Summary
Aspirin, the prototype of the salicylates, is a ubiquitous agent. The availability of aspirin, other salicylates and nonsteroidal anti-inflammatory drugs (NSAIDs) as prescription and over-the-counter medications means there is a wealth of clinical experience with these agents. Among the documented adverse effects of aspirin is the potential for ototoxicity. Tinnitus and hearing loss, usually reversible, are associated with acute intoxication and long term administration of salicylates. A range of measured serum concentrations are reported as correlating with documented ototoxicity (19.6 to >67 mg/dl). Most case reports are based on total serum salicylate concentrations whereas unbound serum salicylate concentrations appear to reflect more closely the risk of ototoxicity.
The pathophysiology of toxicity may be related to biochemical and subsequent electrophysiological changes in the inner ear and eighth cranial nerve impulse transmission. Localised drug accumulation and vasoconstriction in auditory microvasculature may be mediated by the antiprostaglandin activity of these agents. Ototoxicity, although not life-threatening, may add to the morbidity of patients taking salicylates or NSAIDs in therapeutic and toxic doses.
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References
Anniko M. Principles in cochlear toxicity. Archives of Toxicology 8 (Suppl.): 221–239, 1985
April P, Albert M, Deighton MN, Termudo C. Tolmetin: a new non-steroidal antinflammatory. In Ward (Ed.) Proceedings of a Symposium on Tolmetin. pp. 62–70, Excerpta Medica, New York, 1975
Aylward, M. Tinnitus and deafness associated with benorylate. British Medical Journal 2: 118, 1973
Ballantyne J. Iatrogenic deafness. Journal of Laryngology and Otology 84: 967–1000, 1970
Boettcher FA, Bancroft BR, Salvi RJ, Henderson D. Effects of sodium salicylate on evoked-response measures of hearing. Hearing Research 42: 129–142, 1989
Cazals Y, Li XQ, Aurousseau C, Didier A. Acute effects of nor-adrenaline related vasoactive agents on the ototoxicity of aspirin: an experimental study in the guinea pig. Hearing Research 36: 89–96, 1988
Chapman, P. Naproxen and sudden hearing loss. Journal of Laryngology and Otology 96: 163–166, 1982
Crifo S. Aspirin ototoxicity in the guinea pig. Oto-Rhino-Laryngology 37: 27–34, 1975
Davies MG, Briffa DV, Greaves MW. Systemic toxicity from topically applied salicylic acid. British Medical Journal 1: 661, 1979
Davis JD, Struth AB, Turner RA, Pisko EJ, Ruchte IR. Pirprofen and aspirin in the treatment of rheumatoid arthritis. Clinical Pharmacology and Therapeutics 25: 618–623, 1979
Day RO, Graham GG, Bieri D, Brown M, Cairns D, et al. Concentration-response relationships for salicylate-induced ototoxicity in normal volunteers. British Journal of Clinical Pharmacology 28: 695–702, 1989
Diamond HS. Double blind cross over study of fenoprofen and aspirin in osteoarthritis. Journal of Rheumatology 3 (Suppl. 2): 67–70, 1976
Dick-Smith JB. Ibuprofen, aspirin and placebo in the treatment of osteoarthritis — a double blind clinical trial. Medical Journal of Australia 56: 853–859, 1969
Ellenhorn MJ, Barceloux DG. In Medical toxicology: diagnosis and treatment of human poisoning, Elsevier, New York, 1988
Escoubet B, Amsallem P, Ferray E, Tran Ba Huy P. Prostaglandin synthesis by the cochlea of the guinea-pig: influence of aspirin, gentamicin, and acoustic stimulation. Prostaglandins 29: 589–599, 1985
Evans EF, Borerwe TA. Ototoxic effects of salicylates on the responses of of single cochlear nerve fibres and on cochlear potentials. British Journal of Audiology 16: 101–108, 1982
Gum OB. Long-term efficacy and safety of benoxaprofen: comparison with aspirin and ibuprofen in patients with active rheumatoid arthritis. Journal of Rheumatology 7 (Suppl.): 76–88, 1980
Hill HF, Hill AG, Mowat AG, Ansell BM, Matthews JA, et al. Naproxen: a new non-hormonal anti-inflammatory agent. Annals of Rheumatic Diseases 33: 12–19, 1974
Hope-Simpson RE. Toxicity of benorylate. British Medical Journal 1: 296, 1973
Insel PA. Analgesic-antipyretics and antiinflammatory agents: drugs employed in the treatment of rheumatoid arthritis and gout. In Goodman & Gilman (Eds) The pharmacological basis of therapeutics, 8th ed., Pergamon Press, Inc., Elmsford, 1990
