Understanding drug ototoxicity: molecular insights for prevention and clinical management

Abstract

Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and antimalarial medications. Because their benefits in combating certain life-threatening diseases often outweigh the risks, the use of these ototoxic drugs cannot simply be avoided. In this review, the authors discuss some of the most frequently used ototoxic drugs and what is currently known about the cell and molecular mechanisms underlying their noxious effects. The authors also provide suggestions for the clinical management of ototoxic medications, including ototoxic detection and drug monitoring. Understanding the mechanisms of drug ototoxicity may lead to new strategies for preventing and curing drug-induced hearing loss, as well as developing new pharmacological drugs with less toxic side effects.

Keywords::

• aminoglycoside
• auditory system
• drug ototoxicity
• hair cells
• inner ear
• vestibular system

Acknowledgements

This work was made possible by Grants 005220 and 005335 from NIDCD-NIH, and the support of House Ear Institute. The authors would like to thank Drs Anne Anglim and Paul Webster for critically reading the manuscript.