fever or mi l d pa i n i n a n a s thma ti c, a ceta mi nophen i s preferred: i t does not cros s -rea ct. Owi ng to negl i gi bl e effects on
pros ta gl a ndi n s ynthes i s vi a cycl ooxygena s e-dependent pa thwa ys , i t i s not cl a s s i fi ed a s a n NSAID.
302. The answer is b. (Brunton, p 516; Katzung, p 559.) Dextromethorpha n i s a centra l l y a cti ng a nti tus s i ve drug tha t i s a bout a s effi ca ci ous a cough

s uppres s a nt a s codei ne. It i s thought to s uppres s the va ga l a fferent neura l pa thwa y i nvol ved i n the cough refl ex. However, unl i ke codei ne (c) a nd
hydrocodone (d; a nother us eful a nti tus s i ve i n s ome ca s es ), dextromethorpha n i s not a n opi oi d a nd l a cks a na l ges i c effects or the potenti a l for
venti l a tory s uppres s i on or a bus e.
Di phenhydra mi ne (c) a nd prometha zi ne (e) a l s o ha ve a nti tus s i ve a cti on. However, they, too, ca n ca us e genera l i zed CNS a nd venti l a tory
depres s i on. They a l s o exert s i gni fi ca nt a nti mus ca ri ni c effects , but nei ther i s a preferred or even frequentl y us ed drug for cough s uppres s i on i n
mos t pa ti ents , a nd i n a s thma pa ti ents i n genera l . Al though the a tropi ne-l i ke effects of thes e drugs ma y be benefi ci a l i n terms of i nhi bi ti ng AChmedi a ted bronchocons tri cti on i n a pa ti ent wi th a s thma , they ma y a l s o ca us e thi ckeni ng of a i rwa y mucus , fa vori ng pl uggi ng of the a i rwa ys wi th
vi s cous mucus depos i ts tha t ca nnot be removed norma l l y by mucoci l i a ry tra ns port or by coughi ng. Tha t i s , the benefi ts of bronchodi l a ti on ma y be
outwei ghed by the ri s ks of mucus pl uggi ng i n s ome a s thma pa ti ents .
303. The answer is c. (Brunton, pp 458-468, 552-553; Katzung, pp 339-357, 549-552.) As i de from the mi da zol a m, a ny, i f not a l l , the other drugs l i s ted woul d
be a ppropri a te for thi s pa ti ent. The term a s thma deri ves from a Greek word tha t mea ns , l i tera l l y, to pa nt. In s evere a s thma a tta cks s uch a s the
one des cri bed here the hyperpnea precedes the l i kel y devel opment of venti l a tory depres s i on a nd, i n s ome ca s es , venti l a tory a rres t. Thi s
i ncrea s ed venti l a tory ra te i s es s enti a l . It i s a s ometi mes s ucces s ful yet too often i na dequa te compens a tory phys i ol ogi c res pons e el i ci ted to
i ncrea s e venti l a tory oxygen upta ke a nd el i mi na te exces s CO2 (a l though i t ma y be i ns uffi ci ent to ra i s e a rteri a l O2 s a tura ti on a dequa tel y a nd more
tha n s uffi ci ent to i nduce meta bol i c a l ka l os i s from exces s CO2 l os s ). Nonethel es s , i t i s a protecti ve venti l a tory res pons e, a nd brea thi ng too
qui ckl y, even i neffi ci entl y, i s better tha n not brea thi ng a t a l l .
Thi s l ea ds to a n a dmoni ti on: Never gi ve a drug tha t ca n depres s venti l a ti on or the norma l venti l a tory dri ve to a n a s thma pa ti ent unl es s he or
s he ha s a protected a i rwa y a nd venti l a ti on ca n be control l ed a nd s upported mecha ni ca l l y. IV mi da zol a m (or the IV a dmi ni s tra ti on of vi rtua l l y a ny
other benzodi a zepi ne, or, es peci a l l y a n opi oi d) wi l l a l l a y a nxi ety, but wi l l a l s o tend to s uppres s venti l a tory dri ve a nd ha s ten the ons et of
venti l a tory a rres t. In the s cena ri o des cri bed here, di a zepa m i s the wrong drug to gi ve.
Al buterol (a ) or a s i mi l a r 2 -a goni s t bronchodi l a tor, whether gi ven by i nha l a ti on or pa rentera l l y, woul d not be expected to wors en the boys
venti l a tory s ta tus . They s houl d not be the onl y drugs rel i ed-on, but they woul d be a ppropri a te a djuncti ve trea tments , a s woul d be a l l the res t for
the s ta ted purpos es . As a n i mporta nt a s i de, you ma y reca l l tha t a tropi ne (b) a nd other drugs wi th a nti mus ca ri ni c a cti vi ty ha ve bronchodi l a tor
a cti vi ty, but a l s o tend to ma ke a i rwa y mucus s ecreti ons more vi s cous , l ea di ng to a i rwa y mucus pl uggi ng. In the context of thi s s cena ri o, wi th the
a dmi ni s tra ti on of other drugs tha t I l i s ted, a nd the a va i l a bi l i ty of a i rwa y s ucti oni ng devi ces a s needed, the mucus -thi ckeni ng effects of a n
a nti mus ca ri ni c s houl d not be a probl em wi th whi ch we ca nnot ea s i l y dea l by wa y of a i rwa y s ucti oni ng a nd the a dmi ni s tra ti on of mucus -thi nni ng
(mucol yti c) drugs . Gl ucocorti coi ds (d) a nd nebul i zed s a l i ne woul d be va l ua bl e, i f not es s enti a l , a djuncts to thi s boys thera py.
304. The answer is c. (Brunton, pp 1046-1052; Katzung, pp 351-353.) It us ua l l y ta kes a coupl e of weeks of i nha l ed corti cos teroi d us e a s di rected to
s uppres s a i rwa y i nfl a mma ti on, a nd the res ul ti ng bronchocons tri cti on, wel l enough tha t the pa ti ent ca n s ens e cl i ni ca l i mprovement (fewer or
mi l der a s thma s ymptoms ). Unl es s the pa ti ent i s forewa rned a bout thi s s l ow ons et, a nd urged to rema i n compl i a nt, they a re l i kel y to bel i eve the
drug i s i neffecti ve a nd therefore not worth ta ki ng. Cl ea rl y, i nha l ed corti cos teroi ds do not ca us e the obvi ous rus hthe prompt, dra ma ti c, a nd
unmi s ta ka bl e s ymptom rel i ef tha t typi ca l l y occurs wi th a drenergi c bronchodi l a tors . Nonethel es s , gi ven a dequa te ti me, the i nha l ed s teroi ds
us ua l l y prove to be the key to effecti ve l ong-term control of a s thma . Inha l ed corti cos teroi ds a ct l oca l l y; l i ttl e enters the s ys temi c ci rcul a ti on; s uch
s i de effects a s fl ui d retenti on, wei ght ga i n (e), a nd hypergl ycemi a , whi ch a re typi ca l wi th s ys temi c s teroi ds (eg, predni s one), ra rel y occur or
become probl ema ti c. Inha l ed s teroi ds do not ca us e ca rdi a c s ti mul a ti on (a ), di a rrhea (b), or drows i nes s (d).
305. The answer is e. (Brunton, pp 1040-1044; Katzung, pp 345-346.) Theophyl l i ne, a methyl xa nthi ne, i s a ca ffei ne-l i ke drug tha t i s becomi ng outmoded
a s thera py for a s thma i n mos t a dol es cents a nd a dul ts . It s houl d proba bl y not be pres cri bed by a ny phys i ci a n other tha n a pul monol ogi s t who i s
fa mi l i a r wi th the l i mi ta ti ons a nd probl ems wi th thi s cl a s s of drugs . A l ow ma rgi n of s a fety, extreme dependence on a dequa te l i ver functi on (for
meta bol i s m), s us cepti bi l i ty to numerous cl i ni ca l l y s i gni fi ca nt drug i ntera cti ons , a nd a l a ck of a i rwa y a nti -i nfl a mma tory a cti vi ty a re a mong the
rea s ons why. Wi thout proper dos a ge a djus tments a nd moni tori ng, i t i s a l l too ea s y, a nd common, for bl ood l evel s to fa l l i nto s ubthera peuti c
ra nges or, a s we s ee here, i nto toxi c ra nges . The ea rl i es t s i gns a nd s ymptoms of exces s i nvol ve CNS s ti mul a ti on (ji tteri nes s , tremors , di ffi cul ty
s l eepi ng, a nxi ety). As bl ood l evel s ri s e, the CNS i s i ncrea s i ngl y s ti mul a ted. Sei zures ma y occur, a nd when they do, the i na bi l i ty to brea the duri ng
the s ei zures i s the ma i n ca us e of dea th. Thus , a ns wer b i s i ncorrect.
Theophyl l i ne tends to ca us e ta chyca rdi a , i ncrea s es of ca rdi a c contra cti l i ty, a nd, potenti a l l y, ta chya rrhythmi a s . Thi s occurs ma i nl y beca us e
methyl xa nthi nes i nhi bi t phos phodi es tera s e, whi ch norma l l y meta bol i ca l l y i na cti va tes cAMP, the l evel s of whi ch a re i ncrea s ed i n s mooth a nd
ca rdi a c mus cl es by -a drenergi c a goni s ts . Bra dyca rdi a (a ) i s not a t a l l l i kel y. Theophyl l i ne i s not hepa totoxi c (c); i t does not ca us e pa ra doxi ca l
broncho-s pa s m (d), even when pl a s ma l evel s a re very hi gh or trul y toxi c.
306. The answer is a. (Brunton, pp 1005, 1008, 1031-1057; Katzung, pp 108-110.) By now you s houl d be a bl e to reca l l the cl a s s i fi ca ti ons a nd a cti ons of the
drugs l i s ted i n thi s ques ti on. Acetyl chol i nes tera s e i nhi bi tors a nd s uch mus ca ri ni c a goni s ts a s pi l oca rpi ne a re s ometi mes us ed a s topi ca l mi oti cs
for ma na gi ng gl a ucoma (ma i nl y a ngl e-cl os ure/na rrow a ngl e forms of the di s ea s e). Certa i n topi ca l -bl ockers a re us ed for open-a ngl e gl a ucoma ,
proba bl y worki ng by i nhi bi ti ng a queous humor producti on. However, a l l thes e drugs (a nd others i n thes e cl a s s es , us ed s ys temi ca l l y for a hos t of
other common medi ca l condi ti ons ) a re contra i ndi ca ted for a s thma pa ti ents even i f or when they a re us ed topi ca l l y on the eye(s ). An i mporta nt
el ement i n the pa thophys i ol ogy of a s thma i s a i rwa y s mooth-mus cl e hyperres pons i venes s to va ri ous bronchocons tri ctor s ti mul i , a nd mus ca ri ni c
receptor a cti va ti on i s cl ea rl y a phenomenon tha t l ea ds to often i ntens e bronchocons tri cti on.
You ma y reca l l tha t the chol i ne es ter, metha chol i ne, i s us ed to hel p di a gnos e a s thma when the di a gnos i s i s otherwi s e ques ti ona bl e. The ba s i s
of thi s metha chol i ne cha l l enge centers on the concept of a i rwa y hyperrea cti vi ty (i n thi s ca s e, to mus ca ri ni c a goni s ts ) i n a s thma ti cs . Very l ow
dos es of metha chol i ne a re gi ven, by i nha l a ti on, whi l e pul mona ry functi on tes ts a re recorded. As thma ti cs experi ence s i gni fi ca nt (s ometi mes
da ngerous ) bronchocons tri ctor res pons es to metha chol i ne dos es tha t a re fa r l ower tha n thos e tha t woul d provoke even s l i ght cha nges i n
nona s thma ti cs .
Reca l l tha t ACh es tera s e i nhi bi tors ca us e wha t a mounts to a bui l dup of ACh a t the neuroeffector juncti on, l ea di ng to hei ghtened mus ca ri ni c
receptor a cti va ti on. Thes e chol i nes tera s e i nhi bi tors , whether us ed for gl a ucoma or s uch other condi ti ons a s mya s theni a gra vi s , ca n ha ve l etha l
effects i n s ome a s thma pa ti ents . (Note, too, tha t chol i nes tera s e i nhi bi tors a re found i n s ome i ns ecti ci des , s o there i s a n extra a nd s i gni fi ca nt ri s k
to the a s thma pa ti ent i n a gri cul tura l or ga rdeni ng/l a wn ca re s etti ngs .) Mus ca ri ni c a goni s ts , whether thos e us ed for gl a ucoma or for s ti mul a ti ng
the gut or uri na ry tra ct (eg, betha nechol for functi ona l uri na ry retenti on), ma y prove l etha l too. Fi na l l y, a s thma ti cs tend to be extremel y dependent
on the bronchodi l a tor a cti ons of ci rcul a ti ng epi nephri ne. Bl ock the 2 receptors tha t medi a te tha t effect a nd the outcome ca n be di s a s trous . Even
the s o-ca l l ed ca rdi os el ecti ve -bl ockers (a tenol ol , metoprol ol ) ca n ca us e s eri ous probl ems for s ome a s thma ti cs . Tha t i s beca us e thei r a bi l i ty to
bl ock 1 receptors i s rel a ti ve a nd dos e-dependent, not a bs ol ute: they ma y pos e no pul mona ry probl ems for pers ons wi thout a s thma , but ma y be
dea dl y i n thos e who do.

307. The answer is b. (Brunton, pp 1046-1052; Katzung, pp 352-353.) When pul mona ry functi on deteri ora tes s o much tha t res pi ra tory a ci dos i s ens ues
(beca us e s uffi ci ent a mounts of CO2 a rent bei ng el i mi na ted by venti l a ti on) a nd s evere hypoxi a devel ops (beca us e of i na dequa te oxygen tra ns fer),
a cute tol era nce (i n es s ence, des ens i ti za ti on) devel ops to the bronchodi l a tor effects of drugs wi th 2 -a goni s t a cti vi tya l l of them. If thi s poi nt i s
forgotten, repea ted a dmi ni s tra ti on of a 2 a goni s t wi l l l ea d to i ncrea s i ng degrees of ca rdi a c s ti mul a ti on (ra te, contra cti l i ty, a utoma ti ci ty,
conducti on) beca us e under thes e condi ti ons they l os e thei r s el ecti vi ty for 2 receptors a nd a l s o begi n a cti va ti ng 1 receptors very effecti vel y. They
become i s oproterenol -l i ke i n thei r profi l es , a nd i s oproterenol (e) wi l l not be effi ca ci ous .
Even epi nephri ne (d) wont work a s a n effi ca ci ous bronchodi l a tor under thes e condi ti ons , a nd repea ted i njecti ons of i t wi l l do l i ttl e more tha n
ca us e further ca rdi a c s ti mul a ti on vi a 1 a cti va ti on, pl us va s ocons tri cti on owi ng to -a drenergi c receptor a cti va ti on. Through mecha ni s ms tha t a re
not qui te cl ea r, a dmi ni s teri ng s ui ta bl e dos es of a pa rentera l s teroi d under thes e condi ti ons of a ci dos i s a nd hypoxi a res tores a s ubs ta nti a l
degree of a i rwa y res pons i venes s to a goni s ts . Gi vi ng a s teroi d (pl us oxygen, whi ch hel ps correct the underl yi ng bl ood ga s a nd pH cha nges ) i s
es s enti a l .
Under thes e condi ti ons there i s l i ttl e l i kel i hood tha t the s evere a nd refra ctory a i rwa y probl ems i nvol ve exces s i ve a cti va ti on of a i rwa y
l eukotri ene receptors , a nd s o a dmi ni s teri ng a l i poxygena s e i nhi bi tor s uch a s montel uka s t (a ) wi l l be of l i ttl e va l ue. Gi vi ng di phenhydra mi ne (c),
even though i t bl ocks the bronchocons tri ctor effects of both ACh a nd hi s ta mi ne, wi l l not do much good for the a cute a nd l i fe-threa teni ng s i gns a nd
s ymptoms . Therefore, a pa rentera l corti cos teroi d, a dmi ni s tra ti on of oxygen, a nd s upport of venti l a ti on a s needed a re mos t l i kel y to ha ve the bes t
outcome.
308. The answer is e. (Brunton, pp 211-212, 302, 1035-1040; Katzung, pp 343-344, 355.) Long-term, more or l es s round-the-cl ock, expos ure of 2 -a drenergi c
receptors to a n a goni s t eventua l l y ca us es thos e receptors to l os e s ens i ti vi ty to thos e very drugs . The l os s of res pons i venes s to us ua l
bronchodi l a tor a cti ons tha t i s , a i rwa y s mooth mus cl e tol era ncea ffects res pons es not onl y to s a l meterol or the pha rma coki neti ca l l y s i mi l a r
drug, formoterol , but a l s o to a l buterol or s i mi l a r ra pi dl y a cti ng a drenergi c bronchodi l a tors typi ca l l y us ed for res cue thera py.
Of cours e, for mos t drugs overcomi ng tol era nce a nd res tori ng effects to a certa i n i ntens i ty ca n be a chi eved by i ncrea s i ng the dos e, the dos e
frequency, or both. Thi s i s preci s el y wha t a s thma pa ti ents who a re poorl y ma na ged do, es peci a l l y wi th thei r ra pi dl y a cti ng res cue i nha l ers
(a l buterol , etc): four or more puffs a t a ti me, ma ny ti mes ea ch 24 hours . Thus , the s ol uti on to the tol era nce, hi gher a nd more frequent dos es ,
a ctua l l y becomes the ca us e. And s o the us ua l outcome of exces s i ve or exces s i vel y prol onged a drenergi c bronchodi l a tor us e i s a fa s ter ons et a nd
progres s i on of tol era nce a nd a grea ter degree of tol era nce. Tha t i s , i ncrea s i ng dos e a nd/or frequency onl y ma kes ma tters wors e over the l ong run.
So, pa ti ents ta ki ng one or two 2 a goni s ts month a fter month gra dua l l y get l es s a nd l es s bronchodi l a ti on a nd s ymptom rel i ef over ti me; thei r
brea thi ng di ffi cul ty becomes wors e, a nd s houl d s evere bronchocons tri c-ti on occur, us ua l or even rel a ti vel y hi gh dos es of a ra pi dl y a cti ng (res cue)
bronchodi l a tor wi l l fa i l to work wel l , i f a t a l l . Us ua l l y thi s wi l l be a s s es s ed, cl i ni ca l l y, by di mi ni s hi ng i mprovement of forced expi ra tory vol ume i n 1
s econd (FEV1 ) i n res pons e to a ra pi dl y a cti ng a drenergi c bronchodi l a tor (eg, a l buterol ). Thus , the pa ti ent gets i n s evere venti l a tory di s tres s or ma y
even di e. Thus , wha t mi ght be ca l l ed a nti a s thma drugs ca n a ctua l l y l ea d to a s thma -rel a ted fa ta l i ti es under s ome condi ti ons .
Ans wer a i s i ncorrect; a nti bodi es a ga i ns t s a l meterol or other a drener-gi c bronchodi l a tors do not devel op. Ans wer b i s not a ccepta bl e. Al though
hi gh dos es of a s o-ca l l ed s el ecti ve 2 a goni s t ma y i ncrea s e bl ood pres s ure (a t hi gh bl ood l evel s s el ecti vi ty for 2 receptors i s l os t a nd 1
receptors ca n be a cti va ted, ra i s i ng bl ood pres s ure vi a i ncrea s es of both hea rt ra te a nd l eft ventri cul a r contra cti l i ty), a s i gni fi ca nt ri s e of pres s ure i s
very unl i kel y; hypertens i ve cri s i s wi l l not occur. Sa l meterol or other a drenergi c broncho-di l a tors ha ve no di rect or ma jor effects on corti s ol
s ynthes i s , rel ea s e, or a cti ons (c), nor do they ha ve a nti mus ca ri ni c effects , whether on mucus vi s cos i ty, a i rwa y s mooth mus cl e tone, or a ny other
proces s es medi a ted by mus ca ri ni c (chol i nergi c) receptors .
309. The answer is c. (Brunton, pp 138t, 1040-1044; Katzung, pp 344-346.) Theophyl l i ne (or the rel a ted drug a mi nophyl l i ne) i s cl a s s i fi ed a s a
methyl xa nthi ne, jus t l i ke the ca ffei ne a nd other methyl xa nthi nes i n your fa vori te coffee, tea , col a , or chocol a tes . So to a ns wer thi s ques ti on,
s i mpl y i ma gi ne wha t i s l i kel y to ha ppen i f you cons umed, s a y, ei ght cups of s trong ca ffei na ted coffee i n a s hort ti me. Youre typi ca l l y wi de a wa ke
(i f not s i mpl y hyper), ta chyca rdi c, uri na ti ng (from ca rdi a c-medi a ted i ncrea s ed rena l perfus i on a nd GFR), a nd tremorous . Methyl xa nthi nes a re CNS
s ti mul a nts , not jus t bronchodi l a tors or ca rdi a c s ti mul a nts . In overdos es , i rri ta bi l i ty or i ncrea s ed a l ertnes s a nd a wa kenes s devel op fi rs t. As bl ood
l evel s ri s e, ul ti ma tel y s ei zures occur, a nd tha t i s one of the ma jor thi ngs we woul d s ee i f thi s chi l d took a s uffi ci ent overdos e. Methyl xa nthi nes
dont ca us e uri na ry retenti on (a ); a s noted a bove, i ncrea s ed GFR wi l l l ea d to more frequent di ures i s . Bra dyca rdi a a nd hypotens i on (b) a re the
oppos i te of wha t i s a pt to occur i n the ca rdi ova s cul a r s ys tem. Methyl xa nthi nes i nduce nei ther pl a tel et a ggrega ti on (they wea kl y i nhi bi t i t vi a a cAMP-dependent mecha ni s m) nor i s chemi c s troke beca us e of i t. If a nythi ng, ri s es of bl ood pres s ure from exces s i ve ca rdi a c s ti mul a ti on mi ght
(ra rel y) ca us e hemorrha gi c s troke. Methyl xa nthi nes , of cours e, s ti mul a te centra l venti l a tory control mecha ni s ms , tendi ng to ca us e hyperpnea .
(Ca ffei ne ha s been us ed a s a venti l a tory s ti mul a nt, ma i nl y i n newborns .) Tha t, i n turn, woul d l i kel y ca us e res pi ra tory a l ka l os i s , not a ci dos i s (e).
Apnea i s not l i kel y.

Autacoids and Anti-inflammatory Drug Pharmacology

Aceta mi nophen
Ara chi doni c a ci d meta bol i s m
Ergot a l ka l oi ds
Hi s ta mi ne a nd i ts a nta goni s ts
Leukotri ene receptor bl ockers
Ma s t cel l s ta bi l i zers
Nons teroi da l a nti -i nfl a mma tory drugs (cycl ooxygena s e i nhi bi tors )
Pros ta gl a ndi ns a nd rel a ted ei cos a noi ds
Puri ne meta bol i s m, hyperuri cemi a , gout
Serotoni n a goni s ts a nd a nta goni s ts

Questions
310. About 10% to 20% of a s thma pa ti ents a ged 20 yea rs to 30 yea rs devel op wheezi ng or more s evere res pi ra tory s i gns a nd s ymptoms i n res pons e
to a certa i n cl a s s of drugs . The offendi ng drugs i ndi rectl y s hunt (redi rect) a ra chi doni c a ci d meta bol i s m to the forma ti on of l eukotri enes , whi ch
ha ve bronchocons tri ctor a nd proi nfl a mma tory properti es . To whi ch one of the fol l owi ng drugs or drug groups does thi s expl a na ti on mos t l i kel y
a ppl y?
a . Acetyl chol i nes tera s e i nhi bi tors (eg, neos ti gmi ne)
b. -Adrenergi c bl ockers (propra nol ol , ma ny others )
c. Hi s ta mi ne
d. Nons teroi da l a nti -i nfl a mma tory drugs (tra di ti ona l a gents s uch a s a s pi ri n)
e. Opi oi ds s uch a s morphi ne
311. Febuxos ta t i s the fi rs t new drug i n i ts cl a s s i n four deca des . It i s i ndi ca ted for ma na gi ng hyperuri cemi a , i ncl udi ng tha t whi ch i s drug-i nduced,
but i s not i ndi ca ted for s ymptom-s uppres s i on duri ng a n a cute gout a tta ck. Its ba s i c mecha ni s m of a cti on i s i nhi bi ti on of puri ne degra da ti on a t the
forma ti on of hypoxa nthi ne (HX), preventi ng further meta bol i s m of HX to xa nthi ne a nd uri c a ci d. It s houl d not be a dmi ni s tered to pa ti ents recei vi ng
puri ne a nti meta bol i tes (eg, merca ptopuri ne, thi ogua ni ne, for certa i n ca ncers ) beca us e the meta bol i c i na cti va ti on of thos e a nti ca ncer drugs wi l l
be i nhi bi ted a nd toxi ci ty ma y occur. Ba s ed on the des cri pti on gi ven, wha t drug i s mos t s i mi l a r to febuxos ta t?
a . Al l opuri nol
b. As pi ri n
c. Col chi ci ne
d. Indometha ci n
e. Probeneci d
312. A pa ti ent recei ves a drug tha t i nhi bi ts the l i poxygena s e pa thwa y of a ra chi doni c a ci d meta bol i s m. Wha t na tura l l y occurri ng meta bol i te(s ) wi l l
be produced i n l es s er a mounts i n res pons e to thi s drug?
a . Leukotri enes
b. Pros ta cycl i n (PGI 2 )
c. Pros ta gl a ndi ns
d. Thromboxa nes
e. Uri c a ci d
313. A pa ti ent ha s mi l d cuta neous a nd s ys temi c ma ni fes ta ti ons of a s ea s ona l a l l ergi c res pons e. Before you pres cri be a s hort cours e of
di phenhydra mi ne for s ymptom rel i ef, you s houl d rea l i ze tha t thi s drug ha s one mecha ni s m of a cti on res embl i ng, ca us es ma ny s i de effects s i mi l a r
to, a nd s ha res ma ny contra i ndi ca ti ons , tha t a ppl y to a n a utonomi c drug whi ch you s houl d be very fa mi l i a r. Wha t i s tha t drug?
a . Atropi ne
b. Betha nechol
c. Norepi nephri ne
d. Phentol a mi ne
e. Phys os ti gmi ne
f. Propra nol ol
314. A pa ti ent pres ents wi th a hi s tory of frequent a nd s evere mi gra i ne hea da ches . When we gi ve one of the more commonl y us ed drugs for
a borti ve thera py, s uma tri pta n, upon whi ch of the fol l owi ng l oca l control s ubs ta nces i s i t ma i nl y a cti ng?
a . Hi s ta mi ne
b. PGF 2
c. Pros ta cycl i n
d. Serotoni n
e. Thromboxa ne A2
315. A ma l e pa ti ent wi th s evere a rthri ti s wi l l be pl a ced on l ong-term thera py wi th i ndometha ci n. You recogni ze the ri s k of NSAID-i nduced
ga s troi ntes ti na l ul cera ti on, a nd s o wa nt to pres cri be a nother drug for ul cer prophyl a xi s . Whi ch drug woul d you mos t l i kel y choos e, a s a n a dd-on to

i ndometha ci n, a s s umi ng tha t there a re no s peci fi c contra i ndi ca ti ons to i ts us e?

a . Cel ecoxi b
b. Ci meti di ne
c. Di cl ofena c
d. Di phenhydra mi ne
e. Mi s opros tol
316. As pi ri n ca us es s i gni fi ca nt bronchocons tri cti on a nd bronchos pa s m i n a pa ti ent who wa s s ubs equentl y i denti fi ed a s bei ng a s pi ri n-s ens i ti ve.
Whi ch mecha ni s m s umma ri zes bes t why or how a s pi ri n provoked the res pi ra tory probl ems i n thi s pa ti ent?
a . Induced drug-medi a ted hypers ens i ti vi ty of H 1 receptors on a i rwa y s mooth mus cl es
b. Induced drug-medi a ted hypers ens i ti vi ty of mus ca ri ni c receptors on a i rwa y s mooth mus cl es
c. Enha nced forma ti on of a nti bodi es di rected a ga i ns t the s a l i cyl a te on a i rwa y ma s t cel l s
d. Inhi bi ted s ynthes i s of endogenous pros ta gl a ndi ns tha t ha ve bronchodi l a tor a cti vi ty
e. Reduced (bl ocked) epi nephri ne bi ndi ng to 2 -a drenergi c receptors on a i rwa y s mooth mus cl e cel l s
317. A chi l d ta kes wha t comes cl os e to bei ng a l etha l dos e of a ceta mi nophen. Wha t i s the mos t l i kel y pa thol ogy tha t ul ti ma tel y ca n l ea d to dea th
i nvol ved i n thi s drug overdos e?
a . Acute nephropa thy
b. A-V conducti on di s turba nces , hea rt bl ock
c. Li ver fa i l ure
d. Sta tus a s thma ti cus
e. Sta tus epi l epti cus
318. A pa ti ent wi th a s ymptoma ti c hyperuri cemi a i s s ta rted on probeneci d. In a coupl e of da ys , he devel ops a cute gout. Wha t i s the mecha ni s m by
whi ch probeneci d, ea rl y i n the cours e of trea tment wi th i t, tri ggered thi s a cute gouty a rthri ti c epi s ode?
a . Accel era ted s ynthes i s of uri c a ci d
b. Co-preci pi ta ted wi th uri c a ci d i n the joi nts
c. Induced a n i di os yncra ti c res pons e tha t tri ggered ura te preci pi ta ti on
d. Induced s ys temi c a ci dos i s , fa vori ng uri c a ci d crys ta l l i za ti on
e. Reduced rena l excreti on of uri c a ci d
319. Epi demi ol ogi c da ta publ i s hed i n the ea rl y 1980s found a proba bl e rel a ti ons hi p between a s pi ri n a nd a s eri ous a dvers e res pons e when the
drug wa s a dmi ni s tered to chi l dren wi th i nfl uenza , chi ckenpox, a nd other vi ra l i l l nes s es . Al though no ca us a l rel a ti ons hi p between a s pi ri n, vi ra l
i l l nes s , a nd thi s a dvers e effect wa s proven, you s ti l l ca uti on the pa rents or ca regi vers of chi l dren to a voi d gi vi ng a ny a s pi ri n or a s pi ri n-conta i ni ng
product when there i s even a remote pos s i bi l i ty tha t a chi l ds i l l nes s mi ght i nvol ve a vi rus . Avoi da nce of a s pi ri n i s neces s a ry to a voi d whi ch
s peci fi c a dvers e res pons e?
a . As thma
b. Ca rdi omyopa thy
c. Rena l fa i l ure
d. Reye s yndrome
e. Thrombocytopeni a a nd rel a ted bl eedi ng di s orders
320. Such drugs a s methotrexa te, hydroxychl oroqui ne, or peni ci l l a mi ne a re often turned to for ma na gi ng rheuma toi d a rthri ti s tha t i s not control l ed
a dequa tel y wi th tra di ti ona l NSAIDs (eg, a s pi ri n, i buprofen, di cl ofena c, or i ndometha ci n). Whi ch s ta tement mos t correctl y s umma ri zes how thos e
drugs di ffer from a typi ca l NSAID?
a . Acti va te the i mmune s ys tem to neutra l i ze i nfl a mma tory medi a tors
b. Are pri ma ry thera pi es for gouty a rthri ti s
c. Are rema rka bl y free from s eri ous toxi ci ti es
d. Provi de much qui cker rel i ef of a rthri ti s s i gns , s ymptoms
e. Sl ow, s top, pos s i bl y revers e joi nt pa thol ogy i n rheuma toi d a rthri ti s
321. For qui te a whi l e the coxi bs (s el ecti ve COX-2 i nhi bi tors ) were pres cri bed i n preference to nons el ecti ve cycl ooxygena s e i nhi bi tors for
ma na gi ng s uch condi ti ons a s rheuma toi d a rthri ti s . Now we ha ve ba s i ca l l y one drug i n thi s cl a s s , cel ecoxi b. Whi ch s ta tement bes t des cri bes a n
a cti on or property of thi s COX-2 i nhi bi tor?
a . As s oci a ted wi th a l ower ri s k of ga s tri c or duodena l ul cera ti on
b. Cures a rthri ti s , ra ther tha n jus t gi ve s ymptom rel i ef
c. Effecti vel y i nhi bi ts uri c a ci d s ynthes i s
d. Ha s a l ower ri s k of a dvers e or fa ta l ca rdi a c events
e. Ha s s i gni fi ca ntl y fa s ter ons et of a cti on
322. Gl ucocorti coi ds a re wi del y us ed for a hos t of i nfl a mma tory rea cti ons a nd the di s ea s es they ca us e. In terms of i nfl a mma tory res pons es a nd
underl yi ng meta bol i c rea cti ons , whi ch enzyme or proces s i s the ma i n ta rget of thes e drugs when they a re gi ven a t pha rma col ogi c
(s upra phys i ol ogi c) dos es ?
a . Cycl ooxygena s es (COX-1 a nd -2)
b. Hi s ti di ne deca rboxyl a s e

c. 5-l i poxygena s e
d. Phos phol i pa s e A2 (PLA2 )
e. Xa nthi ne oxi da s e
323. Bra dyki ni n pl a ys i mporta nt rol es i n l oca l res pons es to ti s s ue da ma ge a nd a va ri ety of i nfl a mma tory proces s es . It a l s o ha s va s odi l a tor a cti vi ty.
Whi ch s ta tement i s correct a bout thi s endogenous pepti de?
a . Ca ptopri l i nhi bi ts i ts meta bol i c i na cti va ti on
b. Drugs tha t a re meta bol i zed to, or genera te, ni tri c oxi de, countera ct bra dyki ni ns va s cul a r effects
c. Increa s ed bl ood pres s ure i s the predomi na nt ca rdi ova s cul a r res pons e
d. Newer hi s ta mi ne H 1 bl ockers (eg, fexofena di ne; s econd-genera ti on a nti hi s ta mi ne) a l s o competi ti vel y bl ock bra dyki ni n receptors
e. The ma i n rena l res pons es to endogenous bra dyki ni n a re a rteri ol a r cons tri cti on a nd reduced GFR
324. A newborn ha s oxygena ti on a nd hemodyna mi c probl ems beca us e of a pa tent (open) ductus a rteri os us . Whi ch drug us ua l l y woul d be
a dmi ni s tered i n a n a ttempt to cl os e the l es i on?
a . Ci meti di ne
b. Di phenhydra mi ne
c. Indometha ci n
d. Mi s opros tol
e. Pros ta gl a ndi n E1 (PGE1 ; a l pros ta di l )
325. A 29-yea r-ol d woma n devel ops frequent, debi l i ta ti ng mi gra i ne hea da ches . Suma tri pta n i s pres cri bed for a borti ve thera py. Not l ong a fter
ta ki ng the drug s he i s rus hed to the hos pi ta l . Her vi ta l s i gns a re uns ta bl e, a nd s he ha s mus cl e ri gi di ty, myocl onus , genera l i zed CNS i rri ta bi l i ty a nd
a l tered cons ci ous nes s , a nd s hi veri ng. You l ea rn tha t for s evera l months s he ha d been ta ki ng a nother drug wi th whi ch the tri pta n i ntera cted. Whi ch
a dd-on drug mos t l i kel y ca us ed thes e a cute a nd s eri ous probl ems ?
a . Aceta mi nophen
b. Codei ne
c. Di a zepa m
d. Fl uoxeti ne
e. Phenytoi n
326. A pa ti ent (a s s ume he or s he i s ta ki ng no other drugs ) ha s been ta ki ng dos es of a s pi ri n tha t a re too hi gh for s evera l weeks . Low-gra de a s pi ri n
toxi ci ty (s a l i cyl i s m) devel ops . Wha t s i gn or s ymptom woul d be cons i s tent wi th s a l i cyl i s m a nd the hi gh s a l i cyl a te l evel s tha t ca us ed i t?
a . Cons ti pa ti on
b. Cough
c. Hypertens i on
d. Myopi a
e. Ti nni tus
327. As pi ri n genera l l y s houl d be a voi ded a s a n a nti -i nfl a mma tory, a na l ges i c, or a nti pyreti c drug by pa ti ents wi th hyperuri cemi a or gout. Tha t i s
beca us e i t countera cts the effects of one i mporta nt drug the hyperuri cemi c pa ti ent ma y be ta ki ng. Whi ch drug ha s i ts des i red uri c a ci d-rel a ted
effects reduced or el i mi na ted by thi s prototypi c NSAID?
a . Aceta mi nophen
b. Al l opuri nol
c. Col chi ci ne
d. Indometha ci n
e. Probeneci d
328. Mi s opros tol , a n a na l og of PGE1 , i s s ometi mes us ed a djuncti vel y to s ti mul a te ga s tri c mucus producti on a nd hel p reduce the i nci dence of
ga s tri c ul cers a s s oci a ted wi th l ong-term or hi gh-dos e NSAID thera py for a rthri ti s . Wha t i s the other ma i n us e for thi s l i pi d-deri ved a uta coi d?
a . Cl os ure of a pa tent ductus a rteri os us i n newborns
b. Contra cepti on i n women who s houl d not recei ve es trogens or proges ti ns
c. Inducti on of a borti on i n conjuncti on wi th mi fepri s tone (RU486)
d. Prophyl a xi s of a s thma i n l i eu of a corti cos teroi d
e. Suppres s i on of uteri ne contra cti l i ty i n women wi th prema ture l a bor
329. A pa ti ent who wa s tra ns ported by a mbul a nce to the Emergency Depa rtment took a potenti a l l y l etha l overdos e of a s pi ri n. Wha t drug woul d be
a hel pful , i f not l i fes a vi ng, a djunct to ma na ge thi s s evere a s pi ri n poi s oni ng?
a . Aceta mi nophen
b. Ampheta mi nes (eg, dextroa mpheta mi ne)
c. N-a cetyl cys tei ne
d. Phenoba rbi ta l
e. Sodi um bi ca rbona te
330. We l ook a t da ta tha t s umma ri ze the a cti ons of two prototypi c hi s ta mi ne receptor bl ockers : di phenhydra mi ne a s the exempl a r of the ol der
a nti hi s ta mi nes (competi ti ve hi s ta mi ne receptor a nta goni s ts ); a nd fexofena -di ne a s a repres enta ti ve a gent of the s econd-genera ti on

a nti hi s ta mi nes . Whi ch s ta tement correctl y des cri bes , compa res , or contra s ts thes e drugs or the pha rma col ogi c groups to whi ch they bel ong?
a . Di phenhydra mi ne a nd other drugs i n i ts cl a s s (etha nol a mi nes ) tend to ca us e drows i nes s more often tha n fexofena di ne a nd rel a ted s econdgenera ti on a nti hi s ta mi nes
b. Di phenhydra mi ne i s a preferred a nti hi s ta mi ni c for pa ti ents wi th pros ta te hypertrophy or a ngl e-cl os ure gl a ucoma , wherea s fexofena di ne a nd
rel a ted drugs a re contra i ndi ca ted
c. Di phenhydra mi ne overdos es tend to ca us e bra dyca rdi a , wherea s fexofena di ne overdos es tend to ca us e s i gni fi ca nt i ncrea s es of hea rt ra te
d. Fexofena di ne a nd rel a ted s econd-genera ti on hi s ta mi ne a nta goni s ts ha ve i ntri ns i c bronchodi l a tor a cti vi ty, whi ch ma kes them s ui ta bl e a s
pri ma ry/s ol e thera py for peopl e wi th a s thma
e. Fexofena di ne, a nd drugs i n i ts cl a s s , ha ve better effi ca cy i n terms of s uppres s i ng hi s ta mi ne-medi a ted ga s tri c a ci d s ecreti on
331. A pa ti ent ha s been ta ki ng one of the drugs l i s ted bel ow for a bout 4 months , a nd i s experi enci ng the des i red thera peuti c effects from i t. The
phys i ci a n now pres cri bes i ndometha ci n to trea t a pa rti cul a rl y s evere fl a re-up of rheuma toi d a rthri ti s . Wi thi n a ma tter of da ys the thera peuti c
effects of the fi rs t drug wa ne dra ma ti ca l l y, i ts a cti ons a nta goni zed by the i ndo-metha ci n. Whi ch drug wa s a ffected by the i ndometha ci n?
a . Al l opuri nol , gi ven for prophyl a xi s of hyperuri cemi a
b. Ca ptopri l , gi ven for es s enti a l hypertens i on
c. Fexofena di ne, gi ven for ma na gi ng s ea s ona l a l l ergy res pons es
d. Suma tri pta n, gi ven for a borti ve thera py of mi gra i ne hea da ches
e. Wa rfa ri n, gi ven for prophyl a xi s of venous thrombos i s
332. A pa ti ent ta kes a n a cute, ma s s i ve overdos e of a s pi ri n tha t, wi thout proper i nterventi on, wi l l proba bl y be fa ta l . Wha t woul d you expect to occur
i n the a dva nced (l a te) s ta ges of a s pi ri n (s a l i cyl a te) poi s oni ng?
a . Hypothermi a
b. Meta bol i c a l ka l os i s
c. Res pi ra tory a l ka l os i s
d. Res pi ra tory pl us meta bol i c a ci dos i s
e. Venti l a tory s ti mul a ti on
333. A pa ti ent pres ents i n the emergency depa rtment wi th a n overdos e of a drug. The phys i ci a n knows wha t the drug i s , a nd s o orders a ppropri a te
s ymptoma ti c a nd s upporti ve ca re, pl us mul ti pl e dos es of N-a cetyl cys tei ne. Upon whi ch drug di d the pa ti ent overdos e?
a . Aceta mi nophen
b. As pi ri n
c. Col chi ci ne
d. Di phenhydra mi ne
e. Lora ta di ne
f. Methotrexa te
334. A pa ti ent ha s a cute gout. The phys i ci a n i ni ti a l l y thi nks a bout pres cri bi ng jus t one or two ora l dos es of col chi ci ne, 12 hours a pa rt, but then
deci des otherwi s e. Wha t i s the ma i n a nd mos t common rea s on for a voi di ng col chi ci ne, even wi th a very s hort ora l cours e, a nd pres cri bi ng a nother
drug for the a cute gout i ns tea d?
a . Bone ma rrow s uppres s i on
b. Bronchos pa s m
c. GI di s tres s tha t i s a l mos t a s ba d a s the a cute gout di s comfort
d. Hepa totoxi ci ty
e. One or two ora l dos es s el dom rel i eve gout pa i n
f. Refra ctori nes s /tol era nce wi th jus t a dos e or two
335. A pa ti ent wi th hyperuri cemi a i s pl a ced on a n a nti gout drug. Before s ta rti ng the drug you mea s ure the tota l uri c a ci d (a mount, not
concentra ti on) i n a 24-hour uri ne s a mpl e a nd then do the s a me s evera l weeks a fter conti nued drug thera py a t thera peuti c dos es . The pos ttrea tment s a mpl e s hows a s i gni fi ca nt reducti on i n ura te content. There were no new pa thol ogi es devel opi ng duri ng thera py, a nd the pa ti ents
da i l y puri ne i nta ke di d not cha nge a t a l l . Wha t drug mos t l i kel y a ccounted for thes e fi ndi ngs ?
a . Aceta mi nophen
b. Al l opuri nol
c. Col chi ci ne
d. Indometha ci n
e. Probeneci d
336. We a dmi ni s ter s odi um bi ca rbona te to a pa ti ent who ha s s evere hyperuri cemi a a nd i s a t grea t ri s k of devel opi ng ura te s tones i n hi s uri na ry
tra ct. Wha t i s the ba s i s for us i ng the bi ca rbona te?
a . Ca us es a nti di ureti c effect, reduci ng ura te content of the uri ne
b. Ca us es meta bol i c a l ka l os i s tha t i nhi bi ts ca ta l yti c a cti vi ty of xa nthi ne oxi da s e
c. Countera cts meta bol i c a ci dos i s tha t i s cha ra cteri s ti c of s evere hyperuri cemi a
d. Lowers ura te el i mi na ti on by l oweri ng gl omerul a r fi l tra ti on ra te
e. Reduces s ol ubi l i ty of ura te i n the uri ne
337. A pa ti ent wi th a nnoyi ng ha y fever (s ea s ona l a l l ergy) s ymptoms (ma i nl y rhi norrhea ) goes to the s tore, i ntent on purcha s i ng a n ora l medi ca ti on

to ma ke them more comforta bl e. They s ee the pri ces for l ora ta di ne a nd rel a ted s econd-genera ti on a nti hi s ta mi nes a nd a re s hocked a bout how
hi gh they a re. Nea rby on the s hel f they s ee s tore-bra nd a l l ergy rel i ef pi l l s tha t a re much l es s expens i ve, the chea pes t ones ha vi ng
di phenhydra mi ne a s the s ol e a cti ve i ngredi ent. If they were to ta ke ful l thera peuti c dos es of the di phenhydra mi ne, ba s ed on l a bel di recti ons ,
whi ch effects or s i de effects a re they mos t l i kel y to experi ence a s a n a ddi ti ona l pri ce to be pa i d for thei r a l l ergy rel i ef?
a . Bra dyca rdi a
b. Di a rrhea
c. Drows i nes s , s omnol ence
d. Hea rtburn from i ncrea s ed ga s tri c a ci d s ecreti on
e. Uri na ry frequency
338. Your pa ti ent ha s rheuma toi d a rthri ti s tha t ha s been l a rgel y refra ctory to di cl ofena c, i buprofen, i ndometha ci n, a nd s ul i nda c. In a ddi ti on, s he
ha s experi enced s i gni fi ca nt GI di s tres s , a nd s evera l GI bl eeds , fol l owi ng a ttempts to get better a nti -i nfl a mma tory effects by ra i s i ng the dos es . We
s ta rt her on thera py wi th eta nercept. Wha t i s the mos t l i kel y mecha ni s m by whi ch eta nercept s uppres s es the s i gns , s ymptoms , or underl yi ng
pa tho-phys i ol ogy of rheuma toi d a rthri ti s ?
a . Inhi bi ts ei cos a noi d s ynthes i s by i nhi bi ti ng phos phol i pa s e A2
b. Inhi bi ts l eukocyte mi gra ti on by bl ocki ng mi crotubul a r forma ti on
c. Neutra l i zes ci rcul a ti ng tumor necros i s fa ctor (TNF-)
d. Sel ecti vel y a nd effecti vel y i nhi bi ts COX-2
e. Sti mul a tes col l a gen a nd mucopol ys a ccha ri de s ynthes i s i n the joi nts

Autacoids and Anti-inflammatory Drug Pharmacology

Answers
310. The answer is d. (Brunton, pp 973t, 974, 1031-1032; Katzung, pp 320, 638, 639f.) Ara chi doni c a ci d i s a by-product of phos phol i pi d meta bol i s m (vi a
phos phol i pa s es ) i n mos t cel l s . Reca l l tha t there a re two ma i n pa thwa ys for further a ra chi doni c a ci d meta bol i s m: (1) vi a the cycl ooxygena s e
pa thwa y; a nd (2) vi a the l i poxygena s e pa thwa y. Tra di ti ona l NSAIDs , i ncl udi ng a s pi ri n, i nhi bi t both cycl ooxygena s e-1 a nd -2. In thos e pa ti ents wi th
wha t i s generi ca l l y ca l l ed a s pi ri n-s ens i ti ve a s thma (a l s o ca l l ed tra i d or Sa mpter a s thma ), the worki ng hypothes i s i s tha t when a ra chi dona te
meta bol i s m vi a COX i s i nhi bi ted, a ra chi doni c a ci d mus t s ti l l be meta bol i zed. Tha t occurs vi a i ncrea s ed meta bol i s m through the l i poxygena s e
pa thwa y. Thi s res ul ts i n grea ter forma ti on of l eukotri enes tha t ca us e bronchocons tri cti on a nd a ddi ti ona l a i rwa y i nfl a mma ti on.
Acetyl chol i nes tera s e i nhi bi tors (a ) cl ea rl y ca n provoke s evere bronchos pa s m i n a s thma ti c pa ti ents . Tha t i s a di rect effect, a ppa rentl y i nvol vi ng
i ncrea s ed a i rwa y s mooth mus cl e rea cti vi ty to a hos t of bronchocons tri ctor s ubs ta nces , one of whi ch i s a cetyl chol i ne. The res pons e i s i ndependent
of l eukotri ene meta bol i s m. The s a me a ppl i es to -a drenergi c bl ockers (b). In thei r ca s e, a i rwa y probl ems a ri s e from i nhi bi ti on of i mporta nt -2medi a ted bronchodi l a tor effects of epi nephri ne. Hi s ta mi nes effects (c) a re di rect a nd do not i nvol ve a ra chi doni c a ci d meta bol i s m, but there i s no
doubt tha t hi s ta mi ne i s a pa rti cul a rl y powerful bronchocons tri ctor i n pa ti ents wi th a s thma . Opi oi ds (e) ma y ca us e exces s i ve bronchocons tri cti on i n
s ome a s thma pa ti ents . Tha t i s a l mos t certa i nl y due to morphi nes a bi l i ty to rel ea s e hi s ta mi ne from ma s t cel l s a nd ba s ophi l s . It ha s nothi ng to do
wi th s peci fi c i nhi bi ti on of COX or l i poxygena s e pa thwa ys of a ra chi doni c a ci d meta bol i s m.
311. The answer is a. (Brunton, pp 997-998; Katzung, pp 653-654.) The des cri pti on of febuxos ta t i n the ques ti ona cti ons , us es , drug i ntera cti ons a nd
morea ppl i es di rectl y to a l l opuri nol , whi ch i s cl a s s i fi ed a s a xa nthi ne oxi da s e i nhi bi tor a nd ha s been a va i l a bl e for deca des . As you s houl d
reca l l , a l l opuri nol (a nd now febuxos ta t) i s i ndi ca ted for ma na gi ng hyperuri cemi a , whether i di opa thi c, a s s oci a ted wi th certa i n di s ea s es (i ncl udi ng
ma ny ma l i gna nci es ), or drug-i nduced (eg, by thi a zi de or l oop di ureti cs , a nd ca ncer chemothera peuti c a gents ). As pi ri n (b) ha s no effects on puri ne
meta bol i s m i n genera l or s peci fi ca l l y on xa nthi ne oxi da s e. At a l l but very hi gh dos a ges , i t ca n ra i s e pl a s ma uri c a ci d (a nd xa nthi ne) l evel s by
i nhi bi ti ng tubul a r s ecreti on of uri c a ci d, a nd i s genera l l y contra i ndi ca ted for pa ti ents wi th hyperuri cemi a or gout. Col chi ci ne (b) i s a n a nti i nfl a mma tory drug us ed for a cute gout, or for prophyl a xi s , but i t ha s no effect on endogenous puri ne meta bol i s m or the meta bol i s m of puri ne
a nti meta bol i tes s uch a s merca ptopuri ne. Indometha ci n (d) i s a tra di ti ona l NSAID (tNSAID) tha t ha s ma ny i ndi ca ti ons , i ncl udi ng trea ti ng
i nfl a mma ti on s econda ry to gout, but once a ga i n i t s ha res none of the other properti es noted i n the ques ti on. Probeneci d (e) ca n be cons i dered the
prototype uri cos uri c drug: i ndi ca ted for prophyl a xi s , but not for trea tment, of gout. Thera peuti c bl ood l evel s of probeneci d l ower pl a s ma uri c a ci d
l evel s by bl ocki ng tubul a r rea bs orpti on of ura te.
312. The answer is a. (Brunton, pp 939-942; Katzung, pp 349-350, 352.) The a ra chi doni c a ci d (AA) ca s ca de begi ns wi th AA s ynthes i s from membra ne
phos phol i pi ds by phos phol i pa s e A2 . Once a ra chi doni c a ci d i s formed, the meta bol i c pa thwa ys di verge i nto the l i poxygena s e pa thwa y (tha t forms
cys tei nyl l eukotri enes [LTs ]) a nd the cycl ooxygena s e pa thwa ys tha t s ynthes i ze pros ta gl a ndi ns , i ncl udi ng pros ta cycl i n a nd thromboxa ne A2 . One
i mporta nt i ntermedi a te ea rl y on i n the LP pa thwa y i s LTA4 . From tha t we get LTB 4 , whi ch ma i nl y regul a tes chemota xi s (cytoki ne a cti vi ty) a nd
a cti va tes pha gocytos i s i n whi te bl ood cel l s . Al s o deri ved from LTB 4 a re, s equenti a l l y, LTC4 , LTD 4 , a nd LTE4 (cys tei nyl l eukotri enes , hi s tori ca l l y a nd
col l ecti vel y ca l l ed SRS-A, for s l ow-rea cti ng s ubs ta nce of a na phyl a xi s ), whi ch ca us e ma i nl y bronchocons tri cti on. Leukotri ene s ynthes i s ca n be
i nhi bi ted by zi l euton (no l onger us ed cl i ni ca l l y), a 5-l i poxygena s e i nhi bi tor. The l eukotri ene receptors ca n be bl ocked by montel uka s t a nd
za fi rl uka s t, whi ch a re us ed prophyl a cti ca l l y (control meds ) to s uppres s a i rwa y i nfl a mma ti on a nd bronchocons tri cti on i n a s thma . They s houl d not
be us ed i n l i eu of corti cos teroi ds (ora l or i nha l ed) when control of a i rwa y i nfl a mma ti on i s neces s a ry.
Pros ta gl a ndi ns (c), i ncl udi ng pros ta cycl i n (b), a nd thromboxa ne A2 (d) a re s ynthes i zed vi a the cycl ooxygena s e pa thwa ys . Uri c a ci d (e) i s
s ynthes i zed by wha t i s genera l l y referred to a s the ATP (puri ne) degra da ti on pa thwa y, i n whi ch the fi na l two s teps i n the pa thwa y (convers i on of
hypoxa nthi ne to xa nthi ne, a nd convers i on of xa nthi ne to uri c a ci d) a re ca ta l yzed by xa nthi ne oxi da s e.
313. The answer is a. (Brunton, pp 921t, 918-924, 1816; Katzung, p 292.) Di phenhydra mi ne, a n ol der or fi rs t-genera ti on a nti hi s ta mi ne, i s a competi ti ve
a nta goni s t of hi s ta mi nes effects on H 1 receptors , a nd a l s o s trongl y bl ocks mus ca ri ni c chol i nergi c receptors . Other ol der H 1 bl ockers (but none of
the s econd-genera ti on H 1 bl ockers , s uch a s fexofena di ne) pos s es s thi s a tropi ne-l i ke effect, often to a l es s er degree tha n di phenhydra mi ne. (If
you wi s hed to a rgue tha t beca us e di phenhydra mi ne wa s more l i ke s copol a mi ne, beca us e i t ca us es not onl y a nti chol i nergi c effects but a l s o a
cons i dera bl e degree of s eda ti on, you woul d be correct.) Thus , common s i de effects rel a ted to a nti mus ca ri ni c a cti vi ty i ncl ude s eda ti on, dry mouth,
photophobi a , a nd cycl opl egi a (pa ra l ys i s of a ccommoda ti on). Key contra i ndi ca ti ons i ncl ude pros ta ti c hypertrophy, bowel or bl a dder obs tructi on or
hypomoti l i ty, ta chyca rdi a , a nd na rrowa ngl e (a ngl e-cl os ure) gl a ucoma .
To refres h your memory a bout the other drugs l i s ted, betha nechol (b) i s a mus ca ri ni c a goni s t, norepi nephri ne (c) i s a n effecti ve a goni s t for 1 a nd -a drenergi c receptors , phentol a mi ne (d) i s a nons el ecti ve bl ocker, phys os ti gmi ne (e) i s a n a cetyl chol i nes tera s e i nhi bi tor, a nd propra nol ol
(f) i s , of cours e, the prototypi c nons el ecti ve -a drenergi c bl ocker.
314. The answer is d. (Brunton, pp 344-347; Katzung, pp 285, 292.) Acute mi gra i ne thera py often i nvol ves gi vi ng a drug tha t mi mi cs the effects of
endogenous s erotoni n (5-hydroxytrypta mi ne), thereby revers i ng the cerebra l va s odi l a ti on tha t contri butes s i gni fi ca ntl y to mi gra i ne s i gns a nd
s ymptoms . A good exa mpl e i s s uma tri pta n (member of a s ma l l group of drugs ca l l ed tri pta ns ). Thes e a re 5-HT1B/2D receptor a goni s ts . Hi s ta mi ne
(a ), a nd to a l es s er extent pros ta cycl i n (PGI 2 , a ns wer c), a re va s odi l a tors , too, but they dont s eem to ha ve a ppreci a bl e rol es i n mi gra i ne, nor a re
they ta rgets of a nti mi gra i ne drug a cti vi ty. Acti va ti on of 2 -a drenergi c receptors i n the cerebra l va s cul a ture a l s o l ea ds to va s odi l a ti on a nd mi gra i ne
s ymptoms . The -a drenergi c bl ockers (pa rti cul a rl y propra nol ol ) a re us eful for s ome mi gra i neurs , but onl y for prophyl a xi s , not for a borti ve thera py.
315. The answer is e. (Brunton, pp 952, 1837, 1849; Katzung, pp 315, 317, 1090.) Mi s opros tol i s a l ong-a cti ng s yntheti c a na l og of PGE1 , a nd i ts onl y us e
(outs i de of reproducti ve medi ci ne) i s prophyl a xi s of NSAID-i nduced ga s tri c ul cers . Its ma i n effects a re s uppres s i on of ga s tri c a ci d s ecreti on
(modes t); a nd, more i mporta ntl y, enha nced ga s tri c mucus producti on (a s o-ca l l ed mucotropi c or cytoprotecti ve effect). The need for the drug a ri s es ,
of cours e, beca us e s uch drugs a s i ndometha ci n (a nd mos t other COX-nons el ecti ve i nhi bi tors ) i nhi bi t PGE1 s ynthes i s (a s wel l a s tha t of other
pros ta gl a ndi ns , pros ta cycl i n, a nd thromboxa ne A2 ).
Al though ci meti di ne (b) mi ght hel p reduce ga s tri c a ci d s ecreti on (vi a H 2 bl ocka de) a nd di phenhydra mi ne (c) ma y too (vi a a nti mus ca ri ni c effects ),
thei r a nti s ecretory effects (wi th res pect to ga s tri c a ci d) a re wea k, a nd they dont i ncrea s e forma ti on of the s toma chs protecti ve mucus .
Cel ecoxi b (a ), a COX-2 s el ecti ve NSAID, i s a s s oci a ted wi th a l ower ri s k or i nci dence of GI ul cers tha n more tra di ti ona l COX-1/-2 NSAIDs , i ncl udi ng

i ndometha ci n (or di cl ofena c, i buprofen, ma ny others ). However, a ddi ng a COX-2 i nhi bi tor woul d be i rra ti ona l i n terms of reduci ng ul cer ri s k.
Di cl ofena c (c) i s a tra di ti ona l NSAID tha t, when us ed l ong-term (eg, a s a n a l terna ti ve to i ndometha ci n or a ny of the other rea s ona bl e opti ons ), ma y
ca us e ul cers jus t a s i ndometha ci n ma y. In fa ct, a fi xed-dos e combi na ti on product conta i ni ng di cl ofena c a nd mi s opros tol i s a va i l a bl e, the l a tter
drug bei ng us ed to reduce the ri s k of ul cers ca us ed by the former.
316. The answer is d. (Brunton, pp 937-952; Katzung, pp 638-640.) Inhi bi ted s ynthes i s of pros ta gl a ndi ns tha t a re bronchodi l a tors (ma i nl y PGE2 ) a re
thought to be res pons i bl e for s evere or fa ta l res pons es to a s pi ri n i n s ome a s thma ti cs . Note tha t a s pi ri n a nd other tra di ti ona l NSAIDs i nhi bi t the
s ynthes i s of PGF 2 a nd of TXA2 , both of whi ch a re bronchocons tri ctors . As a res ul t, one woul d predi ct reduced bronchocons tri cti on wi th a s pi ri n.
However, i n thos e pa ti ents wi th a s pi ri n-s ens i ti ve a s thma (a bout 20% of a dul t a s thma ti cs overa l l ), the a dvers e effects a ri s i ng from i nhi bi ted PGE2
s ynthes i s tend to predomi na te, a nd s o a s pi ri n a nd other effi ca ci ous NSAIDs a re genera l l y contra i ndi ca ted.
As pi ri n does not ca us e i ncrea s ed res pons i venes s of a i rwa y s mooth mus cl e cel l s to the bronchocons tri ctor effects of hi s ta mi ne (a ) or mus ca ri ni c
a goni s ts (b). It does not el i ci t a nti body forma ti on (c) or ha ve a ny effect on the i ntera cti on between 2 a goni s ts a nd thei r cel l ul a r receptors (e).
317. The answer is c. (Brunton, pp 76, 128, 136; Katzung, p 1032.) The pri ma ry ca us e of dea th from a ceta mi nophen overdos es i s hepa ti c necros i s . The
drugs ma i n toxi c meta bol i te i s N-a cetyl -benzoqi nonei mi ne. It rea cts wi th s ul fhydryl groups tha t a re cons ti tuents of key ma cromol ecul es a nd
meta bol i c cofa ctors (eg, gl uta thi one) i n the l i ver. If a ceta mi nophen dos es a re l ow, gl uta thi one conjuga tes the meta bol i te. Wi th toxi c dos es ,
however, gl uta thi one i s depl eted a nd otherSH groups on hepa tocyte protei ns a re a tta cked a nd i rrevers i bl y a l tered. Concomi ta nt wi th overa l l
hepa ti c da ma ge we fi nd, eventua l l y, profound hypogl ycemi a (a s the l i vers s tores of gl ycogen a re depl eted) a nd coa gul opa thi es (a s hepa ti c
cl otti ng fa ctor s ynthes i s s tops a nd the pa ti ent begi ns bl eedi ng s ponta neous l y).
Nephropa thy (a ) i s not a pri ma ry or i mporta nt cons equence of a ceta mi nophen toxi ci ty. If AV conducti on di s turba nces , hea rt bl ock, or other
ca rdi a c el ectrophys i ol ogi c a noma l i es (b) occur, they a re s econda ry to hepa ti c dys functi on. Sta tus a s thma ti cus (d) a nd a cute s ei zures (e) a re not
l i kel y or di rect cons equences of a ceta mi nophen poi s oni ng.
Note: Lets s umma ri ze the ma i n events or s ta ges (theyre a rbi tra ry) of wha t otherwi s e woul d be a l etha l dos e of a ceta mi nophen: for a n
otherwi s e-hea l thy chi l d, i t i s a round 12 g ta ken a l l a t once; for otherwi s e hea l thy a dul ts i t i s a round 25 g. Va ri ous i l l nes s es , a nd cons umi ng other
drugs (i ncl udi ng a s pi ri n) ca n dra ma ti ca l l y l ower the dos e s uffi ci ent to ca us e s eri ous or l etha l toxi ci ty. A s ta nda rd s trength a ceta mi nophen ta bl et
conta i ns 300 mg. Be a wa re tha t a ceta mi nophen toxi ci ty i s the mos t common drug ca us e of l i ver fa i l ure i n the Uni ted Sta tes . And, mos t of thos e
ca s es a re not ca us ed by s ui ci de a ttempts i n whi ch the drug i s ta ken a l l a t once. More often, the toxi ci ty devel ops gra dua l l y, wi th exces s i ve
a ceta mi nophen us e over ti me. A ma jor contri butor to tha t probl em i s tha t a ceta mi nophen i s found i n s o ma ny products , mos t a va i l a bl e OTC, a nd
the cons umer s i mpl y i s nt a wa re tha t he or s he i s ul ti ma tel y ta ki ng ma ny dos es of a product tha t conta i ns thi s hepa totoxi n.

318. The answer is e. (Brunton, p 999; Katzung, p 656.) It ha s been s a i d tha t the i ni ti a l pha s e of uri cos uri c thera py i s the mos t worri s ome peri od for a
hyperuri cemi c pa ti ent. Probeneci d i s a uri cos uri c drug (one tha t i ncrea s es rena l el i mi na ti on of uri c a ci d), but tha t effect i s hi ghl y dos e-dependent.
Des i red uri cos uri c a cti ons depend on ha vi ng thera peuti c probeneci d bl ood l evel s tha t a re s uffi ci ent to i nhi bi t a cti ve tubul a r rea bs orpti on of ura te.
At s ubthera peuti c bl ood l evel s , the ma i n effect i s i nhi bi ti on of tubul a r s ecreti on of ura te, whi ch reduces net ura te excreti on a nd ra i s es pl a s ma
ura te l evel s (s ometi mes to the poi nt of ca us i ng cl i ni ca l gout). It i s onl y once probeneci d l evel s a re thera peuti c tha t the des i red effects to i nhi bi t
tubul a r ura te rea bs orpti on (i e, i ncrea s e excreti on) predomi na te. Thus , a nd i ntui ti vel y, once a pa ti ent s ta rts probeneci d thera py drug l evel s mus t
ri s e a nd pa s s through tha t s ta ge i n whi ch ura te excreti on wi l l a ctua l l y go down, pl a s ma ura te l evel s up.
Some texts s ugges t us i ng a s hort cours e of col chi ci ne or a nother (non-a s pi ri n) NSAID tha t i s i ndi ca ted for gout when probeneci d thera py i s
s ta rted. Tha t i s for prophyl a xi s of a cute gout tha t mi ght occur. Al though thi s ma y be a ccepta bl e, other rul es a re perha ps more i mporta nt: (1) do not
a dmi ni s ter a uri cos uri c duri ng a gout a tta ck; (2) i f the pa ti ent ha s ha d a gout a tta ck recentl y, s uppres s the i nfl a mma ti on for 2 to 3 months wi th a
s ui ta bl e a nti -i nfl a mma tory; a nd (3) do not us e uri cos uri cs for pa ti ents wi th s evere hyperuri cemi a a nd/or poor rena l functi on. Doi ng otherwi s e i s
a s s oci a ted wi th a grea t ri s k of potenti a l l y s evere rena l tubul a r da ma ge a s the uri cos uri c s hi fts l a rge a mounts of uri c a ci d from the bl ood (wi th i ts
l a rge vol ume, tha t keeps ura te rel a ti vel y di l ute) i nto a s ma l l vol ume of a ci di c uri ne, whi ch concentra tes ura te a nd l owers i ts s ol ubi l i ty vi a pHdependent mecha ni s ms .
(The pa ti ent who s ki ps dos es of probeneci d a l s o becomes very vul nera bl e to the pa ra doxi ca l extra ri s k, beca us e doi ng thi s ma y a l l ow drug
l evel s to fa l l i nto tha t s ubthera peuti c ra nge i n whi ch more ura te i s reta i ned tha n el i mi na ted.)
319. The answer is d. (Brunton, pp 975-976.) Before the wa rni ng wa s i s s ued, over 500 chi l dren wi th a ny vi ra l i l l nes s a nd who recei ved a s pi ri n (even i n
us ua l recommended dos es a t the ti me) devel oped Reye s yndrome. It i s cha ra cteri zed by encepha l opa thy a nd fa tty l i ver degenera ti on. The
morta l i ty ra te ra nged from a bout 20% to 30%, a nd ma ny more pa ti ents devel oped perma nent a nd s eri ous CNS a nd/or l i ver dys functi on. Nowa da ys
there a re fewer tha n fi ve ca s es of Reye s yndrome per yea r a s a res ul t of the a s pi ri n/vi ra l i l l nes s i ntera cti on. (Note: the a ge ra nge for whi ch
a s pi ri n s houl d not be a dmi ni s tered i n the pres ence of vi ra l i l l nes s i s deba ta bl e; s ome s ugges t the ri s k of Reye s yndrome l es s ens dra ma ti ca l l y by
the a ge of 12 yea rs , but ma ny experts s ugges t tha t the ri s k ma y pers i s t up to 18-20 yea rs of a ge.)
As thma (a ) i s the mos t common ca us e of hos pi ta l i za ti ons i n chi l dren, a nd ma ny pa ti ents ha ve thei r a s thma provoked or wors ened by a s pi ri n or
other NSAIDs . However, the potenti a l a s thma NSAID probl ems a re unrel a ted to the pres ence or a bs ence of vi ra l i l l nes s es . There i s no evi dence
of a l i nka ge between a s pi ri n a nd ca rdi omyopa thi es (b). Long-term hi gh dos e a dmi ni s tra ti on of NSAIDs (other tha n a s pi ri n) ma y ca us e rena l
dys functi on or fa i l ure (c). Here, too, there i s no l i nka ge between vi ra l i l l nes s , a nd the ki dney probl ems a re not a t a l l focus ed on the pedi a tri c
popul a ti on. As pi ri n obvi ous l y ha s a nti pl a tel et-a ggrega tory effects , but whether the pa ti ent i s a chi l d or ol der, thrombocytopeni a (e) i s not a
concern.
320. The answer is e. (Brunton, p 960; Katzung, pp 643-648.) Methotrexa te, gol d s a l ts , a nd peni ci l l a mi ne a re members of a di vers e group of drugs ca l l ed
DMARDs (di s ea s e-modi fyi ng a nti rheuma ti c drugs ) or SAARDs (s l ow-a cti ng a nti rheuma ti c drugs ). The former term deri ves from the a bi l i ty of thes e
drugs to s l ow, s top, or i n s ome ca s es revers e joi nt da ma ge a s s oci a ted wi th rheuma toi d a rthri ti s (RA). They do more tha n merel y ma s k or rel i eve RA
s ymptoms , whi ch i s ma i nl y wha t the tra di ti ona l NSAIDs do. The s econd a cronym deri ves from the fa ct tha t i t ma y ta ke a month (or a coupl e more)
for mea ni ngful s ymptom rel i ef to devel op; they a re not a t a l l qui ck-a cti ng drugs . Thei r a cti ons proba bl y a re due to s uppres s i on of i mmune
res pons es tha t often contri bute to the eti ol ogy of RA.
Thei r toxi ci ti es ca n be s eri ous , whi ch i s one rea s on why, unti l not l ong a go, thes e a gents were cons i dered thi rd-l i ne or even l a s t res ort
trea tments for refra ctory rheuma toi d di s ea s e. (Methotrexa te i s now bei ng us ed much ea rl i er, a nd s a fel y, for RA, now tha t we know better how to
us e i t a nd moni tor for s eri ous toxi ci ti es .) Mos t of thes e drugs ca n ca us e s eri ous bl ood dys cra s i a s ; i n a ddi ti on, peni ci l l a mi ne ca n ca us e rena l a nd
pul mona ry toxi ci ty; hydroxychl oroqui ne i s a s s oci a ted wi th vi s i on i mpa i rments /reti nopa thy.
321. The answer is a. (Brunton, pp 941-942, 964-965; Katzung, p 640.) Cel ecoxi b, by vi rtue of s el ecti ve COX-2 i nhi bi ti on, does not i nterfere a s much wi th
s ynthes i s of PGE2 , whi ch norma l l y s uppres s es a component of ga s tri c a ci d s ecreti on a nd s ti mul a tes ga s tri c mucus producti on. Overa l l , then, the
ri s ks of ga s tri c a nd duodena l ul cers a re reduced. The s el ecti vi ty a l s o mea ns tha t COX-2 i nhi bi tors do not i nterfere wi th the producti on of other
ei cos a noi ds , s uch a s TXA2 . Tha t i s both good a nd ba d, cl i ni ca l l y. On the good s i de, thi s mea ns tha t COX-2 i nhi bi tors dont ca us e a nti pl a tel et effects
a nd i ncrea s e the ri s k of exces s i ve or s ponta neous bl eedi ng. On the other ha nd, thi s l a ck of effect renders them uns ui ta bl e for ca us i ng des i red
a nti pl a tel et-a ggrega tory effects , a s mi ght be wa nted when we a dmi ni s ter a s pi ri n. Thi s ma y expl a i n the fi ndi ng tha t s ome COX-2 i nhi bi tors ha ve
been a s s oci a ted wi th (ca us e?) a hi gher ri s k of s udden ca rdi a c dea th (d) i n vul nera bl e pa ti ents , a nd why s ome ha ve been pul l ed off the ma rket
(a nd a re s ubjects of cons i dera bl e l i ti ga ti on).
Sel ecti ve COX-2 i nhi bi tors , s uch a s the nons el ecti ve a l terna ti ves , a rent cures for a rthri ti s (b); they a l l evi a te s i gns a nd s ymptoms but s eem to
ha ve no demons tra bl e i mpa ct on the underl yi ng pa thophys i ol ogy. They ha ve no effect on uri c a ci d meta bol i s m (c) or excreti on. Thei r ons ets of
a cti on a re, overa l l , no fa s ter (e) tha n thos e of a typi ca l NSAID.
322. The answer is d. (Brunton, pp 937-939; Katzung, pp 339-340, 347-348, 639f.) Anti -i nfl a mma tory dos es of gl ucocorti cos teroi ds i nhi bi t phos phol i pa s e
A2 a cti vi ty. In doi ng s o, they i nhi bi t a ra chi doni c a ci d s ynthes i s a nd, therefore, s ynthes i s of a l l s ubs equent products of the cycl ooxygena s e a nd
l i poxygena s e pa thwa ys , both of whi ch ori gi na te wi th a ra chi doni c a ci d. Thi s a cti on of gl ucocorti coi ds i s i ndi rect beca us e thei r i ni ti a l or di rect effect
i s i nduced s ynthes i s of a nnexi ns (previ ous l y ca l l ed l i pocorti ns ), whi ch a re the moi eti es tha t di rectl y i nhi bi t PLA2 a cti vi ty. Gl ucocorti coi ds ha ve no
i ntri ns i c or di rect i nhi bi tory effects on l a ter s teps i n AA meta bol i s m, tha t i s , no di rect effects on cycl ooxygena s e or l i poxygena s e a cti vi ty.
Cycl ooxygena s es (a ) a re i nhi bi ted by tra di ti ona l NSAIDs s uch a s a s pi ri n (nons el ecti ve COX-1 a nd -2 i nhi bi tors ), or the coxi bs (cel ecoxi b), whi ch
rel a ti vel y s el ecti vel y i nhi bi t COX-2. We ha ve no cl i ni ca l l y us eful i nhi bi tors of hi s ta mi ne s ynthes i s (whi ch i nvol ves hi s ti di ne deca rboxyl a s e a cti vi ty;
b). As noted el s ewhere, zi l euton i nhi bi ts 5-l i poxygena s e (c) a nd the s ubs equent forma ti on of l eukotri enes . Al l opuri nol i nhi bi ts the s ynthes i s of
xa nthi ne a nd uri c a ci d by i nhi bi ti ng xa nthi ne oxi da s e (e). The s a me a ppl i es to the new a l l opuri nol a l terna ti ve, febuxos ta t.
323. The answer is a. (Brunton, pp 721-725, 932-933; Katzung, pp 184-185.) Bra dyki ni n i s meta bol i zed to bi ol ogi ca l l y i na cti ve pepti des by a n enzyme tha t
ha s a t l ea s t three na mes : a ngi otens i n-converti ng enzyme (ACE; reca l l tha t the prototype ACE i nhi bi tor i s ca ptopri l ), bra dyki ni na s e, a nd ki ni na s e II.
The na me tha t i s us ed depends on the s ubs tra te. When the s ubs tra te i s a ngi otens i n I, the enzyme i s ca l l ed ACE. When the s ubs tra te i s bra dyki ni n
we ca l l i t ei ther bra dyki ni na s e or ki ni na s e II.
Bra dyki ni n, whether i njected experi menta l l y or deri ved from endogenous s ources (ki ni nogens cl ea ved by s peci fi c protea s es ca l l ed ka l l i krei ns ),
exerts s i gni fi ca nt va s odi l a tor effects tha t ca n l ower s ys tol i c a nd di a s tol i c bl ood pres s ures . Al though thi s ma y not be a n i mporta nt pres s ureregul a ti ng mecha ni s m i n normotens i ve i ndi vi dua l s , i t proba bl y i s i n ma ny (mos t?) pa ti ents wi th es s enti a l hypertens i on. Cl ea rl y, bra dyki ni n does
not i ncrea s e bl ood pres s ure (c) or cons tri ct the rena l va s cul a ture (e).
Reca l l tha t ACE i nhi bi tors l ower bl ood pres s ure i n ma ny hypertens i ve pa ti ents . One mecha ni s m i nvol ves pres ervi ng bra dyki ni n by i nhi bi ti ng

i ts enzyma ti c i na cti va ti on. Bra dyki ni n a l s o ca us es prerena l a rteri ol a r va s odi l a ti on a nd i ncrea s es GFR, l ea di ng to di ureti c effects .
The pepti des va s cul a r effects a re medi a ted by endothel i a l cel l -deri ved ni tri c oxi de, a nd they a re enha nced (not countera cted, b) by other drugs
tha t ca us e va s odi l a ti on by a ni tri c oxi de-rel a ted mecha ni s m.
Bra dyki ni n receptor bl ockers prevent the pepti des va s odi l a tor effects . However, no currentl y a pproved drugs , i ncl udi ng the s o-ca l l ed s econdgenera ti on a nti hi s ta mi nes s uch a s fexofena di ne (d) exert tha t effect.
324. The answer is c. (Brunton, p 966t; Katzung, p 641.) The ductus a rteri os us i n neona tes ma y rema i n pa tent l a rgel y beca us e of the va s odi l a tor effects
of endogenous PGE1 , formed vi a the cycl ooxygena s e pa thwa y. When the goa l i s to cl os e a pa tent ductus a fter bi rth we genera l l y us e a
pros ta gl a ndi n s ynthes i s (COX-1/-2) i nhi bi tor (i ndometha ci n, hi s tori ca l l y; or i buprofen more often nowa da ys ). (Convers el y, there a re ti mes when
s urgi ca l procedures a re requi red on a congeni ta l l y a noma l ous hea rt i n newborns , a nd we wa nt to keep the ductus open unti l s urgery. In tha t ca s e,
a l pros ta di l [PGE1 , a ns wer e] ma y be a dmi ni s tered.)
Mi s opros tol (d) i s a pros ta gl a ndi n a na l og. Gi vi ng i t to a newborn wi th a pa tent ductus i s l i kel y to keep the l es i on open, not cl os e i t. None of the
H 2 bl ockers (eg, ci meti di ne, a ) nor H 1 bl ockers (di phenhydra mi ne, b, a nd ma ny others ) ha ve a ny i mporta nt effects on pros ta gl a ndi n s ynthes i s , nor
a re they us ed ei ther to cl os e a pa tent ductus a rteri os us or to keep i t open for s ubs equent s urgery.
325. The answer is d. (Brunton, pp 399, 405, 410-413, 1537; Katzung, pp 285f, 292, 533-537, 1161t.) Thi s pa ti ent ha s wha t i s a l mos t certa i nl y the s erotoni n
s yndrome. The tri pta n a dds s erotoni n to s erotoni nergi c s yna ps e, a nd s erotoni ns neurona l reupta ke wi l l be bl ocked by fl uoxeti ne (or s ertra l i ne,
others ), whi ch i s cl a s s i fi ed a s a s el ecti ve s erotoni n reupta ke i nhi bi tor (SSRI) a nti depres s a nt. When s uma tri pta n (or other tri pta ns us ed for
mi gra i ne) i s a dded, ra pi d a ccumul a ti on of s erotoni n a nd/or the tri pta n i n the bra i n s yna ps es ca n occur.
The other drugs l i s ted (a ceta mi nophen, a ; codei ne, b; di a zepa m, c; a nd phenytoi n, e) a re not l i kel y to i ntera ct wi th s erotoni nergi c drugs .
326. The answer is e. (Brunton, pp 75, 83t, 977-982; Katzung, pp 62, 1034-1035.) Ti nni tus , a l ong wi th a feel i ng of di zzi nes s or l i ghthea dednes s , GI ups et
(i ncl udi ng na us ea a nd s ome pa i n or other di s comfort, a nd di a rrhea more s o tha n cons ti pa ti on), a nd s uch vi s ua l cha nges a s bl urred or di pl opi a
(but not myopi a , d), a l l a re pa rt of a l ow-gra de a s pi ri n toxi ci ty s yndrome ca l l ed s a l i cyl i s m. It i s not neces s a ri l y worri s ome (provi ded the phys i ci a n
i ntenti ona l l y pres cri bed the drug a t dos a ges l i kel y to produce the s yndrome), da ngerous , or i ndi ca ti ve of i mmi nent a nd s evere toxi ci ty. Indeed,
s ome pa ti ents experi ence one or more s i gns or s ymptoms of s a l i cyl i s m i n res pons e to hi gh (a nti a rthri ti c) dos es of a s pi ri n.
Cons ti pa ti on (a ) or hypertens i on (c) a re not ca us a l l y a s s oci a ted wi th s a l i cyl a te a dmi ni s tra ti on, rega rdl es s of the dos e us ed. Cough (b) ma y
occur, but tha t i s onl y l i kel y to occur i n pa ti ents who ha ve a s pi ri n-s ens i ti ve a s thma , a nd for thos e pa ti ents bronchocons tri cti on i s more l i kel y
tha n cough to be the res pons e.
327. The answer is e. (Brunton, p 999; Katzung, pp 656, 1160t.) Probeneci d (a nd the rel a ted drug, s ul fi npyra zone) a re cl a s s i fi ed a s uri cos uri cs : a t
s uffi ci entl y hi gh (thera peuti c) dos es , they enha nce the rena l el i mi na ti on of uri c a ci d by i nhi bi ti ng tubul a r rea bs orpti on of fi l tered ura te. As pi ri n
s i gni fi ca ntl y i mpa i rs the uri cos uri cs a cti ons .
Importa nt note: As pi ri n (gi ven a l one) ha s bl ood l evel -dependent effects on ura te el i mi na ti on by the ki dneys . At l ow dos es perha ps up to
a bout 1 g/da y, i t s el ecti vel y i nhi bi ts tubul a r s ecreti on of ura te a nd s o ca n ra i s e pl a s ma ura te l evel s . At dos es much hi gher tha n tha t (i ncl udi ng
dos es s ometi mes pres cri bed for a rthri ti s other tha n gout), the predomi na nt effect (a nd the net, or overa l l , effect) i s uri cos uri a due to bl ocka de of
tubul a r rea bs orpti on of ura te (thi s effect i s grea ter tha n the drugs i nhi bi tory effect on tubul a r s ecreti on of ura te). Nonethel es s , a s pi ri n i s not us ed
a s a uri cos uri c drug beca us e the dos es /bl ood l evel s needed to i ncrea s e ura te el i mi na ti on a re s uffi ci entl y hi gh tha t they ca us e s i gni fi ca nt s i de
effects (eg, s a l i cyl i s m; s ee Ques ti on 326) tha t dont a ri s e wi th the tra di ti ona l uri cos uri cs s uch a s probeneci d.
Aceta mi nophen (a ) ha s no a ppreci a bl e or cl i ni ca l l y us eful effects on uri c a ci d el i mi na ti on or s ynthes i s . Al l opuri nol (b, a nd the new rel a ted drug
febuxos ta t) i nhi bi ts uri c a ci d s ynthes i s , but i ts xa nthi ne oxi da s e-i nhi bi tory effects a re not a l tered by a s pi ri n. However, s i nce a l l opuri nol i s us ed to
l ower pl a s ma ura te l evel s i t i s l a rgel y i rra ti ona l to us e a s pi ri n a t the s a me ti me. The s a me a ppl i es to col chi ci ne (c) a nd i ndometha ci n (d), both of
whi ch a re us ed for i n a cute gout a nd nei ther of whi ch ha s i ts ma i n bi ochemi ca l effects (s uppres s i on of i nfl a mma ti on) i mpa i red by a s pi ri n.
328. The answer is c. (Brunton, pp 952, 1837, 1849; Katzung, pp 315, 327, 1090.) In a ddi ti on to mi s opros tol s us e a s a cytoprotecti ve/mucotropi c drug for
s ome pa ti ents ta ki ng NSAIDs , mi s opros tol i s a l s o us ed a s a n a djunct to mi fepri s tone to i nduce thera peuti c a borti on. Thi s ca pi ta l i zes on the
pros ta gl a ndi n a na l ogs s trong uteri ne-s ti mul a ti ng effects (thus , a ns wer e i s i ncorrect). The drug i s s ometi mes us ed to ma i nta i n pa tency of a n
open ductus a rteri os us , not to cl os e i t (a ). It i s not a contra cepti ve i n the typi ca l s ens e, s uch a s we woul d a s s oci a te wi th es trogen-proges ti n ora l
contra cepti ves . Gi ven the drugs a borti fa ci ent effects , i t i s contra i ndi ca ted for women who a re pregna nt, or wi s h to become pregna nt (b).
Mi s opros tol ha s bronchodi l a tor a cti vi ty, but i t i s rel a ti vel y wea k a nd the drug i s not s ui ta bl e a s a s ubs ti tute for corti cos teroi ds (d) or other typi ca l
a s thma medi ca ti ons .
329. The answer is e. (Brunton, pp 75-76, 86t, 983; Katzung, pp 1034-1035.) Adjuncti ve us e of s odi um bi ca rbona te (IV) ca n be a n i mporta nt a djunct to
ma na gi ng s evere s a l i cyl a te poi s oni ng for two ma i n rea s ons : (1) i t hel ps ra i s e bl ood pH, whi ch a s s ta ted ea rl i er i s profoundl y reduced from
meta bol i c pl us res pi ra tory a ci dos i s ; (2) i t a l ka l i ni zes the uri ne, whi ch (vi a a pH-dependent mecha ni s m, a l a Henders on-Ha s s el ba ch) converts more
a s pi ri n mol ecul es i nto the i oni zed form i n the tubul es , thereby reduci ng tubul a r rea bs orpti on of a s ubs ta nce we wa nt to el i mi na te from the body
a s qui ckl y a s pos s i bl e.
Aceta mi nophen (a ), even though i t i s us ua l l y a n effecti ve a nti pyreti c, i s not good for ma na gi ng fever of s evere a s pi ri n poi s oni ng. It woul d a dd
yet a nother drug tha t mi ght compl i ca te the cl i ni ca l pi cture, a nd ordi na ry (a nd ordi na ri l y s a fe) dos es a rent l i kel y to do much to l ower tempera ture
qui ckl y or s uffi ci entl y. (Thus , we us e phys i ca l mea ns to l ower body tempera ture.) N-a cetyl cys tei ne (c), the a nti dote for a ceta mi nophen poi s oni ng,
does nothi ng for s a l i cyl a te poi s oni ng. Ampheta mi nes (b) mi ght s eem ra ti ona l for ma na gi ng venti l a tory depres s i on tha t cha ra cteri zes l a te s ta ges
of s evere a s pi ri n poi s oni ng. The more l i kel y outcome of gi vi ng a n a mpheta mi ne i s s i mpl y to ha s ten the ons et of s ei zures . Phenoba rbi ta l (d), or
other CNS depres s a nts , woul d a ggra va te a n a l rea dy ba d s ta te of CNS/venti l a tory depres s i on. (However, i f s ei zures devel op they mus t be ma na ged
eg, wi th IV l ora zepa m a nd phenytoi n, even though they ca us e CNS depres s i on. Wi thout them, the pa ti ent ma y qui ckl y di e from s ta tus
epi l epti cus .)
Jus t a s I provi ded a ta bl e (a ns wer to Ques ti on 317) to s umma ri ze the genera l s equence of events i n a ceta mi nophen toxi ci ty, Il l provi de one
here for a s pi ri n overdos es . Aga i n, the s ta ges I pres ent a re a rbi tra ry, but they s houl d be hel pful knowi ng wha t i s l i kel y to come next a s toxi ci ty
progres s es hel ps you prepa re for wha t youl l proba bl y need to do next.
Note tha t the a vera ge l etha l dos e for a n otherwi s e hea l thy chi l d i s between a round 5 g a nd 8 g, ta ken a l l a t once. For a dul ts , i t i s between
a round 10 g a nd 30 g. Us ua l s trength a s pi ri n ta bl ets thos e us ed for a ches , pa i ns , mi l d i nfl a mma ti on, a nd feverconta i n 325 mg of the drug.
(Hea rt dos e a s pi ri n ta bl ets conta i n 81 mg.) Hi gher dos es ma y be pres cri bed for a rthri ti s s evera l gra ms a da ya nd a l though thes e us ua l l y a re
not s uffi ci ent to ca us e dea th they a re l i kel y to ca us e s i de effects tha t often a re di s turbi ng enough tha t the phys i ci a n wi l l pres cri be a nother

a nti a rthri ti c drug i ns tea d of pl a i n, chea p, a s pi ri n.

