Ant|ang|na| agents

Coronary artery d|sease

cotoooty beott Jlseose
lscbemlc beott Jlseose
|sorder of myocard|a| b|ood f|ow due to stab|e or unstab|e
coronary atherosc|erot|c p|aque artery |umen narrow|ng
AnlmaLlon myocardlum blood supply
Atherosc|erot|c p|aque
Atherothrombos|s
9rec|p|tate by s|tuat|ons
that |ncrease the work
demand of the heart
9hys|ca|
Co|d
Lmot|ona| stress
9a|n typ|ca||y |s descr|bed
as constr|ct|ng squeez|ng
or suffocat|ng sensat|on
,yocardlal lschemla Lhe accumulaLlon
of meLabollLes
Sensory nerve endlng sLlmulaLlon
Chest pa|n
1he paln ls noL felL ln Lhe hearL buL
referred Lo Lhe skln areas supplled by Lhe
correspondlng splnal nerves the upper
four |ntercosta| nerves the
|ntercostobrach|a| nerve (12)
1he lnLercosLobrachlal nerve
communlcaLes wlLh Lhe med|a|
cutaneous nerve of the arm
9a|n rad|at|ng to the med|a| s|de
of the upper part of the arm
Coronary artery Disease or
Ischemic heart disease
Acute
Coronary
Syndrome
Chronic Ischemic
Heart Disease
Unstable
angina
Myocardial
infarction
Asymptomatic
plaque
Stable
angina
Non-ST
elevation
ST-elevation
Variant
angina
n:M u wn IasospasLlc
C|ass|fy to know
what to do
Acute management |s the s|m||ar
,anagement of ACS
Immed|ate management of
unstab|e] NS1L,I] S1L,I |s
genera||y the same
Increase oxygen supp|y ]
reduce demand
ygen
Asplrln uu
-lLraLes
aln medlcaLlons
uu
AnLlplaLeleL uu
AnLlcoagulanL uu
eLa blocker
" keperfus|on
1hrombolyLlc agenL
uu
ercuLaneous coronary
lnLervenLlon (Cl)
Coronary arLery bypass
grafLlng (CA)
9revent comp||cat|ons
ArrhyLhmla nwt
umplng fallure nwt
A|ms of treatment ACS
1o lmprove prognosls by prevenLlng ,l and deaLh
8educe plaque progresslon
SLablllze plaque
revenL Lhrombosls or plaque rupLure
1o reduce sympLoms
Ang|na
emand
Cxygen consumpt|on
Jall sLress or Lenslon
lnLravenLrlcular pressure
IenLrlcular volume
Jall Lhlckness
PearL raLe
ConLracLlllLy
Supp|y
Coronary b|ood f|ow
erfuslon pressure (aorLlc
dlasLollc pressure)
uuraLlon of dlasLole
(dlasLollc fllllng Llme)
Coronary vascular bed
reslsLance
A-S
,eLabollc producLs
IasoacLlve drug
LndoLhellal cell
Demand Supply
rug act|on |n ang|na 1o re||ef chest pa|n
N|trates
CC8s
8eta b|ockers
A|| reduce oxygen demand by a reducLlon of
PearL raLe
IenLrlcular volume

