Sulphonamides Classification 1) Remedies with systemic action:

a) medium action: (4-6 t. a day) - sulphadia ine - sulphadimidine - streptocide - sulphaethydol - sulphacar%amide %) lon&-action: (1 t a day) - sulphadimetho"ine - sulphametho"ipirida ine c) ultra-lon& action: (1t a wee') - sulphalen !) Remedies with &astrointestinal action: - sulpha&uanide - sulphasala ine - sala odine - phta ine - mesala ine - sala odimedo"ine #) Remedies with local action: - sulphacethamide (sulphacyl) - sulphadia ine spectrum of action (wide): () and (- %acteria* +. coli* ,ycoplasma pneumoniae* To"oplasma* -isteria* .. inhluen a* ,ora"ella Catarralis* /neumococus* ,enin&ococus* (onococus etc* ,echanism of action: They ha0e similar structure with /araamino%en oic acid* they are competiti0e inhi%itors of dihydropteroate synthase and inhi%it synthesis of dihydrofolic and tetrahydrofolic acid. Thus* they inhi%it the purines synthesis. Trimethoprim is a selecti0e inhi%itor of %acterial dihydrofolate reductase that transforms dihydrofolic acid into tetrahydrofolic acid. Thus* 1t decrease the purines 2uantity. Summary Sulfonamides sulfa drugs Synthetic; bacteriostatic; block folic acid synthesis Nausea, skin rashes Septra UTI

Trimethroprim and sulphonamides 1. trimethroprim !. co-trimo"a ole #. poteseptyl 4. lidaprim $ sulphaton

3escription Remedies with systemic action: They ha0e hi&h capacity of distri%ution* a%sorption* partially %indin& with plasmatic protein* penetrate natural %arriers* and are meta%oli ed in the li0er. +limination-%y urine. 1ndications: menin&itis* respiratory infectious* urinary infectious* %iliary infectious. To"oplsmose etc. Remedies with &astrointestinal action: they ha0e power a%sorption* from the intestine* and act in the intestine 1ndications: entherocolitis* colitis* dysenteria* prophyla"is of post operated infectious Remedies with local action: 1ndications: con4uncti0itis* superficial ocular infectious. Side effects of sulphamides and thrimetoprim. 1. dyspepsia ( anore"ia* nausea* 0omitin&) !. S5C distur%ances: (headache* di iness* con0olutions* polyneuritis* #. hematholo&ical : hemolytic anemia* trom%ocytopenia* methhemo&lo%inemia. 4. aller&y $. s'in eruptions 6. an&io-neurotic edema 6. dys%acterious 7. hepatitis 8. nephroto"i"ity Remedies with power solu%ility could produce: 1. cristhaluria !. renal colics #. renal o%struction and anuria Contraindications: 1. renal and hepatic failure !. /orphiria #. .emaphopathy 4. pre&nancy $. new%orns Chino"alin9s deri0ati0es: (chino"idine* dyo"idine) Spectrum of action: /roteus 0ul&aris* /seudomonas aeru&ino a* %acillus :ridlender* +. coli* Shi&ella* salmonella* staphilococus* Clostridium perfrin&ers. 1ndications: se0ere purulent inflamatiouns ( pielitis* pielocystitis* cholecistitis* cholan&itis* pulmonary a%scesses* sepsis. They are reser0ed dru&s. Side effects: dyspepsia* neurolo&ical dere&ulations* aller&y* dys%acteriosis* fe%er* con0ulsions. /harma'ocinetics: ;*!$ & <# time a day. <6-14 days

Cloramphenicol Spectrum of action: 1t has a wide spectrumand is usually %acteriostatic. :or hemophilus influen a and 5eiserria-it may %e %actericidal. 1t is not acti0e a&ainst chlamydia. 1ndications: infectious caused %y salmonella* and for the treatment of pneumococal and menin&ococcal menin&itis in %eta-lactam-sensiti0e persons. =ther indications can %e: ric'ettsial diseases and infectious caused %y anaero%es such as >acterioides fra&ilis. Side effects: 1.&ray %a%y syndrome: this syndrome occurs in infants and is characteri ed %y cyanosis and cardio0ascular collaps. (deficiency of hepatic &lucuronosyltransferase). !. aplastic anemia-it is usually irre0ersi%le and may %e fatal (1 case in !$ ;;;-4; ;;; patients treated) #. %one marrow- inhi%ition of red cell maturation. This action is dose dependent and re0ersi%le. 4.&astrointestinal distur%ances: direct irritation and suprainfectious* especially candidiasis. Summary Chloramphenicol Streptomyces venezuelae Synthetic; bacteriostatic; broad spectrum plastic anemia re!ersible or irre!ersible Treats typhoid fe!er, pen" resist meningococci # $" influen%ae, brain abscess, rickettsial infections &ast drug of choice in U"S" &ong term ner!e inflammation, confusion, delirium, mild to se!ere 'I problems Tetracyclines Spectrum of actionbroad-spectrum antibiotics (inhibit almost all gram-pos" and gram-neg" bacteria), protein synthesis inhibitor, *idely used in human and !eterinary medicine, *idespread resistance is a concern" rickettsia, chlamidia, mycoplasma, and some proto%oa" 1ndications: infectious caused %y ,ycoplasma* chlamidia* ric'ettsia* 0i%rios. Secondary: syphilis* leptospirosis Selecti0e uses: &astrointestinal ulcer caused %y .elico%acter pylori -yme disease* malaria (pre0ention) treatment of ame%iasis. Side effects: &astrointestinal distur%ances* aller&y* phle%itis* leucocytosis* throm%ocytopenia* candidosis. >ony structures and teeth: tooth enamel dysplasia and irre&ularities in %one &rowth. .epatic to"icity Renal to"icity /hotosensiti0ity

