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1、PharmacologyoftheAntibioticsPAULE.MANAIG,M.D.Theanti-infectivedrugsn nAnti-infectiveagentsaredrugs that are designed to act selectively on foreign organismsthathaveinvadedandinfectedthebodyTheanti-infectivedrugsAnti-infectivedrugs-rangefromn nAntibacterialsn nAntifungalsn nAntiprotozoalsn nAntihelmi
2、nthicsn nAntiviralsn nAntimycobacterialGeneralMechanismsofActionofanti-infectiveagentsThemechanismsare:n nInhibitionthebiosynthesisofbacterialcellWALLn nInhibitionofproteinsynthesisn nSomechangethecellmembranepermeabilityn nSomeinhibitDNAsynthesisExamplesCELLWALLCELLWALLINHIBITORSINHIBITORSpenicilli
3、n,penicillin,cephalosporin,cephalosporin,vancomycinvancomycinPROTEINSYNTHESISPROTEINSYNTHESISINHIBITORSINHIBITORSMacrolides,Macrolides,aminogylcosidesaminogylcosidesCELLWALLCELLWALLPermeabilityPermeabilityKetoconazoleKetoconazoleDNASYNTHESISDNASYNTHESISINHIBITORSINHIBITORSQuinolonesQuinolonesSpectru
4、mofActivityofAnti-infectivesn nNarrowspectrumn nBroad-spectrumSpectrumofActivityofAnti-infectivesn nNarrowspectrumanti-infectivesaffectonlyafewbacterialtypesn nTheearlypenicillindrugsareexamples.SpectrumofActivityofAnti-infectivesn nBroad-spectrumanti-infectivesaffectmanybacteria.n nMeropenemisanexa
5、mple.n nBecausenarrowspectrumantibioticsareselective,they are more active against single organismsthanthebroadspectrumantibiotics.SpectrumofActivityofAnti-infectivesAnti-infectiveagentscanalsobe:n nBacteriostaticErythromycin,tetracyclines,clindamycin,chloramphenicol,spectinomycin,sulfonamidesn nBact
6、ericidal-Penicillins,Cephalosphorins,Metronidazole,Aminoglycosides,Vancomycin,PolymyxinSpectrumofActivityofAnti-infectivesn nAnti-infectivesthatinterferewiththeabilityofthecelltoreproduce/replicatewithoutkillingthemarecalledBACTERIOSTATICdrugs.n nTetracyclineisanexample.SpectrumofActivityofAnti-infe
7、ctivesn nAntibioticsthatcanaggressivelycausebacterialdeatharecalledBACTERICIDAL.n nTheseproperties(-cidalandstatic)canalsodependontheantibioticconcentrationintheblood.n n(e.g.ErythromycinandClindamycinmaybebactericidalathigherbloodlevels)FactorsThatDeterminetheLikehoodOfaFactorsThatDeterminetheLikeh
8、oodOfamicroorganismCausinganInfection:microorganismCausinganInfection:1.1.Virulenceofthemicroorganism2.2.Numberofthemicroorganismpresent3.3.ResistanceofthehostPotentiallyPeriodontopathicBacteria:n nAdultpeiodontitis- Bacteriodes gingivalis- Bacteriodes gingivalis- B. intermedius- B. intermedius- Fus
9、obacterium nucleatum- Fusobacterium nucleatum- Veillonella parvula- Veillonella parvula- Actinomyces (naestundii, israelli, viscosus)- Actinomyces (naestundii, israelli, viscosus)LocalizedJuvenilePeriodontitis-Actinobacillus actinomycetemcomitans - Capnocytophaga sp.n nStreptococcus mutanscausingden
10、talcaries(mostcommondentalinfection)treatmentofchoice:localphysicalremovalofmicrobialplaqueonaregularbasis(goodoralhygiene)AntimicrobialuseindentistryAntimicrobialuseindentistryInfection/SituationDrugofChoiceAlternativedrugsPeriodontalDiseaseANUG(Vincent)Abscess(perio)PeriodontitisJuvenileAdultPenic
