31.大環(huán)內(nèi)酯類抗生素-山東大學藥理學英文課件

1、Chapter 38Macrolides, Lincomycins and Polymycins大環(huán)內(nèi)酯類藥物14元大環(huán)內(nèi)酯類：紅霉素、羅紅霉素、克拉霉素、地紅霉素15元大環(huán)內(nèi)酯類：阿奇霉素16元大環(huán)內(nèi)酯類：螺旋霉素、乙酰螺旋霉素、麥迪霉素、麥白霉素、羅他霉素、柱晶白霉素、交沙霉素、米歐卡霉素Macrolides First generation ： 1950serythromycinSecond generation：1970sclaithromycin azithromycinThird generation：Common properties of MacrolidesAntibacte

2、rial activityFirst generationMost G+ organisms: pneumococci, streptococci, staphylococci , diphtheriae etcPart G- organisms:legionella軍團菌,bacillus pertussis(百日咳), brucella(布氏) etcOthers: mycoplasma(支原體), chlamydia trachomatis(沙眼衣原體), rickettsia(立克次體), spirochete ,anaerobes etc. Second generationMore

3、 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 ma

4、crolides: stable poDistribution Metabolism: Erythromycin&clarithromycin: in liverExcretion Erythromycin& azithromycin: bileClarithromycin: kidneyCommomly used macrolidesErythromycin Antimicrobial activityGram-positive organisms: pneumococci, streptococci, staphylococci , diphtheriae etcGram-negative

5、 organisms:legionella軍團菌,bacillus pertussis(百日咳), brucella(布氏) , meningococci, diplococcus gonorrhoeae etcOthers: mycoplasma(支原體), chlamydia trachomatis(沙眼衣原體), rickettsia(立克次體), spirochete ,anaerobes etc. ErythromycinClinical uses As penicillin substitute in penicillin-allergic or resistant patient

6、s with infections caused by staphylococci, streptococci and pneumococciPertussis，diphtheriaeLegionella and mycoplasma pneumoniaH.p infectionErythromycinAdverse reactionsGastrointestinal effectsLiver toxicityCardiotoxicity Erythromycin Erythromycin lactobionate(乳糖酸紅霉素erythromycin estolate無味紅霉素)erythr

7、omycin stearate(硬脂酸紅霉素erythromycin ethylsuccinate琥乙紅霉素， 利君沙 New macrolides antibioticsAdvantage :Broader spectrum, higher activityOrally effectiveHigh blood concentrationLonger t 1/2Less toxicityMainly used in respiratory tract infectionClarithromycin甲紅霉素,克拉霉素Has the strongest activity on Gram-posit

8、ive bacteria, legionella pneumophila, chlamydia pneumoniaeGood pharmacokinetic propertyLow toxicityAzithromycin (阿齊霉素,麗珠奇樂Has the strongest activity against mycoplasma pneumoniae肺炎支原體More effective on Gram-negative bacteriaWell toleratedT1/2 :3548h once dailyMainly used in respitory tract infectionR

9、oxithromycin 羅紅霉素，嚴迪 1987 FranceThe highest blood concentration F 72%85%Respiratory tract infection and soft tissue infectionLow adverse effectsLincomycin and ClindamycinAntimicrobial activityGram-positive organismsBacteroide fragilis and other anaerobesMechanism Binding to 50s ribosome subunit and

10、inhibiting protein synthesisPharmacokineticsAbsorbed wellPenetrate well into most tissues including bone ClindaycinClinical uses Severe anaerobic infection Acute or chronical suppurative osteomylitis , arthritis caused by susceptive organisms especially Staphylococci aureusAdverse reactionsGastroint

11、estinal effects: severe diarrhea and pseudomembranous enterocolitis caused by Clostridium difficile :vancomycin & metronidazoleOther :Impaired liver function , neutropeniaPolypeptide antibioticsVancomycin & TeicoplaninPolymyxinsbactitracinVancomycin Mechanism of actionInhibit cell wall synthesisAnti

12、microbial spectrum:Narrow spectrum, active only against gram-positive bacteria paticularly staphylococciPharmacokineticsPoorly absorbed from intestinal tract, ivExcreted from glomerular filtration 90%VancomycinClinical uses Infection caused by MRSA, MRSE and penicillin-resistant pneumococcusTreatmen

13、t of antibiotic-associated enterocolitis caused by clostridium difficile poAdverse reactionOtotoxicity & nephrotoxicityRed-man syndromeTeicoplanin Similar to vancomycin in mechanism and antimicrobial spectrumCan be given im as well as ivLess adverse reactionsPolymyxins Active only against gram-negative rods, particularly P.aeruginosaMechanism:increase permeability of cell membraneMainly used in P.aeruginosa infection when other dr