Fi na l note: Whi l e trea ti ng a s pi ri n poi s oni ng ma y s ound di ffi cul t, a s k a phys i ci a n or nurs e who ha s ha d to dea l wi th i t ma ny ti mes . They a re
l i kel y to tel l you tha t i t i s a pi ece of ca kea nd more often s ucces s ful tha n dea l i ng wi th a ceta mi nophen poi s oni ng.
330. The answer is a. (Brunton, pp 911, 920, 1313-1314, 1815-1816; Katzung, pp 277-280.) One of the ma i n a dva nta ges of the fi rs t-genera ti on
a nti hi s ta mi nes (fexofena di ne, l ora ta di ne, others ) over the ol der (s econd-genera ti on) H-1 a nta goni s ts s uch a s di phenhydra mi ne i s a rel a ti ve l a ck
of CNS depres s a nt (s eda ti ng) effects when a dmi ni s tered a t us ua l recommended dos es . The i mpl i ca ti on of thi s di fference i s tha t the newer a gents
a re much l es s l i kel y to ca us e da yti me drows i nes s or other probl ems tha t mi ght i nterfere wi th da yti me a cti vi ti es requi ri ng a l ertnes s . Seda ti on i s a
pa rti cul a r probl em wi th di phenhydra mi ne, doxyl a mi ne, a nd other members of the etha nol a mi ne cl a s s of fi rs t-genera ti on a nti hi s ta mi nes , yet i t
a l s o provi des a cl i ni ca l l y us eful effect ba s ed on thi s a cti on: they a re us eful a s OTC (di phenhydra mi ne, doxyl a mi ne) a nd pres cri pti on
(di phenhydra mi ne) s l eep-a i ds .
Di phenhydra mi ne, a nd to a l a rge degree a l l the other fi rs t-genera ti on a nti hi s ta mi nes , tend to ca us e a ppreci a bl e mus ca ri ni c receptor-bl ocki ng
(a tropi nel i ke) effects , a nd s o they a re uns ui ta bl e or potenti a l l y da ngerous for pa ti ents wi th s uch a tropi ne-rel a ted comorbi di ti es a s pros ta ti c
hypertrophy, hypomoti l i ty di s orders of the uri na ry or GI tra cts , ta chyca rdi a , or a ngl e-cl os ure gl a ucoma (s o a ns wer b i s not correct). Owi ng to
a nti mus ca ri ni c effects , di phenhydra mi ne overdos es a re more l i kel y to ca us e ta chyca rdi a (by bl ocki ng pa ra s ympa theti c-ACh-mus ca ri ni c receptor
i nfl uences on the SA node) tha n bra dyca rdi a (c). The s econd-genera ti on a nti hi s ta mi nes do bl ock hi s ta mi ne-rel a ted bronchocons tri cti on, but i n the
a bs ence of hi s ta mi ne they ha ve no i ntri ns i c bronchodi l a tor a cti vi ty. More i mporta nt i s the fa ct tha t thes e drugs pl a y no rol e a s pri ma ry thera py for
a s thma . They ma y be preferred to ol der a nti hi s ta mi nes (l a rgel y beca us e they l a ck the a nti mus ca ri ni c-rel a ted mucus -thi ckeni ng effects of s uch
drugs a s di phenhydra mi ne), but they s houl d be us ed onl y a s a djuncts to more a ppropri a te a s thma drugs s uch a s i nha l ed corti cos teroi ds (to
s uppres s a i rwa y i nfl a mma ti on) a nd i nha l ed -a drenergi c drugs for control or res cue thera py.
None of the H 1 bl ockers fi rs t-genera ti on or s econd-genera ti on a gents ha s H 2 bl ocki ng a cti vi ty tha t i s neces s a ry to s uppres s hi s ta mi nemedi a ted a ci d s ecreti on by ga s tri c pa ri eta l cel l s .
331. The answer is b. (Brunton, pp 730-736, 976; Katzung, pp 183, 299, 1160t.) A ma jor component of the a nti hypertens i ve a cti ons of ca ptopri l a nd other
ACE i nhi bi tors i s pros ta gl a ndi n-dependent. Tha t el ement of drug a cti on i s a nta goni zed by i ndometha ci n due to i ts grea t effi ca cy to i nhi bi t
pros ta gl a ndi n s ynthes i s . Other drugs wi th a cti ons tha t ma y be i nhi bi ted by pros ta gl a ndi n s ynthes i s i nhi bi tors s uch a s i ndometha ci n i ncl ude the
thi a zi de a nd l oop di ureti cs a nd (a l l egedl y) ma ny i f not mos t of the -bl ockers . The a cti ons of none of the other drugs l i s ted a re a nta goni zed by
i ndometha ci n. You s houl d note, however, tha t gi vi ng i ndometha ci n to a pa ti ent ta ki ng wa rfa ri n or a ny of the a nti pl a tel et drugs (us ed for
prophyl a xi s of a rteri a l thrombos i s ) i s ri s ky. One of the ma jor toxi ci ti es of the NSAIDs i s ga s tri c mucos a l da ma ge a nd the ri s k of GI bl eeds . In the
pres ence of a nti coa gul a nts or a nti pl a tel et drugs the ri s k of a s eri ous GI bl eed, perha ps progres s i ng to hemorrha ge, goes up ma rkedl y. However,
thi s i s not due to a typi ca l pha rma codyna mi c or pha rma coki neti c i ntera cti on between the drugs , a nd the a nti coa gul a nts effects certa i nl y a re not
i nhi bi ted by the NSAID.
332. The answer is d. (Brunton, pp 75, 83t; Katzung, pp 1034-1035.) La te, s evere a s pi ri n poi s oni ng i s cha ra cteri zed by a combi na ti on of res pi ra tory a nd
meta bol i c a ci dos i s . In ea rl y s ta ges of a s pi ri n poi s oni ng (or even wi th hi gh thera peuti c dos es of the drug), venti l a tory s ti mul a ti on occurs . Tha t
i nduces a res pi ra tory a l ka l os i s (c; net CO2 l os s , rel a ti ve HCO3 retenti on). The ki dneys compens a te for thi s by i ncrea s i ng HCO3 excreti on to hel p
norma l i ze bl ood pH a nd ca us i ng wha t ha s been ca l l ed compens a ted res pi ra tory a l ka l os i s . As pl a s ma l evel s of a s pi ri n ri s e, however, bl ood pH
fa l l s preci pi tous l y. Pa rt of tha t i s due to the a ccumul a ti on of a ci di c s a l i cyl i c a ci d i n the bl ood, a nd pa rt i s due to i nhi bi ted oxi da ti ve
phos phoryl a ti on tha t s hi fts meta bol i s m from oxi da ti ve to gl ycol yti c (wi th l a cti c a ci d bei ng the key end product). No l onger s ynthes i zi ng ATP
effecti vel y, the mi tochondri a genera te meta bol i c hea t, whi ch contri butes to fever (not hypothermi a ; a ). Venti l a tory fa i l ure (not s ti mul a ti on; e)
ens ues , l ea di ng to res pi ra tory a ci dos i s (from CO2 retenti on) a l ong wi th the meta bol i c a ci dos i s . Ca rdi ova s cul a r col l a ps e a nd s ei zures eventua l l y
ca us e dea th. Note tha t hepa totoxi ci ty i s not a component of thi s : tha t i s the ma i n ca us e of morbi di ty a nd morta l i ty wi th a ceta mi nophen poi s oni ng.
333. The answer is a. (Brunton, pp 75-76, 128t, 136, 982-984; Katzung, pp 60-61, 1032.) Aceta mi nophens ma i n toxi c meta bol i te i s Na cetyl benzoqi nonei mi ne. It rea cts wi th s ul fhydryl groups (pa rti cul a rl y wi th gl uta thi one) i n hepa tocytes , ul ti ma tel y l ea di ng to hepa ti c necros i s
when a ceta mi nophen l evel s a re s uffi ci entl y hi gh. N-a cetyl cys tei ne i s ri ch i nSH groups . It therefore rea cts wi th the i mi ne, hopeful l y s pa ri ng
endogenous s ul fhydryl compounds from further a tta ck a nd, hopeful l y, a l l owi ng ti me for the hepa tocytes to recover from the bi ochemi ca l s tres s .
Thi s foul -s mel l i ng a nti dote mus t be gi ven ea rl y a fter a ceta mi nophen poi s oni ng occurs or i s l i kel y (i t i s us ua l l y gi ven ora l l y), a nd i t mus t be gi ven
repea tedl y (s ee s peci a l ty texts for more i nforma ti on). It i s a preventa ti ve a ga i ns t hepa totoxi ci ty, not a revers i ng a gent. As a n a s i de, va ri ous
nomogra ms a re a va i l a bl e to gi ve s ome rea s ona bl e of whether a pa rti cul a r a ceta mi nophen dos e (more preci s el y, bl ood l evel ) i s l i kel y to be
hepa totoxi c or not. They pl ot pl a s ma a ceta mi nophen l evel s a s a functi on of ti me a fter drug i nges ti on (yi el di ng, ba s i ca l l y, a n el i mi na ti on ra te a nd
a n el i mi na ti on ha l f-l i fe). If the pa ti ents a ceta mi nophen l evel a t a s peci fi ed ti me fol l owi ng i nta ke i s a bove the l i ne, hepa totoxi ci ty i s proba bl e.
Such a fi ndi ng, however, does not mea n tha t N-a cetyl cys tei ne a dmi ni s tra ti on wi l l be wi thout benefi t a nd s o s houl d not be done. (See the
expl a na ti on for Ques ti on 317 for more i nforma ti on, a nd a l ook a t thi s i s s ue from a s omewha t di fferent pers pecti ve.)
Al l of the other drugs l i s ted ca n exert toxi c effects (often s eri ous ) wi th overdos es , but N-a cetyl cys tei ne i s not a n a ppropri a te or effecti ve
a nti dote for a ny of them.
334. The answer is c. (Brunton, pp 995-996; Katzung, pp 651-652.) The ma i n rea s on why ma ny phys i ci a ns a re s hunni ng ora l col chi ci ne for a cute gout i s
tha t ma ny pa ti ents devel op horri bl e GI di s comfort, vomi ti ng, di a rrhea , a nd the l i ke. For s ome, the cure i s a l mos t a s ba d a s the di s order for whi ch
the drug i s gi ven. Thi s GI di s tres s ca n be a l l evi a ted s omewha t by gi vi ng col chi ci ne IV, but more s eri ous s ys temi c res pons es ca n devel op i f the IV
dos e i s too grea t or too ma ny IV dos es a re gi ven i n a s hort peri od of ti me. (Thes e a re a mong the rea s ons why IV formul a ti ons of col chi ci ne a re no
l onger a va i l a bl e.) Indometha ci n s eems to ha ve become one of the preferred a l terna ti ves for a nti -i nfl a mma tory thera py of a cute gout or
prophyl a xi s of recurrences . (And cl ea rl y i ndometha ci n i s not wi thout s i de effects or toxi ci ti es ; the ri s ks a nd di s comforts a re s i mpl y more
a ccepta bl e, for s ome pa ti ents , wi th i t.)
But when col chi ci ne does work i n a cute gout, rel i ef ma y be dra ma ti c a nd occur l i tera l l y overni ght wi th jus t a dos e or two. The l i kel y
mecha ni s m of a cti on i nvol ves i mpa i red mi crotubul a r a s s embl y or functi on i n l eukocytes , whi ch l i mi ts thei r mi gra ti on to the a rea of crys ta l
depos i ti on a nd s o l i mi ts thei r a bi l i ty to a mpl i fy the i nfl a mma tory rea cti on.
Bone ma rrow s uppres s i on ca n occur, but tha t i s ma i nl y wi th l ong-term, hi gh-dos e ora l or pa rentera l col chi ci ne a dmi ni s tra ti on (the l a tter of
whi ch mus t be a voi ded). The s a me a ppl i es to fra nk ga s tri c da ma ge (wi th the pos s i bi l i ty of ga s tri c bl eedi ng or hemorrha ge) a nd to bl ood
dys cra s i a s (bone ma rrow toxi ci ty).
335. The answer is b. (Brunton, pp 996-997; Katzung, pp 653-654.) You ma y thi nk tha t reducti ons i n ura te content i n a 24-hour uri ne s a mpl e woul d be ba d
for the hyperuri cemi c pa ti ent, but tha t i s beca us e you proba bl y a utoma ti ca l l y (a nd i ncorrectl y) equa te l es s uri ne ura te wi th i ncrea s ed pl a s ma
ura te. Not neces s a ri l y s o. Al l opuri nol i nhi bi ts uri c a ci d s ynthes i s by i nhi bi ti ng xa nthi ne oxi da s e: l es s uri c a ci d ma de, l es s to be excreted i n the

uri ne, a nd l es s to be detected there. Thi s i s one ma ni fes ta ti on of a l l opuri nol a t work. Aceta mi nophen (a ) ha s no effects on uri c a ci d s ynthes i s ,
excreti on, or s ol ubi l i ty. Col chi ci ne (c) i s s ometi mes us ed for prophyl a xi s or trea tment of gout, but i ts a cti ons deri ve from i ts a nti -i nfl a mma tory
a cti on a nd, proba bl y, s uppres s i on of neutrophi l chemota xi s by i nterferi ng wi th mi crotubul a r functi on. It ha s no effects on ura te s ynthes i s or
el i mi na ti on. The s a me a ppl i es to i ndometha ci n (d): a nti -i nfl a mma tory a cti ons , but no effects per s e on uri c a ci d. Probeneci d (e) i s a uri cos uri c
drug tha t a cts by i nhi bi ti ng tubul a r rea bs orpti on of ura te when pl a s ma l evel s of the drug a re thera peuti c. As a res ul t, the more l i kel y outcome of
thi s drug i s a n i ncrea s e of ura te concentra ti ons i n a uri ne s a mpl e. Probeneci d does not a ffect uri c a ci d s ynthes i s .
336. The answer is e. (Brunton, pp 995-996, 1000; Katzung, pp 651-654.) The us e of s odi um bi ca rbona te (unl es s otherwi s e contra i ndi ca ted) for
prophyl a xi s of ura te s tone forma ti on i n the rena l tubul es i s ba s ed on the fa ct tha t uri c a ci d (s odi um ura te) i s poorl y s ol ubl e i n body fl ui ds a nd
s ol ubi l i ty i s grea tl y i nfl uenced by l oca l pH. When l oca l pH fa l l s , more ura te crys ta l l i zes (i e, the KSP fa l l s ). Cons i deri ng tha t uri ne pH i s l ower tha n
bl ood (or s ynovi a l fl ui d) pH, a nd s i nce rel a ti vel y l a rge a mounts of ura te i s excreted i n the uri ne (even i n the a bs ence of a uri cos uri c drug, eg,
probeneci d), there i s a grea ter tendency for ura te to crys ta l l i ze i n the uri na ry tra ct. Convers el y, a s uri ne pH ri s es (a s occurs wi th s odi um
bi ca rbona te a dmi ni s tra ti on), ura te i s more s ol ubl e (for a gi ven concentra ti on) a nd l es s l i kel y to preci pi ta te. Thi s pH-rel a ted phenomenon a l s o
contri butes to the vi ci ous cycl e tha t s ta rts when a n a cute gout a tta ck i n a joi nt occurs .
An a ddi ti ona l body l oa d of s odi um bi ca rbona te wi l l i nduce, through norma l rena l compens a tory proces s es , a di ureti c (not a nti di ureti c, a ns wer
a ) effect; thi s s houl d a l s o i ncrea s e the a mount of ura te tha t i s l os t i nto the uri ne. Al though s odi um bi ca rbona te ra i s es bl ood pH, tha t ha s no
cl i ni ca l l y rel eva nt effect on forma ti on of xa nthi ne a nd uri c a ci d by xa nthi ne oxi da s e (b). There i s no meta bol i c a ci dos i s tha t i s cha ra cteri s ti c of
s evere hyperuri cemi a (c). Sodi um bi ca rbona te does not l ower GFR a nd/or ura te el i mi na ti on (d).
337. The answer is c. (Brunton, pp 918-926; Katzung, pp 117-124, 277-280.) Di phenhydra mi ne, a member of the etha nol a mi ne cl a s s of H 1 a nta goni s ts a nd
a rgua bl y the prototype of a l l the ol der (fi rs t-genera ti on a nti hi s ta mi nes ), pos s es s es two ma i n properti es i n a ddi ti on to effecti ve competi ti ve
bl ocka de of H 1 receptors : s eda ti on (c), i n pa rt due to the drugs l i pophi l i ci ty; a nd mus ca ri ni c (chol i nergi c) receptor bl ocka de tha t i s a l s o
competi ti ve. Both effects occur commonl y, a nd ca n be qui te i ntens e. The CNS depres s a nt effects of di phenhydra mi ne a re s uch tha t thi s drug i s the
ma i n (i f not onl y) a cti ve i ngredi ent i n OTC s l eep a i ds , hel pi ng one dri ft off to s l eep even i n the a bs ence of a l l ergy s i gns a nd s ymptoms a nd
proba bl y i n a wa y tha t i s unrel a ted to the drugs peri phera l H-1 bl ocki ng a cti vi ty.
The a nti mus ca ri ni c (a tropi ne-l i ke effects ) woul d be ma ni fes t by s uch s i de effects a s ta chyca rdi a (not bra dyca rdi a ; a ); cons ti pa ti on (not di a rrhea ;
b); a s uppres s i on of ACh-i nduced ga s tri c a ci d s ecreti on (not the oppos i te; d); a nd a tendency for uri na ry retenti on (not frequency; e). The s trong
a nti -mus ca ri ni c effects of di phenhydra mi ne ea rn i t the s a me preca uti ons a nd contra i ndi ca ti ons we norma l l y a ppl y to a tropi ne i ts el f, i ncl udi ng
pros ta ti c hypertrophy a nd a ngl e-cl os ure gl a ucoma . Other s i de effects i ncl ude xeros tomi a , bl urred vi s i on, pa ra l ys i s of a ccommoda ti on, a nd
i nhi bi ti on of s wea ti ng. Di phenhydra mi ne toxi ci ty ma ni fes ts i n wa ys tha t a re ma rkedl y s i mi l a r to wha t occurs wi th a tropi ne poi s oni ng, a nd i s
ma na ged i n the s a me wa y, i ncl udi ng the us e of phys os ti gmi ne (ACh es tera s e i nhi bi tor wi th a cti ons i n both the peri phera l a nd centra l nervous
s ys tems ) for s evere or l i fe-threa teni ng toxi ci ty.
As a n i mporta nt a s i de, l ora ta di ne, des l ora ta di ne, fexofena di ne, a nd rel a ted newer (s econd genera ti on) H-1 bl ockers (pi peri di ne cl a s s ) a re
a s s oci a ted wi th much l es s CNS depres s i on. (they a re a dverti s ed a s nons eda ti ngus ua l l y wi th a di s cl a i mer, i n fi ne pri nt, when ta ken a s
di rected.) Unl i ke di phenhydra mi ne a nd mos t of the ol der H-1 bl ockers , the newer a gents ca us e no a nti mus ca ri ni c effects a nd ha ve no a tropi nerel a ted preca uti ons or contra i ndi ca ti ons .
338. The answer is c. (Brunton, pp 1018, 1826-1827; Katzung, pp 647, 656, 992, 999.) Eta nercept (a nd the rel a ted drug i nfl i xi ma b) bi nds to a nd neutra l i zes
TNF-, whi ch i s one of the pri ma ry pa thophys i ol ogi c medi a tors i n rheuma toi d a rthri ti s a nd Crohn di s ea s e. It functi ons , then, a s a n a nti body.
Eta nercept ha s no effect on ei cos a noi d s ynthes i s (a , d) or l eukocyte mi gra ti on (b). It does not s ti mul a te col l a gen, mucopol ys a ccha ri de, or s ynovi a l
fl ui d s ynthes i s (e).

Gastrointestinal and Urinary Tract Pharmacology, Nutrition (Vitamins)

Aci d s ecreti on i nhi bi tors (H 2 bl ockers , proton pump i nhi bi tors , others )
Anta ci ds
Anti di a rrhea l s
Drugs a ffecti ng GI or uri na ry tra ct mus cul a ture
Emeti cs , a nti emeti cs
Ga l l s tone-di s s ol vi ng drugs
Ga s tri c mucotropi c/cytoprotecti ve protecti ve drugs
Infl a mma tory bowel di s ea s e drugs
La xa ti ves , ca tha rti cs
Pa ncrea ti c enzyme repl a cement
Vi ta mi ns

Questions
339. A 65-yea r-ol d ma n wi l l be undergoi ng el ecti ve tota l knee repl a cement s urgery. He i s urged to s ta rt ta ki ng a s peci fi ed s tool s oftener s evera l
da ys before s urgery, a nd i t wi l l conti nue to be a dmi ni s tered a s needed for s evera l da ys a fter the s urgery. Tha t i s beca us e of one of the drugs he
wi l l recei ve i n the opera ti ve a nd pos t-op peri ods (l i s ted bel ow) routi nel y ca us es s evere cons ti pa ti on. Whi ch drug i s tha t?
a . Ketorol a c to s uppl ement pos topera ti ve a na l ges i a from morphi ne
b. Mi da zol a m for s eda ti on, a nxi ety rel i ef, a nd i nducti on of s hort-term a mnes i a
c. Morphi ne a nd/or a s i mi l a r hi gh-effi ca cy opi oi d for pa i n
d. Neos ti gmi ne a s pa rt of a protocol to revers e s kel eta l mus cl e pa ra l ys i s
e. Onda ns etron for ma na gement of pos topera ti ve na us ea a nd vomi ti ng
340. A pa ti ent wi th mul ti pl e medi ca l probl ems i s ta ki ng s evera l drugs , i ncl udi ng theophyl l i ne, wa rfa ri n, qui ni di ne, a nd phenytoi n. Des pi te the
l i kel i hood of i ntera cti ons , dos a ges of ea ch were a djus ted ca reful l y s o thei r pl a s ma concentra ti ons a nd effects a re a ccepta bl e. However, the
pa ti ent s uffers s ome GI di s tres s a nd s ta rts ta ki ng a drug provi ded by one of hi s wel l -i ntenti oned fri ends . He pres ents wi th exces s i ve or toxi c
effects from all hi s other medi ca ti ons , a nd bl ood tes ts revea l tha t pl a s ma concentra ti ons of a l l the pres cri bed drugs a re hi gh. Whi ch drug di d the
pa ti ent mos t l i kel y s el f-pres cri be a nd ta ke?
a . Anta ci d (typi ca l ma gnes i um-a l umi num combi na ti on)
b. Ci meti di ne
c. Fa moti di ne
d. Ni za ti di ne
e. Ra ni ti di ne
341. A 53-yea r-ol d woma n ha s been ta ki ng wa rfa ri n for prophyl a xi s of venous thromboembol i s m for the l a s t 6 months . Duri ng tha t ti me the degree
of a nti coa gul a ti on, ba s ed on frequent mea s urements of her INR (Interna ti ona l Norma l i zed Ra ti o, a n a djus ted prothrombi n ti me), ha s been i n the
des i red thera peuti c ra nge, 2.5, a nd s he s uffered no a dvers e effects . Two weeks a go, s he devel oped wha t s he bel i eved to be hea rtburn, a nd
wi thout cons ul ti ng her MD bega n ta ki ng a n over-the-counter medi ci ne on a da i l y ba s i s to control i t. She pres ents i n cl i ni c toda y, reporti ng frequent
epi s ta xi s , a nd s a ys her gums bl eed when s he brus hes her teeth. Her INR i s now 9, wel l a bove the norma l thera peuti c ra nge a nd i ndi ca ti ve of
exces s wa rfa ri n effects . Whi ch of the fol l owi ng medi ci nes mos t l i kel y i ntera cted wi th the wa rfa ri n to ca us e thes e s i gns a nd s ymptoms ?
a . Bi s muth s a l ts (eg, Pepto-Bi s mol )
b. Ca l ci um ca rbona te
c. Ci meti di ne
d. Es omepra zol e
e. Ma gnes i um-a l umi num a nta ci d combi na ti on
f. Ni za ti di ne
342. Es omepra zol e i s one of the medi ca ti ons pres cri bed for a pa ti ent you a re s eei ng toda y i n the genera l medi ci ne cl i ni c. Whi ch one of the
fol l owi ng s ta tements bes t des cri bes the a cti ons or effects of es omepra zol e a nd other drugs i n i ts cl a s s ?
a . Ca us e s trong s ys temi c a tropi ne-l i ke (a nti mus ca ri ni c) effects tha t l i mi t thei r us e i n pa ti ents for whom a tropi ne i ts el f i s contra i ndi ca ted
b. Inhi bi t ga s tri c a ci d s ecreti on by s i mul ta neous l y a nd competi ti vel y bl ocki ng the a cti ons of the a goni s ts hi s ta mi ne, a cetyl chol i ne, a nd ga s tri n, on
thei r pa ri eta l cel l membra ne receptors
c. Neutra l i ze ga s tri c a ci d fa s ter tha n a ny other cl a s s es of drugs i ndi ca ted for pepti c ul cer di s ea s e or ga s troes opha gea l refl ux di s ea s e (GERD)
d. Profoundl y i nhi bi t a n ATPa s e l oca ted on pa ri eta l cel l membra nes , thereby i nhi bi ti ng a ci d s ecreti on
e. Tend to ca us e bra dyca rdi a by a nta goni zi ng the pos i ti ve chronotropi c effects of hi s ta mi ne on ca rdi a c H 1 receptors
343. A 60-yea r-ol d ma n ha s epi s odes of s evere ga s tri c a nd es opha gea l pa i n tha t i s ul ti ma tel y l i nked to ga s tri c a ci d. Whi ch one of the fol l owi ng
drugs or drug cl a s s es , whether a va i l a bl e over-the-counter or pres cri bed, i s mos t l i kel y to rel i eve the a ci d-rel a ted s ymptoms the fa s tes t when ta ken
a t us ua l l y effecti ve/recommended dos es ?
a . Anta ci ds (eg, ma gnes i um-a l umi num combi na ti ons )
b. Ci meti di ne (but not other drugs i n i ts cl a s s )
c. H 2 bl ockers , a ny of them

d. Mi s opros tol
e. Proton pump i nhi bi tors
344. Fi ve da ys a fter s ta rti ng s el f-medi ca ti on for di a rrhea a nd other GI compl a i nts tha t a ros e a fter a tri p to Centra l Ameri ca , a very worri ed pa ti ent
ca l l s to report tha t hi s tongue ha s turned bl a ck. Hi s s tool s ha ve da rkened too, but hi s des cri pti on does nt a t a l l fi t wi th wha t woul d be expected i f
the pa ti ent ha d a bl eed a nywhere i n the GI tra ct (eg, no coffee grounds s tool s s ugges ti ve of a ga s tri c bl eed.). Whi ch drug mos t l i kel y ca us ed
thes e s i gns ?
a . Bi s muth s a l ts
b. Ca l ci um ca rbona te
c. Ci meti di ne
d. Es omepra zol e
e. Ma gnes i um-a l umi num a nta ci d combi na ti on
f. Ni za ti di ne
345. A pa ti ent who ha s been a hi gh-dos e a l cohol a bus er for ma ny yea rs pres ents wi th hepa ti c porta l -s ys temi c encepha l opa thy. Wha t drug, gi ven i n
rel a ti vel y hi gh dos es , woul d be mos t s ui ta bl e for the rel i ef of s ome of the s i gns a nd s ymptoms of thi s condi ti on, a nd the l i kel y underl yi ng
bi ochemi ca l a noma l i es ?
a . Di phenoxyl a te
b. Es omepra zol e
c. La ctul os e
d. Lopera mi de
e. Onda ns etron
346. Fa t-s ol ubl e vi ta mi ns , compa red wi th thei r wa ter-s ol ubl e counterpa rts , genera l l y ha ve a grea ter potenti a l toxi ci ty to the us er when ta ken i n
exces s . Wha t property of thos e vi ta mi ns A, D, E, a nd Ki s ba s i ca l l y the ma i n rea s on for thi s fi ndi ng?
a . Admi ni s tered i n l a rger dos es
b. Avi dl y s tored by the body
c. Ca pa bl e of di s s ol vi ng membra ne phos phol i pi ds
d. Invol ved i n more es s enti a l meta bol i c pa thwa ys
e. Meta bol i zed much more s l owl y
347. A pa ti ent i s tra ns ported from a di s ta nt hos pi ta l to your s urgi ca l s ervi ce by a i r a mbul a nce. He ha d a bdomi na l s urgery a nd i n the pos top ca re
uni t he recei ved a drug tha t wa s cl ea rl y not i ndi ca ted. The drug ca us ed i ntens e contra cti on of the detrus or a nd tri gone mus cl es of hi s bl a dder. The
fi rs t dos e fa i l ed to ca us e emptyi ng of the bl a dder, s o a s econd dos e wa s gi ven. However, a nd unknown to hi s pri or ca re tea m, he ha d a ma s s tha t
ra ther s i gni fi ca ntl y obs tructed hi s urethra , a nd pri or a na tomi ca l wea keni ng i n a porti on of hi s bl a dder. Upon a dmi ni s tra ti on of the drug he fi rs t
s uffered retrogra de uri ne fl ow (from hi s bl a dder, ba ck to the ki dneys vi a the ureters ), ca us i ng rena l da ma ge. Soon therea fter hi s bl a dder ruptured
i nto hi s peri toneum. Whi ch drug or drug cl a s s mos t l i kel y ca us ed thes e a dvers e effects ?
a . Al buterol
b. Atropi ne or a s i mi l a r a nti mus ca ri ni c
c. Betha nechol
d. Furos emi de
e. Propra nol ol or a s i mi l a r -bl ocker
348. A pa ti ent pres ents wi th ma l a i s e, a nd s ki n a nd mucous membra nes a ppea r pa l e. Among the key fi ndi ngs from bl ood work a re hypochromi c,
mi crocyti c red cel l s a nd reduced red cel l count/hema tocri t; reduced reti cul ocyte count; a nd reduced tota l hemogl obi n content. Whi ch drug woul d be
i ndi ca ted, ba s ed on the pres enta ti on?
a . Cya nocoba l a mi n (B 12 )
b. Fol i c a ci d
c. Iron
d. Vi ta mi n C
e. Vi ta mi n D
349. A pa ti ent wi l l s ta rt ta ki ng one of the drugs l i s ted bel ow. As we ha nd them the pres cri pti on we a dvi s e them not to ta ke s uppl ementa l vi ta mi n
B 6 (pyri doxi ne), whether a l one or a s pa rt of a mul ti vi ta mi n s uppl ement, beca us e the vi ta mi n i s l i kel y to countera ct a des i red effect of the
pres cri bed drug. To whi ch drug does thi s a dvi ce a ppl y?
a . Ca ptopri l for hea rt fa i l ure or hypertens i on
b. Ha l operi dol for Tourette s yndrome
c. Levodopa /ca rbi dopa for Pa rki ns on di s ea s e
d. Ni a ci n for hypertri gl yceri demi a
e. Phenytoi n for epi l eps y
350. A pa ti ent wi th tubercul os i s i s bei ng trea ted wi th i s oni a zi d. She devel ops pa res thes i a s , mus cl e a ches , a nd uns tea di nes s . Whi ch vi ta mi n
needs to be gi ven i n s uppl ementa l dos es i n order to revers e thes e s ymptoms or us ed from the outs et to prevent them i n hi gh-ri s k pa ti ents ?
a . Vi ta mi n A
b. Vi ta mi n B 1 (thi a mi ne)

c. Vi ta mi n B 6 (pyri doxi ne)

d. Vi ta mi n C
e. Vi ta mi n K
351. A pa ti ent ha s s evere ga s troes opha gea l refl ux di s ea s e (GERD). In a ddi ti on to provi di ng s ome i mmedi a te s ymptom rel i ef, for whi ch you wi l l
pres cri be us ua l l y effecti ve dos es of a n OTC combi na ti on a nta ci d product, you wa nt to s uppres s ga s tri c a ci d compl etel y a s pos s i bl e. Whi ch drug i s
bes t s ui ted for a chi evi ng tha t goa l ?
a . Atropi ne
b. Ca l ci um ca rbona te
c. Ci meti di ne
d. Es omepra zol e
e. Mi s opros tol
352. An opi oi d a bus er, s eeki ng s omethi ng to s el f-a dmi ni s ter for s ubjecti ve res pons es , gets a l a rge a mount of di phenoxyl a te a nd cons umes i t a l l a t
once. He i s not l i kel y to do thi s a ga i n beca us e he ha s cons umed a combi na ti on product tha t conta i ns not onl y the di phenoxyl a te but a l s o a nother
drug tha t ca us es a hos t of unpl ea s a nt s ys temi c res pons es . Wha t i s the other drug found i n combi na ti on wi th the di phenoxyl a te?
a . Apomorphi ne
b. Atropi ne
c. Ipeca c
d. Ma gnes i um s ul fa te
e. Na l trexone
353. Duri ng a regul a r check-up, your pa ti ent s ta tes You know, doc, s ometi mes a fter ea ti ng I get hea rtburn you know, a ci d-i ndi ges ti on. Si nce the
s ymptoms s eem to be mi l d a nd i nfrequent, you s ugges t a n empi ri c tri a l of a n OTC a nta ci d for prompt s ymptom rel i ef, pl us a n ora l a nti -a ci d
s ecretory drug for l ong-term control . You recommend s evera l a nta ci d bra nds for the pa ti ent to try. Al l the products you l i s t a re combi na ti on
products tha t conta i n a ma gnes i um s a l t a nd a n a l umi num s a l t. Wha t i s ma i n ra ti ona l e or rea s on why the va s t ma jori ty of thes e products conta i n
thes e two pa rti cul a r drugs or s a l ts ?
a . Al s a l ts countera ct the ga s tri c mucos a l -i rri ta ti ng effects of Mg s a l ts
b. Al s a l ts requi re a cti va ti on by a n Mg-dependent enzyme i n order to i nhi bi t the pa ri eta l cel l proton pumps
c. Mg s a l ts ca us e a di ures i s tha t hel ps reduce s ys temi c a ccumul a ti on of the Al s a l t by i ncrea s i ng rena l Al excreti on
d. Mg s a l ts potenti a te the a bi l i ty of Al s a l ts to i nhi bi t ga s tri c a ci d s ecreti on
e. Mg s a l ts tend to ca us e a l a xa ti ve effect (i ncrea s ed gut moti l i ty) tha t countera cts the tendency of a n Al s a l t to ca us e cons ti pa ti on
354. A pa ti ent wi th mul ti pl e GI compl a i nts i s recei vi ng urs odeoxychol i c a ci d (urs odi ol ) a s pa rt of hi s drug regi men. Wha t i s the mos t l i kel y purpos e
for whi ch thi s drug i s bei ng gi ven?
a . Di s s ol vi ng chol es terol s tones i n the bi l e ducts
b. Enha nci ng i ntes ti na l di ges ti on a nd a bs orpti on of di eta ry fa ts
c. Hel pi ng to revers e ma l a bs orpti on of fa t-s ol ubl e vi ta mi ns from the di et
d. Sti mul a ti ng ga s tri c a ci d s ecreti on i n a chl orhydri a
e. Suppres s i ng s tea torrhea a nd i ts cons equences
355. Ea rl y-on i n your genera l medi ci ne cl erks hi p you encounter a pa ti ent who i s ta ki ng a proton pump i nhi bi tor, bi s muth, metroni da zol e, a nd
tetra cycl i ne. Wha t i s the mos t l i kel y condi ti on for whi ch thi s drug combi na ti on i s bei ng us ed?
a . Anti bi oti c-a s s oci a ted ps eudomembra nous col i ti s
b. Irri ta bl e bowel s yndrome (IBS)
c. Refra ctory or recurrent, a nd s evere, ga s tri c or duodena l ul cers s econda ry to H. pylori
d. Tra vel ers di a rrhea , s evere, Escherichia coli-i nduced, from dri nki ng conta mi na ted wa ter
e. Ul cers tha t occur i n res pons e to l ong-term, hi gh-dos e NSAID thera py for a rthri ti s
356. Severa l bra nd-na me a nd s tore-bra nd pi nk medi ca ti ons , a dmi ni s tered ora l l y a nd a va i l a bl e wi thout pres cri pti on, a re wi del y us ed to hel p
a l l evi a te occa s i ona l a nd s hort-l i ved na us ea a nd vomi ti ng, nons peci fi c GI di s tres s , a nd di a rrhea . They a re a l s o recommended for prophyl a xi s of
tra vel ers di a rrhea , whi ch typi ca l l y i s ca us ed by i nges ti on of foods or bevera ges conta mi na ted wi th E. coli. Thes e products conta i n bi s muth
s ubs a l i cyl a te, a nd beca us e of the pres ence of a n a s pi ri n-l i ke compound (a s a l i cyl a te) they s houl d not be ta ken by or a dmi ni s tered to certa i n
pa ti ents . Whi ch pa ti ent-rel a ted fa ctor or comorbi di ty contra i ndi ca tes us e of thi s drug or product?
a . Es s enti a l hypertens i on
b. Fl u, chi ckenpox, or other vi ra l i l l nes s i n a chi l d or a dol es cent
c. Hot fl a s hes a nd other s i gns /s ymptoms of menopa us e
d. Pros ta ti c hypertrophy or gl a ucoma i n el derl y men
e. Rheuma toi d or os teoa rthri ti s
f. Severe s ea s ona l a l l ergy s i gns a nd s ymptoms
357. A pa ti ent ha s undi a gnos ed mul ti pl e ga s tri c ul cers . Shortl y a fter cons umi ng a l a rge mea l a nd l a rge a mounts of a l cohol , he experi ences
s i gni fi ca nt GI di s tres s . He ta kes a n over-the-counter hea rtburn remedy. Wi thi n a mi nute or two he devel ops wha t he wi l l l a ter des cri be a s a ba d
bl oa ted feel i ng. Severa l of the ul cers ha ve begun to bl eed a nd he experi ences s ea ri ng pa i n.
The pa ti ent becomes profoundl y hypotens i ve from upper GI bl ood l os s a nd i s tra ns ported to the hos pi ta l . Endos copy confi rms mul ti pl e bl eeds ;
the endos copi s t rema rks tha t i t a ppea rs a s i f the l es i ons ha d been l i tera l l y s tretched a pa rt, ca us i ng a ddi ti ona l ti s s ue da ma ge tha t l ed to the

hemorrha ge. Whi ch drug or product di d the pa ti ent mos t l i kel y ta ke?
a . An a l umi num s a l t
b. An a l umi num-ma gnes i um combi na ti on a nta ci d product
c. Ma gnes i um hydroxi de
d. Ra ni ti di ne
e. Sodi um bi ca rbona te
358. You ha ve a pa ti ent who ha s been cons umi ng extra ordi na ri l y l a rge a mounts of a l cohol for s evera l yea rs , a nd i s genera l l y ma l nouri s hed. He
a bruptl y s tops hi s a l cohol i nta ke a nd goes i nto a cute a l cohol wi thdra wa l . Perti nent s i gns a nd s ymptoms i ncl ude nys ta gmus a nd bi za rre ocul a r
movements , a nd confus i on (Werni cke encepha l opa thy). Al though thi s pa ti ents a l cohol cons umpti on pa ttern ha s been a ccompa ni ed by poor
nutri ent i nta ke overa l l , you need to ma na ge the encepha l opa thy. Whi ch drug i s mos t a ppropri a te for thi s us e?
a . -tocopherol (vi ta mi n E)
b. Cya nocoba l a mi n (vi ta mi n B 12 )
c. Fol i c a ci d
d. Phytona di one (vi ta mi n K)
e. Thi a mi ne (vi ta mi n B 1 )
359. A pa ti ent ha s s tea torrhea s econda ry to cys ti c fi bros i s . Whi ch drug us ua l l y i s cons i dered the mos t rea s ona bl e a nd us ua l l y effecti ve drug for
ma na gi ng the fa tty s tool s ?
a . Atorva s ta ti n (or a ny other HMG Co-A-reducta s e i nhi bi tor)
b. Ci meti di ne (or a n a l terna ti ve, eg, fa moti di ne)
c. Bi l e s a l ts
d. Metocl opra mi de
e. Pa ncrel i pa s e
360. You a re meeti ng wi th a woma n i n whom pregna ncy ha s jus t been confi rmed, a nd a s pa rt of your hol i s ti c pa ti ent educa ti on you gi ve her expl i ci t
a dvi ce to a voi d ta ki ng s uppl ements of a pa rti cul a r vi ta mi n, es peci a l l y i n hi gh dos es , beca us e i t i s hi ghl y tera togeni c. You a l s o note the need to
a voi d a ny drugs tha t a re deri va ti ves of thi s nutri ent duri ng pregna ncy, for the s a me rea s on. To whi ch one of the fol l owi ng vi ta mi ns does thi s
preca uti on a ppl y?
a. A
b. B 12
c. C
d. E
e. Fol i c a ci d
361. A pa ti ent bei ng ca red for by the ga s troenterol ogy s ervi ce i s bei ng trea ted wi th s ul fa s a l a zi ne. Wha t i s the mos t l i kel y purpos e for whi ch i t i s
bei ng gi ven?
a . Anti bi oti c-a s s oci a ted ps eudomembra nous col i ti s
b. E. coli-i nduced di a rrhea
c. Ga s tri c H. pylori i nfecti ons
d. Infl a mma tory bowel di s ea s e
e. NSAID-i nduced ga s tri c ul cer prophyl a xi s
362. A pa ti ent wi th rena l fa i l ure i s undergoi ng peri odi c hemodi a l ys i s whi l e a wa i ti ng a tra ns pl a nt. Between di a l ys i s s es s i ons we wa nt to reduce
the bodys phos pha te l oa d by reduci ng di eta ry phos pha te a bs orpti on a nd removi ng s ome phos pha te a l rea dy i n the bl ood. Whi ch drug woul d be
mos t s ui ta bl e for thi s purpos e?
a . Al umi num hydroxi de
b. Bi s muth s ubs a l i cyl a te
c. Ma gnes i um hydroxi de/oxi de
d. Sodi um bi ca rbona te
e. Sucra l fa te
363. A woma n ha s s evere i rri ta bl e bowel s yndrome (IBS) cha ra cteri zed by frequent, profus e, a nd s ymptoma ti c di a rrhea . She ha s not res ponded to
fi rs t-l i ne thera pi es a nd i s s ta rted on a l os etron. Wha t i s the mos t worri s ome a dvers e effect a s s oci a ted wi th thi s drug?
a . Ca rdi a c a rrhythmi a s (s eri ous , eg, ventri cul a r fi bri l l a ti on)
b. Cons ti pa ti on, bowel i mpa cti on, i s chemi c col i ti s
c. Pa rki ns oni a n extra pyra mi da l rea cti ons
d. Pul mona ry fi bros i s
e. Rena l fa i l ure
364. A pa ti ent undergoi ng ca ncer chemothera py gets onda ns etron for prophyl a xi s of drug-i nduced na us ea a nd vomi ti ng. Whi ch bes t des cri bes thi s
drugs ma i n mecha ni s m of a cti on i n thi s s etti ng?
a . Acti va tes -type opi oi d receptors i n the chemoreceptor tri gger zone (CTZ)
b. Bl ocks centra l s erotoni n (5-HT3 ) receptors

c. Bl ocks dopa mi ne receptors

d. Bl ocks hi s ta mi ne H 1 receptors i n the bra i ns tem a nd i nner ea r
e. Suppres s es ga s tri c moti l i ty a nd a ci d s ecreti on vi a mus ca ri ni c bl ocka de

Gastrointestinal and Urinary Tract Pharmacology, Nutrition (Vitamins)

Answers
339. The answer is c. (Brunton, pp 496, 501-502; Katzung, p 552.) Morphi ne (whi ch i s often us ed for s hort-term pos top pa i n control ) a nd fenta nyl (whi ch
i s often us ed for i ntra opera ti ve pa i n preventi on) ca us e numerous s i de effects . One of the gra ves t concerns for mos t pa ti ents i s venti l a tory
depres s i on, but tha t ca n be ma na ged ea s i l y wi th s uch i nterventi ons a s venti l a tory s upport. Even i n the a bs ence of a ny l i ngeri ng pos t-op
venti l a tory probl ems , cons ti pa ti on from a s trong opi oi d pos es a very common a nd potenti a l l y s eri ous pos t-op ma na gement i s s ue. Tha t i s why
s tool s ofteners or l a xa ti ves ta ke on a n i mporta nt rol e for s uch pa ti ents . Nei ther ketorol a c (a ) nor mi da zol a m (b) ca us e s i gni fi ca nt reducti ons of gut
moti l i ty. Neos ti gmi ne (d), the mos t common a cetyl chol i nes tera s e i nhi bi tor us ed to revers e drug-i nduced s kel eta l mus cl e pa ra l ys i s , woul d not
l i kel y to requi re a s tool s oftener or l a xa ti ve. Indeed, vi a neos ti gmi nes a bi l i ty to i ncrea s e gut moti l i ty (s ti mul a tes l ongi tudi na l gut mus cl e a cti vi ty,
rel a xes s phi ncters ) i t i s proba bl y the l ea s t l i kel y drug to neces s i ta te us e of a s tool s oftener. Onda ns etron (e), qui te effecti ve i n ma na gi ng
peri opera ti ve na us ea a nd vomi ti ng, ha s a cons ti pa ti on-i nduci ng ri s k fa r l ower tha n tha t a s s oci a ted wi th s trong opi oi ds .
340. The answer is b. (Brunton, p 845; Katzung, pp 610t, 1083t, 1111, 1155t.) Ci meti di ne di ffers s i gni fi ca ntl y from the other H 2 bl ockers , fa moti -di ne (c),
ni za ti di ne (d), a nd ra ni ti di ne (e), i n tha t i t i s a very effecti ve i nhi bi tor of the hepa ti c mi xed functi on oxi da s e (P450) drug-meta bol i zi ng enzyme
s ys tems . (Ci meti di ne i nhi bi ts CYP1A2, 2C9, 2D6, a nd 3A4.) The other H 2 bl ockers ha ve no s i gni fi ca nt P450 effects , nor do they ca us e s i de effects a s
frequent or a s probl ema ti c a s thos e ca us ed by ci meti di ne, es peci a l l y a t hi gh dos es . The outcome of P450 i nhi bi ti on, of cours e, i s reduced hepa ti c
cl ea ra nce of the i ntera cta nts , l ea di ng to exces s i ve pl a s ma concentra ti ons a nd effects i f thei r dos a ges a re not reduced properl y. The exa mpl es
ci ted i n the ques ti onphenytoi n, wa rfa ri n, qui ni di ne, a nd theophyl l i nea re a mong the i mporta nt i ntera cta nts wi th ci meti di ne. They ha ve ra ther
l ow ma rgi ns of s a fety (or thera peuti c i ndex: LD50/ED50), s o even a s l i ght i ncrea s es i n pl a s ma l evel s (reducti ons of meta bol i c cl ea ra nce) ma y be
enough to ca us e toxi ci ty. Gi ven the fa ct tha t the a l terna ti ve H 2 bl ockers dont i nhi bi t the P450 s ys tem, theres no ra ti ona l rea s on for pres cri bi ng
ci meti di ne to pa ti ents on mul ti pl e drug thera py (a nd i n thi s ca s e, the pa ti ent s houl d ha ve been wa rned a bout s el f-medi ca ti ng wi th i t).
Anta ci ds (a ; pa rti cul a rl y thos e tha t i ncl ude a n a l umi num s a l t, whi ch a ppl i es to the va s t ma jori ty of OTC a nta ci d combi na ti on products ) tend to
a ds orb other drugs i n the gut a t or a round the s a me ti me, a nd i nhi bi t thei r a bs orpti on (ra te, extent, or both). If thi s pa ti ent ha d ta ken a n a nta ci d
wi th hi s other meds , on a regul a r ba s i s , you woul d s ee reduced bl ood l evel s a nd effects not i ncrea s es a s des cri bed i n the ques ti on.
Note: Not l ong a fter the newer H 2 bl ockers ca me on the ma rket, a nd we knew tha t they ca us ed fewer s i de effects tha n ci meti di ne a nd certa i nl y
di d not i nhi bi t va ri ous CYP enzymes to ca us e drug-drug i ntera cti ons , I a s ked a ga s troenterol ogi s t why one woul d ever pres cri be ci meti di ne. Her
a ns wer? She coul dnt thi nk of a va l i d rea s on except cos t. And now, a s cos ts ha ve come down, even tha ts not a cons i dera ti on. Fi na l l y, i t i s
i mporta nt to remember: ci meti di ne i s s ti l l a va i l a bl e OTC, a nd pa ti ents who s houl d not be ta ki ng i t (ma i nl y beca us e of i ntera cti ons wi th other
drugs they ma y be ta ki ng) ca n s ti l l us e thi s drug wi thout your OK or even your knowl edge.
341. The correct answer is c. (Brunton, pp 845, 918, 1313t; Katzung, pp 610t, 1083t, 1111, 1155t.) Compa red wi th a l l other drugs or drug groups l i s ted,
ci meti di ne s ta nds out i n terms of i ts a bi l i ty to i nhi bi t s trongl y the l i vers P450 s ys tem, whi ch i s i mporta nt for the meta bol i c i na cti va ti on of wa rfa ri n
(a nd ma ny other drugs ). PPIs s uch a s es omepra zol e (d) dont s ha re thi s property, nor do H 2 bl ockers other tha n ci meti di ne (eg, ni za ti di ne).
[Ra ni ti di ne, not l i s ted a s a n a ns wer choi ce, i s a n H 2 bl ocker tha t does ha ve s ome P-450-i nhi bi tory a cti vi ty, but i t i s very wea kpa rti cul a rl y i n
compa ri s on wi th ci meti di nea nd the cons equences of a ny potenti a l drug i ntera cti on by thi s mecha ni s m proba bl y i s not cl i ni ca l l y i mporta nt.]
There i s a n i ntera cti on between wa rfa ri n (a nd ma ny other ora l l y a dmi ni s tered drugs ) wi th bi s muth s a l ts (a ) a nd, es peci a l l y, a nta ci ds (b, e) or
a nta ci d combi na ti ons , pa rti cul a rl y Mg-Al combi na ti ons (e). They a l l tend to reduce the ra te a nd extent of a bs orpti on of ma ny ora l drugs ta ken a t or
nea rl y a t the s a me ti me. In s uch ca s es , the bi oa va i l a bi l i ty of wa rfa ri n woul d be decrea s ed, res ul ti ng i n a n INR tha t i s l owernot hi ghertha n
woul d occur otherwi s e.
342. The correct answer is d. (Brunton, pp 1311-1312; Katzung, pp 1085-1089.) You s houl d l ook a t the s tem of the drugs generi c na me. It ends i n pra zol e, a nd s o you s houl d rea l i ze tha t the drug i s cl a s s i fi ed a s a proton pump i nhi bi tor (PPI). Es omepra zol e, i ndeed a l l other -pra zol es , ha ve
no a nti mus ca ri ni c a cti vi ty (a ). Thei r a nti s ecretory a cti ons occur downs trea m of a goni s ts s uch a s ACh, hi s ta mi ne, a nd ga s tri n, a nd do not i nvol ve
bl ocka de/a nta goni s m of thos e l i ga nds on thei r receptors (b). PPIs ha ve no a ci d-neutra l i zi ng a cti vi ty (c; a nta ci ds work by tha t mecha ni s m, a nd
a nta ci ds provi de the fa s tes t rel i ef of a ci d-rel a ted pa i n); they s i mpl y, yet effecti vel y a nd ra ther profoundl y, i nhi bi t ga s tri c a ci d s ecreti on. Hi s ta mi ne
does exert pos i ti ve chronotropi c effects on the hea rt, but tha t i s not a nta goni zed by a ny PPI, nor do the PPIs tend to ca us e bra dyca rdi a (e).
343. The answer is a. (Brunton, pp 1315-1316; Katzung, pp 1082-1083, 1150t.) Anta ci ds , a t us ua l recommended dos es , rel i eve a ci d-rel a ted pa i n fa s ter
tha n a ny other drugs . Thei r a ci d-neutra l i zi ng effects occur i ns ta nta neous l y upon conta ct wi th ga s tri c (hydrochl ori c) a ci d, a nd pa i n rel i ef occurs
wi thi n mi nutes of ta ki ng a dos e. Al l the other drugs i nhi bi t ga s tri c a ci d s ecreti on, s ome more effecti vel y or compl etel y tha n others , s ome qui cker
tha n others , but none a l l evi a tes a ci d-rel a ted pa i n or di s comfort a s qui ckl y a s a nta ci ds do. Thi s i ncl udes ci meti di ne (b) or a ny other H 2 bl ocker (c),
mi s opros tol (d) a nd a ny of the PPIs (e).
Severa l thi ngs worth noti ng here. Mi s opros tol ha s two ma i n us es . One i s a s a n a djunct to drug-i nduced termi na ti on of pregna ncy, due to i ts
s trong uteri ne s mooth mus cl e s ti mul a ti ng effects . In the context of thi s ques ti on i n the GI s ecti on, mi s opros tol i s s ometi mes us ed a s a n a djunct to
reduce the i nci dence or s everi ty of NSAID-i nduced ga s tri c ul cer forma ti on. For tha t purpos e, mi s opros tol exerts wha t ha s been ca l l ed a mucotropi c
or ga s tri c cytoprotecti ve effect: i t enha nces the forma ti on of mucus i n the ga s tri c mucos a , thereby s trengtheni ng the ba rri er between the NSAID
a nd i ts ta rget of da ma ge.
Remember: No a ci d, no pa i n. Thi s i s a true s ta tement. It ba s i ca l l y mea ns tha t the wa y to reduce ga s tri c a ci d-rel a ted pa i n i s ei ther to neutra l i ze
s uffi ci ent a mounts of a ci d (wi th a n a nta ci d) a nd/or i nhi bi t s uffi ci ent a mounts of ga s tri c a ci d s ecreti on, whi ch ca n be a ccompl i s hed wi th ei ther H 2
bl ocker or, more effecti vel y, a PPI. Note tha t the ra pi di ty of s ymptom rel i ef does NOT pa ra l l el ra te of ul cer hea l i ng. Remember, too, a s omewha t
rel a ted s ta tement tha t i s FALSE: No a ci d mea ns no ul cer. Wha t tha t mea ns , cl i ni ca l l y, i s tha t we ca n neutra l i ze a ci d, or i nhi bi t ga s tri c a ci d
s ecreti on ra ther qui ckl y, but unl es s proper thera py i s conti nued l ong enough, there s ti l l wi l l be ul cers des pi te the l a ck of the ma jor s ymptom, pa i n.
344. The answer is a. (Brunton, p 1337; Katzung, pp 1090-1091.) Among a l l the medi ca ti ons l i s ted, bl a ck tongue a nd bl a ck s tool a re uni quel y
cha ra cteri s ti c of the us e of bi s muth s a l ts , i ncl udi ng bi s muth s ubs a l i cyl a te (mos t wi del y known, perha ps , a s Pepto Bi s mol ). Thes e effects a re not
worri s ome (unl es s the pa ti ent i s nt forewa rned a bout thi s l i kel y occurrence, i n whi ch ca s e they ca n ca us e much a l a rm), a nd otherwi s e i ndi ca te no
toxi ci ty or other potenti a l a dvers e effects . None of the other drugs l i s ted s ha re thi s property.

345. The answer is c. (Brunton, pp 1330-1332; Katzung, p 1093.) La ctu-l os e i s a s yntheti c, nona bs orba bl e di s a ccha ri de (ga l a ctos e-fructos e). In modera te
dos es i t a cts a s a n os moti c l a xa ti ve. In hi gher dos es i t bi nds i ntes ti na l a mmoni a a nd other toxi ns tha t a ccumul a te i n the i ntes ti ne i n s evere l i ver
dys functi on. Thes e toxi ns , a nd perha ps more s o the a mmoni a , contri bute to the s i gns a nd s ymptoms of encepha l opa thy. None of the other drugs
l i s ted provi de thi s benefi t.
Di phenoxyl a te (a ) a nd l opera mi de (c) a re opi oi d-l i ke a nti di a rrhea l drugs . Es omepra zol e (b) i s a proton pump i nhi bi tor us ed to s uppres s ga s tri c
a ci d s ecreti on. And onda ns etron (e), a 5-HT3 a nta goni s t, i s ma i nl y us ed to ma na ge na us ea a nd vomi ti ng i n res pons e to chemothera py.
346. The answer is b. (Brunton, p 1846; Katzung, pp 609, 772, 781.) Fa t-s ol ubl e vi ta mi ns , es peci a l l y A a nd D (the others bei ng vi ta mi ns E a nd K), ca n be
s tored i n ma s s i ve a mounts a nd, hence, ha ve a potenti a l for s eri ous toxi ci ti es . (On the bri ght s i de, thi s a bunda nt s tora ge mea ns tha t rel a ti vel y
bri ef peri ods of i na dequa te i nta ke a re not l i kel y to ca us e cl i ni ca l s i gns a nd s ymptoms of defi ci ency.) Wa ter-s ol ubl e vi ta mi ns a re ea s i l y excreted
by the ki dneys a nd a ccumul a ti on to toxi c l evel s i s much l es s common. However, i na dequa te di eta ry i nta ke wi l l l ea d to ma ni fes ta ti ons of
defi ci ency rel a ti vel y fa s ter.
On a vera ge, mos t peopl e cons ume exces s i ve a mounts (a ) of fa t-s ol ubl e vi ta mi ns no more often tha n they do wa ter-s ol ubl e ones . Even very l a rge
dos es of fa t-s ol ubl e vi ta mi ns tha t mi ght be cons umed wi l l not a l ter membra ne s tructure or functi on (c), a l though s uch effects ca n be
demons tra ted i n certa i n i n vi tro s etti ngs tha t bea r l i ttl e rel eva nce to i nta ct huma ns . Di fferences i nvol vi ng grea ter or more rol es i n overa l l cel l
meta bol i s m (d), or ra tes of the meta bol i s m of the vi ta mi ns thems el ves (e), a re not rea s ona bl e expl a na ti ons for the rel a ti vel y grea ter toxi c
potenti a l of vi ta mi ns A, D, E, a nd K.
347. The answer is c. (Brunton, pp 206t, 222-224; Katzung, pp 99, 107, 112.) Betha nechol i s a mus ca ri ni c a goni s t tha t i s us ed to ma na ge functi ona l uri na ry
retenti ontha t i s , uri na ry retenti on or a s i gni fi ca nt i na bi l i ty to voi d ca us ed by s ome functi ona l defect i n the bl a dder mus cul a ture. It i s
contra i ndi ca ted for pa ti ents wi th bl a dder wa l l s tha t a re da ma ged or una bl e to res pond s a fel y to drugs tha t s ti mul a te the bl a dder mus cul a ture,
a nd pa ti ents wi th mecha ni ca l obs tructi on of the urethra (from, s a y, pros ta ti s m or a pros ta ti c ca ncer). Thi s wa s wha t ca us ed the betha nechol i nduced probl ems for thi s pa ti ent.
Al buterol (a ), predomi na ntl y a 2 a goni s t us ed for i ts bronchodi l a tor effects , ha s no s i gni fi ca nt effects on the hea l thy or da ma ged bl a dder: receptors jus t a rent there. Atropi ne (b) or other a nti mus ca ri ni cs wi l l wea ken contra cti on of the tri gone a nd detrus or, a nd s ti mul a te contra cti on of
the bl a dder s phi ncter, ca us i ng jus t the oppos i te of wha t I des cri bed. Furos emi de (d) a nd other l oop di ureti cs (tors emi de, bumeta ni de, a nd
etha cryni c a ci d) obvi ous l y i ncrea s e the need to uri na te a nd the vol ume of uri ne tha t i s excreted. However, the bl a dder a cti va ti on tha t ens ues i s
medi a ted by refl exes tri ggered by a ful l bl a dder. There i s no di rect s ti mul a ti on or i nhi bi ti on of bl a dder mus cul a ture. Fi na l l y, jus t a s -a goni s ts
ha ve no a ppreci a bl e effect on bl a dder mus cul a ture, nei ther do drugs tha t bl ock -a drenergi c receptors (e).
348. The answer is c. (Brunton, pp 1079-1081; Katzung, pp 581-586.) The des cri pti on conta i ns ma ny of the cha ra cteri s ti cs of i ron-defi ci ency a nemi a .
Ora l i ron s a l ts (eg, ferrous s ul fa te, gl ucona te, or fuma ra te) a re us ua l l y the fi rs t choi ce for ma na gement (a fter rul i ng out s uch ca us es a s bl ood
l os s ). Cha nges of gut moti l i ty (s ometi mes di a rrhea , s ometi mes cons ti pa ti on), na us ea , a nd hea rtburn a re common compl a i nts wi th ora l i ron s a l ts ,
but us i ng the ora l drugs i s often prefera bl e to, jus t a s effecti ve a s , a nd s a fer tha n us i ng pa rentera l i ron products s uch a s i ron-dextra n (ri s k of
a na phyl a xi s ) or other i ron compl exes , whi ch typi ca l l y i nvol ve erythropoi eti n a dmi ni s tra ti on a djuncti vel y.
Mega l obl a s ti c a nemi a (i n contra s t wi th the mi crocyti c a nemi a I des cri bed here) woul d be trea ted di fferentl y. If i t i s ca us ed by vi ta mi n B 12
defi ci ency (vi ta mi n ma l a bs orpti on due to defi ci ency of i ntri ns i c fa ctor; a ns wer a ), we woul d trea t wi th cya nocoba l a mi n. The other ca us e, fol a te
defi ci ency (i na dequa te di eta ry i nta ke) i s ma na ged wi th ora l fol i c a ci d (b). Defi ci enci es of vi ta mi n C or D (a ns wers d a nd e, res pecti vel y) dont
typi ca l l y ca us e a nemi a s .
349. The answer is c. (Brunton, pp 614, 1086; Katzung, pp 484-488, 1157t.) Reca l l tha t DOPA deca rboxyl a s e, a n enzyme whos e a cti vi ty i s dependent on
pyri doxi ne, i s res pons i bl e for meta bol i zi ng ora l l y a dmi ni s tered l evodopa to dopa mi ne i n the gut; a nd tha t onl y unmeta bol i zed l evodopa cros s es
the bl ood-bra i n ba rri er to be effi ca ci ous i n rel i evi ng pa rki ns oni a n s i gns a nd s ymptoms . Reca l l , too, tha t l evodopa i s often a dmi ni s tered wi th
ca rbi dopa , a drug tha t i nhi bi ts the peri phera l deca rboxyl a s e, s pa ri ng l evodopa for entry i nto the bra i n a nd whos e a cti ons a re a nta goni zed by
pyri doxi ne. Admi ni s teri ng s uppl ementa l B 6 wi l l reduce the bi oa va i l a bi l i ty of l evodopa , thereby countera cti ng i ts a nti pa rki ns on effecti venes s .
None of the other drugs l i s ted, whether us ed for the s ta ted purpos e or others , ha s i ts effects a nta goni zed by pyri doxi ne.
350. The answer is c. (Brunton, pp 639, 780, 1086, 1555-1558; Katzung, pp 840-841.) Pyri doxi ne defi ci enci es a ri s e often duri ng i s oni a zi d thera py beca us e
the a nti mycoba cteri a l drug i nterferes wi th meta bol i c a cti va ti on of the vi ta mi n. The trea tment or prophyl a xi s for a t-ri s k pa ti ents i s to a dmi ni s ter
rel a ti vel y l a rge dos es of B 6 (pyri doxi ne).
351. The answer is d. (Brunton, pp 1311-1313; Katzung, pp 1082-1083.) Es omepra zol e a nd rel a ted drugs (l a ns opra zol e, omepra zol e, ra bepra zol e,
pa ntopra zol e) i nhi bi t the pa ri eta l cel l H +-K+ATPa s ethe proton pumptha t i s the fi na l common pa thwa y for a ci d s ecreti on tri ggered by a l l the
ma jor s ti mul i of ga s tri c a ci d s ecreti on. As a res ul t, they a re the mos t effi ca ci ous , ca us i ng nea r compl ete a nti -a ci d s ecretory a cti vi ty.
Reca l l the ma i n a goni s ts tha t provoke a ci d s ecreti on. One i s ga s tri n, for whi ch there a re no cl i ni ca l l y us eful a nta goni s ts a t thi s ti me. Hi s ta mi ne,
a ri s i ng from enterochroma ffi n-l i ke (ECL) cel l s , a cti va tes H 2 receptors , whi ch then tri ggers a ci d s ecreti on. Hi s ta mi nes effects ca n be bl ocked by
ci meti di ne (c) or other H 2 bl ockers (fa moti di ne, ni za ti di ne, a nd ra ni ti di ne; a ny of thes e a l terna ti ves a re preferred to ci meti di ne, beca us e they l a ck
ci meti di nes P450 i nhi bi tory effects ). Acetyl chol i ne i ncrea s es ga s tri c a ci d s ecreti on by a cti va ti ng mus ca ri ni c receptors on both ECL cel l s a nd pa ri eta l
cel l s . Its effects ca n be bl ocked by a tropi ne (a ), propa nthel i ne, pi renzepi ne (wi del y ta ught but never a pproved for us e i n the Uni ted Sta tes ), a nd
s evera l other drugs wi th a nti mus ca ri ni c a cti vi ty. However, bl ocki ng onl y the hi s ta mi nergi c i nfl uences or onl y the chol i nergi c i nfl uences or even
bl ocki ng both types of receptors onl y pa rti a l l y i nhi bi ts a ci d s ecreti on. One a ddi ti ona l di s a dva nta ge of mus ca ri ni c bl ocka de i s the preva l ence of
often di s turbi ng a nd us ua l l y unwa nted a tropi ne-l i ke s i de effects el s ewhere, for exa mpl e, on the eyes , hea rt, uri na ry tra ct, a nd exocri ne gl a nd
s ecreti ons .
Ca l ci um ca rbona te (b), a s wel l a s a l umi num a nd ma gnes i um s a l ts a nd s odi um bi ca rbona te, a re a nta ci ds . They ha ve no i nhi bi tory effects on
a ci d s ecreti on. Ins tea d, they neutra l i ze a component of a ci d tha t ha s a l rea dy been s ecreted (a nd a l umi num s a l ts a l s o a ds orb peps i ns ). Ca l ci um
a nd a l umi num s a l ts tend to ca us e cons ti pa ti on, a nd ma gnes i um s a l ts , di a rrhea /l a xa ti on. Sodi um bi ca rbona te tends to ca us e no cha nges of gut
moti l i ty, but the s i gni fi ca nt a bs orpti on of the s odi um pos es probl ems for ma ny pa ti ents (eg, thos e wi th hypertens i on, hea rt fa i l ure, edema ), a nd
bi ca rbona te a bs orpti on ca us es meta bol i c a l ka l os i s .
Mi s opros tol (e) i s uni que i n s evera l wa ys . One wa y i s tha t thi s pros ta gl a ndi n a na l og mi mi cs the effects of endogenous pros ta gl a ndi ns (ma i nl y
PGE2 ) on pa ri eta l cel l pros ta gl a ndi n receptors . Unl i ke the a goni s ts noted a bove, one res ul t of tha t i s i nhi bi ti on of a ci d s ecreti on. Overa l l , the a nti a ci d s ecretory effects a re rel a ti vel y wea k.
Ul ti ma tel y, however, rega rdl es s of whether ga s tri n, ACh, or hi s ta mi ne i s pres ent, pa ri eta l cel l a ci d s ecreti on ul ti ma tel y funnel s through the

proton pump. Bl ock the receptors for a ny of the medi a tors noted a bove a nd you wi l l s uppres s a ci d s ecreti on ca us ed onl y by tha t medi a torbut
tha t i s onl y a fra cti on of tota l a ci d s ecreti on. Bl ock the proton pump a nd a ci d s ecreti on wi l l be i nhi bi ted nea rl y ful l y, no ma tter whi ch one or more
a goni s ts a re pres ent.
352. The answer is b. (Brunton, pp 504f, 507, 1338; Katzung, pp 558, 1094-1095, 1112.) Di phenoxyl a te i s a n opi oi d tha t ha s predomi na nt a nti di a rrhea l
a cti vi ty, a nd tha t i s i ts s ol e a pproved us e. It i nhi bi ts peri s ta l s i s a nd, hence, i ncrea s es the pa s s a ge ti me of the i ntes ti na l bol us . Typi ca l
a nti di a rrhea l dos es do not ca us e venti l a tory depres s i on, a na l ges i a , or the euphori a for whi ch opi oi ds a re ma i nl y a bus ed. However, s houl d one
a ttempt to ta ke hi gh dos es to become euphori c, unpl ea s a nt effects wi l l a ppea r. Tha t i s beca us e the product conta i ns a s ma l l a mount of a tropi ne
us ua l l y not enough to ca us e s i de effects when the proper dos e of the product i s cons umed, but cl ea rl y a bl e to ca us e a l l the typi ca l a nd
unpl ea s a nt a nti -mus ca ri ni c s i de effects of whi ch you s houl d be a wa re (s ee the cha pter, Autonomi c Nervous Sys tem) when exces s i ve dos es a re
ta ken. Thi s pha rma ceuti ca l ma nufa cturi ng tri ck di s coura ges di phenoxyl a te a bus e.
Apomorphi ne (a ) a nd i peca c (c) a re dopa mi nergi c emeti cs (for pa rentera l a nd ora l a dmi ni s tra ti on, res pecti vel y) tha t a re us ed i n s ome
poi s oni ngs where i nduci ng emes i s i s des i red a nd s a fe. Ma gnes i um s ul fa te (Eps on s a l tcl ea rl y a foul -ta s ti ng s ubs ta nce; a ns wer d) i s
occa s i ona l l y a nd us ua l l y i na ppropri a tel y us ed a s a l a xa ti ve or ca tha rti c. Na l trexone (e) i s a n opi oi d a nta goni s t ( a nd receptors , na l oxone-l i ke,
but gi ven ora l l y.)
353. The answer is e. (Brunton, pp 1014, 1315-1316, 1523, 1531; Katzung, pp 1082-1083.) Ma gnes i um s a l ts (eg, oxi de/hydroxi de, a s found i n ordi na ry mi l k
of ma gnes i a ) us ed a l one tend to ca us e a l a xa ti ve effect. (Indeed, a t dos a ges hi gher tha n thos e us ed for a ci d neutra l i za ti on, ma gnes i um s a l ts a re
us ed for thei r l a xa ti ve or ca tha rti c effects .) Al umi num (a nd ca l ci um) a nta ci ds , gi ven a l one, tend to ca us e cons ti pa ti on. Combi ni ng a ma gnes i um
s a l t wi th a n a l umi num s a l t (a nd/or ca l ci um a nta ci d) i s a n often s ucces s ful a pproa ch to mi ni mi zi ng a nta ci d-i nduced cha nges of net gut moti l i ty.
Ma gnes i um s a l ts do not potenti a te the a nti s ecretory a cti ons of Al or a ny other a nta ci d. Indeed, none of the a nta ci ds i nhi bi t ga s tri c a ci d
s ecreti on (i e, they dont ha ve a n a nti s ecretory effect to begi n wi th). They merel y neutra l i ze a ci d tha t ha s a l rea dy been s ecreted (Mg, Ca , s odi um
bi ca rbona te) or a ds orb a ci d a nd peps i ns (mos t of the a l umi num compounds ). Al though hi gh concentra ti ons of Mg s a l ts ma y ca us e ga s tri c
i rri ta ti on, the a mounts a nd concentra ti ons found i n a nta ci d products a re not s uffi ci ent to do tha t. Remember tha t i n order to mi ni mi ze the ri s ks of
hyperma gnes emi a , even when otherwi s e rea s ona bl e dos es a re ta ken a nd es peci a l l y when dos es a re hi gher tha n tha t, rena l functi on mus t be
a dequa te. As a res ul t, ma ny el derl y pa ti ents a nd pa ti ents of a ny a ge who ha ve rena l dys functi on from other ca us es , a re a t i ncrea s ed ri s k for
hyperma gnes emi a .
Al s a l ts dont protect a ga i ns t a ny s uch potenti a l effect. Ma gnes i um s a l ts do contri bute to a di ures i s , but i t i s not a s i gni fi ca nt effect. Al s a l ts a re
non-s ys temi c a nta ci ds : they a re not a bs orbed to a ny a ppreci a bl e degree, a nd therefore they dont depend on rena l proces s es for thei r
el i mi na ti on. The Al s a l ts a re effecti ve i n the form i n whi ch they a re a dmi ni s tered, a nd dont requi re a ny enzyma ti c (or other type of) a cti va ti on to
exert thei r effects (whi ch i nvol ves a ds orpti on of a ci d, peps i ns , etc).
354. The answer is a. (Brunton, pp 898-899; Katzung, p 1107.) Urs odeoxychol i c a ci d (urs odi ol ), one of s evera l na tura l l y occurri ng bi l e a ci ds , i s effecti ve i n
s ome pa ti ents wi th chol es terol ga l l s tones . Its ma i n i ni ti a l a cti on i s reduced hepa ti c chol es terol s ynthes i s . Tha t, i n turn, l owers the chol es terol
content i n the bi l e, whi ch fa vors the di s s ol uti on of chol es terol s tones tha t ha ve formed a l rea dy a nd reduces the i nci dence of new s tone
forma ti on.
Urs odeoxychol i c a ci d tends to i nhi bi t (not enha nce, a ns wer b) i ntes ti na l fa t di ges ti on a nd a bs orpti on, a nd ma y contri bute to (not revers e,
a ns wer c) i mpa i red a bs orpti on of vi ta mi ns A, D, E, a nd K. The drug does not s ti mul a te ga s tri c a ci d s ecreti on (d) a nd i s not i ndi ca ted for ma na gi ng
a chl orhydri a . Stea torrhea ma y devel op i n res pons e to urs odeoxychol i c a ci d; the i nci dence of fa tty s tool s i s not reduced (e) by the drug.
355. The answer is c. (Brunton, p 1320; Katzung, pp 1087-1088.) Severa l profes s i ona l orga ni za ti ons , i ncl udi ng the Ameri ca n Col l ege of Ga s troenterol ogy,
ha ve gui del i nes for ma na gi ng s evere, refra ctory, or recurrent duodena l a nd/or ga s tri c ul cers , i n whi ch H. pylori cl ea rl y pl a ys a n i mporta nt
pa thophys i ol ogi c rol e. Al though s evera l regi mens ha ve been s ugges ted, a l l of them i ncl ude a n a nti -a ci d s ecretory drug (us ua l l y a proton pump
i nhi bi tor, s ometi mes a n H 2 bl ocker), two or three a nti mi crobi a l s (eg, a moxi ci l l i n, cl a ri thromyci n, or tetra cycl i ne, us ua l l y wi th metroni da zol e), a nd
bi s muth. In ma ny ca s es , thi s s o-ca l l ed era di ca ti ve thera py ca n ca us e a cl i ni ca l cure a nd prevent recurrences a fter a bout 8 weeks of trea tment. (The
trea tment i s expens i ve, but pa l es i n compa ri s on wi th the fi na nci a l a nd pers ona l cos ts of trea ti ng recurrent epi s odes or potenti a l l y s eri ous
compl i ca ti ons s uch a s GI bl eedi ng or hemorrha ge, ei ther pha rma col ogi ca l l y or s urgi ca l l y.)
Anti bi oti c-a s s oci a ted ps eudomembra nous col i ti s (a ) i s typi ca l l y ma na ged wi th va ncomyci n or metroni da zol e, a l ong wi th di s conti nua ti on of the
ca us a ti ve a gent (us ua l l y cl i nda myci n). Di eta ry modi fi ca ti ons (es peci a l l y i ncrea s ed di eta ry fi ber i nta ke) a nd va ri ous drugs tha t a l ter gut moti l i ty
(l a xa ti ves i n cons ti pa ti on-predomi na nt IBS; opi oi d, opi oi d-l i ke, or s erotoni n a nta goni s t a nti di a rrhea l s when di a rrhea predomi na tes ) a re often
chos en to hel p ma na ge i rri ta bl e bowel s yndrome (b). Doxycycl i ne a nd/or bi s muth s a l ts a re often us ed to prevent or trea t E. coli-medi a ted di a rrhea
(d). If the goa l i s to prevent NSAID-i nduced ga s tri c ul cers (e), a proton pump i nhi bi tor (eg, es omepra zol e), or mi s opros tol a re rea s ona bl e choi ces .
356. The answer is b. (Brunton, pp 975-976, 981; Katzung, pp 1090-1091.) Bi s muth s a l ts s uch a s the s ubs a l i cyl a te (bes t known, perha ps , a s the bra ndna me product Pepto Bi s mol ) exert a nti bi oti c a cti vi ty a ga i ns t H. pylori a nd proba bl y E. coli a l s o. They a re commonl y pres cri bed for the era di ca ti ve
thera py of H. pylori-i nduced refra ctory ga s tri c ul cers , a l ong wi th a n a nti bi oti c a nd metroni da zol e. The s a l i cyl a te i n thi s formul a ti on contra i ndi ca tes
i ts us e i n chi l dren wi th i nfl uenza or a ny other vi ra l i l l nes s , owi ng to the ri s k of Reye s yndrome. It i s s omewha t controvers i a l wha t the term
chi l dren mea ns i n thi s Reye-rel a ted context. The ri s k cl ea rl y a ppl i es to chi l dren i n thei r a dol es cent (a nd ea rl i er) yea rs of a ge, but i t ma y a l s o
extend to peopl e younger tha n a bout 21 yea rs of a ge. Thi s i s i mporta nt to know, s i nce chi l dren experi enci ng s uch vi ra l i l l nes s es a s i nfl uenza ,
chi ck-enpox, or even a common col d ma y report tha t thei r tummy hurts a nd they ma y experi ence di a rrhea for a va ri ety of rea s ons . The pi nk
meds des cri bed i n the ques ti on a re qui te wel l known to ma ny pa rents . Si nce they a re a va i l a bl e OTC (tha t a utoma ti ca l l y conveys the noti on tha t
they a re s a fe) a nd effecti ve, i ts not unl i kel y tha t the unknowi ng ca regi ver mi ght gi ve the chi l d preci s el y the wrong drug. Wa rni ngs a ga i ns t the
us e of thes e bi s muth-conta i ni ng medi ca ti ons a re pri nted on the l a bel s of thes e products , but a s you proba bl y know by now ma ny peopl e dont (or
ca nt) rea d product l a bel s .
The s a l i cyl a te component a l s o pos es ri s ks i n other s i tua ti ons for whi ch a s a l i cyl a te s houl d be a voi ded. As pi ri n-s ens i ti ve a s thma i s a pri me
exa mpl e.
Bi s muth s a l ts (or the s a l i cyl a te moi ety s peci fi ca l l y) l a ck s i gni fi ca nt effects on bl ood pres s ure or the effects of a nti hypertens i ve drugs (a ). There
a re no wel l -documented benefi ci a l or a dvers e effects on s i gns a nd s ymptoms typi ca l l y a s s oci a ted wi th menopa us e (c). Li kewi s e, there a re no
known des i red or unwa nted effects on pros ta te, uri na ry tra ct, or ocul a r functi on or di s ea s e (d), whether i n ol der men or not; no effects on a rthri ti c
di s ea s e (the s a l i cyl a te i n bi s muth s ubs a l i cyl a te i s a ppa rentl y s uffi ci ent to wa rra nt the Reye s yndrome wa rni ng, but not s uffi ci ent to fa vora bl y
i nfl uence i nfl a mma tory di s ea s es s uch a s a rthri ti s ); nor a ffect s i gns a nd s ymptoms of s ea s ona l (or other) a l l ergi c res pons es (f).
The drug ha s no H 2 -bl ocki ng or mus ca ri ni c receptor-bl ocki ng a cti vi ty. In the a bs ence of a ny contra i ndi ca ti ons , bi s muth s ubs a l i cyl a te ma y be
us eful for ma na gi ng s ome ca s es of di a rrhea , s uch a s tra vel ers di a rrhea tha t often i s ca us ed by E. coli.