11、illinVPenicillinVTetracyclineTetracyclineMetronidazoleTetracyclineErythromycinTetracycline-MetronidazoleClindamycinOralInfectionsSofttissue(abscess,cellulitis,postsurgicalpericornitis)OsteomyelitisPenicillinase-producingstaphylococciMixedinfectioninsensitivetopenicillinAerobesAnaerobesPenicillinVPen
12、icillinVCloxacillinAmoxicillinClindamycinErythromycin,Cephalosporin,Clindamycin,TetracyclineCephalosporin,Clindamycin,ErythromycinCephalosporin,ClindamycinCephalosporin,Sulfonamides,TetracyclineCephalosporin,Metronidazole,Erythromycin,TetracyclineProphylacticforInfectiveendocarditisRheumaticheartDis
13、easeprostheticHeartvalvePenicillinVAmpicillin+gentamicinErythromycin,(Cephalosporin)I.ProphylaxistreatmentForInfectiveEndocarditis:I.ProphylaxistreatmentForInfectiveEndocarditis:Prophylaxisfordental,oral,upperrespiratorytractoresophagealProphylaxisfordental,oral,upperrespiratorytractoresophagealproc
14、edures:(Grampositiveorganisms)procedures:(Grampositiveorganisms)Oral:Amoxycillin2gorally1hrbeforeprocedure;children50mg/kgorallyOral:Amoxycillin2gorally1hrbeforeprocedure;children50mg/kgorally1hrbeforeprocedure1hrbeforeprocedure Penicillinallergy:Clindamycin600mgorally1hrbeforeprocedureorPenicillina
15、llergy:Clindamycin600mgorally1hrbeforeprocedureorCephalexin2gorally1hrbeforeprocedureCephalexin2gorally1hrbeforeprocedure Parenteral:Ampicillin2gIMorIV30minbeforeprocedureParenteral:Ampicillin2gIMorIV30minbeforeprocedure II.ProphylaxisforGastrointestinalandGenitourinaryProcedures:(Gram-II.Prophylaxi
16、sforGastrointestinalandGenitourinaryProcedures:(Gram-negativeprocedures)negativeprocedures)Parenteral:Ampicillin2gIVplusGentamicin1.5mg/kgIMorIV(nottoParenteral:Ampicillin2gIVplusGentamicin1.5mg/kgIMorIV(nottoexceed80mg)30minbeforeprocedure;followedbyampicillin1gIV6hrexceed80mg)30minbeforeprocedure;
17、followedbyampicillin1gIV6hrlaterlater PenicillinAllergy:Vancomycin1gIVinfusedslowlyover1hrplusPenicillinAllergy:Vancomycin1gIVinfusedslowlyover1hrplusGentamycin1.5mg/kgIMorIV(nottoexceed80mg)1hrbeforeGentamycin1.5mg/kgIMorIV(nottoexceed80mg)1hrbeforeprocedureprocedure CommonAdverseReactionstoAnti-in
18、fectiveTherapyThemostcommonadverseeffectsareduetothedirectactionofthedrugsinthefollowingorgansystem-Neuro,nephroandGIsystemCommonAdverseReactionstoAnti-infectiveTherapy1.1.Nephrotoxicityn nAntibiotics that are metabolized and excreted in the kidney most frequently cause kidney damage.CommonAdverseRe
19、actionstoAnti-infectiveTherapy2.Gastro-intestinaltoxicityn nDirecttoxiceffecttothecellsoftheGItractcancausenausea,vomiting,stomachpainanddiarrhea.n nSomedrugsaretoxictolivercellsandcancausehepatitisorliverfailure.CommonAdverseReactionstoAnti-infectiveTherapy3.CNStoxicityn nWhendrugscanpassthroughthe
20、brainbarrierandaccumulateinthenervoustissues,theycaninterferewithneuronalfunction.CommonAdverseReactionstoAnti-infectiveTherapy4.Hypersensitivityn nMostproteinantibioticscaninducethebodysimmunesystemtoproduceallergicresponses.n nDrugsareconsideredforeignsubstancesandwhentakenbytheindividual,itencoun