ConLracLlllLy
-lLraLes CCs red|str|but|on of coronary flow
lncrease oygen dellvery (supply)
N|trates
N|trog|ycer|n
Isosorb|de d|n|trate
Isosorb|de monon|trate
N|trates
,aln drug for rellevlng chesL paln
SLrucLure slmple nlLrlc and nlLrlc acld esLer of polyalcohols
8apldly absorb reach LherapeuLlc drug level ln mlnuLes
-lLraLe half llfe 28 mlnuLes
,eLabollLe (denlLraLed) longer half llfe 3 hrs
|tn uu organlc nlLraLe |t u -lLrlc
olde
N|trate Crgan system effects
Vascu|ar smooth musc|e ce|| All segmenLs of vessels from large
arLerles Lo large veln are rela (low dose veln/ hlgh dose
arLery)
ulrecL effecLs
,arked re|axat|on of ve|n
lncrease venous capaclLance and decrease venLrlcular
preload
uecrease pulmonary vascular pressure and hearL slze
roblem syncope
Aort|c d||atat|on
roblem Lemporal arLery pulsaLlon and Lhrobblng
headache
lndlrecL effecLs
CompensaLory response evoke by barorecepLor and
hormonal mechanlsm respondlng Lo decrease arLerlal
pressure leadlng Lo n|trate to|erance
1achycardla
lncrease cardlac conLracLlllLy
8eLenLlon of salL and waLer
Coronary b|ood f|ow |ncreases (dllaLe coronary arLery) ln
healLhy sub[ecLs buL noL ln anglna due Lo aLheroscleroLlc
obsLrucLlon
Powever 'redlsLrlbuLlon (lo collaLeral vessel)' may be of
beneflL
Cther smooth musc|e organ
ke|axat|on of smooLh muscle ln bronchl l D
rlef duraLlon no cllnlcal use
Act|on on p|ate|et
-lLrlc olde released from nlLraLe sLlmulaLe guanyl cyclase
ln plaLeleL as ln smooLh muscle lncrease c, reduce
plaLeleL aggregaLlon good ln A,l??????
Powever no survlval beneflL ln A,l
Cther effects N|tr|te |on from organ|c n|trate
lnds Pb (ferrous lon) ,ethemog|ob|n(ferrlc lon)
Low oygen afflnlLy from hlgh dose nlLraLe
seudocyanosls
1lssue hypola
ueaLh
-ormally nlLrlLe lon levels are very low
eware lf paLlenLs recelve nlLraLes from oLher sources
N|trate mechan|sm of c||n|ca| effects
9otent|a| benef|t kesu|ts
uecrease venLrlcular volume 8educe myocardlum oygen demand
uecrease arLerlal pressure
uecrease e[ecLlon Llme
IasodllaLaLlon of eplcardlal coronary
arLerles
8educe coronary spasm
lncrease collaLeral flow lncrease perfuslon Lo lschemlc area
uecrease LI dlasLollc pressure lncrease subendocardlal perfuslon
9otent|a| de|eter|ous effects kesu|ts
8efle Lachycardla lncrease myocardlum oygen demand
8efle lncrease ln conLracLlllLy
uecrease dlasLollc perfuslon Llme 8educe coronary perfuslon
N|trate Lffects |n ang|na
Ang|na
uecrease venous reLurn Lo hearL + decrease lnLracardlac
volume
uecrease arLerlal pressure
uecrease lnLravenLrlcular pressure + LI volume reduce
wall Lenslon reduce oygen demand
Var|ant ang|na
8ela smooLh muscle of eplcardlal coronary arLery
Dnstab|e ang|na
? 8educe chesL paln from dllaLlng eplcardlal coronary
arLery
? LffecL of decrease plaLeleL aggregaLlon may be of beneflL
N|trate 1ox|c|ty
Acute adverse effects
rLhosLaLlc hypoLenslon
1achycardla
1hrobblng headache
ConLralndlcaLe lncrease lnLracranlal pressure
1o|erance vgq
lLnLnluntnMtn u - nMn1
?,echanlsm ?from a reducLlon of Llssue sulfhydryl group
and an lncrease of oygen free radlcals
1achyphylals compleLe Lolerance of smooLh muscle
-lLraLe free perlod of aL leasL hours
Carc|nogen|c|ty of n|tr|te n|trate der|vat|ves
N|trosam|ne nlLraLe + nlLrlLe + amlnes
lound ln Lobacco clgareLLe smoklng
AssoclaLed wlLh esophageal and gasLrlc CA
-1 used ln LherapeuLlc dose ls ok
Ca|c|um channe|
b|ockers
Ierapamll
ullLlazem
-lfedlplne
Vo|tage dependent ca|c|um channe|
CC8 Crgan system effects
Smooth musc|e
ke|ax vasodllaLe reduce perlpheral vascular reslsLance
P1 and anglna LreaLmenL
,osL Lypes of smooLh muscle are dependenL on
Lransmembrane Ca
2+
lnflufor normal resLlng Lone +
conLracLlle response
Iascular smooLh muscle cells
,osL senslLlve Lo CC
ArLery Ieln
Lhers bronchlolar l uLerlne
Card|ac musc|e
CC reduce contract|||ty reduce oygen demand
anglna LreaLmenL
Ca
2+
ls requlred ln
lmpulse generaLe from SA node + conducLlon ln AI
node need Ca
2+
LclLaLlonconLracLlon coupllng ln myocardlum
Ske|eta| musc|e
Not depressed by cc8
Dses lnLracellular pools of Ca
2+
no requlre of Ca
2+
lnflu
CC8 C||n|ca| use
Ang|na
esL for varlanL anglna
Anglna of efforL verapamll/ dllLlazem
ypertens|on
Supraventr|cu|ar tachycard|a
Lhers hyperLrophlc cardlomyopaLhy mlgralne rhaynaud
phenomenon
Aware Ierapamll and dlgoln lncrease dlgoln level Loo
much cardlac depresslon
CC8 1ox|c|ty
Cardlac depresslon
ArresL
radycardla
AI block
PearL fallure
Avold use wlLh beLa blockers
-lfedlplne lncreases rlsk of ,l ln paLlenLs wlLh P1
,lnor LolclLy flushlng dlzzlness nausea consLlpaLlon
perlpheral edema
8eta b|ocker
8etab|ockers Crgan system effects
CVS

