Chpt 44 中 Aminoglycosides.pptVIP

Ⅰ.Introduction 1. Aminoglycosides are a group of bactericidal antibiotics. They are obtained from various Streptomyces species They contain amino sugars linked to an aminocyclitol氨基环醇ring by glycosidic bonds. They share chemical, antimicrobial, pharmacological, and toxic characteristics. 4. Aminoglycosides include: gentamicin 庆大霉素 streptomycin 链霉素 tobramycin 妥布霉素 amikacin 阿米卡星 kanamycin卡那霉素 neomycin新霉素 astromicin阿司米星 netilmicin奈替米星 Streptomycin is the oldest and best-studied of the aminoglycosides. Gentamicin, tobramycin, and amikacin are the most widely employed aminoglycosides at present. Neomycin and kanamycin are now largely limited to topical or oral use. 1. Physical and chemical properties (1) Aminoglycosides have a 6-membered ring, either streptidine 链霉胍 (in streptomycin) or 2-deoxystreptamine 链霉胺 (other aminoglycosides), to which various amino sugars are attached by glycosidic linkages (2) Aminoglycosides are water-soluble, stable in solution, and more active at alkaline than at acid pH. Sodium bicarbonate increases the activity. (3) Aminoglycosides frequently exhibit synergism with beta lactams. (4) At high concentration, aminoglycosides may complex with beta-lactam drugs, resulting in loss of activity, and they should not be mixed together for administration (in buttock, i.m.) 2. Pharmacokinetics (1) Aminoglycosides are hardly absorbed orally. (2) They are well absorbed intramuscularly, giving peak concentrations in blood within 30～90 min. (3) They do not enter cells readily and no significant metabolism by liver. (4) Aminoglycosides are cleared by the kidneys. (5) Normal t 1/2 is 2～3 h. increasing to 24～48 h in patients with significant impairment of renal function. Their monitoring of plasma levels is an important requirement for safe and effective dosage selection. a. Bactericidal activity is in concentration dependent manner. b. Antibacterial activit