?esti%ular to"icity (di iness* 0erti&o) Contraindications: in pre&nancy* in new%orns* in hepatic and renal diseases Summary Tetracyclines Streptomyces +road spectrum, semisynthetic Treat ,hlamydia - synergestic *ith sulfa drugs Side effects nausea, diarrhea, kidney, light sensiti!ity, anemia, fatal li!er damage Interferes birth control pills Stains teeth under No milk or milk products, collard greens ( ,a) (lycopeptides ?ancomycine: Spectrum ( ) @dministration iA0* iAm* elimination 8;B %y urine* duration of action 7-1; hours. 1ndication it is reser0ed remedies in resistance staphilococus infectious* pseudomem%ranous colitis produced %y clindamycine Side effects: throm%ophle%itis* aller&y* oto* nephroto"icity* leucopenia* eo inophilia. Ristomycine: () (resistance cocci )* adm-iAm* iA0* sAc. +lmination %y the urine 7;B Side effects: : throm%ophle%itis* aller&y* rare oto* nephroto"icity* leucopenia* eo inophilia* /olimi"ines Spectrum: (r- ( +. coli* Cle%siela* +ntero%acter* salmonalla* >ordetella* /seudomonas* etc) 1ndications: infectious caused %y (- %acteria* (menin&itis* otitis* ocular infectious* Side effects: nephroto"icity* neuroto"icity* paraly e of s'eletal muscle* aller&y @dfministration local (sol.* un&.*and parenteral iAm* iA0 :usidine: Spectrum: Cocci (- and () no %acillus (1ndications: staphylococcus infectious* pneumoccocus* &onorrhea* >. fra&ilus. Side effects: &astro-intestinal distur%ances* aller&y @dministration: intern* iA0* local* elimination %y &all* Rifampicin: Spectrum: wide* %acteria ()* myco%acteria tu%erculosis* 1n the %i& doses <() %acteria. 1ndications: T>C* +ndocarditis* =stheomielitis* /neumonia* -eprous* Sepsis* ,enin&itis* Drinary infectious etc.

Side effects: hepatoto"icity* di&esti0e dere&ulations* aller&y* neurolo&ical dere&ulations* pseudoflu syndrome* red coloration of urine* sali0a* sweatin& etc. /harma'ocinetics: &ood a%sorption* 78B %indin& with plasmatic protein* #;B elimination %y urine Summary . 5ucleic @cid Synthesis 1nhi%ition Rifampin;blocks .N transcription, cidal; broad spectrum; Treat T+ # meningococcal carriers &i!er damage; interacts *ith oral contracepti!es /rinciples of anti%iotics associations: >actericid anti%iotics 1n phases of &rowth possi%le associations >eta-lactamase ?ancomycine Ristomycine @mino&lycosides /ossi%le association in this &roup 1mpossi%le assoc. >acteriostatic anti%iotics ,acrolides* tetracyclines* Cloramphenicol /ossi%le association &roup (potency* anta&onism* addition) in this often /olymi"ins* @mino&lycosidesE 1mpossi%le association in this &roup (side effect) no >actericid anti%iotics in all phases:

Indications/ 0" mi1ed infectious 2" se!ere and acute diseasedangerous for life 3" possibility of resistance 4" pre!ention of to1ic effects, rapid effect, in the small doses

@nti%iotic resistance in %acteria 1.5aturale: streptomycinic type" (single step) is characteri%ed for streptomycine, rifampicin, macrolids, fu%idine

