PharmacologyoftheAntibioticsPAULE.MANAIG,M.D.Theanti-infectivedrugsn nAnti-infectiveagentsaredrugs that are designed to act selectively on foreign organismsthathaveinvadedandinfectedthebodyTheanti-infectivedrugsAnti-infectivedrugs-rangefromn nAntibacterialsn nAntifungalsn nAntiprotozoalsn nAntihelminthicsn nAntiviralsn nAntimycobacterialGeneralMechanismsofActionofanti-infectiveagentsThemechanismsare:n nInhibitionthebiosynthesisofbacterialcellWALLn nInhibitionofproteinsynthesisn nSomechangethecellmembranepermeabilityn nSomeinhibitDNAsynthesisExamplesCELLWALLCELLWALLINHIBITORSINHIBITORSpenicillin,penicillin,cephalosporin,cephalosporin,vancomycinvancomycinPROTEINSYNTHESISPROTEINSYNTHESISINHIBITORSINHIBITORSMacrolides,Macrolides,aminogylcosidesaminogylcosidesCELLWALLCELLWALLPermeabilityPermeabilityKetoconazoleKetoconazoleDNASYNTHESISDNASYNTHESISINHIBITORSINHIBITORSQuinolonesQuinolonesSpectrumofActivityofAnti-infectivesn nNarrowspectrumn nBroad-spectrumSpectrumofActivityofAnti-infectivesn nNarrowspectrumanti-infectivesaffectonlyafewbacterialtypesn nTheearlypenicillindrugsareexamples.SpectrumofActivityofAnti-infectivesn nBroad-spectrumanti-infectivesaffectmanybacteria.n nMeropenemisanexample.n nBecausenarrowspectrumantibioticsareselective,they are more active against single organismsthanthebroadspectrumantibiotics.SpectrumofActivityofAnti-infectivesAnti-infectiveagentscanalsobe:n nBacteriostaticErythromycin,tetracyclines,clindamycin,chloramphenicol,spectinomycin,sulfonamidesn nBactericidal-Penicillins,Cephalosphorins,Metronidazole,Aminoglycosides,Vancomycin,PolymyxinSpectrumofActivityofAnti-infectivesn nAnti-infectivesthatinterferewiththeabilityofthecelltoreproduce/replicatewithoutkillingthemarecalledBACTERIOSTATICdrugs.n nTetracyclineisanexample.SpectrumofActivityofAnti-infectivesn nAntibioticsthatcanaggressivelycausebacterialdeatharecalledBACTERICIDAL.n nTheseproperties(-cidalandstatic)canalsodependontheantibioticconcentrationintheblood.n n(e.g.ErythromycinandClindamycinmaybebactericidalathigherbloodlevels)FactorsThatDeterminetheLikehoodOfaFactorsThatDeterminetheLikehoodOfamicroorganismCausinganInfection:microorganismCausinganInfection:1.1.Virulenceofthemicroorganism2.2.Numberofthemicroorganismpresent3.3.ResistanceofthehostPotentiallyPeriodontopathicBacteria:n nAdultpeiodontitis- Bacteriodes gingivalis- Bacteriodes gingivalis- B. intermedius- B. intermedius- Fusobacterium nucleatum- Fusobacterium nucleatum- Veillonella parvula- Veillonella parvula- Actinomyces (naestundii, israelli, viscosus)- Actinomyces (naestundii, israelli, viscosus)LocalizedJuvenilePeriodontitis-Actinobacillus actinomycetemcomitans - Capnocytophaga sp.n nStreptococcus