357. The answer is e. (Brunton, pp 1331-1334; Katzung, p 1083.) Youve a l l done the experi ment: mi x vi nega r a nd ba ki ng s oda (s odi um bi ca rbona te) a nd
one product i s CO2 . Thi s ga s i s formed when s odi um bi ca rbona tes ti l l us ed a s a l a y remedy for hea rtburn (es opha gea l refl ux) a nd other a ci drel a ted GI di s turba nces rea cts wi th HCl .
Norma l l y i ntra ga s tri c pres s ure i s kept i n check when the ga s troes opha gea l s phi ncter opens . However, when pres s ure ca nt be rel i eved qui ckl y
enough, or a dequa tel y, the s toma ch di s tends l i ke a ba l l oon. In the pres ence of ul cers , the l es i ons a re s tretched mecha ni ca l l y, fa vori ng further
da ma ge tha t ca n l ea d to a cute bl eedi ng. Even i n the a bs ence of ul cers , a ny wea knes s of the ga s tri c wa l l ca n l ea d to rupture. (Reports a bout thi s
s cena ri o, publ i s hed i n the l a y pres s a whi l e a go a nd l a ced wi th more tha n a l i ttl e hyperbol e, s ta ted tha t [the ma ns ] s toma ch expl oded a fter a
bi g ni ght on the town, fol l owed by i nges ti ng ba ki ng s oda for rel i ef.)
None of the other a nta ci ds l i s ted, whether a l one or i n combi na ti on, l ea d to producti on of CO2 or a ny other ga s tha t mi ght l ea d to the outcome
des cri bed here. Al umi num s a l ts (a ) s el dom a re us ed a l one for neutra l i zi ng ga s tri c a ci d, but a re us ed occa s i ona l l y to reduce ci rcul a ti ng phos pha te
l evel s i n s uch pa ti ents a s thos e wi th rena l fa i l ure. Us ed a l one, a l umi num s a l ts tend to ca us e cons ti pa ti on. Al umi num-ma gnes i um combi na ti on
products (b) a re the mos t commonl y pres cri bed or s el f-pres cri bed a nta ci ds . The ra ti ona l e for thi s combi na ti on, a s i de from overa l l effi ca cy, i s tha t
the l a xa ti ve effects of the ma gnes i um s a l ts (c) a re countera cted by the cons ti pa ti ng effects of the a l umi num s a l ts . (Ca l ci um s a l ts , pa rti cul a rl y
ca l ci um ca rbona te, a l s o ha ve a nta ci d effects a nd, when us ed a l one, tend to ca us e cons ti pa ti on.) Ra ni ti di ne (d; a nd fa moti di ne, ni za ti di ne a nd the
l es s er-us ed ci meti di ne) a re H 2 bl ockers .
358. The answer is e. (Brunton, pp 642-644, 655; Katzung, pp 389-401, 575.) Thi a mi ne, a dmi ni s tered pa rentera l l y before or a t the s a me ti me a s
a dmi ni s teri ng gl ucos e, a nd often i n hi gh dos a ges , i s us ed for Werni cke encepha l opa thy. It dra ma ti ca l l y a mel i ora tes the s i gns a nd s ymptoms .
Thi a mi ne mus t be gi ven i f gl ucos e i s to be gi ven. Thi a mi ne s erves a s a cofa ctor for ma ny enzyma ti c rea cti ons , i ncl udi ng thos e i nvol ved i n
ca rbohydra te meta bol i s m. If gl ucos e i s a dmi ni s tered i n a thi a mi ne-defi ci ent s ta te, wha t l i ttl e vi ta mi n i s l eft i n the ci rcul a ti on wi l l be depl eted,
a berra nt gl ucos e meta bol i s m wi l l conti nue, a nd the pa thol ogy (pa rti cul a rl y neurol ogi c) l i kel y wi l l be wors ened.
Thi a mi ne defi ci ency i s a l s o res pons i bl e for Kors a koff ps ychos i s (or Kors a koff a mnes ti c s yndrome), a nother a ccompa ni ment of s evere, l ong-term
a l cohol cons umpti on (es peci a l l y wi thout a dequa tel y nutri ti ona l di ets ). Unfortuna tel y, the s i gns a nd s ymptoms of Kors a koff (s hort-term memory
probl ems , a tendency to fa bri ca te, pol yneuropa thi es ) a re not revers i bl e.
Vi ta mi n E (a ) i s not i ndi ca ted for Werni cke encepha l opa thy. Suppl ements of tha t fa t-s ol ubl e vi ta mi n a re often us ed (mi s us ed?) by the l a y publ i c
for the vi ta mi ns a nti oxi da nt a nd a nti -a gi ng effects . Cya nocoba l a mi n (B 12 ; b) i s often us ed for ma crocyti c a nemi a s tha t i nvol ve defi ci enci es of
i ntri ns i c fa ctor (s ee Ques ti on 348). Fol i c a ci d (c) s uppl ements ha ve a va ri ety of us es , i ncl udi ng reduci ng the ri s k of tera togeni c or s i mi l a r effects i n
pregna nt women, es peci a l l y i f they a re ta ki ng certa i n a nti epi l epti c drugs . The mos t common us e of phytona di one (vi ta mi n K; d) i s to hel p revers e
exces s i ve a nti coa gul a nt effects of wa rfa ri n.
359. The answer is e. (Brunton, p 1346; Katzung, pp 1106-1107, 1111.) Pa ncrel i pa s e i s a n a l cohol i c extra ct of hog pa ncrea s tha t conta i ns l i pa s e, tryps i n,
a nd a myl a s e. (The rel a ted drug, pa ncrea ti n, i s s i mi l a r.) The goa l i n us i ng i t here i s not s o much to control the s ymptom, di a rrhea , but do s o by
a tta cki ng the ca us e, whi ch i s endogenous pa ncrea ti c enzyme defi ci ency (l i pa s es , a myl a s e, chymotryps i n, a nd tryps i n) tha t l ea ds to i mpa i red fa t
di ges ti on a nd a bs orpti on.
None of the other drugs menti oned (a s ta ti n, a ; a n H 2 bl ocker, b; bi l e s a l ts , c; metocl opra mi de, d) ha ve a cti ons tha t woul d be a s effecti ve (i f
effecti ve a t a l l ) or s peci fi c a s pa ncrel i pa s e. Anti di a rrhea l s , for exa mpl e, woul d onl y trea t the s ymptoms , not the underl yi ng ca us e.
Note: You ma y fi nd pa ncrel i pa s e a dmi ni s tered wi th a nta ci ds , or a n a ci d s ecreti on i nhi bi tor (H 2 bl ocker or proton pump i nhi bi tor). The purpos e
of combi ned thera py i s not rel a ted to preventi ng a dvers e effects of a ci d on the ga s tri c mucos a , but ra ther to ra i s e ga s tri c pH a nd prevent the
pa ncrel i pa s e from bei ng hydrol yzed a nd i na cti va ted by a ci d.
360. The answer is a. (Brunton, pp 1793, 1812; Katzung, pp 1040t, 1070.) Pregna nt women s houl d not ta ke more tha n 25% more tha n the norma l
(recommended) da i l y di eta ry a l l owa nce for vi ta mi n A, beca us e i t i s tera togeni c, es peci a l l y i n the fi rs t tri mes ter of pregna ncy. Note tha t the vi ta mi n
A-l i ke drug i s otreti noi n, whi ch i s ma i nl y i ndi ca ted for trea ti ng refra ctory or s evere a cne vul ga ri s , i s contra i ndi ca ted too.
Of cours e, there a re pregna ncy-rel a ted recommenda ti ons for the other nutri ents l i s ted i n the a ns wer: vi ta mi ns B 12 (b); C (c); E (d); a nd,
es peci a l l y, fol i c a ci d (e). However, a nd a l though exces s i ve i nta ke of thes e nutri ents i s not recommended, a nd doi ng s o ma y pos e ri s ks to the
mother or the fetus , the cons equences a re not hi ghl y tera togeni c.
361. The answer is d. (Brunton, pp 944t, 1352t; Katzung, pp 646, 1101.) Sul fa s a l a zi ne, whi ch i s a combi na ti on of s ul fa pryi di ne a nd 5-a mi nos a l i cyl i c a ci d
(5-ASA) l i nked cova l entl y (a zo bond), i s qui te effecti ve for ma na gi ng i nfl a mma tory bowel di s ea s e (eg, ul cera ti ve col i ti s a nd Crohn di s ea s e). Some
of the s ul fa s a l a zi ne i s a bs orbed, a nd a porti on of tha t i s excreted uncha nged ba ck i nto the col on. Col oni c ba cteri a s pl i t the a zo l i nka ge, rel ea s i ng
the two drugs . The 5-ASA i s res pons i bl e for l oca l a nti -i nfl a mma tory a cti vi ty (s uppres s i on of i nfl a mma tory medi a tors , but how, i s not wel l
unders tood) a nd s ymptom rel i ef. The other meta bol i te, s ul fa pyri di ne, i s pri ma ri l y res pons i bl e for s i de effects a s s oci a ted wi th thi s two drugs i n
one combi na ti on: na us ea , vomi ti ng, a nd hea da ches (dos e-dependent); s ul fona mi de a l l ergi c rea cti ons i n s ul fa -s ens i ti ve pa ti ents ; a nd ra re but
potenti a l l y fa ta l bl ood rea cti ons i ncl udi ng i mmune-medi a ted hemol ys i s a nd a pl a s ti c a nemi a .
A rel a ted drug, mes a l a mi ne, conta i ns onl y the a cti ve 5-ASA. La cki ng a ny s ul fa pyri di ne, the s i de effects , a nd a dvers e res pons es a re very l ow
compa red wi th s ul fa s a l a zi ne. An even nea ter s tra tegy i s us ed by ol s a l a zi ne: the drug i s compri s ed of two a zo-l i nked 5-ASA mol ecul es ; the bond i s
cl ea ved by gut ba cteri a , rel ea s i ng two 5-ASA mol ecul es for every mol ecul e of ol s a l a zi ne a dmi ni s tered.
362. The answer is a. (Brunton, pp 1277, 1288; Katzung, pp 780, 1083, 1111.) Al umi num hydroxi de (a nd a l l other cl i ni ca l l y us eful a l umi num s a l ts other
tha n the phos pha te) ha s a hi gh a ffi ni ty for phos pha te. In the gut, the a l umi num s a l ts bi nd phos pha te a nd prevent i ts a bs orpti on qui te wel l . They
a l s o i nduce a bl ood-to-gut gra di ent tha t fa vors el i mi na ti on of ci rcul a ti ng phos pha te. (Us ed i na ppropri a tel y, i t ma y ca us e hypophos pha temi a :
s us ta i ned, hi gh-dos e us e of a l umi num-conta i ni ng a nta ci ds i s one of the mos t common ca us es of hypophos pha temi a .) None of the other drugs
l i s ted a re effecti ve i n or us ed for reduci ng phos pha te a bs orpti on or l oweri ng pl a s ma l evel s .
The ma i n l i mi ta ti on to us i ng a n a l umi num s a l t by i ts el f i s i ts tendency to ca us e cons ti pa ti on. Thi s i s us ua l l y dea l t wi th, when a l umi num s a l ts
a re us ed a s typi ca l a nta ci ds , by coa dmi ni s teri ng a ma gnes i um s a l t, whi ch a l one tends to ca us e l a xa ti on. (Gi vi ng a ma gnes i um s a l t a l one or i n
combi na ti on wi th a nother a nta ci d woul d be i na dvi s a bl e for pa ti ents wi th rena l fa i l ure, s uch a s thi s di a l ys i s pa ti ent, who a re often una bl e to
excrete the ca ti on a t ra tes s uffi ci ent to a voi d hyperma gnes emi a .)
363. The answer is b. (Brunton, p 1340; Katzung, p 1096.) Cons ti pa ti on i s the mos t common a nd mos t worri s ome a dvers e res pons e to a l os etron, whi ch
i s often us ed for i rri ta bl e bowel s yndrome. Thi s drugs mecha ni s m of des i red a cti on i nvol ves s el ecti ve bl ocka de of s erotoni n receptors (5-HT3 ) i n
the gut; the ma i n outcomes i ncl ude s l owi ng of col oni c tra ns port ti me, i ncrea s ed s odi um a nd wa ter rea bs orpti on from the col on, a nd reduced
s ecreti on of wa ter a nd el ectrol ytes i nto the col on.

Al though cons ti pa ti on (b) mi ght be vi ewed a s a tri vi a l , mi nor, or merel y a nnoyi ng compl a i nt wi th mos t drugs , wi th a l os etron i t i s the mos t
worri s ome one. Cons ti pa ti on ma y (a nd ha s ) progres s ed to feca l i mpa cti on, bowel perfora ti on or obs tructi on, a nd i s chemi c col i ti s . Fa ta l i ti es ha ve
occurred.
The ri s ks a re s uch tha t the drug wa s pul l ed from the ma rket i n ea rl y 2000 a nd rea pproved two yea rs l a ter wi th a l i mi ted i ndi ca ti on (prol onged,
s evere di a rrhea a s s oci a ted wi th IBS i n women); a bunda nt wa rni ngs i n the pa cka ge i ns ert; a nd a comprehens i ve ri s k-ma na gement/a voi da nce
progra m tha t i ncl udes a requi rement for (a mong other thi ngs ) a s peci a l s i gn-off by both the pres cri ber a nd the pa ti ent tha t they unders ta nd a nd
a cknowl edge a nd ca n i denti fy the ri s ks a nd a gree to trea tment a nywa y.
Seri ous ca rdi a c a rrhythmi a s (a ), extra pyra mi da l rea cti ons (c), pul mona ry fi bros i s (d), or rena l fa i l ure (e) a re not the mos t l i kel y or mos t
worri s ome a dvers e effects a s s oci a ted wi th a l os etron.
364. The answer is b. (Brunton, pp 1341-1344; Katzung, pp 287, 1097-1099, 1111.) The a nti emeti c effects of onda ns etrona drug tha t i s wi del y a nd
effecti vel y us ed to ma na ge na us ea a nd emes i s a s s oci a ted wi th chemothera py or ma ny of s evera l drugs typi ca l l y a dmi ni s tered duri ng s urgeryi s
ma i nl y due to bl ocka de of 5-HT3 receptors i n the bra i ns chemoreceptor tri gger zone (CTZ) a nd, proba bl y, i n the s ol i ta ry tra ct nucl eus a nd i n the
s toma ch a nd s ma l l i ntes ti ne.
Acti va ti on of -opi oi d receptors i n the CTZ (a ) i s wha t causes the na us ea a nd emes i s tha t i s s o common wi th s uch drugs a s morphi ne a nd other
opi oi d a na l ges i cs .
Bl ocka de of centra l dopa mi ne receptors (c), pa rti cul a rl y D 2 receptors i n the CTZ, i s the ma i n mecha ni s m by whi ch phenothi a zi nes (eg,
chl orproma zi ne, prochl orpera zi ne) ca us e thei r a nti na us ea /a nti emeti c effects . They a re us eful a nd effecti ve for s ome pa ti ents wi th chemothera pyi nduced na us ea a nd vomi ti ng, but better s ui ted for prophyl a xi s of thes e s ymptoms due to other ca us es or for prophyl a xi s of moti on s i cknes s .
Centra l a nti mus ca ri ni c a nd a nti hi s ta mi ni c a cti ons ma y contri bute to the overa l l effects .
Bl ocka de of H 1 -hi s ta mi ne receptors (d) i n the bra i n (bra i ns tem) a nd ves ti bul a r a ppa ra tus of the i nner ea r a ccounts for the ma i n mecha ni s m of
a cti on of s uch drugs a s cycl i zi ne, di phenhydra mi ne (a nd i ts deri va ti ve, di menhydri na te), a nd hydroxyzi ne. Anti mus ca ri ni c effects of thes e a nti hi s ta mi nes ma y contri bute to the overa l l effect. They a re bes t s ui ted for moti on s i cknes s prophyl a xi s , l es s effecti ve a s genera l a nti emeti cs , a nd
not very or s peci fi ca l l y effecti ve for chemothera py-i nduced s ymptoms .
Anti mus ca ri ni c a gents (e; s copol a mi ne ca n be cons i dered the prototype i n terms of moti on s i cknes s or emes i s control ) do not exert thei r effects
vi a a cti ons on the GI mus cul a ture, a l though s uppres s i on of AChmedi a ted GI moti l i ty a nd tone certa i nl y occurs . Thei r effects a re pri ma ri l y centra l ;
thei r cl i ni ca l uti l i ty i s ma i nl y l i mi ted to prophyl a xi s or trea tment (l ower effi ca cy) of moti on s i cknes s .

Endocrine and Reproductive Pharmacology

Adrena l corti cos teroi ds
Ana bol i c s teroi ds , rel a ted drugs
Ca l ci um-regul a ti ng drugs
Di a betes mel l i tus a nd hypogl ycemi a
Erecti l e dys functi on
Es trogens , proges ti ns , contra cepti ves , ferti l i ty a gents
Tes tos terone
Thyroi d di s orders
Uteri ne s ti mul a nts (oxytoci cs ) a nd rel a xa nts (tocol yti cs )

Questions
365. A 55-yea r-ol d ma l e pa ti ent wi th a 20-yea r hi s tory of type 2 di a betes mel l i tus comes to your cl i ni c for hi s regul a r check-up. He l ooks good, feel s
wel l . However, over the l a s t yea r hi s HbA1c l evel s hovered a round 9.5% (equi va l ent to a n a vera ge pl a s ma gl ucos e of a round 225 mg/dL). Current
di a betes medi ca ti ons a re metformi n a nd gl yburi de. The pa ti ent s a ys he i s doi ng the bes t he ca n wi th recommended di et a nd exerci s e pl a ns . He
ha s other pers ona l a nd fa mi l i a l ri s k fa ctors for corona ry hea rt di s ea s e. He ta kes a s ta ti n a nd metformi n to control hi s l i pi ds , but hi s LDL a nd
tri gl yceri de l evel s a re fa r too hi gh. He i s ta ki ng vera pa mi l for Sta ge 1 hypertens i on, but hi s pres s ure i s s ti l l hi gher tha n youd l i ke i t to be. Two
yea rs a go, he ha d s evere a ngi na from a theros cl eroti c corona ry di s ea s e a nd underwent a ngi opl a s ty a nd pl a cement of a s tent. He ha s ha d no
i s chemi c epi s odes s i nce.
Youre thi nki ng a bout a ddi ng ni a ci n to get further control of tri gl yceri de l evel s , a ddi ng a nother a nti hypertens i ve drug, a nd a djus ti ng hi s
di a betes trea tment by a ddi ng a nother hypogl ycemi c drug (perha ps i ns ul i n). Whi ch comorbi di ty or other fa ctor woul d wei gh against your s el ecti on of
a n a ngi otens i n converti ng enzyme (ACE) i nhi bi tor or a ngi otens i n receptor bl ocker (ARB) a s the a dd-on a nti hypertens i ve drug for thi s pa ti ent?
a . Bi l a tera l rena l a rtery s tenos i s a nd a l bumi nuri a
b. Bra dyca rdi a
c. Ha d two epi s odes of hyperos mol a r hypergl ycemi c nonketoti c s yndrome i n pa s t 2 yea rs
d. Ha s hea rt fa i l ure
e. Ni a ci n wi l l i ndeed be pres cri bed
366. A pa ti ent ha s a n i nopera bl e pa ncrea ti c i s l et cel l ca rci noma a nd i s chroni ca l l y hypogl ycemi c. Whi ch drug woul d be mos t l i kel y chos en for
rel a ti vel y l ong-term ora l thera py tha t a ttempts to ra i s e bl ood gl ucos e l evel s i nto a more a ccepta bl e ra nge?
a . Atenol ol (or metoprol ol )
b. Di a zoxi de
c. Gl uca gon
d. Octreoti de (s oma tos ta ti n a na l og)
e. Oxytoci n
367. A pa ti ent wi th type 2 di a betes mel l i tus i s notori ous l y noncompl i a nt wi th medi ca ti on a nd di et recommenda ti ons . However, he thi nks hes
s ma rt enough to fool the phys i ci a n i nto thi nki ng otherwi s e: he ta kes hi s medi ca ti on a nd el i mi na tes nea rl y a l l ca rbohydra te i nta ke for a few da ys
before ea ch cl i ni c vi s i t, knowi ng he wi l l get a fi nger s ti ck for a s pot check of pl a s ma gl ucos e l evel s . Wha t woul d be the s i mpl es t, mos t cos teffecti ve, a nd mos t i nforma ti ve wa y for the phys i ci a n to a s s es s for pa s t drug a nd di et compl i a nce a nd l ong-term gl ycemi c control ?
a . Gl ucos e concentra ti on i n venous bl ood s a mpl e
b. Gl ucos e tol era nce tes t (ora l )
c. HbA1c
d. Pl a s ma l evel s of the a nti di a beti c drug
e. Uri ne ketone l evel s (i n a s a mpl e dona ted a t the ti me of cl i ni c vi s i t)
f. Uri ne gl ucos e l evel s
368. A 70-yea r-ol d ma n compl a i ns of progres s i ve di ffi cul ty s ta rti ng hi s uri ne s trea m, a nd ha vi ng to get up s evera l ti mes duri ng ea ch ni ght to
uri na te. Recta l exa mi na ti on revea l s a genera l l y enl a rged, s mooth-s urfa ced pros ta te. Pros ta te-s peci fi c a nti gen (PSA) ti ters a re s i gni fi ca ntl y
el eva ted. You deci de to s ta rt fi na s teri de trea tment. Eventua l l y uri ne fl ow i ncrea s es , noctures i s epi s odes decrea s e, a nd overa l l pros ta te s i ze
decrea s es . Whi ch phra s e bes t s umma ri zes the mos t l i kel y mecha ni s m by whi ch fi na s teri de ca us ed s ymptom rel i ef?
a . Bl ocks -a drenergi c receptors
b. Bl ocks tes tos terone receptors
c. Inhi bi ts di hydrotes tos terone s ynthes i s
d. Inhi bi ts tes tos terone s ynthes i s
e. Lowers pl a s ma tes tos terone l evel s by i ncrea s i ng i ts rena l cl ea ra nce
369. A 38-yea r-ol d woma n pres ents i n the endocri nol ogy a nd meta bol i s m cl i ni c toda y. One of the drugs s he i s ta ki ng i s cl a s s i fi ed a s a di pepti dyl
pepti da s e-4 (DPP-4) i nhi bi tor. Whi ch s ta tement bes t des cri bes the ma i n a cti ons of thi s drug?
a . Acti va tes hydroxyl a s es requi red for corti s ol a nd a l dos terone s ynthes i s
b. Cl ea ves a cti ve i ns ul i n from the proi ns ul i n mol ecul e
c. Enzyma ti ca l l y s pl i ts l evothyroxi ne from thyrogl obul i n

d. Hel ps norma l i ze phys i ol ogi c rel ea s e of es trogen a nd proges terone

e. Inhi bi ts i na cti va ti on of i ncreti ns , ra i s es gl uca gon-l i ke pepti de l evel s
370. A 54-yea r-ol d woma n who ha s not s een a phys i ci a n for s evera l yea rs pres ents wi th a previ ous l y undi a gnos ed thyroi d ca ncer a nd
thyrotoxi cos i s . One drug tha t i s a dmi ni s tered a s pa rt of ea rl y ma na gement, a nd ma y be l i fes a vi ng, i s propra nol ol . Whi ch of the fol l owi ng bes t
s umma ri zes the objecti ve for a dmi ni s teri ng thi s drug?
a . Bl ock pa renchyma l cel l receptors for thyroi d hormones
b. Bl ock thyroi d hormone rel ea s e by a di rect effect on the gl a nd
c. Inhi bi t thyroi d hormone s ynthes i s
d. Les s en da ngerous ca rdi ova s cul a r s i gns a nd s ymptoms of thyroi d hormone exces s
e. Lower TSH l evel s
371. A woma n deemed a t hi gh ri s k of pos tmenopa us a l os teoporos i s i s s ta rted on a l endrona te. Wha t i s thi s repres enta ti ve bi s phos phona tes
ma i n mecha ni s m of a cti on?
a . Acti va tes vi ta mi n D a nd s o fa ci l i ta tes a bs orpti on of di eta ry ca l ci um
b. Conta i ns l ots of ca l ci um, whi ch s uppl ements di eta ry ca l ci um i nta ke
c. Di rectl y forms hydroxya pa ti te crys ta l s i n bone
d. Provi des s uppl ementa l phos pha te, whi ch i ndi rectl y el eva tes pl a s ma Ca 2 +
e. Reduces the number a nd a cti vi ty of os teocl a s ts i n bone
372. Some pa ti ents who a re ta ki ng hi gh dos es of a bi s phos phona te for Pa get di s ea s e of the bone devel op a n endocri ne-meta bol i c di s order. Wha t
di s order woul d tha t be?
a . Cus hi ng di s ea s e (cus hi ngoi d s ymptoms )
b. Di a betes i ns i pi dus
c. Di a betes mel l i tus
d. Hyperpa ra thyroi di s m
e. Hyperthyroi di s m
373. Metyra pone i s us eful i n tes ti ng hyper- or hypo-functi on of certa i n endocri ne condi ti ons or bi ol ogi ca l proces s es thos e gl a nds norma l l y control .
When we a dmi ni s ter thi s drug for di a gnos ti c purpos es , whi ch s tructure or functi on a re we mos t l i kel y a s s es s i ng?
a . cel l s of pa ncrea ti c i s l ets
b. cel l s of pa ncrea ti c i s l ets
c. Leydi g cel l s of the tes tes
d. Pi tui ta ry-a drena l a xi s
e. Thyroi d gl a nds res pons e to TSH
374. A 60-yea r-ol d ma n on l ong-term thera py wi th a drug devel ops hypertens i on, hypergl ycemi a , a nd decrea s ed bone dens i ty. Bl ood tes ts i ndi ca te
a nemi a . Some of hi s s tool s a mpl es i ni ti a l l y were pos i ti ve for occul t bl ood, a nd then the s tool devel oped a coffee-grounds a ppea ra nce. Whi ch
drug i s mos t l i kel y res pons i bl e for the pa ti ents s ymptoms ?
a . Becl ometha s one
b. Hydrochl orothi a zi de
c. Metformi n
d. Pa mi drona te
e. Predni s one
375. A woma n wi th a tri a l fi bri l l a ti on i s bei ng trea ted l ong-term wi th a mi oda rone (a nd wa rfa ri n). Thi s a nti a rrhythmi c ca n ca us e bi ochemi ca l
cha nges a nd cl i ni ca l s i gns a nd s ymptoms tha t res embl e thos e a s s oci a ted wi th whi ch endocri ne di s ea s e/di s order?
a . Addi s oni a n cri s i s
b. Cus hi ng s yndrome
c. Di a betes i ns i pi dus
d. Di a betes mel l i tus
e. Hypothyroi di s m
f. Ova ri a n hypers ti mul a ti on s yndrome
376. A 22-yea r-ol d woma n ha s been s exua l l y a s s a ul ted a nd s he wi s hes to ha ve the pregna ncy termi na ted by pha rma col ogi c mea ns . Wha t i s
genera l l y the mos t a ppropri a te drug, a s s umi ng no contra i ndi ca ti ons ?
a . Ergonovi ne (or methyl ergonovi ne)
b. Mi fepri s tone
c. Ra l oxi fene
d. Ri todri ne
e. Ta moxi fen
377. A pa ti ent ha s hyperthyroi di s m from a thyroi d ca ncer, a nd the medi ca l tea m concl udes tha t ora l ra di oi odi ne (s odi um i odi de 131 [131 I]) i s the
preferred trea tment. The dos a ge i s ca l cul a ted correctl y, a nd the drug i s a dmi ni s tered. Wha t s ta tement a bout thi s a pproa ch i s a l s o correct?

a . A -a drenergi c bl ocker s houl d not be us ed for s ymptom control i f or when 131 I i s us ed

b. Hyperthyroi di s m s ymptoms res ol ve a l mos t compl etel y wi thi n 24 to 48 hours a fter dos i ng wi th 131 I
c. Ma ny pa ti ents trea ted wi th 131 I devel op meta s ta ti c nonthyroi d ca ncers i n res pons e to the drug
d. Ora l a nti thyroi d drugs s houl d be a dmi ni s tered up to a nd i ncl udi ng the da y of 131 I a dmi ni s tra ti on
e. There i s a hi gh i nci dence of del a yed hypothyroi di s m a fter us i ng 131 I for era di ca ti on of a thyroi d tumor, a nd s o thyroi d hormone s uppl ements
ma y be needed l a ter on
378. A 20-yea r-ol d woma n, otherwi s e hea l thy, pres ents wi th i rregul a r a nd occa s i ona l l y mi s s ed mens trua l peri ods , oi l y fa ci a l s ki n a nd a cne, a nd
s l i ght hi rs uti s m. She wa s a competi ti ve runner duri ng hi gh s chool a nd now i s i n tra i ni ng for a tri a thl on. She i s not ta ki ng a ny medi ca ti ons other
tha n a n es trogen-proges terone ora l contra cepti ve. A pel vi c ul tra s ound eva l ua ti on revea l s numerous i mma ture ova ri a n fol l i cl es (genera l l y but
i ncorrectl y referred to a s cys ts ). The di a gnos i s i s pol ycys ti c ova ri a n s yndrome (PCOS). Whi ch drug woul d be the mos t ra ti ona l i ni ti a l thera py to
pres cri be to hel p provi de s ymptom rel i ef wi thout compromi s i ng the woma ns a bi l i ty to concei ve?
a . Es trogen (dos e hi gher tha n i n her ora l contra cepti ve)
b. Ketocona zol e
c. Metformi n
d. Predni s one (or a s i mi l a r ora l gl ucocorti coi d)
e. Tes tos terone
379. A 50-yea r-ol d woma n wi th a hi gh ri s k of brea s t ca ncer i s s ta rted on ta moxi fen for prophyl a xi s . Wha t i s the ma i n mecha ni s m of a cti on of thi s
drug?
a . Bl ocks es trogen receptors i n brea s t ti s s ue
b. Bl ocks es trogen receptors i n the endometri um
c. Increa s es the ri s k of os teoporos i s
d. Ra i s es pl a s ma LDL chol es terol a nd tota l chol es terol , l owers HDL
e. Reduces the ri s k of thromboembol i c di s orders
380. A 50-yea r-ol d woma n i s recentl y di a gnos ed wi th type 2 di a betes mel l i tus . Exerci s e a nd di et do not provi de a dequa te gl ycemi c control , s o drug
thera py needs to s ta rt. The phys i ci a n contempl a tes pres cri bi ng metformi n. Whi ch s ta tement a bout thi s drug i s correct?
a . Benefi ci a l a nd unwa nted a cti ons a re una ffected by l i ver functi on s ta tus
b. La cti c a ci dos i s occurs frequentl y, but i t i s s el dom s eri ous
c. Metformi n-i nduced hypogl ycemi a s el dom occurs
d. Us eful for type 1 di a betes a l s o
e. Wei ght ga i n i s a common a nd unwa nted s i de effect
381. Mos t thera peuti c i ns ul i ns nowa da ys a re modi fi ca ti ons of na ti ve huma n i ns ul i n, done by s ubs ti tuti ng s ome a mi no a ci ds i n the na ti ve protei n
us i ng recombi na nt DNA technol ogy. For a l l thes e geneti ca l l y modi fi ed i ns ul i ns , wha t i s the one common res ul t of s uch cha nges ?
a . Cha nges the ons ets , dura ti ons of a cti on
b. Ena bl es a dmi ni s tra ti on by ei ther s ubcuta neous or i ntra venous routes
c. Prevents cel l ul a r K+ upta ke a s gl ucos e enters cel l s
d. Rea cti va tes endogenous (pa ncrea ti c) i ns ul i n s ynthes i s
e. Sel ecti vel y a ffects gl ucos e meta bol i s m, l i ttl e/no effects on l i pi ds
382. You ha ve pres cri bed a n ora l a gent to hel p control a pa ti ents bl ood gl ucos e l evel s . He ha s type 2 di a betes . In expl a i ni ng how the drug works ,
you des cri be i t a s a s ta rch bl ocker tha t i nhi bi ts the i ntes ti na l upta ke of compl ex ca rbohydra tes i n the di et. You a dvi s e a l s o tha t fl a tus or s ome
cra mpi ng or grumbl i ng s ounds i n the bel l y ma y devel op. Whi ch drug fi ts thi s des cri pti on?
a . Aca rbos e
b. Any thi a zol i di nedi one (gl i ta zone)
c. Gl i pi zi de
d. Metformi n
e. Tol buta mi de
383. A pa ti ent wi th type 1 di a betes i s bei ng trea ted wi th i ns ul i n gl a rgi ne. Wha t cl i ni ca l l y i mporta nt property s ets thi s pa rti cul a r i ns ul i n a pa rt, or
otherwi s e di fferenti a tes i t, from nea rl y a l l the other i ns ul i n formul a ti ons tha t mi ght be us ed i ns tea d?
a . Bl ood l evel s , hypogl ycemi c effects , fol l owi ng i ns ul i n gl a rgi ne i njecti on a re more a ccura tel y des cri bed a s a pl a tea u ra ther a s a defi ni te s pi ke
or pea k
b. Di s ul fi ra m-l i ke rea cti ons (a ceta l dehyde a ccumul a ti on from i nhi bi ted EtOH meta bol i s m) more common, s evere, wi th i ns ul i n gl a rgi ne
c. Ha s a n extremel y fa s t ons et, us eful for i mmedi a te pos tpra ndi a l control of pl a s ma gl ucos e el eva ti ons
d. Pos es l i ttl e or no ri s k of hypogl ycemi a i f the pa ti ent s ki ps s evera l mea l s i n a row
e. Sens i ti zes pa renchyma l cel l s to i ns ul i n (eg, the a dmi ni s tered i ns ul i n i ts el f), not s i mpl y provi di ng or repl a ci ng i ns ul i n, thereby enha nci ng
gl ycemi c control
384. A pa ti ent pres ents i n the emergency depa rtment (ED) wi th a ma s s i ve overdos e of a drug. The mos t worri s ome s i gns a nd s ymptoms i ncl ude
exces s i ve ca rdi a c s ti mul a ti on (s evere ta chyca rdi a , pa l pi ta ti ons , a ngi na , etc). The ED phys i ci a n orders IV a dmi ni s tra ti on a -a drenergi c bl ocker,
s a yi ng (correctl y) i t i s the onl y drug l i kel y to norma l i ze ca rdi a c functi on qui ckl y a nd s a ve the pa ti ents l i fe. Wha t wa s the mos t l i kel y drug the
pa ti ent overdos ed on?

a . A s econd-genera ti on s ul fonyl urea (eg, gl i pi zi de, gl yburi de)

b. Ins ul i n
c. Levothyroxi ne
d. Predni s one (ora l gl ucocorti coi d)
e. Propyl thi oura ci l
385. Thi s week fi nds you a ccompa nyi ng a n a ttendi ng i n her outpa ti ent endocri nol ogy cl i ni c. One pa ti ent, a 56-yea r-ol d woma n, i s ta ki ng exena ti de, whi ch i s cl a s s i fi ed a s a n i ncreti n mi meti c. Wha t phra s e bes t des cri bes exena ti des a cti ons or ma i n cl i ni ca l us e?
a . Anta goni zes tes tos terone effects , us eful for trea ti ng hi rs uti s m i n men or women
b. Is a new a djunct to metformi n a nd/or s ul fonyl urea thera py of hyperthyroi di s m
c. Often us ed a s a n a dd-on to a bi s phos phona te for prophyl a xi s of pos tmeno-pa us a l os teoporos i s
d. Preferred s ti mul a nt of corti s ol producti on for trea ti ng Addi s on di s ea s e
e. Us eful a djunct for s ome pa ti ents wi th poorl y control l ed type 2 di a betes mel l i tus
386. A pa ti ent wi th hypothyroi di s m fol l owi ng thyroi dectomy wi l l requi re l i fel ong hormone repl a cement thera py. Wha t drug or formul a ti on genera l l y
woul d be mos t s ui ta bl e?
a . Levothyroxi ne (T4 )
b. Li othyroni ne
c. Li otri x
d. Proti rel i n
e. Thyroi d, des i cca ted
387. A pa ti ent devel ops ma rked s kel eta l mus cl e teta ny s oon a fter a recent thyroi dectomy. The a ttendi ng confi rms the di a gnos i s , i n pa rt, by l i ghtl y
ta ppi ng the pa ti ents cheek i n front of the ea r. Sti mul a ti ng the fa ci a l nerves i n thi s ma nner l ea ds to s pa s ms of the l oca l (ori s ) mus cl e (Chvos tek
s i gn). Whi ch drug i s mos t l i kel y to be chos en to ma na ge thi s a dvers e res pons e to s urgery?
a . Ca l ci toni n
b. Ca l ci um gl ucona te
c. Pl i ca myci n (mi thra myci n)
d. PTH (pa ra thyroi d hormone)
e. Vi ta mi n D
388. A 40-yea r-ol d ma n wi th a s ymmetri ca l l y enl a rged thyroi d gl a nd a s s oci a ted wi th el eva ted l evel s of T3 a nd T4 i s trea ted wi th propyl thi oura ci l
(PTU). Whi ch phra s e bes t s umma ri zes the pri nci pa l mecha ni s m of a cti on of PTU?
a . Bl ocks i odi de tra ns port i nto the thyroi d
b. Increa s es hepa ti c meta bol i c i na cti va ti on of ci rcul a ti ng T4 a nd T3
c. Inhi bi ts proteol ys i s of thyrogl obul i n
d. Inhi bi ts thyroi da l peroxi da s e
e. Rel ea s es T3 a nd T4 i nto the bl ood
389. The a ttendi ng i n the endocri ne/meta bol i c di s ea s es cl i ni c pres cri bes col es evel a m a s a dd-on thera py for a 58-yea r-ol d ma l e wi th type 2
di a betes who i s not getti ng a dequa te gl ycemi c control (ba s ed on hi gh l evel s of HbA1c mea s ured twi ce i n the l a s t 12 months ) from hi s current
medi ca ti ons : metformi n a nd gl yburi de. The ma n ha s been a pa ck-a -da y ci ga rette s moker for 40 yea rs a nd s a ys he ca nt s eem to qui t. In a ddi ti on
to the di a betes a nd ni coti ne a ddi cti on he ha s s evera l other comorbi di ti es tha t a re not opti ma l l y ma na ged wi th hi s current medi ca ti ons for ea ch,
or recommended l i fes tyl e modi fi ca ti ons (he l a rgel y i gnores them). The a ttendi ng s ta tes tha t the col e-s evel a m mi ght jus t hel p one of thos e
comorbi di ti es i n a ddi ti on to pos s i bl y l oweri ng HbA1c l evel s a fter a few months on the drug. Wha t i s the other condi ti on tha t i s mos t l i kel y to be
fa vora bl y a nd ra ther di rectl y i nfl uenced by the col es evel a m?
a . Chroni c bronchi ti s (or emphys ema )
b. Hyperl i pi demi a s
c. Hyperuri cemi a , gout
d. Ni coti ne a ddi cti on
e. Pros ta ti s m (i e, beni gn pros ta ti c hypertrophy)
390. Your pa ti ent, who i s ta ki ng a n ora l contra cepti ve, ha s hea rd a bout a nd a s ks a bout the ri s k of thromboembol i s m a s a res ul t of ta ki ng thes e
drugs . To reduce the ri s k of thi s potenti a l l y s evere a dvers e hema tol ogi c res pons e, but s ti l l provi de rea s ona bl y effecti ve contra cepti on, wha t woul d
you pres cri be?
a . A combi na ti on product wi th a hi gher es trogen dos e
b. A combi na ti on product wi th a hi gher proges ti n dos e
c. A combi na ti on product wi th a l ower es trogen dos e
d. A combi na ti on product wi th a l ower proges ti n dos e
e. A product tha t conta i ns onl y es trogen
391. A 27-yea r-ol d woma n i s di a gnos ed wi th hypercorti s m. To determi ne whether corti s ol producti on i s i ndependent of pi tui ta ry gl a nd control , you
deci de to s uppres s ACTH producti on by gi vi ng a hi gh-potency gl ucocorti coi d. Whi ch drug woul d be the bes t choi ce for thi s purpos e?
a . Dexa metha s one
b. Hydrocorti s one

c. Methyl predni s ol one

d. Predni s one
e. Tri a mci nol one
392. A pa ti ent wi th Cus hi ng s yndrome i s bei ng trea ted by X-i rra di a ti on of the pi tui ta ry. It ma y ta ke s evera l months of thi s thera py for a dequa te
s ymptoma ti c a nd meta bol i c i mprovement. Unti l tha t ti me, whi ch drug woul d be a dmi ni s tered to s uppres s gl ucocorti coi d s ynthes i s ?
a . Ci meti di ne
b. Corti s ol (ma s s i ve dos es )
c. Fl udrocorti s one
d. Ketocona zol e
e. Spi ronol a ctone
393. A woma n who ha s been ta ki ng a n ora l contra cepti ve (es trogen pl us proges ti n) for s evera l yea rs i s di a gnos ed wi th epi l eps y a nd s ta rted on
phenytoi n. Wha t i s the mos t l i kel y cons equence of a ddi ng the phenytoi n?
a . Agra nul ocytos i s or a pl a s ti c a nemi a , requi ri ng s toppi ng both drugs i mmedi a tel y
b. Brea kthrough s ei zures from i ncrea s ed phenytoi n cl ea ra nce
c. Phenytoi n toxi ci ty, s i gni fi ca nt a nd of fa s t ons et
d. Profoundl y i ncrea s ed ri s k of cra ni ofa ci a l a bnorma l i ti es i n the fetus
e. Reduced contra cepti ve effi ca cy
f. Thromboembol i s m from the es trogen component of the contra cepti ve
394. A woma n wa nts a pres cri pti on for a n ora l contra cepti ve, a nd your choi ce i s between a n es trogen-proges ti n combi na ti on a nd a mi ni pi l l
(proges ti n onl y). Compa red wi th a hormone combi na ti on product, wha t i s the ma i n di fference tha t woul d occur when a proges ti n-onl y a pproa ch i s
us ed?
a . Better contra cepti ve effi ca cy
b. Di rect s permi ci da l effects
c. Hi gher ri s k of thromboembol i s m
d. More mens trua l i rregul a ri ti es (i rregul a r cycl e l ength, a menorrhea , s potti ng, etc)
e. Poorer compl i a nce due to ta ki ng the drug on a n i rregul a r cycl e, ra ther tha n da i l y
395. A woma n i s ta ki ng a combi na ti on es trogen-proges ti n combi na ti on ora l contra cepti ve. She experi ences a mul ti tude of s i de effects . Whi ch s i de
effect i s mos t l i kel y due to wha t ca n be des cri bed a s a n es trogen exces s , a nd not l i kel y due to the proges ti n content of the medi ca ti on?
a . Fa ti gue
b. Hypertens i on
c. Hypomenorrhea
d. Increa s ed a ppeti te
e. Wei ght ga i n
396. A coma tos e pa ti ent wi th a n endocri ne di s order undergoes a computed tomogra phy (CT) di a gnos ti c procedure tha t i nvol ves contra s t medi a tha t
ha s a tendency to i nduce l a cti c a ci dos i s . He i s a l s o ta ki ng a drug tha t, i n i ts own ri ght, ma y ca us e l a cti c a ci dos i s . Norma l l y the drug woul d be
s topped, a t l ea s t tempora ri l y, two da ys before the CT, but due to the pa ti ents a cute a nd s eri ous i l l nes s tha t coul d not be done. La cti c a ci dos i s
i ndeed devel ops a nd the pa ti ent nea rl y di es . Whi ch drug wa s the mos t l i kel y ca us e of thi s s evere a nd potenti a l l y fa ta l meta bol i c dera ngement?
a . Ins ul i n gl a rgi ne, pres cri bed for type 1 di a betes mel l i tus
b. Levothyroxi ne, pres cri bed to ma i nta i n euthyroi d s ta tus fol l owi ng thyroi dectomy
c. Metformi n, pres cri bed for type 2 di a betes mel l i tus
d. Propyl thi oura ci l , pres cri bed for hyperthyroi di s m
e. Spi ronol a ctone, pres cri bed for a n a drena l corti ca l tumor
397. A pa ti ent wi th type 2 di a betes mel l i tus begi ns ga i ni ng wei ght a fter s evera l months of thera py wi th a n ora l a nti di a beti c a gent. A compl ete
work-up i ndi ca tes edema a nd other s i gns a nd s ymptoms of heart failure. Whi ch a nti di a beti c drug or group wa s the mos t l i kel y ca us e?
a . Aca rbos e
b. Bi gua ni des
c. Metformi n
d. Pi ogl i ta zone
e. Sul fonyl urea s , both fi rs t- a nd s econd-genera ti on a gents (eg, tol buta mi de, chl orpropa mi de, gl yburi de, gl i pi zi de)
398. A woma n goes i nto prema ture l a bor ea rl y enough tha t there a re grea t concerns a bout i na dequa te feta l l ung devel opment a nd the ri s k of feta l
res pi ra tory di s tres s s yndrome. Sui ta bl e uteri ne-rel a xi ng drug thera py i s s ta rted to s l ow l a bor, but pa rturi ti on s eems i mmi nent. Wha t other a djunct
s houl d be a dmi ni s tered prepa rtum, s peci fi ca l l y for the purpos e of reduci ng the ri s ks a nd compl i ca ti ons of the newborns i mma ture res pi ra tory
s ys tem devel opment?
a . Al buterol (2 a goni s t)
b. Beta metha s one
c. Ergonovi ne (or methyl ergonovi ne)
d. Indometha ci n
e. Ma gnes i um s ul fa te

399. We pres cri be eti drona te for a pos tmenopa us a l woma n who i s a t grea t ri s k for devel opi ng for os teoporos i s . Whi ch s i de effect or a dvers e
res pons e to thi s drug i s the pa ti ent mos t l i kel y to experi ence?
a . Chol el i thi a s i s
b. Es opha gi ti s
c. Fl ui d/el ectrol yte l os s from profus e di a rrhea
d. Hepa ti c necros i s
e. Rena l da ma ge from ca l ci um s tone forma ti on
f. Teta ny
400. A 75-yea r-ol d ma n ha d s urgery for pros ta te ca rci noma , a nd l oca l meta s ta s es were found i ntra opera ti vel y. Wha t i s the mos t a ppropri a te
fol l ow-up drug a i med a t trea ti ng the meta s ta s es ?
a . Ami nogl utethi mi de
b. Fl udrocorti s one
c. Leuprol i de
d. Mi fepri s tone
e. Spi ronol a ctone
401. A 53-yea r-ol d woma n wi th type 2 di a betes mel l i tus i s s ta rted on gl yburi de. Di et, exerci s e, a nd us ua l l y effecti ve dos es of metformi n ha ve not
provi ded a dequa te gl ycemi c control ba s ed on peri odi c mea s urements of HbA1c. Wha t i s the pri ma ry mecha ni s m by whi ch the gl yburi de i s l i kel y to
provi de better gl ycemi c control ?
a . Decrea s e i ns ul i n res i s ta nce by l oweri ng body wei ght
b. Enha nce rena l excreti on of gl ucos e
c. Increa s e i ns ul i n s ynthes i s
d. Promote gl ucos e upta ke by mus cl e, l i ver, a nd a di pos e ti s s ue vi a a n i ns ul i n-i ndependent proces s
e. Rel ea s e i ns ul i n from the pa ncrea s
402. A 75-yea r-ol d woma n wi th type 2 di a betes i s ta ki ng a n ora l a nti -di a beti c drug. One da y s he goes wi thout ea ti ng for 18 hours , but ta kes her
drug nonethel es s . She i s tra ns ported to the emergency a fter pa s s i ng out. Her pl a s ma gl ucos e concentra ti on i s 48 mg/dL (hypogl ycemi c) upon
a rri va l a t the ED, a nd s he i s i n very s eri ous condi ti on. Whi ch drug, tha t mos t l i kel y a ggra va ted thi s fa s ti ng hypogl ycemi a , di d s he ta ke?
a . Aca rbos e
b. Col es evel a m
c. Gl yburi de
d. Metformi n
e. Pi ogl i ta zone
403. A ma n wi th type 2 di a betes i s recei vi ng a combi na ti on of ora l drugs to ma i nta i n gl ycemi c control . He becomes hypogl ycemi c one a fternoon a nd
i nges ts s ome ora nge jui ce a nd two chocol a te ba rs a l l conta i ni ng a bunda nt a mounts of compl ex ca rbohydra tes . Des pi te hi s i nges ti on of ora nge
jui ce a nd s evera l chocol a te ba rs , hi s bl ood gl ucos e l evel s rema i n l ow, hi s s ymptoms pers i s t. Whi ch a nti di a beti c tha t he wa s ta ki ng a ccounted for
the fa i l ure of ora l s uga rs to res tore hi s pl a s ma gl ucos e?
a . Aca rbos e
b. Gl yburi de
c. Metformi n
d. Repa gl i ni de
e. Ros i gl i ta zone
404. A 35-yea r-ol d woma n ha s Gra ves di s ea s e, a s ma l l goi ter, a nd s ymptoms tha t a re deemed mi l d-to-modera te. Propyl thi oura ci l i s pres cri bed.
Wha t i s the mos t s eri ous a dvers e res pons e to thi s drug, for whi ch cl os e moni tori ng i s requi red?
a . Agra nul ocytos i s
b. Chol es ta ti c ja undi ce
c. Gout
d. Rena l tubul a r necros i s
e. Rha bdomyol ys i s
f. Thyroi d ca ncer
405. A 60-yea r-ol d ma n wi th type 2 di a betes mel l i tus i s trea ted wi th pi ogl i ta zone (i n a ddi ti on to a proper di et a nd exerci s e). Whi ch phra s e
s umma ri zes bes t thi s drugs ma i n mecha ni s m of a cti on?
a . Bl ocks i ntes ti na l ca rbohydra te a bs orpti on
b. Ca us es gl ycos uri a (i ncrea s ed rena l gl ucos e excreti on)
c. Increa s es hepa ti c gl uconeogenes i s
d. Increa s es rel ea s e of endogenous i ns ul i n
e. Increa s es ta rget ti s s ue s ens i ti vi ty to i ns ul i n
406. A pa ti ent wi th a hi s tory of type 2 di a betes mel l i tus pres ents i n the ED. Hi s compl a i nts i ncl ude nons peci fi c ga s troi ntes ti na l s ymptoms ,
i ncl udi ng na us ea a nd vomi ti ng. He s ta tes he i s bl oa ted a nd ha s a bdomi na l pa i n. Hi s a ppeti te ha s been s uppres s ed for s evera l da ys . He ha s
ma l a i s e a nd di ffi cul ty brea thi ng. Hi s l i ver i s enl a rged a nd tender; l i ver functi on tes ts i ndi ca te hepa ti c da ma ge. Pl a s ma bi ca rbona te i s l ow a nd

l a cta te l evel s a re hi gh. Ki dney functi on i s fa l l i ng ra pi dl y.

The di a gnos i s i s l a cti c a ci dos i s , a nd the s us pi ci on i s tha t i t wa s ca us ed by a n a nti di a beti c drug. Whi ch of the fol l owi ng drugs i s thi s pa ti ent
mos t l i kel y to be ta ki ng?
a . Aca rbos e
b. Gl i pi zi de
c. Gl yburi de
d. Metformi n
e. Pi ogl i ta zone
407. A pa ti ent i s tra ns ported to the ED s hortl y a fter ta ki ng a ma s s i ve overdos e of her l evothyroxi ne i n a n a ppa rent s ui ci de a ttempt. Whi ch of the
fol l owi ng drugs s houl d be a dmi ni s tered for prompt control of the hormone-rel a ted effects tha t a re mos t l i kel y to l ea d to her dea th i f not correctl y
ma na ged?
a . Iodi ne/i odi de
b. Li othyroni ne
c. Propra nol ol
d. Propyl thi oura ci l
e. Ra di oi odi ne ( 131 I)
408. There a re two ma i n formul a ti ons of ora l contra cepti ves : thos e tha t a re es trogen-proges ti n combi na ti ons , a nd thos e tha t conta i n onl y
proges ti n (mi ni pi l l ). Wha t i s the ma i n mecha ni s m by whi ch thes e drugs exert thei r des i red contra cepti ve effects ?
a . Aci di fy the cervi ca l mucus , thereby ma ki ng the mucus s permi ci da l
b. Di s pl a ce/deta ch a ferti l i zed egg from the endometri um
c. Inhi bi t ni da ti on (i mpl a nta ti on of a ferti l i zed ovum)
d. Inhi bi t ovul a ti on
e. Reduce uteri ne bl ood fl ow s uch tha t the ferti l i zed ovum becomes hypoxi c a nd di es
409. A 55-yea r-ol d pos tmenopa us a l woma n devel ops wea knes s , pol yuri a , pol ydi ps i a , a nd s i gni fi ca nt i ncrea s es of pl a s ma crea ti ni ne
concentra ti on. A computed tomogra m (CT s ca n) i ndi ca tes nephroca l ci nos i s . A drug i s cons i dered to be the ca us e. Whi ch drug wa s mos t l i kel y
res pons i bl e?
a . Es trogens
b. Eti drona te
c. Gl i pi zi de
d. Predni s one
e. Vi ta mi n D
410. A pa ti ent ha s s evere Cus hi ng di s ea s e. Surgery ca nnot be s chedul ed for s evera l months , s o the phys i ci a n pl a ns to trea t the pa ti ent i n the
i nteri m wi th a drug tha t s he des cri bes a s a potent i nhi bi tor of corti cos teroi d s ynthes i s . Whi ch drug bes t fi ts tha t des cri pti on?
a . Dexa metha s one
b. Hydrocorti s one
c. Ketocona zol e
d. Predni s one
e. Spi ronol a ctone
411. You pres cri be bromocri pti ne for a woma n wi th pri ma ry a menorrhea . Norma l mens trua ti on returns a bout a month a fter s ta rti ng thera py. Whi ch
s ta tement bes t des cri bes the mecha ni s m by whi ch bromocri pti ne ca us ed i ts des i red effects ?
a . Bl ocked es trogen receptors , enha nced gona dotropi n rel ea s e
b. Increa s ed fol l i cl e-s ti mul a ti ng hormone (FSH) s ynthes i s
c. Inhi bi ted prol a cti n rel ea s e
d. Sti mul a ted ova ri a n es trogen a nd proges ti n s ynthes i s
e. Sti mul a ted gona dotropi n-rel ea s i ng hormone (GnRH) rel ea s e
412. A pa ti ent ha s ha d hi s pa ra thyroi d gl a nds exci s ed duri ng a tota l thyroi dectomy. In a ddi ti on to requi ri ng s uppl ementa l thyroi d hormone,
i nterventi ons a i med a t correcti ng hypopa ra thyroi di s m wi l l be neces s a ry. Wha t i s the ma i n phys i ol ogi c a cti on or rol e of pa ra thyroi d hormoneone
tha t neces s i ta tes s ui ta bl e thera py?
a . Decrea s es a cti ve a bs orpti on of Ca from the s ma l l i ntes ti ne
b. Decrea s es excreti on of phos pha te
c. Decrea s es rena l tubul a r rea bs orpti on of ca l ci um
d. Decrea s es res orpti on of phos pha te from bone
e. Increa s es mobi l i za ti on of ca l ci um from bone

Endocrine and Reproductive Pharmacology

Answers
365. The answer is a. (Brunton, pp 731-736, 798; Katzung, pp 183-185, 299.) Pers i s tentl y hi gh pl a s ma gl ucos e a nd chol es terol l evel s obvi ous l y ha ve ma ny
untowa rd cons equences , one of whi ch i s renova s cul a r di s ea s e tha t ma y l ea d to eventua l rena l fa i l ure a nd dea th. He a l rea dy ha s
mi croa l bumi nuri a , s o s ome rena l da ma ge i s l i kel y pres ent. When the a rteri a l s uppl y to both ki dneys i s reduced beca us e of s tenos i s (or other
fa ctors ), tha t wei ghs a ga i ns t us i ng a n ACE i nhi bi tor or a n ARB. Angi otens i n II ha s a cri ti ca l rol e i n ma i nta i ni ng gl omerul a r fi l tra ti on by i ncrea s i ng
efferent a rteri ol a r pres s ure. Bl ocki ng A-II s ynthes i s , or i ts receptor-medi a ted va s ocons tri ctor effects , ca n s i gni fi ca ntl y reduce rena l perfus i on a nd
GFR a nd, eventua l l y a nd s ometi mes preci pi tous l y, l ea d to rena l fa i l ure. ACE i nhi bi tors or ARBs do not ca us e bra dyca rdi a (b), whether di rectl y or vi a
ba roreceptor-rel a ted refl ex mecha ni s ms . Pri or epi s odes of hyperos mol a r hypergl ycemi c nonketoti c s yndrome (HHNKA, c) refl ect peri ods of s evere,
s ymptoma ti c hyper-gl ycemi a (a nd poor gl ycemi c control ). In the a bs ence of bi l a tera l rena l di s ea s e or other rena l pa thol ogi es (or i f the pa ti ent i s
not a woma n who i s pregna nt or of chi l d-bea ri ng potenti a l ), a n ACE i nhi bi tor or ARB woul d be a l ogi ca l choi ce for control l i ng hypertens i on; hea rt
fa i l ure does not contra i ndi ca te (d) the us e of thes e medi ca ti ons . Nei ther hyperchol es terol emi a or hypertri gl yceri demi a (or both), nor the us e of
ni a ci n or other drugs for dys l i pi demi a s (e), ha s a ny i mpa ct on the deci s i on to us e a n ACE i nhi bi tor or ARB i n the a bs ence of other
contra i ndi ca ti ons .
366. The answer is b. (Brunton, pp 788, 1248, 1272; Katzung, pp 182-183.) Ora l di a zoxi de i s i ndi ca ted for the very s i tua ti on des cri bed i n the ques ti on. It
i s , chemi ca l l y, a benzothi a di a zi de (l i ke hydrochl orothi a zi de, ma ny other di ureti c/a nti hypertens i ves ), but i t i s more effi ca ci ous i n terms of reduci ng
pa renchyma l cel l (s kel eta l mus cl e, a di pocytes ) res pons i venes s , or s ens i ti vi ty to i ns ul i n, thereby hel pi ng to ra i s e bl ood gl ucos e l evel s . (Reca l l tha t
thi a zi des tend to ca us e hypergl ycemi a a s a s i de effect. Tha t i s due to thei r i ns ul i n-des ens i ti zi ng effects .) Nei ther di a zoxi de or a thi a zi de di ureti c
ha s a ny s i gni fi ca nt effects to i nhi bi t i ns ul i n s ynthes i s , rel ea s e, or bl ood l evel s . Indeed, they tend to ca us e hyperi ns ul i ni s m i n res pons e to
hypergl ycemi a .
Atenol ol , metoprol ol (a ), a nd other drugs tha t bl ock -a drenergi c receptors tend to s uppres s i ns ul i n rel ea s e, ca us e hypogl ycemi a , del a y recovery
from hypogl ycemi c epi s odes by i nhi bi ti ng hepa ti c gl ycogenol ys i s a nd s uppres s i ng i ns ul i n rel ea s e, a nd bl ock ta chyca rdi a (a ti p-off to s ome
di a beti c pa ti ents tha t thei r bl ood gl ucos e l evel s a re getti ng qui te l ow) tha t tends to occur i n res pons e to hypogl ycemi a . (The degree or extent to
whi ch -a drenergi c bl ockers exert thei r effects on gl ucos e depends on the overa l l profi l e of the i ndi vi dua l a gents nons el ecti ve [propra nol ol ,
others ]; a tenol ol or metoprol ol [l a rgel y 1 s el ecti ve]; l a beta l ol or ca rvedi l ol [nons el ecti ve - pl us 1 bl ocka de]; pi ndol ol [nons el ecti ve -bl ocka de
wi th i ntri ns i c s ympa thomi meti c a cti vi ty]).
Gl uca gon (c) i s us ed to ma na ge hypogl ycemi a (a s a s uppl ement to i ntra venous gl ucos e a dmi ni s tra ti on), but i t i s a n i njecta bl e drug us ed onl y a s
a n a djunct (to IV gl ucos e) for s hort-term, s evere, a nd s ymptoma ti c hypogl ycemi a . Octreoti de (d), i denti fi ed a s a s oma tos ta ti n a na l og, i s us ed to
i nhi bi t growth hormone (GH) rel ea s e a nd the effects of GH on i ns ul i n-l i ke growth fa ctor (IGF-1) i n s uch ca s es a s a cromega l y a nd ca rci noi d
s yndrome, a nd i s a l s o us ed to control bl eedi ng from es opha gea l va ri ces . It i s a bout 40% to 50% more potent tha n s oma tos ta ti n i n terms of
s uppres s i ng GH rel ea s e, but rel a ti vel y wea k i n terms of s uppres s i ng i ns ul i n s ecreti on. It woul d not be a rea s ona bl e choi ce here, gi ven the
a l terna ti ves . Oxytoci n (e), a pos teri or pi tui ta ry hormone us ed ma i nl y a s a uteri ne s ti mul a nt (tha ts where we got the terms oxytoci c drug or oxytoci c
effect), ha s no cl i ni ca l l y us eful effects on gl ycemi c control or the res pons es of ta rget ti s s ues to i ns ul i n or gl ucos e defi ci ency or exces s .
367. The answer is c. (Brunton, pp 1244-1256; Katzung, pp 761-762, 764-765.) Bl ood-borne gl ucos e rea cts nonenzyma ti ca l l y wi th hemogl obi n to form
gl yca ted hemogl obi n products (eg, HbA1c). The ra te of HbA1c forma ti on i s rel a ted to a mbi ent gl ucos e l evel s , a nd the a mount of HbA1c mea s ured i n
a ny gi ven bl ood s a mpl e refl ects the a vera ge bl ood gl ucos e l evel s over the l a s t 2 to 3 months . Thus , a l though the pa ti ents pl a s ma gl ucos e l evel s
ma y be a ccepta bl e a fter a coupl e of da ys fa s t, HbA1c mea s urements gi ve the bi g pi cture a bout how good gl ycemi c control wa s on a more l ong-term
(a nd more i mporta nt) ti mel i ne. Note tha t a l though mea s uri ng HbA1c gi ves i mporta nt i nforma ti on a bout the l ong-term, i t does not provi de a ny
i nforma ti on a bout da y-to-da y fl uctua ti ons i n gl ucos e l evel s or wha ts ha ppeni ng ri ght now, a nd s uch i nforma ti on i s i mporta nt to opti ma l control
of di a betes a nd i ts s ymptoms . Nonethel es s , regul a r, peri odi c checks of HbA1c s houl d be pa rt of the moni tori ng for every pa ti ent wi th di a betes
(type 1 or 2), not s o much a s a wa y to a s s es s for noncompl i a nce a s to ma ke s ure tha t the current trea tment pl a n wi th whi ch the pa ti ent i s
compl yi ng i s worki ng. It i s a common a nd rel a ti vel y i nexpens i ve a s s a y.
Ha vi ng the cl i ni ca l l a b mea s ure gl ucos e i n a venous bl ood s a mpl e wont gi ve a ny a ddi ti ona l or mea ni ngful i nforma ti on: ha ndhel d gl ucometers ,
us ed properl y, a re rema rka bl y a ccura te. Gl ucos e tol era nce tes ts , even thos e done wi th ora l gl ucos e, wi l l provi de l i ttl e hi s tori c i nforma ti on, a nd
they a re expens i ve. Few cl i ni ca l l a bs a re s et up to mea s ure pl a s ma concentra ti ons of mos t ora l a nti di a beti c drugs , a nd the cos t for thes e
nons ta nda rd tes ts woul d be qui te expens i ve. Mea s uri ng uri ne ketone l evel s a re of no benefi t for our purpos es . Al l tha t they mi ght prove i s tha t
our pa ti ent ha s fa s ted for s evera l da ys . Uri ne gl ucos e moni tori ng i s not very enl i ghteni ng ei ther. Reca l l tha t gl ucos e a ppea rs i n the uri ne onl y
when pl a s ma concentra ti ons exceed a rena l thres hol d for rea bs orpti on (a round 180 mg/dL or s o). A gl ucos e-free uri ne s a mpl e, then, woul d onl y
i ndi ca te tha t pl a s ma gl ucos e l evel s a re bel ow the thres hol d: they s ti l l coul d be una ccepta bl y hi gh, or norma l , or l ow, a nd you woul d never know
jus t by uri ne tes ti ng.
368. The answer is c. (Brunton, pp 307, 1829-1830, 1841; Katzung, pp 738, 1077.) Fi na s teri de competi ti vel y i nhi bi ts s teroi d 5-reducta s e, the enzyme
neces s a ry for s ynthes i s of the a cti ve form of tes tos terone (di hydrotes tos terone) i n the pros ta te. Tes tos terone s ynthes i s (d) a nd ci rcul a ti ng
tes tos terone l evel s (e) do not fa l l i n res pons e to the drug. PSA ti ters wi l l , however, fa l l .
Reca l l tha t 1 -a drenergi c bl ockers (eg, pra zos i n a s the overa l l prototype a nd, pa rti cul a rl y, ta ms ul os i n i n terms of us e for BPH) provi de
s ymptoma ti c rel i ef i n s ome men wi th enl a rged pros ta tes by rel a xi ng s mooth mus cl e i n the urethra , bl a dder neck, a nd pros ta te ca ps ul e; moreover,
they do s o wi thout a ny effects on tes tos terone or i ts cel l ul a r a cti ons . Fi na s teri de, however, ha s no -a drenergi c receptor bl ocki ng a cti vi ty (a ).
369. The answer is e. (Brunton, pp 1264-1265; Katzung, pp 760-761.) DPP-4 degra des i ncreti ns , whi ch pl a y a cruci a l rol e i n regul a ti ng i ns ul i n a nd
gl uca gons rel ea s e, pa rti cul a rl y i n res pons e to a mea l . The DPP-4 inhibitors (i e, s i ta gl i pti n a nd other gl i pti ns ) thereby i ndi rectl y ra i s e bl ood l evel s
of endogenous gl uca gon-l i ke pepti de-1 (GLP-1). The two mos t i mporta nt cons equences of the now-ra i s ed GLP-1 l evel s a re a n i ncrea s e of bl ood
gl ucos e-medi a ted i ns ul i n rel ea s e, a nd a s i mul ta neous reducti on of gl uca gon rel ea s e. The gl i pti ns a re ora l a gents us ed a s a djuncts to the
trea tment of type 2 di a betes i n certa i n pa ti ents who fa i l to get a dequa te gl ycemi c control i n res pons e to exerci s e, proper di et, a nd more
tra di ti ona l ora l a nti di a beti c a gents (i e, metformi n, a s ul fonyl urea , or even pi ogl i ta zone, a l one or i n combi na ti on).
DPP-4 i nhi bi tors ha ve no a cti ons on, or cl i ni ca l uti l i ty rel a ted to, s teroi dogenes i s (a ), cl ea va ge of i ns ul i n from prei ns ul i n (b), thyroi d hormone
s tora ge or rel ea s e (c), or es trogen or proges terone meta bol i c pa thwa ys (d).

