Jung T T, Rhee C K, Lee C S, Park Y S, Choi D C
Loma Linda University School of Medicine, California.
Otolaryngol Clin North Am. 1993 Oct;26(5):791-810.
Salicylates and most NSAIDS in high doses cause mild to moderate temporary hearing loss, either flat or greater in the high frequencies. Hearing loss is accompanied by tinnitus and suprathreshold changes. Salicylates may or may not exacerbate hearing loss and cochlear damage induced by noise. The mechanism of salicylate ototoxicity seems to be multifactorial. Morphologic studies suggest that no permanent cochlear damage occurs with salicylate ototoxicity. Electrophysiologic, morphologic, and in vitro data conclusively demonstrate that salicylate affects outer hair cells. In addition, salicylates appear to decrease cochlear blood flow. Salicylates and NSAIDs inhibit PG-forming cyclooxygenase, and recent studies suggest that abnormal levels of arachidonic acid metabolites consisting of decreased PGs and increased LTs may mediate salicylate ototoxicity. As with salicylate, quinine ototoxicity appears to be multifactorial in origin. The mechanism includes vasoconstriction and decreases in cochlear blood flow, as measured by laser Doppler flowmetry, motion photographic studies, and histologic studies. Reversible alterations of outer hair cells also appear to play an important role, as demonstrated by histology, electron microscopy, isolated hair cell studies, and cochlear potential evaluations. Unlike with salicylate, however, the role of prostaglandins in quinine ototoxicity has not been clearly demonstrated. Also, one of quinine's principal actions, antagonism of calcium-dependent potassium channels, has yet to be investigated for its potential role in ototoxicity.
高剂量的水杨酸盐和大多数非甾体抗炎药会导致轻度至中度的暂时性听力损失，听力曲线可为平坦型或高频听力损失更明显。听力损失伴有耳鸣和阈上变化。水杨酸盐可能会加重也可能不会加重由噪声引起的听力损失和耳蜗损伤。水杨酸盐耳毒性的机制似乎是多因素的。形态学研究表明，水杨酸盐耳毒性不会导致永久性耳蜗损伤。电生理学、形态学和体外实验数据确凿地表明，水杨酸盐会影响外毛细胞。此外，水杨酸盐似乎会减少耳蜗血流量。水杨酸盐和非甾体抗炎药抑制前列腺素合成环氧化酶，最近的研究表明，由前列腺素减少和白三烯增加组成的花生四烯酸代谢物异常水平可能介导水杨酸盐耳毒性。与水杨酸盐一样，奎宁耳毒性的起源似乎也是多因素的。其机制包括血管收缩和耳蜗血流量减少，这已通过激光多普勒血流仪、动态摄影研究和组织学研究测量得到。外毛细胞的可逆性改变似乎也起重要作用，这已通过组织学、电子显微镜、分离毛细胞研究和耳蜗电位评估得到证实。然而，与水杨酸盐不同，前列腺素在奎宁耳毒性中的作用尚未得到明确证实。此外，奎宁的主要作用之一，即对钙依赖性钾通道的拮抗作用，其在耳毒性中的潜在作用尚未得到研究。