mutanscausingdentalcaries(mostcommondentalinfection)treatmentofchoice:localphysicalremovalofmicrobialplaqueonaregularbasis(goodoralhygiene)AntimicrobialuseindentistryAntimicrobialuseindentistryInfection/SituationDrugofChoiceAlternativedrugsPeriodontalDiseaseANUG(Vincent)Abscess(perio)PeriodontitisJuvenileAdultPenicillinVPenicillinVTetracyclineTetracyclineMetronidazoleTetracyclineErythromycinTetracycline-MetronidazoleClindamycinOralInfectionsSofttissue(abscess,cellulitis,postsurgicalpericornitis)OsteomyelitisPenicillinase-producingstaphylococciMixedinfectioninsensitivetopenicillinAerobesAnaerobesPenicillinVPenicillinVCloxacillinAmoxicillinClindamycinErythromycin,Cephalosporin,Clindamycin,TetracyclineCephalosporin,Clindamycin,ErythromycinCephalosporin,ClindamycinCephalosporin,Sulfonamides,TetracyclineCephalosporin,Metronidazole,Erythromycin,TetracyclineProphylacticforInfectiveendocarditisRheumaticheartDiseaseprostheticHeartvalvePenicillinVAmpicillin+gentamicinErythromycin,(Cephalosporin)I.ProphylaxistreatmentForInfectiveEndocarditis:I.ProphylaxistreatmentForInfectiveEndocarditis:Prophylaxisfordental,oral,upperrespiratorytractoresophagealProphylaxisfordental,oral,upperrespiratorytractoresophagealprocedures:(Grampositiveorganisms)procedures:(Grampositiveorganisms)Oral:Amoxycillin2gorally1hrbeforeprocedure;children50mg/kgorallyOral:Amoxycillin2gorally1hrbeforeprocedure;children50mg/kgorally1hrbeforeprocedure1hrbeforeprocedure Penicillinallergy:Clindamycin600mgorally1hrbeforeprocedureorPenicillinallergy:Clindamycin600mgorally1hrbeforeprocedureorCephalexin2gorally1hrbeforeprocedureCephalexin2gorally1hrbeforeprocedure Parenteral:Ampicillin2gIMorIV30minbeforeprocedureParenteral:Ampicillin2gIMorIV30minbeforeprocedure II.ProphylaxisforGastrointestinalandGenitourinaryProcedures:(Gram-II.ProphylaxisforGastrointestinalandGenitourinaryProcedures:(Gram-negativeprocedures)negativeprocedures)Parenteral:Ampicillin2gIVplusGentamicin1.5mg/kgIMorIV(nottoParenteral:Ampicillin2gIVplusGentamicin1.5mg/kgIMorIV(nottoexceed80mg)30minbeforeprocedure;followedbyampicillin1gIV6hrexceed80mg)30minbeforeprocedure;followedbyampicillin1gIV6hrlaterlater PenicillinAllergy:Vancomycin1gIVinfusedslowlyover1hrplusPenicillinAllergy:Vancomycin1gIVinfusedslowlyover1hrplusGentamycin1.5mg/kgIMorIV(nottoexceed80mg)1hrbeforeGentamycin1.5mg/kgIMorIV(nottoexceed80mg)1hrbeforeprocedureprocedure CommonAdverseReactionstoAnti-infectiveTherapyThemostcommonadverseeffectsareduetothedirectactionofthedrugsinthefollowingorgansystem-Neuro,nephroandGIsystemCommonAdverseReactionstoAnti-infectiveTherapy1.1.Nephrotoxicityn nAntibiotics that are metabolized and excreted in the kidney most frequently cause kidney damage.CommonAdverseReactionstoAnti-infectiveTherapy2.Gastro-intestinaltoxicityn nDirecttoxiceffecttothecellsoftheGItractcancausenausea,vomiting,stomachpainanddiarrhea.n nSomedrugsaretoxictolivercellsandcancausehepatitisorliverfailure.CommonAdverseReactionstoAnti-infectiveTherapy3.CNStoxicityn nWhendrugscanpassthroughthebrainbarrierandaccumulateinthenervoustissues,theycaninterferewithneuronalfunction.CommonAdverseReactionstoAnti-infectiveTherapy4.Hypersensitivityn nMostproteinantibioticscaninducethebodysimmunesystemtoproduceallergicresponses.n nDrugsareconsideredforeignsubstancesandwhentakenbytheindividual,itencountersthebodysimmunecells.CommonAdverseReactionstoAnti-infectiveTherapy5.Super-infectionsn