370. The answer is d. (Brunton, pp 310-316, 320, 1150; Katzung, pp 687t, 691-694.) In thyrotoxi cos i s /thyroi d s torm, es s enti a l l y the onl y effect of
a dmi ni s teri ng a -a drenergi c bl ockera nd i t i s a n i mporta nt effect, to be s urei s to provi de prompt rel i ef of both rel a ti vel y i nnocuous
ma ni fes ta ti ons of thyroi d hormone exces s , s uch a s tremor, a nd thos e tha t a re much more da ngerous , i ncl udi ng s i gni fi ca nt a nd potenti a l l y l i fethrea teni ng i ncrea s es i n ca rdi a c ra te, contra cti l i ty, a nd a utoma ti ci ty. Ci rcul a ti ng thyroi d hormone l evel s modul a te the res pons i venes s of a drenergi c receptors to thei r a goni s ts (eg, epi nephri ne, norepi nephri ne). When thyroi d hormone l evel s a re exces s i ve, s o i s a drenergi c receptor
res pons i venes s . Therefore, we ca n reduce the a drenergi c cons equences of the hormone exces s us i ng a -bl ocker. There a re no effects on thyroi d
hormone l evel s or thyroi d gl a nd functi on or control .
None of the -a drenergi c bl ockers bl ock the a goni s t effects of thyroi d hormones on thei r receptors (a ), nor do they i nhi bi t thyroi d hormone
rel ea s e (b) or s ynthes i s (c). They do not a l ter TSH l evel s (e) di rectl y or i ndi rectl y.
371. The answer is e. (Brunton, pp 1294-1296, 1299-1301; Katzung, p 776.) Whether us ed for os teoporos i s (preventi on or ma na gement, men or women,
i di opa thi c or drug-i nduced) or Pa get di s ea s e of the bone, bi s phos phona tes exert thei r effects on os teocl a s ts a nd os teobl a s ts . The drug i s
i ncorpora ted i nto bone. When drug-conta i ni ng bone i s res orbed by the os teocl a s ts , os teocl a s t functi on (a nd, s o, s ubs equent bone res orpti on) i s
i nhi bi ted. The bi s phos phona tes a l s o recrui t os teobl a s ts , whi ch then produce a s ubs ta nce tha t further i nhi bi ts os teocl a s t a cti vi ty.
Bi s phos phona tes i n genera l , or a l endrona te i n pa rti cul a r, do not a cti va te vi ta mi n D (a ); a re not ca l ci um-ri ch drugs (b) nor phos pha te-ri ch drugs
(d); a nd they do not form or s ti mul a te forma ti on of hydroxya pa ti te crys ta l s i n bone (c).
372. The answer is d. (Brunton, pp 1278-1280, 1290, 1294-1297; Katzung, pp 775, 780, 783.) You s houl d be a bl e to deduce hyperpa ra thyroi di s m a s the
a ns wer by reca l l i ng tha t the bi s phos phona tes ul ti ma tel y a ffect bone Ca 2+ meta bol i s m, a nd the pa ra thyroi d gl a nd i s the ma i n regul a tor of pl a s ma
Ca 2+ l evel s . When a bi s phos phona te i s gi ven to a pa ti ent wi th Pa get di s ea s e of the bone, a fter a bout a week the dra ma ti c i nhi bi ti on of bone
res orpti on ma rkedl y l owers pl a s ma Ca 2+ l evel s (beca us e a n i mporta nt porti on of pl a s ma Ca 2+ a ri s es from bone tha t i s bei ng res orbed). When
pl a s ma Ca 2+ fa l l s cons i dera bl y, pa ra thyroi d hyperfuncti on ca n devel op. The ea s i es t wa y to prevent thi s i s to a dmi ni s ter di eta ry ca l ci um
s uppl ements a l ong wi th the bi s phos phona te.
373. The answer is d. (Brunton, pp 1214, 1233-1236; Katzung, p 710.) Metyra pone, beca us e i t decrea s es pl a s ma l evel s of corti s ol by i nhi bi ti ng the 11hydroxyl a ti on of s teroi ds i n the a drena l , ca n be us ed to a s s es s functi on of the pi tui ta ry-a drena l corti ca l a xi s . When metyra pone i s gi ven to norma l
pers ons , the a denohypophys i s s ecretes more ACTH. Thi s ca us es a norma l a drena l cortex to s ynthes i ze i ncrea s ed a mounts of 17-hydroxyl a ted
s teroi ds , whi ch ca n be mea s ured i n the uri ne. However, pa ti ents who ha ve di s ea s e of the hypotha l a mi c-pi tui ta ry a xi s do not produce ACTH i n
res pons e to metyra pone. As a res ul t, we fi nd no i ncrea s ed l evel s of the s teroi ds i n the uri ne. Before a dmi ni s teri ng metyra pone we need to tes t
res pons i venes s of the a drena l cortex to res pond to a dmi ni s tra ti on of ACTH.
374. The answer is e. (Brunton, pp 1007, 1224-1233, 1668-1669; Katzung, pp 697, 700f, 703, 712, 775.) Thes e fi ndi ngs a re cha ra cteri s ti c of wha t one woul d
expect wi th l ong-term (a nd/or hi gh dos e) s ys temi c gl ucocorti coi d thera py (i e, predni s one a nd ma ny others , but not becl ometha -s one, whi ch i s
gi ven by ora l i nha l a ti on a nd i s not a bs orbed a ppreci a bl y). Ps ychos es , pepti c ul cera ti on wi th hemorrha ge (coffee-grounds s tool , i ndi ca ti ve of
ga s tri c bl eedi ng) or wi thout (pos s i bl y ca us i ng gua i a c-pos i ti ve s tool s ), i ncrea s ed s us cepti bi l i ty to i nfecti on, edema , os teoporos i s , myopa thy, a nd
hypoka l emi c a l ka l os i s ca n occur. Other a dvers e rea cti ons i ncl ude ca ta ra cts , hypergl ycemi a , s l owed l i nea l growth i n chi l dren, a nd i a trogeni c
Cus hi ng s yndrome.
Hydrochl orothi a zi de (a nd other thi a zi de a nd thi a zi de-l i ke di ureti cs , s uch a s chl ortha l i done or metol a zone) ca n i ncrea s e bl ood gl ucos e l evel s .
However, they typi ca l l y l ower bl ood pres s ure (a s evi denced by thei r wi des prea d us e a s a nti hypertens i ves ) a nd tend to ra i s e, not l ower, pl a s ma
ca l ci um l evel s (whi ch woul d be i ncons i s tent wi th the decrea s ed bone dens i ty des cri bed i n thi s ma n). None of the other drugs l i s ted woul d ca us e
a col l ecti on of fi ndi ngs cons i s tent wi th wha t I des cri bed here.
375. The answer is e. (Brunton, pp 834-837, 1153t; Katzung, pp 242-243, 610t, 693-694.) Ami oda rone, a n i odi ne-ri ch drug, ha s s evera l a cti ons tha t ca n l ea d
to cl i ni ca l hypothyroi di s mor, more often a nd ma i nl y i n pers ons wi th i odi ne-defi ci ent di ets , hyperthyroi di s m. How ca n thes e s eemi ngl y oppos i te
outcomes occur? Before we get to tha t, l ets s umma ri ze the other a dvers e res pons es a s s oci a ted wi th a mi oda rone thera py: the potenti a l for
pul mona ry fi bros i s (ma y become s eri ous ); a bnorma l pi gmenta ti on of the s ki n (i s photos ens i ti ve, too); cornea l depos i ts (often des cri bed a s ha l o
vi s i on); neuropa thi es ; a nd hepa totoxi ci ty. Now, the thyroi d i s s ue: a mi oda rone i nhi bi ts a dei odi na s e tha t removes i odi ne on both the 5 a nd 5
pos i ti ons a nd tha t converts thyroxi ne to tri i odothyroni ne (T3 ), ma i nl y i n the l i ver. Thi s proces s i s the ma i n contri butor to the producti on of
endogenous (ci rcul a ti ng) T3 tha t i s us ed by mos t ta rget ti s s ues i n the body. Inhi bi t thi s enzyme a nd the peri phera l ti s s ues ha ve l es s T3 to uti l i ze,
a nd s i gns a nd s ymptoms of hypothyroi di s m ca n ens ue.
The exces s i odi ne deri ved from meta bol i s m of a mi oda rone ma y a l s o contri bute to the hypothyroi di s m. The mecha ni s m i s a na l ogous to the wa y
i n whi ch a dmi ni s teri ng l a rge dos es of i odi de a re cl i ni ca l l y us eful for s uppres s i ng thyroi d functi on i n hyperthyroi d i ndi vi dua l s : i odi de l i mi ts i ts
own tra ns port i nto fol l i cul a r cel l s , a nd, a cutel y a t l ea s t, hi gh ci rcul a ti ng l evel s of i odi de i nhi bi t thyroi d hormone s ynthes i s .
And how mi ght a mi oda rone ca us e hyperthyroi di s m? The i odi ne cl ea ved from the drug duri ng i ts meta bol i s m ca n be i ncorpora ted, a l ong wi th
di eta ry i odi ne, i nto thyroi d hormone s yntheti c pa thwa ys .
Al though a mi oda rone ca n ca us e cl i ni ca l l y s i gni fi ca nt effects on thyroi d s ta tus , i t does not a ffect the meta bol i s m or res pons es to other
hormones , i ncl udi ng corti s ol (a , b), i ns ul i n (d, f), a nd ADH (c).
376. The answer is b. (Brunton, pp 952, 1184-1185, 1837; Katzung, pp 710-711, 731-732.) Mi fepri s tone (perha ps better known a s RU-486) i s a s yntheti c drug
us ed a s a n a borti fa ci ent. (In s ome other countri es , but not i n the Uni ted Sta tes , i t i s us ed a s a pos tcoi ta l contra cepti ve.) Al though the drug bl ocks
gl ucocorti coi d receptors , tha t effect does not a ccount for i ts us e or effects i n the context des cri bed here. Here the a cti ons a ri s e from bl ocki ng
uteri ne proges terone receptors . They i ncl ude deta chment of the conceptus from the uteri ne wa l l , s ofteni ng a nd di l a ti on of the cervi x, a nd
i ncrea s ed myometri a l contra cti on tha t expel s the conceptus . (The l a tter a ri s es from both a drug-i nduced i ncrea s e of l oca l pros ta gl a ndi n s ynthes i s
a nd grea ter myometri a l res pons i venes s to them.) If mi fepri s tone fa i l s to i nduce expul s i on of the fetus , mi s opros tol i s us ua l l y gi ven to i ncrea s e
uteri ne contra cti ons further. (Es trogens us ed a l one or i n combi na ti on wi th proges ti ns ha ve a l s o proven effecti ve i n pos tcoi ta l contra cepti on.)
Ergonovi ne a nd methyl ergonovi ne (a ) a re ergot compounds tha t ca us e uteri ne contra cti on, a nd a re us ed pos tpa rtum to control bl eedi ng, by
i ncrea s i ng uteri ne tone, ma i nl y i n the fa ce of pos tpa rtum uteri ne a tony. They a re a borti fa ci ent drugs , but not us ed for pos tcoi ta l contra cepti on.
Ra l xoi fene (c) a nd ta moxi fen (e) a re es trogen receptor a goni s ts or a nta goni s ts (whi ch effect occurs depends on the ti s s ue) tha t a re us ed to trea t
certa i n es trogen-dependent brea s t ca ncers .
Ri todri ne (d) i s a 2 -a drenergi c a goni s t tha t ha s been us ed to s l ow uteri ne contra cti ons a nd reduce overa l l uteri ne tone i n prema ture l a bor.
377. The answer is e. (Brunton, pp 1154-1157; Katzung, pp 689, 692.) Hypothyroi di s m i s the mos t common a dvers e outcome of us i ng 131 I to trea t

hyperthyroi di s m. No ma tter how a ccura tel y the dos e i s ca l cul a ted, a ccordi ng to s ome s tudi es a bout 8 of 10 trea ted pa ti ents devel op s ymptoma ti c
hypothyroi di s m (tha t needs to be trea ted) by 10 or more yea rs a fter trea tment. It res ul ts , of cours e, from exces s i ve thyroi d cel l des tructi on.
Subs ta nti ve s ymptom rel i ef from 131 I ta kes from s evera l weeks to a coupl e of months to devel op (a l though bl ood chemi s tri es cha nge s omewha t
fa s ter). Unti l a euthyroi d s ta te devel ops , drugs s uch a s -a drenergi c bl ockers or ora l a nti thyroi d drugs ma y be needed for s ymptom control . Ora l
a nti thyroi d drugs ca n be gi ven before 131 I trea tment, but they s houl d be s topped for a coupl e of da ys before ra di othera py s o a s not to prevent
ra di oi odi ne upta ke i nto the gl a nd. Thyroi d a nd other ca ncers , meta s ta ti c or not, a re ra re a fter 131 I thera py.
378. The answer is c. (Brunton, pp 1258-1260, 1841, 1845; Katzung, pp 757, 766.) Pol ycys ti c ova ri a n s yndrome (PCOS) i s the mos t common endocri ne
di s order i n young pos tpuberta l women, a nd i s cha ra cteri zed by not onl y the s i gns a nd s ymptoms noted i n the ques ti on, but a l s o others tha t a re
a ccompa ni ed or ca us ed by rel a ti ve a ndrogen exces s (thus el i mi na ti ng tes tos terone, e, a s a n a ns wer). Jus t a s metformi n i s often hel pful i n type 2
di a betes , through i ts i ns ul i n-s ens i ti zi ng effects on pa renchyma l cel l s (a di pocytes , s kel eta l mus cl e), s o i t i s i n PCOS; a n a dded benefi t, i ndi rectl y,
i s a reducti on of ci rcul a ti ng a ndrogen l evel s . Hi gher dos a ges of es trogen (a ) mi ght hel p the s i gns a nd s ymptoms of PCOS, but obvi ous l y tha t
a pproa ch woul d not pres erve or i mprove ferti l i ty a s l ong a s the drug i s bei ng ta ken. Ketocona zol e (b), a powerful i nhi bi tor of s teroi dogenes i s , i s
too nons el ecti ve i n terms of i ts powerful i nhi bi tory effects on s teroi do-genes i s . Predni s one (d) or a nother gl ucocorti coi d woul d be i rra ti ona l , i f for
no other rea s on tha n the fa ct tha t thes e drugs wi l l further ra i s e bl ood gl ucos e l evel s a pa rti cul a rl y unwa nted effect cons i deri ng the pa renchyma l
cel l i ns ul i n res i s ta nce tha t i s a component of PCOS. Tes tos terone (e) i s obvi ous l y i na ppropri a te gi ven the rel a ti ve a ndrogen exces s a l rea dy pres ent
i n PCOS.
379. The answer is a. (Brunton, pp 1172, 1177-1180, 1299-1300, 1756-1759; Katzung, pp 731, 740.) Ta moxi fen i s often referred to a s a s el ecti ve es trogen
receptor modi fi er (SERM). It bl ocks es trogen receptors i n s ome ti s s ues a nd s ti mul a tes them i n s ome others . The drug ca n be us ed to prevent or
trea t es trogen-dependent brea s t ca ncers , a nd i t works a s a n es trogen receptor a nta goni s t there. A receptor-a goni s t a cti on a l s o a ccounts for one of
the drugs more di s tres s i ng a nd common s i de effects , hot fl a s hes . In contra s t, the drug a cti va tes es trogen receptors i n the uterus , i ncrea s i ng the
ri s k of endometri a l ca ncers . Other es trogen-a cti va ti ng (es trogen-l i ke) cons equences i ncl ude a reduced ri s k of os teoporos i s , des i ra bl e cha nges i n
pl a s ma chol es terol profi l es (reduced LDL a nd tota l chol es terol s ; i ncrea s ed HDL), a nd a n i ncrea s ed ri s k of thromboembol i c events . The rel a ted
drug, ra l oxi fene, i s l a rgel y ta moxi fen-l i ke wi th one ma i n excepti on: i t does not a cti va te uteri ne es trogen receptors , a nd s o does not i ncrea s e the
ri s k of endometri a l ca ncers .
380. The answer is c. (Brunton, pp 1258-1260; Katzung, pp 757, 766.) Metformi n, cl a s s i fi ed a s a bi gua ni de, s ens i ti zes peri phera l cel l s (s kel eta l mus cl e,
a di pocytes ) to i ns ul i n, thereby fa ci l i ta ti ng gl ucos e upta ke a nd meta bol i c us e, a nd s uppres s es rel ea s e of gl ucos e from the l i ver a nd i nto the bl ood.
It i s i neffecti ve i n the a bs ence of i ns ul i n a nd s o i s a pproved onl y for type 2 di a betes (us ed a l one or i n conjuncti on wi th s uch other drugs a s a
s ul fonyl urea or i ns ul i n). Li ke other ora l a gents (a nd s ome pa rentera l drugs s uch a s exena ti de), metformi n ha s no benefi ci a l effect i n pa ti ents wi th
type 1 di a betes (d).
Wei ght l os s duri ng metformi n thera py i s much more common tha n wei ght ga i n (e). Thi s i s proba bl y due to a n a ppeti te-s uppres s i ng effect
(l ea di ng to reduced ca l ori c i nta ke), ra ther tha n beca us e of a s peci fi c drug-rel a ted effect on s ome meta bol i c rea cti on(s ) or a norexi a s econda ry to GI
s i de effects .
Why does metformi n s el domi f not ra rel yca us e hypogl ycemi a ? Ra ther tha n a cti vel y dri vi ng down bl ood gl ucos e l evel s (a s , s a y, i ns ul i n does ),
the drug a cts a s i f i t puts a l i d on phys i ol ogi c ri s es of bl ood gl ucos e concentra ti ons . (Thus , i t ha s been des cri bed a s bei ng a n a nti hypergl ycemi c
drug, ra ther tha n a hypogl ycemi c a gent.)
Metformi n i s not meta bol i zed by the l i ver, but l i ver dys functi on i s one contra i ndi ca ti on. Tha ts ma i nl y beca us e of the ri s ks of the drugs mos t
i mporta nt a dvers e effect, l a cti c a ci dos i s , whi ch i s ra re but often fa ta l (not common a nd s el dom s eri ous , a ns wer b) when i t does occur. Impa i red
l i ver functi on i mpa i rs l a cta te el i mi na ti on a nd fa vors i ts a ccumul a ti on to toxi c l evel s (a nd s o a ns wer a i s not correct).
However the ma i n pri ma ry ca us e of the l a cti c a ci dos i s i s rena l i ns uffi ci ency (pl a s ma crea ti ni ne >1.5 mg/dL i n men, 1.4 mg/dL i n women),
whether ca us ed by rena l di s ea s e or by rena l hypoperfus i on (i s chemi a , a s mi ght occur wi th hea rt fa i l ure a nd/or hypotens i on).
381. The answer is a. (Brunton, pp 1239f, 1251f, 1252-1253; Katzung, pp 743-753.) Ins ul i n modi fi ca ti ons , whether by rDNA technol ogy to s ubs ti tute a mi no
a ci ds , or by phys i ca l mea ns (eg, i n the ca s e of NPH i ns ul i n), a l ter ons ets a nd dura ti ons of a cti on. (Reca l l tha t regul a r i ns ul i n, gi ven by SC i njecti on,
ha s a n ons et of a bout 30 mi nutes , pea ks i n a bout 3 hours , a nd ha s a dura ti on of a bout 7-8 hours . Li s pro a nd a s pa rt i ns ul i ns work fa s ter, pea k
ea rl i er, a nd ha ve the s hortes t dura ti ons [ra pi d/s hort]; NPH i ns ul i ns [i ntermedi a te-a cti ng] ha ve ons ets , ti mes to pea k, a nd dura ti ons l onger tha n
regul a r i ns ul i ns ; a nd i ns ul i n gl a rgi ne ha s the s l owes t ons ets [4-6 hours ], wi th dura ti ons tha t a re on pa r wi th NPH.)
In genera l , the modi fi ed huma n i ns ul i ns ra rel y ca us e a l l ergi c res pons es (not the ca s e wi th the few other i ns ul i ns ). Beyond tha t, however, the
modi fi ca ti ons yi el d cl i ni ca l l y us eful pha rma coki neti cnot bi ochemi ca l cha nges .
382. The answer is a. (Brunton, p 1265; Katzung, pp 759-760.) Aca rbos e a nd the newer rel a ted drug, mi gl i tol , a ct i n i ntes ti na l brus h border cel l s to
i nhi bi t monos a ccha ri de forma ti on from compl ex ca rbohydra tes a nd ol i gos a ccha ri des , a nd i n s o doi ng i nhi bi t/s l ow the a bs orpti on of monos a ccha ri des (eg, gl ucos e) from the gut. The enzyma ti c ta rgets a re -gl ucos i da s es i n the brus h border of i ntes ti na l cel l s . The ma i n cons equence i n terms
of gl ycemi c control i s a bl unti ng of us ua l pos tpra ndi a l ri s es of bl ood gl ucos e. The mos t common s i de effects of a ca rbos e a ffect the GI tra ct, a s
des cri bed i n the ques ti on. Us ed a l one, hypogl ycemi a due to a ca rbos e i s ra re; however, the drug i s often us ed a s a n a djunct to a s ul fonyl urea , a nd
thei r propens i ty for ca us i ng hypogl ycemi a i s not a t a l l reduced by a ca rbos e. It i s i mporta nt to note tha t the us ua l pa ti ent-centered a pproa ch to
ma na gi ng a n epi s ode of hypogl ycemi a , a s mi ght occur when certa i n ora l a nti di a beti c drugs a re us ed (eg, s ul fonyl urea s , gl i ta zones ), i s to i nges t
ta bl e s uga r (s ucros e) or s ome bevera ge or food tha t conta i ns i t. If the hypogl ycemi c pa ti ent i s ta ki ng a ca rbos e, thi s a pproa ch wi l l not correct bl ood
gl ucos e l evel s a dequa tel y or promptl y.
383. The answer is a. (Brunton, pp 1250-1252; Katzung, pp 743-745.) Ins ul i n gl a rgi ne i s a geneti ca l l y engi neered i ns ul i n tha t i s poorl y (but a dequa tel y)
s ol ubl e a t phys i ol ogi c pH va l ues . The drug di s s ol ves a nd enters the bl oods trea m s l owl y a nd i n s uch a wa y tha t there i s more of a s ta bl e pl a tea u
i n terms of bl ood l evel s a nd hypogl ycemi c effects . It does not ca us e a wel l -defi ned pea k i n bl ood l evel s a nd effects (a ). The pl a tea u i s ra ther
fl a t over the typi ca l 24-hour peri od fol l owi ng a s ubcuta neous i njecti on. Thus , the drug i s better a bl e tha n mos t other i ns ul i ns to ma i nta i n roundthe-cl ock gl ycemi c control , but l es s a bl e to s uppres s the pos tpra ndi a l el eva ti on of gl ucos e tha t i s neces s a ry for s ome pa ti ents . Ins ul i n gl a rgi nes
ons et a nd dura ti on of a cti on a re compa ra bl e to s uch prepa ra ti ons a s NPH i ns ul i n. It i s wha t ha ppens i n between, tempora l l y, tha t di s ti ngui s hes
thi s formul a ti on from the res t.
Ins ul i n gl a rgi nei ndeed a l l the i ns ul i n formul a ti ons ha s no di s ul fi ra m-l i ke effects (b). As wi th a l l the i ns ul i ns , i ns ul i n gl a rgi ne pos es a ri s k
of hypogl ycemi a (a nd s o a ns wer d i s i ncorrect). Fi na l l y, the drug ha s no pa renchyma l cel l i ns ul i n-s ens i ti zi ng effects (e), a nd l i ke a l l i ns ul i ns i t i s
gi ven s ol el y a s hormone repl a cement thera py.

384. The answer is c. (Brunton, pp 1150-1151; Katzung, pp 692-693.) Ta chyca rdi a , pa l pi ta ti ons , ta chya rrhythmi a s , a nd the pos s i bi l i ty of a cute myoca rdi a l
i s chemi a a re a mong the ha l l ma rks of thyrotoxi cos i s or thyroi d hormone overdos es . Thyroi d hormone l evel s regul a te the res pons i venes s of a drenergi c receptors to epi nephri ne a nd norepi nephri ne (or exogenous -a goni s ts ), a nd thi s proba bl y contri butes to the cl i ni ca l pi cture. Al though
exces s es of thyroi d hormone a re the ca us e of the probl ems , ma na gement i s s ymptoma ti c a nd a i med a t s uppres s i ng -medi a ted res pons es . Hence
the us e of propra nol ol or s ome other s ui ta bl e -a drenergi c bl ocker for i mmedi a te a nd qui te pos s i bl y l i fes a vi ng s ymptom control . Sul fonyl urea s (a ;
fi rs t or s econd genera ti on) woul d not ca us e the s i gns or s ymptoms noted a bove, a nd -bl ocker thera py for overdos es of one of thos e drugs woul d
do more ha rm tha n good. The s a me a ppl i es to i ns ul i n (b); -bl ockers mi ght control i ncrea s es of ca rdi a c ra te, but they a re more l i kel y to further
l ower bl ood gl ucos e l evel s a nd s l ow or otherwi s e a ttenua te ri s es of bl ood gl ucos e l evel s when a ppropri a te thera py to render the pa ti ent
eugl ycemi c i s s ta rted. Overdos es of predni s one (d) or propyl thi oura ci l (e) a re not l i kel y to pres ent a s des cri bed, a nd they a re not properl y
ma na ged wi th a -bl ocker.
385. The answer is e. (Brunton, pp 1261-1264, 1930t; Katzung, pp 761-762.) Exena ti de wa s the fi rs t i n a new cl a s s of a nti di a beti c a gents , the incretin
mimetics. It i s a dmi ni s tered by s ubcuta neous i njecti on a nd us ed a djuncti vel y to i mprove gl ycemi c control i n type 2 di a betes pa ti ents a l rea dy ta ki ng
metformi n, a s ul fonyl urea , or both. It i s not i ndi ca ted for type 1 di a betes .
Exena ti de i s a s yntheti c a na l og of gl uca gon-l i ke pepti de-1 (GLP-1), a pepti de hormone i n the incretin fa mi l y. Under phys i ol ogi c condi ti ons , GLP-1
a nd other i ncreti ns a re rel ea s ed from cel l s of the GI tra ct a fter a mea l . Exena ti de bi nds to receptors for GLP-1. In doi ng s o i t s l ows ga s tri c emptyi ng,
s ti mul a tes gl ucos e-dependent i ns ul i n rel ea s e, i nhi bi ts pos tpra ndi a l rel ea s e of gl uca gon, a nd s uppres s es a ppeti te.
Dos e-rel a ted hypoglycemia i s common when exena ti de i s combi ned wi th a s ul fonyl urea (but not when us ed wi th onl y metformi n, whi ch s el dom
ca us es hypogl ycemi a ). Na us ea , vomi ti ng, a nd di a rrhea a re the mos t common s i de effects . The drug i s a l s o a ppa rentl y l i nked to the devel opment
of pa ncrea ti ti s , a nd s o moni tori ng for i t i s es s enti a l .
Some pa ti ents ta ki ng exena ti de devel op a nti bodi es di rected a ga i ns t the drug. Anti gen-a nti body rea cti ons to exena ti de do not ca us e a dvers e
effects (eg, a l l ergi c or a na phyl a ctoi d rea cti ons ), but ca n reduce the i ntens i ty of exena ti des effects . At thi s ti me, the drug i s cl a s s i fi ed i n FDA
Pregna ncy Ri s k Ca tegory C. Gi ven the yea rs of experi ence wi th us i ng i ns ul i n for di a betes duri ng pregna ncy, a nd the benefi ts a nd s a fety i t provi des ,
theres l i ttl e jus ti fi ca ti on i n us i ng exena ti de.
Increti n a nd i ncreti n mi meti cs ha ve no effects on tes tos terone (whether a nta goni s m or i ntens i fi ca ti on; a ns wer a ). Metformi n a nd s ul fonyl urea s
a re, of cours e, a nti di a beti c drugs a nd a re not i ndi ca ted for thyroi d di s orders (b). Exena ti de ha s no effects on ca l ci um meta bol i s m or os teoporos i s
ma na gement (c); a nd no di rect effects on corti cos teroi d meta bol i s m (d), whether i n hypos ecretory (Addi s oni a n) or hypers ecretory (cus hi ngoi d)
s ta tes .
386. The answer is a. (Brunton, pp 1141-1143; Katzung, pp 687t, 690-691.) Levothyroxi ne i s us ua l l y cons i dered the fi rs t choi ce for l ong-term ma i ntena nce
thera py of hypothyroi di s m, s uch a s tha t whi ch occurs a fter thyroi dectomy or ra di a ti on thera py of the thyroi d. Once a bs orbed, we get the s l ow-ons et
a nd ra ther s tea dy, l ong-l a s ti ng effects of the T4 . In a ddi ti on, s ome of the a dmi ni s tered T4 i s dei odi na ted i n the ti s s ues to T3 , a utoma ti ca l l y
provi di ng us ua l l y a dequa te l evel s a nd effects of thi s more ra pi dl y a nd s horter-a cti ng hormone wi thout the need to a dmi ni s ter T3 (l i othyroni ne)
s epa ra tel y.
If the pa ti ent devel ops profound hypothyroi di s m (eg, myxedema ), s ome cl i ni ci a ns ma y s ti l l prefer T3 for i ts prompt effects . However, i n thi s
i ns ta nce too, T4 i s genera l l y rega rded a s the preferred wa y to repl a ce both hormones a nd rees ta bl i s h a euthyroi d s ta te (a dmi ni s tered wi th
corti cos teroi ds for myxedema coma ).
Li othyroni ne (b) i s s yntheti c T3 ; l i otri x (c) i s a mi xture of s yntheti c T3 a nd T4 ; proti rel i n (d) i s a s yntheti c tri pepti de, chemi ca l l y i denti ca l to
thyrotropi n-rel ea s i ng hormone (TRH), tha t i s us ed to di a gnos e s ome thyroi d di s orders ; des i cca ted thyroi d products (e) a re outmoded for ma na gi ng
hypothyroi di s m, gi ven the a va i l a bi l i ty of s yntheti c hormone prepa ra ti ons .
387. The answer is b. (Brunton, pp 1291, 1301, 1864; Katzung, pp 259, 779-780.) Were dea l i ng wi th hypoca l cemi a i n thi s pa ti ent wi th teta ny pos tthyroi dectomy, beca us e the pa ra thyroi d gl a nd wa s da ma ged or removed duri ng the s urgery. Admi ni s tra ti on of i ntra venous ca l ci um gl ucona te
woul d i mmedi a tel y correct the teta ny. Pa ra thyroi d hormone (d) coul d be cons i dered a ppropri a te for l ong-term ma na gement of hypoca l cemi a , but i t
ha s a s l ower ons et of a cti on tha t woul d not be of much hel p i n a teta ni c s ta te. We woul d then proba bl y us e vi ta mi n D (e) a nd di eta ry
modi fi ca ti ons for l ong-term control of pl a s ma ca l ci um l evel s .
Ca l ci toni n (a ) i s a hypoca l cemi c a nta goni s t of pa ra thyroi d hormone. (Note tha t ca l ci toni n or ca l ci tri ol wi l l ra i s e pl a s ma ca l ci um l evel s fa s ter
tha n vi ta mi n D, but i n thi s emergent s i tua ti on they wi l l not work fa s t enough, whi ch i s why we need di rect a dmi ni s tra ti on of i oni c ca l ci um.)
Pl i ca myci n (c; mi thra myci n) i s us ed to trea t Pa get di s ea s e a nd hyperca l cemi a . The dos e empl oyed i s a bout one-tenth the a mount us ed for
pl i ca myci ns cytotoxi c a cti on when i t i s us ed a s a chemothera peuti c drug.
388. The answer is d. (Brunton, pp 1146-1157; Katzung, pp 688, 691-692, 695.) Propyl thi oura ci l , a thi oa mi de us e to ma na ge ma ny pa ti ents wi th
hyperthyroi di s m, ha s three ma i n a cti ons . It i nhi bi ts a peroxi da s e, a nd i n doi ng s o i nhi bi ts oxi da ti on of i norga ni c i odi de to i odi ne, a nd the
i odi na ti on of tyros i ne. It a l s o bl ocks coupl i ng of i odotyros i nes a nd i nhi bi ts dei odi na ti on of T4 to T3 i n the peri phery. Propyl thi oura ci l , a nd the
thi oa mi des i n genera l , do not: bl ock thyroi d upta ke of i odi de (a ); a ffect meta bol i c i na cti va ti on of T3 a nd T4 (b); i nhi bi t thyrogl obul i ns proteol ys i s
(c); or di rectl y rel ea s e thyroi d hormones i nto the ci rcul a ti on (e).
Note: Mos t texts a nd other publ i ca ti ons refer to thi s group of drugs a s I ha ve: thi oa mi des . However, occa s i ona l l y you wi l l fi nd a n a l terna ti ve
term us ed: thi ona mi de, thi oa mi ne, a nd even thi ona mi ne.
389. The answer is b. (Brunton, pp 898-899; Katzung, pp 629-630, 633, 760.) Col es evel a ms ori gi na l a pproved i ndi ca ti on, a nd i ts mos t common us e, i s for
ma na gi ng hyperchol es terol emi a . It i s cl a s s i fi ed a s a bi l e a ci d s eques tra nt: i t bi nds the chol es terol -ri ch bi l e a ci ds i n the gut, preventi ng thei r
enterohepa ti c reci rcul a ti on. The ma i n outcome i s l owered LDL l evel s . In ea rl y 2008, i t wa s a pproved a s a n a djunct for s ome pa ti ents wi th type 2
di a betes , s uch a s the gentl ema n des cri bed here. Its a nti hypergl ycemi c mecha ni s m of a cti on i s not ful l y unders tood. There a re other bi l e a ci d
s eques tra nts (chol es tyra mi ne, col es ti pol ), but they a re not i ndi ca ted for not a ppa rentl y effecti ve a s a n a djunct to thera py of type 2 di a betes . There
i s a t l ea s t one proba bl e a dva nta ge of col es evel a m over the a l terna ti ve bi l e a ci d s eques tra nts . Chol es tyra mi ne a nd col es ti pol bi nd to a nd i nhi bi t
the a bs orpti on (ra te, extent, or both) of ma ny other ora l drugs tha t a re i n the GI tra ct a t the s a me ti me. Tha t i s , they pa rti ci pa te i n ma ny drug-drug
i ntera cti ons . They a l s o tend to bi nd to a nd i nhi bi t a bs orpti on of fa t-s ol ubl e vi ta mi ns (A, D, E, a nd K), whether from di eta ry or vi ta mi n s uppl ement
s ources . Col es evel a m does not s i gni fi ca ntl y i nhi bi t the a bs orpti on of other ora l medi ca ti ons or fa t-s ol ubl e vi ta mi ns .
Ba s ed on wha t i s known a bout col es evel a ms mecha ni s m of a cti on there i s nothi ng to s ugges t tha t i t ha s a ny benefi ci a l effects on the
pa thophys i ol -ogy or cl i ni ca l cours e of COPD (a ), hyperuri cemi a (c), ni coti ne (or a ny other) a ddi cti on/dependency (d), or pros ta te di s ea s e (beni gn or
not).
See Ques ti on 256 i n the Cha pter on Ca rdi ova s cul a r Pha rma col ogy for more i nforma ti on a bout col es evel a m.

390. The answer is c. (Brunton, pp 1169-1170, 1174-1175, 1669-1670, 1833-1834; Katzung, pp 725t, 726-731.) Thromboembol i s m a s s oci a ted wi th OC
a dmi ni s tra ti on i s a ttri buted to the es trogen component. If thromboembol i s m i s a concern, then one a pproa ch to reduci ng the ri s k woul d be
s el ecti ng a product wi th a l owernot hi gher (e)es trogen dos e. (Us i ng es trogen a l one [e] woul d be i rra ti ona l , then; tha t pa rti a l l y expl a i ns why
there a re no es trogen-onl y ora l contra cepti ves .) Even reduci ng the es trogen dos e i n a combi na ti on contra cepti ve ma y not be s uffi ci ent, l ong term,
to provi de a s ui ta bl e reducti on i n thromboembol i c ri s k. Proges ti ns s eem to ha ve l i ttl e i mpa ct on the devel opment of thromboembol i c di s orders
duri ng OC thera py, a nd s o i ncrea s i ng (b) or decrea s i ng (d) proges ti n content wi l l do l i ttl e more tha n nothi ng for mos t pa ti ents .
Smoki ng i s a ma jor ri s k fa ctor for thromboembol i s m, es peci a l l y for women ta ki ng a n ora l contra cepti ve, s o i ts es s enti a l to encoura ge the
pa ti ent to qui t (or not s ta rt) s moki ng. As noted a bove there a re no OCs tha t conta i n es trogen onl yunl i ke the a va i l a bi l i ty of proges ti n-onl y OCs
the s o-ca l l ed mi ni pi l l s (s ee Ques ti on 394).
391. The answer is a. (Brunton, pp 1228, 1233; Katzung, pp 703t, 712.) Of the drugs l i s ted, dexa metha s one i s by fa r the mos t potent i n terms of rel a ti ve
gl ucocorti coi d effects . The dexa metha s one s uppres s i on tes t ha s s evera l us es : i t a l l ows not onl y compl ete s uppres s i on of pi tui ta ry ACTH
producti on, but a l s o a ccura te mea s urement of endogenous corti cos teroi ds , s uch a s 17-ketos teroi ds , i n the uri ne. The s ma l l a mount of
dexa metha s one pres ent contri butes mi ni ma l l y to thi s mea s urement. None of the other drugs l i s ted woul d be s ui ta bl e for thi s tes t, a nd a l l a re
l es s potent tha n dexa metha s one.
392. The answer is d. (Brunton, pp 1588, 1766-1767, 1841, 1817; Katzung, pp 709f, 710, 712, 737, 853f, 858.) Ketocona zol e, l ong us ed a s a n a nti funga l a gent
(s ee Cha pter 10), i s one of the mos t effi ca ci ous i nhi bi tors of corti cos teroi d s ynthes i s . It i s not a pri ma ry thera py for pi tui ta ry tumors /Cus hi ng
s yndrome, but i s a us eful a djunct. The ma i n probl em a s s oci a ted wi th thi s drug i s the ri s k of hepa totoxi ci ty a nd the potenti a l for i ntera cti ons wi th
s ome other drugs . An a l terna ti ve to ketocona zol e i s a mi nogl utethi mi de, whi ch a l s o i nterferes wi th s ynthes i s of a l l the a drena l s teroi ds .
Ci meti di ne, the H 2 hi s ta mi ne bl ocker tha t i s wel l known a s a n i nhi bi tor of P450-medi a ted meta bol i s m of ma ny drugs , woul d be of no benefi t.
Ma s s i ve dos es of corti s ol , a l though theoreti ca l l y rea s ona bl e (feedba ck s uppres s i on of pi tui ta ry functi on), woul d be of l i ttl e hel p i n terms of
regul a ti ng the pi tui ta rys a cti vi ty a nd cl ea rl y woul d a ggra va te s i gns a nd s ymptoms of a drena l corti cos teroi d exces s tha t we a l rea dy ha ve.
Fl udrocorti s one ha s i ntens e mi nera l ocorti coi d a cti vi ty a nd i s the onl y drug i ndi ca ted for repl a cement thera py i n chroni c mi nera l ocorti coi d
defi ci enci es . Spi ronol a ctone bl ocks a l dos terone receptors ; i t woul d countera ct onl y the a l dos terone-rel a ted res pons es to corti cos teroi d exces s
a nd woul d not ha ve a ny effects on a drena l corti cos teroi d s ynthes i s .
393. The answer is e. (Brunton, pp 845, 1012, 1524, 1529; Katzung, pp 407-409, 427, 1159t.) Phenytoi n i s one of s evera l a gents tha t ca n enha nce the
hepa ti c meta bol i s m of ora l contra cepti ves (es peci a l l y the es trogen component), l ea di ng to reduced contra cepti ve l evel s a nd uni ntended
pregna ncy (contra cepti ve fa i l ure). It i s a l s o one tha t i ntera cts by i nduci ng s ynthes i s of hormone-bi ndi ng gl obul i ns : more hormone mol ecul es a re
bound to the protei n, a nd s o l es s free (a cti ve) drug i s i n the ci rcul a ti on. Severa l other common a nti convul s a nts i ntera ct wi th the s a me potenti a l
outcome, es peci a l l y ba rbi tura tes (i ncl udi ng phenoba rbi ta l , mephoba rbi ta l , a nd pri mi done), ca rba ma zepi ne, a nd oxca rba zepi ne. Be s ure to reca l l
tha t ri fa mpi n (a nd ri fa buti n) a nd protea s e i nhi bi tors (ri tona vi r, others ) a re a l s o i mporta nt i ntera cta nts wi th OCs vi a a meta bol i s m-i nduci ng
mecha ni s m. Fi na l l y, s ome a nti bi oti cs (eg, tetra cycl i nes ) i ntera ct wi th OCs , but here the mecha ni s m di ffers : the a nti bi oti cs s uppres s gut fl ora tha t
pa rti ci pa te i n enterohepa ti c recycl i ng of the OCs . When the ba cteri a a re s uppres s ed, OCs tha t a re s ecreted i nto the gut a re l os t i n the feces , ra ther
tha n bei ng rea bs orbed.
394. The answer is d. (Brunton, pp 1174-1175, 1182, 1833-1836; Katzung, pp 723-726, 730-731, 740.) Proges ti n-onl y ora l contra cepti ves (mi ni pi l l s ) a re
a s s oci a ted wi th a hi gher ri s k of mens trua l i rregul a ri ti es tha n the more common es trogen-proges ti n prepa ra ti ons . Tha t i s l a rgel y due to the l a ck of
es trogen. However, the a bs ence of es trogen a l s o l owers the ri s k (not i ncrea s es , c) of thromboembol i c di s orders a ma jor a dva nta ge, es peci a l l y,
for women who s moke. Proges ti n-onl y formul a ti ons a re, overa l l , l es s effecti ve i n terms of preventi ng pregna ncy tha n combi na ti on products (a nd s o
a ns wer a i s i ncorrect); l i ke combi na ti on products they l a ck defi ni ti ve s permi ci da l effects (b) but they thi cken cervi ca l mucus , reta rd s perm moti l i ty
i n tha t wa y, a nd reduce the l i kel i hood of ni da ti on, a nd thei r a dmi ni s tra ti on s chedul e i s conti nuous every da y (not a ns wer e), ra ther tha n the
cycl i c s chedul e us ed for combi na ti on products .
395. The answer is b. (Brunton, pp 890t, 1174-1175; Katzung, pp 716-723, 740, 1157t.) Hypertens i on, whi ch ma y occur (a nd us ua l l y tra ns i entl y) i n res pons e
to OCs , i s ma i nl y due to es trogen exces s . Fa ti gue (a ), wei ght ga i n (e; us ua l l y tri ggered by i ncrea s ed a ppeti te), a nd i nfrequent or mi s s ed mens es (c)
a re ma i nl y a s s oci a ted wi th proges ti n exces s . Hypomenorrhea (c) ma y a l s o be due to i na dequa te es trogen l evel s i n the combi na ti on product.
Unus ua l l y frequent mens es hypermenorrhea tends to be rel a ted to too l i ttl e proges ti n i n the product.
396. The answer is c. (Brunton, pp 1258-1260; Katzung, pp 757, 766.) Metformi n, a common drug for ma na gi ng ma ny pa ti ents wi th type 2 di a betes
mel l i tus , i s a very wel l -tol era ted a nd effecti ve drug. Thi s bi gua ni de not onl y l owers ci rcul a ti ng gl ucos e l evel s , but s uppres s es a ppeti te, thereby
l oweri ng di eta ry ca l ori c i nta ke. One of the ma i n probl ems a s s oci a ted wi th metformi n i s the devel opment of l a cti c a ci dos i s a dmi ttedl y ra re but
potenti a l l y fa ta l a dvers e res pons e to thi s drug, a nd a s s oci a ted wi th none of the other drugs l i s ted a s a ns wer choi ces (i ns ul i n gl a rgi ne or other
i ns ul i ns (a ); thyroi d hormones (b); s ul fonyl urea s (d), ol der or newer; or s pi ronol a c-tone or the rel a ted drug epl erenone (e)).
397. The answer is d. (Brunton, pp 1260-1262; Katzung, pp 758t, 786.) Tol buta mi de a nd the ol der s ul fonyl urea s (e) ha ve been a s s oci a ted wi th a n
i ncrea s ed ri s k of s udden dea th. The gl i ta zones , however, ha ve been a s s oci a ted wi th a n i ncrea s ed ri s k of hea rt fa i l ure, whi ch i s why pa ti ents
ta ki ng thes e drugs s houl d be moni tored for wei ght ga i n, edema , a nd other expected s i gns a nd s ymptoms of hea rt fa i l ure. The hea rt fa i l ure ri s k i s
a l s o a ma jor rea s on why pi ogl i ta zone i s the onl y gl i ta zone to rema i n on the ma rket: others , s uch a s ros i gl i ta zone a nd trogl i ta zone, ha ve been
wi thdra wn owi ng to ca rdi ova s cul a r a nd/or hepa totoxi c concerns .
Aca rbos e (a ), a n i nhi bi tor of ga s troi ntes ti na l ca rbohydra te upta ke, i s rel a ti vel y free of a ny s eri ous toxi ci ti es . Bi gua ni des (b), of whi ch metformi n
(d) i s a n exa mpl e, a re wi del y us ed a nti di a beti c drugs . The ma jor toxi ci ty or a dvers e res pons e i s a ri s k of l a cti c a ci dos i s .
398. The answer is b. (Brunton, pp 1046-1052; Katzung, p 703t.) We woul d gi ve beta metha s one to enha nce feta l s urfa cta nt s ynthes i s a nd s uppres s
a i rwa y i nfl a mma ti on, thereby l es s eni ng the cha nce or s everi ty of feta l res pi ra tory di s tres s s yndrome a t bi rth. (The a cti on proba bl y i nvol ves
s ti mul a ti ng s ynthes i s of fi brobl a s t pneumocyte fa ctor, whi ch then s ti mul a tes s urfa cta nt s ynthes i s by pneumocytes i n the fetus . Reca l l tha t
s urfa cta nt l owers a l veol a r s urfa ce tens i on, thereby reduci ng the l i kel i hood of a l veol a r col l a ps e a nd i ts cons equences on ga s excha nge.)
Note: Other corti cos teroi ds , es peci a l l y dexa metha s one, coul d be us ed. However, beta metha s one i s preferred beca us e i t bi nds l es s to pl a s ma
protei ns tha n corti s ol a nd mos t other gl ucocorti coi ds , a l l owi ng more s teroi d to cros s the pl a centa .
Even though a l buterol i s us ed a s a bronchodi l a tor (eg, for a s thma or COPD), i t i s cl a s s i fi ed, pha rma col ogi ca l l y, preci s el y a s we cl a s s i fy ri todri ne,
a rel a ti vel y s el ecti ve 2 a goni s t. In obs tetri cs , ergonovi ne or methyl ergonovi ne i s gi ven pos tpa rtum onl y; thei r s trong uteri ne contra cti ng effects a re
us ed to reduce pos tpa rtum bl eedi ng, a nd s uch i ntens e a nd prol onged uteri ne effects woul d be di s a s trous for the unborn chi l d beca us e pl a centa l

bl ood fl ow woul d be compromi s ed. As i de from bei ng contra -i ndi ca ted before del i very, they ha ve no pul mona ry effects of the s ort we wa nt.
Indometha ci n (d) i s s ometi mes us ed to s l ow prema ture l a bor. It a nd a nother nons teroi da l a nti -i nfl a mma tory drug, i buprofen, work by bl ocki ng
s ynthes i s of pros ta gl a ndi ns tha t ha ve oxytoci c a cti vi ty, but pros ta gl a ndi n s ynthes i s i nhi bi ti on a l s o ca us es cl os ure of the ductus a rteri os us (whi ch,
i n thi s s etti ng, woul d be unwa nted). Ma gnes i um s ul fa te woul d not ca us e the des i red pul mona ry effects ; i t i s us ed i n obs tetri cs to prevent
s ei zures i n preecl a mps i a /ecl a mps i a . The drug ha s uteri ne rel a xa nt a cti vi ty too, but the jury i s out on jus t how effecti ve a nd s a fe the drug i s when
us ed to s uppres s prema ture uteri ne contra cti ons .
Note: Three pha rma ceuti ca l prepa ra ti ons of s urfa cta nt a re now a va i l a bl e: ca l fa cta nt, bera cta nt, a nd pora cta nt a l fa . They a re gi ven to neona tes
wi th res pi ra tory di s tres s s yndrome by di rect i ntra tra chea l i ns ti l l a ti on.
399. The answer is b. (Brunton, p 1296; Katzung, p 776.) Es opha gi ti s , s ometi mes wi th es opha gea l ul cers , i s the mos t worri s ome a dvers e res pons e to
bi s phos phona tes s uch a s eti drona te. It i s not due to a ny s peci fi c meta bol i c a l tera ti on ca us es by the drug, but ra ther by di rect, prol onged conta ct of
the drug wi th the es opha gus i f the ora l dos e l odges there wi thout pa s s i ng qui ckl y enough to the s toma ch. Thi s i s why the drug s houl d not be
a dmi ni s tered to pa ti ents wi th es opha gea l di s ea s e, di ffi cul ty s wa l l owi ng, or a n i na bi l i ty to s i t or s ta nd up for a t l ea s t 30 mi nutes (to hel p gra vi ty
bri ng the ta bl et to the s toma ch) a fter ta ki ng the drug. There i s a l s o s ome concern tha t l ong-term thera py wi th bi s phos phona tes ma y ca us e
os teonecros i s of the ja w. Nonethel es s , overa l l the bi s phos phona tes ca us e rema rka bl y few s i de effects i n the va s t ma jori ty of pa ti ents .
400. The answer is c. (Brunton, pp 1122, 1668-1670, 1765; Katzung, p 678.) Leuprol i de i s a pepti de tha t i s rel a ted to GnRH or l utei ni zi ng hormonerel ea s i ng hormone (LHRH), a nd i t i s us ed to trea t meta s ta ti c pros ta te ca rci noma . By i nhi bi ti ng gona dotropi n rel ea s e i t i nduces a hypogona da l
s ta te; tes tos terone l evel s i n the body fa l l s i gni fi ca ntl y, a nd thi s a ppea rs to be the mecha ni s m for s uppres s i on of the ca ncer. Ami nogl utethi mi de
(a ) i s a n a roma ta s e i nhi bi tor ma i nl y us ed to trea t Cus hi ng di s ea s e (i t i nhi bi ts s ynthes i s of a drena l corti cos teroi ds ), a nd s ome pa ti ents wi th meta s ta ti c brea s t ca rci noma . Fl udrocorti cone (b) i s a mi nera l ocorti coi d us ed for chroni c a drena l i ns uffi ci ency (a l ong wi th gl ucocorti coi ds ) or congeni ta l
a drena l hypopl a s i a . Mi fepri s tone (d) i s a n a borti fa ci ent/oxytoci c drug. Spi ronol a ctone (e) i s a n a l dos terone receptor bl ocker tha t i s us ed ma i nl y
a s for pa ti ents wi th pri ma ry or s econda ry hypera l dos teroni s m, a nd a s a n a djunct to the ma na gement of s evere hea rt fa i l ure. It i s a l s o cl a s s i fi ed a s
a pota s s i um-s pa ri ng di ureti c.
401. The answer is e. (Brunton, pp 1256-1258; Katzung, pp 753-762, 755t.) Gl yburi de i s one of s evera l s ul fonyl urea a nti di a beti c drugs . Reca l l tha t the
s ul fonyl urea s s i mpl i s ti ca l l y fa l l i nto two ma i n cl a s s es , ba s ed l a rgel y on how l ong they ha ve been us ed: the s o-ca l l ed fi rs t-genera ti on a gents , s uch
a s tol buta mi de a nd chl orpropa mi de, a nd the newer s econd-genera ti on drugs , gl i pi zi de, gl yburi de, a nd gl i mepi ri de. Whether ol der or newer, thes e
drugs ma i nl y l ower bl ood gl ucos e l evel s by enha nci ng i ns ul i n rel ea s e from the cel l s of the pa ncrea s . The mecha ni s m i nvol ved bi ndi ng to a nd
bl ocki ng a n ATP-s ens i ti ve K+ cha nnel on -cel l membra nes . Thi s depol a ri zes the membra ne, a nd res ul ti ng Ca 2+ i nfl ux tri ggers i ns ul i n rel ea s e. The
mecha ni s ti c dependence on i ns ul i n rel ea s e, of cours e, expl a i ns why thes e drugs a re i neffecti ve i n type 1 di a betes .
Other proba bl e a cti ons of the s ul fonyl urea s i ncl ude reduced pl a s ma gl uca gon l evel s a nd i ncrea s ed bi ndi ng of i ns ul i n to pa renchyma l ti s s ue
cel l s . Thes e drugs ha ve no di rect effects on rena l ha ndl i ng of gl ucos e (b) or i ns ul i n s ynthes i s (c). Unl i ke s ome other ora l a nti di a beti c drugs , s uch
a s the gl i ta zones (thi a zol i di nedi ones ), they do not i ncrea s e pa renchyma l cel l res pons i venes s to i ns ul i n (d) or do s o i n a ny other wa ys tha t mi ght
be des cri bed a s i ns ul i n s ens i ti zi ng. They do not decrea s e i ns ul i n res i s ta nce (a ), whi ch i s a common probl em for ma ny pa ti ents wi th type 2
di a betes mel l i tus , whether by l oweri ng body wei ght or a ppeti te or by other mecha ni s ms .
402. The answer is c. (Brunton, pp 75t, 1257-1258; Katzung, pp 753-755.) Of the ma i n groups or chemi ca l cl a s s es of ora l a nti di a beti c a gents ,
s ul fonyl urea s a re the ones typi ca l l y a s s oci a ted wi th ca us i ng hypogl ycemi a , whether from overdos e or a s a ra ther expected res pons e i n s ome
pa ti ents , pa rti cul a rl y before mea l s . As noted i n the previ ous ques ti on, s ul fonyl urea s rel ea s e i ns ul i n from pa ncrea s even i f bl ood gl ucos e l evel s
a l rea dy a re l ow. Even i n a fa s t-i nduced hypogl ycemi c s ta te a s ul fonyl urea wi l l rel ea s e i ns ul i n a nd dri ve bl ood gl ucos e down even further, wi th a
l i kel y outcome bei ng hypogl ycemi a .
The el derl y a re pa rti cul a rl y s us cepti bl e to s ul fonyl urea -i nduced hypogl ycemi a . Pa rt of thi s ma y rel a te to di et. However, expected a ge-rel a ted
fa l l s of rena l a nd/or hepa ti c functi on ca n reduce el i mi na ti on of thes e drugs , thereby i ncrea s i ng thei r pl a s ma l evel s a nd thei r effects unl es s
dos a ges a re reduced a ccordi ngl y.
Thi s propens i ty for prepra ndi a l hypogl ycemi a i s s ha red by the megl i ti ni des repa gl i ni de a nd na tegl i ni debeca us e they, too, i ncrea s e
pa ncrea ti c i ns ul i n rel ea s e. However, they a re not pres cri bed nea rl y a s often a s a s ul fonyl urea (or metformi n) when ora l thera py i s i ndi ca ted.
Indeed, repa gl i ni de a nd na tegl i ni de a re s el dom pres cri bed for di a betes a nymore.
Pi ogl i ta zone (e), the onl y rema i ni ng gl i ta zone on the ma rket, s el dom ca us es s ymptoma ti c hypogl ycemi a beca us e i t does not rel ea s e i ns ul i n.
Ra ther, i t i s a n i ns ul i n s ens i ti zer, a cti ng on ta rgets s uch a s s kel eta l mus cl e cel l s a nd a di pocytes . The l ow ri s k of hypogl ycemi a a l s o a ppl i es to
metformi n (d), the bi gua ni de; a nd to a ca rbos e (a ; a n -gl ucos i da s e i nhi bi tor, a s i s mi gl i tol ). Col es evel a m (b), a l s o a n ora l a gent, i s cl a s s i fi ed a s a
bi l e a ci d s eques tra nt. It i nhi bi ts enterohepa ti c reupta ke of chol es terol from the gut. Its ori gi na l a pproved us e wa s a s a chol es terol -l oweri ng
a djunct for certa i n pa ti ents wi th hyperl i pi demi a s . It i s a l s o a pproved now a djuncti ve trea tment for certa i n pa ti ents wi th type 2 di a betes mel l i tus .
Its mecha ni s m of gl ucos e-l oweri ng effects i s not known for certa i n.
403. The answer is a. (Brunton, p 1265; Katzung, pp 759-760.) Aca rbos e, cl a s s i fi ed a s a n -gl ucos i da s e i nhi bi tor, s l ows the ra te a nd extent of compl ex
ca rbohydra te a bs orpti on from the i ntes ti nes . (The rel a ted drug, mi gl i tol , does the s a me. It i s s el dom pres cri bed.) The cons equence of thi s for the
hypogl ycemi c pa ti ent i s tha t a ttempts to res tore bl ood gl ucos e l evel s by cons umi ng s uga r or s ucros e-conta i ni ng foods or bevera ges (eg, ora nge
jui ce i s a popul a r choi ce, a s a re products s uch a s the one our pa ti ent took) wi l l be l es s effecti ve, i f effecti ve a t a l l a nd certa i nl y s l ower i n terms
of s ymptom rel i ef. None of the other ora l di a betes drugs ha ve thi s mecha ni s m of a cti on a nd s o wi l l not hi nder a ttempts to res tore eugl ycemi a
when compl ex ca rbohydra tes a re cons umed. If the pa ti ent who i s ta ki ng a ca rbos e becomes hypogl ycemi c, but not to the extent tha t i t becomes
s evere or s eri ous , ora l gl ucos e mus t be us ed. Severa l gl ucos e-conta i ni ng products a re on the ma rket a nd a re ma de for s uch pa ti ents .
404. The answer is a. (Brunton, pp 1141-1142, 1146-1151; Katzung, pp 688-689, 695.) The i nci dence of a gra nul ocytos i s due to propyl thi oura ci l , or the
rel a ted thi o[n]a mi de, methi ma zol e, i s not ra re. It ma y devel op wi thi n the fi rs t few weeks of s ta rti ng thera py, a nd s o a routi ne bl ood tes t
s chedul ed for s evera l months or more a fter s ta rti ng the drug ma y not ca tch i t. However, i f i t i s detected ea rl y (eg, the pa ti ent promptl y reports a
s ore throa t or other fl u-l i ke s ymptoms ) a nd the drug i s s topped, i t i s us ua l l y s ponta neous l y revers i bl e. The mos t common s i de effect wi th the
thi oa mi des i s urti ca ri a . It ma y a ba te s ponta neous l y or requi re s ymptoma ti c ma na gement wi th a n a nti hi s ta mi ne (ei ther fi rs t or s econd genera ti on)
or wi th a corti cos teroi d.
None of the other res pons es l i s ted a re recogni zed a s bei ng a s s oci a ted wi th thi oa mi des .
405. The answer is e. (Brunton, pp 1259-1261; Katzung, pp 757-759, 766.) Pi ogl i ta zone, l i ke a l l the gl i ta zone ora l a nti di a beti c drugs , works by i ncrea s i ng
pa renchyma l cel l res pons i venes s to i ns ul i n. The mecha ni s m s eems to i nvol ve a cti va ti on of peroxi s ome prol i fera tor-a cti va ted receptors (PPARs ).

Thi s a ppa rentl y i ncrea s es tra ns cri pti on of i ns ul i nres pons i ve genes tha t control gl ucos e (a nd l i pi d) meta bol i s m a nd cel l ul a r gl ucos e upta ke vi a
gl ucos e tra ns porters . The net effects i ncl ude not onl y l owered pl a s ma l evel s of gl ucos e, but a l s o fa tty a ci ds a nd (i ndi rectl y) of i ns ul i n. Gi ven the
neces s a ry i nvol vement of i ns ul i n i n the drugs effects , i t wi l l not work (a l one) for pa ti ents wi th type 1 di a betes . When us ed for pa ti ents who ha ve
type 2 di a betes , a nd who nonethel es s requi re i ns ul i n, a thi a zol i di nedi one ca n be a va l ua bl e a djunct tha t hel ps l ower da i l y i ns ul i n requi rements .
406. The answer is d. (Brunton, pp 1258-1260; Katzung, pp 757, 761-762.) Metformi n (a bi gua ni de) pos es the grea tes t ri s k, of a l l the a nti di a beti c drugs , of
ca us i ng l a cti c a ci dos i s . Al though the overa l l ri s k of l a cti c a ci dos i s from thi s drug i s l ow, s houl d i t occur, morta l i ty i s qui te common. Al cohol
cons umpti on or rena l or hepa ti c di s ea s e i ncrea s es the ri s k of l a cti c a ci dos i s a s s oci a ted wi th metformi n.
Aca rbos e (a ), a n -gl ucos i da s e i nhi bi tor (bl ocks s ta rch upta ke from the gut), the s ul fonyl urea s (ol der ones s uch a s tol buta mi de or newer ones
s uch a s gl i pi zi de a nd gl yburi de; b a nd c), a nd ros i gl i ta zone (e; a nd other gl i ta zones , eg, pi ogl i ta zone) a re not a s s oci a ted wi th l a cti c a ci dos i s
(unl es s they a re coa dmi ni s tered wi th metformi n).
407. The answer is c. (Brunton, pp 211-212, 320, 1150; Katzung, pp 691-694.) Ca rdi ova s cul a r a nd rel a ted hemodyna mi c cha nges , mos tl y a ri s i ng from or
rel a ted to ta chyca rdi a , i ncrea s ed ventri cul a r contra cti l i ty, a nd potenti a l l y l ea di ng to a cute myoca rdi a l i s chemi a , a re a mong the ha l l ma rks of
thyroi d hormone exces s , whether drug-i nduced or i di opa thi c (eg, thyrotoxi cos i s of other ca us es ). Increa s ed thyroi d hormone l evel s up-regul a te
the -a drenergi c receptors , l ea di ng to hei ghtened a nd potenti a l l y l etha l res pons es tha t i nvol ve overa cti va ti on of thos e receptors . Beta -bl ocka de
provi des i mporta nt a nd prompt s ymptom rel i ef, a nd ma y be l i fes a vi ng i n s i tua ti ons s uch a s thi s . Other i nterventi ons a i med a t l oweri ng thyroi d
hormone s ynthes i s or rel ea s e (i odi ne/i odi des , a ; a thi oa mi de s uch a s propyl thi oura ci l , d) ul ti ma tel y ma y be i mporta nt, but s a vi ng the pa ti ents
l i fe wi th a dmi ni s tra ti on of propra nol ol or a s ui ta bl e a l terna ti ve i s the mos t i mporta nt fi rs t s tep.
Li othyroni ne (b) woul d be a whol l y i rra ti ona l choi ce for a cute thyroi d hormone overdos es . Ra di oi odi ne (e) i s a l s o i rra ti ona l for a cute a nd
i nfrequent epi s odes of hyperthyroi di s m s uch a s thos e tha t occur wi th thyroi d hormone overdos es . It i s , of cours e, one opti on for ma na gi ng
hyperthyroi di s m due to a thyroi d gl a nd ca ncer i n s ome pa ti ents .
408. The answer is d. (Brunton, pp 1185-1186; Katzung, pp 725-731.) There a re two ma i n mecha ni s ms by whi ch OCs exert thei r ma i n effects . Argua bl y the
mos t i mporta nt i s i nhi bi ti on of ovul a ti on. Thi s prevents (or reduces the ri s k of) ferti l i za ti on, a proces s tha t mus t come before s uch others a s
i mpa i ri ng ni da ti on (c). The other i s thi ckeni ng of cervi ca l mucus . Tha t i mporta nt effect, ma i nl y ca us ed by the proges ti n component, provi des a
phys i ca l ba rri er tha t s l ows or s tops s perm moti l i ty. There a re cha nges of cervi ca l mucus pH (a ), but tha t does not ca us e a s permi ci da l effect per s e,
nor i s i t the ma jor mecha ni s m by whi ch the contra cepti ve a cts . Deta chi ng a ferti l i zed ovum (b) or reduci ng uteri ne or endometri a l bl ood fl ow (e)
a re not el ements of the mecha ni s ms of a cti on.
409. The answer is e. (Brunton, p 1294; Katzung, pp 772-773, 780.) Over-medi ca ti on wi th vi ta mi n D ma y l ea d to a toxi c s yndrome ca l l ed hypervi ta mi nos i s
D. The i ni ti a l s ymptoms ca n i ncl ude wea knes s , na us ea , wei ght l os s , a nemi a , a nd mi l d a ci dos i s . As the exces s i ve dos es a re conti nued, s i gns of
nephrotoxi ci ty ca n devel op, s uch a s pol yuri a , pol ydi ps i a , a zotemi a , a nd eventua l l y nephroca l ci nos i s . In a dul ts , os teoporos i s ca n occur. Al s o, there
i s CNS i mpa i rment, whi ch ca n res ul t i n menta l reta rda ti on a nd s ei zures .
The s i gns a nd s ymptoms des cri bed i n the ques ti on a re not a s s oci a ted wi th es trogens (a ) or proges ti ns ; eti drona te (b) or other
bi s phos phona tes ; gl i pi zi de (c) or a ny other s ul fonyl urea s ; or predni s one (d) or other gl ucocorti coi ds .
410. The answer is c. (Brunton, pp 1766-1767; Katzung, pp 709-710, 712, 737, 854.) Ketocona zol e i s typi ca l l y remembered a s a n a zol e a nti funga l drug, a nd
a common ca us e of drug i ntera cti ons due to i ts powerful cyto-chrome P450 i nhi bi tor effects . At dos es hi gher tha n thos e us ed when the drug i s
pres cri bed a s a n a nti funga l , i t i nhi bi ts corti cos teroi d s ynthes i s a nd i s one of the preemi nent drugs for nonopera bl e Cus hi ng di s ea s e. Al terna ti ves
a re metyra pone a nd a mi nogl utethi mi de, not l i s ted here. Dexa metha -s one (a ) i s a s yntheti c corti cos teroi d wi th powerful gl ucocorti coi d effects a nd
l i ttl e or no mi nera l ocorti coi d a cti vi ty. Hydrocorti s one (b) i s corti s ol ; a n effi ca ci ous gl ucocorti coi d wi th us eful (but s l i ght) mi nera l ocorti coi d a cti vi ty.
The s a me a ppl i es to predni s one (d), predomi na tel y a gl ucocorti coi d us ed a s a n ora l a nti -i nfl a mma tory drug for a s thma , s ome a rthri ti des , a nd
other s teroi d-res pons i ve condi ti ons . Spi ronol a ctone (e) i s a n a l dos terone receptor a nta goni s t, us ed ma i nl y for pri ma ry or s econda ry
hypera l dos teroni s m, for hea rt fa i l ure, a nd for i ts pota s s i um-s pa ri ng di ureti c effects .
411. The answer is c. (Brunton, p 1114; Katzung, pp 290, 672-673.) Pri ma ry a menorrhea i s a s s oci a ted wi th hyperprol a cti nemi a . Women who a re
a menorrhei c from hyperprol a cti nemi a a l s o often pres ent wi th ga l a ctorrhea a nd i nferti l i ty. Bromocri pti ne, a dopa mi ne receptor a goni s t, i nhi bi ts
prol a cti n rel ea s e. The s i te of a cti on i s the pi tui ta ry, a nd i t i nvol ves the s a me s i te a nd ul ti ma te mecha ni s m by whi ch dopa mi ne, rel ea s ed from the
hypotha l a mus , norma l l y s uppres s es prol a cti n rel ea s e. Some ca us es of hyperprol a cti nemi a , i n both men a nd women, i ncl ude pi tui ta ry ca ncer,
hypotha l a mi c dys functi on, a nd s ome drugs (eg, a nti ps ychoti cs , es trogens ). Reca l l tha t bromocri pti ne, by vi rtue of i ts centra l dopa mi nergi c a cti vi ty,
i s s ometi mes us ed to hel p correct the dopa mi ne-ACh i mba l a nce tha t underl i es Pa rki ns on di s ea s e.
Effects on es trogens or proges ti n (a , d), gona dotropi ns (a ), FSH (b), or GnRH (e) a re not res pons i bl e for the thera peuti c a cti ons of bromocri pti ne
i n the context of ma na gi ng pri ma ry a menorrhea .
412. The answer is e. (Brunton, pp 1278-1280; Katzung, pp 769-771.) Pa ra thyroi d hormones ma i n rol e i s to ma i nta i n norma l pl a s ma Ca 2+ l evel s . When
pl a s ma Ca 2+ concentra ti ons become s uffi ci entl y l ow, pa ra thyroi d hormone s ynthes i s a nd rel ea s e i ncrea s e, a nd i t hel ps res tore a normoca l cemi c
s ta te by promoti ng (i n concert wi th vi ta mi n D) Ca 2+ a bs orpti on from the i ntes ti nes , promotes rena l tubul a r Ca 2+ rea bs orpti on a nd phos pha te
excreti on, a nd i ncrea s es mobi l i za ti on of Ca 2+ a nd phos pha te from bone (i e, bone res orpti on).

Antimicrobial and Antiviral Pharmacology

Anti ba cteri a l s
Anti mycoba cteri a l s
Anti funga l s
Anti vi ra l s /Anti retrovi ra l s
Anti protozoa l s

Questions
413. You a re a phys i ci a n a nd epi demi ol ogi s t empl oyed by the US Centers for Di s ea s e Control a nd Preventi on. You get a n urgent phone ca l l s ta ti ng
tha t a n envel ope wa s opened i n the ma i l room of a l a rge corpora ti on, a nd s i mi l a r ones were del i vered to va ri ous government offi ces . Some s ort of
whi te powder fel l out a nd wa s bl own a round the room, expos i ng dozens of workers . The s us pi ci on i s a nthra x. Whi ch drug woul d be bes t, mos t
properl y i ndi ca ted, for prophyl a xi s i f the s ubs ta nce tes ts pos i ti ve for Bacillus anthracis?
a . Azi thromyci n
b. Cl a ri thromyci n
c. Doxycycl i ne
d. Hydroxychl oroqui ne
e. Metroni da zol e
414. A ja undi ced 1-da y-ol d prema ture i nfa nt wi th a n el eva ted free bi l i -rubi n i s s een i n the prema ture ba by nurs ery. The mother ha d recei ved a n
a nti bi oti c combi na ti on for a uri na ry tra ct i nfecti on (UTI) 1 week before del i very. Whi ch a nti bi oti c drug or cl a s s wa s the mos t l i kel y ca us e of the
ba bys kerni cterus ?
a . An a mi nopeni ci l l i n (eg, a moxi ci l l i n)
b. Azi thromyci n
c. Erythromyci n
d. Fourth-genera ti on cepha l os pori n
e. Sul fa methoxa zol e pl us tri methopri m
415. You a re ca ri ng for a pa ti ent wi th HIV i nfecti on a nd wi l l s ta rt drug thera py i ni ti a l l y wi th the nucl eos i de a na l og zi dovudi ne (formerl y ca l l ed
a zi dothymi di ne, or AZT). Whi ch s ta tement mos t correctl y des cri bes zi dovudi ne or the di deoxynucl eos i de cl a s s to whi ch i t bel ongs ?
a . Level s of a cti ve meta bol i te i n cerebros pi na l fl ui d us ua l l y a re not detecta bl e (i e, zero) beca us e i t ca nnot cros s the bl oodbra i n ba rri er
b. Res i s ta nce to thes e a nti vi ra l s devel ops ra pi dl y a fter monothera py s ta rts , i nvol ves decrea s ed i ncorpora ti on of a cti ve meta bol i te i nto vi ra l DNA
c. The di deoxynucl eos i de s tops vi ra l nucl ei c a ci d s ynthes i s
d. The a cti ve meta bol i te i s a n equa l l y effecti ve s ubs tra te for vi ra l revers e tra ns cri pta s e a nd ma mma l i a n DNA pol ymera s e, whi ch expl a i ns the hi gh
i nci dence of hos t toxi ci ty
e. Zi dovudi ne i s dephos phoryl a ted to form the a cti ve meta bol i te, whi ch i s i ncorpora ted i nto vi ra l nucl ei c a ci d vi a HIV revers e tra ns cri pta s e
416. A pa ti ent on a nti mi crobi a l thera py devel ops the fol l owi ng s i gns a nd s ymptoms tha t ul ti ma tel y a re found to be drug-i nduced: cough, dys pnea ,
a nd pul mona ry i nfi l tra tes ; neutropeni a a nd bl eedi ng tendenci es ; a nd pa res thes i a s . Wha t wa s the mos t l i kel y ca us e of thi s pa ti ents s ymptoms ?
a . Amoxi ci l l i n
b. Azi thromyci n
c. Ci profl oxa ci n
d. Is oni a zi d
e. Ni trofura ntoi n
417. A pa ti ent pres ents wi th s evere, unrel enti ng di a rrhea , a nd the fl ui d a nd el ectrol yte i mba l a nces one woul d expect from tha t. She ha d been
s ta rted on a n a nti bi oti c recentl y, a nd the l i kel y di a gnos i s i s a nti bi oti c-a s s oci a ted ps eudomembra nous col i ti s (AAPMC). Wha t drug wa s the mos t
l i kel y ca us e?
a . Amoxi ci l l i n
b. Azi thromyci n
c. Cl i nda myci n
d. Metroni da zol e
e. Tri methopri m pl us s ul fa methoxa zol e (TMP-SMZ)
418. A 35-yea r-ol d woma n compl a i ns of i tchi ng i n the vul va l a rea . Ha ngi ng-drop exa mi na ti on of the uri ne revea l s tri chomona ds . Wha t i s the
preferred trea tment for the tri chomoni a s i s ?
a . Doxycycl i ne
b. Emeti ne
c. Metroni da zol e
d. Penta mi di ne
e. Pyra zi na mi de
419. A pa ti ent wi l l be s ta rted on pri ma qui ne to trea t a cti ve Plasmodium vivax ma l a ri a , s peci fi ca l l y to ta rget the hepa ti c forms of the pa ra s i te. Before
you a dmi ni s ter the drug you s houl d s creen the pa ti ent to a s s es s thei r rel a ti ve ri s k of devel opi ng a rel a ti vel y common a nd s evere a dvers e

res pons e to the drug. Wha t i s tha t pri ma qui ne-a s s oci a ted ri s k?
a . Ca rdi a c conducti on di s turba nces
b. Hemol yti c di s ea s e
c. Nephrotoxi ci ty
d. Reti nopa thy
e. Sei zures , convul s i ons
420. On morni ng rounds i n the hos pi ta l you encounter a pa ti ent bei ng trea ted wi th l i nezol i d, the fi rs t a pproved member of the oxa zol i di ne cl a s s of
a nti mi crobi a l s . Whi ch s ta tement a ccura tel y des cri bes a cha ra cteri s ti c of thi s drug?
a . Exerts s trong ba cteri ci da l effects
b. Ma i nl y us ed for rel a ti vel y mi nor i nfecti ons wi th gra m-nega ti ve orga ni s ms
c. Preferred a l terna ti ve to a moxi ci l l i n for chi l dren wi th oti ti s medi a
d. Preferred a l terna ti ve to ci profl oxa ci n for B. anthracis i nfecti ons
e. Sui ta bl e for va ncomyci n-res i s ta nt enterococci
421. A 59-yea r-ol d woma n i s di a gnos ed wi th tubercul os i s (TB). Before pres cri bi ng a mul ti drug regi men, you ta ke a ca reful medi ca ti on hi s tory
beca us e one of the drugs commonl y us ed to trea t TB i nduces s ome of the mi cros oma l cytochrome P450 enzymes i n the l i ver, a nd i s a common
ca us e of drugdrug i ntera cti ons . Wha t i s the mos t l i kel y drug?
a . Etha mbutol
b. Is oni a zi d
c. Pyra zi na mi de
d. Ri fa mpi n
e. Vi ta mi n B 6
422. A pa ti ent wi th HIV i nfecti on i s recei vi ng a combi na ti on of protea s e i nhi bi tors a s pa rt of overa l l a nti vi ra l thera py. Wha t i s , ordi na ri l y, the mos t
l i kel y/mos t common s i de effect(s ) of the protea s e i nhi bi tors ?
a . Anemi a a nd neutropeni a
b. Hypergl ycemi a a nd hyperl i pi demi a
c. La cti c a ci dos i s
d. Neuropa thy
e. Pa ncrea ti ti s
423. A 27-yea r-ol d woma n ha s jus t returned from a tri p to Southea s t As i a . Over the pa s t 24 hours s he ha s devel oped s ha ki ng, chi l l s , a nd a
tempera ture of 104F. A bl ood s mea r revea l s Plasmodium vivax. Wha t drug woul d you pres cri be to era di ca te the extra erythrocyti c pha s e of the
orga ni s m?
a . Chl orogua ni de
b. Chl oroqui ne
c. Pri ma qui ne
d. Pyri metha mi ne
e. Qui na cri ne
424. A pa ti ent ha s a s evere ba cteri a l i nfecti on tha t norma l l y woul d res pond to a n ora l peni ci l l i n or cepha l os pori n. However, hi s cha rt documents
a na phyl a ctoi d rea cti ons to both cl a s s es of drugs . Gi ven the hi s tory, wha t drug woul d be preferred for trea ti ng the i nfecti on, a nd a l s o pos es the
l ea s t ri s k of cros s -rea cti vi ty a nd a n a l l ergi c res pons e?
a . Cl otri ma zol e
b. Genta mi ci n
c. Metroni da zol e
d. Tetra cycl i ne
e. Va ncomyci n
425. A 40-yea r-ol d ma n i s HIV-pos i ti ve a nd ha s a cl us ter-of-di fferenti a ti on-4 (CD4) count of 200/mm 3 . Wi thi n 2 months a fter s ta rti ng drug thera py for
hi s HIV he devel ops a peri phera l whi te bl ood cel l count of 1000/mm 3 a nd a hemogl obi n of 9.0 mg/dL. Whi ch drug mos t l i kel y ca us ed the
hema tol ogi c a bnorma l i ti es ?
a . Acycl ovi r
b. Di deoxycyti di ne
c. Fos ca rnet
d. Ri ma nta di ne
e. Zi dovudi ne
426. An 86-yea r-ol d ma n compl a i ns of cough a nd bl ood i n hi s s putum for the pa s t 5 da ys . On a dmi s s i on, hi s tempera ture i s 103F. Phys i ca l
exa mi na ti on revea l s ra l es i n hi s ri ght l ung, a nd x-ra y exa mi na ti on s hows i ncrea s ed dens i ty i n the ri ght mi ddl e l obe. A s putum s mea r s hows ma ny
gra mpos i ti ve cocci , confi rmed by s putum cul ture a s peni ci l l i na s e-produci ng Staphylococcus aureus. Whi ch a nti bi oti c woul d be bes t to a dmi ni s ter
fi rs t?
a . Ampi ci l l i n
b. Mezl oci l l i n

c. Oxa ci l l i n
d. Peni ci l l i n (G or V)
e. Ti ca rci l l i n
427. When cons i deri ng a l l the ma i n a nti ba cteri a l drugs tha t work by i nhi bi ti ng protei n s ynthes i s i n one wa y or a nother, vi rtua l l y every one exerts
ba cteri os ta ti c a cti ons . Whi ch drug or drug cl a s s di ffers from the res t beca us e the us ua l cons equence of thera peuti c pl a s ma l evel s i s ba cteri ci da l ,
ra ther tha n mere i nhi bi ti on of ba cteri a l growth a nd repl i ca ti on?
a . Ami nogl ycos i des
b. Cl i nda myci n
c. Erythromyci ns
d. Li nezol i d
e. Tetra cycl i nes
428. A pa ti ent wi th HIV i nfecti on a nd cl i ni ca l AIDS i s trea ted wi th a combi na ti on of a gents , one of whi ch i s zi dovudi ne. Whi ch enzyme or repl i ca ti ve
proces s i s the ma i n ta rget of thi s a nti vi ra l drug?
a . Nonnucl eos i de revers e tra ns cri pta s e
b. Nucl eos i de revers e tra ns cri pta s e
c. RNA s ynthes i s
d. Vi ra l pa rti cl e a s s embl y
e. Vi ra l protea s es
429. A pa ti ent wi th HIV/AIDS, bei ng trea ted wi th mul ti pl e a nti vi ra l a nd i mmunos uppres s i ve drugs , devel ops a n opportuni s ti c i nfecti on ca us ed by P.
jiroveci. Whi ch drug a re you mos t l i kel y to us e to trea t the pul mona ry i nfecti on ca us ed by thi s protozoa n?
a . Ca rbeni ci l l i n
b. Metroni da zol e
c. Ni furti mox
d. Peni ci l l i n G
e. Penta mi di ne
430. A 25-yea r-ol d woma n wi th a n upper res pi ra tory tra ct i nfecti on ca us ed by H. influenzae i s trea ted wi th tri methopri m-s ul fa methoxa zol e. She
res ponds wel l i n a ma tter of da ys a fter s ta rti ng the TMP-SMZ. Whi ch ba cteri a l proces s i s i nhi bi ted by thi s combi na ti on, a nd a ccounts for the
a nti ba cteri a l effects ?
a . Cel l -wa l l s ynthes i s
b. Protei n s ynthes i s
c. Fol i c a ci d s ynthes i s
d. Topoi s omera s e II (DNA gyra s e)
e. DNA pol ymera s e
431. A ma n who ha s been a t the l oca l ta vern, dri nki ng a l cohol hea vi l y, i s a s s a ul ted. He i s tra ns ported to the hos pi ta l . Among va ri ous fi ndi ngs i s a n
i nfecti on for whi ch prompt a nti bi oti c thera py i s i ndi ca ted. Gi ven hi s hi gh bl ood a l cohol l evel , whi ch a nti bi oti c s houl d be a voi ded beca us e of a
hi gh potenti a l of ca us i ng a s eri ous di s ul fi ra m-l i ke rea cti on tha t mi ght provoke venti l a tory or ca rdi ova s cul a r fa i l ure? (As s ume tha t were i t not for
the a l cohol cons umpti on, the a nti bi oti c woul d be s ui ta bl e for the i nfecti ous orga ni s ms tha t ha ve been detected.)
a . Amoxi ci l l i n
b. Cefoteta n
c. Erythromyci n ethyl s ucci na te
d. Li nezol i d
e. Peni ci l l i n G
432. A 43-yea r-ol d woma n i s recoveri ng from ma jor s urgery, fol l owi ng di s cha rge from the hos pi ta l , i n a n a s s i s ted-ca re fa ci l i ty. She devel ops fever,
ra l es , dys pnea , cough, a nd purul ent s putum. Res ul ts of a ches t ra di ogra ph i ndi ca te bi l a tera l pul mona ry i nfi l tra tes . We s end bl ood a nd s putum
cul tures to the cl i ni ca l pa thol ogy l a b for cul turi ng, but now mus t turn our a ttenti on to wha t we bel i eve i s communi ty-a cqui red pneumoni a ca us ed
by a nti bi oti c-res i s ta nt pneumococci . We wa nt to s ta rt empi ri c a nti bi oti c thera py unti l cul ture res ul ts a re a va i l a bl e. Whi ch drug woul d be bes t for
thi s i ni ti a l thera py?
a . Amoxi ci l l i n
b. Cefa zol i n
c. Erythromyci n
d. Levofl oxa ci n
e. Peni ci l l i n G
f. Va ncomyci n
433. Bl ood a nd s putum cul tures ta ken i n a cri ti ca l l y i l l 26-yea r-ol d woma n i ndi ca te the pres ence of MRSAmethi ci l l i n-res i s ta nt Staph. aureus.
Whi ch drug i s mos t l i kel y to be effecti ve i n trea ti ng thi s i nfecti on?
a . Amoxi ci l l i n pl us cl a vul a ni c a ci d
b. Cl i nda myci n
c. Erythromyci n

d. Tri methopri m-s ul fa methoxa zol e (TMP-SMZ)

e. Va ncomyci n
434. Compa red wi th mos t other cepha l os pori ns , the a dmi ni s tra ti on of cefmeta zol e, cefopera zone, or cefoteta n i s a s s oci a ted wi th a hi gher
i nci dence of a n a dvers e res pons e tha t i s pa rti cul a rl y da ngerous for s ome pa ti ents . Wha t i s tha t ra ther uni que a dvers e res pons e?
a . Acute hea rt fa i l ure
b. Acute rena l fa i l ure
c. Bl eedi ng tendenci es i n pa ti ents ta ki ng wa rfa ri n
d. Hypertens i on
e. Ototoxi ci ty
435. A pa ti ent devel ops mus cl e a ches a nd pa i ns duri ng the cours e of a nti bi oti c thera py. A mus cl e bi ops y woul d cl ea rl y s how myopa thy. Whi ch drug
mos t l i kel y (a nd ra ther uni quel y) ca us ed thi s a dvers e effect on s kel eta l mus cl e?
a . Da ptomyci n
b. Erythromyci n
c. Genta mi ci n
d. Li nezol i d
e. Va ncomyci n
436. A pa ti ent wi th a n i nfecti ous di s ea s e routi nel y ta kes thei r a nti mi crobi a l medi ca ti on wi th mi l k or other da i ry products i n a n a ttempt to reduce
s toma ch ups et from the drug. The a nti bi oti c fa i l s to work a dequa tel y beca us e ca l ci um i n the da i ry products chel a tes the drug a nd reduces i ts ora l
bi oa va i l a bi l i ty. Whi ch a nti mi crobi a l drug or drug cl a s s wa s the pa ti ent mos t l i kel y ta ki ng?
a . Ami nogl ycos i de
b. Anti mycoba cteri a l drug, s peci fi ca l l y i s oni a zi d
c. Cepha l os pori n, fi rs t genera ti on
d. Cepha l os pori n, thi rd genera ti on
e. Peni ci l l i n
f. Tetra cycl i ne
437. A pa ti ent devel ops profus e, wa tery di a rrhea , fever, a bdomi na l pa i n, a nd l eukocytos i s i n res pons e to a nti bi oti c thera py. C. difficile i nfecti on i n
the gut i s confi rmed. Wha t i s the preferred a gent for thera py of thi s a nti bi oti c-a s s oci a ted ps eudomembra nous col i ti s (AAPMC)?
a . Amphoteri ci n B
b. Cl i nda myci n
c. Genta mi ci n
d. Metroni da zol e
e. Tri methopri m pl us s ul fa methoxa zol e (TMP-SMZ)
438. A pa ti ent ha s been ta ki ng wa rfa ri n for s evera l months a nd hi s INR (norma l i zed prothrombi n ti me) ha s been kept wi thi n the des i red
thera peuti c ra nge cons i s tentl y. They devel op a n i nfecti on a nd a re s ta rted on a nti bi oti c thera py. Shortl y therea fter thei r INR ri s es to ei ght (very
hi gh) a nd they devel op epi s ta xi s a nd other i ndi ca tors of exces s i ve bl eedi ng. Whi ch a nti bi oti c mos t l i kel y i ntera cted wi th the wa rfa ri n, i ncrea s i ng
i ts bl ood l evel s a nd effects , by i nhi bi ti ng wa rfa ri ns meta bol i s m by the hepa ti c P-450 s ys tem?
a . Azi thromyci n
b. Erythromyci n
c. Genta mi ci n
d. Peni ci l l i n G
e. Ri fa mpi n
439. Ampi ci l l i n a nd a moxi ci l l i n a re i n the s a me group of peni ci l l i ns (broa d s pectrum, or a mi nopeni ci l l i ns ). However, there i s one cl i ni ca l l y
i mporta nt di fference. Whi ch phra s e bes t s ta tes how a moxi ci l l i n differs from a mpi ci l l i n?
a . Ha s better ora l bi oa va i l a bi l i ty, pa rti cul a rl y when ta ken wi th mea l s
b. Is effecti ve a ga i ns t peni ci l l i na s e-produci ng orga ni s ms
c. Is a broa d-s pectrum peni ci l l i n
d. Does not ca us e hypers ens i ti vi ty rea cti ons
e. Ha s grea t a nti ps eudomona l a cti vi ty
440. A pa ti ents hi s tory notes a documented s evere (a na phyl a ctoi d) rea cti on to a peni ci l l i n. Wha t other a nti bi oti c or cl a s s i s l i kel y to cros s -rea ct
a nd s o s houl d be a voi ded i n thi s pa ti ent?
a . Ami nogl ycos i des
b. Azi thromyci n
c. Cepha l os pori ns
d. Erythromyci n
e. Li nezol i d
f. Tetra cycl i nes
441. A 30-yea r-ol d woma n devel ops a s evere P. aeruginosa i nfecti on. The phys i ci a n choos es to trea t i t wi th a mi ka ci n, not wi th genta mi ci n. Whi ch

phra s e bes t des cri bes how a mi ka ci n di ffers from genta mi ci n?

