6Ototoxicity — drugs that damage the ear

FThe main offenders

Three drug classes account for most clinically important ototoxicity. The aminoglycoside antibiotics (gentamicin, amikacin, streptomycin, and the anti-tuberculosis agents) are the archetype. Platinum chemotherapy — above all cisplatin — is the leading ototoxin in oncology, and a major cause of acquired deafness in children treated for cancer. Loop diuretics (furosemide) round out the trio. Salicylates and quinine cause a usually temporary loss and are a lesser concern.

FTBase-first, high-frequency-first

The shared signature is anatomical. The outer hair cells of the basal turn — which code the high frequencies — are the most vulnerable, so damage begins there and extends apically with continued exposure. The audiogram therefore drops at the top frequencies first and only later involves the speech range. This is why ototoxicity monitoring uses high-frequency audiometry and otoacoustic emissions to catch the loss before it reaches frequencies the patient would notice.

CAminoglycosides & the mitochondrial trap

Aminoglycosides accumulate in hair cells and generate reactive oxygen species that kill them; the loss is permanent, because human outer hair cells do not regenerate. Crucially, susceptibility is partly genetic: the mitochondrial variant m.1555A>G makes the ribosome resemble the bacterial target, so a carrier can be left profoundly deaf by a single, normal dose. Because mitochondrial inheritance is maternal, a family history of “deafness after an injection” down the maternal line is a red flag — and a reason to avoid aminoglycosides in at-risk relatives.[2000]

CCisplatin & loop diuretics

Cisplatin works through similar oxidative damage to outer hair cells (and the stria), is dose-cumulative, and is especially damaging in young children — a growing source of implant candidates as childhood-cancer survival improves. Loop diuretics act differently, on the stria vascularis, lowering the endocochlear potential; their effect is usually reversible — but they potentiate aminoglycoside and platinum toxicity, so the combination is far more dangerous than either alone.

TWhy it implants well

For the implant, ototoxic deafness is relatively good news. It is a sensory lesion — dead hair cells — and the spiral ganglion is comparatively spared, at least early, so the implant's target is intact and outcomes are generally favourable. The caution is time: long-standing, complete deafness eventually drags the ganglion down too (Chapter 4), so the sparing is relative, not permanent. The ear poisoned recently is a better target than the ear poisoned decades ago.