The effect of gentamicin and furosemide given in combination on cochlear potentials in the guinea pig.
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.
Mulheran
M
M
The MRC Toxicology Unit, Centre for Mechanisms of Human Toxicity, University of Leicester.
Harpur
E S
ES
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology*; D004357:Drug Synergism; D005665:Furosemide / Q000494:pharmacology*; D005839:Gentamicins / Q000494:pharmacology*; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects; D013997:Time Factors
D000900:Anti-Bacterial Agents; D004232:Diuretics; D005839:Gentamicins; D005665:Furosemide