21、tersthebodysimmunecells.CommonAdverseReactionstoAnti-infectiveTherapy5.Super-infectionsn nOpportunisticinfectionsthatdevelopduringthecourseofantibiotictherapyarecalledSUPERINFECTIONS.ThePENICILLINSNarrow spectrum penicillinsNarrow spectrum penicillinsn nPenicillin GPenicillin Gn nPenicillin VPenicil
22、lin VBroad Spectrum Penicillins (aminopenicillin)Broad Spectrum Penicillins (aminopenicillin)n nAmoxicillinAmoxicillinn nAmpicillinAmpicillinn nBacampicillinBacampicillinPenicillinase-resistant Penicillin (anti-staphyloccocal penicillins)Penicillinase-resistant Penicillin (anti-staphyloccocal penici
23、llins)n nCloxacillinCloxacillinn nNafcillinNafcillinn nMethicillinMethicillinn nDicloxacillinDicloxacillinn nOxacillin Oxacillin Extended-Spectrum penicillins (Anti-pseudomonal penicillins)Extended-Spectrum penicillins (Anti-pseudomonal penicillins)n nCarbenicillinCarbenicillinn nMezlocillinMezlocil
24、linn nPiperacillinPiperacillinn nTicacillinTicacillinBeta-lactamase inhibitorsBeta-lactamase inhibitorsn nClavulanic acidClavulanic acidn nSulbactamSulbactamn nTazobactamTazobactamPenicillinPenicillinisabeta-lactamdrug,withabeta-lactamring.Thegroupofpenicillinsiscalledbetalactamantibiotics.Penicilli
25、nTheactionofPenicillinsn nThepenicillinandpenicillinase-resistantpenicillinsproduceBACTERICIDALeffectsbyinterfering with the ability of susceptible bacteria from biosynthesizing the framework of the cell wall. Penicillinn nThebacteriumwillhaveweakenedcellwall,willswellandthenburstfromtheosmoticpress
26、urewithinthecell.PenicillinPharmacokinetics:AmoxicilliniswellabsorbedintheGIT.ThisinNOTaffectedbyfoodintake!PenicillinTherapeuticIndicationsofpenicillinn nThepenicillinsareindicatedforthetreatmentofstreptococcalinfectionsn nSyphilisn nTetanusAdverseEffectsofPenicillinsn nGIsystemeffects-the major ad
27、verse effects of penicillin therapy involve the GIT.n nNausea,vomiting,diarrhea,abdominalpain,glossitis,stomatitis,gastritis,soremouthandfurrytongue.n nThereasonforsomeoftheseeffects(superinfection)isassociatedwiththelossofbacterialflora.AdverseEffectsofPenicillinsn nHypersensitivity reactions- rash
28、es, pruritus, fever and urticaria n nTheseindicatemildallergicreaction.Wheezinganddiarrheamayalsooccur.n nAnaphylaxiscanalsohappenleadingtoshockordeath.Itoccursin5-10%ofthosereceivingpenicillins.n nPainandinflammationoninjectionsitesTHECEPHALOSPORINSThe cephalosporins also belong to the beta-lactam
29、group of antibiotics THECEPHALOSPORINSn nFirstGenerationcephalosporinn nSecondgenerationcephalosporinn nThirdGenerationcephalosporinn nFourthgenerationcephalosporinTHECEPHALOSPORINSn nFirstGenerationcephalosporins-arelargelyeffectiveagainstthesamegram-positiveorganismsaffectedbypenicillin.n nSecondg
30、enerationcephalosporins-areeffectiveagainstthosestrainsaswellasHaemophilusinfluenza,EntreobacteraerogenesandNesseriasp.ThesedrugsarelesseffectiveagainstgrampositivebacteriaTHECEPHALOSPORINSn nThirdGenerationcephlosporins-arerelativelyweakagainstgram-positivebacteriabutmorepotentagainstgram-negativeb
