Ototoxicity is the property of being toxic to the ear (oto-), specifically the cochlea or auditory nerve and sometimes the vestibular system, for example, as a side effect of a drug. The effects of ototoxicity can be reversible and temporary, or irreversible and permanent. It has been recognized since the 19th century. There are many well-known ototoxic drugs used in clinical situations, and they are prescribed, despite the risk of hearing disorders, to very serious health conditions.

Ototoxicity came to the forefront of clinical attention with the discovery of streptomycin in 1944. Streptomycin was used successfully in the treatment of tuberculosis; however, a substantial number of treated patients were found to develop irreversible cochlear and vestibular dysfunction.

Ototoxic drugs

Ototoxic drugs include antibiotics such as gentamicin, streptomycin, tobramycin, loop diuretics such as furosemide and platinum-based chemotherapy agents such as cisplatin and carboplatin. A number of nonsteroidal anti-inflammatory drugs (NSAIDS) have also been shown to be ototoxic. This can result in sensorineural hearing loss, dysequilibrium, or both. Some environmental and occupational chemicals have also been shown to affect the auditory system and interact with noise.

Factors affecting ototoxicity: Dose, Duration of therapy, Concurrent renal failure, Infusion rate, Lifetime dose, Coadministration with other drugs having ototoxic potential and Genetic susceptibility.

Ototoxic drugs should not be used for otic topical application when the tympanic membrane is perforated because the drugs might diffuse into the inner ear.

Prevention

Ototoxic antibiotics should be avoided during pregnancy, because they can damage the fetal labyrinth. The elderly and people with preexisting hearing loss should not be treated with ototoxic drugs if other effective drugs are available. The lowest effective dosage of ototoxic drugs should be used and levels should be closely monitored, particularly for aminoglycosides (both peak and trough levels).

If possible before treatment with an ototoxic drug, hearing should be measured and then monitored during treatment; symptoms are not reliable warning signs. The risk of ototoxicity increases with the use of multiple drugs with ototoxic potential and the use of ototoxic drugs excreted through the kidneys in patients with renal compromise; in such cases, closer monitoring of drug levels is advised. In patients known to have mitochondrial DNA mutations that predispose to aminoglycoside toxicity, aminoglycosides should be avoided.

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Regards

Mary Wilson

Editorial office

Clinical Pharmacology and Toxicology Research

E-mail: pharmatoxicol@eclinicalsci.com