Chapter37Aminoglycosides（氨基糖苷类）Polymyxins(.pptVIP

Chapter 37Aminoglycosides(氨基糖苷类) Polymyxins(多黏菌素类) Huifang Tang tanghuifang@zju.edu.cn Aminoglycosides （氨基苷类） Summarization of aminoglycosides The aminoglycosides are compounds contanining characteristic amino sugars joined to a hexose nucleus in glycosidic(糖苷） linkage. Most amino- glycosides, which are prepared by natural fermentation from various species of streptomyces, are a group of bactericidal drugs sharing chemical, antimicrobial, pharmacological, and toxic characteristics. Structure of streptomycin Structures of several important aminoglycoside antibiotics. Aminoglycosides （氨基苷类） Natural Aminoglycosides 链霉素(streptomycin) 庆大霉素(gentamicin) 新霉素(neomycin) 西索米星(sisomicin) 妥布霉素(tobramycin) 小诺米星(micronomicin) 卡那霉素(kanamycin) 大观霉素(spectinomycin) Semisynthetic Aminoglycosides 阿米卡星 (amikacin) 奈替米星(netilmicin) Aminoglycosides Spectrum of activity Aminoglycosides are effective against aerobic gram-negative bacteria, especially in bacteremia, sepsis, or endocarditis. Mechanism of action The mechanism of Aminoglycosides is to inhibit protein synthesis in susceptible microorganisms?. by interfering with the initiation complex of peptide formation. inducing misreading of the code on the mRNA template, which causes incorporation of inappropriate amino acid into peptide. by rupturing the polysomes into monosome, which become nonfunctional. Inhibiting protein synthesis Mechanisms of resistance Three principal mechanisms have been established: (1) production of a transferase enzyme or enzymes inactivates the aminoglycoside by adenylylation, acetylation, or phosphorylation. This is the principal type of resistance encountered clinically. (Specific transferase enzymes are discussed below.) (2) There is impaired entry of aminoglycoside into the cell. This may be genotypic, ie, resulting from mutation or deletion of a porin protein or protei