nOpportunisticinfectionsthatdevelopduringthecourseofantibiotictherapyarecalledSUPERINFECTIONS.ThePENICILLINSNarrow spectrum penicillinsNarrow spectrum penicillinsn nPenicillin GPenicillin Gn nPenicillin VPenicillin VBroad Spectrum Penicillins (aminopenicillin)Broad Spectrum Penicillins (aminopenicillin)n nAmoxicillinAmoxicillinn nAmpicillinAmpicillinn nBacampicillinBacampicillinPenicillinase-resistant Penicillin (anti-staphyloccocal penicillins)Penicillinase-resistant Penicillin (anti-staphyloccocal penicillins)n nCloxacillinCloxacillinn nNafcillinNafcillinn nMethicillinMethicillinn nDicloxacillinDicloxacillinn nOxacillin Oxacillin Extended-Spectrum penicillins (Anti-pseudomonal penicillins)Extended-Spectrum penicillins (Anti-pseudomonal penicillins)n nCarbenicillinCarbenicillinn nMezlocillinMezlocillinn nPiperacillinPiperacillinn nTicacillinTicacillinBeta-lactamase inhibitorsBeta-lactamase inhibitorsn nClavulanic acidClavulanic acidn nSulbactamSulbactamn nTazobactamTazobactamPenicillinPenicillinisabeta-lactamdrug,withabeta-lactamring.Thegroupofpenicillinsiscalledbetalactamantibiotics.PenicillinTheactionofPenicillinsn nThepenicillinandpenicillinase-resistantpenicillinsproduceBACTERICIDALeffectsbyinterfering with the ability of susceptible bacteria from biosynthesizing the framework of the cell wall. Penicillinn nThebacteriumwillhaveweakenedcellwall,willswellandthenburstfromtheosmoticpressurewithinthecell.PenicillinPharmacokinetics:AmoxicilliniswellabsorbedintheGIT.ThisinNOTaffectedbyfoodintake!PenicillinTherapeuticIndicationsofpenicillinn nThepenicillinsareindicatedforthetreatmentofstreptococcalinfectionsn nSyphilisn nTetanusAdverseEffectsofPenicillinsn nGIsystemeffects-the major adverse effects of penicillin therapy involve the GIT.n nNausea,vomiting,diarrhea,abdominalpain,glossitis,stomatitis,gastritis,soremouthandfurrytongue.n nThereasonforsomeoftheseeffects(superinfection)isassociatedwiththelossofbacterialflora.AdverseEffectsofPenicillinsn nHypersensitivity reactions- rashes, pruritus, fever and urticaria n nTheseindicatemildallergicreaction.Wheezinganddiarrheamayalsooccur.n nAnaphylaxiscanalsohappenleadingtoshockordeath.Itoccursin5-10%ofthosereceivingpenicillins.n nPainandinflammationoninjectionsitesTHECEPHALOSPORINSThe cephalosporins also belong to the beta-lactam group of antibiotics THECEPHALOSPORINSn nFirstGenerationcephalosporinn nSecondgenerationcephalosporinn nThirdGenerationcephalosporinn nFourthgenerationcephalosporinTHECEPHALOSPORINSn nFirstGenerationcephalosporins-arelargelyeffectiveagainstthesamegram-positiveorganismsaffectedbypenicillin.n nSecondgenerationcephalosporins-areeffectiveagainstthosestrainsaswellasHaemophilusinfluenza,EntreobacteraerogenesandNesseriasp.ThesedrugsarelesseffectiveagainstgrampositivebacteriaTHECEPHALOSPORINSn nThirdGenerationcephlosporins-arerelativelyweakagainstgram-positivebacteriabutmorepotentagainstgram-negativebacteria,toincludeSerratiamarcescens.n nFourthgenerationcephalosporins-aredevelopedtofightagainsttheresistantgram-negativebacteria.Thefirstdrugiscefepime.n nFirst generation