It is characteri%ed by spontaneous mutation after 0-2 antibiotic administration" It doesn5t dependence on the doses 2" -streptomycinic type (multiple step)- it is characteri%ed by multiple mutations *ith increasing the doses ( penicillins, cephalosporines, tetracyclines, cloramphenicol, polimi1ins, !ancomycine) - cromosomic type It is characteri%ed by 6N transfer from one organism to another" - e1trachromosomal . factors (plasmids)- the information about resistance is contained in plasmids 'enetic mechanism of resistance5s transmission/ -con7ugation (se1ual process ) transformation (from lesion cell to health cell) transmission (by bacteriophags) +iochimic mechanisms - synthesis of en%ymes - modification of permeability - antimetabolits formation - metabolic deregulation 8ay of the resistance5s elimination / 0" ne* antibiotics synthesis 2" synthesis of the substance that inacti!ate microbial en%ymes 3" utili%ation of big doses 4" e1act diagnoses -" 9-02 months *ithout antibiotics The Search for Ne* ntimicrobial 6rugs The production of ne* analogs of e1isting antimicrobial compounds is often producti!e since they mimic the original drugs to some e1tent and ha!e a predictable mechanism of action, but may be different enough to act on organisms resistant to the original form of the drug" pplication of automated robotic chemistry methods to drug disco!ery : combinatorial chemistry" ;any different deri!ati!es of an antimicrobial agent can be generated in a short time, e1" <2- different tetracycline deri!ati!es from only 9 different reagents in only a fe* hours" ccording to the pharmaceutical industry, =< million candidate compounds must be screened to yield a single useful clinical drug" Ne* drug disco!ery/ 0>-2- years and ?->> million for each ne* drug appro!ed (@6 )" ,omputeri%ed drug design can facilitate the design of completely ne* drugs, e1" a protease inhibitor currently used to treat $IA"

" Resistance to dru&s ;icrobes once susceptible to antibiotic , no longer affected; many anti%iotics < %acteriostatic < inhi%it when present @ntimicro%ial dru& resistance: ac2uired a%ility of an or&anism to resist the effects of a chemotherapeutic a&ent to which it is normally suscepti%le. ,ost antimicro%ial resistance in0ol0es resistance &enes that are transferred %y means of &enetic e"chan&e. @nti%iotic producers de0elop resistance mechanisms to ena%le them to %e resistant to their own anti%iotics. Resistance can %e ac2uired %y 5on&enetic +0asion < microbe hides in tissue , produces progeny , released progeny still susceptible to drug BC" T+ Re0ersion no cell *all; become resistant (enetic Spontaneous mutations < 0D0> million to 0D0> billion organisms ntibiotics do not induce mutations +UT can create fa!orable en!ironment for mutant sur!i!al" (enetic resistance changes in bacterial chromosome - 6N mutated, one antibiotic /lasmid (s) acEuiring e1trachromosomal 6N 0F-F Shigella . factor : .esistance plasmids .esistance to multiple antibiotics (9-<) Transferred transduction (most) , con7ugation; interspecies or interstrain ;echanisms of .esistance 1. @lteration of tar&et +acterial ribosomes altered by 6N mutation , antimicrobial agent no longer binds; erythromycin, rifamycin, antimetabolites !. @lteration mem%rane permea%ility ;embrane transport or pores; antimicrobials cannot cross; tetracyclines, Euinolones, aminoglycosides #. 3e0elopment of en ymes

+eta lactamase inacti!ate penicillin # cephalosporins; Staphylococci, Streptococci, 'onococci 'ram negati!e en%ymes against aminoglycosides # chloramphenicol 4. +n yme alteration Sulfonamide resistant bacteria ha!e ability to acEuire needed G + *hen drug is present $. ,eta%olic pathway alteration +y-pass reaction inhibited by antimicrobial agent Sulfonamide resistant bacteria can by-pass production of @olic acid and use ready made folic acid from en!ironment &imiting 6rug .esistance 0" ;aintain high le!els - antibiotic in patient kill or inhibit pathogen Ta'e @-- of prescription. 3o not stop when symptoms su%side. 2" T*o antibiotics more effecti!e than one Synergistic effect 3" .estrict antibiotic use; bacterial infections only, not !iral; narro* spectrum ; NH NTI+IHTI,S IN NI; & @BB6" ,6, -> ; of 0-> ; outpatient prescriptions no need Testing ;icrobial Sensiti!ity to ntimicrobial gents Cir%y < >auer method disk diffusion Spread microbe to test o!er agar plate Glace drug impregnated disks on agar surface; incubate; look for IHNBS H@ IN$I+ITIHN ( clear %ones) around disks ;easure %one diameters, compare to table, determine, sensiti!ity or resistance of microbe to drug &arger diameter more sensiti!e to drug