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Aminoglycosides.

Source

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.
2019 Apr 12.

Excerpt

The aminoglycosides are natural products and semisynthetic derivatives from a variety of actinomycetes and have potent activity against many gram negative bacteria. The first aminoglycoside used in clinical practice was streptomycin which was derived from Streptomyces griseus and was the first effective agent against mycobacterium tuberculosis. The discovery and characterization of the antibacterial activity of streptomycin led to the award of the Nobel Prize in Medicine to Selman Waksman and his coworkers. The aminoglycosides have a common structure of two or more amino sugars joined in glycosidic linkage to a hexose nucleus. The aminoglycosides are believed to act by binding to ribosomes of bacteria and blocking protein synthesis. Aminoglycosides in current use in the United States include streptomycin, gentamicin, tobramycin, amikacin, plazomicin and neomycin. The aminoglycosides are poorly absorbed orally and typically are given parenterally, either by intravenous or intramuscular injection. Gentamicin, tobramycin and amikacin are given parenterally and are used for severe gram negative bacterial infections usually in combination with penicillins or cephalosporins. Streptomycin is now rarely used and largely as adjunctive therapy of multi-drug resistant tuberculosis. Plazomicin is a recently introduced agent and is given intravenously as monotherapy for complicated urinary tract infections or acute pyelonephritis. Plazomicin is a semi-synthetic aminoglycoside which has been modified to evade conventional forms of aminoglycoside resistance. Neomycin is used orally to treat hepatic encephalopathy. Because it is poorly absorbed orally, neomycin causes a decrease in intestinal bacteria, thereby decreasing ammonia production and absorption from the colon. The aminoglycosides all have serious toxicities which often limit their applicability and the dose and duration of therapy. The common serious adverse effects of the aminoglycosides are ototoxicity, neuropathy and nephrotoxicity. Liver injury from the aminoglycosides is rare, perhaps because the other side effects of aminoglycosides limit the amount that can be given. Isolated case reports of idiosyncratic hepatotoxicity have been published for most, but not all of the aminoglycosides. These resports have not always been very convincing.

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