title: Biochemical basis of aminoglycoside ototoxicity.
abstract: The basis for the development of a rational explanation of aminoglycoside toxicity now appears to exist. The acute effects of these drugs are primarily based on calcium antagonism and block of ion channels. The chronic toxicity requires metabolism, and the expression of tissue-specific toxicity is a balance between synthesis of the toxin and its detoxification. Further investigations into the nature of the toxic metabolite should allow us to combine this information with previously established intracellular actions of aminoglycosides to create a unified hypothesis of action. The ability of glutathione to block toxin formation or to increase detoxification (or both) may have clinical implications for the prevention of aminoglycoside-induced ototoxicity. The clinical use of aminoglycosides has somewhat decreased over the last decade because of the introduction of the less toxic cephalosporins of the third generation and the quinolones, which are effective against Pseudomonas infections. Development of bacterial resistance against aminoglycosides is another factor, although resistance to the cephalosporins is also rapidly becoming a serious problem that eventually will limit their usefulness. Only through a detailed knowledge of the molecular basis of toxicity can we rationally pursue the development of new aminoglycosides with less ototoxic and nephrotoxic potential and devise treatments that will prevent the adverse side effects of these antibiotics.
authors.affiliation: Kresge Hearing Research Institute, University of Michigan School of Medicine, Ann Arbor.
authors.forename: J
authors.initials: J
authors.lastname: Schacht
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D001669:Biochemical Phenomena; D001671:Biochemistry; D003051:Cochlea / Q000187:drug effects*; D006311:Hearing Disorders / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents