《药理学》英文课件 Chemotherapeutic medicine 3

β－LactamAntibiotics【Antibacterialactivity】PenicillinsGram-positivecoccusGram-negativecoccusGram-positivebacilliHelicoidsSemisyntheticpenicillinPenicillinase-resistantpenicillin(Oxacillin)

(1)Theykillpenicillinase-producingstaphylococci(2)Theycan’tkillMethicillin-resistantstrainsofStaphylococcusaureus(MRSA)Extendedspectrumpenicillins(Ampicillin)Theyaremoreeffectiveagainstgram-negativebacilliTheycannotkillpseudomonasaeruginosaAntipseudomonal

penicillinsCarbenicillinPiperacillinCephalosporinsFeature＋＋＋

First

Second

ThirdG＋＋＋＋＋＋＋G－＋＋＋＋＋＋Pseudomonasaeruginosa－－＋anaerobes－＋＋nephrotoxic＋＋＋－Imipenem

+cilastatinClavulanicacid+AmoxicillinOtherβ-lactamsantibioticsCarbapenemsβ-lactamaseinhibitorsMacrolides

Lincomycins

PolypeptideantibioticsChapter37

MacrolidesErythromycinClarithromycinAzithromycin

一、Erythromycin【Pharmacokinetics】ErythromycinbaseisdestroyedbygastricacidItdistributeswelltoallbodyfluidsincludingprostaticfluid,butitdoesnotenterthecerebrospinalfluid(CSF)Erythromycinisextensivelymetabolizedandisexcretedinthebile,andonly5%isexcretedintheurine.

【Antibacterialactivity】Erythromycinisbacteriostatic

Itiseffectiveagainstgram-positiveorganismsItisactiveagainstsomegram-negativeorganismsMycoplasma,Chlamydozoan,Legionellaandcampylobacteriaaresusceptible.PAPAPAtranslocaseErythromycin(50S)Inhibitproteinsynthesis【Mechanismofaction】【Clinicaluses】Gram-positivecoccusinfection

staphylococci:bouton(boil)streptococci:pharyngitis,febris

rubra

streptococcuspneumoniae:pneumoniagenuina2.Corynebacterium

diphtheriae

3.Chlamydialinfectionsurethral,endocervical,rectal,epididymal,urogenital

4.Mycoplasmalpneumonia5.Legionellapneumonia【Adverseeffect】1.GastrointestinaleffectsAnorexia,nausea,vomiting,anddiarrhea2.Cholestaticjaundice

estolateformoferythromycin3.OtotoxicityTransientdeafnessContraindications:hepaticdysfunction【Drugresistance】1.Reducedpermeabilityofthecellmembraneoractiveefflux2.Modificationoftheribosomalbindingsite3.Productionofesterasesthathydrolyzemacrolides

methylationofanadenineofthe23SbacterialribosomalRNA

二、Clarithromycin

ItsactivityagainstChlamydia,LegionellaandUreaplasmaishigherthanthatoferythromycin.Ithaslowerfrequencyofgastrointestinalintolerance三、Azithromycin

AzithromycinismoreactiveagainstHaemophilus

influenzaeandChlamydiathanerythromycinItislessactiveagainststreptococciandstaphylococciItisnowusedforurethritiscausedbyChlamydiatrachomatis.Itisrapidlyabsorbedandwelltoleratedorally.Section2Lincomycins

LincomycinClindamycin【AntibacterialactionandClinicaluses】1.Clindamycinissignificantlyeffectiveagainstanaerobicbacteria2.Itisemployedprimarilyinthetreatmentofinfectionscausedbyanaerobicbacteria3.Enterococciandclostridiumdifficileareresistant4.Itdistributeswellintobone,sotreatsmedullitis

5.Itdoesnotpenetrateintocerebrospinalfluid,notusetotreatEpidemicmeningitisalone

【Adverseeffect】FatalpseudomembranouscolitisImpairedliverfunctionvancomycin

metronidazole

Section3Polypeptideantibiotics

Vancomycinspolymyxins一、Vancomycin【Antibacterialactivity】ItisbactericidalagentItisprimarilyactiveagainstgram-positivebacteria(MRSAandMRSE),butenterococciareresistant3.Allspeciesofgram-negativebacilliandmycobacteriaareresistanttovancomycin