31、acteria,toincludeSerratiamarcescens.n nFourthgenerationcephalosporins-aredevelopedtofightagainsttheresistantgram-negativebacteria.Thefirstdrugiscefepime.n nFirst generation cephalosporinsFirst generation cephalosporinsn ncefadroxilcefadroxiln nCefazolinCefazolinn nCephalexinCephalexinn nCephalotinCe
32、phalotinn nCephapirinCephapirinn nCephadrineCephadrinen nSecond Generation cephalosporinsSecond Generation cephalosporinsn nCefaclorCefaclorn nCefamandoleCefamandolen nCefonizindCefonizindn nCefotetanCefotetann nCefoxitinCefoxitinn nCefmetazoleCefmetazolen nCefprozilCefproziln nCefuroximeCefuroximen
33、 nThird Generation CephaosporinsThird Generation Cephaosporinsn nCefnidirCefnidirn nCefiximeCefiximen nCefoperazoneCefoperazonen nCefotaximeCefotaximen nCefpodoximeCefpodoximen nCeftazidimeCeftazidimen nCeftibutenCeftibutenn nMoxalactamMoxalactamn nFourth Generation CephalosporinFourth Generation Ce
34、phalosporinn nCefepimeCefepimeCephalosporinn nThemechanismofactionn nThecephalosporinsareprimarilyBACTERICIDAL.n nThey interfere with the cell-wall building ability of bacteria when they divide.n nTheypreventthebacteriafrombiosynthesizingtheframeworkoftheircellwall.n nTheweakenedcellwallwillswelland
35、burstcausingcelldeath.Cephalosporinn nPharmacokineticsn nOnlyafewcephalosporinsareadministeredorally,mostareadministeredparenterally.n nTheirhalf-livesareshortandtheyareexcretedmainlyintheurine.n nContraindicationsandPrecautionsn nThe drugs are contraindicated in patients with known allergies to cep
36、halosporins and penicillins.CephalosporinAdverseEffectsn nGIsystem-Nausea,vomiting,diarrhea,anorexia,abdominalpainandflatulencearecommoneffects.n nCNSheadache,dizziness,lethargyandparesthesiashavebeenreported.n nRenalsystem-nephrotoxicityinindividualswithpre-existingrenaldiseasen nHypersensitivityCe
37、phalosporinDrug-Druginteractionsn nALCOHOL-manypatientsexperienceadisulfiram-likereactionswhentakenwithsomespecificcephlosporins(cefamandole,cefoperazoneormoxalactam).n nThepatientmayexperienceflushing,headache,nausea,vomitingandmuscularcramps.Thismayoccurevenupto72hoursofcephalosporindiscontinuance
38、.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
39、the bacterial cell membrane, which causes cell death. TheAminoglycosidesTherapeuticUseoftheAminoglycosidesn nThesedrugsareusedtotreatseriousinfectionscausedbygram-NEGATIVEbacteria.n nThesedrugsarecontraindicatedinknownallergiestoaminoglycosides,inpatientswithrenalfailure,hepaticdisease,pre-existingh
40、earingloss,myastheniagravis,Parkinsons,pregnancyandlactation.TheAminoglycosidesAdverseEffectsofAminoglycosidesn nCNS-irreversibledeafness,vestibularparalysis,confusion,depression,disorientation,numbness,tinglingandweaknessrelatedtodrugeffects.n nKidney-renaltoxicity,whichmayprogresstorenalfailurecau
41、sedbythedirecttoxicityoftheaminoglycosides.n nHema-bonemarrowdepressionresultingfromdirectdrugeffectmayleadtoimmunesuppressionandsuper-infection.n nOtotoxicityTheAminoglycosidesAdverseEffectsofAminoglycosidesn nGIsystem-nausea,vomiting,diarrhea,weightloss,stomatitisandhepatictoxicityn nSkineffects-p