a . Does not requi re moni tori ng of bl ood l evel s duri ng thera py
b. Exerts s i gni fi ca nt ba cteri ci da l effects a ga i ns t a na erobes too
c. Ha s broa der s pectrum a ga i ns t gra m-nega ti ve ba ci l l i
d. La cks ototoxi c potenti a l
e. Protects a ga i ns t typi ca l a mi nogl ycos i de nephrotoxi ci ty
442. A 19-yea r-ol d bei ng trea ted for l eukemi a devel ops a fever. You gi ve s evera l a gents tha t wi l l cover ba cteri a l , vi ra l , a nd funga l i nfecti ons . Two
da ys l a ter, he devel ops a cute rena l fa i l ure. Whi ch drug wa s mos t l i kel y res pons i bl e?
a . Acycl ovi r
b. Amphoteri ci n B
c. Cefta zi di me
d. Peni ci l l i n G
e. Va ncomyci n
443. Peni ci l l i ns , cepha l os pori ns , a nd a mphoteri ci n B a re qui te di fferent s tructura l l y, a nd the a nti mi crobi a l s pectrum of a mphoteri ci n B i s deci dedl y
di fferent from thos e of the other a gents . Nonethel es s , they a l l s ha re a common property or a cti on. Whi ch s ta tement i denti fi es wha t tha t i s ?
a . Act, though va ri ous mecha ni s ms , on cel l wa l l s or membra nes of s us cepti bl e orga ni s ms
b. Contra i ndi ca ted i n i mmunocompromi s ed pa ti ents
c. Intera ct wi th ma ny drugs by i nduci ng thei r hepa ti c meta bol i s m
d. Leukopeni a (decrea s ed whi te cel l counts ) i s a common s i de effect
e. Nephrotoxi ci ty i s common
444. Gi ven the peri odi c worl dwi de outbrea ks of s wi ne fl u (pa rti cul a rl y i nfl uenza A vi rus s ubtype H1N1) there ha s been a grea t need for
prophyl a cti c mea s ures i n certa i n a t-ri s k popul a ti ons who ma y be s us cepti bl e. Whi ch drug i s genera l l y recommended by the US Centers for Di s ea s e
Control a nd Preventi on for thi s purpos e?
a . Acycl ovi r
b. Ama nta di ne
c. Lopi na vi r
d. Os el ta mi vi r
e. Ri tona vi r
445. A pa ti ent wi th a P. aeruginosa i nfecti on i s recei vi ng i ntra venous genta mi ci n. The a mi nogl ycos i de bl ood l evel s a re wel l a bove the mi ni mum
i nhi bi tory concentra ti on (MIC), but the cl i ni ca l res pons e i s not s a ti s fa ctory. A new medi ca ti on order ca l l s for a ddi ng a peni ci l l i n, a dmi ni s tered i n a
s epa ra te IV l i ne to a voi d a phys i ca l i ncompa ti bi l i ty. If thi s order i s ca rri ed out, wha t i s mos t l i kel y to occur?
a . The a mi nogl ycos i de wi l l i na cti va te the peni ci l l i n
b. The a mi nogl ycos i de wi l l chemi ca l l y neutra l i ze a nd a bol i s h the effects of the peni ci l l i n
c. The pa ti ent i s l i kel y to devel op Clostridium difficile col i ti s (s uperi nfecti on)
d. The peni ci l l i n wi l l a ct s ynergi s ti ca l l y wi th the a mi nogl ycos i de
e. The peni ci l l i n wi l l i ncrea s e the ri s k of a mi nogl ycos i de nephrotoxi ci ty
f. The ri s k of i nduci ng res i s ta nce to both drugs i ncrea s es dra ma ti ca l l y
446. Na rrow s pectrum peni ci l l i ns , both peni ci l l i na s e-s ens i ti ve a nd -res i s ta nt, ha ve rel a ti vel y poor a cti vi ty a ga i ns t gra m-nega ti ve ba cteri a . Wha t i s
the ma i n property or cha ra cteri s ti c tha t expl a i ns why thes e mi cro-orga ni s ms do not res pond wel l to the peni ci l l i ns ?
a . Acti vel y tra ns port a ny a bs orbed peni ci l l i n ba ck to the extra cel l ul a r s pa ce
b. Ha ve a n outer membra ne tha t s erves a s a phys i ca l ba rri er to the peni ci l l i ns
c. La ck a s urfa ce enzyme neces s a ry to meta bol i ca l l y a cti va te the peni ci l l i ns
d. La ck peni ci l l i n-bi ndi ng protei ns
e. Meta bol i ca l l y i na cti va te thes e peni ci l l i ns by mecha ni s ms not i nvol vi ng -l a cta ma s e
447. We ha ve a pa ti ent wi th a n i ntra a bdomi na l i nfecti on, a nd Bacteroides fragilis i s the ma i n orga ni s m found upon cul ture. Whi ch cepha l os pori n
ha s the grea tes t a cti vi ty a ga i ns t a na erobes s uch B. fragilis?
a . Cefa cl or
b. Cefoxi ti n
c. Cefuroxi me
d. Cepha l exi n
e. Cepha l othi n
448. A pa ti ent wi th a s eri ous i nfecti on recei ved i ntens i ve a nti bi oti c thera py tha t l ea ds to hea ri ng l os s . Whi ch a nti bi oti c mos t l i kel y ca us ed the
ototoxi ci ty?
a . Ami nogl ycos i de (eg, genta mi ci n)
b. Cepha l os pori n, fi rs t-genera ti on
c. Cepha l os pori n, thi rd-genera ti on
d. Fl uoroqui nol one (eg, ci profl oxa ci n)

e. Peni ci l l i n
449. A 26-yea r-ol d woma n wi th a cqui red i mmunodefi ci ency s yndrome (AIDS) devel ops cryptococca l meni ngi ti s . She refus es i ntra venous medi ca ti on.
Whi ch a nti funga l a gent i s the bes t choi ce for ora l thera py of the meni ngi ti s ?
a . Amphoteri ci n B
b. Fl ucona zol e
c. Ketocona zol e
d. Metroni da zol e
e. Nys ta ti n
450. An a dul t pa ti ent i s bei ng trea ted wi th a pa rentera l a mi nogl ycos i de for a s eri ous Pseudomonas aeruginosa i nfecti on. He requi res i mmedi a te
s urgery. He i s premedi ca ted wi th mi da zol a m, fol l owed by a dmi ni s tra ti on of pro-pofol for i nducti on. A dos e of s ucci nyl chol i ne i s often gi ven for
i ntuba ti on (due to i ts ra pi d ons et), wi th s kel eta l mus cl e pa ra l ys i s ma i nta i ned duri ng s urgery wi th vecuroni um or a nother neuromus cul a r bl ocker
i n the s a me cl a s s (nondepol a ri zi ng, or competi ti ve ni coti ni c receptor bl ocker). Other components of ba l a nced a nes thes i a i ncl ude ni trous oxi de,
i s ofl ura ne, a nd oxygen. Wha t i s the mos t l i kel y outcome of ha vi ng the a mi nogl ycos i de on boa rd i n the peri opera ti ve s etti ng a l ong wi th a l l thes e
other drugs ?
a . Acute hepa totoxi ci ty from a n a mi nogl ycos i de-i s ofl ura ne i ntera cti on
b. Anta goni s m of mi da zol a ms a mnes ti c a nd s eda ti ve effects
c. Enha nced a mi nogl ycos i de toxi ci ty to hos t cel l s
d. Increa s ed or prol onged res pons e to neuromus cul a r bl ockers
e. Reduced ri s k of ca techol a mi ne-i nduced ca rdi a c a rrhythmi a s
451. A pa ti ent wi th tubercul os i s i s s ta rted on i s oni a zi d (INH) a s pa rt of a mul ti drug regi men. The phys i ci a n a l s o s ta rts thera py wi th vi ta mi n B 6 a t
the s a me ti me. Wha t i s the ma i n rea s on for gi vi ng the vi ta mi n B 6 prophyl a cti ca l l y?
a . Fa ci l i ta tes INH rena l excreti on, thereby protecti ng a ga i ns t nephrotoxi ci ty
b. Inhi bi ts meta bol i s m of INH, thereby i ncrea s i ng INH bl ood l evel s
c. Is a cofa ctor requi red for a cti va ti on of the INH to i ts a nti mycoba cteri a l meta bol i te
d. Potenti a tes the a nti tubercul a r a cti vi ty of the INH
e. Prevents s ome a dvers e effects of INH thera py
452. One a nti bi oti c i s cons i dered very effecti ve i n trea tment of Rickettsia, Mycoplasma, a nd Chlamydia i nfecti ons ? It i s a l s o us ed to ma nge s ome
pa ti ents wi th a cne vul ga ri s l es i ons . To whi ch drug does thi s des cri pti on a ppl y?
a . Ba ci tra ci n
b. Genta mi ci n
c. Peni ci l l i n G
d. Tetra cycl i ne
e. Va ncomyci n
453. You a re s ta rti ng thera py for a n es ta bl i s hed HIV i nfecti on i n a 28-yea r-ol d ma n. The drugs a re ri tona vi r, l opi na vi r, zi dovudi ne, a nd di da nos i ne.
Thi s i nvol ves , of cours e, us i ng two protea s e i nhi bi tors a nd two nucl eos i de revers e tra ns cri pta s e i nhi bi tors (NRTIs ). Wha t i s the ma i n purpos e of
us i ng the ri tona vi r?
a . Hel ps ma i nta i n a dequa te s a qui na vi r l evel s by i nhi bi ti ng i ts meta bol i s m
b. Induces the meta bol i c a cti va ti on of the NRTIs , whi ch a re prodrugs
c. Prevents the l i kel y devel opment of hypogl ycemi a
d. Reduces , or hopeful l y el i mi na tes , l opi na vi r-medi a ted hos t toxi ci ty
e. Serves a s the ma i n, mos t a cti ve, i nhi bi tor of vi ra l protea s e i n thi s combi na ti on
454. As pa rt of a mul ti drug a tta ck on a pa ti ents i nfecti on wi th Myco bacterium tuberculosis, a phys i ci a n pl a ns to us e a n a mi nogl ycos i de a nti bi oti c.
Whi ch drug i s mos t a cti ve a ga i ns t the tubercl e ba ci l l us a nd s eems to be a s s oci a ted wi th the fewes t probl ems wi th res i s ta nce or typi ca l
a mi nogl ycos i de-i nduced a dvers e effects ?
a . Ami ka ci n
b. Ka na myci n
c. Neomyci n
d. Streptomyci n
e. Tobra myci n
455. Such a gents a s cl a vul a ni c a ci d, s ul ba cta m, or ta zoba cta m a re often a dded to s ome propri eta ry (ma nufa ctured) peni ci l l i n combi na ti on
products . Wha t i s the ma i n rea s on for i ncl udi ng them, or des cri bes thei r a cti on bes t?
a . Add a nti bi oti c a cti vi ty a ga i ns t Pseudomonas a nd ma ny Enterobacter s peci es
b. Fa ci l i ta te a nti bi oti c penetra ti on i nto the centra l nervous s ys tem a nd cerebro-s pi na l fl ui d
c. Inhi bi t cel l wa l l tra ns pepti da s es
d. Inhi bi t i na cti va ti on of peni ci l l i n by -l a cta ma s e-produci ng ba cteri a
e. Inhi bi t the norma l l y s i gni fi ca nt hepa ti c meta bol i s m of the peni ci l l i n
f. Reduce the ri s k a nd/or s everi ty of a l l ergi c rea cti ons i n s us cepti bl e pa ti ents

456. A pa ti ent wi th a cti ve tubercul os i s i s bei ng trea ted wi th i s oni a zi d (INH) a nd etha mbutol a s pa rt of the overa l l regi men. Wha t i s the ma i n effect
expected of the etha mbutol ?
a . Fa ci l i ta ted entry of the INH i nto the mycoba cteri a
b. Fa ci l i ta ted penetra ti on of the bl ood-bra i n ba rri er
c. Reta rded a bs orpti on a fter i ntra mus cul a r i njecti on
d. Reta rded devel opment of orga ni s m res i s ta nce
e. Sl owed rena l excreti on of INH to hel p ma i nta i n effecti ve bl ood l evel s
457. A pa ti ent ha s a s evere i nfecti on ca us ed by a na erobi c ba cteri a . The fi rs t-yea r hous e offi cer wri tes a n order for genta mi ci n. Thi s a pproa ch i s
doomed to fa i l beca us e a mi nogl ycos i des ha ve no a cti vi ty a ga i ns t a na erobes . Whi ch bes t expl a i ns why a na erobes wi l l be res i s ta nt?
a . Ca nnot meta bol i ze the a mi nogl ycos i des , whi ch a re a l l prodrugs , to thei r ba cteri ci da l free ra di ca l forms
b. Ca nnot oxi da ti vel y meta bol i ze a mi nogl ycos i des to moi eti es tha t a re nontoxi c to hos t cel l s
c. La ck mol ecul a r oxygen tha t i s a prerequi s i te for drug bi ndi ng to the 50S s ubuni t of ba cteri a l ri bos omes
d. La ck the a bi l i ty to tra ns port a mi nogl ycos i des from the extra cel l ul a r mi l i eu i n the a bs ence of oxygen
e. Synthes i ze more, a nd more a cti ve, res i s ta nce fa ctors tha n do a erobi c ba cteri a
458. In pa ti ents wi th hepa ti c coma or porta l -s ys temi c encepha l opa thy decrea s i ng the producti on a nd a bs orpti on of a mmoni a from the
ga s troi ntes ti na l (GI) tra ct wi l l be benefi ci a l . Wha t a nti bi oti c woul d be mos t us eful i n thi s s i tua ti on?
a . Cepha l othi n
b. Chl ora mpheni col
c. Neomyci n
d. Peni ci l l i n G
e. Tetra cycl i ne
459. A 19-yea r-ol d gi rl who previ ous l y wa s hea l thy devel ops ba cteri a l meni ngi ti s . Wha t woul d you cons i der to be the drug of choi ce for thi s
s i tua ti on?
a . Ceftri a xone
b. Erythromyci n
c. Peni ci l l i n G
d. Peni ci l l i n V
e. Proca i ne peni ci l l i n
460. A pa ti ent i s bei ng trea ted wi th a n a nti bi oti c for a va ncomyci n-res i s ta nt enterococca l (VRE) i nfecti on. They cons ume a n over-the-counter
medi ca ti on conta i ni ng ephedri ne a nd devel op a s i gni fi ca nt s pi ke of bl ood pres s ure tha t l ea ds to a poundi ng hea da che. They a re tra ns ported to
the hos pi ta l . As pa rt of the work-up, bl ood tes ts i ndi ca te s ome bone ma rrow s uppres s i on. Whi ch a nti bi oti c i s mos t l i kel y a s s oci a ted wi th thi s
cl i ni ca l pi cture?
a . Azi thromyci n
b. Ci profl oxa ci n
c. Erythromyci n es tol a te
d. Genta mi ci n
e. Li nezol i d
461. You jus t s ta rted a rota ti on on the Infecti ous Di s ea s e cons ul t s ervi ce. It i s a t a n a ca demi c medi ca l center tha t i s i n a ma jor hub ci ty for
i nterna ti ona l tra vel , s o unus ua l or uncommon di s ea s es a re commonl y s een here. One of the pa ti ents i s recei vi ng etha mbutol . Wha t i s the mos t
l i kel y rea s on for whi ch thi s drug i s bei ng gi ven?
a . Amphoteri ci n-res i s ta nt Candida i nfecti on
b. E. coli i nfecti on, s evere, wi th profound fl ui d a nd el ectrol yte l os s
c. Entamoeba dispar i nfecti on (a mebi a s i s )
d. M. tuberculosis i nfecti on
e. Plasmodium (ma l a ri a l ) i nfecti on

Antimicrobial and Antiviral Pharmacology

Answers
413. The answer is e. (Brunton, pp 1468-1470, 1817; Katzung, p 832t.) Sul fona mi des cros s the pl a centa a nd enter the fetus i n concentra ti ons s uffi ci ent to
produce toxi c effects . They compete wi th a nd di s pl a ce bi l i rubi n from pl a s ma protei n bi ndi ng s i tes , ra i s i ng free bi l i rubi n l evel s a nd ca us i ng the
ja undi ce a nd other ma ni fes ta ti ons of kerni cterus . For the s a me rea s on, s ul fona mi des s houl d a l s o not be gi ven to neona tes , es peci a l l y prema ture
i nfa nts . Thi s woma n s houl d not ha ve been gi ven the s ul fona mi de, whether a l one or i n combi na ti on wi th tri methopri m. Ni trofura ntoi n us ua l l y
woul d be preferred for uncompl i ca ted uri na ry tra ct i nfecti ons i n pregna nt women. None of the other drugs a re a s s oci a ted wi th thi s neona ta l
hyperbi l i rubi nemi a : a moxi ci l l i n or other a mi nopeni ci l l i ns , a ; a zi thromyci n, b; erythromyci n, c; or cepha l os pori ns , fourth-genera ti on or other, d.
414. The answer is e. (Brunton, pp 1632-1633; Katzung, pp 863, 872, 875-876.) Res i s ta nce devel ops ra pi dl y when onl y zi dovudi ne or a nother nucl eos i de
a na l og i s us ed to trea t HIV. It mos t l i kel y i nvol ves decrea s ed i ncorpora ti on of the a cti ve meta bol i te i nto vi ra l DNA, or i ncrea s ed exci s i on of i t from
vi ra l DNA. Zi dovudi ne a nd other nucl eos i de a na l ogs mus t be phos phoryl a ted (not dephos phoryl a ted, a ) to form the a cti ve meta bol i te, the
di deoxynucl eoti de tri phos pha te. It occurs vi a the a cti ons of s evera l ki na s es i n hos t cel l s . Tha t l evel s of a cti ve meta bol i te i n CSF a re undetecta bl e
(a ) i s fa l s e. In mos t ca s es CSF concentra ti ons of a cti ve drug rea ch a bout 60% of thos e mea s ured i n the pl a s ma a t the s a me ti me. The ul ti ma te
effect of thes e drugs i s , i ndeed, to s top vi ra l nucl ei c a ci d s ynthes i s (c), but tha t occurs onl y a fter the a dmi ni s tered drug i s phos phoryl a ted (to form
the nucl eoti de/tri phos pha te). The a cti ve meta bol i te i s a good s ubs tra te for HIV revers e tra ns cri pta s e, but a very poor one for DNA pol ymera s es i n
hos t cel l s (a nd s o e i s i ncorrect).
And the ma i n a dvers e res pons es to or s i de effects a s s oci a ted wi th zi dovudi ne? They i ncl ude bone ma rrow toxi ci ty,
l eukopeni a /gra nul ocytopeni a , a nd a nemi a ; potenti a l l y s evere or pers i s tent i ns omni a a nd hea da che, na us ea , a nd vomi ti ng. The s i de effects
profi l es di ffer s omewha t a mong the other di deoxynucl eos i des .
415. The answer is e. (Brunton, pp 1474-1475; Katzung, pp 892-893, 898.) Al though s evera l of the a nti mi crobi a l a gents l i s ted here ca n ca us e one (or
perha ps two) of the a dvers e res pons es noted here, ni trofura ntoi n i s the mos t l i kel y ca us e. GI s i de effects (a norexi a , na us ea , a nd vomi ti ng) a re the
mos t common s i de effects ca us ed by thi s drug, whi ch i s s ti l l wi del y us ed for ma na gi ng a cute l ower uri na ry tra ct i nfecti ons (eg, from ma ny s tra i ns
of E. coli, s taphylococci, streptococci, Neisseria, Bacteroides). However, the drug ca n a l s o ca us e a cute or s uba cute pul mona ry rea cti ons s uch a s thos e
des cri bed, va ri ous hema tol ogi c rea cti ons (i n pa rti cul a r, l eukopeni a a nd thrombocytopeni a ), a nd peri phera l s ens ory a nd motor neuropa thi es .
Amoxi ci l l i n (a )a nd mos t other peni ci l l i ns ma y ca us e centra l neurotoxi ci ty i f pres ent a t extra ordi na ri l y hi gh pl a s ma l evel s . Beyond tha t,
a l l ergi c rea cti ons a re the mos t i mporta nt a dvers e res pons es . Pul mona ry, hema tol ogi c, a nd peri phera l neuropa thi c a dvers e res pons es a re not
a s s oci a ted wi th thes e drugs .
Azi thromyci ns (b) profi l e of a dvers e effects i s qui te s i mi l a r to tha t of erythromyci n a nd other ma crol i des , a nd tha t profi l e does not i ncl ude the
s i gns a nd s ymptoms noted here (GI ups et, mi l d to s evere, a re the mos t common compl a i nts , a nd a zi thromyci n ma y be ototoxi c, a property not
s ha red by other ma crol i des ).
Ci profl oxa ci n (c; or other fl uoroqui nol ones ) i s not l i kel y to ca us e a ny of the a dvers e res pons es noted. They a re qui te wel l tol era ted a nd ca us e a
va ri ety of s i de effects tha t, i n genera l , a re mi l d. If one were to reca l l one uni que toxi ci ty, i t woul d be a l tera ti ons of col l a gen meta bol i s m tha t
ma y l ea d to tendon rupture. There i s a l s o evi dence tha t the drug ca n prol ong the QT i nterva l , l ea di ng to a rrhythmi a s , pa rti cul a rl y i n pa ti ents wi th
l ong QT s yndrome.
Is oni a zi d (d) ca n ca us e peri phera l neuropa thy (ma i nl y from a drug-i nduced pyri doxi ne defi ci ency) a nd hepa totoxi ci ty. Pul mona ry a nd bl eedi ng
probl ems a re not a t a l l common i n terms of drug-i nduced probl ems .
416. The answer is c. (Brunton, pp 1521-1523, 1534-1535; Katzung, p 815.) More s o tha n a ny other a nti bi oti c, cl i nda myci n i s a s s oci a ted wi th the hi ghes t
ri s k of AAPMC (C. difficile s uperi nfecti on). Thus , i t i s ma i nl y res erved for certa i n a na erobi c i nfecti ons l oca ted outs i de the CNS (s us cepti bl e
a na erobes i ncl ude B. fragilis, Fusobacterium, a nd Clostridium perfringens, pl us a na erobi c streptococci). Tetra cycl i ne us e i s a l s o a s s oci a ted wi th AAPMC.
The phenomenon i s not typi ca l l y a ttri buted to trea tment wi th a moxi ci l l i n (a ), a zi thromyci n (b), or the tri methopri m-s ul fa methoxa zol e combi na ti on
(e). Metroni da zol e (d) or va ncomyci n (not l i s ted) a re cons i dered preferred trea tments for AAPMCa nd the offendi ng drug s houl d be s topped a s
s oon a s AAPMC i s s us pected.
417. The answer is c. (Brunton, pp 1428-1430, 1523; Katzung, pp 891-892, 927-929.) Metroni da zol e i s di s tri buted to a l l body fl ui ds a nd ti s s ues . Its
s pectrum of a cti vi ty i s l i mi ted l a rgel y to a na erobi c ba cteri a i ncl udi ng B. fragilisa nd certa i n protozoa . It i s cons i dered to be the drug of choi ce for
tri chomoni a s i s i n fema l es a nd ca rri er s ta tes i n ma l es , a s wel l a s for i ntes ti na l i nfecti ons wi th Giardia lamblia.
Doxycycl i ne (a ), emeti ne (b, a n a nti protozoa l ), penta mi di ne (d; us ed for trea tment of P. jirovecii, pneumoni a , or prophyl a cti ca l l y for tha t condi ti on
i n hi gh-ri s k HIV-pos i ti ve pa ti ents ), a nd pyra zi na mi de (e, a ba cteri ci da l a gent us ed for M. tuberculosis i nfecti ons ) woul d not be a ppropri a te for the
pa ti ent des cri bed i n the ques ti on.
418. The answer is b. (Brunton, pp 1409-1415; Katzung, pp 923-924.) Hemol ys i s i s the mos t common a nd s eri ous a dvers e res pons e to pri ma -qui ne. The
ri s k i s cl ea rl y hi ghes t i n pa ti ents who ha ve red cel l defi ci enci es i n gl ucos e-6-phos pha te dehydrogena s e, a heri ta bl e tra i t a nd one tha t ca n be
s creened for before gi vi ng the drug. (Thi s G6PD defi ci ency i s more common i n bl a cks , a nd whi tes wi th da rker s ki n [eg, s ome from certa i n regi ons of
the Mi ddl e Ea s t or the Medi terra nea n countri es ].) Rega rdl es s of the res ul ts of pretrea tment s creeni ng, peri odi c bl ood counts s houl d be done, a nd
the uri ne checked for unus ua l da rkeni ng (i ndi ca ti ng the pres ence of hemogl obi n from l ys ed red cel l s ), duri ng trea tment.
El ectrophys i ol ogi c cha nges , whether they a ffect the conducti ng ti s s ues of the hea rt (a ) or the bra i n (e) a re not commonl y a s s oci a ted wi th pri ma qui ne. The s a me a ppl i es to rena l (c) or reti na l (d) pa thol ogy, whi ch occur a t fa r l ower ra tes tha n the hemol yti c di s ea s e.
Note: If you a ns wered reti nopa thy (d), you were proba bl y thi nki ng a bout chl oroqui ne, beca us e tha t a dvers e res pons e (a ccompa ni ed by vi s ua l
cha nges ) i s a s s oci a ted wi th tha t other commonl y us ed a nti ma l a ri a l drug.
419. The answer is e. (Brunton, pp 1521-1522, 1537-1538; Katzung, pp 817, 819.) Li nezol i d i s a ba cteri os ta ti c (not ci da l , s o a ns wer a i s wrong) i nhi bi tor of
protei n s ynthes i s . Its uni que mecha ni s m of a cti on, bi ndi ng to the 23S porti on of the 50S ri bos oma l s ubuni t, ul ti ma tel y bl ocks forma ti on of the
i ni ti a tor compl ex tha t i s neces s a ry for ba cteri a l repl i ca ti on. Thi s uni que mecha ni s m mea ns l i nezol i d i s not s us cepti bl e to cros s -res i s ta nce tha t
ma y ha ve devel oped to other a nti bi oti cs , but the more the drug i s us ed the grea ter the l i kel i hood tha t res i s ta nce to i t wi l l devel op.
Li nezol i d i s , i ndeed, the preferred drug for va ncomyci n-res i s ta nt enterococci . Va ncomyci n i s often us ed a s a drug of l a s t res ort for s eri ous
i nfecti ons tha t ca nnot be trea ted wi th fi rs t-l i ne a l terna ti ves . Another ma jor us e i s for methi ci l l i n-res i s ta nt Staph. aureus, for whi ch l i nezol i d a nd

va ncomyci n s eem to be equa l l y effi ca ci ous . (There a re other a pproved us es for l i nezol i d, but s i nce few ba cteri a a re res i s ta nt to i ts o fa ri t
s houl d be us ed s pa ri ngl y, onl y when a bs ol utel y needed.) It i s not a t a l l i ndi ca ted for rel a ti vel y mi nor i nfecti ons , es peci a l l y thos e wi th gra mnega ti ve ca us es (b). It i s not a preferred a l terna ti ve to a moxi ci l l i n for oti ti s medi a (c). Doxycycl i ne, not l i nezol i d, i s the preferred a l terna ti ve to
ci profl oxa ci n for a nthra x prophyl a xi s or trea tment (d).
The mos t s eri ous a dvers e effect a s s oci a ted wi th l i nezol i d i s revers i bl e myel os uppres s i on. Compl ete bl ood counts need to be done a t l ea s t
once a week i f thi s drug i s bei ng a dmi ni s tered to myel os uppres s ed pa ti ents (i ncl udi ng thos e ta ki ng other myel os uppres s i ve drugs ) or i f l i nezol i d
thera py l a s ts more tha n a bout 14 da ys .
420. The answer is d. (Brunton, pp 1012-1013, 1524-1525, 1529, 1534, 1549-1554; Katzung, pp 840-842, 848, 1160t.) Ri fa mpi n i nduces cytochrome P450
enzymes , whi ch ca us es a s i gni fi ca nt i ncrea s e i n el i mi na ti on ra tes of ma ny i ntera cti ng drugs , s uch a s ora l contra cepti ves , a nti coa gul a nts ,
ketocona zol e, cycl os pori ne, a nd chl ora mpheni col . It a l s o promotes uri na ry excreti on of metha done, whi ch ma y preci pi ta te wi thdra wa l .
Etha mbutol (a ), i s oni a zi d (b), pyra zi na mi de (c), a nd vi ta mi n B 6 (e) a re not P450 i nducers , a l though the meta bol i s m of s ome of thes e drugs ca n be
i nduced by ri fa mpi n.
421. The answer is b. (Brunton, pp 1650-1654; Katzung, pp 870-871, 878-881.) Protea s e i nhi bi tors , a s a cl a s s , tend to ca us e hypergl ycemi a (proba bl y
i nvol ves i ns ul i n res i s ta nce i n pa renchyma l cel l s ) a nd hyperl i pi demi a (preci s e mecha ni s m not known).
The other a dvers e res pons es l i s ted a re more typi ca l of thos e ca us ed by nucl eos i de revers e tra ns cri pta s e i nhi bi tors (NRTIs ; zi dovudi ne, others ),
a nd i t i s worthwhi l e commenti ng on tha t here. Anemi a s a nd neutropeni a (myel os uppres s i on, a ) a re fa i rl y common wi th NRTIs . The ri s k of NRTIi nduced l a cti c a ci dos i s i s ra re, but the ri s ks go up s i gni fi ca ntl y i f the pa ti ent recei ves more tha n one NRTI. La cti c a ci dos i s tends to devel op a l ong
wi th hepa tomega l y a nd fa tty l i ver degenera ti on (s tea tos i s ). Peri phera l neuropa thi es (d) tend to be a s s oci a ted wi th di da nos i ne a nd s ta vudi ne but
not wi th other members of the NRTI cl a s s i ncl udi ng the prototype, zi dovudi ne. Pa ncrea ti ti s (e) i s a l s o ma i nl y a s s oci a ted wi th NRTIs (a nd a mong
the cl a s s , ma i nl y di da nos i ne a nd s ta vudi ne), not wi th protea s e i nhi bi tors .
422. The answer is c. (Brunton, pp 1409-1410, 1534, 1819; Katzung, pp 919t, 923-924.) Pri ma qui ne i s effecti ve a ga i ns t the extra erythrocyti c forms of P. vivax
a nd P. ovale, a nd i s a l s o i ndi ca ted for s ome ca s es of P. falciparum. It hel ps era di ca te pl a s modi a from the l i ver, a nd i n doi ng s o i t not onl y provi des a
cure but a l s o hel ps prevent rel a ps e.
Chl orogua ni de (a ) i s a very ol d a nti ma l a ri a l drug but i s s el dom us ed i ns tea d of pri ma qui ne. Chl oroqui ne (b) woul d not be us ed beca us e i t i s
effecti ve onl y i n the erythrocyti c pha s e of the ma l a ri a l pa ra s i tes l i fe s pa n: i t wi l l not work a ga i ns t the exoerythrocyti c forms of ma l a ri a pa ra s i tes ,
nor ca n i t s erve a s pri ma ry preventi on. Thi s 4-a mi noqui nol i ne deri va ti ve i s a wea k ba s e tha t s el ecti vel y concentra tes i n i nfected red bl ood cel l s .
There i t proba bl y i nterferes wi th the a bi l i ty of plasmodia to convert hemea toxi n to the pa ra s i teto nontoxi c meta bol i tes .
Pyri metha mi ne (d) a nd qui na cri ne (e) a re not s ui ta bl e a gents for trea ti ng the pa ti ent des cri bed i n the ques ti on.
423. The answer is e. (Brunton, pp 1521, 1537, 1539-1542, 1545; Katzung, pp 798t, 802-803, 808.) Va ncomyci n, whi ch mus t be gi ven i ntra venous l y, ha s a n
a nti mi crobi a l s pectrum cl os es t to thos e of peni ci l l i ns a nd cepha l os pori ns , a nd i t does not cros s rea ct i n i mmunol ogi ca l l y s us cepti bl e pa ti ents .
Li ke peni ci l l i ns a nd cepha l os pori ns , there i s a growi ng ri s k of res i s ta nce to va ncomyci n (pa rti cul a rl y i n hos pi ta l s etti ngs , where the drug i s ma i nl y
us ed), but i t nonethel es s i s cons i dered the bes t (i f not the l a s t res ort) drug for thes e pa ti ents . Cl otri ma zol e (a ) i s a n a nti funga l drug, ma i nl y us ed
for s uch funga l i nfecti ons a s thos e i nvol vi ng Candida. Metroni da zol e (c) i s a l s o us ed ma i nl y for s ys temi c or uri na ry tra ct funga l i nfecti ons , a l though
i t does ha ve s ome a nti ba cteri a l a cti vi ty. Genta mi ci n (b) woul d be i na ppropri a te, i n pa rt beca us e i ts s pectrum of a cti vi ty i s not l i kel y to i ncl ude
orga ni s ms ki l l ed or i nhi bi ted by peni ci l l i ns , cepha l os pori ns , or va ncomyci n. The s a me a ppl i es to tetra cycl i nes (d).
424. The answer is e. (Brunton, pp 1632-1633; Katzung, pp 863f, 872t, 875-876, 889.) One of zi dovudi nes ma jor a dvers e effects i s bone ma rrow depres s i on
tha t a ppea rs to be dos e- a nd l ength-of-trea tment-dependent. The s everi ty of the di s ea s e a nd a l ow CD4 count contri bute to the bone ma rrow
depres s i on.
425. The answer is c. (Brunton, pp 1479t, 1488; Katzung, pp 790-797.) Unl i ke the other l i s ted drugs , oxa ci l l i n i s res i s ta nt to peni ci l l i na s e (-l a cta ma s e)
a nd i t i s one of a rel a ti vel y few peni ci l l i ns cl a s s i fi ed a s a nti -s ta phyl ococca l a gents . (The ma i n other ones a re cl oxa ci l l i n, di cl oxa ci l l i n, a nd
na fci l l i n.) Oxa ci l l i n a nd the rel a ted drugs a re genera l l y s peci fi c for gra m-pos i ti ve mi croorga ni s ms . The other drugs l i s ted a re broa d- (or extended-)
s pectrum peni ci l l i ns . Peni ci l l i n G (the i ntra venous dos a ge form) or V (ora l ) i s i ndi ca ted for s ta ph i nfecti ons provi ded the s tra i ns do ha ve l a cta ma s e a cti vi ty.
426. The answer is a. (Brunton, pp 1507-1509, 1512-1515, 1543; Katzung, pp 821-827.) Of a l l the protei n s ynthes i s i nhi bi tors , onl y the a mi nogl ycos i des
routi nel y ca us e ba cteri a l dea th (ba cteri ci da l effect), not jus t s uppres s i on of growth or repl i ca ti on (ba cteri os ta ti c effect). Cl i nda myci n (b) a nd
erythromyci n (c) ha ve ba cteri os ta ti c effects , the ma i n mecha ni s m bei ng bi ndi ng to the 50S s ubuni t of ba cteri a l ri bos omes . Li nezol i d (d) i s a l s o
ma i nl y a ba cteri os ta ti c drug (a ga i ns t staphylococci, a nd enterococci, for exa mpl e), a l though i n s ome ca s es i t ca n exert ba cteri ci da l effects on s ome
s tra i ns of streptococci. Tetra cycl i nes (e) a re l a rgel y ba cteri os ta ti c a nd ha ve a broa d s pectrum of a cti vi ty. They bi nd revers i bl y to the ri bos oma l 30S
s ubuni t. The ul ti ma te effect i s i nhi bi ti on of a mi no a ci d i ncorpora ti on i nto pepti des tha t otherwi s e woul d be formed vi a RNA a cti vi ty.
427. The answer is b. (Katzung, pp 869-876.) Zi dovudi ne competi ti vel y i nhi bi ts HIV-1 nucl eos i de revers e tra ns cri pta s e. Zi dovudi ne i s a prodrug: i t mus t
be meta bol i ca l l y a cti va ted (phos phoryl a ted) to zi dovudi ne tri phos pha te. The a cti ve meta bol i te i s i ncorpora ted i n the growi ng vi ra l DNA cha i n, a nd
i n doi ng s o prevents revers e tra ns cri pta s e from a ddi ng more ba s es . As a res ul t, DNA s tra nd growth s tops . Zi dovudi ne decrea s es the ra te of cl i ni ca l
di s ea s e progres s i on a nd prol ongs s urvi va l i n HIV-i nfected pa ti ents when us ed a s pa rt of a mul ti drug trea tment pl a n.
An exa mpl e of a nonnucl eos i de revers e tra ns cri pta s e i nhi bi tor (a ) i s efa vi renz. Unl i ke zi dovudi ne, i t i s not a s tructura l a na l og of na tura l l y
occurri ng nucl eos i des , a nd does not work by ca us i ng prema ture termi na ti on of DNA growth. It a nd other nonnucl eos i de revers e tra ns cri pta s e
i nhi bi tors work ma i nl y by di rectl y bi ndi ng to, a nd i nhi bi ti ng, revers e tra ns cri pta s e.
Protea s e i nhi bi tors (e) bl ock the fi na l s tep i n HIV ma tura ti on. Reca l l tha t HIV protei ns a re s ynthes i zed together a s one l ong pepti de tha t i s
l a rgel y wi thout bi ol ogi ca l a cti vi ty. Protea s e cl ea ves the pol yprotei n i nto s evera l s epa ra tea nd functi ona l protei ns . Wi thout thi s fi na l proces s i ng
s tep HIV ca nnot form new, a nd i nfecti ous , vi rus pa rti cl es . Typi ca l l y, protea s e i nhi bi tor thera py i nvol ves two drugs , l opi na vi r pl us ri tona vi r bei ng the
mos t common.
428. The answer is d. (Brunton, pp 1629-1640; Katzung, pp 834-836, 1160t.) Ba cteri a l DNA gyra s e i s compos ed of four s ubuni ts . Ci profl oxa ci n, l evofl oxa ci n,
a nd other qui nol ones bi nd to the s tra nd-cutti ng s ubuni ts a nd i n doi ng s o i nhi bi ts ba cteri a l growth a nd repl i ca ti on. (The ori gi na l member of thi s
group wa s na l i di xi c a ci d.) Thes e a nti bi oti cs ha ve a broa d s pectrum of a nti bi oti c a cti vi ty a nd a re rel a ti vel y free from common or s eri ous s i de effects
(s ome members a s s oci a ted wi th s i gni fi ca nt toxi ci ti es were wi thdra wn from the ma rket), a nd tend not to be a s s oci a ted wi th ra pi dl y devel opi ng

a nti bi oti c tol era nce to thei r a cti ons .

429. The answer is e. (Brunton, pp 1434-1435; Katzung, pp 929-932, 935.) Penta mi di ne i s effecti ve i n pneumoni a ca us ed by P. jiroveci. (So i s the
tri methopri m-s ul fa methoxa zol e combi na ti on, not l i s ted.) Thi s protozoa l di s ea s e us ua l l y occurs i n i mmunodefi ci ent pa ti ents , s uch a s thos e wi th
AIDS. Ni furti mox (c) i s effecti ve i n trypa nos omi a s i s , a nd metroni da zol e (b) i n a mebi a s i s a nd l ei s hma ni a s i s , a s wel l a s i n a na erobi c ba cteri a l
i nfecti ons . Peni ci l l i ns (a or d) a re not cons i dered drugs of choi ce for protozoa l di s ea s es s uch a s thos e menti oned here.
430. The answer is c. (Brunton, pp 599, 692, 1086-1088, 1094, 1400, 1410-1411, 1414, 1421, 1468-1470; Katzung, pp 833-834.) Tri methopri m i nhi bi ts
di hydrofol i c a ci d reducta s e. Sul fa methoxa zol e i nhi bi ts p-a mi nobenzoi c a ci d (PABA) from bei ng i ncorpora ted i nto fol i c a ci d by competi ti ve
i nhi bi ti on of di hydropteroa te s yntha s e. Ei ther a cti on i nhi bi ts the s ynthes i s of tetra hydrofol i c a ci d, but by gi vi ng the combi na ti on we i nhi bi t two
es s enti a l a nd sequential s teps i n the forma ti on of fol a te-dependent meta bol i tes tha t a re neces s a ry for ba cteri a l vi a bi l i ty a nd repl i ca ti on.
431. The answer is b. (Brunton, pp 1478-1481, 1494t, 1496-1499; Katzung, pp 797-801, 807.) Cefoteta n (s econd-genera ti on cepha l os pori n)a s wel l a s
cefopera zone (thi rd-genera ti on) i nhi bi t a l dehyde dehydrogena s e a nd ca us e a ccumul a ti on of a ceta l dehyde (a s does di s ul fi ra m, whi ch i s us ed to
curb a l cohol i nta ke), a nd s o ca n ca us e a l l the typi ca l a nd potenti a l l y s eri ous cons equences of a di s ul fi ra m-l i ke rea cti on. Cefmeta zol e, a s econdgenera ti on cepha l os pori n, a nd metroni da zol e, a l s o ca us e a s i mi l a r a dvers e i ntera cti on wi th a l cohol . (Note tha t thes e three cepha l os pori ns a re
a l s o the ones tha t a re a s s oci a ted wi th vi ta mi n K-rel a ted bl eedi ng probl ems , a s a ddres s ed i n Ques ti on 434.)
Erythromyci n (whether a dmi ni s tered a s the ba s e or one of the common s a l ts , eg, ethyl s ucci na te, es tol a te, or s tea ra te) ca n i nhi bi t the hepa ti c
P450 s ys tem s uffi ci ent to ca us e a dvers e i ntera cti ons wi th (exces s i ve effects of) s uch drugs a s wa rfa ri n, ca rba ma zepi ne, a nd theophyl l i ne. However,
ba s ed on current evi dence there i s no s peci fi c i nhi bi ti on of a l dehyde dehydrogena s e, nor res ul ti ng a ccumul a ti on of a ceta l dehyde, tha t woul d
correctl y qua l i fy a s a di s ul fi ra m-l i ke i ntera cti on.
Amoxi ci l l i n, peni ci l l i n G, a nd other peni ci l l i ns do not pa rti ci pa te i n di s ul fi ra m-l i ke rea cti ons .
Li nezol i d i nhi bi ts monoa mi ne oxi da s e (MAO), a l bei t wea kl y, a nd s o ca n tri gger potenti a l l y s i gni fi ca nt a dvers e i ntera cti ons i n pers ons recei vi ng
s uch s ympa thomi meti cs a s coca i ne, ephedri ne, or ps eudoephedri ne; or thos e cons umi ng tyra mi ne-ri ch foods or bevera ges . However, the drug
does not i nhi bi t a l cohol meta bol i s m or ca us e the a dvers e res pons es noted i n thi s ques ti on.
432. The answer is d. (Brunton, pp 1470-1474, 1532-1533, 1560; Katzung, pp 835-837.) Levofl oxa ci n or a nother qui nol one bl ocks ba cteri a l DNA s ynthes i s by
i nhi bi ti ng ba cteri a l DNA gyra s e (topoi s omera s e II). Ei ther woul d be a good choi ce, not onl y beca us e of thei r a nti bi oti c s pectrum of a cti vi ty, but
a l s o beca us e the worki ng hypothes i s i s tha t were dea l i ng wi th a communi ty-a cqui red res pi ra tory i nfecti on ca us ed by res i s ta nt ba cteri a . The
res i s ta nce i s l i kel y to render peni ci l l i ns (a , e), cepha l os pori ns (b), a nd even erythromyci n or other ma crol i des (c) i neffecti ve. Res i s ta nce to
fl uoroqui nol ones ha s not become tha t much of a probl em yet. Note tha t cefa zol i n (b), a fi rs t-genera ti on cepha l os pori n, i s i neffecti ve a ga i ns t
pneumococci , a nd i s ma i nl y s ui ta bl e onl y for i nfecti ons wi th S. aureus or s treptococci tha t a re not res i s ta nt to peni ci l l i ns . Va ncomyci n (f) mi ght
ul ti ma tel y be needed, but s i nce i t mus t be gi ven pa rentera l l y (there wa s no menti on tha t the pa ti ent wa s una bl e to ta ke ora l medi ca ti ons ) i t
woul d be prema ture to us e thi s otherwi s e l a s t res ort a nti bi oti c.
433. The answer is e. (Brunton, pp 1521-1522, 1537, 1539-1542; Katzung, pp 802-803.) The onl y s ui ta bl e drug l i s ted for thi s potenti a l l y fa ta l i nfecti on i s
va ncomyci n. The fi ndi ng of MRSA i s not uncommon, pa rti cul a rl y i n hos pi ta l s , renderi ng thera py wi th peni ci l l i ns (i ncl udi ng a moxi ci l l i n wi th
cl a vul a na te, the -l a cta ma s e i nhi bi tor; a ) i neffecti ve. Ma crol i des (i ncl udi ng cl i nda myci n, b; a nd erythromyci n, c) a re a l s o uns ui ta bl e, i n pa rt
beca us e of a growi ng res i s ta nce probl em. Res i s ta nce to the tri methopri m-s ul fa -methoxa zol e (d) combi na ti on i s a l s o a ma jor probl em, rega rdl es s
of the i nfecti ons for whi ch thi s fol a te reducta s e i nhi bi tor thera py i s pres cri bed.
434. The answer is c. (Brunton, pp 1494t, 1525; Katzung, pp 800-801.) Cefmeta zol e a nd cefoteta n, both s econd-genera ti on cepha l os pori ns , a nd
cefopera zone (thi rd genera ti on) ca n i nterfere wi th hepa ti c vi ta mi n K meta bol i s m, ca us i ng hypoprothrombi nemi a a nd wha t a mounts to a defi ci ency
of vi ta mi n K-dependent cl otti ng fa ctor a cti vi ty. Beca us e thi s i s the genera l mecha ni s m by whi ch wa rfa ri n exerts i ts a nti coa gul a nt effects , combi ned
us e of one of thes e cepha l os pori ns ca n ca us e further (a nd potenti a l l y da ngerous ) prol onga ti ons of the Interna ti ona l Norma l i zed Ra ti o (or
prothrombi n ti me); the cl i ni ca l cons equence ca n be s ponta neous , prol onged, or exces s i ve bl eedi ng. One s houl d a l s o be ca uti ous when thes e
cepha l os pori ns a re gi ven to pa ti ents ta ki ng a s pi ri n or other a nti pl a tel et drugs (eg, cl opi dogrel ) or thrombol yti cs .
Al though mos t cepha l os pori ns a re excreted uncha nged by the ki dneys , rena l fa i l ure (b, es peci a l l y s evere a nd a cute) s el dom occurs wi th thes e
or other cepha l os pori ns . There i s no l i nk between a dmi ni s tra ti on of even hi gh dos es of thes e cepha l os pori ns (or others ) wi th the devel opment of
a cute hea rt fa i l ure (a ). Hypertens i on (d) or other s ubs ta nti a l cha nges of bl ood pres s ure a re not a s s oci a ted wi th cepha l os pori ns , nor a re thes e
drugs ototoxi c (e).
Al though a hi s tory of s evere a l l ergi c rea cti ons to peni ci l l i ns requi res ca uti on when cons i deri ng a cepha l os pori n (i ndeed, cepha l os pori ns
s houl d be a voi ded, i f pos s i bl e, i n s uch pa ti ents ), there i s nothi ng uni que a bout cefmeta zol e, cefopera zone, or cefoteta n i n thi s context. None of
the cepha l os pori ns a re contra i ndi ca ted for pa ti ents wi th mi l d a l l ergi c rea cti ons due to peni ci l l i ns .
435. The answer is a. (Brunton, pp 1521, 1542-1543, 1545; Katzung, pp 803-804, 808.) Da ptomyci n, cl a s s i fi ed a s a cycl i c l i popepti de a nd ra pi dl y
ba cteri ci da l a ga i ns t nea rl y a l l gra m-pos i ti ve ba cteri a , i s uni quel y a s s oci a ted (a mong a nti mi crobi a l a gents ) wi th myopa thy a nd i ts typi ca l s i gns
a nd s ymptoms . Da i l y dos a ges currentl y recommended pos e a l ow ri s k of myos i ti s a nd myopa thy, but neverthel es s crea ti ne ki na s e l evel s (ma rker
of mus cl e da ma ge) s houl d be mea s ured peri odi ca l l y duri ng the cours e of thera py a nd the pa ti ent s houl d be a dvi s ed to report a ny rel eva nt
s ymptoms a t once.
None of the other drugs l i s ted a re a s s oci a ted wi th myopa thy. GI s i de effects a re qui te common wi th us ua l dos es of erythromyci n (b) a nd other
ma crol i des , a nd s udden ca rdi a c dea th (from QT prol onga ti on) ha s been reported when erythromyci n bl ood l evel s get too hi gh. The es tol a te s a l t of
erythromyci n es tol a te (s a l t) ma y ca us e chol es ta ti c hepa ti ti s . Genta mi ci n (c, a nd mos t other a mi nogl ycos i des ) genera l l y ca us e few mi nor s i de
effects ; thei r ma jor a dvers e effects a re ototoxi ci ty a nd nephrotoxi ci ty. The ma i n common s i de effects a s s oci a ted wi th l i nezol i d (d) a re na us ea a nd
di a rrhea , a nd the potenti a l for us ua l l y revers i bl e myel os uppres s i on a nd pa ncytopeni a . Va ncomyci n (e) tends to ca us e fa ci a l a nd neck fl us hi ng,
pruri tus , a nd urti ca ri a (s o-ca l l ed red ma n s yndrome), proba bl y s econda ry to l oca l hi s ta mi ne rel ea s e; hi s ta mi ne rel ea s e ma y a l s o contri bute to
the devel opment of ta chyca rdi a a nd hypotens i on. As wi th the a mi nogl ycos i des , va ncomyci n i s ototoxi c a t hi gh pl a s ma l evel s .
436. The answer is f. (Brunton, pp 1520-1526, 1528, 1532, 1544, 1817; Katzung, pp 810-813.) Tetra cycl i nes i ntera ct wi th ma ny pol yva l ent meta l ca ti ons s uch
tha t a nti bi oti c a bs orpti on from the gut (i e, bi oa va i l a bi l i ty) i s reduced. The extent of thi s reducti on ca n be cl i ni ca l l y s i gni fi ca nt, tha t i s , l ea di ng to
i na dequa te bl ood l evel s a nd effects of the a nti bi oti c.
Ca l ci um i s , of cours e, a bunda nt i n da i ry products , s ome OTC a nta ci d products , a nd i n s uppl ements touted for bone hea l th. Other meta l s tha t
ca n i ntera ct wi th tetra cycl i nes by thi s mecha ni s m i ncl ude i ron, ma gnes i um, a l umi num, a nd zi nc. Note tha t one or s evera l of thes e i ntera cta nts a re

typi ca l l y found i n a nta ci d products , mul ti vi ta mi n/mi nera l s uppl ements , a nd even (the trend i s growi ng) i n s ome (mi nera l -) forti fi ed foods , s uch a s
cerea l s , a nd ci trus jui ces .
Al though foods (i n genera l ) ma y i nterfere wi th the ora l a bs orpti on of s evera l other a nti bi oti cs , the ca ti on-a nti bi oti c i ntera cti on i s s peci fi c for
a nd i mporta nt to the tetra cycl i nes .
437. The answer is d. (Brunton, pp 1429-1430, 1523; Katzung, pp 891-892, 927-929.) Among the i ndi ca ti ons for metroni da zol e i s ma na gement of C. difficile
(a nd other clostridia) i nfecti ons , i ncl udi ng AAPMC. Ma ny other obl i ga te a na erobes , ma i nl y gra m-pos i ti ve ba ci l l i , wi l l res pond. So wi l l va ri ous types
of i ntes ti na l or s ys temi c a mebi a s i s i nfecti ons (the drug i s genera l l y us ed a djuncti vel y wi th i odoqui nol for gut i nfecti ons s ymptoma ti c
a mebi a s i s ); a nd for gi a rdi a s i s a nd Trichomonas vaginalis i nfecti ons (genera l l y the drug of choi ce). An a l terna ti ve to metroni da zol e i n the s etti ng of
AAPMC woul d be va ncomyci n.
None of the other drugs l i s ted woul d be s ui ta bl e. Amphoteri ci n B (a ) i s a n a nti funga l a gent. Cl i nda myci n (b) i s not a t a l l the preferred
trea tment; i ndeed, i t i s the mos t l i kel y ca us e of the s uperi nfecti on. Genta mi ci n (c) i s not effecti ve a ga i ns t a na erobes , C. difficile of cours e i ncl uded.
Tri m-ethopri m pl us s ul fa methoxa zol e (e) i s not i ndi ca ted for C. difficile i nfecti ons . The ma i n us es of thi s broa d-s pectrum a nti bi oti c combi na ti on
a re trea ti ng mos t uncompl i ca ted uri na ry tra ct i nfecti ons (es peci a l l y i f chroni c or recurrent), a nd trea ti ng pneumoni a a nd other P. jiroveci i nfecti ons
(ma i nl y i n i mmunocompromi s ed pa ti ents wi th AIDS, ca ncer, or orga n tra ns pl a nts ).
I hope you ha ve l ea rned tha t the mos t effecti ve trea tment for entera l C. difficile i nfecti ons , es peci a l l y thos e tha t a re s evere or refra ctory to
ordi na ri l y preferred drug thera py, i s not s ome bra nd new medi ci ne. It i s a fecal transplant, a nd i n es s ence, i t i nvol ves jus t wha t the term i mpl i es .
The wonders of modern medi ci ne!
438. The answer is b. (Brunton, pp 1012, 1327-1328, 1529, 1534; Katzung, pp 813-814.) Erythromyci n (a nd cl i nda myci n) a re ma crol i de a nti bi oti cs tha t ra ther
powerful l y i nhi bi t meta bol i s m of ma ny other drugs , ra i s i ng bl ood l evel s of the i ntera cta nts . Wa rfa ri n i s el i mi na ted a l mos t excl us i vel y by
meta bol i s m, a nd s o the exces s i ve effects des cri bed i n the ques ti on a re qui te l i kel y. Al though a zi thromyci n (a ) i s a ma crol i de, i t i s not a P-450
i nhi bi tor (or i nducer). Genta mi ci n (c) a nd other a mi nogl yco-s i des a re el i mi na ted s ol el y by rena l excreti on a nd ha ve no di rect effects on hepa ti c
drug meta bol i s m or a ny other i mporta nt a s pects of l i ver functi on. The s a me a ppl i es to peni ci l l i n G (d) a nd other peni ci l l i ns , i ncl udi ng thos e
cl a s s i fi ed a s peni ci l l i na s e-res i s ta nt, broa d s pectrum (a mi nopeni ci l l i ns ), a nd extended s pectrum (ma i nl y us ed a ga i ns t Pseudomonas i n
combi na ti on wi th a n a mi nogl ycos i de). Ri fa mpi n (e) i s a P-450 i nducer, not a n i nhi bi tor, a nd i s obvi ous l y a ca us e of ma ny drug-drug i ntera cti ons a s
a res ul t of i ts s ti mul a tory effect on hepa ti c meta bol i s m.
439. The answer is a. (Brunton, pp 1483, 1487-1490, 1814; Katzung, pp 39t, 795-796.) Compa red wi th a mpi ci l l i n, a moxi ci l l i n a bs orpti on i s a ffected l es s by
the pres ence of food i n the gut, s o the bi oa va i l a bi l i ty i s better a nd dos i ng ma y be more conveni ent for ma ny pa ti ents . Both drugs a re i na cti va ted
by -l a cta ma s es , a nd s o nei ther i s effecti ve a ga i ns t peni ci l l i na s e-produci ng orga ni s ms (b). Both drugs a re broa d s pectrum (c) a nd s ha re the s a me
a nti mi crobi a l s pectrum a s peni ci l l i n G, a nd a ddi ti ona l l y a re effecti ve, for exa mpl e, a ga i ns t E. coli, H. influenzae, Salmonella, a nd Shigella; both a l s o
ca n cros s rea ct i n pa ti ents wi th a hi s tory of hypers ens i ti vi ty rea cti ons (d) to other peni ci l l i ns . Nei ther a moxi ci l l i n nor a mpi ci l l i n ha s
a nti ps eudomona l a cti vi ty. The peni ci l l i ns ca pa bl e of tha t a re the extended-s pectrum peni ci l l i ns , for exa mpl e, pi pera ci l l i n a nd ti ca rci l l i n; note tha t
the extended-s pectrum peni ci l l i ns a re s us cepti bl e to i na cti va ti on by -l a cta ma s e a nd s o a re not effecti ve a ga i ns t s evera l s tra i ns of orga ni s ms ,
nota bl y S. aureus.
440. The answer is c. (Brunton, pp 1477-1493, 1494-1499; Katzung, pp 796, 800.) Unl es s there a re no rea s ona bl e a l terna ti ves , cepha l os pori ns s houl d be
a voi ded for pa ti ents wi th pri or s evere a l l ergi c res pons es to peni ci l l i ns beca us e of thei r cros s -rea cti vi ty. None of the other drugs or drug groups
l i s ted here cros s rea ct i n peni ci l l i n-s ens i ti ve pa ti ents . Mi l d a l l ergi c rea cti ons to peni ci l l i ns do not neces s a ri l y contra i ndi ca te cepha l os pori n
us e.
441. The answer is c. (Brunton, pp 1516-1517; Katzung, pp 821-826.) Ami ka ci n s ta nds out a mong a l l the a mi nogl ycos i des i n two ma i n wa ys : i t ha s the
broa des t s pectrum a ga i ns t gra m-nega ti ve ba ci l l i , a nd i t i s l ea s t s us cepti bl e to ba cteri a l enzymes tha t i na cti va te a mi nogl ycos i des a nd l ea d to
res i s ta nce. (Reca l l tha t a mong gra m-nega ti ve ba cteri a , geneti c i nforma ti on tha t codes for the producti on of thes e i na cti va ti ng enzymes i s
tra ns ferred vi a R fa ctors .)
442. The answer is b. (Brunton, pp 1424, 1571-1575; Katzung, pp 849-852, 934.) Amphoteri ci n B, gi ven i ntra venous l y, often a l ters ki dney functi on. The mos t
common a nd mos t ea s i l y detected ma ni fes ta ti on of thi s i s decrea s ed crea ti ni ne cl ea ra nce. If thi s occurs , the dos e mus t be reduced. Amphoteri ci n
B a l s o commonl y i ncrea s es pota s s i um (K+) l os s , l ea di ng to hypoka l emi a ; a nd ca n ca us e a nemi a a nd neurol ogi c s ymptoms . A l i pos oma l
prepa ra ti on of a mphoteri ci n B ma y reduce the i nci dence of rena l a nd neurol ogi c toxi ci ty (s ee expl a na ti on for the next ques ti on). Va ncomyci n (e)
ma y ca us e rena l da ma ge, but the overa l l i nci dence i s l ower, the s everi ty l es s . Acycl ovi r (a ), cefta zi di ne (c), a nd peni ci l l i ns (d) ra rel y a re ca us a l l y
rel a ted to the devel opment of a cute rena l fa i l ure.
443. The answer is a. (Brunton, pp 1478-1481, 1571-1575; Katzung, pp 790-792, 849-852, 857t.) Peni ci l l i ns , cepha l os pori ns , a nd a mphoteri ci n B exert thei r
des i red cl i ni ca l effects by a l teri ng the s tructure or functi on of cel l wa l l s of s us cepti bl e orga ni s ms . Peni ci l l i ns i nterfere wi th ba cteri a l cel l wa l l
s ynthes i s : thei r -l a cta m s tructures bi nd to a nd i nhi bi t enzyma ti c functi on of tra ns pepti da s es tha t norma l l y provi de s us cepti bl e ba cteri a wi th cel l
wa l l s tha t a re ca pa bl e of ma i nta i ni ng a n os moti ca l l y s ta bl e i ntra cel l ul a r mi l i eu. Cepha l os pori ns , by vi rtue of thei r -l a cta m ri ng, work i n
es s enti a l l y the s a me wa y. Amphoteri ci n B (a pol yene a nti funga l drug) bi nds to ergos terol i n the funga l cel l membra ne; the ul ti ma te outcome i s
i ncrea s ed cel l permea bi l i ty. Nonethel es s , the ul ti ma te effect i s os moti c i ns ta bi l i ty of the orga ni s m, l ea di ng to cel l dea th.
Nei ther peni ci l l i ns , cepha l os pori ns , or a mphoteri ci n B a re contra i ndi ca ted i n pa ti ents wi th i mmunodefi ci enci es (b). Indeed, they ma y pl a y a key
rol e i n ma na gi ng opportuni s ti c i nfecti ons i n s uch pa ti ents .
They do not i nduce the meta bol i s m of other drugs (c), or i ntera ct i n mos t of the typi ca l pha rma coki neti c wa ys .
Amphoteri ci n B ca n ca us e decrea s ed pl a tel et counts a nd l eukopeni a , but thi s i s ra re. The mos t common hema tol ogi c a dvers e res pons e to thi s
drug i s a normochromi c, normocyti c a nemi a . Peni ci l l i ns a nd cepha l os pori ns do not s ha re thes e properti es (a nd s o a ns wer d i s i ncorrect).
Fi na l l y, a mphoteri ci n B i s cl ea rl y nephrotoxi c (s ee the note bel ow). When gi ven i ntra venous l y, rena l dys functi on i s the mos t s eri ous a nd mos t
common l ong-term ma ni fes ta ti on of thi s a nti funga l drugs toxi c s pectrum. Peni ci l l i ns a nd cycl os pori ns ma y ca us e i nters ti ti a l nephri ti s , but
compa red wi th a mphoteri ci n B the i nci dence a nd cl i ni ca l cons equences a re qui te l ow.
Note: There a re new l i pi d formul a ti ons of a mphoteri ci n Ba mphoteri ci n B col l oi da l di s pers i on, l i pos oma l a mphoteri ci n B, a nd a l i pi d compl ex
of the druga ppa rentl y ca us e much l es s nephrotoxi ci ty tha n conventi ona l a mphoteri ci n B formul a ti ons . Tha t i s proba bl y beca us e thes e newer
formul a ti ons a l ter di s tri buti on of the a nti funga l drug s uch tha t rena l concentra ti ons , a nd s o the nephrotoxi c potenti a l , a re l ower.
444. The answer is d. (Brunton, pp 1607-1608; Katzung, pp 886-887.) Os el ta mi vi r i s us ua l l y the recommended a nti -i nfl uenza drug; za na mi vi r i s a

recommended a l terna ti ve. The bi ochemi ca l mecha ni s m of a cti on i s i nhi bi ti on of vi ra l neura mi ni da s e; tha t, i n turn, i nhi bi ts the a bi l i ty of newl y
formed vi ri ons to bud off of hos t cel l membra nes a nd s prea d the vi rus to other cel l s . Os el ta mi vi r or za na mi vi r a re a l s o us ed prophyl a cti ca l l y for
outbrea ks of other i nfl uenza A (or B) i nfecti ons .
Acycl ovi r (a ) i s a cti ve onl y a ga i ns t herpes vi rus es (i ncl udi ng herpes s i mpl ex,[whi ch i s mos t s ens i ti ve to a cycl ovi r]; va ri cel l a -zos ter; a nd
cytomega l ovi rus [but mos t s tra i ns a re res i s ta nt]). Acycl ovi r mus t form a n a cti ve meta bol i te, a cycl o-GTP, whi ch i n turn i nhi bi ts vi ra l DNA pol ymera s e.
Ama nta di ne (b) i s a n a nti vi ra l drug for fl u prophyl a xi s (ma i nl y A s tra i ns ) a nd trea tment, but i ts us e ha s decl i ned s ha rpl y (a s os el ta mi vi r or
za na mi vi r us e ha s grown) beca us e ma ny vi ra l s tra i ns qui ckl y devel op res i s ta nce. In a ddi ti on, a ma nta di ne tends to ca us e di s turbi ng CNS effects
(di zzi nes s , i rri ta bi l i ty, i ns omni a , a nd i mpa i red menta l concentra ti on) i n a l a rge number of pa ti ents a nd ca rdi ova s cul a r depres s i on. Ama nta di ne i s
a l s o us ed occa s i ona l l y a s a n a djunct to trea tment of Pa rki ns on di s ea s e. Lopi na vi r (c) a nd ri tona vi r (e) a re protea s e i nhi bi tors /a nti retrovi ra l drugs .
Thos e two drugs a re us ed i n combi na ti on, a nd wi th a nucl eos i de/-ti de revers e tra ns cri pta s e i nhi bi tor (eg, zi dovudi ne) for HIV i nfecti ons .
Note: Gi ven the number of H1N1 ca s es , a nd worri es a bout a pa ndemi c, i n 2009 the FDA ga ve forma l a uthori za ti on to us e ei ther of thes e drugs for
fl u-rel a ted i ndi ca ti ons for whi ch they were not previ ous l y FDA-a pproved, i ncl udi ng chi l dren younger tha n the prea pproved mi ni mum a ge.
445. The answer is d. (Brunton, pp 1365-1378, 1478-1481, 1505-1518, 1533; Katzung, p 825.) The ra ti ona l e behi nd thi s combi na ti on i s tha t peni ci l l i ns
es s enti a l l y wea ken the cel l wa l l s of s us cepti bl e ba cteri a , whi ch i n turn fa ci l i ta tes a cces s of the a mi nogl ycos i de to i ts s i te of a cti on, the ba cteri a l
ri bos omes . Thi s us ua l l y provi des better a nti bi oti c res pons e tha n wi th ei ther a nti bi oti c us ed a l one, a nd wi th the a mi nogl ycos i de, pl a s ma l evel s
a rent neces s a ri l y s o hi gh tha t they a re more l i kel y to ca us e ototoxi ci ty, nephrotoxi ci ty, or other a dvers e res pons es .
You s houl d a l s o reca l l a t l ea s t two other thi ngs : (1) the peni ci l l i n i n thi s combi na ti on i s us ua l l y a n extended-s pectrum peni ci l l i n, s uch a s
ti ca rci l l i n; a nd (2) a s I s peci fi ca l l y noted i n the ques ti on, the a dmi ni s tra ti on of thes e drugs i s by s epa ra te IV l i nes . Tha t i s beca us e i f the two drugs
were mi xed together i n s uffi ci entl y hi gh concentra ti ons , the peni ci l l i n ma y chemi ca l l y i na cti va te the genta mi ci n.
446. The answer is b. (Brunton, pp 1481-1483, 1529; Katzung, pp 792-793, 796.) Both s us cepti bl e a nd res i s ta nt gra m-nega ti ve a nd gra m-pos i ti ve ba cteri a
ha ve peni ci l l i n-bi ndi ng protei ns (PBPs ). Res i s ta nce to the na rrow s pectrum peni ci l l i ns by gra m-nega ti ve ba cteri a a ri s es from the pres ence of a n
outer membra ne wi th pores tha t a re too s ma l l to a l l ow a dequa te penetra ti on of the drug a nd a cces s to the PBPs . Thus , we a re dea l i ng wi th wha t
a mounts to a phys i ca l ba rri er to the drug.
Mos t peni ci l l i ns (wi th few excepti ons , s uch a s ba ca mpi ci l l i n) a re a cti ve i n the form i n whi ch they a re a dmi ni s tered (i e, they a re not prodrugs ),
a nd s o no s ubs equent meta bol i c a cti va ti on i s requi red.
447. The answer is b. (Brunton, pp 1494t, 1496t, 1525; Katzung, pp 798t, 799.) Cefoxi ti n, a s econd-genera ti on cepha l os pori n, i s s ui ta bl e for trea ti ng
i ntra a bdomi na l i nfecti ons ca us ed by ma ny a erobi c a nd a na erobi c gra mnega ti ve ba cteri a , i ncl udi ng a nd es peci a l l y B. fragilis. (Al terna ti ve s econdgenera ti on cepha l os pori ns tha t woul d be s ui ta bl e a re cefmeta zol e a nd cefoteta n.) Cefoxi ti n a l one ha s been s hown to be a s effecti ve a s the
tra di ti ona l thera py of cl i nda myci n pl us genta mi ci n. The other cepha l os pori ns ha ve much l ower a nti bi oti c a cti vi ty a ga i ns t thes e orga ni s ms , a nd s o
genera l l y a re not a ppropri a te.
448. The answer is a. (Brunton, pp 1512-1514, 1543; Katzung, p 824.) Ami nogl ycos i des (genta mi ci n, tobra myci n, etc) a re cl a s s i c exa mpl es of ototoxi c
drugs , a nd they ca n a ffect both bra nches of the ei ghth cra ni a l nerve.
The ri s ks of a mi nogl ycos i de-i nduced ototoxi ci ty (a nd nephrotoxi ci ty) a re a mong the rea s ons why i t i s i mporta nt to keep a n eye on pea k a nd
trough drug l evel s duri ng thera py, a djus t dos a ges a ccordi ngl y, a nd a voi d concomi ta nt us e of other ototoxi c drugs . Tha t i s beca us e the hea ri ng l os s
i s bl ood l evel -dependent (a s oppos ed to bei ng a n i di os yncra ti c or a l l ergi c rea cti on). Ami nogl ycos i de-i nduced ototoxi ci ty i s us ua l l y i rrevers i bl e.
The ri s k a nd s everi ty of hea ri ng l os s from a mi nogl ycos i des a re i ncrea s ed i f they a re a dmi ni s tered wi th other ototoxi c drugs (bel ow).
Reca l l tha t there a re two ma i n forms of drug-i nduced ototoxi ci ty. Cochl ea r toxi ci ty i ncl udes hea ri ng l os s , ti nni tus (ri ngi ng i n the ea rs ), or
occa s i ona l l y both. Hea ri ng l os s ma y a l s o occur wi th l oop di ureti cs (pa rti cul a rl y etha cryni c a ci d), ci s pl a ti n, a nd the vi nca a l ka l oi ds (a nti ca ncer
drugs ). Thes e drugs a re i ntri ns i ca l l y ototoxi c; us e one or more of them together or wi th a n a mi nogl ycos i de a nd the ri s k of ototoxi ci ty i ncrea s es
grea tl y.
Ti nni tus (us ua l l y revers i bl e) i s typi ca l l y a s s oci a ted wi th s uch drugs a s a s pi ri n (a nd, pos s i bl y, s ome other NSAIDs ) a nd qui ni di ne.
The other ma i n form of ototoxi ci ty i s ves ti bul a r toxi ci ty, whi ch i s typi ca l l y ma ni fes t a s ba l a nce a nd ga i t probl ems , verti go, a nd na us ea res ul ti ng
from ves ti bul a r a ppa ra tus dys functi on.
Nephrotoxi ci ty ma y devel op duri ng or a fter the us e of a n a mi nogl yco-s i de. It i s genera l l y more common i n the el derl y when there i s preexi s ti ng
rena l dys functi on. In mos t pa ti ents , rena l functi on gra dua l l y i mproves a fter di s conti nua ti on of thera py. Ami nogl ycos i des ra rel y ca us e
neuromus cul a r bl ocka de tha t ca n l ea d to progres s i ve fl a cci d pa ra l ys i s a nd potenti a l fa ta l res pi ra tory a rres t. Hypers ens i ti vi ty a nd derma tol ogi c
rea cti ons occa s i ona l l y occur fol l owi ng us e of a mi nogl ycos i des .
None of the other a nti bi oti cs l i s ted a re l i nked to ototoxi ci ty, whether from exces s i ve bl ood l evel s or due to a hypers ens i ti vi ty or true a l l ergi c
rea cti on. Azi thromyci n (not a n a ns wer choi ce) i s , however, a nother a nti bi oti c for whi ch there i s growi ng evi dence of a l i nk to s udden ons et hea ri ng
l os s . The mecha ni s m i s unknown, a nd the i nci dence i s nei ther dos e-dependent nor predi cta bl e.
449. The answer is b. (Brunton, pp 1579-1580; Katzung, pp 853-855.) Fl ucona zol e, a n a zol e a nti funga l , penetra tes i nto cerebros pi na l fl ui d, where i t
exerts good a nti funga l a cti vi ty a ga i ns t Cryptococcus neoformans. When i t i s gi ven ora l l y, bl ood l evel s a re a l mos t a s hi gh a s when i t i s gi ven
pa rentera l l y. Amphoteri ci n i s a dmi ni s tered i ntra venous l y a nd even when gi ven i ntra theca l l y does not a ppea r to be hi ghl y effecti ve i n funga l
meni ngi ti s .
450. The answer is d. (Brunton, p 1543; Katzung, pp 467-469, 475, 824) Ami nogl ycos i des , a t s uffi ci entl y hi gh bl ood l evel s , ca n ca us e s kel eta l
neuromus cul a r bl ocka de i n thei r own ri ght. Thi s proba bl y a ri s es from a combi na ti on of effects : i nhi bi ti on of neurona l ACh rel ea s e a nd perha ps
di rect bl ocka de of ni coti ni c receptors on s kel eta l mus cl e. Thi s woul d a dd to a nd prol ong the effects of both neuromus cul a r bl ockers the pa ti ent
ha s recei ved. In a ddi ti on, i s ofl ura ne a nd other ha l ogena ted hydroca rbon vol a ti l e l i qui d a nes theti cs (whi ch a re bei ng us ed l es s a nd l es s beca us e
of the a va i l a bi l i ty of effecti ve i ntra venous a nes theti cs ) ha ve s ome neuromus cul a r bl ocki ng effects i n thei r own ri ghtbut not to a degree tha t i s
s uffi ci ent to obvi a te the need for s ucci nyl chol i ne a nd/or nondepol a ri zi ng bl ockers when s kel eta l mus cl e pa ra l ys i s i s i ndi ca ted. So here we ha ve a
combi na ti on of drugs tha t a ffect s kel eta l mus cl e a cti va ti on.
The grea tes t concern, of cours e, woul d be the prol onga ti on of neuromus cul a r bl ocka de. A grea ter degree of pa ra l ys i s i s l a rgel y
i ncons equenti a l , s o l ong a s venti l a ti on i s s upported. It i s the prol onged bl ocka dea nd es peci a l l y the return of s kel eta l mus cl e wea keni ng a nd
venti l a tory i ns uffi ci ency a fter mecha ni ca l venti l a ti on ha s been di s conti nued a nd a ddi ti ona l dos es of a mi nogl ycos i de a re gi venwhi ch pos es the
grea tes t ri s k i f the pa ti ent ha d a l rea dy been ta ken off venti l a tory s upport.
(Note, too, i n your s tudi es , tha t s ome other a nti mi crobi a l s s eem to ha ve s ome s kel eta l neuromus cul a r bl ocki ng a cti vi ty, i ncl udi ng pol ymyxi n B

a nd cl i nda myci n.)

You s houl d reca l l tha t a l though s uch a gents a s i s ofl ura ne a nd other ha l ogena ted hydroca rbon vol a ti l e l i qui d a nes theti cs ma y potenti a te the
effects of a neuromus cul a r bl ocker, once they a re el i mi na ted (tha t occurs fa i rl y ra pi dl y when a dmi ni s tra ti on s tops ) there i s no a dded ri s k of
prol onged or grea ter s kel eta l mus cl e wea knes s or pa ra l ys i s .
I s houl d a dd tha t i n s etti ngs (eg, hos pi ta l s ) where the overa l l i nci dence of a mi nogl ycos i de res i s ta nce i s l ow (or i n the a bs ence of documented
res i s ta nce to a pa rti cul a r a mi nogl ycos i de i n a pa rti cul a r pa ti ent), tobra myci n or genta mi ci n i s us ua l l y the a mi nogl ycos i de of choi ce. Ami ka ci n
s houl d be res erved for s i tua ti ons where there i s proven res i s ta nce to the a l terna ti ves .
As wi th other a mi nogl ycos i des , peri odi c moni tori ng of pea k a nd trough bl ood l evel s i s es s enti a l to hel p i ns ure opti ma l a nti bi oti c effects whi l e
reduci ng the ri s k of ototoxi ci ty a nd nephrotoxi ci tyboth of whi ch ca n be ca us ed by a ny a mi nogl ycos i de (a l though wi th va ryi ng rel a ti ve ri s ks ). No
a mi nogl ycos i de ha s nephroprotecti ve effects .
Fi na l l y, no a mi nogl ycos i de ca n ki l l a na erobes .
451. The answer is e. (Brunton, pp 137-138t, 145, 1555-1558; Katzung, pp 840-841, 848.) Is oni a zi d (INH) i nhi bi ts cel l -wa l l s ynthes i s i n mycoba cteri a .
Increa s i ng vi ta mi n B 6 l evel s prevents s ome common a nd potenti a l l y s i gni fi ca nt compl i ca ti ons a s s oci a ted wi th thi s i nhi bi ti on, i ncl udi ng
peri phera l neuri ti s , i ns omni a , res tl es s nes s , mus cl e twi tchi ng, uri na ry retenti on, convul s i ons , a nd ps ychos i s , wi thout a ffecti ng the
a nti mycoba cteri a l a cti vi ty of INH.
452. The answer is d. (Brunton, pp 1520-1526, 1528, 1532; Katzung, pp 810-813.) Tetra cycl i nes a re drugs of choi ce i n the trea tment of Rickettsia,
Mycoplasma, a nd Chlamydia i nfecti ons . The a nti bi oti cs tha t a ct by i nhi bi ti ng cel l -wa l l s ynthes i s ha ve no effect on Mycoplasma beca us e the orga ni s m
does not pos s es s a cel l wa l l ; peni ci l l i n G (c), va ncomyci n (e), a nd ba ci tra ci n (a ) wi l l be i neffecti ve. Genta mi ci n (b) a l s o ha s l i ttl e or no
a nti mi crobi a l a cti vi ty a ga i ns t thes e orga ni s ms .
453. The answer is a. (Brunton, pp 1623-1660; Katzung, pp 871t, 874t, 880, 889.) Ri tona vi r i s a powerful i nhi bi tor of the l i vers P450 s ys tem. Ri tona vi r i s
us ed i n combi na ti on wi th l opi na vi r s ol el y to i nhi bi t l opi na vi rs meta bol i s m a nd enha nce i ts a bi l i ty i nhi bi t the fi na l s tep i n HIV ma tura ti on. Thus ,
the ri tona vi r hel ps keep l opi na vi rs pl a s ma concentra ti on i n a thera peuti c ra nge l onger. Ri tona vi r does ha ve protea s e i nhi bi tory a cti va ti on, but i t
i s wea k (es peci a l l y a t the dos a ges us ed i n combi na ti on wi th other protea s e i nhi bi tors : i n thi s combi na ti on the ri tona vi r dos e woul d be
s ubthera peuti c i f i t were the onl y protea s e i nhi bi tor us ed). In thi s combi na ti on i t i s the l opi na vi r, not the ri tona vi r (e) tha t i s ca us i ng the ma i n
thera peuti c effect. The protea s e i nhi bi tors do not ca us e hypogl ycemi a (c), nor does ri tona vi r reduce the a bi l i ty of l opi na vi r to a l ter pl a s ma gl ucos e
l evel s . In fa ct, whether us ed a l one or i n combi na ti on, protea s e i nhi bi tors typi ca l l y ca us e hypergl ycemi a (a nd ma y ca us e cl i ni ca l di a betes mel l i tus ,
a nd qui te often ra i s e chol es terol a nd tri gl yceri des l evel s too).
The NRTIs (zi dovudi ne, di da nos i ne) a re, i ndeed, prodrugs tha t mus t be meta bol i ca l l y a cti va ted to the tri phos pha te form i n order to s erve a s a
s ubs tra te for revers e tra ns cri pta s e. However, nei ther l opi na vi r nor ri tona vi r fa ci l i ta te tha t meta bol i s m (b).
454. The answer is d. (Brunton, pp 1505-1509, 1514-1515, 1517, 1525; Katzung, pp 822f, 824-825, 828, 840t, 843, 848.) Streptomyci n i s ba cteri ci da l for the
tubercl e ba ci l l us orga ni s m. Other a mi nogl ycos i des (eg, genta mi ci n, tobra myci n, neomyci n, a mi ka ci n, a nd ka na myci n) ha ve a cti vi ty a ga i ns t thi s
orga ni s m but a re s el dom us ed cl i ni ca l l y beca us e of toxi ci ty or devel opment of res i s ta nce. Streptomyci n i s a rgua bl y the mos t ototoxi c
a mi nogl ycos i de.
455. The answer is d. (Brunton, pp 1489-1490; Katzung, p 801.) Thes e a gents a re i nhi bi tors of peni ci l l i na s e (-l a cta ma s e) a nd a re us ed i n conjuncti on
wi th -l a cta ma s e-s ens i ti ve peni ci l l i ns to potenti a te thei r a cti vi ty. Thes e drugs a re found i n s evera l bra nd-na me fi xed-dos e peni ci l l i n combi na ti on
products (a moxi ci l l i n a nd cl a vul a ni c a ci d; s ul ba cta m wi th a mpi ci l l i n; ta zoba cta m wi th pi pera ci l l i n). Cl a vul a ni c a ci d i s a n i rrevers i bl e i nhi bi tor.
Thes e a gents do not, per s e, a dd a cti vi ty a ga i ns t Ps eudomona s or Enteroba cter (a n a cti vi ty a l rea dy pos s es s ed by pi pera ci l l i n but not by a mpi ci l l i n
or a moxi ci l l i n). Li kewi s e, they ha ve no i ntri ns i c effect to fa ci l i ta te entry i nto the CNS or CSF. They do not i nhi bi t hepa ti c meta bol i s m of the
peni ci l l i ns , a nd you s houl d reca l l tha t rena l excreti on (not meta bol i s m) i s the ma i n pa thwa y for peni ci l l i n el i mi na ti on. Importa ntl y, the
peni ci l l i na s e i nhi bi tors ha ve a bs ol utel y no i mpa ct on the ri s ks or s everi ti es of a l l ergi c rea cti ons to peni ci l l i ns .
456. The answer is d. (Brunton, pp 1533, 1558-1559; Katzung, pp 840t, 842.) An i mporta nt probl em i n the chemothera py of TB i s ba cteri a l drug res i s ta nce.
For thi s rea s on, concurrent a dmi ni s tra ti on of two or more drugs s houl d be empl oyed to del a y the devel opment of res i s ta nce. Etha mbutol i s often
gi ven a l ong wi th INH for thi s purpos e. Streptomyci n or ri fa mpi n ma y a l s o be a dded to the regi men to del a y even further the devel opment of drug
res i s ta nce.
457. The answer is d. (Brunton, pp 1507-1509; Katzung, pp 821-825.) Ami nogl ycos i des , whi ch a re ma i nl y us ed for pa rentera l thera py of s evere i nfecti ons
from a erobi c gra m-nega ti ve ba ci l l i (eg, E. coli, Serratia, Klebsiella), requi re oxygen i n order for the drug to be tra ns ported a cros s the ba cteri a l cel l
membra ne. Such i ncorpora ti on i s neces s a ry for thes e drugs to exert thei r ba cteri ci da l effects , whi ch a ri s e from bi ndi ng to the 30S s ubuni t of
s us cepti bl e ba cteri a . Ul ti ma tel y the a mi nogl ycos i de-ri bos oma l bi ndi ng l ea ds to prema ture termi na ti on of ba cteri a l protei n s ynthes i s a nd the
forma ti on of a bnorma l ba cteri a l protei ns . Such a bnorma l protei ns ul ti ma tel y i ns ert i nto the ba cteri a l cel l membra ne, ca us i ng l ea ki nes s a nd cel l
dea th.
The a mi nogl ycos i des a re not prodrugs , a nd s o meta bol i s m (whether a erobi c or otherwi s e) i s not neces s a ry for a cti vi ty; forma ti on of a n oxygen
free ra di ca l or a n a mi nogl ycos i de free ra di ca l ha s nothi ng to do wi th thei r a nti bi oti c effects . Moreover, meta bol i s m by hos t cel l s i s not a n
i mporta nt proces s i n the el i mi na ti on of a mi nogl ycos i des , nor of reduci ng hos t cel l toxi ci ty (eg, to the ki dneys or a udi tory nerve). Rena l excreti on i s
the ma i n route of el i mi na ti on for thes e drugs , whi ch expl a i ns why rena l functi on i s s uch a n i mporta nt cons i dera ti on i n dos i ng a djus tments .
Cl ea rl y, both a erobi c a nd a na erobi c ba cteri a ca n el a bora te res i s ta nce fa ctors (or devel op res i s ta nce i n other wa ys ) to a va ri ety of a nti bi oti c
cl a s s es . From a cl i ni ca l vi ewpoi nt, the pres ence or a bs ence of mol ecul a r oxygen i s not a cruci a l or even rel eva nt i s s ue i n thi s ma tter, however.
458. The answer is c. (Brunton, p 1518; Katzung, pp 826-827.) Neomyci n, a n a mi nogl ycos i de, i s not s i gni fi ca ntl y a bs orbed from the GI tra ct. After ora l
a dmi ni s tra ti on, the i ntes ti na l fl ora a re s uppres s ed or modi fi ed a nd the drug i s excreted i n the feces . Thi s effect of neomyci n i s us ed i n hepa ti c
coma to decrea s e col i form fl ora , thus decrea s i ng the producti on of a mmoni a a nd reduci ng l evel s of free ni trogen i n the bl oods trea m. Other
a nti mi crobi a l a gents (eg, tetra cycl i ne, peni ci l l i n G, chl ora mpheni col , a nd cepha l othi n) do not ha ve the effi ca cy or potency of neomyci n i n ca us i ng
thi s effect. Note tha t chl ora mpheni col i s no l onger a va i l a bl e i n the Uni ted Sta tes .
459. The answer is a. (Brunton, pp 1494t, 1496t, 1525, 1538; Katzung, pp 773-780, 781t, 783-784, 888-890.) Peni ci l l i ns were us ed i n the trea tment of
meni ngi ti s beca us e of thei r a bi l i ty to pa s s a cros s a n i nfl a med bl ood-bra i n ba rri er. We dont us e them tha t wa y a nymore, a nd s o a ns wers c, d, a nd
e a re i ncorrect. Erythromyci n (b) di s tri butes wi del y throughout the body, but not to the bra i n or cerebros pi na l fl ui d. The thi rd-genera ti on

cepha l os pori n, ceftri a xone, i s preferred beca us e i t i s effecti ve a ga i ns t -l a cta ma s e produci ng s tra i ns of H. influenzae tha t ma y ca us e meni ngi ti s i n
chi l dren.
460. The answer is e. (Brunton, pp 1531, 1533; Katzung, p 817.) There a re s evera l pi eces of i nforma ti on you s houl d l i nk together to hel p a rri ve a t the
a ns wer, for whi ch a rel a ti vel y new drug i s the correct a ns wer. (1) Al though l i nezol i d ha s s evera l us es , i t i s bes t res erved for va ncomyci n-res i s ta nt
enterococci (VRE) a nd methi ci l l i n-res i s ta nt S. aureus (MRSA) i nfecti ons . (Its s el dom a fi rs t-l i ne a nti bi oti c beca us e of the ri s k of res i s ta nce.) (2)
Li nezol i d i s occa s i ona l l y l i nked to bone ma rrow s uppres s i on tha t i s us ua l l y revers i bl e upon di s conti nua ti on of the drug. (Gra nted, s uch other
a nti bi oti cs a s chl ora mpheni col [no l onger us ed i n the Uni ted Sta tes ] pos e grea ter ri s ks of bone ma rrow s uppres s i on, but thi s property i s
nonethel es s a s s oci a ted wi th l i nezol i d.) (3) The thi rd pi ece of evi dence i s the ri s e of bl ood pres s ure i n res pons e to ephedri ne, a mi xed-a cti ng
s ympa thomi meti c tha t works , i n pa rt, by rel ea s i ng neurona l norepi nephri ne. Li nezol i d ha s monoa mi ne oxi da s e i nhi bi tory a cti vi ty (a l bei t rel a ti vel y
wea k compa red wi th tra di ti ona l MAO i nhi bi tors ). Pi ece thes e three l i nes of evi dence together a nd the onl y rea s ona bl e choi ce i s l i nezol i d.
461. The answer is d. (Brunton, pp 1558-1159; Katzung, pp 840-842.) Etha mbutol , i n combi na ti on wi th i s oni a zi d, ri fa mpi n, a nd pyra zi na mi de, i s
cons i dered fi rs t-l i ne thera py for M. tuberculosis i nfecti on. It ha s l a rgel y repl a ced a mi nos a l i cyl i c a ci d a s a pa rt of the trea tment pl a n, ma i nl y
beca us e i t i s tol era ted better. Etha mbutol i nhi bi ts cel l wa l l s ynthes i s ; res i s ta nce devel ops qui ckl y unl es s a djuncts (l i s ted a bove) a re gi ven
concomi ta ntl y. (Les s common us es for etha mbutol i ncl ude i nfecti ons wi th M. avium compl ex, M. kansasii, a nd M. marinum.)
Amphoteri ci n-res i s ta nt Candida i nfecti ons (a ) a re rel a ti vel y uncommon (s ome res i s ta nt s tra i ns ha ve been i s ol a ted); nonethel es s etha mbutol
ha s no a nti funga l a cti vi ty. Etha mbutol a l s o ha s no a cti vi ty a ga i ns t i nfecti ons wi th col i form ba cteri a (b), or wi th Entamoeba (c). Infecti ons wi th P.
falciparum or P. vivax (ma l a ri a ; e) ma i nl y requi re ma na gement (prophyl a xi s , or trea tment of a cti ve di s ea s e) wi th s uch drugs a s chl oroqui ne,
mefl oqui ne, doxycycl i ne, or s evera l other a gents but not etha mbutol .

