《药理学》英文课件 Chemotherapeutic medicine 1-Antimicrobial Agents

ChemotherapeuticMedicineLiChenDepartmentofPharmacologySchoolofBasicMedicalScienceJilinUniversityAntimicrobialagentsAntiparasiticagents(44)Anticancerdrug(45)Antibacterialdrugs(35-40)Antifungaldrugs(41)AntiviraldrugsClassificationAntimicrobialAgents:GeneralConsiderationGeneralconceptMechanismofactionBacterialResistanceSection1GeneralConceptofAntimicrobialDrugsAntibacterialdrugs

Thedrugsthatinhibitorkillthebacterial,includingantibioticsandartificialdrugsAntibiotics

Theagentswhichareproducedbymicrobes,couldinhibitorkillothermicrobesgrowthandfinallydestroythem.Antibacterialspectrum

Theantibacterialrangeoftheanti-bacterialdrugsbroad-spectrumantibacterialdrugsnarrow-spectrumantibacterialdrugsBroad-spectrumantibacterialdrugsaffectawidevarietyofmicrobialspeciestetracycline,chloramphenicol,fluoroquinolonesNarrow-spectrumantibacterialdrugsactonlyonasingleoralimitedgroupsofmicroorganisms

isoniazid

Antibacterialactivity

Antibacterialdrug’scompetenceofinhibitingandkillingbacteriumBacteriostaticdrugs

Drugsthatinhibitthegrowthofthebacteriawithoutcausing

celldeathtetracyclines,macrolides,clindamycin,chloramphenicolandsulfonamidesBactericidaldrugs

Drugsthatkillbacteriaβ-lactams,Vancomycin,aminoglycosidesandfluoroquinolones.Minimalinhibitoryconcentration,MIC

ThelowestconcentrationofdrugthatinhibitsgrowthofthemicrobesMinimalbactericidalconcentration,MBCThelowestconcentrationofdrugthatkillmicrobesChemotherapeuticindex

Theratioofthetoxicdosetothetherapeuticdoseofchemotherapeuticmedicines

Post-antibioticeffect,PAE

AntibacterialactivitypersistsbeyondthetimethatmeasurabledrugispresentSection2MechanismofAntimicrobialActioncellwallsynthesisplasmamembraneintegrityProteinsynthesisnucleotide

synthesisfolatesynthesis.1.InhibitionsynthesisofbacterialcellwallFunction：1).MaintainBacterialshape2).Barrierfunction3).permeation

Cellwall:

peptidoglycanN-acetylatedmuramicacid(NAM)

N-acetylatedglucosamine(NAG)Vancomycin

-Lactamcytoplasmplasmamembranecellwall2.Increasedpermeabilityofcytoplasmicmembranes

Bacteriumlipid(phospholipid,glucolipid)proteinpolysaccharide(peptidoglycan)Fungi

ergosterol

1).Polymyxins:interactwithphospholipid2).Antifungalagents:

Polyenesbindtoergosterol

Azolesblockergosterolbiosynthesis3.InhibitionofproteinbiosynthesisRibosomeBigsubunitSmallsubunitBacterium70S50S23S,5SrRNA31proteins

30S16SrRNA21proteinsMammalian80S60S28S,5SrRNA49proteins

40S16SrRNA33proteinsPADecodingProteinBiosynthesisPAPAPATetracyclines(30S)Aminoglycosides(30S)Peptidyl

transferaseChloramphenicolLincomycin(50S)TranslocaseMacrolides(50S)Aminoglycosides(30S)1).DNAuncoiling：helicase2).primosomeandprimer：primase3).DNAreplication：

DNApolymerase DNAgyrase DNAligase4.Interferencewithnucleotidesynthesis

Rifampin:inhibitDNA-directedRNApolymeraseQuinolones:inhibitDNAgyrase,andDNAReplication5.InhibitionofthefolatemetabolismPABA+PteridineDihydropteroicacidDihydropteroate

synthaseDihydrofolateDihydrofolatereductase(DHFR)TetrahydrofolateprecursorPurine、pyrimidinenucleotideGlutamateSulfonamidesTrimethoprim

(TMP)MechanismofactionQuinolonesTetracyclinesAminoglycosides

Macrolides

ChloramphenicolLincomycinPolymyxinPolyenesAzoles

-lactamVancomycinDNAPlasmamembraneCellwallPABADHFATHFA50S50S50S30S30S30SmRNARifampinTMPSulfonamidesSection3BacterialResistance1.ClassificationofbacterialresistanceIntrinsicresistanceAcquiredresistanceGram-negativeorganismsVancomycinPseudomonasaeruginosa

Ampicillin

2.MechanismsofResistanceProductionofenzymesthatinactivatethedrugModificationoftargetsitesDecreasethepermeabilityofcellmembraneActivedrugeffluxfromthecellPenicillineresistance:

penicillinaseCephalosporinsresistance：

superbroadspectrumβ-Lactamase

（ESBLs）Lactamaseinhibitorresistance:

AmpCtypeenzymeβ-Lactamase

:1)ProductionofenzymesthatinactivatethedrugChloramphenicols:

acetyltransferase nucleosidetransferaseAminoglycosides:

phosphotransferase

acetyltransferaseMacrolides:

acetyltransferaseNonβ-Lactamase

：Modifytargetproteinbindingsite2)Modificationoftargetsites(2)ProducenewtargetproteinMacrolide

Methylationofanadenineofthe23SbacterialribosomalRNAMethicillinresistanceinstaphylococcipenicillinresistanceinpneumococciand

enterococci

NewPBPs

3)Decreasethepermeabilityofcelloutmembrane4)IncreasedactiveeffluxsystemOmpF

-lactam,Tetracyclines,Quinolones,ChloramphenicolEffluxtransporter：Accessoryprotein：outermembraneprotein：

DrugeffluxsystemIncreasedactiveeffluxsystem

-lactam,Tetracyclines,Quinolones,Chloramphenicol,Macrolides,MutationTransductionTransformationConjugation3.Transference