Negat|ve |notrop|cnMu1ttMl
Negat|ve chronotrop|cnMMn|Mu
kesp|ratory
2
8ronchoconstr|ct|on
8etab|ockers |n ang|na
Wanted act|ons |n ang|na hemodynamlc effecLs
8educe hearL raLe
8educe
8educe conLracLlllLy
All of Lhese reduce oygen demand+ lncrease supply
(lncrease dlasLollc perfuslon Llme)
Dndes|rab|e effects
lncrease end dlasLollc volume
lncrease e[ecLlon Llme
oLh lncrease oygen demand musL be balanced by Lhe
use of nlLraLe
ConLralndlcaLlon
AsLhma bradycardla AI block severe LI fallure
1olclLy
laLlque lnsomnla nlghLmare lmpoLence
Comb|ned reg|men
N|trate a|one 88 or CC8
a|one
N|trate + 88 or
CC8
eart rate eflex locteose ecrease ecrease
Arter|a|
pressure
ecrease ecrease ecrease
Lnd d|asto||c
vo|ume
ecrease locteose None or decrease

Contract|||ty eflex locteose ecrease None

L[ect|on t|me ecrease locteose None
Ang|na treatment newer drug group
Why not [ust d||ate the artery"
Pydralazlne/ dlpyrldamole dllaLe arLery
uuvnM|n MuM1uu1tnM n lu MMuun:vn1MM
Mu uulLlM |n M shlfL lt1M uuu1tnML |n M
wu unl
Coronary Stea| 9henomenon
-lLraLe ls ok
Coronary stea| phenomenon
ydra|az|ne or
d|pyr|damo|e
Not d||ate
-o blood
Coronary stea| phenomenon
N|trate
||ate
8|ood
,a|ntenance treatment for ang|na
Ang|na of effort
SLable anglna
-lLraLe/ CC/ eLa blocker
JlLh P1 CC/ eLa blocker
-o P1 long acLlng nlLraLe
DnsLable anglna
-lLraLe/ CC/ eLa blocker
ASA
Var|ant ang|na
-lLraLe/ CC
A|ms of treatment
1o |mprove prognos|s by prevenLlng ,l and deaLh
8educe plaque progresslon
SLablllze plaque
revenL Lhrombosls or plaque rupLure
1o reduce sympLoms
rugs to |mprove prognos|s
Categor|es Lv|dence
AnLlLhromboLlc Low dose asplrln ln all paLlenLs l A
Clopldogrel as alLernaLlve lla
Llpld lowerlng SLaLln for all l A
Plgh dose sLaLln for hlgh rlsk paLlenLs
wlLh esLabllshed CAu
lla
llbraLe for low PuL and hlgh 1 for
Lhose wlLh u, or meLabollc
syndrome
llb
llbraLe or nlcoLlnlc acld as ad[uncLlve
Lherapy Lo sLaLln ln paLlenLs wlLh low
PuL and hlgh 1 aL hlgh rlsk
lla C
rugs to |mprove prognos|s
Categor|es Lv|dence
ACLls aLlenLs wlLh colncldence lndlcaLlon
for ACLl
l A
All paLlenLs wlLh anglna and
esLabllshed CAu
lla
eLa blockers osL ,l or wlLh hearL fallure l A
LN