TAILIEUCHUNG - Chapter 127. Treatment and Prophylaxis of Bacterial Infections (Part 3)

Inhibition of Protein Synthesis Most of the antibacterial agents that inhibit protein synthesis interact with the bacterial ribosome. The difference between the composition of bacterial and mammalian ribosomes gives these compounds their selectivity. Aminoglycosides Aminoglycosides (gentamicin, kanamycin, tobramycin, streptomycin, neomycin, and amikacin) are a group of structurally related compounds containing three linked hexose sugars. They exert a bactericidal effect by binding irreversibly to the 30S subunit of the bacterial ribosome and blocking initiation of protein synthesis. Uptake of aminoglycosides and their penetration through the cell membrane constitute an aerobic, energy-dependent process. Thus, aminoglycoside activity is markedly reduced in an anaerobic environment | Chapter 127. Treatment and Prophylaxis of Bacterial Infections Part 3 Inhibition of Protein Synthesis Most of the antibacterial agents that inhibit protein synthesis interact with the bacterial ribosome. The difference between the composition of bacterial and mammalian ribosomes gives these compounds their selectivity. Aminoglycosides Aminoglycosides gentamicin kanamycin tobramycin streptomycin neomycin and amikacin are a group of structurally related compounds containing three linked hexose sugars. They exert a bactericidal effect by binding irreversibly to the 30S subunit of the bacterial ribosome and blocking initiation of protein synthesis. Uptake of aminoglycosides and their penetration through the cell membrane constitute an aerobic energy-dependent process. Thus aminoglycoside activity is markedly reduced in an anaerobic environment. Spectinomycin an aminocyclitol antibiotic also acts on the 30S ribosomal subunit but has a different mechanism of action from the aminoglycosides and is bacteriostatic rather than bactericidal. Macrolides Ketolides and Lincosamides Macrolide antibiotics erythromycin clarithromycin and azithromycin consist of a large lactone ring to which sugars are attached. Ketolide antibiotics including telithromycin replace the cladinose sugar on the macrolactone ring with a ketone group. These drugs bind specifically to the 50S portion of the bacterial ribosome and inhibit protein chain elongation. Although structurally unrelated to the macrolides lincosamides clindamycin and lincomycin bind to a site on the 50S ribosome nearly identical to the binding site for macrolides. Streptogramins Streptogramins quinupristin streptogramin B and dalfopristin streptogramin A which are supplied as a combination in Synercid are peptide macrolactones that also bind to the 50S ribosomal subunit and block protein synthesis. Streptogramin B binds to a ribosomal site similar to the binding site for macrolides and lincosamides whereas streptogramin A binds to a

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