Vancomycin【Mechanismofaction】【ClinicaluseandAdverseeffect】1.Gram-positivebacteriainfections:pneumonia,empyema,endocarditis,osteomyelitis,andsoft-tissueabscesses,MRSAinfection2.FatalpseudomembranouscolitisduetoClostridium

difficileorstaphylococci3.Adverseeffects:ototoxicity,nephrotoxicity,"redmansyndrome二、PolymyxinsTheyarebactericidalagent,activeagainstgram-negativebacilli2.Theyincreasedpermeabilityofthebacterialmembraneresultingbacterialcelldeath3.Theyareavailableforexternalotitis,cornealulcerscausedbyPseudomonas4.Adverseeffects:nephrotoxicity,neurotoxicity,hypersensitivereactionChapter38AminoglycosidesStreptomycinNeomycinKanamycinAmikacinGentamicinTobramycin【Antibacterialactivity】

Antibacterialspectrum:AllaminoglycosidesarebactericidalTheyareeffectiveagainstaerobicgram-negativebacilliTheyareineffectiveagainstanaerobicorganismsPAPAPAaminoglycosides(30S,A)interferewiththeinitiationcomplexnonfunctionalortoxicproteinsynthesis

PADecodingbreakupofpolysomesintononfunctionalmonosomes

【Mechanismofaction】Aminoglycosidesmustbegivenparenterally

HighconcentrationsaccumulateintherenalcortexandintheendolymphandperilymphoftheinnerearAllmayaccumulateinfetalplasmaandamnioticfluid.Allarerapidlyexcretedintotheurine【Pharmacokinetics】【Clinicaluses】Aminoglycosidesaremostlyusedtotreatinfectioncausedbygram-negativebacteriaPenicillincombinationwithaminoglycosideisusedfortreatmentofenterococcal

endocarditis,streptococcalandstaphylococcalendocarditis【Adverseeffect】Ototoxicity

：vestibulardysfunctionInjuryofcochlearauditorynerveNephrotoxicity:3.Neuromuscularparalysis:4.Allergicreactions:dizziness,visualextinction,oculartremor,nausea,vomiting,ataxia.earnoiseshearingdiminutionpermanentdeafness

【Drugresistance】Synthesisofenzymesthatmodifyandinactivateaminoglycosideantibiotics.AlteredtargetsiteDecreaseduptakeofdrugChapter39TetracyclinesandChloramphenicol

Section1Tetracyclines

TetracyclineDoxycyclineDemeclocycline

Minocycline

【Antibacterialactivity】Tetracyclinesarebroadspectrumbacteriostatic

antibiotics2.Theyareactiveagainstmanygram-positiveandgram-negativebacteria3.TheyarealsoactiveagainstRickett'sorganism,helicoid,mycoplasmaandChlamydia【Mechanismofaction】tetracyclinesentermicroorganismbypassivediffusionandanenergy-dependentprocessofactivetransport.

tetracyclinesbindreversiblytothe30SsubunitofthebacterialribosomePAPATetracyclines(30S,A)【Pharmacokinetics】Tetracyclinesareadequatelybutincompletelyabsorbedafteroralingestion2.Tetracyclinescrosstheplacentalbarrierandconcentrateinfetalbonesanddentition3.Tetracyclinesaremetabolizedinliverandthenareexcretedfromkidney,exceptdoxycycline

【Clinicaluses】Rickettsialinfection:fever,chill,acheinbonesandjointsChlamydiaeinfection:pneumonia,urethritis,trachelitis,ophthalmiaandtrachomaMycoplasmainfection:mycoplasmalpneumoniaSpirochetalinfection:lymediseaseBacterialinfection:cholera【Adverseeffect】Gastricdiscomfort:Nausea,vomiting,anddiarrheaBonystructuresandTeeth:discolorationandhypoplasiaoftheteethandatemporarystuntingofgrowthFatalhepatotoxicity:inpregnantwomen

Phototoxicity:severesunburn4.Vestibularproblems:dizziness,nausea,vomiting5.Pseudotumor

cerebri:Benignintracranialhypertension,headache,blurredvision6.Superinfections:pseudomembranous

enterocolitiscausedbyClostridiumdifficile.7.Contraindications:renally-impairedpatients,pregnantorbreast-feedingwomen,orinchildren\under8yearsofage.【Drugresistance】

DecreasedintracellularaccumulationproductionofprotectedproteinsthatinterferewithtetracyclinebindingtotheribosomeEnzymaticinactivationoftetracyclinesSection2Chloramphenicol【Antibacterialaction】ChloramphenicoliseitherbacteriostaticorbactericidalItisactiveagainstbothaerobicandanaerobicgram-positiveandgram-negativeorganismsIthaseffectiveagainstrickettsiae,helicoids,Chlamydiaandmycoplasma.PAPAPeptidyl