Structure side-effect sorting of drugs. VI. Ototoxicities

From a literature survey, over 130 (about 7.8%) drugs and chemicals have been associated with ototoxicities. The major classes are basic aminoglycoside and other antibiotics, anti-inflammatory drugs, antimalarials, beta-blockers, antineoplastic agents, heavy metals, diuretics, some topical agents and various miscellaneous drugs. Possible mechanisms of action are presented and discussed. These include inhibition of protein synthesis, the glycolytic cycle, the TCA cycle, energy utilization, energy generation and the respiratory system within the mitochondria membrane of the hair cell, and also alteration of the permeability of the endolymphatic membrane or alteration of the excretion system for the basic aminoglycosides in the lateral wall of the membranous cochlea. The relative rank order of ototoxicity and reactivity toward mucopolysaccharides of five aminoglycosides is found to be related to the number of basic groups in each molecule.