Cancer and Immune System Pharmacology

Questions
Cel l cycl e, cel l cycl e s peci fi ci ty
Al kyl a ti ng a gents
Anti ca ncer hormones a nd thei r a nta goni s ts
Anti tumor a nti bi oti cs
Anti meta bol i tes
Pl a nt a l ka l oi ds
Immunomodul a tors
462. Whi l e revi ewi ng cha rts i n a genera l medi ci ne cl i ni c you s ee tha t a pa ti ent, 55-yea r-ol d a nd wi th no hi s tory of ca ncer a t a l l , i s ta ki ng
methotrexa te (MTX). Wha t i s the mos t l i kel y condi ti on for whi ch thi s a nti ca ncer drug i s bei ng gi ven?
a . As thma or emphys ema
b. Hyperthyroi di s m
c. Hyperuri cemi a or cl i ni ca l gout
d. Mya s theni a gra vi s
e. Rheuma toi d a rthri ti s or ps ori a s i s
463. A 47-yea r-ol d woma n wi th chori oca rci noma i s trea ted wi th methotrexa te (MTX), gi ven a t dos a ges tha t you bel i eve ma y ca us e s i gni fi ca nt hos t
cel l toxi ci ty. Whi ch drug woul d you gi ve to l i mi t the toxi c effects of the drug on norma l hos t cel l s ?
a . Deferoxa mi ne
b. Leucovori n
c. N-a cetyl cys tei ne
d. Peni ci l l a mi ne
e. Vi ta mi n K
464. You order vi ncri s ti ne, the prototype of the vi nca a l ka l oi ds , to a pa ti ent wi th a tumor tha t i s l i kel y to be res pons i ve to thi s drug. Wha t i s the
mos t l i kel y a dvers e res pons e to thi s drug?
a . Nephrotoxi ci ty, rena l dys functi on or fa i l ure
b. Neutropeni a
c. Peri phera l s ens ory a nd motor neuropa thy
d. Pul mona ry da ma ge
e. Thrombocytopeni a , bl eedi ng
465. A ca ncer pa ti ent devel ops s evere, i rrevers i bl e ca rdi omyopa thy beca us e the ma xi mum l i feti me dos e of a n a nti ca ncer drug wa s exceeded. Wha t
drug wa s mos t l i kel y res pons i bl e for thi s ?
a . As pa ra gi na s e
b. Bl eomyci n
c. Ci s pl a ti n
d. Cycl ophos pha mi de
e. Doxorubi ci n
f. Vi ncri s ti ne
466. A pa ti ent wi th Wi l ms tumor i s recei vi ng a chemothera peuti c a gent tha t i s des cri bed a s worki ng by i nterca l a ti ng i nto DNA s tra nds , a nd tha t i s
effi ca ci ous rega rdl es s of whi ch s ta ge of the cel l cycl e the tumor cel l s a re i n. Whi ch drug bes t fi ts thi s des cri pti on?
a . Ana s trozol e
b. Cyta ra bi ne (cytos i ne a ra bi nos i de)
c. Doxorubi ci n
d. Fl uoroura ci l
e. Ta moxi fen
467. A 42-yea r-ol d woma n i s di a gnos ed wi th meta s ta ti c brea s t ca ncer. You cons i der us e of ta moxi fen, toremi fene, or ful ves tra nt. Why mi ght
ful ves tra nt be the bes t choi ce, a l l other fa ctors bei ng equa l ?
a . Exerts a nti pl a tel et, ra ther tha n thromboti c, effects
b. La cks a bi l i ty to ca us e hot fl a s hes or other di s turbi ng s i de effects
c. Lower ri s k of ca us i ng endometri a l ca ncer
d. Provi des cl i ni ca l cure, ra ther tha n pa l l i a ti on, i n a l l pa ti ents
e. Si gni fi ca ntl y i mproves mi nera l dens i ty i n, s trength of, l ong bones
468. A pa ti ent wi th chroni c myel ogenous l eukemi a (CML) i s bei ng trea ted wi th i ma ti ni b. Whi ch s i de effect or other s i tua ti on s houl d you a nti ci pa te
i n res pons e to i ma ti ni b thera py?

a . A hi gh ra te of thera peuti c fa i l ure, a nd the need to s wi tch to i nterferons -2a a nd -2b

b. Hypotens i on a nd hypovol emi a due to s i gni fi ca nt drug-i nduced di ures i s
c. Intera cti ons wi th other drugs tha t depend on or a ffect the cytochrome P450 s ys tem
d. Si gni fi ca nt toxi ci ty to norma l hos t cel l s due to profound i nhi bi ti on of tyros i ne ki na s e
e. Thrombocytos i s , wi th a hi gh ri s k of i ntra va s cul a r cl otti ng
469. As a rul e, l a rge (a nd ol der) s ol i d tumors a re more di ffi cul t to era di ca te when chemothera py i s s ta rted. Whi ch tumor-ba s ed property expl a i ns
bes t the rea s on for thi s chemothera peuti c l i mi ta ti on?
a . Growth fra cti on s l ows , more cel l s enter G 0
b. Hi gher tumor bl ood fl ow wa s hes a wa y a nti ca ncer drugs fa s ter
c. P-gl ycoprotei n a cti vi ty decrea s es a s tumors get ol der
d. Thei r hi gher meta bol i c ra te ma kes them l es s vul nera bl e to chemothera peuti c a gents
e. Topoi s omera s e a cti vi ty (a bi l i ty to s el f-repa i r DNA s tra nd da ma ge) i ncrea s es wi th tumor s i ze
470. A ma n ha s pros ta te ca ncer tha t wi l l be trea ted wi th l euprol i de. Whi ch drug a re you mos t l i kel y to us e a djuncti vel y when s ta rti ng
chemothera py?
a . An a roma ta s e i nhi bi tor (eg, a na s trozol e)
b. Fl uta mi de
c. Predni s one or a nother potent gl ucocorti coi d
d. Ta moxi fen
e. Tes tos terone
471. As pa rt of the trea tment pl a n for a Hodgki n di s ea s e pa ti ent we ha ve gi ven mechl oretha mi ne. Whi ch phra s e bes t des cri bes the a nti ca ncer
mecha ni s m of a cti on of thi s drug?
a . Al kyl a tes DNA, ca us i ng cros s -l i nks between pa ra l l el DNA s tra nds
b. Bl ocks mi crotubul a r a s s embl y a nd mi tos i s duri ng M-pha s e
c. Inhi bi ts topoi s omera s e, preventi ng repa i r of DNA s tra nd brea ks
d. Interca l a tes i n DNA s tra nds , thereby preventi ng DNA repl i ca ti on by mRNA
e. Sta bi l i zes mi crotubul a r a rra ys , thereby preventi ng mi tos i s
472. The oncol ogy tea m ha s trea ted ma ny pa ti ents wi th a cute l ymphocyti c l eukemi a us i ng a combi na ti on of drugs . One drug tends to ca us e a hi gh
i nci dence of l umba r a nd a bdomi na l pa i n, s i gni fi ca nt i ncrea s es of pl a s ma a myl a s e a nd tra ns a mi na s e a cti vi ty, a nd other s ymptoms of hepa ti c
a nd/or pa ncrea ti c dys functi on. Some pa ti ents devel oped s eri ous hypers ens i ti vi ty rea cti ons upon drug a dmi ni s tra ti on, a nd there ha ve been
occa s i ona l s udden dea ths . Whi ch drug bes t fi ts thi s des cri pti on?
a . As pa ra gi na s e
b. Aza thi opri ne
c. Doxorubi ci n
d. Methotrexa te
e. Vi ncri s ti ne
473. A 30-yea r-ol d woma n bei ng trea ted for ova ri a n ca ncer devel ops hi gh frequency hea ri ng l os s a nd decl i ni ng rena l functi on i n res pons e to
a nti ca ncer drug thera py. Whi ch drug i s the mos t l i kel y ca us e?
a . Bl eomyci n
b. Ci s pl a ti n
c. Doxorubi ci n
d. 5-Fl uoroura ci l
e. Pa cl i ta xel
474. A 41-yea r-ol d woma n comes to the outpa ti ent a rea of the hema tol ogy-oncol ogy center for her fi rs t cours e of a djuva nt chemothera py for
meta s ta ti c brea s t ca ncer fol l owi ng a l eft modi fi ed ra di ca l ma s tectomy a nd a xi l l a ry l ymph node di s s ecti on for i nfi l tra ti ng ducta l ca rci noma of the
brea s t. Two bi ops i es were pos i ti ve for ca ncer.
Fol l owi ng premedi ca ti on wi th dexa metha s one a nd onda ns etron, s he wi l l recei ve combi na ti on chemothera py wi th doxorubi ci n,
cycl ophos pha mi de, a nd fl uoroura ci l . Twenty-four hours a fter the fi rs t cours e of chemothera py s he wi l l s ta rt a 10-da y regi men wi th fi l gra s ti m. Wha t
i s the mos t l i kel y rea s on for a dmi ni s teri ng the fi l gra s ti m?
a . Control of na us ea a nd emes i s
b. Potenti a te the a nti ca ncer effects of the chemothera peuti c a gents
c. Prevent doxorubi ci n-i nduced ca rdi otoxi ci ty
d. Reduce the ri s k/s everi ty of chemo-i nduced neutropeni a , a nd rel a ted i nfecti ons
e. Sti mul a te the ga s tri c mucos a to repa i r da ma ge ca us ed by the chemothera py drugs
475. A ca ncer pa ti ent recei ves prophyl a cti c a l l opuri nol before a cours e of chemothera py. Wha t i s the ma i n rea s on for gi vi ng the a l l opuri nol ?
a . Fa ci l i ta te hos t cel l detoxi fi ca ti on of the chemothera peuti c drug, thereby reduci ng hos t cel l toxi ci ti es
b. Inhi bi t the potenti a l for DNA repa i r, by topoi s omera s es , tha t otherwi s e mi ght l ea d to chemothera py fa i l ure
c. Potenti a te the a cti on of a ni trogen mus ta rd or ni tros ourea to bi nd to (cros s -l i nk) puri ne moi eti es i n DNA s tra nds
d. Prevent myel os uppres s i on a nd rel a ted bl ood dys cra s i a s

e. Reduce the ri s k of hyperuri cemi a a nd i ts ma i n cons equences (rena l da ma ge, gout) tha t ca n occur wi th a ma s s i ve cel l ki l l
476. The FDA requi res ma nufa cturers of a n a nti ca ncer drug to a voi d concomi ta nt a dmi ni s tra ti on of certa i n SSRI a nti depres s a nts (fl uoxeti ne,
pa roxeti ne, a nd s ertra l i ne) to woma n recei vi ng a pa rti cul a r a nti ca ncer drug. The drug i n ques ti on i s ma i nl y us ed to trea t certa i n types of brea s t
ca ncers a nd i s a l s o us ed to prevent brea s t ca ncer recurrence. It commonl y ca us es hot fl a s hes a nd i s a s s oci a ted wi th a hi gh i nci dence of na us ea
a nd vomi ti ng. The SSRIs l i s ted a bove a re s trong i nhi bi tors of CYP2D6 a nd s o they ca n i nterfere wi th the a nti ca ncer drugs meta bol i c a cti va ti on,
whi ch i s requi red for thei r chemothera peuti c effects . Whi ch drug i s the mos t l i kel y ta rget of i ntera cti ons wi th thes e SSRIs ?
a . Bl eomyci n
b. Interferon a l pha
c. Merca ptopuri ne
d. Ta moxi fen
e. Vi nbl a s ti ne
477. Al l opuri nol or the newer rel a ted drug febuxos ta t i s commonl y a dmi ni s tered before i ni ti a ti ng chemothera py of l eukemi a s a nd other bl oodba s ed ca ncers to prevent hyperuri cemi a a nd i ts cons equences . It i s a l s o i mporta nt i n preventi ng hyperuri cemi a i n res pons e to chemothera py of
s ome s ol i d tumors . However, i t ma y potenti a te the hos t toxi ci ty of certa i n a nti ca ncer drugs by i nhi bi ti ng thei r meta bol i c i na cti va ti on a nd
detoxi fi ca ti on. Wi th whi ch drug s houl d concomi ta nt us e of a l l opuri nol or febuxos ta t be a voi ded?
a . Bl eomyci n
b. Ci s pl a ti n
c. Cycl ophos pha mi de
d. Doxorubi ci n
e. Merca ptopuri ne
478. A 48-yea r-ol d pa ti ent wa s i n rena l fa i l ure, but fortuna tel y s he recei ved a ki dney tra ns pl a nt. We s ta rt her on cycl os pori ne to reduce the ri s k of
gra ft rejecti on. Wha t a re the mos t common a nd worri s ome a dvers e res pons es a s s oci a ted wi th thi s i mmunos uppres s a nt?
a . Ca rdi otoxi ci ty a nd hepa totoxi ci ty
b. Hepa totoxi ci ty a nd nephrotoxi ci ty
c. Hypotens i on a nd pul mona ry fi bros i s
d. Nephrotoxi ci ty a nd i nfecti on ri s k
e. Thrombos i s a nd pul mona ry embol i s m or i s chemi c s troke

Cancer and Immune System Pharmacology

Answers
462. The answer is e. (Brunton, pp 1018, 1690-1694; Katzung, pp 645, 958, 989, 1104.) The ma i n us es of methotrexa te (MTX) for condi ti ons other tha n
res pons i ve ca ncers a re ma na gement of rheuma toi d a rthri ti s (RA) a nd ps ori a s i s tha t i s us ua l l y not res pons i ve to other drugs . Dos es a nd dos a ge
s chedul es di ffer from thos e typi ca l l y us ed for ca ncers .
MTX i s one of ma ny di s ea s e-modi fyi ng a nti rheuma ti c drugs (DMARDs ), whi ch a re a l s o ca l l ed s l ow-a cti ng a nti rheuma ti c drugs (SAARDs ) beca us e
thei r ons et of s ymptom rel i ef i s much s l ower tha n tra di ti ona l NSAIDs (s a l i cyl a tes a nd other fi rs t-genera ti on COX-1/-2 i nhi bi tors , or s econdgenera ti on/COX-2 i nhi bi tors , i e, the coxi bs ).
Nonethel es s , a l though the ons et i s cons i dered s l ow, mea ni ngful s ymptom rel i ef us ua l l y occurs wi th a s l i ttl e a s 3 to 4 weeks of thera pyfa s ter
tha n mos t of the other DMARDs . Note tha t other DMARDs , of whi ch there a re ma ny, ha ve no ca ncer-rel a ted us es . Al l the potenti a l s i de effects ,
a dvers e res pons es , a nd contra i ndi ca ti ons tha t a ppl y to us i ng MTX for ca ncer a ppl y to the drugs us e for RA or ps ori a s i s .
463. The answer is b. (Brunton, pp 1074-1095, 1673, 1690, 1693-1694, 1820; Katzung, pp 645, 958, 959t, 1104.) Thi s es s enti a l techni que to reduce hos t cel l
toxi ci ty i n res pons e to methotrexa te (MTX) thera py i s often referred to a s l eucovori n (fol i ni c a ci d) res cue. Methotrexa te, a fol i c a ci d
a na l og/a nti meta bol i te, ca n be cura ti ve for women wi th chori oca rci noma a nd i s a l s o us eful for non-Hodgki n l ymphoma s a nd a cute l ymphocyti c
l eukemi a s (ALLs ) i n chi l dren. The drug ki l l s res pons i ve ca ncer cel l s by i nhi bi ti ng di hydrofol a te, a n enzyme neces s a ry for formi ng tetra hydrofol i c
a ci d (FH 4 ). The FH 4 , i n turn, i s cri ti ca l for eventua l s ynthes i s of DNA, RNA, a nd protei ns . Inhi bi ti on of thymi dyl a te s ynthes i s i s proba bl y the s i ngl e
mos t i mporta nt cons equence i n the overa l l rea cti on s cheme.
Some ca ncer cel l s a re res i s ta nt to MTX beca us e they l a ck a dequa te mecha ni s ms for tra ns porti ng the drug i ntra cel l ul a rl y. Thes e i ncl ude s ome
hea d a nd neck ca ncers a nd os teogeni c s a rcoma s . In s uch ca s es we need to gi ve very l a rge dos es of MTX to es ta bl i s h a hi gh concentra ti on gra di ent
tha t es s enti a l l y dri ves i t i nto the cel l s . Unfortuna tel y, norma l hos t cel l s depend on fol a te meta bol i s m, they ta ke up MTX wel l , a nd they wi l l be
a ffected.
To protect norma l cel l s we a dmi ni s ter l eucovori n (a l s o ca l l ed ci trovorum fa ctor or fol i ni c a ci d) ri ght a fter gi vi ng the MTX. It i s ta ken up by the
norma l cel l s , bypa s s es the bl ock i nduced by the MTX, a nd s o s pa res norma l cel l meta bol i s m. The l eucovori n does not s pa re ca ncer cel l s : jus t a s
they ca nnot ta ke up MTX wel l , they ca nnot ta ke up the res cue a gent a nd s a ve thems el ves from cytotoxi ci ty.
Leucovori n res cue i s not done a utoma ti ca l l y i n every ca s e when MTX i s gi ven. When l ow MTX dos es a re us ed l eucovori n ma y be wi thhel d unti l
a nd unl es s bl ood counts s how evi dence of MTX-i nduced bone ma rrow s uppres s i on. However, i t i s qui te us ua l l y gi ven a l ong wi th MTX when MTX
dos es a re very hi gh (a s i n s evere or MTX-res i s ta nt ca s es ), a nd hos t toxi ci ty i s very proba bl e.
There i s a nother i mporta nt a nd growi ng us e of MTX: a s a di s ea s e-modi fyi ng or s l ow-a cti ng a nti rheuma ti c drug (DMARD, SAARD, res pecti vel y).
Owi ng to toxi ci ty (s ee bel ow) i t ha d been rel ega ted to s econd- or thi rd-l i ne thera py of s evere a nd/or refra ctory rheuma toi d a rthri ti s . Now tha t we
ha ve a better a ppreci a ti on of the drugs toxi ci ty, a nd how to recogni ze i t ea rl i er a nd mi ni mi ze i ts occurrences , i t i s bei ng us ed much more, ea rl i er
on i n thera py, for rheuma toi d a rthri ti s tha t i s modera te a nd l i kel y to progres s ra pi dl y.
The ma i n a dvers e res pons es to MTX, rega rdl es s of the purpos e for whi ch i t i s gi ven, i ncl ude bone ma rrow s uppres s i on, pul mona ry da ma ge
(i nfi l tra tes , fi bros i s ), s toma ti ti s , a nd l es i ons el s ewhere i n the GI tra ct. Hi gh dos es ca n be nephrotoxi c (ri s k reduced by ma i nta i ni ng a dequa te
hydra ti on a nd a l ka l i ni zi ng the uri ne). MTX i s a l s o tera togeni c.
Reca l l tha t deferoxa mi ne (a ) i s us ed to trea t i ron poi s oni ng (i t i s a n i ron chel a tor). N-a cetyl cys tei ne (c) i s ma i nl y us ed ei ther a s a mucol yti c
(mucus -thi nni ng) drug for certa i n pul mona ry di s orders (eg, COPD) or a s a n a nti dote for a ceta mi nophen poi s oni ng. Peni ci l l a mi ne (d) i s ma i nl y a
copper chel a tor, us ed for copper poi s oni ng or Wi l s on di s ea s e. Vi ta mi n K (e) i s us ed for defi ci ency s ta tes , for comba ti ng exces s i ve effects of
wa rfa ri n, or for ma na gi ng bl eedi ng di s orders i n newborns of mothers who ha ve been ta ki ng certa i n drugs (eg, a nti convul s a nts s uch a s phenytoi n)
duri ng pregna ncy.
464. The answer is c. (Brunton, pp 1705-1707; Katzung, pp 962-964.) Vi ncri s ti ne i s one of rel a ti vel y few cytotoxi c a nti ca ncer drugs , whi ch does not ca us e
bone ma rrow s uppres s i on (a nd a l l the potenti a l cons equences of tha t) a s i ts ma i n toxi ci ty. Ra ther, i t ca us es neuropa thi es i nvol vi ng both s ens ory
a nd motor nerves . Pa res thes i a s a re a common exa mpl e of the former (hea ri ng l os s ca n a l s o occur); mus cl e wea knes s a nd obtunded refl exes a re
exa mpl es of the l a tter. Importa nt note: Vi ncri s ti ne di ffers from the other two vi nca a l ka l oi ds , vi nbl a s ti ne a nd vi norel bi ne, whi ch do ca us e bone
ma rrow s uppres s i on (a nd not neuropa thi es ) a s thei r ma i n dos e-l i mi ti ng toxi ci ty.
465. The answer is e. (Brunton, pp 1713-1715; Katzung, pp 965-966.) Doxorubi ci n, a n a nti tumor a nti bi oti c, i s ca rdi otoxi c, a nd the ri s k for a nd s everi ty of
ca rdi omyopa thy i s dos e-rel a ted. (There i s a ma xi mum recommended l i feti me [cumul a ti ve] dos e for thi s drug, a nd i f i t i s exceeded the ri s k of
ca rdi a c da ma ge ri s es s i gni fi ca ntl y.)
As pa ra gi na s e (a ), us ed onl y for a cute l ymphocyti c l eukemi a , tends to ca us e ma i nl y pa ncrea ti ti s , hepa ti c dys functi on, a nd
a l l ergi c/hypers ens i ti vi ty rea cti ons . The ma i n orga n-s peci fi c toxi ci ty of bl eomyci n (b), a l s o a n a nti tumor a nti bi oti c, i s pul mona ry da ma ge tha t
pres ents i ni ti a l l y us ua l l y a s pneumoni ti s . It occurs i n a bout 1 of 10 pa ti ents trea ted wi th thi s drug. In s ome ca s es the pul mona ry da ma ge wi l l
progres s to pul mona ry fi bros i s tha t i s , of cours e, i rrevers i bl e.
Ci s pl a ti ns (c) ma i n dos e-l i mi ti ng toxi ci ty i s rena l da ma ge, whi ch ca n be prevented s omewha t by ens uri ng tha t the pa ti ent i s a dequa tel y
hydra ted a nd produci ng a dequa te a mounts of uri ne. Di ureti cs ma y be us ed a s a djuncts . The goa l i s to mi ni mi ze a ccumul a ti on of the nephrotoxi c
drug i n the rena l tubul es a nd uri ne. (A rel a ted drug, oxa l i pl a ti n, tends to ca us e peri phera l s ens ory neuropa thi es a nd does s o i n mos t pa ti ents
who recei ve thi s drug.)
Cycl ophos pha mi de (d) ha s no pa rti cul a r orga n-s peci fi c toxi ci ty. Ra ther, ma i n ma ni fes ta ti ons of toxi ci ty i nvol ve ra pi dl y growi ng cel l s s uch a s
thos e i n the bone ma rrow, i ntes ti na l tra ct mucos a e, a nd ha i r fol l i cl es .
Vi ncri s ti nes (f) ma jor dos e-l i mi ti ng toxi ci ty i s peri phera l nerve da ma ge: motor, s ens ory, a nd i n s ome ca s es a utonomi c. It proba bl y a ri s es i n a
ma nner rel a ted to the drugs a nti ca ncer effect: i nhi bi ti on of mi crotubul a r functi onor, i n the ca s e of nerves , neurotubul es a s a res ul t of drug
bi ndi ng to tubul i n.
466. The answer is c. (Brunton, pp 1713-1715; Katzung, pp 965-966.) Anthra cycl i ne-type a nti tumor a nti bi oti cs (doxorubi ci n, da unorubi ci n, i da rubi ci n, etc)
i nterca l a te between a nd eventua l l y bi nd to DNA ba s e pa i rs . Thi s di s torti on of the DNA cha i ns ma kes the DNA a n uns ui ta bl e templ a te for RNA
pol ymera s e, a nd ul ti ma tel y RNA a nd protei n s ynthes i s i s i nhi bi ted. Da cti nomyci n i s pha s e-nons peci fi c.
Ana s trozol e (a ) i s a rel a ti vel y new a roma ta s e i nhi bi tor. Thi s ora l a gent i s us ed for pos tmenopa us a l women wi th ea rl y or a dva nced brea s t

ca ncer. In pos tmenopa us a l women, the ma jor s ource of es trogen (whi ch s upports growth a nd repl i ca ti on of es trogen-dependent tumors ) i s
a drena l a ndrogens . Thos e a ndrogens a re meta bol i zed by a roma ta s e to es trogens . As a res ul t, a na s trozol e depl etes es trogens a nd ca n a rres t
tumor cel l growth.
Cyta ra bi ne (b, a l s o ca l l ed cytos i ne a ra bi nos i de) i s a pyri mi di ne a na l og (a nti meta bol i te) tha t i s meta bol i zed to the a cti ve moi ety, a ra -CTP. The
a ra -CTP becomes i ncorpora ted i nto DNA, wi th the ma i n ul ti ma te effect bei ng s uppres s i on of DNA s ynthes i s . It i s hi ghl y s peci fi c for cel l s i n S-pha s e.
Fl uoroura ci l (d), a l s o a n a nti meta bol i te, i nhi bi ts thymi dyl a te s yntheta s e through i ts a cti ve meta bol i te, 5-fl uoro-2-dexoyuri di ne-5monophos pha te (FdUMP). It i s not pha s e-s peci fi c, but i ts a cti vi ty depends on cel l s not bei ng i n the G 0 s ta ge.
Ta moxi fen (e) i s us ed for brea s t ca ncers . It bl ocks es trogen receptors on the brea s t ca ncer cel l s (for whi ch the ma i n phys i ol ogi c a goni s t i s
es tra di ol ). Reca l l tha t ta moxi fen i s cl a s s i fi ed a s a s el ecti ve es trogen receptor modi fi er (SERM). Al though i t bl ocks es trogen receptors on
res pons i ve brea s t ca ncer cel l s a nd i s thera peuti c for them, i t a cts a s a n es trogen receptor a goni s t i n the uterus . Thus , one of the ma i n ri s ks of
thera py wi th ta moxi fen i s endometri a l hyperpl a s i a tha t ma y l ea d to endometri a l ca ncer. Beca us e the drug a cts a s a n es trogen receptor a goni s t i n
s ome ti s s ues a nd a n a nta goni s t i n others , ri s k-benefi t ra ti os mus t be cons i dered ca reful l y. The benefi ci a l effects i n a cti ve brea s t ca rci noma ma y
outwei gh the ri s ks of i nduci ng endometri a l di s ea s e. However, the preventa ti ve us e i n the a bs ence of brea s t ca ncer ha s a much l ower benefi t-tori s k ra ti o.
467. The answer is c. (Brunton, pp 1759-1760, 1177-1179, 1756; Katzung, pp 733, 740.) Ful ves tra nt i s a s s oci a ted wi th a much l ower ri s k of ca us i ng
endometri a l pa thol ogy, i ncl udi ng ca ncer. It i s a pure es trogen a nta goni s t. Tha t effect, i n brea s t ti s s ue, i s wha t a ccounts for the drugs benefi ci a l
effects i n s ome pa ti ents wi th meta s ta ti c, es trogen-s upported, brea s t ca ncer. In contra s t, ta moxi fen a nd toremi fene a re cl a s s i fi ed a s s el ecti ve
es trogen receptor modi fi ers (SERMs ). Al though they bl ock es trogen receptors i n brea s t ti s s ue (jus t a s ful ves tra nt does ), they a l s o ha ve es trogeni c
(a goni s t) a cti vi ty i n s ome other ti s s ues , nota bl y the uterus . There they ca n ca us e endometri a l prol i fera ti on, hyperpl a s i a , a nd (a ppa rentl y) a n
i ncrea s ed ri s k of endometri a l ca ncer.
Beca us e ful ves tra nt l a cks es trogen a goni s t a cti vi ty, i t wi l l not enha nce bone mi nera l i za ti on nor fa vora bl y modi fy chol es terol profi l es , a s the
SERMs tend to do. The SERMs s l i ghtl y i ncrea s e the ri s k of thromboembol i s m. Ful ves tra nt ma y too, but i t a l s o l a cks a ny a bi l i ty to prevent pl a tel et
a ggrega ti on or thromboembol i s m. Hot fl a s hes a re fa i rl y common wi th a ny of thes e drugs .
468. The answer is c. (Brunton, pp 1732-1734; Craig, p 653; Katzung, pp 966-967.) One of s evera l probl ems wi th i ma ti ni b thera py i s tha t i t i s a s ubs tra te
for, a nd ra ther powerful i nhi bi tor of, s evera l cytochromes (CYP3A4, 2C9, a nd 2D6) tha t a re i mporta nt for the meta bol i s m of ma ny other drugs
wa rfa ri n, theophyl l i ne, a nd ma ny others whos e a cti ons ca n be i ncrea s ed exces s i vel y i f dos a ges a re not a djus ted a ccordi ngl y. Convers el y,
i ma ti ni b i s a ta rget of i ntera cti ons by thi s mecha ni s m. Phenytoi n, ca rba ma zepi ne, ba rbi tura tes , a nd ri fa mpi n a re exa mpl es of drugs tha t ca n
i nduce i ma ti ni b meta bol i s m a nd reduce the cl i ni ca l res pons e to i t; a nd s uch drugs a s a zol e a nti funga l s a nd erythromyci n ca n reduce i ma ti ni bs
cl ea ra nce a nd i ncrea s e the ri s k of toxi ci ty.
Beca us e of the i s s ue of drug i ntera cti ons , a hi gh frequency of a dvers e res pons es , l i mi ted us e (s ee bel ow), a nd even cos t, i ma ti ni b i s genera l l y
res erved for us e a fter a tri a l of i nterferons ha s proven i na dequa te. The revers eus i ng i ma ti ni b fi rs tus ua l l y i s nt done.
Hypotens i on a nd hypovol emi a (b) a re not wha t one woul d expect wi th thi s drug. Ra ther, we s ee a ra ther hi gh i nci dence of fl ui d retenti on tha t
ma y not onl y a ffect bl ood pres s ure, but a l s o ca us e s uch other probl ems a s a s ci tes , peri ca rdi a l a nd pl eura l effus i ons , a nd pos s i bl y pul mona ry
edema . Li kewi s e, thrombocytos i s (e) i s the oppos i te of wha t typi ca l l y occurs : thrombocytopeni a a nd bl eedi ng probl ems , pl us neutropeni a a nd a n
i ncrea s ed ri s k of i nfecti on a re fa i rl y common.
Reca l l tha t chroni c myel ogenous l eukemi a cel l s do s ynthes i ze a n a bnorma l cons ti tuti vel y a cti ve tyros i ne ki na s e (Bcr-Abl ) tha t i s i nvol ved i n
(a bnorma l ) protei n phos phoryl a ti on. It i s tha t a berra nt tyros i ne ki na s enot ones found i n norma l hos t cel l s tha t i s a ffected by the drug a nd tha t
confers s el ecti vi ty for the drugs a cti ons . Thus , tyros i ne ki na s e i nhi bi ti on does not s eem to a ccount for the a dvers e effects of thi s drug on hos t
cel l s .
469. The answer is a. (Brunton, pp 1667-1674; Katzung, pp 951-953.) Gompertzi a n a na l ys i s (a pl ot of the l og of the number of ca ncer cel l s i n a tumor vs
ti me) s hows tha t a fter a tumor ha s rea ched a certa i n s i ze, the ra te of tumor growth (a nd overa l l meta bol i c ra te) s l ows : l ower growth fra cti on or,
s ta ted di fferentl y, the l onger i t ta kes for the tumor to doubl e i n s i ze. Thi s s l owed growth i s pa rti a l l y due to more cel l s enteri ng the G 0 (res ti ng)
pha s e of the cel l cycl e, where res pons i venes s to ma ny chemothera peuti c a gents i s l ower. (One rea s on for thi s i s the s heer s i ze of the tumor a s
rel a ted to bl ood fl ow a nd the del i very of nutri ents tha t the ra pi dl y di vi di ng cel l s need. Reduced nutri ent a nd oxygen del i very not onl y reduce cel l
repl i ca ti on, but a l s o del i very of the chemothera peuti c a gents . Therefore a ns wer b i s i ncorrect.)
P-gl ycoprotei n a cti vi ty (c) does not neces s a ri l y decrea s e wi th ti me or tumor s i ze. However, even i f i t di d, tha t woul d predi ct i ncrea s ed
res pons i venes s to mos t a nti ca ncer drugs , beca us e i t i s P-gl ycoprotei n tha t norma l l y pumps drugs out of the ca ncer cel l . Sel f-repa i r mecha ni s ms , a s
by topoi s omera s e (e), i s not a fa ctor i n expl a i ni ng reduced vul nera bi l i ty of very l a rge tumors .
470. The answer is b. (Brunton, pp 1205, 1766, 1841; Katzung, pp 738-740.) Fl uta mi de, one of a s ma l l number of a ndrogen receptor bl ockers us ed for
ma na gi ng pros ta te ca ncer, i s us ed a s a n a djunct to l euprol i de. Leuprol i de a cts l i ke gona dotropi n-rel ea s i ng hormone (GnRH; or l utei ni zi ng
hormone-rel ea s i ng hormone). When l euprol i de thera py i s s ta rted, i t s ti mul a tes rel ea s e of i nters ti ti a l cel l -s ti mul a ti ng hormone from the pi tui ta ry,
thereby i ncrea s i ng tes tos terone producti on a nd s upporti ng tumor growth. It i s onl y wi th conti nued expos ure to l euprol i de tha t GnRH receptors
become des ens i ti zed, a nd the eventua l i nhi bi ti on of tes tos terone producti on (a nd, thereby, s upport of tumor growth) occurs . Fl uta mi de, by
bl ocki ng a ndrogen receptors , prevents the potenti a l wors eni ng of the tumor i n the ea rl y pha s e of l euprol i de thera py when tes tos terone l evel s
ri s e. Even when l euprol i des pi tui ta ry-des ens i ti zi ng effects occur, a ndrogens tha t ca n s upport pros ta te tumor growth wi l l come from the a drena l
gl a nd. Thei r effects , too, a re bl ocked by the fl uta mi de.
471. The answer is a. (Brunton, pp 1677-1681, 1683; Katzung, pp 953-955, 956t.) Mechl oretha mi ne, l i ke cycl ophos pha mi de (a nd ca rmus ti ne a nd s evera l
others ), i s a n a l kyl a ti ng a gent. They a re ca l l ed bi functi ona l a l kyl a ti ng a gents beca us e they ca n cova l entl y bi nd to DNA i n two pl a ces (nucl eophi l i c
a tta ck), thereby formi ng cros s -l i nks between two a dja cent s tra nds or between two ba s es i n one s tra nd. Thi s ul ti ma tel y di s rupts DNA a nd RNA
s ynthes i s or ma y ca us e s tra nd brea ka ge. Cycl ophos pha mi de (whi ch ca n be cons i dered the prototype of the a l kyl a ti ng a gents ) i s a ctua l l y a prodrug
i t requi res meta bol i c a cti va ti on i n order for i ts effects to occur. Cycl ophos pha mi des (a nd other a l kyl a ti ng a gents ) a re cel l cycl e-nons peci fi c,
a l though thei r effi ca cy i s grea ter when cel l s a re not i n G 0 .
Bl eomyci n, da cti nomyci n, a nd doxorubi ci n a re good exa mpl es of drugs tha t i nterca l a te i n DNA s tra nds (d). Thus , the a l tered DNA no l onger
s erves a s a n a dequa tel y preci s e templ a te for eventua l s ynthes i s of more functi ona l DNA a nd RNA. They a re cl a s s i fi ed a s a nti tumor a nti bi oti cs .
Etopos i de a nd topoteca n a re exa mpl es of drugs tha t i nhi bi t topoi s om-era s e II (c). The cons equence i s i nhi bi ted a bi l i ty of a ffected cel l s to
repa i r DNA s tra nd brea ks . Thi s s tops the cel l cycl e i n G 2 .
The ta xoi ds (eg, pa cl i ta xel ) i mpa i r mi tos i s (b), but by s ta bi l i zi ng a s s embl ed mi crotubul es ra ther tha n by exerti ng a vi nca a l ka l oi d-l i ke i nhi bi ti on

of mi crotubul a r a s s embl y.
472. The answer is a. (Brunton, pp 1720-1721; Katzung, pp 967-969.) As pa ra gi na s e i s a n enzyme tha t ca ta l yzes the hydrol ys i s of pl a s ma a s pa ra gi ne to
a s pa rti c a ci d a nd a mmoni a . Ma jor toxi ci ti es from a s pa ra gi na s e a re rel a ted to a nti geni ci ty (i t i s a forei gn protei n, a nd s ome fa ta l a na phyl a cti c
rea cti ons ha ve occurred), pa ncrea ti ti s , a nd a 50% i nci dence of s ome hepa ti c dys functi on ba s ed on the pres ence of el eva ted tra ns a mi na s es . The
drug, whi ch i s l a rgel y G 1 pha s e-s peci fi c, i s not cytotoxi c to cel l s other tha n l eukemi c l ymphobl a s ts . Hos t (a nd other cel l s ) ca n s ynthes i ze a nd
repl a ce a s pa ra gi ne tha t ha s been hydrol yzed by the drug; the l ymphobl a s ts ca nnot, a nd s o they a re ki l l ed.
The res pons es ci ted a re not typi ca l of a za thi opri ne (b), doxorubi ci n (c) or other a nti bi oti c a nti ca ncer a gents , methotrexa te (d), or the vi nca
a l ka l oi ds (eg, vi ncri s ti ne, e).
473. The answer is b. (Brunton, pp 685-686, 1541, 1682t, 1688-1689; Katzung, pp 956-958.) Ci s pl a ti n, whi ch i s s ometi mes cl a s s i fi ed a l ong wi th tra di ti ona l
a l kyl a ti ng a gents , i s uni que a mong a l l the common a nti ca ncer a gents i n terms of the rel a ti ve i nci dence of hea ri ng l os s (ototoxi ci ty) a nd
nephrotoxi ci ty.
You a re correct i n a s s oci a ti ng vi ncri s ti ne wi th hea ri ng l os s , but nephrotoxi ci ty i s very ra re; i n contra s t, you ma y ha ve reca l l ed tha t methotrexa te
ca n ca us e nephrotoxi ci ty, but i t does not ca us e hea ri ng l os s , a nd i t i s i ndi ca ted for a va ri ety of ca ncers , but not ova ri a n.
Bl eomyci ns (a ) ma i n ta rgeted toxi ci ty i s the l ungs (pul mona ry i nfi l tra tes , fi bros i s , etc). Doxorubi ci n (c), a s noted el s ewhere, i s ca rdi otoxi c. The
drug i s ma i nl y us ed for tes ti cul a r ca rci noma s , s qua mous cel l ca ncers , a nd l ymphoma s . 5-FU (d), a pyri mi di ne a nti meta bol i te, i s us ed for a va ri ety
of s ol i d tumors . However, peri phera l neuri ti s or neuropa thy (a nd, es peci a l l y, hea ri ng l os s ) or rena l da ma ge a re uncommon; ra ther, there i s a
rel a ti vel y hi gh i nci dence of bone ma rrow s uppres s i on a nd ora l a nd GI mucos a l da ma ge. Pa cl i ta xel (e) i s a mi crotubul a r s ta bi l i zi ng drug (a nd pl a nt
a l ka l oi d). It i s cons i dered fi rs t-l i ne for s ome pa ti ents wi th a dva nced ova ri a n ca ncer or non-s ma l l -cel l l ung ca ncers , ca us es dos e-dependent bone
ma rrow s uppres s i on a nd peri phera l neuropa thy, a nd a fa i rl y hi gh i nci dence of a cute i nfus i on-rel a ted hypers ens i ti vi ty rea cti ons (proba bl y due to
the vehi cl e i n whi ch the drug i s del i vered).
474. The answer is d. (Brunton, pp 1074-1075, 1745, 1750; Katzung, p 598.) Fi l gra s ti m, a l s o known a s gra nul ocyte col ony-s ti mul a ti ng fa ctor (GCSF),
enha nces neutrophi l producti on. One us e, therefore, i s to prevent neutropeni a a nd i nfecti on a s s oci a ted wi th bone ma rrow depres s i on from ca ncer
chemothera py. (Hi nt: Look a t the generi c na me, fi l gra s ti m: granu-l ocyte stimul a ti ng.) The drug l a cks a nti emeti c effects (a ), potenti a tes the
chemothera peuti c a cti ons of no drug (b), a nd ha s no effect on doxorubi ci n-medi a ted ca rdi otoxi ci ty (c) or on chemothera py-rel a ted a dvers e effects
on the ga s tri c mucos a (e).
475. The answer is e. (Brunton, pp 997, 1000; Katzung, pp 653-654.) Hyperuri cemi a i s a s s oci a ted wi th ma ny ca ncers a nd i s a common outcome of ma s s i ve
cel l ki l l s i nduced by chemothera peuti c drugs , es peci a l l y wi th bl ood-i nvol ved (di s s emi na ted) ca ncers s uch a s l eukemi a s . The uri c a ci d i s deri ved
from cel l ul a r puri ne degra da ti on, eventua l l y formed from hypoxa nthi ne a nd xa nthi ne vi a xa nthi ne oxi da s e, the enzyme tha t i s i nhi bi ted by
a l l opuri nol . Reca l l tha t rena l da ma ge (a nd other da ma ge, s uch a s gout) i s due to uri c a ci ds poor s ol ubi l i ty i n body fl ui ds , es peci a l l y a t l ow pH.
Al l opuri nol ha s no effect on the P450 s ys tem or on cel l ul a r tra ns i ti ons from one pha s e of the cel l cycl e to a nother. There i s no effect on DNA
s ynthes i s or repa i r, or a ny di rect cytoprotecti ve effect on myel oi d or other ti s s ues .
Be s ure to remember tha t the meta bol i c detoxi fi ca ti on of a za thi opri ne a nd i ts a cti ve meta bol i te 6-merca ptopuri ne (i ts el f a n a nti ca ncer drug)
depends i n pa rt on xa nthi ne oxi da s e. Inhi bi ti ng tha t enzyme wi th a l l opuri nol (or the rel a ti vel y new rel a ted xa nthi ne oxi da s e i nhi bi tor,
febuxos ta t), therefore, ma y i ncrea s e the ri s k of toxi ci ty to hos t cel l s .
476. The answer is d. (Brunton, pp 1177-1180, 1299-1300, 1756-1759; Katzung, pp 731, 740.) Of a l l the drugs l i s ted a s pos s i bl e a ns wers , onl y ta moxi fen, a
s el ecti ve es trogen receptor modi fi er (SERM), fi ts the des cri pti on: i t requi res meta bol i c a cti va ti on for a nti ca ncer effects (the a cti ve meta bol i te i s
a bout 100-ti mes more potent tha n ta moxi fen i ts el f), i t i s i ndi ca ted for es trogen-s ens i ti ve brea s t ca rci noma (trea tment or prophyl a xi s a ga i ns t
recurrence), i s a s s oci a ted wi th a hi gh i nci dence of s evere na us ea a nd vomi ti ng, a nd tends to ca us e hot fl a s hes i n ma ny women (typi ca l l y a
del a yed res pons e occurri ng l a te i n, or a fter, trea tment wi th ta moxi fen). Da ta s ugges t tha t women ta ki ng one of the l i s ted SSRIs wi th ta moxi fen,
us ed for brea s t ca ncer prophyl a xi s , ha ve hi gher ra tes of recurrence tha n thos e ta ki ng other SSRIs , or no a nti depres s a nts a t a l l .
The i ntera cti on does not a ppl y to bl eomyci n (a ), i nterferons (b), merca ptopuri ne (c; a l though merca ptopuri ne i s a cri ti ca l ta rget of certa i n drug
i ntera cti ons , di s cus s ed el s ewhere), or vi nca a l ka l oi ds (eg, vi nbl a s ti ne, e).
Note: It s houl d not be s urpri s i ng tha t ma ny women who ha ve ca ncer, or a re a t ri s k of recurrences , mi ght benefi t from a n a nti depres s a nt, a nd
SSRIs genera l l y a re the preferred drugs . Fl uoxeti ne, pa roxeti ne, a nd s ertra -l i ne i ntera ct a dvers el y wi th ta moxi fen, due to s trong CYP2D6 i nhi bi ti on,
not a l l SSRIs do. Ci ta l opra m, es ci ta l opra m, a nd fl uvoxa mi ne a re not s trong 2D6 i nhi bi tors , a nd s o they a re genera l l y preferred when concomi ta nt
SSRI thera py i s wa rra nted.
477. The answer is e. (Brunton, pp 997, 1701-1702; Katzung, pp 653-654.) Merca ptopuri ne i s a (thi o)puri ne a nti meta bol i te tha t i s meta bol i ca l l y
i na cti va ted (detoxi fi ed) by xa nthi ne oxi da s e. Thi s puri ne degra da ti on pa thwa y i n whi ch xa nthi ne oxi da s e pa rti ci pa tes not onl y l ea ds to forma ti on
of uri c a ci d, but a l s o i s i mporta nt to reduci ng hos t cel l toxi ci ty to the thi opuri nes . Thus , concomi ta nt us e of a l l opuri nol i ncrea s es the ri s k of hos t
cel l toxi ci ty. The s a me a ppl i es to the newes t a pproved xa nthi ne oxi da s e i nhi bi tor, febuxos ta t. Note tha t a za thi opri ne (a n i nhi bi tor of B a nd T
l ymphocyte prol i fera ti on, typi ca l l y us ed a s a n i mmunos uppres s a nt) i s meta bol i zed to merca ptopuri ne. As a res ul t, i ts meta bol i s m i s a l s o
i nhi bi ted by a l l opuri nol .
The meta bol i s m of the other drugs l i s ted i s not xa nthi ne oxi da s e-dependent, a nd s o i s not a ffected by a l l opuri nol .
478. The answer is d. (Brunton, pp 1011-1012, 1821; Katzung, pp 644, 986, 999, 1156t.) Nephrotoxi ci ty, or a t l ea s t s ome cl i ni ca l l y s i gni fi ca nt degree of
rena l dys functi on, occurs i n a bout 8 of 10 pa ti ents recei vi ng cycl os pori ne. It i s typi ca l l y dos e-dependent a nd, pa rti cul a rl y i n rena l tra ns pl a nt
pa ti ents , coul d be due to ei ther the drug (too much) or to rejecti on. Infecti on occurs a bout a s often a s rena l dys functi on. Cycl os pori ne ca n ca us e
hepa totoxi ci ty (a ), but the i nci dence i s fa r l ower tha n tha t of a dvers e rena l res pons es or i nfecti on. Ca rdi otoxi ci ty i s not a n i s s ue. Bl ood pres s ure
cha nges (c) ca n occur, but wi th cycl os pori ne the cha nge more l i kel y i nvol ves i ncrea s ed pres s ure. Ca rdi a c or pul mona ry toxi ci ti es a nd
thromboembol i s m (e) due to the drug i ts el f a re extremel y uncommon.

Toxicology, Bioterrorism, and Chemical Warfare Agents

Al cohol s , ethyl ene gl ycol
Anti dotes for common drugs
Bi oterrori s m or chemi ca l wa rfa re a gents
Hea vy meta l s
Poi s oni ngs of unknown ca us e
Poi s oni ng s yndromes
Toxi c ga s es

Questions
479. A pa ti ent devel ops s ta tus epi l epti cus from a n unknown poi s oni ng. Whi ch of the fol l owi ng i s the mos t a ppropri a te fi rs t IV drug to gi ve?
a . Ca rba ma zepi ne
b. Lora zepa m
c. Phenoba rbi ta l
d. Phenytoi n
e. Va l proi c a ci d
480. A fi refi ghter who i s tryi ng to exti ngui s h a ca r fi re ha s a l ea k i n hi s protecti ve a i r ma s k. He devel ops cya ni de poi s oni ng from the combus ti on of
pl a s ti c. As i de from renderi ng s ymptoma ti c, s upporti ve ca re, whi ch mi ght be a dmi ni s tered to comba t the cya ni de poi s oni ng?
a . Ammoni um chl ori de
b. Deferoxa mi ne
c. Di merca prol (BAL; Bri ti s h a nti -l ewi s i te)
d. Ma nni tol
e. Pra l i doxi me
f. Sodi um thi os ul fa te
481. A 28-yea r-ol d ma l e pa ti ent i s tra ns ported to the emergency depa rtment a fter a ma s s i ve expos ure to ca rbon tetra chl ori de (CCl 4 ), a s ol vent us ed
a t hi s work. Whi ch one of the fol l owi ng bes t des cri bes a cha ra cteri s ti c of poi s oni ng wi th thi s toxi ca nt, or i ts cl i ni ca l ma na gement?
a . Ca us es a s l ow dea th due to bone ma rrow s uppres s i on
b. Ca us es wi des prea d ATP depl eti on by uncoupl i ng oxi da ti ve phos phoryl a ti on
c. Meta bol i zed to free ra di ca l s (tri chl oro ra di ca l s ) tha t a re di rectl y cytotoxi c to l i ver a nd ki dney cel l s
d. N-Acetyl cys tei ne effecti vel y s ca venges ca rbon tetra chl ori des cytotoxi c meta bol i te
e. Toxi c cons equences reduced or prevented by a dmi ni s tra ti on of methyl ene bl ue
482. A pa ti ent who ha s been on l ong-term thera py wi th a drug devel ops a l upus -l i ke s yndrome i n res pons e to i t. Wi th whi ch drug i s thi s res pons e,
proba bl y medi a ted by a n a utoi mmune rea cti on, mos t l i kel y to occur?
a . Di oxi n
b. Hydra l a zi ne
c. Orga ni c mercury
d. Pri ma qui ne
e. Tri cycl i c a nti depres s a nts (eg, a mi tri ptyl i ne)
483. A pa ti ent pres ents i n the emergency depa rtment wi th a drug overdos e. Among other thi ngs , the phys i ci a n correctl y orders IV i nfus i on of
s odi um bi ca rbona te to a l ka l i ni ze the uri ne, whi ch i ncrea s es the toxi ns el i mi na ti on through pH-dependent i nhi bi ti on of i ts tubul a r rea bs orpti on,
a nd hel ps correct the combi ned meta bol i c a nd res pi ra tory a ci dos i s the toxi n ca us ed. Whi ch one of the fol l owi ng drugs mos t l i kel y ca us ed the
toxi ci ty?
a . Ampheta mi ne
b. As pi ri n (a cetyl s a l i cyl i c a ci d)
c. Coca i ne
d. Morphi ne
e. Phencycl i di ne (PCP)
484. A pa ti ent ha s ta ken a potenti a l l y l etha l dos e of a ceta mi nophen. The emergency depa rtment tea m begi ns a dmi ni s teri ng repea ted dos es of Na cetyl cys tei ne, whi ch ca n be a l i fes a vi ng a nti dote i n ma ny s uch ca s es . Wha t i s the ma i n mecha ni s m by whi ch thi s a nti dote exerts i ts benefi ci a l
effects ?
a . Al ka l i ni zes the uri ne to fa ci l i ta te a ceta mi nophen excreti on
b. Ca us es meta bol i c a ci dos i s to countera ct meta bol i c a l ka l os i s ca us ed by a toxi c a ceta mi nophen meta bol i te
c. Inhi bi ts P450 enzymes , thereby i nhi bi ti ng forma ti on of a ceta mi nophens toxi c meta bol i te
d. Inhi bi ts s ynthes i s of s uperoxi de a ni on ra di ca l a nd hydrogen peroxi de
e. Is ri ch i n s ul fhydryl (SH) groups tha t rea ct wi th a nd i na cti va te the toxi c a ceta mi nophen meta bol i te, s pa ri ng hepa tocytes from a tta ck by the
meta bol i te

485. Your pa ti ent devel oped a cute poi s oni ng a s a res ul t of i nha l i ng cya ni de ga s i n a n i ndus tri a l a cci dent. In a ddi ti on to provi di ng s ymptoma ti c,
s upporti ve ca re, a nd other a ppropri a te i nterventi ons , a dmi ni s teri ng whi ch one of the fol l owi ng woul d be mos t l i kel y to be effecti ve a s a n
a djuncti ve drug, i n trea ti ng the cya ni de poi s oni ng?
a . Ammoni um chl ori de
b. Deferoxa mi ne
c. Di merca prol (BAL; Bri ti s h a nti -Lewi s i te)
d. N-a cetyl cys tei ne
e. Pra l i doxi me
f. Sodi um thi os ul fa te
486. A 5-yea r-ol d boy cons umed a l i qui d from a conta i ner i n the fa mi l y ga ra ge. He pres ents wi th centra l nervous s ys tem (CNS) depres s i on,
obtunded refl exes , a nd venti l a tory depres s i on. A bl ood s a mpl e i ndi ca tes profound meta bol i c a ci dos i s a nd a n a ni on ga p. A check of the uri ne
revea l s crys ta l s tha t a re pres umed to be oxa l a te. Wha t i s the mos t l i kel y ca us e of the poi s oni ng?
a . A ha l ogena ted hydroca rbon from a ca n of s pra y pa i nt
b. An i ns ecti ci de
c. Ethyl ene gl ycol
d. Ga s ol i ne
e. Pa i nt thi nner
487. A fa rm worker i n Ca l i forni a i s brought emergentl y, a nd decl a red dea d on a rri va l , to a l oca l emergency depa rtment. He ha d been expos ed to a n
a gri cul tura l toxi n. A coworker, who wa s not poi s oned but wa s nea rby ri ght a fter the ti me of expos ure, s a i d, He jus t s ta rted s ha ki ng ba d, col l a ps ed,
a nd i mmedi a tel y s topped brea thi ng. I di dnt s ee a nythi ng el s e ha ppen. He l ooked perfectl y norma l one mi nute, then he wa s jus t dea d. Wha t wa s
the mos t l i kel y ca us e of thi s ma ns dea th?
a . Chol i nes tera s e i nhi bi tor i ns ecti ci de, s pra yed by a crop dus ter a i rpl a ne
b. Keros ene from a ba rn hea ter, i nges ted
c. Long-term a nd cumul a ti ve cuta neous expos ure to a rs eni c, toda ys expos ure provi ng ra pi dl y fa ta l
d. Petrol eum di s ti l l a tes us ed to cl ea n grea s e off fa rm ma chi nery, i nha l ed
e. Strychni ne, i nges ted
Questions 488 to 489
Here i s a n excerpt from news pa per a rti cl e enti tl ed Weed Users Chase High all the Way to the Hospital. Us e i t to a ns wer the next two ques ti ons , a nd
note tha t the weed referred to does not i ncl ude ma ri jua na or a ny other pl a nts tha t conta i n tetra hydroca nna bi nol or a n opi oi d.
Teena gers s eeki ng a ha l l uci nogeni c hi gh from the s eeds of a poi s onous weed tha t now i s i n bl oom a re l a ndi ng i n hos pi ta l s a cros s the country,
pol i ce a nd hea l th offi ci a l s s a y Luna ti c, cra zy ki ds , s a ys Dodge County, Wi s ., Sheri ff Todd Nehl s , whos e deputi es pi cked up three ha l l uci na ti ng
teena gers i n October.
Poi s on centers l a s t yea r recorded 975 i nci dents i nvol vi ng pl a nts s uch a s [the] weed a ccordi ng to the Ameri ca n As s oci a ti on of Poi s on Control
Centers a nnua l report.
[The weed ha s ] pods tha t conta i n s eeds tha t when ea ten or brewed i n a tea ca n ca us e s evere ha l l uci na ti ons [del i ri um] a nd other rea cti ons ,
i ncl udi ng dry mouth, overhea ti ng [fever], a gi ta ti on, [a nd] uri na ry retenti on Some ca nnot uri na te a nd need to ha ve a ca theter i ns erted [Severe]
overdos es ca n l ea d to s ei zures , coma , or dea th Mos t peopl e hos pi ta l i zed a fter ea ti ng [the] weed ha ve ha l l uci na ti ons tha t ma ke them s o erra ti c
they a re a da nger to thems el ves
a . Acetyl chol i ne
b. Ampheta mi ne
c. Bel l a donna a l ka l oi ds
d. Betha nechol
e. Coca i ne
f. Cya ni de
g. Fl uoxeti ne
h. Neos ti gmi ne
i . Phencycl i di ne (PCP)
j. Phys os ti gmi ne
k. Strychni ne
488. Whi ch drug l i s ted a bove ca us es s i gns a nd s ymptoms tha t a re mos t s i mi l a r toi ndeed, vi rtua l l y i denti ca l tothos e des cri bed i n the s cena ri o?
489. Whi ch drug woul d be mos t ra ti ona l a nd mos t effecti ve for trea ti ng the overdos e, a s s umi ng the overdos e i s s evere enough to wa rra nt drug
thera py?
490. A mother ca l l s to report tha t her 6-yea r-ol d chi l d a ppea rs to ha ve s wa l l owed a l a rge a mount of a n over-the-counter s l eep a i d a bout 5 hours
a go. The product conta i ned onl y one a cti ve drug, a nd knowi ng your drugs you s us pect the poi s oni ng i s due to di phenhydra mi ne. As s umi ng your
rea s oned gues s a bout the ca us e of poi s oni ng wa s correct, whi ch of the fol l owi ng s i gns or s ymptoms woul d you expect to fi nd, upon phys i ca l exa m,
to confi rm your hunch?
a . Fever; cl ea r l ungs ; a bs ence of bowel s ounds ; uri na ry retenti on, dry, fl us hed s ki n; mydri a s i s a nd photophobi a ; bi za rre beha vi or
b. Bra dyca rdi a a nd profus e di a rrhea
c. Mi os i s wi th l i ttl e/no pa pi l l a ry res pons e to bri ght l i ghts ; s ponta neous mi cturi ti on; l a ck of res pons e to pa i nful s ti mul i
d. Hypothermi a ; boundi ng pul s e; hypertens i on

e. Skel eta l mus cl e wea knes s or pa ra l ys i s ; profound hypermoti l i ty of gut a nd bl a dder s mooth mus cl e; bronchos pa s m
491. A 3-yea r-ol d gi rl i nges ts 30 ta bl ets of a s pi ri n, 325 mg ea ch. Weve gotten her to the emergency depa rtment wi thi n 30 mi nutes of the poi s oni ng.
Whi ch one of the fol l owi ng drugs woul d be the mos t ra ti ona l a nd hopeful l y effecti ve to a dmi ni s ter a s pa rt of the i ni ti a l trea tment pl a n for wha t
otherwi s e coul d ha ve a fa ta l outcome?
a . Acti va ted cha rcoa l
b. Deferoxa mi ne
c. Di merca prol
d. N-Acetyl cys tei ne
e. Peni ci l l a mi ne
492. A 50-yea r-ol d ma n ha s been cons umi ng l a rge a mounts of etha nol on a n a l mos t da i l y ba s i s for ma ny yea rs . One da y, una bl e to fi nd a ny
etha nol , he i nges ts a l a rge a mount of metha nol (wood a l cohol ) tha t he ha d bought for hi s ca mp l a ntern. Whi ch of the fol l owi ng i s the mos t l i kel y
cons equence of hi s metha nol poi s oni ng?
a . Atri oventri cul a r conducti on defect (bl ock)
b. Bl i ndnes s
c. Bronchos pa s m
d. Del i ri um tremens
e. Meta bol i c a l ka l os i s
493. A 15-yea r-ol d boy a ttempts s ui ci de wi th a l i qui d tha t he found i n hi s pa rents greenhous e. Hi s da d us ed i t to get ri d of va rmi nts a round the
ya rd. The toxi n ca us es i ntens e a bdomi na l pa i n, s kel eta l mus cl e cra mps , projecti l e vomi ti ng, a nd s evere di a rrhea tha t l ea ds to fl ui d a nd
el ectrol yte i mba l a nces , hypotens i on, a nd di ffi cul ty s wa l l owi ng. On exa mi na ti on he i s found to be vol ume depl eted a nd i s s howi ng s i gns of a
reduced l evel of cons ci ous nes s . Hi s brea th s mel l s meta l l i c. Whi ch of the fol l owi ng proba bl y a ccounts for thes e s ymptoms ?
a . Ars eni c
b. Ca dmi um
c. Iron
d. Lea d
e. Zi nc
494. A 22-yea r-ol d i s brought to the emergency depa rtment by a fri end. They ha d been a t a ba r for a bout a n hour, a nd then the pa ti ent s uddenl y
beca me drows y but wa s s ti l l cons ci ous . She fel l a nd cut her hea d, a nd ha s l i ttl e di ffi cul ty feel i ng the pa i n from the tra uma . Her venti l a tory ra te
a nd depth a re depres s ed, but not to a worri s ome degree. Her pa tel l a r refl exes a re bl unted a nd s he i s a ta xi c. She res ponds s l owl y to ques ti ons but
i s una bl e to reca l l a nythi ng tha t ha ppened a fter a rri vi ng a t the ba r a nd s i ppi ng her fi rs t (a nd l a s t) a dul t bevera ge. Her fri end s ta ted tha t s he ha d
onl y one Cos mopol i ta n a nd ha dnt been dri nki ng before they went out. Wi th wha t wa s thi s pa ti ents dri nk mos t l i kel y s pi ked?
a . A ba rbi tura te
b. A benzodi a zepi ne
c. An opi oi d
d. Chl ora l hydra te
e. Coca i ne
f. Pure (gra i n) a l cohol
495. Lets a s s ume the profoundl y CNS-depres s ed pa ti ent i n the previ ous ques ti on i ndeed wa s overdos ed wi th a benzodi a zepi ne. Whi ch drug i s
mos t l i kel y to be effecti ve, i ndeed woul d be a preferred pha rma col ogi c a nti dote, i f tha t were the ca s e?
a . Ampheta mi ne
b. Fl uma zeni l
c. Methyl pheni da te
d. Na l trexone
e. Phys os ti gmi ne
496. Recent occupa ti ona l hea l th s tudi es i n s evera l hea vi l y popul a ted urba n a rea s ha ve revea l ed a n a s toni s hi ngl y l a rge number of homes tha t
ha ve l ea d-ba s ed pa i nt a nd chi l dren l i vi ng i n them. However, a number of envi ronmenta l poi s ons tha t coul d l ea d to a cute or chroni c poi s oni ng
ha ve a l s o been found there. Whi ch s i gns a nd s ymptoms woul d be cons i s tent wi th chroni c expos ure to toxi c l evel s of i norga ni c l ea d?
a . Anorexi a a nd wei ght l os s ; wea knes s , es peci a l l y of extens or mus cl es (eg, wri s t drop); recurrent a bdomi na l pa i n
b. Gi ngi vi ti s , di s col ored gums , l oos ened teeth, or s toma ti ti s ; tremor of the extremi ti es ; s wol l en pa roti d or other s a l i va ry gl a nds
c. Ha l l uci na ti ons , i ns omni a , hea da che, genera l i zed CNS i rri ta bi l i ty
d. Hyperventi l a ti on i n res pons e to meta bol i c a ci dos i s ; hypotens i on; a bdomi na l pa i n, di a rrhea , brown or bl oody vomi tus ; pa l l or or cya nos i s
e. Severe, wa tery di a rrhea ; ga rl i cky or meta l l i c brea th; encepha l opa thy, hypovol emi a a nd hypotens i on
497. La b tes ts conducted by the l oca l hea l th depa rtment a re pos i ti ve for chroni c l ea d expos ure i n a chi l d. Lea d l evel s a re s i gni fi ca ntl y el eva ted, but
s ymptoms fortuna tel y a re mi l d a nd not a t a l l i mmi nentl y l i fe-threa teni ng. Wha t i s the mos t a ppropri a te a nti dote for reduci ng the chi l ds body l oa d
of l ea d?
a . Ca -Na 2 -EDTA
b. Deferoxa mi ne
c. Di merca prol

d. N-Acetyl cys tei ne

e. Peni ci l l a mi ne
f. Succi mer
498. Not l ong a go, s evera l pa ti ents (a nd a ra ther s ha dy hea l th ca re provi der who i s now i nca rcera ted) s eeki ng rel i ef from fa ci a l wri nkl es nea rl y
di ed beca us e they recei ved i njecti ons of botul i num toxi n tha t wa s i mproperl y obta i ned a nd i na dequa tel y di l uted. Whi ch i s a correct cha ra cteri s ti c,
fi ndi ng, or mecha ni s m a s s oci a ted wi th thi s toxi n?
a . Compl ete fa i l ure of a l l chol i nergi c neurotra ns mi s s i on
b. Fa vora bl e res pons e to a dmi ni s tra ti on of pra l i doxi me
c. Impa i rment of pa ra s ympa theti c, but not s ympa theti c, nervous s ys tem a cti va ti on
d. Ma s s i ve overs ti mul a ti on of a l l s tructures ha vi ng mus ca ri ni c chol i nergi c receptors
e. Sel ecti ve pa ra l ys i s of s kel eta l mus cl e
499. A terrori s t drops a vi a l of nerve ga s i nto a crowded s ubwa y a t rus h hour. The pa ti ents a re brought to the nea res t emergency centers a nd a re
gi ven a tropi ne. Whi ch effect of the nerve ga s wi l l pers i s t a fter gi vi ng the a tropi ne?
a . Bra dyca rdi a
b. Bronchos pa s m
c. Exces s i ve l a cri ma l , mucus , s wea t, a nd s a l i va ry s ecreti ons
d. GI hypermoti l i ty, fl ui d a nd el ectrol yte l os s from profus e di a rrhea
e. Skel eta l mus cl e hyperfuncti on or pa ra l ys i s
500. A nei ghbor ca l l s you for a dvi ce a nd hel p. She knows you a re not a veteri na ry s tudent, but s i nce youre goi ng to be a phys i ci a n s oon s he fi gures
you know everythi ng. Her pet puppy, Pooki e, a Peki nges e, ha s ea ten a l a rge a mount of rodent (ra t a nd mous e) poi s on. Shes pa ni cked a nd pl ea ds
to know i f the preci ous pooch i s poi s oned. The rodenti ci de i ndeed conta i ns a powerful poi s on i ntended to ki l l ra ts a nd mi ce, but i t ca n do the
s a me to a ny other a ni ma l s tha t ha ve i nges ted i t too, i ncl udi ng huma ns . Wha t i s the mos t l i kel y toxi c i ngredi ent i n thes e rodenti ci des , a nd
proba bl y wi l l ca us e poor Pooki e pronounced probl ems ?
a . Ampheta mi ne-coca i ne combi na ti on
b. Morphi ne
c. Succi nyl chol i ne
d. Vecuroni um (or a s i mi l a r neuromus cul a r bl ocker)
e. Wa rfa ri n

Toxicology, Bioterrorism, and Chemical Warfare Agents

Answers
479. The answer is b. (Brunton et al., pp 452-455; Katzung, pp 394, 397-398, 985.) Intra venous l y a dmi ni s tered l ora zepa m i s the i ni ti a l drug of choi ce for
trea tment of s ta tus epi l epti cus , es peci a l l y when the ca us e of thi s l i fe-threa teni ng s ei zure (a nd a s peci fi c a nti dote) a re unknown. Lora zepa m, l i ke
the benzodi a zepi nes i n genera l , i ncrea s es the a ppa rent a ffi ni ty of the i nhi bi tory neurotra ns mi tter GABA for bi ndi ng s i tes on bra i n cel l
membra nes . The effects of l ora zepa m (or di a zepa m) a re s hort-l a s ti ng. Immedi a tel y a fter gi vi ng i t ei ther phenytoi n or fos -phenytoi n s houl d be
gi ven to provi de l onger s ei zure s uppres s i on a nd covera ge beca us e the effects of l ora zepa m wea r off i n a compa ra ti vel y s hort ti me. Other drugs
tha t ca n be us ed for s ta tus epi l epti cus i ncl ude phenoba rbi ta l (not a drug of choi ce) a nd (pa ra doxi ca l l y) l i doca i ne for refra ctory s ei zures (ma i nl y a
drug of l a s t res ort). None of the other drugs l i s ted i n the ques ti on a re a ppropri a te for s ta tus epi l epti cus , des pi te thei r wi des prea d us e for ora l
thera py of s ei zure di s orders l ong term.
480. The answer is f. (Brunton, p 86t; Katzung, p 1036.) Cya ni de rea cts wi th Fe(III) i n mi tochondri a l cytochrome oxi da s e, i nhi bi ti ng oxi da ti ve
phos phoryl a ti on. The s hi ft i n meta bol i s m from a erobi c to gl ycol yti c s oon l ea ds to not onl y ATP depl eti on, but a l s o s evere l a cti c a ci dos i s .
Cya ni de norma l l y rea cts wi th endogenous s ul fur-conta i ni ng compounds , ma i nl y thi os ul fa te, a nd under ca ta l ys i s by rhoda nes e forms rel a ti vel y
l es s toxi c thi ocya na te tha t i s formed a nd excreted i n the uri ne. In cya ni de poi s oni ng, endogenous s ul fur-conta i ni ng s ubs tra te s tores a re qui ckl y
depl eted. We ma na ge thi s , then, by IV i nfus i on of a n a queous s odi um thi os ul fa te s ol uti on. (Thi s i s the s a me a pproa ch we us e for thera peuti c
cya ni de poi s oni ng, a s ca n a ri s e when ni troprus s i de dos es a re too grea t.)
Ammoni um chl ori de woul d be i neffecti ve, a nd ma y a ctua l l y ma ke ma tters wors e by exa cerba ti ng meta bol i c a ci dos i s . Deferoxa mi ne, a n i ron
chel a tor, woul d be of no benefi t i n terms of s i gns , s ymptoms , or thei r ca us es or cons equences . Di merca prol i s a hea vy meta l (ma i nl y l ea d)
chel a tor tha t woul d be of no benefi t. Ma nni tol a nd os moti c di ureti c tha t i s s ometi mes us ed to ha s ten the rena l excreti on of s ome toxi ns (vi a
forced di ures i s ) woul d not a l l evi a te or s horten s i gns a nd s ymptoms . Pra l i doxi me i s a chol i nes tera s e rea cti va tor tha t i s effecti ve onl y for
poi s oni ng wi th orga nophos pha te i ns ecti ci des , nerve ga s es (s a ri n, s oma n), or other drugs tha t ca us e profound a nd l a rgel y perma nent i na cti va ti on
of a cetyl chol i nes tera s e.
481. The answer is c. (Katzung, p 1005.) The pri ma ry toxi c meta bol i te of ca rbon tetra chl ori de i s a tri chl oro ra di ca l , a nd the l i ver a nd ki dneys a re the
pri ma ry ta rgets . Al though a l l the bi ochemi ca l mecha ni s ms i nvol ved i n CCl 4 poi s oni ng a re not known, i t s eems cl ea r tha t uncoupl i ng of
mi tochondri a l oxi da ti ve phos phoryl a ti on i s not i nvol ved (b), a s i s cl ea rl y the ca s e wi th, for exa mpl e, cya ni de. There i s no a nti dote for poi s oni ng
wi th CCl 4 , a nd s o onl y s ymptoma ti c a nd s upporti ve ca re a re l i kel y to hel p reduce the ri s k of dea th. Aceta mi nophen (d) i s , of cours e, meta bol i zed to
hepa totoxi c ra di ca l s , a nd prompt a nd proper a dmi ni s tra ti on of N-a cetyl cys tei ne ca n reduce the ri s ks a nd cons equences of hepa totoxi ci ty. However,
there i s no evi dence tha t thi s a nti dote for a ceta mi nophen ha s a ny benefi ci a l effects on CCl 4 toxi ci ty. Another orga ni c s ol vent, benzene, i s the
a gent tha t typi ca l l y ca us es bone ma rrow s uppres s i on (a ) a nd, wi th chroni c expos ure, certa i n l eukemi a s .
Fi na l l y, methyl ene bl ue i s of no va l ue i n ma na gi ng CCl 4 poi s oni ng. Reca l l , however, tha t methyl ene bl ue does ha ve a n i mporta nt rol e i n
ma na gi ng toxi ci ty from a va ri ety of drugs tha t tend to oxi di ze hemogl obi n to methemogl obi n: ni tri tes (eg, a myl ni tri te), certa i n a ni l i ne dyes ,
benzoca i ne, ni trogl yceri n, pri ma qui ne, a nd certa i n s ul fona mi des .
482. The answer is b. (Brunton, pp 787-797; Katzung, pp 181-190, 220.) Hydra l a zi ne, ma i nl y us ed a s a n a fterl oa d-reduci ng drug for pa ti ents wi th s evere
hea rt fa i l ure a nd/or hypertens i on, i nduces a utoa nti bodi es a ga i ns t myel operoxi da s e, a nd more s o tha n ma ny other drugs ca us es a l upus -l i ke
s yndrome i n s ome pa ti ents . Is oni a zi d, a n el ement i n mos t thera pi es of tubercul os i s , does the s a me. The l upus -l i ke s yndrome from proca i na mi de, a now s el dom us ed a nti a rrhythmi c drug, i s a l s o a n a utoi mmune phenomenon, but i n thi s ca s e the s ubcel l ul a r mecha ni s m i nvol ves
a utoa nti bodi es di rected a ga i ns t DNA. Methyl dopa , a n a nti hypertens i ve drug, a l s o ca us es a n a utoi mmune-medi a ted s yndrome i n s ome pa ti ents ,
but i n thi s ca s e the more typi ca l cons equence i s hemol yti c a nemi a , not the l upus -l i ke probl ems .
Al l the other drugs l i s ted pa rti ci pa te i n i mporta nt a nd often s eri ous toxi c rea cti ons , but the mecha ni s ms dont i nvol ve a n a utoi mmune
res pons e. Di oxi n (a ), whi ch ma y be ca rci nogeni c wi th l ong-term expos ure, i ntera cts wi th a cel l ul a r a ryl hydroca rbon receptor a nd i nduces the
cytochrome P450 s ys tem. Orga ni c mercury compounds (c; eg, methyl or other a l kyl compounds ) a re di rect neurotoxi ns tha t a ddi ti ona l l y ca us e s uch
res pons es a s rena l fa i l ure, mus cl e tremors , ps ychos i s , a nd dementi a . Pri ma qui ne (d), a n a nti ma l a ri a l , oxi di zes hemogl obi n to methemogl obi n.
Seconda ry cons equences of thi s i ncl ude cya nos i s , na us ea , ca rdi a c s ti mul a ti on, a nd fi na l l y convul s i ons tha t precede dea th. The toxi ci ty of tri cycl i c
a nti depres s a nts (e) i s mul ti fa ceted, a nd i ncl udes prol onga ti on of the QRS compl ex (i e, prol onged ca rdi a c a cti on potenti a l s res embl i ng thos e
ca us ed by qui ni di ne, a s odi um cha nnel -bl ocker), a hos t of other ventri cul a r a rrhythmi a s , a nd s trong a nti mus ca ri ni c (a tropi ne-l i ke) effects on the
hea rt a nd el s ewhere.
483. The answer is b. (Katzung, pp 640, 1034-1035.) Al ka l i ni zi ng the uri ne i nterferes wi th the rena l tubul a r rea bs orpti on of orga ni c a ci ds (s uch a s
a s pi ri n [s a l i cyl a te] a nd phenoba rbi ta l ) by i ncrea s i ng the i oni zed form of the drug i n the uri ne (per the Henders on-Ha s s el ba ch equa ti on). Thi s
i ncrea s es thei r net rena l excreti on. Convers el y, excreti on of orga ni c ba s es (s uch a s a mpheta mi ne, coca i ne, phencycl i di ne, a nd morphi ne) woul d be
reduced by a l ka l i ni zi ng the uri ne.
Note tha t other cons equences of s evere a s pi ri n (s a l i cyl a te) toxi ci ty a re both meta bol i c a nd res pi ra tory a ci dos i s . So i n a ddi ti on to enha nci ng
uri na ry excreti on of s a l i cyl a te, the a dmi ni s tra ti on of s odi um bi ca rbona te a l s o tends to countera ct the fa l l of bl ood pH. See the a ns wer expl a na ti on
for Ques ti on 329 (pp 369-373) for more i nforma ti on on the s equence of events tha t occur wi th a potenti a l l y l etha l overdos e of a s pi ri n.
484. The answer is e. (Brunton, pp 86t, 75-76, 982-984; Katzung, p 1032.) N-a cetyl cys tei ne i s us ed a nd often effecti ve for a ceta mi nophen poi s oni ng
beca us e i t i s a s ul fhydryl -ri ch drug tha t, i f gi ven s oon enough a nd properl y enough, ca n prevent hepa ti c necros i s . At s a fe bl ood l evel s , the ma jor
pa thwa ys of a ceta mi nophen el i mi na ti on i nvol ve gl ucuroni da ti on a nd s ul fa ti on. When thes e pa thwa ys a re overwhel med, a s occurs wi th
a ceta mi nophen poi s oni ng, a cytochrome P450-dependent pa thwa y a ttempts to ha ndl e the meta bol i c l oa d. The a cti ve toxi c meta bol i te, N-a cetyl benzoqui nonei mi ne, i s formed i n l evel s tha t exceed the a bi l i ty of i ntri ns i c s ul fhydryl compounds to i na cti va te i t. So l ong a s a mpl e hepa tocyte
s tores of gl uta thi one (a -SH compound) a re a va i l a bl e, cytotoxi ci ty wi l l not occur. However, s evere poi s oni ng depl etes -SH s tores , a nd s o the
hepa totoxi c meta bol i te a tta cks key cel l ul a r ma cromol ecul es . Tha t l ea ds to hepa ti c necros i s .
N-a cetyl cys tei ne a cts a s a s ubs ti tute for endogenous gl uta thi one to rea ct wi th the toxi c meta bol i te, thereby s pa ri ng -SH groups on key
hepa tocyte ma cromol ecul es .
Al ka l i ni za ti on of the uri ne i s of no benefi t wi th a ceta mi nophen poi s oni ng, a s i t ca n be wi th s evere s a l i cyl a te poi s oni ng (beca us e ra i s i ng uri ne

