Huang M Y, Schacht J
Kresge Hearing Research Institute, University of Michigan, Ann Arbor.
Med Toxicol Adverse Drug Exp. 1989 Nov-Dec;4(6):452-67. doi: 10.1007/BF03259926.
Ototoxicity is a disabling adverse effect of several widely used classes of drugs, such as diuretics, anti-inflammatory agents, antineoplastic agents and aminoglycoside antibiotics. High-dose therapy with either diuretics or anti-inflammatory agents is primarily associated with acute and transient impairment of hearing or tinnitus. In contrast, long term treatment with antineoplastic agents or aminoglycoside antibiotics is typically associated with delayed and irreversible loss of hearing; lesion in the organ of Corti include the destruction of auditory sensory cells. Vestibular function can also be compromised by ototoxic drugs. Occasional cases of ototoxicity have been reported for a variety of other therapeutic compounds and environmental toxins. In addition, the simultaneous administration of multiple agents which are potentially ototoxic can lead to synergistic loss of hearing. Exposure to loud noise may also potentiate the hearing loss due to cochleotoxic drugs. Ototoxic agents can impair the sensory processing of sound at many cellular or subcellular sites. However, the molecular mechanisms of ototoxicity have not been established for most of these drugs, and structure-toxicity relationships have not been determined. It has therefore been difficult to predict the ototoxic potential of new drugs, and rational approaches to the prevention of ototoxicity are still lacking. The clinical and experimental features of ototoxicity are reviewed for several classes of drugs, with an emphasis on current knowledge of the mechanism and the possibilities for the prevention of ototoxicity for each.
耳毒性是几类广泛使用的药物的一种致残性不良反应，如利尿剂、抗炎药、抗肿瘤药和氨基糖苷类抗生素。大剂量使用利尿剂或抗炎药主要与听力急性短暂受损或耳鸣有关。相比之下，长期使用抗肿瘤药或氨基糖苷类抗生素通常与听力延迟且不可逆丧失有关；柯蒂氏器的病变包括听觉感觉细胞的破坏。耳毒性药物也会损害前庭功能。已报道多种其他治疗性化合物和环境毒素偶尔会导致耳毒性。此外，同时使用多种具有潜在耳毒性的药物可导致协同性听力丧失。暴露于高强度噪声也可能增强由耳蜗毒性药物引起的听力损失。耳毒性药物可在许多细胞或亚细胞位点损害声音的感觉处理。然而，大多数这类药物的耳毒性分子机制尚未明确，结构与毒性的关系也未确定。因此，很难预测新药的耳毒性潜力，目前仍缺乏预防耳毒性的合理方法。本文综述了几类药物耳毒性的临床和实验特征，重点介绍了目前对其机制的认识以及各类药物预防耳毒性的可能性。
