抗生素话题英文Topical课件

TopicalAntibioticsTopicalantibioticshelppreventinfectionscausedbybacteriathatgetintominorcuts,scrapes,andburns.Treatingminorwoundswithantibioticsallowsquickerhealing.Ifthewoundsareleftuntreated,thebacteriawillmultiply,causingpain,redness,swelling,itching,andoozing.Untreatedinfectionscaneventuallyspreadandbecomemuchmoreserious.Whichbacteria?MosttopicalantibioticsaredirectedagainstStaphylococcusaureusandStreptococcuspyogenes.TheanaerobicGram-positivebacterialspeciesPropionibacteriumacneshasbeenlinkedtoacne.Whichtopicalantibioticsarecommon?Somewidelyusedtopicalantibioticsarebacitracin,neomycin,mupirocin,andpolymyxinB.AmongtheproductsthatcontainoneormoreoftheseingredientsareBactroban(aprescriptionitem),Neosporin,Polysporin,andTripleAntibioticOintmentorCream.ClassesoftopicalantibioticsCellwallsynthesisinhibitorsRibosomefunctioninhibitorsSulfadrugsBurntreatmentagentsMiscellaneousMupirocin(90%PseudomonicacidA)IsolatedfromPseudomonasfluorescensAntibacterialactivityofsubstancefromP.fluorescensnotedin1887Purifiedinthe1960’s.MupirocinworksagainstGram-positivebacteriaonlyCanbeusedtotreatMRSA(althoughresistanceisrising)Esterlinkageisrapidlyhydrolyzedhepatically,thusprecludingutilityasanoralorintravenousantibioticMupirocininhibitsbacterialisoleucyl-tRNAsynthetase.ProductscontainingMupirocinPolymyxinBPolymixinBMemberofthelipopeptideclassofantibiotics,similartodaptomycinDaptomycinPolymixinBPolymyxin:AntibacterialactivityHowever,thepolymyxinsareonlyactiveagainstgramnegativebacteria(P.aeruginosa,E.coli,K.pneumoniae),whiledaptomycinisusedtotreatgrampositivebacteriaThepolymyxinsarehighlynephrotoxicandarethusonlyusedtopicallyPolymyxins:MechanismofactionBindthethelipopolysaccharideintheoutermembrane,thusdestroyingOMintegrity.Bindtothecytoplasmicmembrane(tothephosphatidylethanolamine)andmakethemembranemorepermeable.ProductscontainingpolymyxinBBacitracinABacitracin:HistoryIsolatedbyJohnT.Goorleyin1943FoundintheinfectedcompoundfractureofthepatientMargaretTracyBacitracin:AntibacterialActivityPrimarilyusedagainstgrampositivebacteriaS.aureusandStreptococcispp.MostgramnegativeorganismsareresistantBacitracin:MechanismBacitracininterfereswithbacterialcellwallsynthesisActsbyblockingastepintheprocesswherebythekeysubunitsaretransferredfromthecytoplasmSpecificallybacitracintightlybindsundecaprenylpyrophosphate,preventingthehydrolysisintoundecaprenylphosphateThisstepisessentialforrecyclingofthecarrierLinkProductscontainingBacitracinGramicidinGramicidinSGramicidinsTheGramicidinsaresmallpeptides(15aminoacids)Some,suchasgramicidinS,arecyclicOthers,includingGramicidinA,B,C,andD,arelinearCommercialgramicidinisamixtureofcompounds,withgramicidinAbeingmajorGramicidinsGramicidinSisapowerfulantibacterialagent,withbroadrangeagainstanumberofGrampositiveandGramnegativemicroorganisms.Unfortunately,GramicidinSishemolytic,andthusislimitedtotopicaluse.Mechanismofactionisbelievedtobeatthecytoplasmicmembrane.Gramicidins:MechanismofactionThegramicidinsbehaveasionophoricsubstancesThegramicidinsselfassociate,thusformingsmallporesthatcauseleakageofessentialcationsfromthecytoplasmAgramicidinchannelGramicidinisanunusualpeptide,withalternatingD&Laminoacids.Inlipidbilayermembranes,gramicidindimerizes&foldsasaright-handedb-helix.Thedimerjustspansthebilayer.Primarystructureofgramicidin(A):HCO-L-Val-Gly-L-Ala-D-Leu-L-Ala-D-Val-L-Val-D-Val-L-Trp-D-Leu-L-Trp-D-Leu-L-Trp-D-Leu-L-Trp-NHCH2CH2OHNote:Theaminoacidsareallhydrophobic;bothpeptideendsaremodified(blocked).Theoutersurfaceofthegramicidindimer,whichinteractswiththecoreofthelipidbilayer,ishydrophobic.Ionspassthroughthemorepolarlumenofthehelix.Ionflowthroughindividualgramicidinchannelscanbeobservedifasmallnumberofgramicidinmoleculesispresentinalipidbilayerseparating2compartmentscontainingsaltsolutions.NeomycinHistorical:AminoglycosidesWaksmanandSchatzdemonstratedtheantibacterialactivityofStreptomycesgriseusin1943Streptomycinisolatedin1944NeomycinisolatedfromStreptomycesfradiaein1949NeomycinNeomycinisextremelynephrotoxic,thuslimitingitsusetoatopicalantibioticNeomycinhasexcellentactivityagainstgramnegativebacteriaandpartialactivityagainstgrampositivestrainsSomepeoplehaveallergiestoneomycinLikeotheraminoglycosides,neomycinworksbybindingtothebacterial30Sribosomalsubunit,thusinhibitingproteinsynthesis.SilversulfadiazineSulfadrugworksbynormalmechanismofinterferingwiththebiosynthesisoffolicacidHeavymetals,likesilver,seemtobetoxictobacteria,probablyduetotheirabilitytodenatureproteinsthroughreactionwithdisulfidebondsUsesUsedtotreatburnpatientsTreatmentofAcneVulgarisWhatCausesAcne?Acneisaresultofcloggingofahairfollicle,andsimultaneousactivationofthesebaceousgland(thusproducingmoresebum).Acommensalbacterium,Propionibacteriumacnes,whichlivesontheskin,butisalsopresentinthefollicle,causesinflammationandthuscontributestotheproblem.PropionibacteriumacnesKillingthebacteriacanhelpwithtreatmentofacneBenzoylPeroxideExactantibacterialmechanismisunknown,butpr