大环内酯类药物.pptx

Chapter 38Macrolides, Lincomycins and Polymycins大环内酯类药物14元大环内酯类：红霉素、罗红霉素、克拉霉素、地红霉素15元大环内酯类：阿奇霉素16元大环内酯类：螺旋霉素、乙酰螺旋霉素、麦迪霉素、麦白霉素、罗他霉素、柱晶白霉素、交沙霉素、米欧卡霉素Macrolides First generation ： 1950’s—erythromycinSecond generation：1970’s—claithromycin azithromycinThird generation：Common properties of MacrolidesAntibacterial activityFirst generationMost G+ organisms: pneumococci, streptococci, staphylococci , diphtheriae etcPart G- organisms:legionella（军团菌）,bacillus pertussis(百日咳), brucella(布氏) etcOthers: mycoplasma(支原体), chlamydia trachomatis(沙眼衣原体), rickettsia(立克次体), spirochete ,anaerobes etc. Second generationMore active on G- organismsMechanism of actionTarget 50s ribosomal RNAMechanism inhibition of translocation of mRNAMechanism of resistanceProduction of inactivating enzymesModification of the ribosomal binding siteActive efflux systemMLSRPharmokinetics AbsorptionErythromycin: not stable at acid pHNew macrolides: stable poDistribution Metabolism: Erythromycinclarithromycin: in liverExcretion Erythromycin azithromycin: bileClarithromycin: kidneyCommomly used macrolidesErythromycin Antimicrobial activityGram-positive organisms: pneumococci, streptococci, staphylococci , diphtheriae etcGram-negative organisms:legionella（军团菌）,bacillus pertussis(百日咳), brucella(布氏) , meningococci, diplococcus gonorrhoeae etcOthers: mycoplasma(支原体), chlamydia trachomatis(沙眼衣原体), rickettsia(立克次体), spirochete ,anaerobes etc. ErythromycinClinical uses As penicillin substitute in penicillin-allergic or resistant patients with infections caused by staphylococci, streptococci and pneumococciPertussis，diphtheriaeLegionella and mycoplasma pneumoniaH.p infectionErythromycinAdverse reactionsGastrointestinal effectsLiver toxicityCardiotoxicity Erythromycin Erythromycin lactobionate(乳糖酸红霉素）erythromycin estolate（无味红霉素)erythromycin stearate(硬脂酸红霉素）erythromycin ethylsuccinate（琥乙红霉素， 利君沙） New macrolides antibioticsAdvantage :Broader spectrum, higher activityOrally effectiveHigh blood concentrationLonge