Selimoglu Erol
Inonu University, Department of Otorhinolaryngology, Malatya, Turkey.
Curr Pharm Des. 2007;13(1):119-26. doi: 10.2174/138161207779313731.
It has long been known that the major irreversible toxicity of aminoglycosides is ototoxicity. Among them, streptomycin and gentamicin are primarily vestibulotoxic, whereas amikacin, neomycin, dihydrosterptomycin, and kanamicin are primarily cochleotoxic. Cochlear damage can produce permanent hearing loss, and damage to the vestibular apparatus results in dizziness, ataxia, and/or nystagmus. Aminoglycosides appear to generate free radicals within the inner ear, with subsequent permanent damage to sensory cells and neurons, resulting in permanent hearing loss. Two mutations in the mitochondrial 12S ribosomal RNA gene have been previously reported to predispose carriers to aminoglycoside-induced ototoxicity. As aminoglycosides are indispensable agents both in the treatment of infections and Meniere's disease, a great effort has been made to develop strategies to prevent aminoglycoside ototoxicity. Anti-free radical agents, such as salicylate, have been shown to attenuate the ototoxic effects of aminoglycosides. In this paper, incidence, predisposition, mechanism, and prevention of aminoglycoside-induced ototoxicity is discussed in the light of literature data.
长期以来,人们一直知道氨基糖苷类药物的主要不可逆毒性是耳毒性。其中,链霉素和庆大霉素主要具有前庭毒性,而阿米卡星、新霉素、双氢链霉素和卡那霉素主要具有耳蜗毒性。耳蜗损伤可导致永久性听力丧失,而前庭器官损伤则会导致头晕、共济失调和/或眼球震颤。氨基糖苷类药物似乎会在内耳中产生自由基,随后对感觉细胞和神经元造成永久性损伤,导致永久性听力丧失。此前有报道称,线粒体12S核糖体RNA基因中的两种突变会使携带者易患氨基糖苷类药物所致耳毒性。由于氨基糖苷类药物在治疗感染和梅尼埃病方面都是不可或缺的药物,人们已付出巨大努力来制定预防氨基糖苷类药物耳毒性的策略。已证明抗自由基药物(如水杨酸盐)可减轻氨基糖苷类药物的耳毒性作用。本文根据文献数据对氨基糖苷类药物所致耳毒性的发生率、易感性、机制及预防进行了讨论。