Ototoxicity, drug-induced

Schacht J, Hawkins JE (2006) Sketches of otohistory. Part 11 ototoxicity drug-induced hearing loss. Audiol Neurootol ll(l) l-6... 

The ototopical antimicrobial preparations stated earlier suffice for most cases of otitis externa and selected cases of chronic suppurative otitis. However, these compounds have a limited effect in certain patients with resistant strains of bacteria, drug-induced allergies, or a tympanic membrane perforation that requires administration into the middle ear space. In the last case, ototopical preparations may cause pain because of the acidic pH or the presence of alcohol. Ototoxicity of neomycin, polymyxin B, and colistin is also of concern, and many otolaryngologists prefer topical ophthalmic preparations.f Ophthalmic preparations are discussed in the article Ocular Drug Formulation and Delivery in this volume. 

Huang MY, Schacht J. Drug-induced ototoxicity. Pathogenesis and prevention. Med Toxicol Adverse Drug Exp 1989 4(6) 452-67. 

It serves to illustrate this point that kanamycin — an ototoxic drug — has been found to increase the expression of EAATl in the inner ear (Matsuda et al., 1999). This change is likely to be compensatory and to have a neuroprotective effect. A possibility to be tested is whether EAATl expression is induced by high glutamate concentrations, such as those that are likely to occur when glutamate is lost from collapsing hair cells (Matsuda et al., 2000). 

Matsuda K, Komune S, Tono T, Yamasaki M, Haruta A, Kato E (2000) A role of glutamate in drug-induced ototoxicity in vivo microdialysis study combined with on-line enzyme fluorometric detection of glutamate in the guinea pig cochlea. Brain Res 852 492-495. 

The primary symptoms of drug-induced ototoxicity are the occasional to frequent cochlear signs of tinnitus and, in most cases, reversible hearing loss and the vestibular signs of light-headedness, nystagmus, ataxia, and vertigo. 

G. Occupational ototoxicity is common but is usually noise induced rather than chemical related. Preexisting noise-induced hearing loss may magnify the impact of common ototoxic drugs. 

Lue A, Brownell W (1999) Salicylate induced changes in outer hair cell lateral wall stiffness. Hear Res 135(1-2) 163-168. doi 10.1016/80378-5955(99)00102-1 Matsuda K, Komune S, Tono T, Yamasaki M, Haruta A, Kato E (2000) A role of glutamate in drug-induced ototoxicity in vivo microdialysis study combined with on-line enzyme fluoro-metric detection of glutamate in the guinea pig cochlea. Brain Res 852(2) 492-495. doi 10. 1016/80006-8993(99)02265-9... 

In man, differences in the ototoxic risks of the currently used aminoglycosides are difficult to evaluate (20). There have been no prospective comparisons of more than two drugs using the same criteria in similar patient populations. However, several controlled comparisons of two aminoglycosides are available and provide some information. A survey of 24 such trials showed the following mean frequencies of ototoxicity gentamicin 7.7%, tobramycin 9.7%, amikacin 13.8%, netilmicin 2.3% (28). There was also a lower incidence of netilmicin-induced inner ear damage compared with tobramycin in two studies (29,30). 

The risk of ototoxicity from gentamicin in children is probably less than in adults. In many studies of serious neonatal infections treated with gentamicin there have been very few cases that have provided unequivocal evidence of gentamicin-induced ototoxicity. Gentamicin can be an excellent drug in neonatal sepsis, and its potential toxicity should not preclude its use when it is needed. 

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