cephalosporinsFirst generation cephalosporinsn ncefadroxilcefadroxiln nCefazolinCefazolinn nCephalexinCephalexinn nCephalotinCephalotinn nCephapirinCephapirinn nCephadrineCephadrinen nSecond Generation cephalosporinsSecond Generation cephalosporinsn nCefaclorCefaclorn nCefamandoleCefamandolen nCefonizindCefonizindn nCefotetanCefotetann nCefoxitinCefoxitinn nCefmetazoleCefmetazolen nCefprozilCefproziln nCefuroximeCefuroximen nThird Generation CephaosporinsThird Generation Cephaosporinsn nCefnidirCefnidirn nCefiximeCefiximen nCefoperazoneCefoperazonen nCefotaximeCefotaximen nCefpodoximeCefpodoximen nCeftazidimeCeftazidimen nCeftibutenCeftibutenn nMoxalactamMoxalactamn nFourth Generation CephalosporinFourth Generation Cephalosporinn nCefepimeCefepimeCephalosporinn nThemechanismofactionn nThecephalosporinsareprimarilyBACTERICIDAL.n nThey interfere with the cell-wall building ability of bacteria when they divide.n nTheypreventthebacteriafrombiosynthesizingtheframeworkoftheircellwall.n nTheweakenedcellwallwillswellandburstcausingcelldeath.Cephalosporinn nPharmacokineticsn nOnlyafewcephalosporinsareadministeredorally,mostareadministeredparenterally.n nTheirhalf-livesareshortandtheyareexcretedmainlyintheurine.n nContraindicationsandPrecautionsn nThe drugs are contraindicated in patients with known allergies to cephalosporins and penicillins.CephalosporinAdverseEffectsn nGIsystem-Nausea,vomiting,diarrhea,anorexia,abdominalpainandflatulencearecommoneffects.n nCNSheadache,dizziness,lethargyandparesthesiashavebeenreported.n nRenalsystem-nephrotoxicityinindividualswithpre-existingrenaldiseasen nHypersensitivityCephalosporinDrug-Druginteractionsn nALCOHOL-manypatientsexperienceadisulfiram-likereactionswhentakenwithsomespecificcephlosporins(cefamandole,cefoperazoneormoxalactam).n nThepatientmayexperienceflushing,headache,nausea,vomitingandmuscularcramps.Thismayoccurevenupto72hoursofcephalosporindiscontinuance.TheAminoglycosidesThefollowingaretheaminoglycosides1. Gentamycin2. Tobramycin3. Amikacin4. Netilmicin5. KanamycinTheAminoglycosidesMechanismofactionn nTheseareBACTERICIDAL.n nThey inhibit protein synthesis in susceptible strains of gram-negative bacteria, leading to loss of functional integrity of the bacterial cell membrane, which causes cell death. TheAminoglycosidesTherapeuticUseoftheAminoglycosidesn nThesedrugsareusedtotreatseriousinfectionscausedbygram-NEGATIVEbacteria.n nThesedrugsarecontraindicatedinknownallergiestoaminoglycosides,inpatientswithrenalfailure,hepaticdisease,pre-existinghearingloss,myastheniagravis,Parkinsons,pregnancyandlactation.TheAminoglycosidesAdverseEffectsofAminoglycosidesn nCNS-irreversibledeafness,vestibularparalysis,confusion,depression,disorientation,numbness,tinglingandweaknessrelatedtodrugeffects.n nKidney-renaltoxicity,whichmayprogresstorenalfailurecausedbythedirecttoxicityoftheaminoglycosides.n nHema-bonemarrowdepressionresultingfromdirectdrugeffectmayleadtoimmunesuppressionandsuper-infection.n nOtotoxicityTheAminoglycosidesAdverseEffectsofAminoglycosidesn