Chapter 38 Aminoglycosides Shutcm-MBL 1

Commonly used aminoglycosides Gentamicin (庆大霉素) Streptomycin (链霉素) Amikacin （ 阿米卡星、丁胺卡那霉素） Netilmicin (奈替米星) Kanamycin (卡那霉素) Tobramycin (妥布霉素) Neomycin (新霉素) Shutcm-MBL

Pharmacokinetics 1. Oral absorption: poor (be given parenterally); be given orally to eradicate intestinal bacteria; 2. Excretion: rapidly excreted by the kidney; short half-lives; 3. Distribution: do not cross the blood-brain barrier, but they cross the placenta; Blood concentrations should be measured to guide dosing. Shutcm-MBL

Antibacterial mechanism: Spectrum of activity: 1. Active against many Gram-negative bacteria (including Pseudomonas species ) and some Gram-positive bacteria. 2. Streptomycin: Mycobacterium tuberculosis 3. Inactive against anaerobes, which are unable to take up the aminoglycosides; Antibacterial mechanism: Inhibit bacterial protein synthesis (bactericidal) 假单胞菌 结核杆菌 Shutcm-MBL

Indications: infections caused by sensitive gram-negative bacilli (urinary, respiratory, and biliary systems); Drug resistance: 1. Production of enzymes that acetylate, phosphorylate or adenylyl aminoglycosides; 2. Reduced penetration of the drug (can be overcome by co-administration of antibacterials that disrupt cell wall synthesis , such as penicillins); 3. Changes in the ribosomal proteins in bacteria; Streptomycin has cross-resistance with getamicin, kanamycin and neomycin Shutcm-MBL

Adverse reactions Ototoxicity: disturbances of balance or deafness that are often irreversible; caused by accumulation of the aminoglycoside in the inner ear. Nephrotoxicity: usually reversible; defect in the concentrating ability of the kidney, with mild proteinuria followed by a reduction in the glomerular filtration rate; caused by retention of aminoglycosides in the proximal tubular cells of the kidney; Neuromuscular blockade: usually occurs when used with anesthetic drugs; Allergic reactions Shutcm-MBL

Gentamycin [,dʒentə‘maisin] 庆大霉素 Uses: 1. Infection by gram-negative bacilli 2. Pseudomonas aeruginosa: in combination with carbencillin; 3. bacterial endocarditis: with penicillin 4. Polyinfection: with cephalosporin or carbencillin ； 5. Oral: bowel infection, helicobacter pylori ulcer. 绿脓杆菌 羧苄西林 幽门螺杆菌溃疡 Shutcm-MBL

Streptomycin Uses: pestis , tuberculosis (second line) Amikacin Uses: Infection by gram-negative bacilli more resistant to modifying enzyme Shutcm-MBL