pH reduces tubul a r rea bs orpti on of s a l i cyl a te a nd i ncrea s es i ts excreti on). Moreover, N-a cetyl cys tei ne does not di rectl y cha nge uri ne pH.
Superoxi de a ni on ra di ca l , or hydrogen peroxi de, i s not di rectl y i nvol ved i n the cytotoxi ci ty (d).
See the a ns wer to Ques ti on 317, on pa ges 362-363, for a s umma ry of the s ta ges of a ceta mi nophen poi s oni ng.
485. The answer is f. (Brunton, p 86t; Katzung, p 1038.) Whether cya ni de poi s oni ng occurs from l ea ka ge of ga s , the combus ti on of pl a s ti cs ,
ni troprus s i de overdos es , or other ca us es , ma na gement i ncl udes ma ny common el ements . Cya ni de rea cts wi th Fe(III) i n mi tochondri a l cytochrome
oxi da s e, i nhi bi ti ng oxi da ti ve phos phoryl a ti on. The s hi ft i n meta bol i s m from a erobi c meta bol i s m to gl ycol ys i s s oon l ea ds not onl y to ATP
depl eti on, but a l s o to s evere l a cti c a ci dos i s a s the gl ycol yti c end-product a ccumul a tes .
We ma na ge cya ni de poi s oni ng first by dea l i ng wi th the hi gh rea cti vi ty of CN wi th Fe(II) i n hemogl obi n a nd the s ubs equent forma ti on of Fe(III)
hemogl obi n. We do tha t by a dmi ni s teri ng s odi um ni tri te (IV) to regenera te a cti ve cytochromes a nd oxi di ze hemogl obi n to the more cya ni derea cti ve methemogl obi n (formi ng cya nmethemogl obi n). (Amyl ni tra te ca n be a dmi ni s tered by i nha l a ti on unti l venous a cces s i s es ta bl i s hed a nd
s odi um ni tri te a nd s odi um thi os ul fa te ca n be gi ven). Once the ni tri te i s on boa rd we a dmi ni s ter s odi um thi os ul fa te IV. Cya ni de norma l l y rea cts
wi th endogenous thi os ul fa te, a nd the hepa ti c enzyme rhoda nes e ca ta l yzes the forma ti on of rel a ti vel y l es s toxi c a nd more ea s i l y excreted
thi ocya na te. In cya ni de poi s oni ng endogenous thi os ul fa te s tores a re qui ckl y depl eted, s o thi s provi des the ba s i s for i nfus i ng s odi um thi os ul fa te
(f, the correct a ns wer) to l ower cya nmethemogl obi n l evel s . In ca s es of s evere methemogl obi nemi a , we ca n a l s o gi ve methyl ene bl ue
i ntra venous l y. (Note tha t l a rge dos es of i norga ni c ni tri tes ca n be i ntri ns i ca l l y toxi c a s a res ul t of methemogl obi n forma ti on. However, i n the
context of cya ni de poi s oni ng we ca n ca pi ta l i ze on the rea cti vi ty of otherwi s e toxi c i norga ni c ni tri te, i n conjuncti on wi th thi os ul fa te a dmi ni s tra ti on,
to hel p trea t a n otherwi s e fa ta l toxi c s cena ri o.)
Ammoni um chl ori de (a ) woul d be i neffecti ve a nd ma y a ctua l l y ma ke ma tters wors e by exa cerba ti ng meta bol i c a ci dos i s . Deferoxa mi ne (b), a n
i ron chel a tor, woul d be of no benefi t, nor woul d di merca prol (c), a hea vy meta l (ma i nl y l ea d) chel a tor. N-a cetyl cys tei ne (d), routi nel y us ed a s a n
a nti dote for a ceta mi nophen poi s oni ng, woul d not a l l evi a te or s horten s i gns a nd s ymptoms i n cya ni de poi s oni ng. Pra l i doxi me (e) i s a
chol i nes tera s e rea cti va tor tha t i s us ed for poi s oni ng wi th orga nophos pha te i ns ecti ci des , nerve ga s es (s a ri n, s oma n), or other drugs tha t ca us e
profound a nd i rrevers i bl e i na cti va ti on of a cetyl chol i nes tera s e.
486. The answer is c. (Brunton, p 86t; Katzung, p 1037.) The ti p-off to the correct a ns wer s houl d come from the meta bol i c a ci dos i s , the a ni on ga p [=
(Na +) (HCO3 + Cl )], a nd the oxa l a te crys ta l s i n the uri ne. (Weve omi tted s erum K+ concentra ti on from the equa ti on, a s i s common pra cti ce,
beca us e i t i s norma l l y s o l ow tha t i t contri butes l i ttl e to the ca l cul a ted i on ga p.) Ethyl ene gl ycol (ordi na ry a nti freeze) forms , a mong other
meta bol i tes , gl ycol i c, hi ppuri c, a nd oxa l i c a ci ds . It i s the l a tter tha t tends to crys ta l l i ze i n the rena l tubul es , whi ch ma y l ea d to a cute rena l fa i l ure.
Ethyl ene gl ycol i s ba s i ca l l y a n a l cohol , a nd a s wi th a n overdos e of etha nol ca n ca us e CNS depres s i on a nd a n overa l l s ta te of i nebri a ti on. None of
the other a gents l i s ted tend to ca us e a s i mi l a r poi s oni ng s yndrome.
Note: The s i gns a nd s ymptoms of metha nol poi s oni ng refl ect, i n s ome wa ys (eg, CNS depres s i on, s tupor) thos e of ethyl ene gl ycol or etha nol .
However, metha nol s ma i n toxi ci ty a ri s es from i ts meta bol i s m to formi c a ci d, the cons equences of whi ch ca n l ea d to perma nent bl i ndnes s .
Whether the poi s oni ng i s from ethyl ene gl ycol or metha nol , trea tment i ncl udes a dmi ni s tra ti on of etha nol ; i t wi l l be preferenti a l l y meta bol i zed by
a l cohol dehydrogena s e, reduci ng the meta bol i s m of the toxi n to i ts cytotoxi c products .
Fi na l l y, the ma jori ty of hos pi ta l s i gnore the contri buti on of K+ i n the a ni on ga p equa ti on, whi ch then s i mpl i fi es to Na + (HCO3 + Cl ).
487. The answer is e. (Katzung, p 366t.) Strychni ne i s a convul s a nt, a nd dea th from expos ure i s jus t a s des cri bed i n the ques ti on. The mecha ni s m
i nvol ves s trychni nes a bi l i ty to a nta goni ze the neurona l -i nhi bi tory effects of gl yci ne, whi ch i s a n i mporta nt neurotra ns mi tter, pa rti cul a rl y i n the
s pi na l cord. Thos e s pi na l cord receptors a re s ometi mes ca l l ed s trychni ne-s ens i ti ve receptors . They a re coupl ed to a chl ori de cha nnel , a nd i n the
pres ence of s trychni ne the motor neurons become hyperpol a ri zed. The ul ti ma te effect i s a di s i nhi bi ti on of (pri ma ri l y) s kel eta l motor neurons ; tha t
ra pi dl y l ea ds to genera l i zed convul s i ons (he jus t s ta rted s ha ki ng ba d) a nd s oon therea fter venti l a tory fa i l ure a nd dea th (s topped brea thi ng,
di dnt s ee a nythi ng el s e ha ppeni ng [to hi m]). There i s no a nti dote.
Chol i nes tera s e i nhi bi tors (a ) a re the mos t often us ed i ns ecti ci des us ed i n a gri cul ture. They ca n ca us e s eri ous ha rm, a nd s ometi mes dea th, to
huma ns expos ed to them. However, a nd dependi ng on whi ch i nhi bi tor i s i nvol ved, a nd dependi ng on the expos ure route (ora l , cuta neous ,
pul mona ry) the ti me-cours e l ea di ng to dea th ca n be up to s evera l (or ma ny) mi nutes or hours . Expos ure i s a ccompa ni ed, a nd dea th i s preceded, by
a l l the expected s kel eta l mus cl e-s ti mul a ti ng (NM) a nd peri phera l mus ca ri ni c a cti va ti ng effects (hea rt, gut, a i rwa ys , exocri ne s ecreti ons ) tha t a re
cons i s tent wi th wha t a mounts to peri phera l ACh exces s . Dependi ng on the ca us a ti ve a gent, CNS/s pi na l cord ma ni fes ta ti ons ma y occur a nd be
promi nent too.
As a genera l i za ti on, keros ene (b) a nd other petrol eum di s ti l l a tes (d; found i n ma ny s ol vents /cl ea ners /degrea s ers , i ncl udi ng thos e for
hous ehol d us e) tend to a ffect mul ti pl e orga n s ys tems , i ncl udi ng: the l ungs (pul mona ry compl i ca ti ons a re the mos t common a nd i ncl ude a l veol a r
hemorrha ge, a l veol a r edema a nd i nfl a mma ti on, a nd a s pi ra ti on tha t contri butes further to pneumoni ti s ); hea rt (ca rdi omyopa thy from chroni c
expos ure, ca techol a mi ne-enha nced a rrhythmi a s ma i nl y wi th a cute poi s oni ng); bra i n (medul l a ry s ti mul a ti on, then depres s i on; remember tha t
mos t of thes e petrol eum-ba s ed products a re hi ghl y l i pi d s ol ubl e a nd enter the CNS rea di l y); gut (typi ca l l y a pa i nful burni ng s ens a ti on a nd
frequent vomi ti ng i f the toxi n i s i nges ted); l i ver (chroni c hepa totoxi ci ty wi th centrol obul a r necros i s , us ua l l y ca us ed by free ra di ca l -medi a ted
peroxi da ti on of membra ne l i pi ds ); a nd ki dneys (rena l tubul a r necros i s a nd meta bol i c a ci dos i s ). Long-term expos ure ca n a l s o ca us e a pl a s ti c
a nemi a , myel oma s , a nd l eukemi a s (ma i nl y a cute myel ogenous ).
Ars eni c toxi ci ty (c) a nd i ts ma na gement a re des cri bed i n the a ns wer to Ques ti on 493. The cl i ni ca l pres enta ti on i s much di fferent tha n the
s udden, convul s i ve dea th des cri bed here. You s houl d a l s o reca l l tha t a rs eni c, too, i s wi del y us ed a s a pes ti ci de a nd for other pes t- a nd pl a ntdi s ea s e control a ppl i ca ti ons .
Note: Before we a ppreci a ted the extreme toxi ci ty of s trychni ne, ma ny deca des a go, the drug wa s us ed thera peuti ca l l y, for huma ns , a s a
s ti mul a nt, a l a xa ti ve, a nd a remedy for a hos t of other common but ordi na ri l y i nnocuous GI ma l a di es . Not a ny more, of cours e. However, thi s
dea dl y poi s on i s s ti l l rea di l y a va i l a bl e i n pes ti ci des (ma i nl y thos e us ed to ki l l pes ky bi rds ). Accordi ng to a qui ck web s ea rch, i n Ca l i forni a a l one
more tha n ha l f a ton of s trychni ne wa s us ed a gri cul tura l l y a mere 2 to 3 yea rs a go.
488. The answer is c. (Brunton, pp 225-226; Katzung, p 1034.) The weed i n ques ti on i s Ji ms on Weed, a l s o known a s s ti nkweed, l ocoweed, a nd a few
other na mes . The s i gns a nd s ymptoms des cri bed i n the a rti cl e a re a mong the cl a s s i c ones a s s oci a ted wi th s evere a tropi ne (or, i n genera l ,
a nti mus ca ri ni c drug) poi s oni ngthe ori gi na l pha rma col ogi c s ource bei ng a l ka l oi ds i s ol a ted from va ri ous s peci es of Belladonna. No other drug
l i s ted ca us es res pons es tha t even come cl os e to thes e i n terms of the peri phera l a utonomi c res pons es des cri bed a bove.
489. The answer is k. (Brunton, pp 86t, 239, 242; Katzung, p 1034.) Atropi ne poi s oni ng, more genera l l y ca l l ed the anticholinergic syndrome, ca n be ca us ed
by a hos t of drugs a nd by the pl a nts noted i n the ques ti on. It i s trea ted s ymptoma ti ca l l y a nd s upporti vel y a nd wi th a dmi ni s tra ti on of
phys os ti gmi ne. Phys os ti gmi ne i s ba s i ca l l y the onl y cl i ni ca l l y us eful AChE i nhi bi tor tha t gets i nto the bra i n, a ma jor ta rget of

a tropi ne/a nti mus ca ri ni c poi s oni ng. Tha t i s beca us e i t l a cks the qua terna ry s tructure tha t nea rl y a l l the other common a l terna ti ves pos s es s . Si nce
i t i s not cha rged, i t ca n cros s the bl ood-bra i n ba rri er rea di l y to revers e the CNS cons equences of the poi s oni ngnot jus t thos e i n the peri phery,
where the qua terna ry chol i nes tera s e i nhi bi tors work. Of cours e, a s i s true for a l l the other chol i nes tera s e i nhi bi tors , i t works wel l i n the peri phery
too, i ntens i fyi ng the effects of ACh on both mus ca ri ni c a nd s kel eta l mus cl e ni coti ni c (NM) receptors a nd competi ti vel y overcomi ng the receptor
bl ocka de.
Al terna ti ves s uch a s neos ti gmi ne, pyri dos ti gmi ne, a nd others wi l l comba t peri phera l effects of a tropi ne poi s oni ng, jus t a s phys os ti gmi ne wi l l .
Unfortuna tel y, s ome of the CNS ma ni fes ta ti ons (eg, s evere fever, l ea di ng to s ei zures ) contri bute grea tl y to the morbi di ty a nd morta l i ty a s s oci a ted
wi th hi gh dos es of a nti mus ca ri ni cs , a nd the qua terna ry a gents s i mpl y wi l l not comba t them i n the CNS.
You wont encounter too ma ny pa ti ents overdos ed on a tropi ne i ts el f, beca us e a tropi ne i s s el dom us ed. But youl l s ee ma ny peopl e poi s oned
wi th ol der a nti hi s ta mi nes (eg, di phenhydra mi ne); s ome of the centra l l y a cti ng a nti mus ca ri ni cs tha t a re us ed for pa rki ns oni s m (eg, benztropi ne
a nd tri hexypheni dyl ); s copol a mi ne (us ed for moti on s i cknes s ); mos t of the ol der phenothi a zi ne a nti ps ychoti cs (eg, chl orproma zi ne); a nd mos t of
the ol der tri cycl i c a nti depres s a nts s uch a s a mi tri ptyl i ne a nd i mi pra mi ne. Owi ng to the often s trong a nti mus ca ri ni c s i de effects of thes e drugs ,
trea ti ng overdos es of mos t of them proba bl y wi l l i nvol ve ma na gi ng wha t a mounts to a tropi ne poi s oni nga nd ma ny other probl ems too.
490. The answer is a. (Brunton, pp 225-235, 918-926, 1314, 1815; Katzung, pp 123-125, 1034.) Mos t OTC s l eep a i ds conta i n a fi rs t-genera ti on a nti hi s ta mi ne
(s eda ti ng a gent, a l mos t a l wa ys a n etha nol a mi ne, us ua l l y di phenhydra mi ne or the very s i mi l a r drug, doxyl a mi ne). The prepondera nt s i gns a nd
s ymptoms of toxi ci ty a ri s e not from a ny hi s ta mi ne receptor-bl ocki ng a cti vi ty, but from i ntens e a nti mus ca ri ni c (a tropi ne-l i ke) effects , pl us dos edependent CNS depres s i on tha t ul ti ma tel y (a nd ea rl y on, i n chi l dren) ca n l ea d to s ei zures . The s i gns a nd s ymptoms of thi s a nti chol i nergi c
s yndrome i ncl ude ma ny, i f not a l l , tha t you wi l l s ee i n a tropi ne poi s oni ng. As i de from s ymptoma ti c a nd s upporti ve ca re, i ncl udi ng the us e of
tra di ti ona l drugs for s ta tus epi l epti cus , phys os ti gmi ne (the nonqua terna ry, centra l l y a nd peri phera l l y a cti ng a cetyl chol i nes tera s e i nhi bi tor) ma y
be l i fes a vi ng. It wi l l certa i nl y hel p revers e ma ny of the centra l a nd peri phera l s i gns a nd s ymptoms of the overdos e.
491. The answer is a. (Brunton, pp 84-85; Katzung, pp 640, 1034-1035.) Acti va ted cha rcoa l , a fi ne, bl a ck, powder wi th a hi gh a ds orpti ve ca pa ci ty, i s
cons i dered to be a va l ua bl e a gent i n the trea tment of ma ny ki nds of ora l drug poi s oni ngs pri ma ri l y i f a dmi ni s tered ea rl y on a nd then removed by
ga s tri c l a va ge. Drugs tha t a re wel l a ds orbed by a cti va ted cha rcoa l i ncl ude pri ma qui ne, propoxyphene, dextroa mpheta mi ne, chl orpheni ra mi ne,
phenoba rbi ta l , ca rba ma zepi ne, di goxi n, a nd a s pi ri n. Mi nera l a ci ds , a l ka l i s , tol buta mi de, a nd other drugs tha t a re i ns ol ubl e i n a ci di c a queous
s ol uti on a re not wel l a ds orbed.
Deferoxa mi ne (b), di merca prol (c; a l s o known a s BAL, or Bri ti s h a nti -Lewi s i te), a nd peni ci l l a mi ne (e) a re pol yva l ent ca ti on chel a tors (i ron, l ea d,
copper) a nd pl a y no rol e i n ma na gi ng a s pi ri n (s a l i cyl a te) poi s oni ng, nor poi s oni ng wi th a ny s ubs ta nces other tha n the meta l s they chel a te. NAcetyl cys tei ne (d) i s the preferred a nti dote for a ceta mi nophen overdos es (Ques ti on 333).
Notes : the term a ds orb mea ns to bi nd; i t i s deci dedl y di fferent from the more common pha rma col ogi c/thera peuti c term a bs orb.
492. The answer is b. (Brunton, pp 86t, 631-632; Katzung, p 1037.) Metha nol i s meta bol i zed by the s a me enzymes tha t meta bol i ze etha nol , but the
products a re di fferent: forma l dehyde a nd formi c a ci d i n the ca s e of metha nol . Hea da che, verti go, vomi ti ng, a bdomi na l pa i n, dys pnea , a nd bl urred
vi s i on ca n occur from a ccumul a ti on of thes e meta bol i c i ntermedi a tes . However, the mos t da ngerous (or a t l ea s t perma nentl y di s a bl i ng)
cons equence i n s evere ca s es i s hyperemi a of the opti c di s c, whi ch ca n l ea d to bl i ndnes s . The ra ti ona l e for a dmi ni s teri ng etha nol to trea t
metha nol poi s oni ng i s fa i rl y s i mpl e. Etha nol ha s a hi gh a ffi ni ty for a l cohol a nd a l dehyde dehydrogena s es a nd competes a s a s ubs tra te for thos e
enzymes , reduci ng meta bol i s m of metha nol to i ts more toxi c products . Importa nt a djuncti ve trea tments i ncl ude hemodi a l ys i s to enha nce remova l
of metha nol a nd i ts products ; a nd a dmi ni s tra ti on of s ys temi c a l ka l i ni zi ng s a l ts (eg, s odi um bi ca rbona te) to countera ct meta bol i c a ci dos i s .
Admi ni s tra ti on of s ys temi c a ci di fyi ng s ubs ta nces s uch a s a s corbi c a ci d woul d a ggra va te the condi ti on.
493. The answer is a. (Brunton, pp 1867-1871; Katzung, pp 1014t, 1017-1019.) Ars eni c i s a cons ti tuent of fungi ci des , herbi ci des , a nd pes ti ci des . Symptoms
of a cute toxi ci ty i ncl ude ti ghtnes s i n the throa t, di ffi cul ty i n s wa l l owi ng, a nd s toma ch pa i ns . Projecti l e vomi ti ng a nd s evere di a rrhea ca n l ea d to
hypovol emi c s hock, s i gni fi ca nt el ectrol yte dera ngements , a nd dea th. Chroni c poi s oni ng ma y ca us e peri phera l neuri ti s , a nemi a , s ki n kera tos i s , a nd
ca pi l l a ry di l a ti on l ea di ng to hypotens i on. Di merca prol (Bri ti s h a nti -Lewi s i te [BAL]) i s the ma i n a nti dote us ed for a rs eni c poi s oni ng.
Note: If di merca prol i s a l s o known a s anti-Lewi s i te, wha t i s Lewi s i te? It i s a n obs ol ete orga ni c a rs eni ca l (As -conta i ni ng s ubs ta nce, s peci fi ca l l y
chl orovi nyl di chl oroa rs i nedont memori ze tha t!) devel oped a s a chemi ca l wa rfa re a gent i n Worl d Wa r II. Ars eni c rea cts a nd forms chel a tes wi th
s ul fhydryl moi eti es on va ri ous s ubs ta nces , i ncl udi ng ma ny enzymes i nvol ved i n es s enti a l meta bol i c rea cti ons . It i s a ves i ca nt (ca us es bl i s teri ng)
tha t ta rgets ma ny body ti s s ues , but exerts i ts ma i n toxi c effects i n the l ungs when i nha l ed. Di merca prol i s a rel a ti vel y s i mpl e mol ecul e wi th two
s ul fhydryl groups i n i ts s tructure. It rea cts wi th the Lewi s i te, chel a ti ng i t a nd thereby reduci ng a tta ck on a nd i na cti va ti on of cel l ul a r SH-ri ch
enzymes .
494. The answer is b. (Brunton, pp 458-468; Katzung, pp 373-387, 569t, 575.) Argua bl y the mos t i mporta nt ti p-off i n thi s pres enta ti on i s the a ntegra de
a mnes i a , whi ch (a mong other thi ngs ) i s ra ther uni quel y a s s oci a ted wi th benzodi a zepi nes . The mos t l i kel y benzodi a zepi ne us ed i n thi s s cena ri o
wa s rohypnol (fl uni tra zepa m, better known a s roofi es on the s treet a nd by thos e who us e i t a s a da te-ra pe drug).
Unl es s thi s pa ti ent were a very a typi ca l res ponder, i t i s unl i kel y tha t a ny of the other CNS depres s a nts a ba rbi tura te, a n opi oi d, chl ora l hydra te
woul d ca us e the s a me res pons es . Shes ha d one dri nk yet s ti l l feel s pa i n from her hea d ga s h. She a ppa rentl y ha s nt ha d enough a l cohol to be
s o obtunded tha t s he does nt feel pa i n, a nd a ba rbi tura te i s l i kel y to enha nce the s ens a ti on of pa i n (hypera l ges i c effect). Chl ora l hydra te i s s ti l l
us ed medi ca l l y, ma i nl y a s a s eda ti ve for chi l dren, a l though i ts us e i s decl i ni ng dra ma ti ca l l y. It i ndeed ca us es powerful CNS depres s a nts when
us ed i n combi na ti on wi th jus t a l i ttl e a l cohol : chl ora l hydra te ha s been known for yea rs a s knock-out drops a nd the combi na ti on wi th a l cohol
ha s been ca l l ed a Mi ckey Fi nn. However, chl ora l hydra te i s not nea rl y a s rea di l y a va i l a bl e a s the i l l i ci t benzodi a zepi nes ; i t does not ca us e
a ntegra de a mnes i a (i mporta nt to the perpetra tor, beca us e he or s he a nti ci pa tes no reca l l of wha t ha ppened by the vi cti m), but i t i s not rea di l y
a va i l a bl e, a nd i t s i mpl y does nt ha ve the reputa ti on a s a preferred da te-ra pe drug a mong thos e who us e s uch drugs .
495. The answer is b. (Brunton, pp 83t, 86t, 468-469; Katzung, pp 379, 381-382.) Fl uma zeni l i s the s peci fi c benzodi a zepi ne receptor a nta goni s t, a nd i t i s
both s peci fi c a nd a l mos t a l wa ys effecti ve for exces s i ve effects of a ny benzodi a zepi ne. Its tempti ng to us e a CNS s ti mul a nt (a , a mpheta mi nes ; or c,
methyl pheni da te) to overcome the effects of a ny CNS depres s a nt. It ma y hel p, but more l i kel y the outcome of gi vi ng a s ti mul a nt i s exces s i ve effects
ma ni fes t a s s ei zures a nd unwa nted ca rdi ova s cul a r s ti mul a tory effects . Na l trexone, l i ke na l oxone, s peci fi ca l l y bl ocks opi oi d receptors a nd wi l l be
of no benefi t to thi s poi s oned pa ti ent. Some benzodi a zepi nes do ca us e a nti -mus ca ri ni c effects , but wea kl y. For tha t rea s on, a nd others ,
phys os ti gmi ne (or a ny other AChE i nhi bi tor) woul d not a t a l l a n effecti ve or probl em-free drug to gi ve.
496. The answer is a. (Brunton, pp 1861-1864; Katzung, pp 1013-1017.) The pres enta ti on of chroni c l ea d expos ure, a s from bei ng expos ed to (or even
ea ti ng) ol der l ea d-ba s ed pa i nts , di ffers from the typi ca l pres enta ti on of a cute orga ni c l ea d poi s oni ng (a ns wer c), whi ch us ua l l y a ri s es from

s ni ffi ng l ea ded ga s ol i ne (a nd jus t a bout a l l ga s ol i nes nowa da ys a re orga ni c l ea d-enri ched). Ans wer b, wi th the predomi na nt gi ngi va l /hea d/neck
s i gns a nd s ymptoms , i s typi ca l of chroni c or a cute mercury i ntoxi ca ti on. Ans wer d, wi th the hyperventi l a ti on, GI di s turba nces (i ncl udi ng di s col ored
vomi tus ) a nd pa l l or, i s wha t you a re l i kel y to encounter i n a cute i ron poi s oni ng (a s from a cons umi ng ferrous s ul fa te s uppl ements i n l a rge dos es ).
A cha ra cteri s ti c brea th (ga rl i cky or meta l l i c), profus e di a rrhea , encepha l opa thy, a nd hypotens i on (a ns wer e) a re typi ca l of a cute i norga ni c a rs eni c
poi s oni ng. Knowi ng more a bout the pa ti ents hi s tory a nd envi ronment wi l l hel p i mmens el y i n s orti ng out wha t the mos t l i kel y ca us e of
i ntoxi ca ti on i s .
497. The answer is f. (Brunton, p 1874; Katzung, pp 1013-1017.) Succi mer (a more pol a r s a l t of di merca prol ; Bri ti s h a nti -Lewi s i te; BAL) woul d be the
choi ce, gi ven the proof of l ea d poi s oni ng, the l a ck of a cute s ymptoms , a nd the fa ct tha t our pa ti ent i s a chi l d. Succi mer i s ea s y to gi ve ora l l y a nd i s
tol era ted fa r better tha n the a l terna ti ves : Ca -Na 2 -EDTA (a ), peni ci l l a mi ne (e; tra di ti ona l l y vi ewed a s a copper chel a tor, but i t a l s o chel a tes l ea d),
or di merca prol (c) i ts el f. Al though the hea vy meta l chel a ti on profi l es for s ucci mer a re not dra s ti ca l l y di fferent from thos e of di merca prol , the fa ct
tha t s ucci mer i s more pol a r (a nd, therefore, l es s l i kel y to enter cel l s ) s eems to a ccount for fa r fewer a nd mi l der s i de effects tha n thos e of
di merca prol (es peci a l l y wi th res pect to ri s ks of ta chyca rdi a a nd hypertens i on). N-Acetyl cys tei ne (d), a s noted el s ewhere, i s the drug of choi ce for
a ceta mi nophen poi s oni ng. It ha s no a bi l i ty to chel a te l ea d or other ca ti ons .
498. The answer is a. (Brunton, pp 186f, 266, 1792; Katzung, pp 84, 479, 481.) Botul i nus (botul i num) toxi n prevents rel ea s e of a cetyl chol i ne (from s tora ge
ves i cl es ) by vi rtua l l y a l l chol i nergi c nerves . Thus , there i s no a cti va ti on of a ny chol i nergi c receptors , whether ni coti ni c or mus ca ri ni c. Noteworthy
fi ndi ngs , then, i ncl ude a n i na bi l i ty to a cti va te a l l pos tga ngl i oni c neurons (s ympa theti c a nd pa ra s ympa theti c), no phys i ol ogi c rel ea s e of
epi nephri ne from the a drena l medul l a , a nd fl a cci d s kel eta l mus cl e pa ra l ys i s due to fa i l ure of ACh rel ea s e from motor nerves . The ca us e of dea th
i s venti l a tory fa i l ure beca us e the i ntercos ta l mus cl es a nd di a phra gm a re nonfuncti ona l .
Pra l i doxi me i s a chol i nes tera s e rea cti va tor, a n a nti dote a nd a djunct (a l ong wi th a tropi ne) for poi s oni ngs wi th i rrevers i bl e chol i nes tera s e
i nhi bi tors s uch a s s oma n, s a ri n, VX (nerve ga s es ), a nd ma ny orga no-phos phorus i ns ecti ci des . Beca us e no ACh i s bei ng rel ea s ed i n botul i nus
poi s oni ng, rea cti va ti on of the enzyme tha t norma l l y meta bol i zes the neurotra ns mi tter i s i rrel eva nt (a nd i neffecti ve).
499. The answer is e. (Brunton, pp 239, 242, 249-250; Katzung, pp 1035-1036.) Mos t of the a dvers e res pons es to nerve ga s es (i rrevers i bl e ACh es tera s e
i nhi bi tors s uch a s s oma n a nd s a ri n) a re due to a bui l d-up of ACh a t mus ca ri ni c receptors (i e, ACh rel ea s ed from pos tga ngl i oni c pa ra s ympa theti c
nerves or s ympa theti c/chol i nergi c nerves i nnerva ti ng s wea t gl a nds ). Thos e res pons es wi l l be a ttenua ted by a tropi ne, beca us e i t i s a hi ghl y
s peci fi c competi ti ve mus ca ri ni c a nta goni s t. However, s kel eta l mus cl e s ti mul a ti on (or eventua l pa ra l ys i s ) i nvol ves ni coti ni c receptor a cti va ti on.
Tha t wi l l not be a ffected by a tropi ne, a nd unl es s other s upporti ve mea s ures a re provi ded, the pa ti ent i s l i kel y to di e from venti l a tory
a rres t/a pnea .
500. The answer is e. (Brunton, pp 35, 855-857, 862; Katzung, pp 608-611.) No, thi s i s not a fri vol ous ques ti on. Someda y you ma y be worki ng i n a n
emergency depa rtment or a poi s on center, s o you need to know. The cri tters tha t ea t the rodenti ci de ul ti ma tel y bl eed to dea th from a wa rfa ri n
overdos e. When trea ti ng s uch poi s oni ngs i n huma ns or poi s oned pets , the a pproa ch i s the s a me a s wi th thera peuti c wa rfa ri n: a dmi ni s ter vi ta mi n
K (ora l l y or pa rentera l l y, whi chever i s i ndi ca ted), a nd provi de other s ymptoma ti c a nd s upporti ve mea s ures . Ampheta mi ne or coca i ne, a l one or i n
combi na ti on (a ), a s wel l a s morphi ne (b), a re control l ed s ubs ta nces wi th hi gh potenti a l for dependence a nd a bus e. Such s ubs ta nces s i mpl y
woul dnt be permi tted i n products tha t vi rtua l l y a nyone coul d obta i n a t thei r l oca l home ca re or ha rdwa re s tore. Wha t a bout s ucci nyl chol i ne (c)?
Its i neffecti ve when i nges ted; i t ha s to be i njected. The s a me a ppl i es the nondepol a ri zi ng bl ockers (d), vecuroni um, a nd the other curoni ums or
curi nes . (Youl l remember tha t s ome peopl es i ndi genous to the Ama zon ki l l ed thei r prey wi th cura re-ti pped da rts . And they a te tha t cura re-l a ced
mea t wi th a bs ol utel y no i l l effects from the drug.)

Appendix A
Drug Interactions Involving the P450 System

Appendix B
Common Serum Chemistries (Normal Values)

Appendix C
Web Sites for More Information
Mos t texts tha t ha ve been publ i s hed i n the l a s t few yea rs , a nd ma ny tha t wi l l be publ i s hed, ha ve a va ri ety of onl i ne res ources tha t a re wel l worth
a l ook. Thes e a re us ua l l y free, but of cours e tha t us ua l l y mea ns theyre free i f you purcha s ed the book on whi ch the web s i te i s ba s ed.
However, there a re ma ny other s i tes where you ca n get good i nforma ti on (a nd l ots more where the i nforma ti on you get i s s ketchy or of dubi ous
a ccura cy or objecti vi ty, a t bes t). Acces s to s ome s i tes i s free, but others requi re pa yment. Here a re a s el ected few tha t I vi s i t frequentl y, a nd bel i eve
a re worth your ti me a nd trus t. Ive l i s ted them a l pha beti ca l l y.
Drug Facts and Comparisons (http://www.fa cts a ndcompa ri s ons .com). Thi s i s us ua l l y my go-to web s i te for a l l the need-to-know i nforma ti on a bout
drugs a nd drug products , i ncl udi ng drug-drug i ntera cti ons . The s i te provi des excel l ent s umma ry ta bl es a bout a l l s orts of thi ngs pha rma col ogi c a nd
thera peuti c, a nd i n a wa y tha t wi l l hel p you gl ea n wha ts i mporta nt. Acces s to the i nforma ti on i s not free. However, your s chool s houl d ha ve a s i te
l i cens e for a cces s ; i f they dont, pes ter the a ppropri a te a dmi ni s tra ti ve pers on to buy one. After a l l , l ook a t how much tui ti on youre pa yi ng!
FDA (Food a nd Drug Admi ni s tra ti on) (http://www.fda .gov). The FDA ha s a grea t (a nd free!) s i te for a l l thi ngs medi ca l , not jus t drugs . Some pa rts
a re ta rgeted to the publ i c; others a re for hea l th ca re profes s i ona l s . You ca n s ta y on top of l a tes t drug or devi ce a pprova l s , concerns , wa rni ngs , or
reca l l s , a nd get much more i nforma ti on tha t ul ti ma tel y wi l l be of i nteres t a nd i mporta nce to you.
One pa rt of the web s i te, MedWa tch (http://www.fda .gov/medwa tch) i s a mus t-s ee, es peci a l l y once you hi t the wa rds . The i nforma ti on there wi l l
keep you up-to-da te on the l a tes t drug s a fety concerns , reca l l s , a nd s o on. You ca n s ubs cri be, for free, to get pers ona l e-ma i l s a bout the very l a tes t
concerns a nd wa rni ngs . Tha ts i mporta nt to you a s a future pra cti ti oner a nd ca regi ver. (And once you hi t the wa rds i t wi l l gi ve you current a nd
i mporta nt i nforma ti on tha t you ca n ca s ua l l y menti on to your cl i ni ca l tea mor the a ttendi ng who gi ves you your cl erks hi p gra des howi ng tha t
youre rea l l y on top of thi ngs .)
Journal Watch (http://www.jwa tch.org). Journa l Wa tch, publ i s hed by the Ma s s a chus etts Medi ca l Soci ety (the publ i s hers of NEJM), ha s expert
revi ewers who provi de s ucci nct a nd objecti ve s umma ri es a nd eva l ua ti ons of the l a tes t a rti cl es from nea rl y 200 top medi ca l journa l s . The topi cs
ra nge from genera l i nterna l medi ci ne to s peci a l ti es a nd s ubs peci a l ti es . The revi ews a re l i nked to the ori gi na l publ i s hed a rti cl es , s ome of whi ch
ca n be a cces s ed for free.
JWa tch i s a s ubs cri pti on s ervi ce (your medi ca l l i bra ry l i kel y s ubs cri bes ), a nd mos t i ndi vi dua l s ubs cri bers opt for e-ma i l del i very of the
s umma ri es , whi ch often a rri ve da i l y.
Journa l Wa tch ha s a s i bl i ng s i te, Fi rs t Wa tch (fi rs twa tch.jwa tch.org), tha t provi des free da i l y a l erts , del i vered to your e-ma i l i nbox, on current
medi ca l l y rel a ted news .
Cl ea rl y, not a l l the s umma ri es on ei ther s i te a re drug-rel a ted, but ma ny a re, a nd you ma y fi nd them qui te i nteres ti ng a nd hel pful i f you wa nt a n
ea s y wa y to keep up wi th the newes t l i tera ture.
The Medical Letter (http://www.medi ca l l etter.com). Thi s i s a nother excel l ent web s i te tha t wi l l keep you up to da te. One i mporta nt a nd ra ther
uni que fa cet of The Medi ca l Letters upda tes i s a n unbi a s ed l ook a t, for exa mpl e, whether a new drug i s a ny better or s a fer tha n ol der
a l terna ti ves . The publ i s her frequentl y provi des excel l ent ta bl es tha t compa re, for exa mpl e, cos ts of otherwi s e s i mi l a r a nd a l terna ti ve drugs ;
s umma ri es of recommended drugs for a pa rti cul a r condi ti on, a nd much more.
The Medi ca l Letter a l s o publ i s hes Treatment Guidelines from the Medical Letter, whi ch col l ects a nd pres ents i n a conci s e a nd unbi a s ed wa y key
i nforma ti on us ua l l y deri ved from pri or Medi ca l Letter i s s ues . Acces s to The Medi ca l Letter requi res a s ubs cri pti on (a nd you ca n a l s o s ubs cri be to
s na i l -ma i l upda tes ). Here, too, s ee i f your s chool ha s a s i te l i cens e, a nd i f they dont urge them to get one.
Prescribers Letter (http://www.pres cri bers l etter.com) tops my l i s t of recommended web-ba s ed res ources for a va ri ety of rea s ons , not the l ea s t of
whi ch i s i ts s i ngul a r focus on drugs a nd drugs thera py. Thi s i s a nother web s i te for whi ch youl l ei ther ha ve to pa y, or pes ter your med ed dea n or
medi ca l l i bra ry fol ks to get a s i te l i cens e. Pres cri bers Letter keeps you upda ted wi th new a nd pra cti ca l i nforma ti on on the l a tes t drugs a nd drug
thera pi es i n jus t a bout a ny a rea you mi ght fi nd of i nteres t. It i s objecti ve a nd unbi a s ed, a nd excel s (i n my opi ni on) i n terms of debunki ng myths
a bout new drugs or thera pi es , a nd gi vi ng you a decent hea ds up a bout drug-rel a ted i s s ues tha t a re l i kel y to be i mporta nt to you. Youl l get
rel eva nt i nforma ti on much s ooner wi th Pres cri bers Letter tha n wi th jus t a bout a ny other web s i te Ive vi s i ted. Wi th a s ubs cri pti on you ca n a cces s
a l l s orts of good i nforma ti on a bout drugs , a nd be a s s ured tha t youre not getti ng a nythi ng but current a nd i mporta nt i nforma ti on.
RxList (http://www.rxl i s t.com). Thi s i s a nother comprehens i ve s i te where you ca n fi nd a bunda nt, current, a nd objecti ve i nforma ti on a bout drugs .
You ca n a l s o get i nteres ti ng (i f not i mporta nt) i nforma ti on a bout, for exa mpl e, the mos t pres cri bed drugs , the l a tes t news , a nd s o on. Al l the
i nforma ti on on rxl i s t.com i s free.

Index
Please note that index links point to page beginnings from the print edition. Locations are approximate in e-readers, and you may need to page down one or more
times after clicking a link to get to the indexed material.
A
AAPMC. See Anti bi oti c-a s s oci a ted ps eudomembra nous col i ti s ; Cl i nda myci n
Abci xi ma b 227, 269, 279. See also Anti pl a tel et drugs
a cute corona ry s yndrome a nd, 205, 284285
Aborti fa ci ents , 270, 431, 442
Aca rbos e, 433, 440, 443444. See also Anti di a beti c drugs
hypogl ycemi a a nd, 420, 433
s i de effects of, 402, 426427
ACE i nhi bi tors . See Angi otens i n-converti ng enzyme i nhi bi tors ; Anti hypertens i ve drugs
Acebutol ol , 1516. See also -Adrenergi c a goni s ts
a s pa rti a l a goni s t, 42, 67, 92, 107
Aceta mi nophen, 26, 247, 270, 339340, 350. See also Ana l ges i cs ; Anti pyreti cs
l i ver fa i l ure from overdos e of, 50, 362363
N-a cetyl cys tei ne for overdos e of, 339340, 355, 363, 370, 375376, 492
s ta ges of fa ta l poi s oni ng of, 363
Aceta zol a mi de, 296, 299, 301, 313314, 316317, 320. See also Ca rboni c a nhydra s e i nhi bi tors ; Di ureti cs
for a l ti tude s i cknes s , 302, 316317
a s a nti epi l epti c drug a djunct, 316
ca us es coma , 301, 316
for chroni c open a ngl e gl a ucoma , 302, 316
hypera mmonemi a ca us i ng coma from, 301, 316317
hypoka l emi a ca us ed by, 309, 319
meta bol i c a ci dos i s ca us ed by, 309310, 316317, 320
ura te s ol ubi l i ty i ncrea s ed by, 297, 310311
uri na ry a l ka l i ni za ti on ca us ed by, 310, 317, 326
uri ne el ectrol yte profi l es a nd, 319
Acetyl chol i ne, 63, 84, 90, 99, 103, 114, 359, 397, 521
a i rwa y s mooth mus cl e contra cti on ca us ed by, 103
botul i nus toxi n prevents rel ea s e of, 521
a s endogenous receptor a goni s ts , 63
endothel i um remova l a ffecti ng res pons es to, 77, 121, 210, 247248
es tera s e i nhi bi tors , 65, 90, 98, 115116, 122, 173, 192, 268, 281, 283, 286, 332, 343344, 358, 360, 378, 515, 517, 521
ga s tri c a ci d s ecreti on i ncrea s ed by, 393
overs ti mul a ti on from, 97, 122
a s peri phera l neurotra ns mi tter, 83, 281
va s ocons tri cti on from, 77, 122
Acetyl chol i nes tera s e (AChE), 65, 83, 90, 98, 110, 115116, 122, 173, 177, 192, 283, 332, 343, 358, 360, 391, 511, 514, 517
pra l i doxi me rea cti va ti on of, 124, 511, 514, 521
Acetyl chol i nes tera s e i nhi bi tors
Al zhei mer di s ea s e a nd, 143, 178
a s thma a nd a dvers e effects of, 122, 274
mya s theni a gra vi s a nd, 65, 102, 122, 123, 344
poi s oni ng by, 62, 103
ACh. See Acetyl chol i ne
AChE. See Acetyl chol i nes tera s e
Acti va ted cha rcoa l i n ora l poi s oni ngs , 506, 517518
Acti va ted pa rti a l thrombopl a s ti n ti me (APTT), 219, 267
Acute corona ry s yndrome, 151, 188, 205, 227, 229, 284, 297
thrombol yti cs for, 227, 268270, 276, 279
Acycl ovi r, 475476
Adenos i ne, 219, 237, 242, 268, 292, 338
a s ca roti d s i nus ma s s a ge a l terna ti ve, 236
pa roxys ma l s upra ventri cul a r ta chyca rdi a a nd, 204, 230231, 236, 242
Adenos i ne monophos pha te (AMP), 6. See also Cycl i c AMP
Adenyl yl cycl a s e, 4546
ADH. See Anti di ureti c hormone
ADHD. See Attenti on defi ci t-hypera cti vi ty di s order
Adrena l corti ca l tumor, 312314. See also Cus hi ng di s ea s e
Adrena l corti cos teroi ds . See also Corti cos teroi ds
Cus hi ng di s ea s e, s ynthes i s i nhi bi ted, 441

s i gns a nd s ymptoms of, 438

s ynthes i s , 438
Adrena l (s upra rena l ) medul l a , 74, 84, 88, 107, 118, 124, 339340, 523
-Adrenergi c a goni s ts
epi nephri ne, 19, 42, 58, 60, 6364, 74, 82, 85, 88, 90, 95, 97, 99101, 103, 107108, 118, 120, 124125, 213, 242244, 249, 254, 272, 275, 284285, 291292,
335336, 339340, 344, 358, 427, 434, 521
norepi nephri ne, 39, 42, 5356, 66, 74, 8284, 8688, 92, 99, 103105, 107108, 117120, 124, 126, 155, 164, 170, 172, 181, 186, 196197, 241, 244, 258, 270
271, 275, 278, 335, 339, 360, 427, 434, 483
phenyl ephri ne, 7980, 88, 108, 117, 119, 125126, 159160, 227, 241, 258, 268, 280, 283
-Adrenergi c a goni s ts
a l buterol , 39, 96, 113, 213, 254, 328329, 335, 338, 341, 345, 395, 440
epi nephri ne, 19, 42, 58, 60, 6364, 74, 82, 85, 88, 90, 95, 97, 99101, 103, 107108, 118, 120, 124125, 213, 242244, 249, 254, 272, 275, 284285, 291292,
335336, 339340, 344, 358, 427, 434, 521
i s oproterenol , 89, 99100, 103, 107108, 113, 116, 119120, 125, 242, 248, 258, 281, 292, 345
norepi nephri ne, 39, 42, 5356, 66, 74, 8284, 8688, 92, 99, 103105, 107108, 117120, 124, 126, 155, 164, 170, 172, 181, 186, 196197, 241, 244, 258, 270
271, 275, 278, 335, 339, 360, 427, 434, 483
s a l meterol , 328, 335336, 345346
-Adrenergi c bl ockers , 89, 101, 107, 119120, 124, 159, 254, 265, 275, 280281, 283, 285, 289, 427
phenoxybenza mi ne, 88, 190, 204, 213, 243, 254
phentol a mi ne, 65, 8889, 101102, 117118, 159, 241, 289, 360
pra zos i n, 32, 65, 86, 88, 101102, 107, 119120, 124126, 159, 204, 214, 240241, 243, 248, 257, 258, 265, 267, 270, 275, 280, 283, 427
tera zos i n, 120, 280
-Adrenergi c bl ockers , 60, 67, 94, 105, 203, 231, 238, 240, 245, 256, 262, 270, 275, 283, 285286, 358, 360361, 414, 425, 427, 430, 434. See also La beta l ol ,
metoprol ol , propra nol ol
a brupt di s conti nua ti on of, 271272
-a drenergi c bl ocki ng properti es of, 191, 197, 253
a ngi na pectori s a nd, 202, 229, 240, 244, 414
a s a nti hypertens i ves , 63, 79, 99, 203, 231
a s thma a nd, 67, 105
AV noda l conducti on a nd, 105, 268
contra i ndi ca ti ons for, 97, 105106
es s enti a l hypertens i on a nd, 58, 96, 203
hea rt fa i l ure a nd, 106, 239
hyperthyroi di s m or thyrotoxi cos i s a nd, 67, 105106, 435, 445
pheochromocytoma s a nd, 9596, 231, 285
va s odi l a ti ng properti es of, 286
Adrenergi c bronchodi l a tors . See Al buterol ; Sa l meterol
Adrenergi c nerves a nd neurotra ns mi s s i on, 5355, 63, 66, 74, 82, 86, 8992, 95, 99, 107, 109, 118, 121, 179, 192
-Adrenergi c receptors , 54, 56, 8283, 8789, 94, 101, 109, 117118, 120, 124125, 160, 167, 186, 188, 193, 243244, 254, 258, 280, 285, 290291, 345, 360
pres yna pti c, 56, 8789, 92, 101102, 104, 241, 275
-Adrenergi c receptors , 16, 42, 54, 56, 58, 85, 90, 98, 105, 107108, 110, 118, 125, 159, 244, 254, 281, 285286, 292293, 335, 339, 345, 361, 395, 425, 427, 434,
445
Adrenergi c receptors , s ubtypes a nd l oca ti ons of, 8283, 118
Adrenomi meti c res pons es , 55, 89
Age a ffecti ng drug thera py, 8, 12, 32, 38
Agra nul ocytos i s , 153, 187, 193, 443
AIDS, drugs for. See Anti vi ra l /a nti retrovi ra l drugs
Ai rwa y s mooth mus cl e, a drenergi c control of, 39, 85, 103, 109, 113114, 118119, 159, 170, 255, 328, 335, 346, 359, 363
Aka thi s i a s , 135, 157
Al bumi nuri a , 238, 408
Al buterol , 39, 96, 113, 213, 254255, 327328, 336, 339, 341, 345, 395, 440. See also -Adrenergi c a goni s ts ; As thma
a s thma , l a beta l ol a nd, 9192, 9495, 110, 205, 239241, 245, 249, 254, 260, 271, 275, 286, 425
a s thma i na ppropri a tel y trea ted wi th, 327, 334335
s kel eta l mus cl e tremors from, 329, 338
Al cohol . See Etha nol
Al dos terone, 256, 308, 312314, 316318, 322324, 438, 442, 446
receptor bl ocka de by s pi ronol a ctone or epl erenone, 316, 438, 441, 446
Al endrona te, 410, 428
Al l opuri nol . See also Anti gout/a nti hyperuri cemi c drugs
a za thi opri ne toxi ci ty ri s k wi th, 488, 499500
ca ncer a nd, 348, 360, 489490, 498500
febuxos ta t compa red to, 246, 348, 359, 366, 369, 490, 499500
merca ptopuri ne toxi ci ty ri s k wi th, 489490, 499500
uri c a ci d s ynthes i s i nhi bi ti on by, 369, 377
Al os etron, 391, 405406
Al tepl a s e, 220, 263, 268, 276, 279. See also Thrombol yti cs

Al ti tude s i cknes s , 302, 316317

Al umi num s a l t a nta ci ds , 387, 393, 398, 401404
ma gnes i um s a l ts wi th, 385, 397399, 401
phos pha te a nd, 390, 401, 404
Al zhei mer di s ea s e, drugs for, 47, 143, 178
Ama nta di ne, 174, 184, 199, 476. See also Anti pa rki ns on drugs ; Anti vi ra l /a nti retrovi ra l drugs
Amenorrhea , 135, 167, 181, 199, 423, 446
Ami ka ci n, 456, 475, 480481. See also Anti bi oti cs , a mi nogl ycos i des
Ami l ori de, 257, 271, 304, 317319, 321325. See also Di ureti cs
hypoka l emi a a nd, 304, 319
i denti fyi ng us e of, 306, 325
Ami ne pump, 82, 8687, 89, 104
-Ami nobutyri c a ci d (GABA), 25, 46, 152, 173, 176, 192, 512
Ami noca proi c a ci d, 263264, 270, 276
Ami nogl ycos i des , 11, 304, 321, 457, 459461, 468, 472, 474475, 477482. See also Anti bi oti cs , i ndi vi dua l cl a s s es
furos emi de wi th, 216, 221, 224, 230, 240, 249, 255, 259, 264, 271272, 274, 289, 298300, 303, 308312, 317, 319324, 395
neuromus cul a r bl ockers a nd, 459, 479480
ototoxi ci ty from, 458, 477480
peni ci l l i n a nd, 451, 456458, 460, 464, 467468, 470472, 474
Ami oda rone, 220, 261, 269, 281, 283, 411, 429431. See also Anti a rrhythmi c drugs
for a tri a l fi bri l l a ti on, 220, 252253, 255, 269, 281, 411
pul mona ry fi bros i s from, 261, 269, 493
thyroi d a bnorma l i ti es from, 410, 427428
Amoxa pi ne, 181182
Amoxi ci l l i n, 400, 456, 464, 466, 470471, 474, 481. See also Anti bi oti cs ; Peni ci l l i ns
a mpi ci l l i n compa red to, 456, 474
Ampheta mi nes , 39, 57, 86, 89, 107108, 110, 122, 124, 126, 137, 164, 169170, 172, 179, 183, 189, 203, 241, 353, 369, 371, 514, 518, 520, 522
toxi ci ty of, 504, 517
Amphoteri ci n B, 457, 473, 475
Ampi ci l l i n, 456, 474, 481. See also Anti bi oti cs ; Peni ci l l i ns
Ana l ges i cs
a ceta mi nophen, 26, 247, 270, 339340, 350
a s pi ri n, other NSAIDs
a s pi ri n, 26, 32, 41, 47, 204, 207, 208, 219220, 229, 233234, 239, 242, 246, 249250, 260, 267, 269, 277, 282283, 285, 287, 290, 299, 309, 330, 339340,
349351, 353355, 358359, 361362, 364366, 368373, 375, 387, 400, 471, 478, 506, 512, 518
di cl ofena c, 247, 351, 357, 361
i buprofen, 26, 246247, 351, 357, 361, 367, 441
i ndometha ci n, 349, 351, 355, 357, 359, 361, 367, 369, 374377, 441
ketorol a c, 72, 133, 161163, 391
na proxen, 246247
opi oi ds
codei ne, 144, 173, 180, 261, 341, 368
fenta nyl , 156, 168, 173, 181, 197, 391
hydrocodone, 342
meperi di ne, 32, 138, 170171, 182
metha done, 150, 171, 189, 194, 466
morphi ne, 26, 72, 109, 113, 138, 147, 149, 161162, 171, 179, 184185, 187190, 197, 199, 202, 261, 358, 391, 405, 512, 522
oxycodone, 144
penta zoci ne, 147, 184185
Ana phyl a xi s , 100, 103, 291, 335336, 359, 396
Anes theti cs , genera l
i nha l a ti on a gents , 341
ha l otha ne, 161162, 191
i s ofl ura ne, 191, 459, 479
i njecta bl e a gents , 136, 161, 177, 425
ma l i gna nt hyperthermi a a nd, 46, 161162, 191192
mi ni mum a l veol a r concentra ti on of, 163, 175
ni trous oxi de a s , 141, 175, 181, 459
potency of i nha l ed a gents , 177. See also Mi ni mum a l veol a r concentra ti on of i nha l ed a nes theti cs
Anes theti cs , l oca l . See also l i doca i ne; Proca i ne
a l l ergi c rea cti ons to, 142, 176177
epi nephri ne i n, 64, 100101
a s es ter or a mi de, 177
ni trous oxi de a nd, 141, 175
recogni zi ng chemi ca l cl a s s by na me, xxi xxxx, 176177

Angel dus t. See Phencycl i di ne

Angi na pectori s , 202, 225, 229. See also Anti a ngi na l drugs
-a drenergi c bl ockers , ni trogl yceri n a nd, 202, 225, 229
ni trova s odi l a tors a nd, 225
Angi otens i n II, 92, 238, 257, 266, 271272, 277278, 280, 286287, 311, 314, 322, 424
Angi otens i n converti ng enzyme, 254255, 271272, 322, 367, 408
Angi otens i n receptor bl ockers , 238, 244, 248, 253, 255256, 263, 270, 272, 274, 277278, 280, 409
bi l a tera l rena l a rtery s tenos i s contra i ndi ca ti ng, 238, 252, 408
l os a rta n, 226, 238, 244, 248, 256, 263, 266, 270, 274, 277278, 280
pregna ncy a nd, 248249, 253
Angi otens i n-converti ng enzyme (ACE) i nhi bi tors
bi l a tera l rena l a rtery s tenos i s contra i ndi ca tes , 238, 252, 408
bl ood pres s ure l owered wi th, 367
ca ptopri l , 205, 221, 223, 230, 240, 255256, 259, 270271, 277, 282, 285, 323, 367, 374
ena l a pri l , 224, 274
hea rt fa i l ure a nd, 217, 228, 239, 259, 264, 278, 280, 312, 424
hypertens i on a nd, 190, 217, 228, 238239, 305, 312, 323, 367
l i s i nopri l , 225226, 277278, 305
mecha ni s ms of a cti on of, pregna ncy a nd, 248249, 253
ra mi pri l , 211, 252, 255, 283
thi a zi des a dded to, 217, 283
Angl e cl os ure gl a ucoma . See gl a ucoma
Anorexi geni c drugs , 57, 108
Anta ci ds , 387, 393394, 397399, 401, 403404, 473. See also individual drugs
Anthra x, 447, 466
Anti a ngi na l drugs
a drenergi c bl ockers
a cebutol ol , 1516, 42, 67, 92, 107
a tenol ol , 92, 105, 109, 126, 221, 244, 254, 275, 286, 345, 425
metoprol ol , 92, 105, 109, 232, 254, 275, 286, 344, 425
na dol ol , 62, 92, 97
nebi vol ol , 95, 203, 241, 245, 286
pi ndol ol , 37, 92, 107, 254, 426
propra nol ol , 32, 60, 86, 9495, 99, 105, 110, 114, 116117, 119, 121, 126, 160, 206, 231, 245, 254, 268, 275, 283286, 289, 360361, 409, 425, 434, 445
ti mol ol , 92, 98, 125, 240
ca l ci um cha nnel bl ockers , 172, 216, 223, 240, 242, 244246, 249, 251, 255256, 259, 266, 270, 273274, 283, 286, 290, 297, 309, 312
ni tra tes , ni trogl yceri n, 202, 206, 223225, 232, 240, 242, 245, 253, 257, 259, 262, 264267, 270, 272273, 277, 282, 285, 289, 513
Anti a rrhythmi c drugs
a denos i ne, 242, 268, 292, 337
a mi oda rone, 211, 220, 261, 269, 281, 412, 429, 430
a tropi ne, 62, 8284, 89, 97, 99100, 103, 106108, 111112, 115117, 119121, 123, 125127, 159, 167, 171, 173, 178, 199, 214, 258, 281, 289, 292, 338, 341,
343, 360, 374, 378, 395, 397398, 509, 512, 516517, 521
di goxi n, 32, 205, 215216, 224, 230, 244, 252, 255257, 259261, 268, 272, 274, 284, 288, 292, 298, 303, 311, 319320, 520
fl eca i ni de, 216
l i doca i ne, 32, 177, 240, 242, 281, 292, 512
proa rrhythmi c effects of, 261
proca i na mi de, 254, 269, 512
qui ni di ne, 32, 211, 216, 242, 252254, 260261, 269, 383, 392, 478, 512
Va ugha n-Wi l l i a ms cl a s s i fi ca ti on of, 216
Anti bi oti c-a s s oci a ted ps eudomembra nous col i ti s
cl i nda myci n ca us i ng, 450
metroni da zol e for trea ti ng, 401, 456
Anti bi oti cs
a mi nogl ycos i des , 11, 304, 321, 458461, 468, 472, 474475, 477482
a nti mycoba cteri a l s . See Anti tubercul a r drugs
cepha l os pori ns , 195, 451, 454, 457459, 463, 467, 470472, 474, 478, 483
fl uoroqui nol ones , 464, 471
l i nezol i d, 450, 466, 468, 470, 472, 483
ma crol i des , 464, 471472, 474
peni ci l l i ns , 254, 451, 456458, 461, 463464, 467468, 470472, 474477, 480483
s ul fona mi des , 254, 403, 463, 511
tetra cycl i nes , 388, 400, 465, 468, 472473, 480, 482
va ncomyci n, 400, 465468, 471473, 475, 480, 483
Anti ca ncer drugs
a l kyl a ti ng a gents ca rmus ti ne, 497

a nti meta bol i tes

cyta ra bi ne, 486, 494
fl uoroura ci l , 488, 494
a nti tumor a nti bi oti cs
bl eomyci n, 493, 497499
da cti nomyci n, 30, 494, 497
da unorubi ci n, 30, 494
doxorubi ci n, 30, 488, 493494, 497498
hormone a nta goni s ts
ful ves tra nt, 486, 494495
ra l oxi fene, 431
ta moxi fen, 30, 412, 430431, 494495, 499
pl a ti num-ba s ed a gents ci s pl a ti n, 478, 493, 497
s el ecti ve es trogen receptor modi fi ers
ra l oxi fene, 431
ta moxi fen, 30, 412, 430431, 494495, 499
ta xa nes /mi toti c i nhi bi tors , pa cl i ta xel , 497498
topoi s omera s e i nhi bi tors
etopos i de, 30, 497
topoteca n, 497
vi nca a l ka l oi ds
vi nbl a s ti ne, 30, 493, 499
vi ncri s ti ne, 486, 493, 497498
Anti chol i nergi c drugs . See Atropi ne
Anti coa gul a nts
di rect thrombi n i nhi bi tor, bi va l i rudi n, 249250, 276
hepa ri ns , 217, 225, 243244, 250, 253, 263264, 267, 276, 279
wa rfa ri n, 21, 32, 39, 194, 220, 225, 243244, 247, 249250, 253, 263264, 267269, 272, 276, 288, 375, 382, 392393, 402, 455, 470471, 474, 492, 495, 521
Anti convul s a nt drugs , 192193
ethos uxi mi de a s , 151, 189
fos phenytoi n a s , 176, 189
l ora zepa m a s , 32, 160, 176, 189, 197, 370, 510
phenytoi n a s , 136137, 166, 168170, 174, 176, 189190, 194, 197, 307, 368, 370, 382, 392, 417, 438, 492, 495, 510
s ta tus epi l epti cus a nd, 142, 145, 160, 176, 189, 370, 510, 517
Anti depres s a nts
a typi ca l , 166, 196
bupropi on, 146, 183, 194, 196198
bus pi rone, 134, 166, 193, 196
venl a fa xi ne, 155, 196
monoa mi ne oxi da s e i nhi bi tors , 105, 110, 145, 179, 181, 483
s el ecti ve s erotoni n reupta ke i nhi bi tors (SSRIs ), 105, 110, 145, 179, 181
fl uoxeti ne a s , 37, 139, 173, 181, 187, 195, 198, 200, 273, 307, 368, 489, 499
s ertra l i ne a s , 181, 187, 195, 200, 273, 368, 489, 499
tri cycl i c/heterocycl i c, 73, 82, 84, 86, 104, 109, 116, 119, 122, 135, 166167, 173, 181183, 186, 196197, 200, 512, 517
i mi pra mi ne, 32, 73, 84, 86, 116, 119, 135, 156, 173, 181, 196198, 517
Anti di a beti c drugs
a myl i n a nd i ncreti n-rel a ted drugs , exena ti de, 415, 433, 435436
-gl ucos i da s e i nhi bi tors , a ca rbos e, 434, 440, 443444
i ns ul i ns , 25, 46, 90, 238239, 289, 307, 408, 413, 425, 427, 430435, 440, 442444, 467
metformi n (bi gua ni des ), 211, 251, 289, 408, 416, 420, 428, 431432, 434435, 439440, 443444
s ul fonyl urea s , 195, 289, 427, 432435, 440, 442444
gl i mepi ri de, 442
gl i pi zi de, 442, 444445
gl yburi de, 407, 415, 419, 442, 444
tol buta mi de, 195, 440, 442, 444, 518
thi a zol i di nedi ones (gl i ta zones ), 443, 445
pi ogl i ta zone, 421, 427, 440, 443444
Anti di ureti c hormone, 197, 307, 310, 315
Anti epi l epti c drugs . See Anti convul s a nt drugs
Anti freeze poi s oni ng. See Ethyl ene gl ycol poi s oni ng
Anti funga l drugs
a mphoteri ci n B, 457, 473
cefmeta zol e, 454, 470472, 477
es omepra zol e, 225, 383, 392394, 400
fl ucona zol e, 458, 479

ketocona zol e, 431, 438, 446, 466

metroni da zol e, 387, 400, 465, 468470, 473
s ul fa methoxa zol e, 470, 473
Angl e-cl os ure gl a ucoma . See Gl a ucoma
Anti gout/a nti hyperuri cemi c drugs
a nti -i nfl a mma tory drugs
col chi ci ne, 356, 359, 364, 369, 376, 377
di cl ofena c, 247, 351, 357, 361
i buprofen, 26, 246247, 351, 357, 361, 367, 441
i ndometha ci n, 349, 351, 355, 357, 359, 361, 367, 369, 374377, 441
uri cos uri cs
probeneci d, 350, 359, 363364, 368369, 377
s ul fi npyra zone, 368
xa nthi ne oxi da s e i nhi bi tors
a l l opuri nol , 246, 359, 369, 377, 489490, 498500
febuxos ta t, 246, 348, 359, 366, 369, 490, 499500
Anti hi s ta mi nes . See also H 1 a nta goni s ts ; H 2 bl ockers
di phenhydra mi ne, 73, 7879, 96, 103, 106, 115116, 123127, 151, 153, 178179, 193, 195, 198, 341, 345, 348, 354, 357, 360361, 368, 374, 378, 405, 505,
517
doxyl a mi ne, 80, 126127, 374, 517
fexofena di ne, 34, 354, 360, 367, 374, 378
l ora ta di ne, 125, 173, 357, 374, 378
Anti hyperl i pi demi c drugs
bi l e a ci d s eques tra nts
chol es tyra mi ne, 172, 259, 287288, 437
col es evel a m, 233, 287288, 415, 436437, 443
col es ti pol , 287288, 437
ezeti mi be, 226, 278
fi bra tes , 278
HMG Co-A reducta s e i nhi bi tors (s ta ti ns )
a torva s ta ti n, 76, 120, 172, 223224, 260, 285, 297
pra va s ta ti n, 211, 251
ros uva s ta ti n, 247
ni a ci n, 211, 234, 251, 278, 288, 290, 408, 424
Anti hypertens i ve drugs , 63, 79, 8788, 99, 150, 159, 188, 201, 206207, 210, 212214, 222, 224, 227, 230231, 248, 255, 272, 400, 408, 512
Anti -i nfl a mma tory drugs , nons teroi da l nons el ecti ve COX-1/-2 i nhi bi tors
a s pi ri n, 26, 32, 41, 47, 204, 207208, 219220, 229, 233234, 239, 242, 246, 249250, 260, 267, 269, 277, 282283, 285, 287, 290, 299, 309, 330, 339340,
349351, 353355, 358359, 361362, 364366, 368373, 375, 387, 400, 471, 478, 506, 512, 518
di cl ofena c, 247, 351, 357, 361
i buprofen, 26, 246247, 351, 357, 361, 367, 441
i ndometha ci n, 349, 351, 355, 357, 359, 361, 367, 369, 374377, 441
ketorol a c, 72, 133, 161163, 391
na proxen, 246247
s el ecti ve COX-2 i nhi bi tor, cel ecoxi b, 42, 340, 351, 361, 365366
Anti ma l a ri a l drugs
chl oroqui ne, 466, 468, 484
hydroxychl oroqui ne, 351, 365, 464
pri ma qui ne, 449, 466468, 511512, 518
qui ni ne, 242
Anti mus ca ri ni c drugs , 93, 96, 106, 111112, 120121, 195, 199, 516
Anti mus ca ri ni c poi s oni ng, 117, 516. See also Atropi ne, poi s oni ng
Anti nucl ea r a nti body ti ters , 220
Anti pa rki ns on drugs
a nti mus ca ri ni cs , centra l l y-a cti ng
benztropi ne, 93, 116, 178, 184185, 195, 198199, 517
di phenhydra mi ne, 73, 7879, 96, 103, 106, 115116, 123127, 151, 153, 178179, 193, 195, 198, 341, 345, 348, 354, 357, 360361, 368, 374, 378, 405,
505, 517
tri hexypheni dyl , 143, 178, 185, 195, 198199, 517
dopa mi nergi c drugs
a ma nta di ne, 174, 184, 199, 478
bromocri pti ne, 141, 164, 174, 176, 182, 184186
ca rbi dopa , 88, 134, 154, 164165, 174, 184, 195, 199, 396
enta ca pone, 87, 194195, 199
l evodopa , 37, 88, 134, 154, 164165, 174176, 179, 184, 195, 396
ropi ni rol e, 142, 175176

s el egi l i ne, 164, 178179, 184185, 195, 199

Anti pl a tel et drugs
a bci xi ma b, 227, 269, 279
a s pi ri n, 26, 32, 41, 47, 204, 207208, 219220, 229, 233234, 239, 242, 246, 249250, 260, 267, 269, 277, 282283, 285, 287, 290, 299, 309, 330, 339340, 349
351, 353355, 358359, 361362, 364366, 368373, 375, 387, 400, 471, 478, 506, 512, 518
cl opi dogrel , 216, 247, 249250, 267, 269270, 279, 471
Anti ps ychoti c drugs
a typi ca l
cl oza pi ne, 153, 187, 193194, 200
ol a nza pi ne, 187, 193, 200
ri s peri done, 200
butyrophenones , ha l operi dol , 138, 145, 167168, 171, 175, 193, 198, 200, 307
neurol epti c ma l i gna nt s yndrome a nd, 46, 157, 175, 183, 191192, 200
phenothi a zi nes , chl orproma zi ne, 73, 116, 138, 146, 151, 167168, 171, 181, 185187, 190191, 194, 198, 200, 406, 519
thi ori da zi ne, 524t
Anti pyreti cs
a ceta mi nophen, 26, 247, 270, 339340, 350
a s pi ri n, 26, 32, 41, 47, 204, 207208, 219220, 229, 233234, 239, 242, 246, 249250, 260, 267, 269, 277, 282283, 285, 287, 290, 299, 309, 330, 339340, 349
351, 353355, 358359, 361362, 364366, 368373, 375, 387, 400, 471, 478, 506, 512, 518
i buprofen, 26, 246, 247, 351, 357, 361, 367, 441
Anti thyroi d drugs
i odi nes /i odi des , 411, 421, 429, 431, 436, 445
thi oa mi des . See Propyl thi oura ci l
Anti tubercul a r drugs
i s oni a zi d, 385, 396, 461, 464, 466, 480, 483, 512
ri fa mpi n, 439, 466, 481, 483, 495
Anti vi ra l /a nti retrovi ra l drugs
efa vi renz, 469
l opi na vi r, 460, 469, 476, 480481
ri tona vi r, 439, 460, 469, 476, 480481
s a qui na vi r, 30, 460
zi dovudi ne, 276, 448, 451452, 460, 463464, 467469, 476, 481
Anxi ol yti c drugs , 166, 196, 307
Apl a s ti c a nemi a , 404, 516
petrol eum di s ti l l a tes ca us i ng, 515
s ul fa s a l a zi ne ca us i ng, 403
Apomorphi ne, 199, 386, 398
Appeti te s uppres s i on. See Anorexi geni c drugs
APTT. See Acti va ted pa rti a l thrombopl a s ti n ti me
Ara chi doni c a ci d, 41, 339340, 358359, 366. See also Nons teroi da l a nti -i nfl a mma tory drugs
ARBs . See Angi otens i n receptor bl ockers
Area under the curve, 6, 10, 3435
bi oa va i l a bi l i ty determi ned wi th, 34
Arrector pi l i mus cl es , i nnerva ti on of, 50, 52, 8284
Ars eni c, 516, 518520
As pa ra gi na s e, 493, 497
As pi ri n, 26, 260, 368373, 478, 506, 512, 518. See also Sa l i cyl i s m
a cti va ted cha rcoa l for poi s oni ng from, 517518
a nti pl a tel et effects of, 47, 246247, 269270, 277, 366
a s thma , probl ems wi th, 329330, 340
bl eedi ng ti me a ffected by, 218, 267
bronchocons tri cti on/bronchos pa s m from, 72, 349, 359360
cl opi dogrel a s a l terna ti ve to, 219, 269
hemorrha gi c s troke from, 229, 283284
myoca rdi a l i nfa rcti on a nd, 233, 250
NSAIDs a nta goni zi ng a nti pl a tel et effects of, 246247
poi s oni ng from, 354, 374
Reye s yndrome a nd, 350, 365
toxi ci ty a nd ma na gement, 260, 353, 365372
uri cos uri c drug effects i nhi bi ted by, 359, 369
As thma , 72, 92, 9697, 105, 108109, 113114, 213, 224, 239, 254, 262, 274, 280, 328330, 332346
a l buterol a nd, 39, 96, 113, 213, 254, 327328, 336, 339, 341, 345, 395, 440
a s pi ri n a ggra va ti ng, 330, 340
chol i nes tera s e i nhi bi tors provoki ng, 332, 343344
corti cos teroi ds a nd, 331, 342

l eukotri ene modi fi ers a nd, 339

mus ca ri ni c a goni s ts provoki ng, 343
oma l i zuma b a nd, 328, 336337
refra ctory, 329
s a l meterol a nd, 328, 335336
theophyl l i ne for, 329, 337338
venti l a tory depres s a nts contra i ndi ca ted i n, 161, 331, 341
Atenol ol , 92, 105, 109, 126, 221, 244, 254, 275, 286, 344, 425
hypertens i on a nd, 206, 275
Atorva s ta ti n, 76, 120, 172, 223224, 260, 285, 297. See also Anti hyperl i pi demi c drugs
ATP s ynthes i s , 8586
ATPa s e, 320. See also Sodi um-pota s s i um a denos i ne tri phos pha ta s e
Atri a l fi bri l l a ti on, 205, 211, 216, 220, 252253, 255, 269, 281, 411
a mi oda rone a nd, 211, 220, 269, 281, 411
qui ni di ne a nd, 211, 216, 252253
Atri oventri cul a r node, 74
Atropi ne, 62, 8284, 89, 97, 99100, 103, 106108, 111112, 115117, 119121, 123, 125127, 159, 167, 171, 173, 178, 199, 214, 258, 281, 289, 292, 338, 341,
343, 360, 374, 378, 395, 397398, 509, 512, 516517, 521. See also Anti mus ca ri ni c drugs
chol i nes tera s e i nhi bi tor poi s oni ng trea ted wi th, 516517
di phenhydra mi ne s i mi l a r to, 73, 341, 348
di phenoxyl a te wi th, 386, 398
poi s oni ng, 106107, 117, 123, 167, 378, 516517
s i de effects , 73, 117
for s i nus bra dyca rdi a , 228, 281282
Attenti on defi ci t-hypera cti vi ty di s order, drugs for, 68
AUC. See Area under the curve Autonomi c nervous s ys tem, 49127
AV noda l conducti on/bl ock, 221, 228, 242, 255, 264265, 268, 270271, 286, 292
Aza thi opri ne, 488, 497, 499500
Azi thromyci n, 3, 25, 463465, 474, 478. See also Anti bi oti cs
B
Bacillus anthracis, 447
Bacteroides fragilis, 458, 465, 477
BAL. See Bri ti s h a nti -Lewi s i te
Ba rbi tura tes
benzodi a zepi nes compa red to, 161162
l a ryngos pa s m from pa rentera l , 132, 161
l ora zepa m a nd wi thdra wa l from, 155, 197
ma rgi n of s a fety/thera peuti c i ndex of, 166167
Ba roreceptor refl ex, 94, 96, 99, 101, 110, 112, 115, 117, 160, 236, 240, 245, 256, 262, 268, 274, 282, 289, 291, 293
a nti mus ca ri ni cs a nd, 117
-bl ockers a nd, 107
ca roti d ma s s a ge i nduci ng, 236237, 291
ga ngl i oni c bl ockers a nd, 114
va s ocons tri ctors a nd, 64, 117, 289, 293
va s odi l a tors a nd, 94, 112, 117, 160, 245, 270
vol ume depl eti on a nd, 289
Becl ometha s one, 328329, 334, 338, 410
for a s thma , 328
i n s ys temi c gl ucocorti coi d thera py, 428
Bel l a donna a l ka l oi ds , 157, 199, 505, 516
Beni gn pros ta ti c hypertrophy, 76, 228, 280
Benzodi a zepi nes , 32, 160162, 166
a l cohol potenti a ti ng effects of, 507, 519520
a mnes ti c effects of, 132
ba rbi tura tes compa red to, 161162
di a zepa m, 32, 140, 173
effects bl ocked by fl uma zeni l , 146, 167, 169, 173, 182, 507, 519
fl uni tra zepa m, 146, 182
fl ura zepa m, 194
l ora zepa m, 32, 160, 176, 189, 197, 370, 510
mi da zol a m, 68, 109, 132, 136, 145, 160161, 168, 173, 181, 262, 331, 341, 392, 460
s ei zures trea ted wi th, 160161
Benzothi a di a zi des . See Hydrochlorothiazide;
Thi a zi de di ureti cs

Benztropi ne, 93, 116, 178, 184185, 195, 198199, 517

extra pyra mi da l rea cti ons ma na ged wi th, 198199
Beta metha s one, 419, 440
Betha nechol , 72, 94, 111113, 115, 122, 126, 145, 344, 360, 395
for functi ona l uri na ry retenti on, 344, 395
s i de effects of, 72, 112
Bi l a tera l di a beti c nephropa thy, 303
Bi l a tera l rena l a rtery s tenos i s , a ngi otens i n modi fi ers contra i ndi ca ted i n, 238, 252, 408
Bi l e a ci d-s eques tra nts , 287
chol es tyra mi ne, 172, 259, 287288, 437
col es evel a m, 233, 287288, 415, 436437, 443
col es ti pol , 287288, 437
Bi l e s a l ts , 287288, 402
Bi oa va i l a bi l i ty, 2, 5, 21, 24, 2931, 3339, 43, 154, 172, 189, 393, 396, 455, 473474
a rea under the curve to determi ne, 3435
of drugs , 29, 3031, 39
Bi oterrori s m a gents
a nthra x, 447, 466
chol i nes tera s e i nhi bi tors , 89, 91, 97, 102, 120, 122124, 199
nerve ga s es , 103, 124, 173, 509, 511, 514, 521
ra di oi odi ne, 412, 431, 445
Bi otra ns forma ti on rea cti ons . See Drugs , meta bol i s m
Bi pol a r i l l nes s , 198, 223, 307
a nti depres s a nts for, 198, 307
l i thi um for, 198, 223, 307
Bi s phos phona tes , 410, 427428, 441, 445
Bi va l i rudi n, 249250, 276. See also Anti coa gul a nts
Bl a dder functi on, drugs a nd, 71, 89
Bl eedi ng ti me, 219, 267
Bl eomyci n, 493, 497499
-bl ockers , 16, 37, 61, 89, 9197, 99, 105107, 116, 120, 125126, 160, 188, 198, 203, 206, 224, 232, 238241, 243245, 249, 251252, 254255, 259260, 262,
266, 268, 272, 274275, 278, 282283, 285286, 289, 312, 320, 332, 335, 343344, 375, 427, 434, 512
Bl ood pres s ure. See a l s o Anti hypertens i ve drugs
-a drenergi c a goni s ts ra i s i ng, 215, 227
-a drenergi c a goni s ts ra i s i ng, 289
-a drenergi c bl ockers l oweri ng, 231, 289
a ngi otens i n modi fi ers l oweri ng, 238, 246, 249
cha nges a cti va ti ng ba roreceptors , 94, 96, 99, 101, 110, 112, 115, 117, 160, 236, 240, 245, 256, 262, 268, 274, 282, 289, 291
equa ti on for ca l cul a ti ng, 9495
ni fedi pi ne, i na ppropri a te us e to l ower, 223, 273
pra zos i n compa red to
phenoxybenza mi ne for l oweri ng, 243
va s odi l a tors l oweri ng, 222, 234, 275, 290291
Bone ma rrow s uppres s i on, drugs ca us i ng, 376, 483, 492493, 498, 511
Botul i num toxi n a nd botul i s m, 77, 83, 121, 248, 508, 521
BPH. See Beni gn pros ta ti c hypertrophy
Bra dyca rdi a , 59, 67, 9394, 105, 115, 120, 123, 228, 257258, 281, 291, 293, 335, 343, 346, 374, 378, 424
a tropi ne for, 228, 281282
i s oproterenol for, 281
s i nus , 228, 281282
Bra dyki ni n, 222, 271272, 278, 352, 367
ca ptopri l a nd, 352, 367
Bra dyki ni na s e. See Angi otens i n converti ng enzyme
Brea s t ca ncer
ful ves tra nt a nd, 488, 494495
ta moxi fen a nd, 412, 430432, 494495
Bri ti s h a nti -Lewi s i te, 518520
Bromocri pti ne, 134, 147148, 164, 174, 176, 182, 184186, 190, 199, 293, 423, 446
hyperprol a cti nemi a a nd, 149, 186, 190, 199, 293, 446
neurol epti c ma l i gna nt s yndrome a nd, 157, 200
Pa rki ns on di s ea s e a nd, 151, 157, 198199
pri ma ry a menorrhea a nd, 423, 446
Bronchocons tri cti on, 72, 113114
a s pi ri n ca us i ng, 349, 361362
Bronchodi l a ti on, 39, 62, 70, 72, 82, 85, 97, 109, 113114, 116, 170, 336, 338, 341342, 346

Bronchos pa s m, 47, 92, 103, 105, 113, 170, 175, 254, 278, 328, 330, 334, 340, 343, 349, 358
Bupropi on, 146, 183, 194, 196198
epi l eps y/s ei zures from, 156, 197198
s exua l dys functi on a nd, 146, 183
Bus pi rone, 134, 166, 193, 196
Butyrophenone a nti ps ychoti cs . See Anti ps ychoti c drugs ; ha l operi dol
C
Ca dmi um poi s oni ng, 506
Ca l ci toni n, 415, 436
Ca l ci um, 244, 250, 255, 259, 272, 397398, 401, 428429, 436437, 455, 473
Ca l ci um ca rbona te, 397, 401
Ca l ci um cha nnel bl ockers , 240
corona ry va s os pa s m a nd, 259260
di hydropyri di nes , ni fedi pi ne, 172, 216, 242, 250, 256, 262, 270, 273
di hydropyri di nes compa red wi th nondi hydropyri di nes , 216, 242, 250251
for es s enti a l hypertens i on a nd, 240, 249, 297, 312
nondi hydropyri di nes
di l ti a zem, 216, 223, 239240, 244, 249250, 255256, 259, 262, 270, 273274, 283
vera pa mi l , 25, 34, 174, 216, 239240, 242, 249250, 252, 255, 256, 259, 262, 266, 268, 270, 273274, 282284, 286, 407
Ca l ci um gl ucona te, 415, 436
cAMP. See Cycl i c AMP
Ca ncer chemothera peuti c drugs . See Anti ca ncer drugs
Ca ptopri l , 205, 221, 223, 230, 240, 255256, 259, 270271, 277, 282, 285, 323, 367, 374
bl ood concentra ti ons a nd, 323324
bra dyki ni n a nd, 352, 367
bra dyki ni na s e a nd, 222, 271, 368
cough from, 221, 271
hea rt fa i l ure a nd, 221
hypertens i on a nd, 218, 221, 386
mecha ni s ms of a cti on, 270, 375
NSAIDs a ffecti ng, 375376
pregna ncy a nd, 210
Ca rba ma zepi ne, 439, 470, 495, 518
Ca rbi dopa , 88, 134, 154, 164165, 174, 184, 195, 199, 396
a cti ons i n gut, 147, 184185
l evodopa us ed wi th, 37, 88, 134, 154, 164165, 174176, 179, 184, 195, 396
pyri doxi ne countera cti ng, 385, 396
Ca rboni c a nhydra s e i nhi bi tors , 309, 311, 316320, 324
a ceta zol a mi de a s , 316317
uri ne el ectrol yte profi l es a nd, 314, 317
Ca rdi a c gl ycos i des . See Di goxi n
Ca rdi a c mus cl e, a drenergi c receptors a nd, 82, 86, 90, 227, 343
Ca rdi a c output
equa ti on for, 94
hea rt fa i l ure a nd, 98, 214, 262
pos i ti ve i notropes a nd, 303, 320
Ca rdi omyopa thy, 350, 486, 493, 515
Ca rdi os el ecti ve -bl ockers . See -bl ockers ; a tenol ol ; metoprol ol
Ca roti d s i nus ma s s a ge, a rrhythmi a termi na ti on by, 236237, 291
Ca rvedi l ol , 91, 9495, 110, 205, 208, 222, 225, 230, 239, 241, 245, 254, 260, 271, 277, 286, 425
Ca techol O-methyl tra ns fera s e (COMT), 104, 154, 194
enta ca pone i nhi bi ti ng, 87, 194195, 199
Ca techol a mi ne, 42, 55, 58, 86, 8889, 91, 9596, 99, 107, 110, 120, 126127, 164, 179, 186, 190, 239240, 254, 285, 291, 515
CCBs . See Ca l ci um cha nnel bl ockers
Cefa zol i n, 453, 471. See also Anti bi oti cs , cepha l os pori ns
Cefmeta zol e, 454, 470472, 477. See also Anti bi oti cs , cepha l os pori ns
Cefopera zone, 454, 470472. See also Anti bi oti cs , cepha l os pori ns
Cefoteta n, 455, 470472, 478. See also Anti bi oti cs , cepha l os pori ns
Cefoxi ti n, 458, 477478. See also Anti bi oti cs , cepha l os pori ns
Ceftri a xone, 462, 483. See also Anti bi oti cs , cepha l os pori ns
Cel ecoxi b, 42, 340, 351, 361, 365366. See also Anti -i nfl a mma tory drugs , nons teroi da l
a cti ons /properti es of, 351, 365
Centra l nervous s ys tem, 129200
Cepha l os pori ns . See also Anti bi oti cs , i ndi vi dua l cepha l os pori ns

i ntera cti ons wi th a l cohol , 470

mecha ni s m of a cti on of, 457, 477
prol onged INR from, 471472
vi ta mi n K defi ci enci es a nd, 475
Chemoreceptor tri gger zone, 163, 185, 391, 406
Chemothera py. See Anti ca ncer drugs
Chl ora l hydra te, 196, 521
Chl ordi a zepoxi de, 156, 198
Chl oroqui ne, 466467, 484
Chl orothi a zi de, 296, 320. See also Di ureti cs , thi a zi des
Chl orproma zi ne, 30, 116, 138, 148, 157, 167168, 171, 175, 185187, 193, 196, 198, 200, 405, 517. See also Anti ps ychoti c drugs
ha l operi dol compa red to, 138, 167168
neurol epti c ma l i gna nt s yndrome a nd, 46, 157, 175, 183, 191192, 200
orthos ta ti c hypotens i on from, 186, 193
s chi zophreni a a nd, 148, 198
s chi zophreni a trea ted wi th benztropi ne a nd, 157, 198
Chl ortha l i done. See also Di ureti cs , thi a zi des
hea rt fa i l ure, furos emi de repl a ci ng, 289, 298, 300
i denti fyi ng us e of, 307, 325326
rena l pota s s i um l os s from, 299, 313
Chol es terol , drugs us ed to modi fy l evel s of. See Anti hyperl i pi demi c drugs
Chol es terol ga l l s tones , 399
Chol es terol s ynthes i s a nd drugs i nhi bi ti ng i t, 226, 399. See also Anti hyperl i pi demi c drugs , s ta ti ns
Chol es tyra mi ne, 172, 259, 287288, 437
Chol i nergi c cri s i s , 65, 78, 102, 122123
edrophoni um for di fferenti a l di a gnos i s of, 78, 122123
mya s theni c cri s i s compa red to, 122123
Chol i nergi c receptors , 8284, 93, 97, 121, 159, 170, 186, 346, 360, 378
s ubtypes a nd l oca ti ons , 8284
Chol i nes tera s e. See Acetyl chol i nes tera s e
Chroni c myel ogenous l eukemi a , 487, 495496
Chroni c obs tructi ve pul mona ry di s ea s e, 62, 9697, 327346
i pra tropi um for, 96, 329, 337338
N-a cetyl cys tei ne a nd, 330, 339340
Chroni c open a ngl e gl a ucoma . See Gl a ucoma
Ci meti di ne, 361, 368, 391393, 397, 401, 438. See also Hi s ta mi ne receptor a nta goni s ts
Ci nchona a l ka l oi ds . See Chl oroqui ne; Hydroxychl oroqui ne; Qui ni di ne
Ci nchoni s m. See Qui ni di ne, toxi ci ty
Ci profl oxa ci n, 464, 466, 469. See also Anti bi oti cs , fl uoroqui nol ones
l ong QT s yndrome a nd, 464
Ci s pl a ti n, 478, 493, 497
Ci ta l opra m, 181, 196, 251, 499
Cl a vul a ni c a ci d, 460, 481
Cl ea ra nce of drugs , 24, 36
Cl i nda myci n, 400, 465, 468, 471, 473474, 478479
Cl oni di ne, 8788, 159, 188, 253, 271272. See also Anti hypertens i ve drugs
a brupt di s conti nua ti on of, 271272
Cl opi dogrel , 216, 247, 249250, 267, 269270, 279, 471. See also Anti pl a tel et drugs
a s a l terna ti ve to a s pi ri n for TIAs , 220, 269
Cl os ed-hea d i njury, 136, 187
morphi ne a nd, 149, 187
Clostridium difficile, 455, 465, 473
Cl os tri di um toxi n, 77
Cl oza pi ne, 153, 187, 193194, 200. See also Anti ps ychoti c drugs , a typi ca l
a gra nul ocytos i s from, 153, 187, 193194
Coca i ne, 55, 82, 84, 8687, 89, 100, 104, 109, 119, 121, 148, 177, 186, 470, 512, 522
a dvers e effects of, 148, 186
i nhi bi ti on of norepi nephri ne reupta ke by, 82, 86, 104, 119, 121, 186
a s l oca l a nes theti c, 186
Codei ne, 144, 173, 180, 261, 341, 368
Col chi ci ne, 356, 359, 364, 369, 376377
a cute gout a nd, 356, 376
Col es evel a m, 233, 287288, 415, 436437, 443
di a betes mel l i tus a nd, 415, 436437
hyperl i pi demi a s a nd, 415, 443