nGIsystem-nausea,vomiting,diarrhea,weightloss,stomatitisandhepatictoxicityn nSkineffects-photosensitivity,purpura,rash,urticariaandexfoliativedermatitisn nCardiac-palpitations,hypotensionorhypertensionTheAminoglycosidesDrugtodruginteractionsn nDiuretics-increasedincidenceofototoxicity,nephrotoxicityandneurotoxicity.n nAnesthetics and Neuromusular blockers- increased neuromuscular blockage and paralysis may be possiblen nPenicillin-synergisticactionTheMacrolidesThemacrolidesarenAzithromycinnClarithromycinnDirithromycinnErythromycinTheMacrolidesMechanismofActionoftheMacrolidesn nTheyexerttheireffectbybindingtothebacterialcellribosomesandchangingoralteringproteinproduction/functionn nThiswillleadtoimpairedcellmetabolismanddivision.TheMacrolidesn nPharmacokineticsn nErythromycinisdestroyedbythegastricjuice,whichiswhyslatsareaddedtostabilizethedrug.n nFooddoesnotinterferewiththeabsorptionofthemacrolides.TheMacrolidesTherapeuticUseofMacrolidesn nTheseareindicatedforthetreatmentofthefollowingconditions:n nSteptococcalinfection,Mycoplasmainfection,ListeriainfectionandgroupAbetahemolyticstrepinfection. TheMacrolidesContraindicationsandPrecautionsintheUseContraindicationsandPrecautionsintheUseofMacrolidesofMacrolidesn nTheseagentsarecontraindicatedinthepresenceofknownallergytoanymacrolide,becausecross-sensitivityoccurs.n nCautionshouldbeusedinpatientswithhepaticdysfunctionthatcouldalterthemetabolismofthedrug;inlactatingwomenbecauseofdrugexcretioninbreastmilkandinpregnantwomenbecausepotentialadverseeffectsonthedevelopingfetus.TheMacrolidesAdverseEffectsofMacrolidesAdverseEffectsofMacrolidesn nGIsystem-abdominalcramping,anorexia,GIsystem-abdominalcramping,anorexia,diarrhea,vomitinganddiarrhea,vomitingandpseudomembranouscolitis.pseudomembranouscolitis.HEPATOTOXICITY can occur if the drug is HEPATOTOXICITY can occur if the drug is taken in high doses with other hepatotoxic taken in high doses with other hepatotoxic drugs. drugs. n nCNS-confusion,abnormalthinkingandCNS-confusion,abnormalthinkinganduncontrollableemotions.uncontrollableemotions.n nHypersensitivityreactionsHypersensitivityreactionsTheLincosamidesTheseagentsaresimilartotheMacrolidesbutaremoretoxic.n nClindamycinn nlincomycinTheLincosamidesPharmacodynamics:TheMechanismofActionofLincosamidesn nTheseagentspenetratethecellTheseagentspenetratethecellmembraneandbindtotheribosomeinmembraneandbindtotheribosomeinthebacterialcytoplasmtopreventthethebacterialcytoplasmtopreventtheproteinproductionproteinproductionTheLincosamidesSideeffectsandAdverseReactionsSideeffectsandAdverseReactionsn nGIT-GIirritation,nausea,vomitingandGIT-GIirritation,nausea,vomitingandstomatitisstomatitisn nAllergicreactionsAllergicreactionsDrugInteractionsDrugInteractionsn nLincomycinandclindamycinareLincomycinandclindamycinareincompatiblewithaminophyline,incompatiblewithaminophyline,phenytoin,barbituratesandampicillin.phenytoin,barbituratesandampicillin.TheTetracyclinesTheseagentswerefirstisolatedfromTheseagentswerefirstisolatedfromStreptomycesaureofaciensStreptomycesaureofaciensThefollowingarethetetracyclinesThefollowingarethetetracyclinesn