《药理学》课程PPT教学课件（Antimicrobial Drugs）40 Macrolides, Lincomycin, Clindamycin

Macrolides 大环内酯类Lincomycin 林肯霉素Clindamycin氯林可霉素

Macrolides 大环内酯类 Lincomycin 林肯霉素 Clindamycin 氯林可霉素

1. Overview2.Macrolides 大环内酯类3. Lincomycin 林肯霉素4.Clindamycin 氯林可霉素

1. Overview 2. Macrolides 大环内酯类 3. Lincomycin 林肯霉素 4. Clindamycin 氯林可霉素

1. Overviewbacterialeucaryotic70S80Sribosomeribosomesubunits30S40S50S60SS=Svedbergunitsof sedimentationRibosomes 核糖体 are made ofRNA and proteinsatomicTheytranslate informationfromstructureofthe50smessengerRNAintonewproteinssubunitTheribosomesofbacterialandeukaryotorganismsshowdifferences

1. Overview Ribosomes 核糖体 are made of RNA and proteins They translate information from messenger RNA into new proteins The ribosomes of bacterial and eukaryot organisms show differences

Protein SynthesisaminoAAribosomeacidAAAAtransferantiRNAAAcodon(tRNA)anticodoncodoncodonPAmessengerRNA(mRNA)Tetracyclines四环素类EcompetewithtRNAfortheAsite

Protein Synthesis Tetracyclines 四环素类 compete with tRNA for the A site

bindingoftRNAAAattheAsiteaccordingtotheAAcodon-anticodonrecognitionAAAAthe P sitecontains theprotein informationantianticodoncodoncodoncodonPAAminoglycosides氨基糖贰类cause anabnormal codon-anticodon recognition by binding to the 3oS subunit

Aminoglycosides 氨基糖甙类 cause an abnormal codon￾anticodon recognition by binding to the 30S subunit

AAtranspeptidationAAAAAAantianticodoncodoncodoncodonPAChloramphenicol 氯霉素 inhibits transpeptidation

Chloramphenicol 氯霉素 inhibits transpeptidation

translocationAAAAAAAAanticodonanticodoncodoncodoncodonA4Macrolides大环内酯类Einhibits translocation

Macrolides 大环内酯类 inhibits translocation

AAAAAAAAantiAAcodonanticodoncodoncodonPA

2.Macrolides 大环内酯类Erythromycin,discovered in 1952,isproducedbyaStreptomyces bacterium. Clarithromycin and azithromycin aresemisynthetic derivatives.Like penicillin G, they are essentially active against Gram(+)organisms.Differences include:.someactivity against Mycoplasma and Chlamydia.a lesser risk of allergic reactions·abettersafetyduringpregnancy·no use against meningitidis

2. Macrolides 大环内酯类 Erythromycin, discovered in 1952, is produced by a Streptomyces bacterium. Clarithromycin and azithromycin are semisynthetic derivatives. Like penicillin G, they are essentially active against Gram(+) organisms. Differences include: •some activity against Mycoplasma and Chlamydia •a lesser risk of allergic reactions •a better safety during pregnancy •no use against meningitidis

Structures of Major MacrolidesMHCH,CHN(CHa)2OHH,CHOKCHN(CH,2HOH.CoHOOH1414H,COCHSCHHCHHOCHH,CCHSOHCHOHH.COCH,clarithromycin克拉霉素红霉素erythromycinMacrolides containalargelactoneH40N(CH)2ring.Clarithromycin andHOHCazithromycindiffer onlyslightlyHOfromerythromycin.ThosesmallOCHsCHdifferencesbroadenthedistributionCHsOHand spectrum.Thegain isessentially in pharmacokinetics.阿齐霉素azithromycin

Structures of Major Macrolides 红霉素 阿齐霉素 克拉霉素 Macrolides contain a large lactone ring. Clarithromycin and azithromycin differ only slightly from erythromycin. Those small differences broaden the distribution and spectrum. The gain is essentially in pharmacokinetics