Col es ti pol , 287288, 437

Coma , 167, 185, 316317, 435
due to a ceta zol a mi de, 301, 316
hepa ti c, neomyci n effect, 461
COMT. See Ca techol O-methyl tra ns fera s e
Coni va pta n, 315
Cons ti pa ti on
a l os etron a nd, 391, 405406
vera pa mi l ca us i ng, 216, 262263
Coombs -pos i ti ve tes t, drugs ca us i ng, 254
COPD. See Chroni c obs tructi ve pul mona ry di s ea s e Corona ry a rtery di s ea s e, 241, 281
Corona ry s tea l , 246
Corona ry va s os pa s m, 105, 151, 174, 186, 190, 202, 206, 211, 215, 229, 245, 250, 259260, 283
Corti cos teroi ds , 187, 213, 328, 331, 334, 336338, 342, 345, 422, 435, 438, 444, 446
a s thma a nd, 331, 342
res pi ra tory a ci dos i s a nd, 332, 344
Corti s ol , 346, 416, 428, 430, 438, 440, 446
Cough, 144, 180
ca ptopri l ca us i ng, 221, 270
dextromethorpha n trea ti ng, 330, 340341
COX. See Cycl ooxygena s es
COX-2 i nhi bi tors , 42, 340, 351, 361, 366, 492. See also Cel ecoxi b; Anti -i nfl a mma tory drugs , nons teroi da l
Crohn di s ea s e, 379, 403
Cromol yn, 329, 338
Cura re. See Neuromus cul a r bl ockers ; Tubocura ri ne
Cus hi ng di s ea s e, 314, 422, 441, 446
a drena l corti cos teroi d s ynthes i s i nhi bi ti on, 441
Cya ni de
ni troprus s i de ca us i ng poi s oni ng by, 215, 258259
poi s oni ng a nd trea tment, 225, 263, 277, 501, 510511
Cya nocoba l a mi n, 263, 385, 388, 396, 402
Cycl i c AMP (cAMP), 2, 241
Cycl ooxygena s es , 41, 249, 267, 269, 290, 298, 339340, 351, 358360, 366367
See also Nons teroi da l a nti -i nfl a mma tory drugs ; Anti pyreti cs
Cycl os pori ne
gra pefrui t jui ce a ffecti ng bi oa va i l a bi l i ty of, 9, 3334
nephrotoxi ci ty a nd, 490, 500
Cys ti c fi bros i s , pa ncrel i pa s e for s tea torrhea i n, 389
Cyta ra bi ne, 486, 494
Cytochrome P450 s ys tem, 29, 42, 514
genera l rea cti on s chemes i nvol vi ng, 41
i nducers a nd i nhi bi tors of, 29
a s monooxygena s e, 41
D
Da cti nomyci n, 30, 494, 497
Da ntrol ene, 141, 157, 191, 200
Da ptomyci n, 454, 472
Da unorubi ci n, 30, 494
Depres s i on, 37, 78, 94, 100, 103, 109, 134, 145, 155156, 158, 160, 162, 166171, 175, 178180, 182185, 187, 189191, 194, 196198, 200, 211, 270, 341, 370,
378, 391, 398, 468, 476, 498, 503, 514515, 517. See also Anti depres s a nts
bus pi rone a nd, 134, 196
monoa mi ne oxi da s e i nhi bi tors a nd, 179180
Des ens i ti za ti on of receptors , 39, 344
Dexa metha s one, 188, 438, 440, 446, 488
Dextroa mpheta mi ne, 57, 89, 173, 518
Dextromethorpha n, 144, 180, 330, 340341
Di a betes i ns i pi dus
l i thi um ca us i ng, 307
nephrogeni c, 313
thi a zi de di ureti cs for, 319
Di a betes mel l i tus . See Anti di a beti c drugs
Di a rrhea , 63, 93, 99, 127, 191, 215, 342, 368, 376377, 383, 387, 395, 397, 400402, 404, 435, 448, 455, 472, 506, 518, 520
Di a zepa m, 32, 140, 173, 176, 183, 189, 194195, 197, 262, 307, 341, 368, 510. See also Benzodi a zepi nes
effects a nta goni zed by fl uma zeni l , 169, 172

Di a zoxi de, 234, 289, 307, 424425. See also Anti hypertens i ve drugs
bl ood gl ucos e l evel s ra i s ed wi th, 289, 307
Di cl ofena c, 247, 351, 357, 361
Di eta ry Suppl ement Hea l th a nd Educa ti on Act, 47
Di gi ta l i s . See Di goxi n
Di goxi n, 29, 32, 205, 215216, 224, 230, 244, 252, 255257, 259261, 268, 272, 274, 284, 288, 292, 298, 303, 311, 319320, 520
a s a nti a rrhythmi c, 216, 252
ATPa s e i nhi bi ti on by, 259
AV noda l conducti on/bl ock a nd, 216, 255, 268, 286, 292
chroma tops i a from, 274, 303
corona ry a rtery di s ea s e, furos emi de wi th, 215, 255
el ectroca rdi ogra phi c effects of, 230, 284
hea rt fa i l ure a nd, 205, 215, 230, 259, 284, 319
hypoka l emi a a nd, 259, 274, 318319
toxi ci ty of, 216, 224, 259260, 274, 303, 319
Di hydropyri di nes , 216, 242, 250, 256, 262, 270, 273. See also Ca l ci um cha nnel bl ockers ; Ni fedi pi ne
vera pa mi l /di l ti a zem compa red to, 270
Di l ti a zem, 30, 216, 223, 239240, 244, 249250, 255256, 259, 262, 270, 273274, 283. See also Ca l ci um cha nnel bl ockers
AV noda l conducti on/bl ock a nd, 270271
di hydropyri di nes compa red to, 270
us e for hypertens i on, 224, 274
va s os pa s ti c a ngi na a nd, 211, 244245
Di merca prol . See Bri ti s h a nti -Lewi s i te
Di pepti dyl phos pha te (DPP4) i nhi bi tors . See Anti di a beti c drugs .
Di phenhydra mi ne, 73, 7879, 96, 103, 106, 115116, 123127, 151, 153, 178179, 193, 195, 198, 341, 345, 348, 354, 357, 360361, 368, 374, 378, 405, 505, 517.
See also Anti hi s ta mi nes
a nti mus ca ri ni c (a tropi ne-l i ke) effects of, 71, 115116, 379, 517
a s fi rs t-genera ti on a nti hi s ta mi ne prototype, 73, 115, 123, 126, 360
peri phera l a utonomi c a cti ons of, 78, 123
phys os ti gmi ne for overdos es of, 116, 505, 517
poi s oni ng, 505, 517
prometha zi ne a nd, 151, 191
for s ea s ona l a l l ergi es , 357
s econd-genera ti on a nti hi s ta mi nes compa red wi th, 354, 374
s eda ti on ca us ed by, 126, 360, 374
s i de effects of, 73, 78, 348, 357
Di phenoxyl a te, 384, 386, 394, 398
Di pyri da mol e, 264, 270
Di s ea s e-modi fyi ng a nti rheuma ti c drugs , 365, 491
Di s s oci a ti ve a nes thes i a . See Keta mi ne
Di s ul fi ra m, 154, 195, 434, 453, 470
a nti mi crobi a l s wi th a cti ons res embl i ng, 470
s ul fonyl urea s wi th a cti ons res embl i ng, 195
Di ureti cs , 139, 172, 188, 240, 246, 249, 253, 255, 295326
l oop, 249250, 255, 264, 271, 289, 308, 310315, 317326, 359, 375, 395, 478
NSAID effects on a cti ons of, 311, 359
os moti c, 187, 318, 321, 511
ma nni tol , 187, 315, 318, 321, 511
pota s s i um-s pa ri ng, 257, 281, 311313, 317, 321, 323, 325, 442, 446
a mi l ori de, 257, 271, 304, 317319, 321325
epl erenone, 300, 313314, 316317, 319, 323, 441
s pi ronol a ctone, 257, 307, 311314, 316319, 321324, 438
tri a mterene, 216, 224, 230, 257, 271, 274, 283, 307, 311, 317, 321324, 326
pregna ncy a nd, 249
thi a zi des , 240, 244, 246, 253, 296, 319, 325, 425
chl ortha l i done, 299, 307308, 312, 317, 320, 324325, 429
hydrochl orothi a zi de, 223, 230, 244, 253, 255, 273, 296, 297, 310313, 317318, 320, 322, 324325, 410, 424, 429
metol a zone, 239, 244, 255, 273, 299, 307308, 312313, 316317, 319321, 325, 430
DMARDs . See Di s ea s e-modi fyi ng a nti rheuma ti c drugs
Dobuta mi ne, 56, 66, 74, 104, 107, 117118, 258, 285286, 308. See also Hea rt fa i l ure, drugs for
a l terna ti ves to, 74, 117118
bl ood pres s ure ra i s ed by, 232, 286
DOPA deca rboxyl a s e, i nhi bi tors of, 91, 154, 164165, 195, 396
Dopa mi ne, 19, 5556, 63, 74, 8688, 91, 93, 98, 104, 107, 117, 148149, 164165, 167, 172, 174176, 178, 181182, 184187
hi gh dos a ges of, 73, 117

rena l effects of, 308

Dopa mi ne receptors , bl ocka de of, 142, 157, 164165, 167, 175, 181182, 184187, 199, 406
Dos e-res pons e curves , 4, 126, 164
Down-regul a ti on of receptors , 39
Doxorubi ci n, 30, 486, 488, 493494, 497498. See also Anti ca ncer drugs , a nti tumor a nti bi oti cs
Doxycycl i ne, 400, 465466, 484
Doxyl a mi ne, 80, 126127, 374, 517. See also Di phenhydra mi ne
DPP4 i nhi bi tors . See Anti di a beti c drugs .
Drona bi nol , 163, 186
Droperi dol , 145, 181
l ong QT s yndrome a nd probl ems wi th, 181
Drugs . See also specific drugs
a ge a ffecti ng thera py wi th, 32
bi oa va i l a bi l i ty of, 29, 3031, 39
cl ea ra nce of, 56, 14, 17, 21, 24, 3233, 3536, 3940, 4344, 169
di s pl a cement of bound, 39
dos e-res pons e curves for, 4
effi ca cy vs potency of, 26
el i mi na ti on ra te cons ta nt of, 10, 3435, 4344
exces s i ve dos es of, 237
extra cti on ra ti o of, 25, 36
ha l f-l i fe of, 8, 10, 18, 39
hepa ti c cl ea ra nce of, 32
i oni za ti on of, 2324
l oa di ng dos e ca l cul a ti ons for, 14, 40
ma i ntena nce dos e ca l cul a ti ons for, 5, 18, 205
ma rgi n of s a fety of, 167, 343. See also Thera peuti c i ndex
meta bol i s m, 19, 38, 475
off-l a bel us e of, 11, 37, 48
ora l vs i ntra venous a dmi ni s tra ti on, 67
OTC regul a ti ons , 20, 47
a s pa rti a l a goni s ts , 16, 42
recogni zi ng cl a s s ba s ed on generi c na me, xxvi i xl i i
thera peuti c i ndex of, 167, 338
ti me to rea ch s tea dy-s ta te concentra ti on of, 5, 10, 18
vol ume of di s tri buti on of, 1, 11, 14, 1718, 27, 33
DSHEA. See Di eta ry Suppl ement Hea l th a nd Educa ti on Act
Ductus a rteri os us , pa tent, 353, 367369, 441
E
Echothi opha te, 58, 9091, 98. See also Acetyl chol i nes tera s e i nhi bi tors
Edrophoni um, 78, 102, 122123, 268, 281, 283. See also Acetyl chol i nes tera s e i nhi bi tors
for di fferenti a l di a gnos i s of mya s theni c, chol i nergi c cri s i s , 78, 122123
Efa vi renz, 469
Emes i s , drugs for, 161, 186, 199, 399, 406
onda ns etron, 133, 163, 186, 391, 394, 405, 488
Emetogeni c drug. See Apomorphi ne
Ena l a pri l , 224, 274. See also Angi otens i n-converti ng enzyme i nhi bi tors
Endothel i um remova l , ACh a nd, 210, 247248
Endothel i um-deri ved rel a xi ng fa ctor (EDRF). See Ni tri c oxi de
Enta ca pone, 87, 194195, 199
Enterochroma ffi n-l i ke cel l s , 397
Ephedri ne, 70, 86, 108110, 117, 164, 179, 241, 462, 470, 483
Epi l eps y/s ei zures , 136, 140, 148, 151152, 176, 188189, 198, 385, 417. See also Anti convul s a nt drugs
bupropi on ca us i ng, 197198
ethos uxi mi de for, 151, 189
phenytoi n for, 136, 140, 189
thera py of duri ng pregna ncy, 152
va l proi c a ci d for, 140
Epi nephri ne, 19, 42, 58, 60, 6364, 74, 82, 85, 88, 90, 95, 97, 99101, 103, 107108, 118, 120, 124125, 213, 242244, 249, 254, 272, 275, 284285, 291292,
335336, 339340, 344, 358, 427, 434, 521
a na phyl a xi s a nd, 64, 100, 103
l oca l a nes theti cs a nd, 64, 100101
Epl erenone, 300, 313314, 316317, 319, 323, 441. See also Spi ronol a ctone
Epoeti n a l fa , 225, 276

Eps on s a l t, 398
Erecti l e dys functi on
drugs for, 312
s i l dena fi l , 218, 264265
ta da l a fi l , 264
va rdena fi l , 264
s pi ronol a ctone ca us i ng, 312
Ergonovi ne, 293, 411
Ergota mi ne, 189190, 292293
myoca rdi a l i s chemi a from overdos e of, 231, 292293
Erythromyci n, 463464, 468, 470472, 474, 483, 495. See also Anti bi oti cs , ma crol i des
l ong QT s yndrome a nd, 464
wa rfa ri n a nd, 455, 474
Escherichia coli, 388, 400401, 462, 464, 474, 482
Es ci ta l opra m, 196, 200, 211, 251, 501
Es mol ol , 94, 230, 232, 283, 286. See also -Adrenergi c bl ockers
Es omepra zol e, 225, 383, 394395
for ga s troes opha gea l refl ux di s ea s e, 383, 394395
Es opha gi ti s , 419, 441
Es s enti a l hypertens i on. See Hypertens i on
Es trogen, 407, 422
hypertens i on a nd exces s , 417, 440
thromboembol i s m a nd, 416, 438
Eta nercept, 358, 379
Etha cryni c a ci d, 297, 308, 310312, 318, 321323, 395, 478
ototoxi ci ty a nd, 321
Etha mbutol , 450, 461462, 466, 481, 483484
Etha nol , 155, 196
benzodi a zepi nes i n wi thdra wa l from, 155, 193194, 507, 519520
cepha l os pori ns i ntera cti ng wi th, 454, 470
di s ul fi ra m i ntera cti ng wi th, 154, 195
Ethos uxi mi de, 151, 189
Ethyl ene gl ycol poi s oni ng, 503, 514515
Eti drona te, 419, 441, 445
Etopos i de, 30, 497
Exena ti de, 414, 432, 434435
Extra cti on ra ti o, 25, 36
Ezeti mi be, 226, 278
F
Fa moti di ne, 391, 397, 401. See also Anti hi s ta mi nes , hi s ta mi ne receptor a nta goni s ts
FDA. See Food a nd Drug Admi ni s tra ti on
Febuxos ta t, 246, 348, 359, 366, 369, 490, 499500. See also Al l opuri nol ;
Anti hyperuri cemi c drugs
Fenta nyl , 156, 168, 173, 181, 197, 391
na l oxone to trea t exces s i ve effects of, 156, 197
Ferrous s ul fa te, 225, 276, 395, 520
Fes toterodi ne, 57, 8889
Feta l res pi ra tory di s tres s s yndrome, 418, 440
Fexofena di ne, 314, 360, 367, 374, 378
di phenhydra mi ne compa red to, 354, 373374
Fi bra tes , 278
Fi bri nol yti c drugs . See Thrombol yti cs
Fi l gra s ti m, 488, 498
Fi na s teri de, 409, 426
Fl a voprotei ns (FP), 4142
Fl eca i ni de, 216
Fl ucona zol e, 458, 479
Fl udrocorti s one, 416, 438
Fl uma zeni l , 137, 140, 146, 167, 169, 172173, 182, 197, 507, 519
Fl uni tra zepa m, 146, 160, 182, 519
Fl uoroqui nol ones . See Anti bi oti cs , fl uoroqui nol ones
Fl uoxeti ne, 37, 173, 181, 187, 195, 198, 200, 273, 307, 368, 489, 499
s erotoni n reupta ke a nd, 196, 200
s uma tri pta n a nd, 139, 173, 352, 368

Fl ura zepa m, 194

Fl uta mi de, 487, 496
Fol i c a ci d (fol a te)
defi ci ency, 396
pregna ncy a nd, 402
s uppl ements , 152, 192193, 402
s ynthes i s a nd i nhi bi tors , 453, 470
Food a nd Drug Admi ni s tra ti on (FDA), 11, 2021, 37, 4648, 96, 108, 144, 151, 191, 333, 435, 477, 489
nutri ti ona l s uppl ements a nd, 20, 46
pregna ncy cl a s s i fi ca ti ons a nd, 21, 192
prometha zi ne wa rni ng of, 151, 191
s a l meterol wa rni ng of, 333
Fos phenytoi n, 176, 189
Ful ves tra nt, 486, 494495
Furos emi de, 205, 216, 221, 224, 230, 234, 240, 249, 255, 259, 264, 271272, 274, 289, 298300, 308312, 317, 319324, 395. See also Di ureti cs ; Loop di ureti cs ;
Ototoxi ci ty
a mi nogl ycos i de wi th, 304, 321
corona ry a rtery di s ea s e, di goxi n wi th, 215, 259
hea rt fa i l ure, thi a zi de repl a ced by, 297, 308309
hypoka l emi a from, 259, 274
hypona tremi a a nd, 304, 322
hypovol emi a from, 298, 311312
i denti fyi ng us e of, 305
G
GABA. See -Ami nobutyri c a ci d
Ga l a ctorrhea , 135, 145, 170, 172, 181, 199
Ga l l bl a dder di s ea s e
ga l l s tones di s s ol ved by drugs i n, 399
opi oi ds i n, 171
Ga ngl i oni c bl ocka de, 59, 94, 115
Ga s tri c a ci d-a nti s ecretory drugs
ci meti di ne, 349, 361, 383, 393, 416, 438
es omepra zol e, 225, 382383, 392394, 396
fa moti di ne, 382, 391
ni za ti di ne, 382, 391392
omepra zol e, 392, 524
ra ni ti di ne, 382, 388, 391392, 401
Ga s tri c ul cers , 388, 400

Ga s troes opha gea l refl ux di s ea s e (GERD), 383, 386

es omepra zol e for, 382, 392
Genta mi ci n, 321, 454, 456459, 468, 472474, 478, 480481. See also Anti bi oti cs , a mi nogl ycos i des
a mi ka ci n compa red to, 460, 475
a na erobi c ba cteri a a nd, 465, 469, 482
GERD. See Ga s troes opha gea l refl ux di s ea s e
Gl a ucoma , drugs a nd, 5859, 62, 80, 9093, 9798, 103, 127, 202, 240, 301, 309, 316, 318, 332, 343344, 360, 374
Gl i mepi ri de, 442. See also Anti di a beti c drugs
Gl i pi zi de, 442, 444445. See also Anti di a beti c drugs
Gl i ta zones . See Pi ogl i ta zone
GLP-1. See Gl uca gon-l i ke pepti de-1
Gl uca gon, 25, 241, 425, 427, 434435, 442
Gl uca gon-l i ke pepti de-1, 427, 434
Gl ucocorti coi ds , 342, 351, 366, 431, 438, 440. See also specific individual agents
Gl ucos e tol era nce tes ts , 307, 426
Gl uta thi one, 362, 375, 513
Gl yburi de
hypogl ycemi a a nd, 407, 420
i ns ul i n rel ea s e a nd, 419, 442
Gl ycopyrrol a te, 71, 111112
Gl ycos uri a , 300, 314, 321
Gout. See Anti gout/a nti hyperuri cemi c drugs
Gra m-nega ti ve ba cteri a , 458, 475, 477
Gra pefrui t jui ce, 9, 3334
Gra ves di s ea s e, 420
Gua na drel , 63, 9899
H
H 1 bl ockers . See Di phenhydra mi ne, hi s ta mi ne receptor a nta goni s ts
H1N1 vi rus , 457, 477
H 2 bl ockers . See a nti hi ta mi nes , hi s ta mi ne receptor a nta goni s ts
Haemophilus influenzae, 453, 474, 483
Ha l operi dol , 147, 181, 184, 186. See also Anti ps ychoti c drugs , butyrophenones
chl orproma zi ne compa red to, 138, 171
Ha l otha ne, 161162, 191. See also Anes theti cs , genera l
Ha y fever, 357
HbA1c. See Hemogl obi n A1c
Hea da ches , 26, 37, 60, 237, 295, 312, 349
s uma tri pta n mi mi cki ng s erotoni n for, 349, 360
Hea ri ng l os s . See also Ototoxi ci ty a mi nogl ycos i des a nd, 459, 479480
ci s pl a ti n a nd, 488, 498499
l oop di ureti cs a nd, 318
Hea rt bl ock, 216, 264
vera pa mi l ca us i ng, 220, 269270
Hea rt fa i l ure, 64, 66, 71, 102, 105, 112113
a ngi otens i n converti ng enzyme i nhi bi tors a nd, 279
-bl ockers a nd, 241, 253, 257, 279, 288
chl ortha l i done repl a ced by furos emi de for, 295, 307308
di goxi n a nd, 202, 211, 230, 239, 253254, 286, 319
furos emi de ca us i ng hypotoni c uri ne i n trea ti ng, 299, 313
gl i ta zones a nd, 419, 442
qui ni di ne a nd, 214, 259260
Hea rt fa i l ure, drugs for
-a drenergi c bl ockers
a cebutol ol , 16, 42
a tenol ol , 70, 109, 206, 244, 425
metoprol ol , 58, 70, 92, 109, 222, 232, 425
na dol ol , 58, 62, 92, 97
nebi vol ol , 241
pi ndol ol , 58, 67, 92, 107
propra nol ol , 55, 60, 63, 70, 73, 86, 9495, 99, 105, 110, 114, 119, 126, 224, 228232, 254, 284, 286, 425
ti mol ol , 58, 62, 92, 98
a fterl oa d reducers . See Anti hypertens i ve drugs ; Di ureti cs ; Furos emi de
a ngi otens i n modi fi ers
ca ptopri l , 202, 210, 212, 222, 226228, 255256, 270271, 282, 323, 352, 355, 367, 374

ena l a pri l , 224, 275

l i s i nopri l , 225, 278, 305
l os a rta n, 206, 226, 244, 278
ra mi pri l , 211, 230
i notropes
di goxi n, 30, 205, 214215, 222, 224, 230, 240, 255, 257, 259260, 272
dobuta mi ne, 66, 68, 74, 104, 117118, 232, 258, 285286
dopa mi ne, 5556, 63, 74, 8687, 104, 117, 308
norepi nephri ne, 39, 5355, 6364, 74, 8284, 92, 9899, 103, 119, 124, 186
Helicobacter pylori, 399400
Hemogl obi n A1c, 201
Hemol yti c a nemi a , drug-i nduced, 212, 225, 254, 277, 515
Hemorrha gi c s troke, 222, 233, 272, 283, 346
Henders on-Ha s s el ba ch equa ti on, 23, 370, 512
Hepa ri ns , 205, 217, 225, 244
da ngers from us e wi th thrombol yti cs , 279
prota mi ne s ul fa te countera cti ng, 217, 263
thrombocytopeni a i nduced by, 243, 250, 276
Hepa ti c ci rrhos i s , 299, 301, 313
Hepa ti c cl ea ra nce of drugs , 2, 32, 392
Herba l s uppl ements , regul a ti on by FDA of, 20, 4647
Hexa methoni um, 110, 114
Hi s ta mi ne, 19, 25, 349, 352, 354, 360
Hi s ta mi ne receptor a nta goni s ts . See Anti hi s ta mi nes
HIV/AIDS, 450, 469. See also Anti vi ra l /a nti retrovi ra l drugs
zi dovudi ne a nd, 448, 452, 460, 463464, 469, 476
Homa tropi ne, 76, 120121, 125
Hydra l a zi ne
for hypertens i on, 214, 257
unwa nted ca rdi ova s cul a r res pons es of, 256
va s odi l a tor effects of, 219, 264
Hydrochl orothi a zi de, 223, 230, 244, 253, 255, 273, 296297, 310313, 317318, 320, 322, 324325, 424, 429. See also Thi a zi de di ureti cs
hypertens i on a nd, 305
hypona tremi a a nd, 304, 322323
i denti fyi ng us e of, 325
Hydrocodone, 342
Hydrocorti s one, 416, 446
Hydroxychl oroqui ne, 351, 365, 447. See also Anti ma l a ri a l s
Hypera l dos teroni s m, 312, 319, 442, 446
Hypera mmonemi a , 316
Hyperchol es terol emi a , 76, 218, 223, 226, 231, 251, 288, 297, 300, 436. See also Anti hyperl i pi demi c drugs
Hypercorti s m, 416
Hypergl ycemi a , 113, 289, 307, 314, 342, 410, 424425, 429, 467, 481
Hyperka l emi a , 152, 191, 221, 248, 257, 271, 281, 283, 312, 320
Hyperl i pi demi a s , 221, 234, 251, 281, 290, 443, 467. See also Drugs for hyperl i pi demi a s
Hyperpa ra thyroi di s m, 410, 428
Hyperprol a cti nemi a , 149, 186, 190, 199, 293
Hypertens i on. See also Anti hypertens i ve drugs
drug i nduced, 59, 93
emergency ma na gement of, 60
es s enti a l , 58, 60, 62, 76, 91, 9697, 203, 207, 213214, 217218, 221
es trogen a nd, 417
ma l i gna nt, 46
methyl dopa for, 248, 253254
pheochromocytoma s a nd, 60, 9596
Hyperthermi a . See Ma l i gna nt hyperthermi a
Hyperthyroi di s m
-a drenergi c bl ockers a nd, 67, 105
a nti thyroi d drugs for, 430431
hi gh dos e i odi des for, 411, 429, 436
ra di oi odi ne for, 411, 431
thyroi d s torm/thyrotoxi cos i s a nd, 105
Hyperuri cemi a , 207, 226, 233, 246, 297, 348, 350, 353, 356, 359, 364, 378, 437, 490. See also Anti gout/a nti hyperuri cemi c drugs
Hypervi ta mi nos i s D, 445
Hypoca l cemi a , 436

Hypogl ycemi a
a ca rbos e a nd, 421, 444
metformi n a nd, 412, 432
s ul fonyl urea s ca us i ng, 432433
thi a zol i di nedi ones ca us i ng, 442
Hypoka l emi a
a ceta zol a mi de ca us i ng, 304, 323
a mi l ori de for, 303, 321
di goxi n a nd, 303, 319320
furos emi de ca us i ng, 224, 274
Hypona tremi a
di l uti ona l , 322
furos emi de a nd, 304, 322323
hydrochl orothi a zi de a nd, 304, 322
l i thi um a nd, 223, 273
Hypotens i on. See also Orthos ta ti c hypotens i on
pra zos i n i nduci ng, 79, 126
propofol ca us i ng, 132, 160
res erpi ne i nduci ng, 79, 126
Hypothyroi di s m, 21, 59, 93
a mi oda rone a nd, 411, 429430
l evothyroxi ne a nd other thyroi d hormones for, 414
Hypotoni c uri ne, 295, 300
Hypovol emi a , 227, 249, 253, 283, 298, 311, 495
from furos emi de, 298, 310312
Hypoxa nthi ne, 348, 360, 498
I
Ibuprofen, 26, 246247, 351, 357, 361, 367, 441
a s pi ri n ta ken wi th, 208, 246
Ima ti ni b, 487, 495
Imi pra mi ne, 70, 84, 86, 116, 119, 135, 155156, 173, 181, 196198, 517
nocturna l enures i s a nd, 156, 197
Increti n mi meti cs , 414, 434435. See also Anti di a beti c drugs .
Indometha ci n, 350, 352, 355, 357, 359, 361, 367, 369, 374377, 441. See also Anti -i nfl a mma tory drugs , nons teroi da l
a ngi otens i n converti ng enzyme i nhi bi tors a ffected by, 347, 441
pa tent ductus a rteri os us cl os ure wi th, 353, 368
ul cer prophyl a xi s , mi s opros tol wi th, 349
Infl a mma tory bowel di s ea s e, 389, 403
Inos i tol tri s phos pha te (IP3 ), 2
INR. See Interna ti ona l Norma l i zed Ra ti o, wa rfa ri n
Ins ul i n, 90
gl a rgi ne, 413, 434
gl i ta zones a nd receptor s ens i ti vi ty to, 422, 446
gl yburi de a nd rel ea s e of, 420, 444
mea l s a nd rel ea s e of, 425
mol ecul a r modi fi ca ti on of, 413, 433
NPH, 433
pi ogl i ta zone a nd s ens i ti vi ty to, 421, 444
Interna ti ona l Norma l i zed Ra ti o, 219, 268
cepha l os pori ns prol ongi ng, 456
wa rfa ri n effects on, 225, 269, 272, 455
Intri ns i c s ympa thomi meti c a cti vi ty of -bl ockers , 67, 92, 107, 254, 425
Iodi nes /i odi des , 411, 429, 431, 436, 445
Ipeca c, 386, 398
Ipra tropi um, 62, 96, 329, 337
chroni c obs tructi ve pul mona ry di s ea s e a nd, 62, 329, 337338
Iron, 385, 395
Irri ta bl e bowel s yndrome, 387, 390, 400, 404
Is ofl ura ne
ha l otha ne compa red to, 191
ma l i gna nt hyperthermi a a nd, 191
Is oni a zi d, 480, 483
etha mbutol wi th, 461, 483484
pyri doxi ne a nd, 385, 396

tubercul os i s , vi ta mi n B 6 a nd, 459, 480

Is oproterenol , 57, 6364, 73, 75, 89, 99100, 103, 107108, 116, 119, 258, 281, 292, 344. See also -Adrenergi c a goni s ts
effects of, 73, 116
s i gns of us i ng, 75, 119
s i nus bra dyca rdi a a nd, 228, 281
Is otreti noi n, 403
J
Ji ms on weed, 516. See also a nti mus ca ri ni c drugs , a tropi ne
K
Kerni cterus from s ul fona mi des , 463
Keta mi ne, 136, 146, 168, 183
Ketocona zol e, 416, 422, 431, 438, 446, 466
Cus hi ng di s ea s e a nd, 416, 422, 438, 446
Ketorol a c, 72, 133, 161163, 391
Ki ni na s e II. See Angi otens i n converti ng enzyme
Kors a koff ps ychos i s , 402
L
La beta l ol , 9192, 9495, 110, 205, 239241, 245, 249, 254, 260, 271, 275, 286, 425. See also -Adrenergi c bl ockers
-La cta ma s e (peni ci l l i na s e), 458, 468, 471, 474, 481, 483
ceftri a xone res i s ta nt to, 462, 483
i nhi bi tors of, 471
oxa ci l l i n res i s ta nt to, 451, 468
La cti c a ci dos i s , 258, 418, 421, 432, 439440, 444, 467, 510, 513
La ctul os e, 384, 394
La ryngos pa s m, 103, 132, 161
ba rbi tura tes a nd, 132, 161
Lea d poi s oni ng, 520
Leucovori n, 485, 491492
Leukemi a , 456, 487491, 493, 495, 498, 511, 516
Leukotri enes , 336, 338339, 345, 347, 358359, 366
montel uka s t, 329, 338339
za fi rl uka s t, 338
Leuprol i de, 419, 441, 487, 496
fl uta mi de wi th, 487, 496
Levodopa . See also Anti pa rki ns on drugs , dopa mi nergi c
ca rbi dopa us ed wi th, 134, 154, 164, 195
pyri doxi ne countera cti ng, 385, 396
Levofl oxa ci n, 453, 469, 471
Levothyroxi ne, 409, 414, 418, 421, 435. See also hypothyroi di s m.
Lewi s i te, 518. See also British anti-Lewisite
LHRH. See Lutei ni zi ng hormone-rel ea s i ng hormone
Li doca i ne, 32, 177, 202, 228, 237, 240, 242, 281, 292, 510. See also Anes theti cs , l oca l ; Anti a rrhythmi c drugs
Li ga nds , 2, 25
bi ndi ng of, 45
Li nea r ki neti cs , 18
Li nezol i d, 449, 452453, 456, 466, 468, 470, 472, 483
va ncomyci n-res i s ta nt enterococca l i nfecti ons a nd, 449, 466
Li othyroni ne, 414, 435, 445. See also Thyroi d hormones
Li otri x, 414, 435. See also Thyroi d hormones
Li s i nopri l . See also Angi otens i n-converti ng enzyme i nhi bi tors
l os a rta n compa red to, 226, 277278
tri a mterene wi th, 296, 305
Li thi um, 139, 156, 172, 198, 223, 273, 307
hypona tremi a a nd, 223, 273
pol yuri a /pol ydi ps i a from, 307
Li vedo reti cul a ri s , 174
Li ver fa i l ure, 350, 362
Loa di ng dos e, 5, 14, 16, 18, 40, 44, 205, 243244
Loca l a nes theti cs . See Anes theti cs , l oca l ; Li doca i ne; Proca i ne
Long QT s yndrome, drugs pos i ng ri s ks i n, 181, 252, 464
Loop di ureti cs , 249, 255256, 264, 271, 289, 299, 308, 310315, 317, 319325, 375, 395, 478. See also Furosemide
uri ne el ectrol yte profi l es a nd, 306
uri ne pota s s i um concentra ti on a nd, 298, 311

Lopera mi de, 384, 394

Lopi na vi r, 460, 469, 476, 480481
Lora ta di ne, 125, 173, 357, 374, 378
Lora zepa m, 32, 140, 142, 160, 176, 189. See also Benzodi a zepi nes
ba rbi tura te/a l cohol wi thdra wa l a nd, 150, 155, 196
s ta tus epi l epti cus a nd, 142, 176
Los a rta n, 206207, 244, 248, 256
l i s i nopri l compa red to, 225, 277278
Lugol s ol uti on. See Strong i odi ne s ol uti on
Lutei ni zi ng hormone-rel ea s i ng hormone, 441, 496
M
MAC. See Mi ni mum a l veol a r concentra ti on of i nha l ed a nes theti cs
Ma gnes i um s a l ts , 386, 397398, 401
a l umi num s a l ts wi th, 386, 398
rena l di s ea s e a nd da ngers of, 404
Ma gnes i um s ul fa te, 386, 397399, 401
Ma i ntena nce dos e a nd i ts ca l cul a ti on, 5, 18, 205, 244
Ma l a thi on, 65, 102
Ma l i gna nt hypertens i on, 19, 46
Ma l i gna nt hyperthermi a , 46, 132, 161162, 191192
da ntrol ene for, 191
drugs ca us i ng, 150, 191
Ma nni tol , 299, 315
ca rdi a c functi on a nd, 302, 318
fl ui d el i mi na ti on i ncrea s ed wi th, 321
MAO. See monoa mi ne oxi da s e
Ma rfa n s yndrome, 234
Ma rgi n of s a fety. See Thera peuti c i ndex
Mechl oretha mi ne, 487, 497
Mega l obl a s ti c a nemi a , 396
Meni ere di s ea s e, 313
Meni ngi ti s , 458, 462, 479, 483
Menopa us e, 400
Mens trua l i rregul a ri ti es , 181, 439
Meperi di ne
i ntera cti ons wi th monoa mi ne oxi da s e i nhi bi tors a nd, 144, 181
morphi ne compa red to, 138, 171
Merca ptopuri ne, 348, 359, 489, 499500
Mes a l a mi ne, 403
Meta bol i c s yndrome, 41, 233
Metformi n, 211, 251, 289, 407, 412, 415, 418420, 427, 431432, 434435, 439440, 443444
a ppeti te s uppres s ed by, 432
di a betes mel l i tus a nd, 439
hypogl ycemi a a nd, 412, 432
l a cti c a ci dos i s from, 418, 421, 444
pol ycys ti c ova ri a n s yndrome a nd, 412, 431
Metha done, 150, 171, 189, 194, 466
Metha mpheta mi ne, 89, 144
Metha nol poi s oni ng, 155, 196197, 506, 514, 518
Methi ci l l i n-res i s ta nt staphylococcus aureus, 454, 466, 483
Methohexi ta l , 132, 161
Methotrexa te, 365, 485, 491, 497498
ca ncer a nd, 485, 491
l eucovori n res cue a nd, 492
Methyl dopa , 212, 253254, 512
Coombs -pos i ti ve tes t a nd, 254
Methyl ene bl ue, 511, 514
Methyl ergonovi ne, 430, 440
Methyl pheni da te, 86, 107, 124, 138, 170
Methyl predni s ol one, 331, 416
Methyl xa nthi nes , 329, 337, 342343, 346. See also Theophyl l i ne
overdos es of, 346
Metocl opra mi de, 186, 389, 402
Metol a zone, 76, 239, 244, 255, 273, 299, 307308, 312

hypertens i on a nd, 299, 311

Metoprol ol , 58, 70, 92, 105, 109, 286, 408, 425
a ngi na or hypertens i on a nd, 202, 240
Metroni da zol e, 387, 399400, 465, 468470, 473
Metyra pone, 410, 428, 446
Mi da zol a m, 68, 109, 132, 160161, 168, 173, 181, 331, 341, 391, 459.
See also Benzodi a zepi nes a mnes ti c effects of, 132
Mi fepri s tone, 30, 369, 419, 430, 441
Mi gl i tol , 433, 443
Mi gra i ne hea da ches , 174, 189, 200, 237, 349, 352
Mi l k of ma gnes i a . See Ma gnes i um s a l ts
Mi ni mum a l veol a r concentra ti on of i nha l ed a nes theti cs , 141, 163, 175
Mi ni pi l l s , 417, 422, 437, 439
Mi s opros tol , 353, 361, 367, 369, 393, 397, 400, 430
a borti on wi th mi fepri s tone a nd, 353, 369
contra i ndi ca ti ons for, 369
cytoprotecti ve/mucotropi c effects of, 361
for NSAID-i nduced ul cer prophyl a xi s , 349, 361
Monoa mi ne oxi da s e (MAO), 15, 42, 5556, 58, 104105, 110, 134, 145, 179, 181, 183, 200, 470, 483
depres s i on, i nhi bi ti ng, 144, 178179
i nhi bi tors of, 42, 70, 86, 104, 110, 134, 144, 164, 173, 178180, 182184, 195, 199, 200, 483
meta bol i c i na cti va ti on by, 74, 119
types of, 135
Monoa mi ne oxi da s e i nhi bi tors , 42, 70, 86, 104, 110, 134, 144, 164, 173, 178180, 182184, 195, 199200, 483
a nd depres s i on, 144, 178179
drug i ntera cti ons i nvol vi ng, 167
fl uoxeti ne, other SSRIs , a nd, 172, 182183
a nd hypertens i on, 179
meperi di ne a nd, 145, 182
pa rgyl i ne a s , 55, 86
Montel uka s t, 329, 338339, 345, 359
Mood s ta bi l i zi ng drugs
a nti depres s a nts a s , 198
l i thi um a s , 198
Morphi ne. See also Opi oi ds
cl os ed-hea d i njury a nd, 149, 187
drugs a nta goni zi ng effects of, 185
meperi di ne compa red to, 138, 170
pos topera ti ve pa i n control , s wi tchi ng to penta zoci ne from, 147, 184185
Moti on s i cknes s , 59, 108, 116, 405, 517
MRSA. See Methi ci l l i n-res i s ta nt s ta phyl ococcus a ureus
MTX. See Methotrexa te
Mul ti drug res i s ta nce-a s s oci a ted protei n, 29
Mus ca ri ni c receptors , 51, 62, 7172, 8284, 89, 9394, 9798, 103, 111, 113116, 120126, 149, 159, 171172, 178, 184, 187, 195, 197, 247248, 258, 281, 291
292, 343, 374, 397, 401, 521. See also Chol i nergi c receptors
Mya s theni a gra vi s , 65, 78, 102, 122123, 344
Mya s theni c cri s i s , 65, 78, 122123
chol i nergi c cri s i s compa red to, 65, 78, 122123
di fferenti a l di a gnos i s of, 65, 123
Mydri a s i s , 74, 79, 90, 92, 99, 115, 118120, 124, 228
Myel os uppres s i on, 467, 472
Myoca rdi a l i nfa rcti on, 217, 220, 227, 233, 239, 250
a nti pl a tel et drugs a nd, 250
a s pi ri n i n, 233, 290
hepa ri n a nd, 217, 250
ni tra tes a nd, 277
thrombol yti cs a nd, 227
wa rfa ri n a nd, 220, 250
Myoca rdi a l i s chemi a , 105, 141, 151, 174, 190, 206, 229, 231, 250, 265, 277, 284, 293, 434, 444
ergota mi ne overdos e ca us i ng, 237, 293
Myogl obi nuri a , 208
Myopa thy, drug-i nduced
from da ptomyci n, 454, 472
from s ta ti ns a nd other l i pi d-l oweri ng drugs , 247, 278

N
N-a cetyl cys tei ne, 354, 370
a ceta mi nophen overdos e a nd, 362, 518
mucol yti c effects of, 340, 492
Na dol ol , 58, 62, 92, 97. See also -Adrenergi c bl ockers
NADPH. See Ni coti na mi de a deni ne di nucl eoti de phos pha te
Na +-K+-ATPa s e. See Sodi um-pota s s i um a denos i ne tri phos pha ta s e
Na l oxone, 156157, 171, 183, 188189, 197, 398, 520
a nta goni s m of opi oi d effects by, 156, 197
dura ti on of a cti on compa red wi th opi oi d a goni s ts , 197
Na l trexone, 140, 173, 188, 386, 398
Na proxen, 246247
Na rrow a ngl e gl a ucoma . See Gl a ucoma
Nebi vol ol , 203, 241, 286. See also -Adrenergi c bl ockers
Neomyci n, 460461, 481482
Neos ti gmi ne, 57, 62, 71, 73, 89, 98, 110112, 114116, 119
Nephropa thy, drug-i nduced, 238, 252, 283, 297, 303, 310, 362
Nerve ga s es , 103, 124, 173, 509, 511, 514, 521
Neurol epti c drugs . See Anti ps ychoti c drugs
Neurol epti c ma l i gna nt s yndrome, 46, 157, 175, 183, 191192, 200
a nti ps ychoti c drugs a nd, 175, 184, 200
bromocri pti ne for, 157, 199
di a gnos i ng, 157
Neuromus cul a r bl ockers , 84, 97, 107, 110, 112, 114, 161162, 168, 191, 459, 479
depol a ri zi ng, 84, 93, 111, 168
nondepol a ri zi ng, 84, 107, 110, 114, 161, 180, 459, 479
Neutropeni a , 250, 448
Ni a ci n, 211, 234, 251, 278, 288, 290, 408, 424
pros ta gl a ndi ns a nd, 234, 290
Ni coti na mi de a deni ne di nucl eoti de phos pha te (NADP), 15, 40
Ni coti ne, 59, 83, 9394, 198, 415
Ni coti ni c a ci d. See Ni a ci n
Ni coti ni c receptors , 46, 8384, 94, 97, 99, 116, 122124, 479, 521. See also Chol i nergi c receptors
Ni fedi pi ne, 139, 172, 216, 223, 239, 242, 250, 256, 259, 262, 266, 270, 272273. See also Ca l ci um cha nnel bl ockers
a brupt di s conti nua ti on of, 271
nondi hydropyri di ne ca l ci um cha nnel bl ockers compa red to, 242, 270
ri s i ng bl ood pres s ure a nd, 223, 274
Ni tri c oxi de, 9395, 121, 245, 248, 264, 266, 272, 282, 367
a nd endothel i um, 121, 247, 371
nebi vol ol a nd, 203, 241
s ynthes i s by ni tri c oxi de s yntha s e, 60
a nd va s odi l a tors , 256, 264, 266
Ni trofura ntoi n, 448, 463464
Ni trogl yceri n, 202, 206, 223, 232, 240, 253, 257, 259, 277, 282, 285
a cute corona ry s yndrome a nd, 285
a ngi na a nd, 202, 218, 240, 277
erecti l e dys functi on drugs i ntera cti ng wi th, 312
myoca rdi a l i nfa rcti on a nd, 231
tol era nce to, 225, 277
tra ns derma l a dmi ni s tra ti on of, 225
Ni troprus s i de
a nti hypertens i ve effect of, 234
cya ni de poi s oni ng from, 263, 277, 511, 513
Ni trous oxi de, 141, 175, 181, 459
Ni trova s odi l a tors . See Ni trogl yceri n
Ni za ti di ne, 382, 391392, 397, 401
NMS. See Neurol epti c ma l i gna nt s yndrome
NNRTIs . See Non-nucl eoti de/nucl eos i de revers e tra ns cri pta s e i nhi bi tors ; Efa vi renz
Nocturna l enures i s , 156, 197
Nondi hydropyri di ne, 216, 240, 242, 244, 250251, 255, 262, 270, 273274, 283, 286
Non-nucl eoti de/nucl eos i de revers e tra ns cri pta s e i nhi bi tors , 469
Nons teroi da l a nti -i nfl a mma tory drugs , 10, 42, 283, 290, 298, 339340, 441
a nta goni s m of other drugs by, 302, 317
a s pi ri n a s prototype of tra di ti ona l , 41, 340
cycl ooxygena s es i nhi bi ted by, 340

Nora drenergi c nerves . See Adrenergi c nerves

Norepi nephri ne, 19, 39, 42, 5356, 63, 66, 74, 8284, 8688, 92, 99, 103105, 107108, 118120, 126, 155, 164, 170, 181, 186, 196
a s a drenergi c a goni s t, 328, 335
coca i ne a nd tri cycl i c a nti depres s a nt effects on reupta ke of, 82, 84, 86, 104, 109, 119, 122, 186
depl eti on of i ntra neurona l , 55, 85, 99
phentol a mi ne wi th, 74, 117
reupta ke of, 51, 55, 66, 74, 82, 84, 86, 104, 109, 119
a s s ympa theti c neurotra ns mi tter, 74, 82, 92
s ynthes i s of, 54, 85, 87
Normeperi di ne, 171, 182
NPH i ns ul i n, 432434
NRTIs . See Nucl eos i de revers e tra ns cri pta s e i nhi bi tors ; Zi dovudi ne
NSAIDs . See Nons teroi da l a nti -i nfl a mma tory drugs
NTG. See Ni trogl yceri n
Nucl eos i de/nucl eoti de revers e tra ns cri pta s e i nhi bi tors , 460, 467, 469. see also Zi dovudi ne
Nutri ti ona l s uppl ements /nutri ceuti ca l s , 20, 4647
Nys ta ti n, 458
O
Octreoti de, 408, 425
Off-l a bel drug us e, 11, 37, 48
Ol a nza pi ne, 187, 193, 200
Oma l i zuma b, 328, 336337
Omepra zol e, 396, 524
Onda ns etron, 30, 133, 163, 186, 390391, 394, 405, 488
ca ncer chemothera py a nd, 390, 405
Opi oi ds . See also specific individual drugs
a nta goni s ts of, 129, 172, 188, 195
na l oxone, 171, 183, 188, 197
na l trexone, 173, 386, 398
codei ne, 144, 173, 180, 261, 341
fenta nyl , 156, 168, 173, 181, 197, 391
hydrocodone, 342
meperi di ne, 32, 138, 170171, 182
metha done, 150, 171, 189, 194, 466
morphi ne, 26, 72, 109, 113, 138, 147, 149, 161162, 171, 179, 184185, 187190, 197, 199, 202, 261, 358, 391, 405, 512, 522
overdos es of, 173
oxycodone, 144
penta zoci ne, 147, 184185
receptors ( a nd k) for, 173, 184
res pi ra tory depres s i on by, 171, 184185
wi thdra wa l from, 188
Orthos ta ti c hypotens i on, 76, 120, 146, 153, 183, 186
chl orproma zi ne a nd, 153, 193
Os el ta mi vi r, 457, 476
Os teoporos i s , 410, 419, 427. See also Bi s phos phona tes
OTC drugs . See Over-the-counter drugs
Ototoxi ci ty, 269, 321, 458
a mi nogl ycos i des a nd, 455461, 468, 472
l oop di ureti cs a nd, 321
Over-the-counter drugs , 20, 60, 106
Oxa ci l l i n. See also Anti bi oti cs , peni ci l l i ns
peni ci l l i n a nd, 451, 468
Staphylococcus aureus a nd, 451
Oxyba rbi tura tes . See Phenoba rbi ta l
Oxycodone, 144
Oxytoci n, 293, 425
P
P450. See Cytochrome P450
Pa cl i ta xel , 488, 497498, 525
Pa get di s ea s e, 410, 427428, 436
Pa ncrel i pa s e, 389, 402403
Pa ncuroni um, 53, 68, 72, 107, 114
Pa ra s ympa theti c nervous s ys tem, control of effectors , 114, 281
Pa ra thyroi d hormone, 415, 423, 436, 446

Pa rgyl i ne, 55, 86, 110, 179

Pa rki ns on di s ea s e, 88, 93, 134, 140, 143, 147, 151, 154, 157, 175, 198
bromocri pti ne a nd, 149, 157, 190, 199
ropi ni rol e a nd, 142, 175
s el egi l i ne a nd, 147, 199
tri hexypheni dyl i n drug pl a n for, 143, 178, 185
Pa rki ns oni s m, 88, 93, 116, 147148, 157, 164, 178, 184, 190, 195
s el egi l i ne a nd, 147, 184185
Pa roxys ma l s upra ventri cul a r ta chyca rdi a
a denos i ne for, 219, 268
vera pa mi l for, 202, 239
Pa rti a l a goni s ts , 16, 42, 92, 107, 184, 254
Pa tent ductus a rteri os us , 353, 368
PCOS. See Pol ycys ti c ova ri a n s yndrome
PCP. See Phencycl i di ne
Peni ci l l a mi ne, 351, 365, 492
Peni ci l l i na s e. See -La cta ma s e
Peni ci l l i n-bi ndi ng protei ns , 477
Peni ci l l i ns , 32, 54, 451, 456458, 460, 475477, 480. See also Anti bi oti cs , peni ci l l i ns
a mi nogl ycos i des a nd, 458, 478479
mecha ni s m of a cti on of, 466, 477
oxa ci l l i n a nd, 451, 468
va ncomyci n a nd, 451, 467468
Penta mi di ne, 465, 469
Penta zoci ne, 147, 184185. See also Ana l ges i cs , opi oi ds
Peri phera l nervous s ys tems , 49127
Peri phera l va s odi l a ti on, 245, 262, 267
Peroxi s ome prol i fera tor-a cti va ted receptors , 444
P-gl ycoprotei ns , 6, 28, 30
i nducers a nd i nhi bi tors of, 29
s ubs tra tes /i nducers /i nhi bi tors of, 29
Pha rma coki neti cs , 5, 6, 910, 1314, 29, 32, 71, 111, 160, 162, 169170, 475
Pha rma col ogy, genera l pri nci pl es of, 148
Pha s e I meta bol i c rea cti ons , 19, 45
Pha s e II meta bol i c rea cti ons , 8
Phencycl i di ne (a ngel dus t PCP), 139, 172
Phenel zi ne, 164, 179, 181
Phenoba rbi ta l , 135, 166, 170, 174, 192, 195, 370, 438, 510, 512, 518
Phenothi a zi ne a nti ps ychoti cs . See Chl orproma zi ne
Phenoxybenza mi ne, 88, 190, 204, 213, 243, 254
bl ood pres s ure control , pra zos i n compa red to, 283
pheochromocytoma s a nd, 213, 254
Phentol a mi ne, 65, 8889, 101102, 117118, 159, 241, 275, 281, 289, 360
norepi nephri ne wi th, 117
pra zos i n compa red to, 65, 102
Phenyl ephri ne, 7980, 88, 117, 119, 125126, 129, 159160, 172, 203, 241242, 258, 268, 280, 283
pra zos i n bl ocki ng effects of, 227, 280
s upra ventri cul a r ta chyca rdi a a nd, 230231, 242
Phenyl etha nol a mi ne N-methyl tra ns fera s e, 56, 88
Phenytoi n, 136137, 152, 166, 168169, 176, 189190, 194. See also Anti convul s a nt drugs
epi l eps y/s ei zures a nd us e of, 135136, 142, 152, 156, 166
ora l contra cepti ve effi ca cy reduced by, 417418, 437, 439440
pha rma coki neti cs of, 169
pregna ncy a nd, 152
Pheochromocytoma s , 60, 9596, 190, 204, 213, 224, 284285
effects of -bl ockers i n, 9596, 243, 254, 285
phenoxybenza mi ne a nd, 213, 254
Phos pha te, a l umi num s a l ts a nd, 388, 392, 404
Phos phol i pa s e A2, 357
Photophobi a , drug-i nduced, 75, 120, 360
Phys os ti gmi ne, 98, 102, 112, 115117, 123, 173, 360, 378, 516
Phytona di one. See Vi ta mi n K
Pi l oca rpi ne, 59, 62, 64, 76, 94, 9798, 121, 125, 332, 343
Pi ndol ol , 58, 92, 425
i ntri ns i c s ympa thomi meti c a cti vi ty a nd, 67, 107

Pi ogl i ta zone, 420421, 427, 440, 442444. See also Anti di a beti c drugs
i ns ul i n s ens i ti zi ng effects of, 443
Pi tui ta ry tumor, 190, 293, 438
Pi tui ta ry-a drena l corti ca l a xi s , 428
Pl a s ma concentra ti on. See Stea dy-s ta te concentra ti on
Plasmodium vivax, 449, 450
Pl a tel et-a cti va ti ng fa ctor (PAF), 279
Pl i ca myci n, 415, 436
Pneumococci , 453, 471
Poi s on s yndromes
a nti chol i nergi c/a nti mus ca ri ni c, 106107, 111, 115116, 121, 383, 512, 516
chol i nes tera s e i nhi bi tor, 504, 515, 517, 521
Pol ycys ti c ova ri a n s yndrome, 412, 431
Pol ydi ps i a , 307, 422, 445
Pol yuri a , 307, 323, 422, 445
Pos tga ngl i oni c s ympa theti c nerves , 5152, 82, 84, 118
Pos topera ti ve na us ea , 133, 181
Pos topera ti ve pa i n control , 14, 133, 147
morphi ne, s wi tchi ng to penta zoci ne for, 147, 184185
Pos ts yna pti c ta rget cel l s , 8283
Pota s s i um-s pa ri ng di ureti cs
a mi l ori de a nd tri a mterene a s , 257, 271, 303, 307, 318, 321
s pi ronol a ctone a nd epl erenone a s , 307, 311
uri ne el ectrol yte profi l es a nd, 306
Pota s s i um-wa s ti ng di ureti cs . See furos emi de, hydrochl orothi a zi de
Pra l i doxi me, 78, 103, 124, 173, 511
Pra va s ta ti n, 211, 251
Pra zos i n, 32, 65, 86, 88, 101102, 107, 119, 240, 270, 275. See also -Adrenergi c bl ockers .
beni gn pros ta ti c hypertrophy a nd, 228, 280
bl ood pres s ure control , phenoxybenza mi ne compa red to, 243
hypotens i on from, 79, 126
phentol a mi ne compa red to, 65, 102
phenyl ephri nes effects bl ocked by, 227, 280
Predni s one, 334, 336, 342, 428, 431, 434, 445446. See a l s o Corti cos teroi ds
Pregna ncy
a ngi otens i n modi fi ers a nd, 249
ca ptopri l a nd, 210
di ureti cs a nd, 249
fol i c a ci d s uppl ements a nd, 152, 192
fol i c a ci d s uppl ements duri ng, 402
phenytoi n duri ng, 152, 194
vi ta mi n A a nd, 389, 403
wa rfa ri n a nd, 212, 253
Pregna ncy cl a s s i fi ca ti ons , 249
Pri ma qui ne
hemol yti c a nemi a from, 512
Plasmodium vivax a nd, 449450
Pri nci pa l cel l s of nephron, 321
effects of pota s s i um-s pa ri ng di ureti cs on, 257, 281, 311312, 317, 321, 323, 325
s odi um-pota s s i um excha nge by, 299, 313314
Probeneci d, 350, 359, 363364, 368369, 377
a cute gout ca us ed by, 350, 364
a s pi ri n i mpa i ri ng a cti ons of, 353, 368
Proca i na mi de, 254, 269, 512
l upus -l i ke s yndrome from, 257, 269, 502, 512
Proca i ne, 177
Proges ti n-onl y ora l contra cepti ves , 439
Prometha zi ne, 151, 185, 187, 190191, 341
Propa fenone, 216, 524
Propofol , 109, 132, 160161, 181, 459
Propoxyphene, 171, 518
Propra nol ol , 32, 60, 86, 94, 110, 114, 116117, 119. See also -Adrenergi c bl ockers
a nti hypertens i ve mecha ni s m of a cti on of, 63, 99
bl ood pres s ure control , ni troprus s i de wi th, 234
pheochromocytoma s a nd, 275

thyrotoxi cos i s a nd, 409, 434

Propyl thi oura ci l , 415, 420, 434, 436, 443, 445
a nti thyroi d effects of, 415, 421, 436, 445
bl ood dys cra s i a s from, 186, 194
Pros ta cycl i n, 41, 287, 339, 359361
Pros ta gl a ndi ns , 41, 162, 290, 311, 330, 339340, 359361, 367369, 374, 397, 430, 441
Pros ta te s peci fi c a nti gen, 409
Pros ta ti c hypertrophy. See also Beni gn pros ta ti c hypertrophy
drugs contra i ndi ca ted i n, 360, 378
drugs for trea ti ng, 217, 263, 276
Prota mi ne s ul fa te, 225, 276
hepa ri n a nta goni zed by, 217, 263
Protea s e i nhi bi tors , 439, 450, 460, 467, 469. See also Lopi na vi r, ri tona vi r
Prothrombi n ti me, 267268. See also Interna ti ona l norma l i zed ra ti o
Proti rel i n, 414, 435
Proton pump i nhi bi tors , 225, 387, 393, 394, 397, 400
Pruri tus , 234, 290, 472
Ps eudoephedri ne, 144, 180
a s i l l ega l s ource of metha mpheta mi nes , 144
Ps eudomembra nous col i ti s , 400, 448, 455. See also Anti bi oti c-a s s oci a ted
ps eudomembra nous col i ti s , cl i nda myci n
Pseudomonas aeruginosa, 456457, 459
PSVT. See Pa roxys ma l s upra ventri cul a r ta chyca rdi a
PTU. See Propyl thi oura ci l
Pul mona ry edema , 72, 188, 239, 289, 495
Pul mona ry fi bros i s , drug-i nduced, 211, 261, 269, 429, 493
Pul mona ry functi on tes ts , 269, 327, 334, 338, 343
Pyri dos ti gmi ne, 78, 102, 122. See also Acetyl chol i nes tera s e i nhi bi tors
Pyri doxi ne (Vi ta mi n B 6 ), 165, 257, 385, 396, 459, 466, 480
i s oni a zi d a nd, 385, 396
l evodopa /ca rbi dopa countera cted by, 385, 396
Q
Qui ni di ne. See also Anti a rrhythmi c drugs
a dvers e effects i n l ong QT s yndrome, 252
a tri a l fi bri l l a ti on a nd, 211, 252253
hea rt fa i l ure a nd, 214, 259
reduci ng rena l di goxi n cl ea ra nce, 259
s a l i cyl i s m res embl i ng overdos es of, 242
toxi ci ty, 216, 260, 269
Qui ni ne, 242
R
Ra di oi odi ne, 411, 431, 445
Ra l oxi fene, 411, 431
Ra mi pri l , 207, 211, 252, 255, 283
hyperka l emi a a nd, 283
Ra ni ti di ne, 225, 382, 388, 391392, 397, 401
Recogni zi ng drug cl a s s by generi c na me, xxvi i xl i i
Red ma n s yndrome a nd va ncomyci n, 472
Rena l a rtery s tenos i s , 408
Rena l cl ea ra nce of drugs , 13, 39, 43
Rena l pota s s i um l os s , 271, 299, 313, 324
Reni n
-a drenergi c receptors i nhi bi ti ng, 58, 286
a nd a ngi otens i n-a l dos terone s ys tem, 256, 358
rel ea s e, 83, 91, 95, 118, 286
Repa gl i ni de, 420, 443. See also Anti di a beti c drugs .
Res cue thera py i n a s thma
a drenergi c bronchodi l a tors for, 213, 328, 335, 337
Res erpi ne, 86, 9899, 120, 126
gua na drel compa red to, 63, 9899
hypotens i on from, 7980, 120, 126
Res pi ra tory a ci dos i s , 332, 344, 370, 372, 375, 502, 512
Res tl es s l eg s yndrome, 142

Reupta ke of norepi nephri ne, 155, 186

Reye s yndrome, 350, 364, 400401
a s pi ri n a nd, 350, 364
Rha bdomyol ys i s , drug-i nduced, 247, 271, 278
Rheuma toi d a rthri ti s
ca ptopri l a ffected by i ndometha ci n for, 355
di s ea s e-modi fyi ng a nti rheuma ti c drugs a nd, 365, 491
eta nercept a nd, 357, 379
Rhi norrhea , 79, 357
Ri fa mpi n, 30, 439, 450, 466, 481, 483, 495
Ri s peri done, 200
Ri tona vi r, 439, 460, 469, 476, 480481, 523. See also Protea s e i nhi bi tors
Rodenti ci des , 509, 521
Rohypnol , 146, 160, 182, 519
fl uma zeni l a nta goni zi ng, 146, 182
Roofi es . See Rohypnol
Ropi ni rol e, 140, 175, 176
Ros i gl i ta zone. See Pi ogl i ta zone
Ros uva s ta ti n, 208, 247. See also Anti hyperl i pi demi c drugs
S
SAARDs . See Di s ea s e-modi fyi ng a nti rheuma ti c drugs
Sa l i cyl i s m, 204, 242, 353, 368369, 371
qui ni di ne a nd, 242
ti nni tus a nd, 204, 242, 353, 368
Sa l meterol , 113, 328, 333, 335336, 345346
a s thma a nd, 328, 335336
FDA wa rni ng on, 333
Sa qui na vi r, 30, 460, 525
Schi zophreni a . See also Anti ps ychoti c drugs
a typi ca l a nti ps ychoti cs for, 153
chl orproma zi ne a nd, 148, 193
chl orproma zi ne wi th benztropi ne for, 155, 198
Scopol a mi ne, 59, 9394, 107, 405, 417
Seda ti ve, hypnoti c, a nxi ol yti c drugs
ba rbi tura tes , phenoba rbi ta l , 135, 166, 354, 370
chl ordi a zepoxi de, 155, 196
di a zepa m, 32, 140, 173
l ora zepa m, 140, 142, 160, 176
mi da zol a m, 68, 109, 132, 160161, 181, 262, 341, 391, 459
zol pi dem, 166, 173, 174, 193
Sei zure thres hol d, reduced by drugs , 176, 185
Sei zures . See Epi l eps y/s ei zures
Sel ecti ve es trogen receptor modi fi ers (SERMs ), 431, 494, 495, 499
Sel ecti ve s erotoni n reupta ke i nhi bi tors (SSRIs ), 200, 368
fl uoxeti ne a s , 37, 139, 307, 368, 389
s ertra l i ne a s , 145, 149, 181, 187
ta moxi fen a nd, 486, 494
Sel egi l i ne, 146, 164, 178, 184185
monoa mi ne oxi da s e i nhi bi ti on by, 134, 173, 178179, 184, 195, 199
Pa rki ns on di s ea s e a nd, 134, 167
pa rki ns oni s m a nd, 147, 184, 186
SERM. See Sel ecti ve es trogen receptor modi fi ers
Serotoni n. See also Sel ecti ve s erotoni n reupta ke i nhi bi tors
fl uoxeti ne a nd reupta ke of, 155, 196
hea da ches , s uma tri pta n mi mi cki ng, 349, 360
Serotoni n s yndrome, 172, 182, 349, 368
Sertra l i ne, 145, 149, 181, 187
Sexua l dys functi on
bupropi on a nd, 145, 183
s i l dena fi l a nd, 218, 264
SIADH. See Syndrome of i na ppropri a te
a nti di ureti c hormone s ecreti on
Si gna l tra ns ducti on, 45
Si l dena fi l , 218, 264

Si nus bra dyca rdi a . See Bra dyca rdi a

Si nus ta chyca rdi a . See Ta chyca rdi a
Skel eta l mus cl e tremors , a l buterol ca us i ng, 329, 338
Skel eta l mus cl es
neuromus cul a r bl ockers a nd, 84
pa ra l ys i s of, 59, 97
Sl ow-a cti ng a nti rheuma ti c drugs . See Di s ea s e-modi fyi ng a nti rheuma ti c drugs
SMZ. See Sul fa methoxa zol e
Sodi um bi ca rbona te
a nta ci d effects of, 397, 401
a s pi ri n poi s oni ng a nd, 354, 370
for hyperuri cemi a , 356, 377
Sodi um thi os ul fa te
cya ni de poi s oni ng a nd, 503, 513
for ni troprus s i de toxi ci ty, 215, 263
Sodi um-pota s s i um a denos i ne
tri phos pha ta s e (Na +-K+-ATPa s e), i nhi bi ti on by di goxi n, 244
Soma ti c nervous s ys tem, 49127
Spi ronol a ctone, 257, 298, 307, 311314, 416, 438
a drena l corti ca l a denoma a nd, 303
for a drena l corti ca l tumor, 303, 312314
SSRIs . See Sel ecti ve s erotoni n reupta ke i nhi bi tors
Staphylococcus aureus, 451
Sta tus a s thma ti cus a nd i ts trea tment, 332, 335, 362
Sta tus epi l epti cus , drugs for, 142, 160, 176, 179, 370, 501
l ora zepa m for, 140, 142, 160, 510, 517
(fos )phenytoi n for, 142, 145, 176, 370, 501, 510
Stea dy-s ta te concentra ti on of drugs , 5, 10, 18, 43, 44
Streptoki na s e. See Thrombol yti cs
Streptomyci n, 321, 481482
Stroke, 57, 64, 88, 94, 99, 104, 129, 159, 160, 186, 233, 244, 271272, 279, 346
Strychni ne poi s oni ng, 515516
Succi mer, 508, 520
Succi nyl chol i ne, 71, 111112, 133, 161162, 168, 170, 191, 459, 479, 522
a mi nogl ycos i des prol ongi ng effects of, 479
compa ri s on wi th nondepol a ri zi ng neuromus cul a r bl ockers , 71, 84
ma l i gna nt hyperthermi a a nd, 161, 191
pha s e II bl ock a nd, 112
Sul ba cta m, 460, 481
Sul fa methoxa zol e
fol i c a ci d s ynthes i s a nd, 453, 470
kerni cterus a nd, 451, 463
TMP wi th, 448
Sul fa pyri di ne, 403
Sul fa s a l a zi ne, 389, 403
Sul fi npyra zone, 368
Sul fona mi des . See Anti bi oti cs , s ul fona mi des
Sul fonyl urea s , 434435, 443445
gl i mepi ri de, 442
gl i pi zi de, 442
gl yburi de, 407, 419, 421, 442, 444
tol buta mi de, 195, 413, 418, 440, 442, 444, 518
Suma tri pta n
cerebra l va s ocons tri ctor effects of, 174
fl uoxeti ne a nd, 139, 173, 352, 368, 489, 499, 524
hea da ches , s erotoni n mi mi cked by, 349, 360, 368
Supra rena l medul l a . See Adrena l medul l a
Supra ventri cul a r ta chyca rdi a , 204, 230231, 242
Swea t gl a nds , i nnerva ti on of, 50, 52, 8284, 118, 123
Swi ne fl u 457
Sympa theti c nervous s ys tem, control of effectors , 15, 53, 85, 92, 114, 120, 124, 136, 179, 265, 270271, 285286
Syndrome of i na ppropri a te a nti di ureti c hormone s ecreti on (SIADH)
coni va pta n a nd, 301, 315
Sys temi c va s cul a r res i s ta nce. See Tota l peri phera l res i s ta nce

T
Ta chyca rdi a , 59, 63, 94, 98, 105
a denos i ne to termi na te, 204, 219, 268
-a drenergi c bl ockers for, 97, 105106, 231, 288, 414, 434, 436
ba roreceptor-i nduced refl ex, 112, 262, 283
ca roti d s i nus ma s s a ge to termi na te, 236
edrophoni um for pa roxys ma l , 268, 283
va s opres s ors for, 291
Ta chyphyl a xi s , 13, 3940
Ta cri ne, 154, 178, 195, 199
Ta da l a fi l , 264
Ta moxi fen, 30, 412, 431, 486, 494495
brea s t ca ncer ri s k from, 412, 431
SSRIs a nd, 489, 499
Ta ms ul os i n, 76, 119120
Ta zoba cta m, 460, 481
TB. See Tubercul os i s
Tera zos i n, 120, 280. See a l s o -Adrenergi c bl ockers .
Terbuta l i ne, 68, 108, 113, 328, 335
Tes tos terone, 426, 431, 435
Tes tos terone s ynthes i s , 409, 426
Teta ny pos tthyroi dectomy, 436
Tetra ca i ne, 142, 176177
Tetra cycl i nes , 387, 399, 439, 465, 468, 472473, 480, 482. See also Anti bi oti cs , tetra cycl i nes
mi nera l s a l ts i nhi bi ti ng ora l a bs orpti on of, 473
P450 i nhi bi ti on by, 480
Theophyl l i ne, 32, 329, 332333, 335, 337
a s thma a nd, 329, 337338
toxi ci ty, 332333, 337, 343, 382
Thera peuti c i ndex, 167, 337, 392
Thi a mi ne (Vi ta mi n B 1 ), 388, 402
Thi a myl a l , 132, 161
Thi a zi de di ureti cs . See also Hydrochl orothi a zi de
a nd a ngi otens i n modi fi ers , 246, 249
a s a nti hypertens i ve drugs , 201, 211, 246, 253
for edema , 319
uri ne el ectrol yte profi l es a nd, 306
Thi a zol i di nedi ones (gl i ta zones ). See pi ogl i ta zone
Thi oa mi des (thi oa mi nes ). See Propyl thi oura ci l
Thi oba rbi tura tes . See Thi a myl a l ; Thi openta l
Thi openta l , 132, 161, 168, 181
a nes theti c dura ti on of, 132, 145, 161, 168
Thi ori da zi ne, 524
Thrombocytopeni a , hepa ri n-i nduced. See Hepa ri n-i nduced thrombocytopeni a
Thromboembol i s m, 382, 416, 437, 495
Thrombol yti cs , 227, 264, 268270, 276, 279, 471
a l tepl a s e, 220, 263, 268, 276, 279
s treptoki na s e, 227, 269270, 279
Thromboti c thrombocytopeni c purpura , 250
Thromboxa ne A2, 359, 360
Thyroi d hormones
a nd a drenergi c receptor res pons i venes s , 427
a mi oda rone a nd, 429
effects of i odi ne on, 269, 429, 436, 445
l evothyroxi ne, 414, 423, 435
Thyroi d s torm, 105, 427
Ti cl opi di ne, 249250, 267, 270. See also Cl opi dogrel
Ti mol ol , 92, 98, 125, 240. See also -Adrenergi c bl ockers
Ti nni tus , 204, 242, 269, 321, 368, 478
Ti otropi um, 96
Tocol yti c drugs , 113
Tol buta mi de, 195, 440, 442, 444, 518
Tol era nce to, 3940, 166, 258, 273, 277, 307, 344345, 469
ba rbi tura tes , 166
benzodi a zepi nes , 166

ni trova s odi l a tors , 225, 265, 277

opi oi ds , 150, 171, 184, 187
Topoi s omera s e II, 453, 471, 497
Topoteca n, 497
Tors a des de poi ntes , drugs i nduci ng, 181, 252
Tors emi de, 299, 308, 311, 320323. See also Furos emi de; Loop di ureti cs
Tota l body wa ter, 2526
Tota l peri phera l res i s ta nce
a drenergi c control of, 88, 94, 203, 285, 286
a ngi otens i n II a nd, 214
i n ca l cul a ti on of bl ood pres s ure, 9495, 286
va s odi l a tors a nd, 6061
Tra ns i ent i s chemi c a tta cks , 220
Tra nyl cypromi ne, 164, 179, 181, 195. See also Monoa mi ne oxi da s e i nhi bi tors
Tra vel ers di a rrhea , 387, 401
Tri a mci nol one, 416
Tri a mterene, 216, 224, 230, 257, 271, 274, 283, 307, 311, 317, 321322, 324, 326
Tri chomoni a s i s , 449, 465
Tri cycl i c a nti depres s a nts , 73, 82, 84, 86, 104, 109, 119, 122, 135, 167, 173, 186, 197, 200
a nti chol i nergi c effects of, 135
nocturna l enures i s a nd, 197
Tri hexypheni dyl , 93, 116, 143, 178, 185, 195, 198199, 517
Tri metha pha n, 70, 73, 110, 114115
Tri methopri m
fol i c a ci d s ynthes i s a nd, 453, 470
s ul fa methoxa zol e wi th, 448, 465
Tri pta ns . See s uma tri pta n
TTP. See Thromboti c thrombocytopeni c purpura
Tubercul os i s , 385, 450, 459461, 465, 483
i s oni a zi d wi th vi ta mi n B 6 a nd, 459, 480
ri fa mpi n for, 450, 466, 483
Tubocura ri ne, 170
TXA2. See Thromboxa ne A2
Tyra mi ne, 55, 86, 179
Tyros i ne hydroxyl a s e, 56, 58, 88, 91
U
Ura te nephropa thy, 310
Uri c a ci d, 348, 359
Uri c a ci d s ynthes i s , 356, 369, 377378
Uri cos uri c drugs , 368. See also Anti gout/a nti hyperuri cemi c drugs
a nta goni s m by a s pi ri n, 368
probeneci d, 359, 363364, 369
s ul fi npyra zone, 368
Uri na ry retenti on, betha nechol a nd, 384, 395
Uri na ry tra ct i nfecti ons
fl uoroqui nol ones for, 464
ni trofura ntoi n for, 448, 463464
tri methopri m a nd s ul fa methoxa zol e for, 448, 465
Uri ne, hypotoni c, 295, 300, 315
Uri ne gl ucos e moni tori ng, 408, 426
Urs odeoxychol i c a ci d, 387, 399
Urs odi ol , 387, 399
Urti ca ri a , 72, 103, 179, 220, 340, 444, 472
Uteri ne contra cti ons , drugs a ffecti ng, 72, 113, 430, 441
Uteri ne rel a xa nts
a s a drenergi c bronchodi l a tor, 335
s uppres s i on of prema ture uteri ne contra cti ons , 441
Uteri ne s ti mul a nts . See Oxytoci n
V
Va l proi c a ci d, 192193
Va ncomyci n, 451, 453454, 465468, 471473, 475, 480
MRSA a nd, 454, 471
peni ci l l i n a nd, 451, 468

Va ncomyci n-res i s ta nt enterococci (VRE) i nfecti on, 462, 483

Va rdena fi l , 264
Va s ocons tri ctor, 72, 92, 100105, 108109, 121122, 126, 241, 244245, 258, 275, 280
Va s odi l a ti on, 9496, 98, 100105, 112, 115, 117118, 121, 126, 187, 190, 203, 206, 209, 219, 234, 241, 244245
from hydra l a zi ne, 219, 266267
peri phera l , 267
Va s os pa s ti c a ngi na , 67, 105
vera pa mi l /di l ti a zem for, 211, 244245
Va ugha n-Wi l l i a ms a nti a rrhythmi cs cl a s s , 216
Venl a fa xi ne, 196
Venti l a tory a rres t, 171, 259, 331, 341, 521
Ventri cul a r ectopy, 202, 224, 239240, 274, 292, 303
Vera pa mi l , 2, 25, 34, 174, 239240, 242, 250, 252, 255, 262, 266, 268, 270, 273. See also Ca l ci um cha nnel bl ockers , ni fedi pi ne
AV noda l conducti on/bl ock a nd, 221, 270
cons ti pa ti on from, 218, 226
di hydropyri di nes compa red to, 242, 259, 262, 270, 273
hea rt bl ock from. See AV noda l conducti on/bl ock
for hypertens i on, 407
for PSVT, 204, 242
va s os pa s ti c a ngi na a nd, 211
Vi ga ba tri n, 152, 192
Vi nbl a s ti ne, 30, 493, 499
Vi nca a l ka l oi ds . See Vi nbl a s ti ne, vi ncri s ti ne
Vi ncri s ti ne, 486, 493
Vi ta mi n A, 384, 395, 399, 403, 437
Vi ta mi n B 1 . See Thi a mi ne
Vi ta mi n B 6 . See Pyri doxi ne
Vi ta mi n D, 422, 428, 445
Vi ta mi n E, 178, 384, 395, 399, 402
Vi ta mi n K, 153, 253, 257, 263264, 268269, 276, 288, 384, 394395, 399, 402, 437, 470471, 492, 521
toxi ci ty, 384, 437
Vi ta mi ns . See also specific individual vitamins fa t s ol ubl e vs wa ter s ol ubl e, 384, 395
toxi ci ty of, 383, 395
Vol ume of di s tri buti on, 1, 1314, 29, 32
VRE i nfecti on. See Va ncomyci n-res i s ta nt enterococci i nfecti on
W
Wa rfa ri n, 21, 32, 39, 194, 220, 225, 243244, 247, 249250, 253, 263264, 267269, 272, 276, 288, 375, 382, 392393, 402, 411, 455, 470471, 474, 492, 495, 521
a s pi ri n us e wi th, 247, 267, 471
da ngers of l oa di ng dos es , 243244
embryopa thy from, 21
myoca rdi a l i nfa rcti on a nd, 220, 250
pregna ncy a nd, 21, 212, 253
prothromboti c s ta te from, 243
vi ta mi n K a s a nti dote for, 263264, 268269, 276, 402, 471, 492, 521
Werni cke encepha l opa thy, 388, 402
Wi l ms tumor, 486
X
Xa nthi ne oxi da s e
a l l opuri nol or febuxos ta t i nhi bi ti on of, 369
forma ti on of uri c a ci d by, 359360, 369, 378, 498
Xenobi oti c meta bol i s m, 28, 42
Y
Yohi mbi ne, 59, 92
Z
Za fi rl uka s t, 338, 360
montel uka s t compa red to, 329, 338339, 345, 359
Zero-order el i mi na ti on of drugs , 18
Zi dovudi ne, 276, 448, 452, 460, 463464, 467469, 476
Zol pi dem, 166, 173174, 193