nShort-actingtetracyclinesShort-actingtetracyclinesn ntetracyclinen noxytetracyclinen nIntermediateactingtetracyclinesIntermediateactingtetracyclinesn ndemeclocyclinen nmethacyclinen nLongactingtetracyclinesLongactingtetracyclinesn ndoxycyclinen nminocyclineTheTetracyclinesPharmacodynamicsn nThetetracyclinesinhibitproteinsynthesisinsusceptiblebacterialeadingtotheinabilityofthebacteriatomultiply.TheTetracyclinesContraindicationsandPrecautionsintheuseofTetracyclinesContraindicationsandPrecautionsintheuseofTetracyclinesn nItisnotrecommendedforuseinpregnancyandlactationbecausethedrugcanaffectthebonesandteeth,causingpermanentdiscolorationandsometimesarrestofgrowth.n nTetracyclinesarealsoavoidedinchildrenlessthan8(eight)yearsofagebecauseofthepotentialdamagetothebonesandpermanentdiscolorationoftheteeth.TheTetracyclinesAdverseEffectsoftheTetracyclineAdverseEffectsoftheTetracyclinen nGIsystem-nausea,vomiting,diarrhea,abdominalGIsystem-nausea,vomiting,diarrhea,abdominalpain,glossitisanddysphagia.pain,glossitisanddysphagia.n nFatalhepatotoxicityrelatedtotetracyclinesFatalhepatotoxicityrelatedtotetracyclinesirritatingeffectonthelivercellshasbeenirritatingeffectonthelivercellshasbeenreported.reported.n nMusculoskletal-TetracyclineshaveanaffinityforMusculoskletal-Tetracyclineshaveanaffinityforteethandbones;theyaccumulatethere,leadingteethandbones;theyaccumulatethere,leadingtoweakeningofthebone/teethandpermanenttoweakeningofthebone/teethandpermanentstainingandpitting.stainingandpitting. n nSkin-Skin-photosensitivityandrashareexpectedphotosensitivityandrashareexpected. .n nLessfrequent-bonemarrowdepression,Lessfrequent-bonemarrowdepression,hypersensitivity,superinfections,painandhypersensitivity,superinfections,painandhypertensionhypertensionTheTetracyclinesDrug-DrugInteractionsDrug-DrugInteractionsn nPenicillin-iftakenwithtetracyclines,willPenicillin-iftakenwithtetracyclines,willdecreasetheeffectivenessofpenicillin.decreasetheeffectivenessofpenicillin.n nOralcontraceptives-iftakenwithOralcontraceptives-iftakenwithtetracycline,willhavedecreasedtetracycline,willhavedecreasedeffectiveness.effectiveness.n nDigoxin-digoxintoxicityriseswhenDigoxin-digoxintoxicityriseswhentetracyclinesareusedtogethertetracyclinesareusedtogetherTheTetracyclinesDrug-FoodInteractionn nDairyproducts-cancomplexwithtetracyclineandrenderunabsorbable.n nTetracyclinesshouldthenbegivenonanEMPTYstomach1hourbeforemealsor2-3hoursafteranymealorothermedications.TheFluoroquinolonesThefluoroquinolonesarebroad-spectrumThefluoroquinolonesarebroad-spectrumantibiotics.Theyareusuallymanufacturedantibiotics.Theyareusuallymanufacturedsyntheticallyandareassociatedwithmildsyntheticallyandareassociatedwithmildadversereactions.adversereactions.Theexamplesare:Theexamplesare:1.Nalidixicacid1.Nalidixicacid2.ciprofloxacin2.ciprofloxacin3.ofloxacin3.ofloxacin4.norfloxacin4.norfloxacinTheFluoroquinolonesPharmacodynamics:MechanismofactionoftheFluoroquinolonesn nTheseagentsenterthebacterialcellbydiffusionthroughcellchannel.n