42、hotosensitivity,purpura,rash,urticariaandexfoliativedermatitisn nCardiac-palpitations,hypotensionorhypertensionTheAminoglycosidesDrugtodruginteractionsn nDiuretics-increasedincidenceofototoxicity,nephrotoxicityandneurotoxicity.n nAnesthetics and Neuromusular blockers- increased neuromuscular blockag
43、e and paralysis may be possiblen nPenicillin-synergisticactionTheMacrolidesThemacrolidesarenAzithromycinnClarithromycinnDirithromycinnErythromycinTheMacrolidesMechanismofActionoftheMacrolidesn nTheyexerttheireffectbybindingtothebacterialcellribosomesandchangingoralteringproteinproduction/functionn n
44、Thiswillleadtoimpairedcellmetabolismanddivision.TheMacrolidesn nPharmacokineticsn nErythromycinisdestroyedbythegastricjuice,whichiswhyslatsareaddedtostabilizethedrug.n nFooddoesnotinterferewiththeabsorptionofthemacrolides.TheMacrolidesTherapeuticUseofMacrolidesn nTheseareindicatedforthetreatmentofth
45、efollowingconditions:n nSteptococcalinfection,Mycoplasmainfection,ListeriainfectionandgroupAbetahemolyticstrepinfection. TheMacrolidesContraindicationsandPrecautionsintheUseContraindicationsandPrecautionsintheUseofMacrolidesofMacrolidesn nTheseagentsarecontraindicatedinthepresenceofknownallergytoany
46、macrolide,becausecross-sensitivityoccurs.n nCautionshouldbeusedinpatientswithhepaticdysfunctionthatcouldalterthemetabolismofthedrug;inlactatingwomenbecauseofdrugexcretioninbreastmilkandinpregnantwomenbecausepotentialadverseeffectsonthedevelopingfetus.TheMacrolidesAdverseEffectsofMacrolidesAdverseEff
47、ectsofMacrolidesn 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 hepatotoxi
48、c taken in high doses with other hepatotoxic drugs. drugs. n nCNS-confusion,abnormalthinkingandCNS-confusion,abnormalthinkinganduncontrollableemotions.uncontrollableemotions.n nHypersensitivityreactionsHypersensitivityreactionsTheLincosamidesTheseagentsaresimilartotheMacrolidesbutaremoretoxic.n nCli
49、ndamycinn nlincomycinTheLincosamidesPharmacodynamics:TheMechanismofActionofLincosamidesn nTheseagentspenetratethecellTheseagentspenetratethecellmembraneandbindtotheribosomeinmembraneandbindtotheribosomeinthebacterialcytoplasmtopreventthethebacterialcytoplasmtopreventtheproteinproductionproteinproduc
50、tionTheLincosamidesSideeffectsandAdverseReactionsSideeffectsandAdverseReactionsn nGIT-GIirritation,nausea,vomitingandGIT-GIirritation,nausea,vomitingandstomatitisstomatitisn nAllergicreactionsAllergicreactionsDrugInteractionsDrugInteractionsn nLincomycinandclindamycinareLincomycinandclindamycinarein
51、compatiblewithaminophyline,incompatiblewithaminophyline,phenytoin,barbituratesandampicillin.phenytoin,barbituratesandampicillin.TheTetracyclinesTheseagentswerefirstisolatedfromTheseagentswerefirstisolatedfromStreptomycesaureofaciensStreptomycesaureofaciensThefollowingarethetetracyclinesThefollowinga