Jardini L, Findlay R, Burgi E, Hinderer K, Agarwal A. Auditory changes associated with moderate blood salicylate levels. Rheumatology and Rehabilitation 17: 233–236, 1978
Jung TTK, Woo HY, Baer W, Miller S, Juhn SK. Effect of non-steroidal anti-inflammatory drugs on the hearing and prostaglandin levels in the perilymph. Otolaryngology and Head and Neck Surgery 99: 154–155, 1988
Koegel Jr RL. Ototoxicity: a contemporary review of aminoglycosides, loop diuretics, acetylsalicylic acid, quinine, erythromycin, and cisplatinum. American Journal of Otolaryngology 6: 190–199, 1985
Majerus PW, Broze GJ, Miletich JP, Tolefson D. Anticoagulant, thrombolytic, and antiplatelet drugs. In Goodman & Gilman (Eds) The pharmacological basis of therapeutics, 8th ed., Pergamon Press, Inc., Elmsford, 1990
McCabe PA, Dey FL. The effect of aspirin upon auditory sensitivity. Annals of Otolaryngology 74: 312–325, 1965
McFadden D, Plattsmeier HS. Aspirin abolishes spontaneous otoacoustic emissions. Journal of the Accoustical Society of America 76: 433–438, 1984
McFadden D, Plattsmeier HS, Pasanen EG. Aspirin-induced hearing loss as a model of sensorineural hearing loss. Hearing Research 16: 251–260, 1984
Miller JJ. Nonsteroidal anti-inflammatory drugs. In CRC Handbook of Ototoxicity, pp. 73–85, CRC Press, Boca Raton, 1985
Miller RR. Deafness due to plain and long-acting aspirin tablets. Journal of Clinical Pharmacology 18: 468–471, 1978
Mitchell C, Brummett RE, Himes D, Vernon J. Electrophysiological study of the effect of sodium salicylate upon the cochlea. Archives of Otolarynology 98: 297–301, 1973
Mongan E, Kelly P, Nies K, Porter WW, Paulus HE. Tinnitus as an indication of therapeutic serum salicylate levels. Journal of the American Medical Association 226: 142–145, 1973
Myers EN, Bernstein JM. Salicylate ototoxicity. Archives of Otolaryngology 82: 483–493, 1965
Pinals RS, Frank S. Relative efficacy of indomethacin and acetylsalicylic acid in rheumatoid arthritis. New England Journal of Medicine 276: 512–514, 1967
Porter J, Jick H. Drug induced anaphylaxis, convulsions, deafness and extrapyramidal symptoms. Lancet 1: 587–578, 1977
Ramsden RT, Latif A, O’Malley S. Electrocochleographic changes in acute salicylate overdosage. Journal of Laryngolology and Otology 9: 1269–1273, 1985
Rowland M, Tozer TN. Clearance and renal excretion. In Clinical pharmacokinetics: concepts and applications, Lea & Febiger, Philadelphia, 1980
Schulz P, Perrier CV, Ferber-Perret F, Vanden Heuval WJA, Steelman SL. Diflunisal, a new acting analgesic and prostaglandin inhibitor: effect of concomitant acetylsalicylic acid therapy on ototoxicity and on disposition of both drugs. Journal of International Medical Research 7: 61–68, 1979
Silverstein H, Griffin WL. Biochemistry of the inner ear fluids in the cat. In Paparella (Ed.) Biochemical mechanisms in hearing and deafness, Research Otology Symposium, University of Minneapolis, Minneapolis 1969, pp. 221–248, CC Thomas, Springfield, 1970
Stebbins WC. Studies of hearing and hearing loss in the monkey. In Stebbins (Ed.) Animal psychophysics, pp. 41–66, Appleton-Century-Crofts, New York, 1970
Tempero KF, Cirillo VJ, Steelman SL. Diflunisal: a review of pharmacokinetics and pharmacodynamic properties, drug interactions, and special tolerability studies in humans. British Journal of Clinical Pharmacology 4 (Suppl. 1): 31S–36S, 1977
Viara M. Essai clinique, en double ensu, du clopirac et de l’in-dométhacine dans l’arthrite rhumatoide. Journal Belgique de Rhumatologie et de Médecine Physique 30: 123–130, 1975
Wasner C, Britton MC, Kraines G, Kaye RL, Bobrow AM, et al. Non-steroidal anti-inflammatory agents in rheumatoid arthritis and ankylosing spondylitis. Journal of the American Medical Association 246: 2168–2172, 1981
Woodford, CM, Henderson D, Hamernik RP. Effects of combinations of sodium salicylate and noise on the auditory threshold. Annals of Otology Rhinology and Laryngology 87: 117–127, 1978
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Brien, Ja. Ototoxicity Associated with Salicylates. Drug-Safety 9, 143–148 (1993). https://doi.org/10.2165/00002018-199309020-00006
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DOI: https://doi.org/10.2165/00002018-199309020-00006