general outline for antibiotics课件

GeneralOutlineforAntibiotics Chemistry MIPEffectonmicrobes MIPSpectrumofcoverageMechanism s ofactionMechanism s ofresistancePharmacologyofantibioticclass mostlynewinfoAbsorbanceFateafterabsorptionExcretionPharmacologyofselectagents mostlynewinfoTherapeuticuses somewhatnewinfoToxicity contraindications mostlynewinfoCommon 10 Uncommon 1 9 Rare 1 SirAlexanderFleming Sulfonamides AnaloguesofPABABroadspectrumCompetitiveinhibitorsofdihydropteroatesynthase neededforfolicacidsynthesisCidalinurineMechanismsofresistanceAlteredaffinityofenzymefordrugDecreasedpermeabilityoractiveeffluxNewpathwayoffolicacidsynthesis GerhardDomagkgetsaNobelforMedicine 1939 Sulfonamides MostlyabsorbedfromGItractBindsvariablytoserumalbuminWidetissuedistribution includingtransplacentallyVariablyinactivatedinliverbyacetylationandthenexcretedinurineSomeagentscanprecipitateinacidurine RapidlyAbsorbedandEliminatedSulfonamides Sulfisoxazole sulfamethoxazole sulfadiazineBindextensivelytoplasmaproteinsHighlyconcentratedinurine cidal Sulfamethoxazolecombinedwithtrimethoprim Bactrim iswidelyusedtotreatavarietyofinfections esp UTI PoorlyAbsorbedSulfonamides SulfasalazinePoorlyabsorbedinGItractUsedtotreatulcerativecolitisandirritablebowelsyndromeGutflorametabolizedruginto2compounds 1toxic 1therapeutic 5 aminosalicylate UlcerativeColitis SulfonamidesforTopicalUse SulfacetamideGoodpenetrationineyeNon irritatingSilversulfadiazinePreventionandtreatmentofburnwoundinfections Bacterialcornealinfection LongActingSulfonamide SulfadoxineSerumhalf lifeismeasuredindaysratherthanminutesorhoursCombinedwithpyirethaminetotreatmalaria Plasmodiumvivax TherapeuticUsesofSulfonamides UrinarytractinfectionsNocardiosisToxoplasmosis avoidusinginpregnantwomen Nocardiaasteroides Toxicity ContraindicationsofSulfonamides UT CrystallizationinacidurineCommontouncommondependingondrugAlkalizeurineorincreasehydration Toxicity ContraindicationsofSulfonamides blood AcutehemolyticanemiaRaretoextremelyrareAssociatedwithglucose 6 phosphatedehydrogenaseactivityinRBCAgranulocytosis extremelyrare Aplasticanemia extremelyrare Toxicity ContraindicationsofSulfonamides immune Hypersensitivityreactions commontouncommon Skinandmucousmembranemanifestations rashes SerumsicknessFocalordiffusenecrosisoftheliver rare ToxicEpidermalNecrolysis TEN Toxicity ContraindicationsofSulfonamides miscellaneous Nausea anorexia vomiting common KernicterusDisplacementofbilirubinfromplasmaalbumintobrainresultinginencephalopathyNevergivesulfadrugstoapregnantorlactatingwomanPotentiationoforalcoagulants sulfonylureahypoglycemicdrugs andhydrantoinanticonvulsants Bilirubindepositsinneonatalbrain TheQuinolones NaladixicacidwasabyproductofchloroquinesynthesisCurrentdrugsarefluoridated4 quinolonesBroadcoverage somebroaderthanothers TargetsDNAgyrase G andtopoisomeraseIV G Resistanceduetoeffluxandmutationsintargets Quinolones FavorablepharmacologicalattributesOrallyadministered quicklyabsorbed evenwithafullstomachExcellentbioavailabilityinawiderangeoftissuesandbodyfluids includinginsidecells MostlyclearedbythekidneysExceptionsarepefloxacinandmoxifloxacinwhicharemetabolizedbyliverCiprofloxacin ofloxacin andpefloxacinareexcretedinbreastmilk GotCipro TherapeuticUsesofQuinolones UrinarytractinfectionsProstatitisSTD sChlamydiaChancroidNotsyphilisorgonorrhea duetoincreasedresistance TherapeuticUsesofQuinolones GIandabdominalTravelersdiarrheaShigellosisTyphoidfeverRespiratorytractAllworkwellagainstatypicalsNewagentsforstrep pneumonia TherapeuticUsesofQuinolones Bone joint softtissueIdealforchronicosteomylitisResistancedevelopinginS aureus P aeruginosa andS marcesensGoodagainstpolymicrobialinfectionslikediabeticfootulcers TherapeuticUsesofQuinolones CiprofloxacinforanthraxandtuleremiaCombinedwithotherdrugs usefulforatypicalMycobacteriumsp orforprophylaxisinneutropenicpatients PulmonaryAnthrax Toxicity ContraindicationsofQuinolones Nausea vomiting abdominaldiscomfort common Diarrheaandantibiotic associatedcolitis uncommontorare CNSsideeffectsMildheadacheanddizziness commontorare Hallucinations delirium andseizures rare Arthropyinimmatureanimals common QuinolonesnotgiventochildrenunlessbenefitsoutweightherisksLeukopenia eosinophila heartarythmias rare TheBeta Lactams Penicillins