非beta内酰胺类抗生素（英文ppt）nonbetalactam

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1、Assoc.Prof.IvanLambeve-mail:itlambev@mail.bgNONBETA-LACTAMANTIBIOTICSMedicalUniversityofSofia,FacultyofMedicineDepartmentofPharmacologyandToxicologyβ-lactamsGlycopeptidesAminoglycosidesTetracyclinesChloramphenicolMacrolidesLincosamidesRifampicinPolymyxinsANTIBIOTICS–mechanismofac

2、tionAminoglycosideshaveahexosering,eitherstreptidine(instreptomycin)or2-deoxystreptamine(otheraminoglycosides),towhichvariousaminosugarsareattachedbyglycosidiclinkages.Theyarewater-soluble,stableinsolution,andmoreactiveatalkalinethanatacidpH.I.AMINOGLYCOSIDESStreptomycinStreptomy

3、cinisanaminoglycosideantibiotic.Itsantibacterialactivityisduetoitbindingtothe30Ssubunitofthebacterialribosomeandinhibitingofproteinsynthesis.Ithasawidespectrumofanti-bacterialactivitybutisprimarilyusetotreatmycobacterialinfections(i.m.).Themainproblemsareeighthnervetoxi-city(vest

4、ibulotoxicitymorethandeaf-ness),nephrotoxicity,allergicreactions.GentamicinTobramycinMechanismsofactionAminoglycosidesareirreversibleinhibitorsofproteinsynthesis,buttheprecisemechanismforbactericidalactivityisnotknown.Theinitialeventispassivediffusionviaporinchannelsacrossthecell

5、wall.Drugisthenactivelytransportedacrossthecellmembraneintothecytoplasm.Thetransmembraneelectrochemicalgradientsuppliestheenergyforthisprocess.LowextracellularpHandanaerobicconditionsinhibittransportbyreducingthegradient.Transportmaybeenhancedbycellwall-activedrugssuchaspenicilli

6、norvancomycin;thisenhancementmaybethebasisofthesynergismoftheseantibioticswithaminoglycosides.Insidethecell,aminoglycosidesbindtospecific30S-subunitribosomalproteins.Proteinsynthesisisinhibitedbyaminoglycosidesinatleastthreeways:interferencewiththeinitiationcomplexofpeptideformat

7、ion;(2)misreadingofmRNA,whichcausesincorporationofincorrectaminoacidsintothepeptide,resultinginanonfunctionalortoxicprotein;(3)breakupofpolysomesintononfunctionalmonosomes.Theseactivitiesoccurmoreorlesssimultaneously,andtheoveralleffectisirrever-sibleandlethalforthecell.Aminoglyc

8、osidesactbactericidalondividingandnodivi