52、rethetetracyclinesn nShort-actingtetracyclinesShort-actingtetracyclinesn ntetracyclinen noxytetracyclinen nIntermediateactingtetracyclinesIntermediateactingtetracyclinesn ndemeclocyclinen nmethacyclinen nLongactingtetracyclinesLongactingtetracyclinesn ndoxycyclinen nminocyclineTheTetracyclinesPharma
53、codynamicsn nThetetracyclinesinhibitproteinsynthesisinsusceptiblebacterialeadingtotheinabilityofthebacteriatomultiply.TheTetracyclinesContraindicationsandPrecautionsintheuseofTetracyclinesContraindicationsandPrecautionsintheuseofTetracyclinesn nItisnotrecommendedforuseinpregnancyandlactationbecauset
54、hedrugcanaffectthebonesandteeth,causingpermanentdiscolorationandsometimesarrestofgrowth.n nTetracyclinesarealsoavoidedinchildrenlessthan8(eight)yearsofagebecauseofthepotentialdamagetothebonesandpermanentdiscolorationoftheteeth.TheTetracyclinesAdverseEffectsoftheTetracyclineAdverseEffectsoftheTetracy
55、clinen nGIsystem-nausea,vomiting,diarrhea,abdominalGIsystem-nausea,vomiting,diarrhea,abdominalpain,glossitisanddysphagia.pain,glossitisanddysphagia.n nFatalhepatotoxicityrelatedtotetracyclinesFatalhepatotoxicityrelatedtotetracyclinesirritatingeffectonthelivercellshasbeenirritatingeffectonthelivercel
56、lshasbeenreported.reported.n nMusculoskletal-TetracyclineshaveanaffinityforMusculoskletal-Tetracyclineshaveanaffinityforteethandbones;theyaccumulatethere,leadingteethandbones;theyaccumulatethere,leadingtoweakeningofthebone/teethandpermanenttoweakeningofthebone/teethandpermanentstainingandpitting.sta
57、iningandpitting. n nSkin-Skin-photosensitivityandrashareexpectedphotosensitivityandrashareexpected. .n nLessfrequent-bonemarrowdepression,Lessfrequent-bonemarrowdepression,hypersensitivity,superinfections,painandhypersensitivity,superinfections,painandhypertensionhypertensionTheTetracyclinesDrug-Dru
58、gInteractionsDrug-DrugInteractionsn nPenicillin-iftakenwithtetracyclines,willPenicillin-iftakenwithtetracyclines,willdecreasetheeffectivenessofpenicillin.decreasetheeffectivenessofpenicillin.n nOralcontraceptives-iftakenwithOralcontraceptives-iftakenwithtetracycline,willhavedecreasedtetracycline,wil
59、lhavedecreasedeffectiveness.effectiveness.n nDigoxin-digoxintoxicityriseswhenDigoxin-digoxintoxicityriseswhentetracyclinesareusedtogethertetracyclinesareusedtogetherTheTetracyclinesDrug-FoodInteractionn nDairyproducts-cancomplexwithtetracyclineandrenderunabsorbable.n nTetracyclinesshouldthenbegiveno
60、nanEMPTYstomach1hourbeforemealsor2-3hoursafteranymealorothermedications.TheFluoroquinolonesThefluoroquinolonesarebroad-spectrumThefluoroquinolonesarebroad-spectrumantibiotics.Theyareusuallymanufacturedantibiotics.Theyareusuallymanufacturedsyntheticallyandareassociatedwithmildsyntheticallyandareassoc
61、iatedwithmildadversereactions.adversereactions.Theexamplesare:Theexamplesare:1.Nalidixicacid1.Nalidixicacid2.ciprofloxacin2.ciprofloxacin3.ofloxacin3.ofloxacin4.norfloxacin4.norfloxacinTheFluoroquinolonesPharmacodynamics:MechanismofactionoftheFluoroquinolonesn nTheseagentsenterthebacterialcellbydiff
