Mulheran M, Harpur E S
The MRC Toxicology Unit, Centre for Mechanisms of Human Toxicity, University of Leicester.
Br J Audiol. 1998 Feb;32(1):47-56. doi: 10.3109/03005364000000050.
Single doses of gentamicin and furosemide given in combination result in a rapid and profound loss of cochlear function. In this study, measurement of three gross cochlear potentials (cochlear microphonics, compound action potentials and the endocochlear potential) were carried out in order to determine the ototoxic sites of action of the drugs given in combination. The rapidity and severity of the cochlear deficit is dose dependent and with the doses employed in this study (80 mg/kg gentamicin i.v. 80 mg/kg furosemide i.v.), complete loss of cochlear function is seen after about 72 hours. Twenty-four hours after i.v. administration of the drugs, significant increases in compound action potential thresholds between 6 and 32 kHz were seen. In contrast, over this frequency range the generation of cochlear microphonics in response to stimulus levels of 70 dB SPL appeared to be unaffected. The endocochlear potential remained unaffected at 24 and 72 hours after administration. These findings are taken as evidence that the primary site of ototoxic action of the two drugs in combination may be at the level of the inner hair cells and/or the afferent synapse.
单次联合给予庆大霉素和速尿会导致耳蜗功能迅速且严重丧失。在本研究中，通过测量三种总体耳蜗电位（耳蜗微音电位、复合动作电位和内淋巴电位）来确定联合用药的耳毒性作用部位。耳蜗功能缺损的速度和严重程度取决于剂量，在本研究使用的剂量下（静脉注射80mg/kg庆大霉素和80mg/kg速尿），约72小时后耳蜗功能完全丧失。静脉给药24小时后，6至32kHz之间的复合动作电位阈值显著升高。相比之下，在此频率范围内，对70dB SPL刺激水平产生的耳蜗微音电位似乎未受影响。给药后24小时和72小时，内淋巴电位均未受影响。这些发现被视为联合使用这两种药物的耳毒性作用主要部位可能在内毛细胞和/或传入突触水平的证据。