Penicilliumnotatumproducestheonlynaturallyoccuringagent penicillinGorbenzylpenicillinDosageandpotencybasedonIU 1IU 0 6microgramspurepenicillinG P chrysogenumproduces6 aminopenicillanicacid rawmaterialforsemi syntheticsDosageandpotencybasedonweight Penicillins SpectrumofactivitybasedonRgroupsaddedto6 aminopenicillanicacidcoreAllarebactericidalandinhibittranspeptidasesMechanismsofresistanceAlteraffinityoftranspeptidaseEnzymaticallycleavethebeta lactamringEffluxpumpsPoorpenetrationintocell Penicillins Administeredorally intramuscularly orintravenouslydependingonagentAfteroraldose widelydistributedintissuesandsecretions exceptCNS prostaticfluid andtheeye DonotkillintracellularpathogensFoodinterfereswithadsorptionRapideliminationthroughkidney secretedinbreastmilk PenicillinsGandV EffectiveagainstaerobicG organismsexceptStaphylococcus PenGactiveagainstNeisseriaandanaerobes2 3oforalPenGdestroyedbystomachacid PenVismoreresistantsomoreisdeliveredtoserumRapideliminationthroughkidneysoprobenecid procaine ofbenzathineaddedtoslowexcretionMostdrugisboundtoserumalbuminbutsignificantamountsshowupinliver bile kidney semen jointfluid lymph etc CautioususeinneonatesandinfantsbecauserenalfunctionisnotfullyestablishedPatientswithrenalfailureclearthedrugsthroughliveralthoughataslowpace PenicillinsGandVTherapeuticUses StreptococcuspneumoniaeinfectionsS pyogenesinfectionsViridansstrependocarditis alsogivenprophylactically AnaerobesexceptBacteroidesfragilisgroupMeningococcalinfectionsSyphilisandotherdiseasescausedbyspirochetes IsoxazolylPenicillins Oxacillin cloxacillin dicloxacillin nafcillinDesignedtoresiststaphylococcalbeta lactamasesLikePenV stableinstomachacidbutusuallygivenparentallyforseriousstaphinfectionsMRSAnotcoveredAbsorptionandfateofdrugsafterabsorption excretionsimilartoPenGandPenV Aminopenicillins AmpicillinandamoxicillinBroadspectrumNoteffectiveagainstbeta lactamaseproducersBeta lactamaseinhibitorsextendspectrumBothareacidresistantbutamoxicillinisbetterabsorbed evenwithfoodDon tbindplasmaproteinsasmuchaspredecessorsSecretedthroughthekidney AminopenicillinsTherapeuticUses UpperrespiratorytractinfectionsOtitismediaUncomplicatedUTIAcutebacterialmeningitisinkidsTyphoidfever ACarboxypenicillinandaUreidopenicillin TicarcillinandpiperacillinTicarcillinisanti PseudomonasdrugPiperacillin tazobactamhasthebroadestspectrumGiveparentallyUsedforseriousinfections Toxicity ContraindicationsofPenicillins Hypersensitivityreactions uncommon Rash fever bronchospasm vasculitis serumsickness exfoliativedermatitis SJS anaphylaxisDrugsactashaptenswhenboundtoserumproteinsRasheswilldisappearwhendrugiswithdrawnorcantreatwithantihistaminesForpatientswithallergies switchtoadifferentclassofantibioticsortrytodesensitize Toxicity ContraindicationsofPenicillins Painandsterileinflammatoryreactionatinjectionsite dose related Largedosesgiventopatientswithrenalfailurecancauselethargy confusiontwitchingandseizuresSuddenreleaseofprocainecancausedizziness tinnitus headacheandhallucinationsPseudomembranouscolitis Cephalosporins Basemoleculeis7 aminocephalosporanicacidproducedbyaSardiniansewermoldRgroupsdeterminespectrumofactivityandpharmacologicalpropertiesMechanismofaction resistanceandclasspharmacologyessentiallythesameaspenicillins FirstGenerationCephalosporins Cefazolin cephalexin cephadroxilExcellentagainstsusceptiblestaphandstrepModestactivityagainstG Cefazolingivenparentally othersorallyMorethanhalfofthedrugisboundtoplasmaproteinsExcretedbykidneysunmetabolizedGoodforstaphandstrepskinandsofttissueinfections SecondGenerationCephalosporins Cefaclor cefuroxime cefprozilModestactivityagainstG increasedactivityagainstG worksagainstanaerobesCefaclorandcefprozilgivenorallyAbsorptionandexcretionsameasfirstgen Goodfortreatingrespiratorytractinfections intra abdominalinfections pelvicinflammatorydisease diabeticfootulcers ThirdGenerationCephalosporins Ceftaxime ceftriaxzone cefoperazone cefpodoximeBroadspectrumkillersDrugsofchoiceforseriousinfectionsNoeffectagainstListeriaandbeta lactamaseproducingpneumococciCefpodoximegivenorally othersparentallyMostexcretedbykidneyTherapeuticusesBacterialmeningitis 2exceptions LymediseaseLife threateningG sepsis FourthGenerationCephalosporin CefepimeSameantimicrobialspectrumasthirdgenerationbutresistsmorebeta lactamasesGivenparentally excellen