nOnceinsidetheyinterferewiththeactionofDNAenzymes(DNAgyrase)necessaryforthegrowthandreproductionofthebacteria.Thiswillleadtocelldeath.TheFluoroquinolonesn nContraindicationsandPrecautionsPregnancyandlactationarealsoPregnancyandlactationarealsocontraindications.contraindications.TheseagentsarefoundtocauseTheseagentsarefoundtocausesignificantdamagetothecartilagessignificantdamagetothecartilagessuchthattheyaregivencautiouslytosuchthattheyaregivencautiouslytogrowingchildrenandadolescentslessgrowingchildrenandadolescentslessthan18yearsofagethan18yearsofageTheFluoroquinolonesAdverseEffectsoftheFluoroquinolonesAdverseEffectsoftheFluoroquinolonesn nCNS-dizziness,insomnia,headache,andCNS-dizziness,insomnia,headache,anddepressionrelatedtopossibleeffectsondepressionrelatedtopossibleeffectsontheCNSmembrane.theCNSmembrane.n nGIsystem-nausea,vomiting,diarrheaandGIsystem-nausea,vomiting,diarrheaanddrymouthrelatedtothedirecteffectondrymouthrelatedtothedirecteffectontheGITtheGITn nHema-bonemarrowdepressionrelatedtoHema-bonemarrowdepressionrelatedtothedirecteffectofthedrugonthecellsofthedirecteffectofthedrugonthecellsofthebonemarrowthatrapidlyturnoverthebonemarrowthatrapidlyturnover. .n nOthereffects-skinreactions,rash,feverOthereffects-skinreactions,rash,feverandphotosensitivityandphotosensitivitySulfonamidesThefollowingarethesulfonamides:1.Sulfazalazine2.Sulfamethoxazole3.Sulfadiazine4.SulfixoxazoleSulfonamidesPharmacodynamicsPharmacodynamicsn nThesulfadrugscompetitivelyblockthepara-aminobenzoicacidtoprevent the synthesis of folic acidinsusceptiblebacteriathatsynthesizetheirownfolatesfortheproductionofRNAandDNA.SulfonamidesContraindicationsandprecautionsContraindicationsandprecautionsn nTheseagentsarecontraindicatedtopatientsTheseagentsarecontraindicatedtopatientswithknownallergytosulfadrugs,withknownallergytosulfadrugs,sulfonylureasandthiazidediureticsbecausesulfonylureasandthiazidediureticsbecausetheysharesimilarstructures.theysharesimilarstructures.n nIt is not recommended for use in pregnancy It is not recommended for use in pregnancy because it can cross the placenta and cause because it can cross the placenta and cause birth defects and kernicterus.birth defects and kernicterus.n nLactatingwomenwhotakethesedrugswillLactatingwomenwhotakethesedrugswillexcretetheminthebreastmilkpotentiallyexcretetheminthebreastmilkpotentiallycausingkernicterus,diarrheaandrashinthecausingkernicterus,diarrheaandrashinthenewborn.newborn.SulfonamidesAdverseEffectsoftheSulfonamidesAdverseEffectsoftheSulfonamidesn nGIsystem-nausea,vomiting,diarrhea,abdominalGIsystem-nausea,vomiting,diarrhea,abdominalpain,anorexia,stomatitisandhepaticinjury,pain,anorexia,stomatitisandhepaticinjury,whichareallrelatedtothedirectirritationofthewhichareallrelatedtothedirectirritationoftheGITanddeathofnormalflora.GITanddeathofnormalflora.n nRenalsystem-crystalluria,hematuriaandRenalsystem-crystalluria,hematuriaandproteinuriawhichcanprogresstoanephroticproteinuriawhichcanprogresstoanephroticsyndromesyndrome. .n