62、usionthroughcellchannel.n nOnceinsidetheyinterferewiththeactionofDNAenzymes(DNAgyrase)necessaryforthegrowthandreproductionofthebacteria.Thiswillleadtocelldeath.TheFluoroquinolonesn nContraindicationsandPrecautionsPregnancyandlactationarealsoPregnancyandlactationarealsocontraindications.contraindicat
63、ions.TheseagentsarefoundtocauseTheseagentsarefoundtocausesignificantdamagetothecartilagessignificantdamagetothecartilagessuchthattheyaregivencautiouslytosuchthattheyaregivencautiouslytogrowingchildrenandadolescentslessgrowingchildrenandadolescentslessthan18yearsofagethan18yearsofageTheFluoroquinolon
64、esAdverseEffectsoftheFluoroquinolonesAdverseEffectsoftheFluoroquinolonesn nCNS-dizziness,insomnia,headache,andCNS-dizziness,insomnia,headache,anddepressionrelatedtopossibleeffectsondepressionrelatedtopossibleeffectsontheCNSmembrane.theCNSmembrane.n nGIsystem-nausea,vomiting,diarrheaandGIsystem-nause
65、a,vomiting,diarrheaanddrymouthrelatedtothedirecteffectondrymouthrelatedtothedirecteffectontheGITtheGITn nHema-bonemarrowdepressionrelatedtoHema-bonemarrowdepressionrelatedtothedirecteffectofthedrugonthecellsofthedirecteffectofthedrugonthecellsofthebonemarrowthatrapidlyturnoverthebonemarrowthatrapidl
66、yturnover. .n nOthereffects-skinreactions,rash,feverOthereffects-skinreactions,rash,feverandphotosensitivityandphotosensitivitySulfonamidesThefollowingarethesulfonamides:1.Sulfazalazine2.Sulfamethoxazole3.Sulfadiazine4.SulfixoxazoleSulfonamidesPharmacodynamicsPharmacodynamicsn nThesulfadrugscompetit
67、ivelyblockthepara-aminobenzoicacidtoprevent the synthesis of folic acidinsusceptiblebacteriathatsynthesizetheirownfolatesfortheproductionofRNAandDNA.SulfonamidesContraindicationsandprecautionsContraindicationsandprecautionsn nTheseagentsarecontraindicatedtopatientsTheseagentsarecontraindicatedtopati
68、entswithknownallergytosulfadrugs,withknownallergytosulfadrugs,sulfonylureasandthiazidediureticsbecausesulfonylureasandthiazidediureticsbecausetheysharesimilarstructures.theysharesimilarstructures.n nIt is not recommended for use in pregnancy It is not recommended for use in pregnancy because it can
69、cross the placenta and cause because it can cross the placenta and cause birth defects and kernicterus.birth defects and kernicterus.n nLactatingwomenwhotakethesedrugswillLactatingwomenwhotakethesedrugswillexcretetheminthebreastmilkpotentiallyexcretetheminthebreastmilkpotentiallycausingkernicterus,d
70、iarrheaandrashinthecausingkernicterus,diarrheaandrashinthenewborn.newborn.SulfonamidesAdverseEffectsoftheSulfonamidesAdverseEffectsoftheSulfonamidesn nGIsystem-nausea,vomiting,diarrhea,abdominalGIsystem-nausea,vomiting,diarrhea,abdominalpain,anorexia,stomatitisandhepaticinjury,pain,anorexia,stomatit
71、isandhepaticinjury,whichareallrelatedtothedirectirritationofthewhichareallrelatedtothedirectirritationoftheGITanddeathofnormalflora.GITanddeathofnormalflora.n nRenalsystem-crystalluria,hematuriaandRenalsystem-crystalluria,hematuriaandproteinuriawhichcanprogresstoanephroticproteinuriawhichcanprogress
