Ototoxins

Ototoxins are substances, including certain medications and environmental agents, that can cause damage to the inner ear and vestibular system, leading to sensorineural hearing loss, tinnitus, or balance disturbances. They may affect cochlear hair cells, the stria vascularis, the spiral ganglion, or the vestibular apparatus, and effects can be temporary or permanent. The risk depends on dose, duration, individual susceptibility, and interactions with other risk factors.

Major classes of ototoxins include aminoglycoside antibiotics (such as gentamicin, amikacin, tobramycin, streptomycin), platinum-based chemotherapies (cisplatin, carboplatin, oxaliplatin), and loop diuretics (furosemide, bumetanide, ethacrynic acid). Aminoglycosides and platinum agents commonly cause irreversible cochlear damage or widespread sensorineural loss, often with high-frequency loss. Loop diuretics can cause reversible ototoxicity, particularly with rapid administration or renal impairment and in combination with other ototoxins. Other agents associated with ototoxicity include salicylates and nonsteroidal anti-inflammatory drugs at high doses (often reversible), vancomycin, certain macrolides, and exposure to industrial solvents such as toluene or n-hexane. Genetic factors, such as mitochondrial mutations, can increase susceptibility to aminoglycoside toxicity.

Clinical features typically begin as bilateral, symmetric, high-frequency sensorineural hearing loss with tinnitus; vertigo or imbalance may occur with vestibular involvement. Onset may be rapid with drugs given intravenously or gradually with chronic exposure. Risk factors include advanced age, preexisting hearing loss, kidney disease, dehydration, and concomitant use of multiple ototoxins.

Diagnosis relies on baseline and serial audiometry, otoacoustic emissions, and vestibular testing when indicated. Prevention emphasizes minimizing exposure, therapeutic drug monitoring and dose adjustments, hydration, and substituting safer alternatives when feasible. Management focuses on hearing rehabilitation, including hearing aids or cochlear implants, and vestibular therapy as needed. Prognosis varies by agent and exposure, with many cases more favorable when detected early and the offending agent withdrawn.