nCNS-headache,dizziness,vertigo,ataxia,CNS-headache,dizziness,vertigo,ataxia,convulsionsanddepressionrelatedtodrugconvulsionsanddepressionrelatedtodrugeffectsonthenerveseffectsonthenervesn nHema-bonemarrowdepressionrelatedtodrugHema-bonemarrowdepressionrelatedtodrugeffectsonthecellsofthebonemarrowthatturneffectsonthecellsofthebonemarrowthatturnoverrapidly.overrapidly.n nDermatologiceffects-photosensitivityandrashDermatologiceffects-photosensitivityandrashandhypersensitivityandhypersensitivityTheantitubercularn nIsoniazidn nRifampicinn nPyrazinamiden nEthambutolMechanismsofactionIsoniazidIsoniazidInterfereswithDNAInterfereswithDNAsynthesisofsynthesisofbacteriumbacteriumRifampicinRifampicinInterfereswithRNAInterfereswithRNAsynthesissynthesisPyrazinamidePyrazinamideInterfereswithInterfereswithbacterialwallbacterialwallsynthesissynthesisEthambutolEthambutolPreventPreventmultiplicationmultiplicationCommonSideeffectsIsoniazidIsoniazidInterfereswithB6InterfereswithB6PeripheralneuritisPeripheralneuritisRifampicinRifampicinRed-orangediscolorationofRed-orangediscolorationofthesecretionsthesecretionsHepatitisHepatitisPyrazinamidePyrazinamideHyperuricemiaHyperuricemiaEthambutolEthambutolOpticneuritisOpticneuritisPrecautionsIsoniazidIsoniazidLiverimpairmentLiverimpairmentRifampicinRifampicinLiverimpairmentLiverimpairmentPyrazinamidePyrazinamideLiverimpairmentLiverimpairmentGoutGoutPregnancyPregnancyEthambutolEthambutolLiverimpairmentLiverimpairmentChildrenlessthan6yearsChildrenlessthan6yearsoldoldGeneralResponsibilitiesn nAdvisepatienttotaketheDRUGSasprescribedn nMultipledrugsaretakentopreventRESISTANCEn nPeriodicallychecktheliverfunctiontestsn nSupplementalIntakeofVitaminB6Anti-fungalsn nTheseagentsALTERthefungalcellwallcausingfungaldestructionAnti-fungalsn nThe“AZOLES”n nKetoconazoleKetoconazolen nCLotrimazoleCLotrimazolen nMiconazoleMiconazolen nIV:AMPHOTERICINAntifungalsIndicationsn nFungalinfectionsn nCandidiasisn nTineaAntifungalsImportantsideeffectsImportantsideeffectsn nHypersensitivityHypersensitivityn nHeadacheHeadachen nDizzinessDizzinessn nPruritusPruritusn nIrritationIrritationn nAMPHOTERICIN:HYPOKALEMIA,AMPHOTERICIN:HYPOKALEMIA,arrhythmiaandkidneydamagearrhythmiaandkidneydamageGeneralResponsibilitiesn nTaketheoraldrugswithfoodn nEvaluatethelivertest,kidneytestandCBCn nInstitutesafetymeasuresn nFORamphotericin:EvaluateECGandPotassium,administersteroid,evaluateIVsite,givewithINFUSIONpumpAntiviralsn nGeneralActionn nTheseagentsinterferewiththeDNAorTheseagentsinterferewiththeDNAorRNAsynthesisandreplicationoftheRNAsynthesisandreplicationofthevirusvirusAntiviralsn nThe“Vir”n nAcyclovirAcyclovirn nFamcyclovirFamcyclovirn nValacyclovirValacyclovirn nGancyclovirGancyclovirn nAIDSanti-viraln nZidovudine(AZT)Zidovudine(AZT)Antiviralsn nPrecautionwithusen nHypersensitivityHypersensitivityn nPregnancyPregnancyn nRenalandhepaticimpairmentRenalandhepaticimpairmentAntiviralsn nAdverseeffectsn nAnorexiaAnorexian nNauseaNausean nVomitingVomitingn nBleedingBleedingn nPhlebitisPhlebitisn nReportable:bonemarrowdepressionReportable:bonemarrowdepressionandnephrotoxicityandnephrotoxicity