72、toanephroticsyndromesyndrome. .n nCNS-headache,dizziness,vertigo,ataxia,CNS-headache,dizziness,vertigo,ataxia,convulsionsanddepressionrelatedtodrugconvulsionsanddepressionrelatedtodrugeffectsonthenerveseffectsonthenervesn nHema-bonemarrowdepressionrelatedtodrugHema-bonemarrowdepressionrelatedtodruge
73、ffectsonthecellsofthebonemarrowthatturneffectsonthecellsofthebonemarrowthatturnoverrapidly.overrapidly.n nDermatologiceffects-photosensitivityandrashDermatologiceffects-photosensitivityandrashandhypersensitivityandhypersensitivityTheantitubercularn nIsoniazidn nRifampicinn nPyrazinamiden nEthambutol
74、MechanismsofactionIsoniazidIsoniazidInterfereswithDNAInterfereswithDNAsynthesisofsynthesisofbacteriumbacteriumRifampicinRifampicinInterfereswithRNAInterfereswithRNAsynthesissynthesisPyrazinamidePyrazinamideInterfereswithInterfereswithbacterialwallbacterialwallsynthesissynthesisEthambutolEthambutolPr
75、eventPreventmultiplicationmultiplicationCommonSideeffectsIsoniazidIsoniazidInterfereswithB6InterfereswithB6PeripheralneuritisPeripheralneuritisRifampicinRifampicinRed-orangediscolorationofRed-orangediscolorationofthesecretionsthesecretionsHepatitisHepatitisPyrazinamidePyrazinamideHyperuricemiaHyperu
76、ricemiaEthambutolEthambutolOpticneuritisOpticneuritisPrecautionsIsoniazidIsoniazidLiverimpairmentLiverimpairmentRifampicinRifampicinLiverimpairmentLiverimpairmentPyrazinamidePyrazinamideLiverimpairmentLiverimpairmentGoutGoutPregnancyPregnancyEthambutolEthambutolLiverimpairmentLiverimpairmentChildren
77、lessthan6yearsChildrenlessthan6yearsoldoldGeneralResponsibilitiesn nAdvisepatienttotaketheDRUGSasprescribedn nMultipledrugsaretakentopreventRESISTANCEn nPeriodicallychecktheliverfunctiontestsn nSupplementalIntakeofVitaminB6Anti-fungalsn nTheseagentsALTERthefungalcellwallcausingfungaldestructionAnti-
78、fungalsn nThe“AZOLES”n nKetoconazoleKetoconazolen nCLotrimazoleCLotrimazolen nMiconazoleMiconazolen nIV:AMPHOTERICINAntifungalsIndicationsn nFungalinfectionsn nCandidiasisn nTineaAntifungalsImportantsideeffectsImportantsideeffectsn nHypersensitivityHypersensitivityn nHeadacheHeadachen nDizzinessDizz
79、inessn nPruritusPruritusn nIrritationIrritationn nAMPHOTERICIN:HYPOKALEMIA,AMPHOTERICIN:HYPOKALEMIA,arrhythmiaandkidneydamagearrhythmiaandkidneydamageGeneralResponsibilitiesn nTaketheoraldrugswithfoodn nEvaluatethelivertest,kidneytestandCBCn nInstitutesafetymeasuresn nFORamphotericin:EvaluateECGandP
80、otassium,administersteroid,evaluateIVsite,givewithINFUSIONpumpAntiviralsn nGeneralActionn nTheseagentsinterferewiththeDNAorTheseagentsinterferewiththeDNAorRNAsynthesisandreplicationoftheRNAsynthesisandreplicationofthevirusvirusAntiviralsn nThe“Vir”n nAcyclovirAcyclovirn nFamcyclovirFamcyclovirn nVal
81、acyclovirValacyclovirn nGancyclovirGancyclovirn nAIDSanti-viraln nZidovudine(AZT)Zidovudine(AZT)Antiviralsn nPrecautionwithusen nHypersensitivityHypersensitivityn nPregnancyPregnancyn nRenalandhepaticimpairmentRenalandhepaticimpairmentAntiviralsn nAdverseeffectsn nAnorexiaAnorexian nNauseaNausean nVomitingVomitingn nBleedingBleedingn nPhlebitisPhlebitisn nReportable:bonemarrowdepressionReportable:bonemarrowdepressionandnephrotoxicityandnephrotoxicity
