药理学教学课件：1-Introduction to antibacterial drugs

ChemotherapeuticDrugs

Chemotherapyisindicatedasthesubstancesthatkillorinhibitthegrowthofmicroorganisms,suchasbacteria,fungi,virusorprotozoans,orthegrowthoftumorcells.

TheyincludeI.AntimicrobialdrugAntibacterialdrugsAntifungaldrugsAntiviraldrugsII.AntiparasiticdrugsIII.Antineoplastic(anticancer)drugsAbsorption,DistributionMetabolism,Excretiondiseaseresistance

ResistanceAggressionTherelationshipsamongantimicrobialdrugs,pathogenandhostdrughostpathogenTherapeuticeffectsand

sidereactionspathopoiesis

SpecialTermsAntibiotics

arethesubstancesproduced

byvariousspeciesofmicroorganismsthatcansuppressandkillthegrowthofothermicroorganisms.

Bacteriostaticdrugs---

caninhibit

thegrowthandproliferationsofmicroorganisms,butcannotkillthem.(Macrolides-erythromycin)Bactericidaldrugs---

cannotonlysuppressthegrowthandproliferationsofmicroorganismsbutalsodestroythem.

(penicillins)Antimicrobialspectrum---

istherangeofantimicrobialaction.Itmeansthenumberofmicroorganismsthatthedrugcansuppressorkill.

broadspectrum–Ampicillin,affectawidevarietyofmicrobialspecies

narrowspectrum--Isoniazid(anantituberculosisdrug),actingonlyonasingleorlimitedgroupofmicroorganismsMinimuminhibitoryconcentration(MIC)--Thelowestconcentrationofantibioticsthatinhibitthegrowthofmicroorganismstoadegreeofvisiblenumberafterincubationinstandardconditionforabout24hours.Toprovideeffectiveantimicrobialtherapy,theclinicallyobtainableantibioticconcentrationinbodytissuesandfluidsshouldbegreaterthantheMIC.Minimumbactericidalconcentration(MBC)--Thelowestconcentrationofantimicrobialagentthatresultsina99.9%declineincolonycountafterovernightbrothdilutionincubations.Chemotherapeuticindex(CI)---usedtoevaluatethesafetyofthechemotherapeuticdrugs,expressedasLD50/ED50orLD5/ED95value,thelargerofthevalue,thesaferofthedrug.Postantibioticeffect(PAE)---isapersistentsuppressionofmicrobialgrowththatoccursafterlevelsofantibiotichavefallenbelowMIC.Isdefinedasthelengthoftimeittakesfortheculturetoachievelog-phasegrowth.Drugresistance

thereductionineffectivenessofadrugsuchasanantimicrobial,anthelmintic

oranantineoplastic

incuringadiseaseorconditionPrinciplesofAntimicrobialDrugsClassificationandMechanismofAction

InhibitingthesynthesisofthecellwallPenicillinsIncreasingthepermeabilityof

themembraneofthemicroorganism,leadingtoleakageofintracellularcompounds.(Polymyxin)InhibitingtheproteinsynthesisAminoglycosides,tetracyclines(30Sribosomalsubunits),chloramphenicol,andmacrolides(50Sribosomalsubunits).

Interferingthebacterialnucleicacid

metabolismQuinolones(inhibittoposomerases)Rifampicin(inhibitRNApolymerase)

Inhibitingfolicacidmetabolisms.Sulphonamides,Trimethoprim

DrugresistanceItreferstounresponsivenessofamicroorganismtoanAMAandisaphenomenonoftoleranceseeninhigherorganism.Resistancetoantibacterialdrugsincludenaturalandacquiredresistance.Naturalresistance

SomemicrobeshavealwaysbeenresistanttocertainAMAs.isacharacteristicofaparticularspeciesofbacteria.AGram-negativebacilliarenormallyunaffectedbypenicillinG.Thebacterialackthemetabolicprocessorthetargetsitewhichisaffectedbytheparticulardrug.Thistypeofresistancedoesnotposesignificantclinicalproblem.Acquiredresistance

Itisthedevelopmentofresistancebyanorganism(whichwassensitivebefore)duetotheuseofanAMAoveraperiodoftime.Thiscanhappenwithanymicrobeandisamajorclinicalproblem.Developmentofresistanceisdependentonthemicroorganismaswellasthedrug.ThemechanismsofdrugresistanceProductionofinactivatingenzyme.β-lactamase(penicillinases)isthemostimportantinactivatingenzyme,thathydrolyticallyinactivatetheβ-lactamringofpenicillin,cephalosporins,andrelateddrugs.ChangingthetargetstructureofthedrugactionAlterationofanantibiotic’stargetsitethroughmutationleadstoreductionofdrugaffinitytothetargetandconferorganismalresistancetooneormorerelatedantibiotics.Alterationofbacterialpenicillin-bindingproteins,resultingindecreasedbindingofβ-lactamantibiotictoitstarget.Producingmoretargetproteininordertomaintainnormalstructureandfunctionofthegerms.Producinganewtargetproteinwhichhasnormalfunction,loweraffinitytotheantibioticsandwhichdoesn’texistinthosesensitivegerms