药理学教学课件：Chapter 34 Principles of Antimicrobial Therapy

Chapter34:PrinciplesofAntimicrobialTherapyI.ConceptsofChemotherapy

1.Antibiotics:2.Antimicrobialagents:3.Chemotherapy:4.Relationbetweeninteractionsofbody,Antibacterialdrugsandpathogen:BodyAntibioticsPothogen5.

ChemotherapeuticIndex:CI=LD50/ED50SafetyIndex:SI=LD5/ED956.AntibacterialSpectrum:7.AntibacterialActivity:

bacteriostatic,

minimalinhibitoryconcentration(MIC);bactericide,

minimalbactericidalconcentration(MBC).8.Postantibioticeffect(PAE):II.ThemechanismsofAntibacterialdrugs(inlater)1.inhibitthesynthesisofbacterialcellwalls:suchaspenicillins,cephalosporins;2.affectthepermeabilityofbacterialcellmembrane:suchaspolymyxin,polyeneantifungalagents;3.inhibitthesynthesisofbacterialproteins:aminoglycosides,erythromycin,tetracyclines,chloramphenicol,etc.4.influencethemetabolismofbacterialnucleicacid:suchasrifamycin,quinolones;5.blockfolatemetabolism(antimetabolites):includingTMP,Sulfonamidesetc.III.BacterialResistanceanditsformingmechanismA.

Resistance:

1.natural(intrinsic)resistance:2.acquiredresistance:mutations(1)fromapersontoanotherperson;(2)plasmid-mediated;(3)transposons-mediated.B.Multi-drugresistence:genecassette-integrons(整合子)system.C.Thetransferringwaysofdrug-resistantgene:

1.Conjugation:性纤毛or结合桥2.Transformation:recombination3.Transduction:byphageD.ThemechanismsofbacterialresistanceonAntibiotics1.

Thedrugscan’treachitstargetsite:

Permeabilityofcellwallorbarrier,

porins(孔蛋白)deficiency,activeeffluxsystem.2.Theenzymesproducedbybacteriainactivatedrugs:3.Thechangesoftargetstrucureinbacterialbody:4.Others:changesofbacterialmetabolicpathway,PABA↑E.CrossresistanceIV.ThebasicprinciplesofapplicationinAntibacterialdrugs

A.ThechoiceofdrugsstrictlyaccordingtoindicationB.TheCombinationofAntibacterialdrugs1.Theaimofdrugcombination:2.Indicationofdrugcombination:3.InteractionofdrugcombinationClassI:

bactericideinbreedingperiod,oracutebactericide.eg.Genicillins,Cephalosporins.ClassII:

bactericideinstaticperiod.eg.Aminoglycosides&Polymyxins.ClassIII:

acutebacteriostatic.eg.Macrolides,Lincomycins,Tetracyclines&Chloramphenicol.ClassIV:

chronicbacteriostatic.eg.sulfonamides,etc.I+II→potentiationI+III→antagonismI+IV→noobviousinfluence,sometimesOK.eg.P