Ototoxicity

Ototoxicity
Classification and external resources
ICD-10 H91.0
DiseasesDB 2874
eMedicine ent/699

Ototoxicity is damage to the ear (oto-), specifically the cochlea or auditory nerve and sometimes the vestibular system, by a toxin. It is commonly medication-induced; ototoxic drugs include antibiotics such as the aminoglycoside gentamicin, loop diuretics such as furosemide, and platinum-based chemotherapy agents such as cisplatin. A number of nonsteroidal anti-inflammatory drugs (NSAIDS) such as Meloxicam have also been shown to be ototoxic. This can result in sensorineural hearing loss, dysequilibrium, or both. Either may be reversible and temporary, or irreversible and permanent.

Contents

Ototoxic agents

Antibiotics

Antibiotics in the aminoglycoside class, such as gentamicin and tobramycin, may produce cochleotoxicity through a poorly understood mechanism.[1] It may result from antibiotic binding to NMDA receptors in the cochlea and damaging neurons through excitotoxicity.[2] Aminoglycoside-induced production of reactive oxygen species may also injure cells of the cochlea.[3] Once-daily dosing[4] and co-administration of N-acetylcysteine[5] may protect against aminoglycoside-induced ototoxicity. The ototoxicity of gentamicin can be exploited to treat some individuals with Ménière's disease by destroying the inner ear, which stops the vertigo attacks but causes permanent deafness.[6]

Macrolide antibiotics, including erythromycin, are associated with reversible ototoxic effects.[7] The underlying mechanism of ototoxicity may be impairment of ion transport in the stria vascularis.[7] Predisposing factors include renal impairment, hepatic impairment, and recent organ transplantation.[7]

Loop diuretics

The loop diuretic furosemide is associated with ototoxicity, particularly when doses exceed 240 mg per hour.[8] The related compound ethacrynic acid is particularly ototoxic.[7] Bumetanide confers a decreased risk of ototoxicity compared to furosemide.[7]

Chemotherapeutic agents

Platinum-containing chemotherapeutic agents, including cisplatin and carboplatin, are associated with cochleotoxicity characterized by high-frequency hearing loss and tinnitus (ringing in the ears).[9] Ototoxicity is less frequently seen with the related compound oxaliplatin.[10] Cisplatin-induced ototoxicity is dose-dependent, typically occurring with doses greater than 60 mg/m2, and tend to occur when chemotherapy is given every two weeks compared to every one week.[9] Cisplatin and related agents are absorbed by the cochlear hair cells and result in ototoxicity through the production of reactive oxygen species.[11] The decreased incidence of oxaliplatin ototoxicity has been attributed to decreased uptake of the drug by cells of the cochlea.[10] Administration of amifostine has been used in attempts to prevent cisplatin-induced ototoxicity, but the American Society of Clinical Oncology recommends against its routine use.[12]

The vinca alkaloids, including vincristine, are also associated with reversible ototoxicity.[7]

Others

Ototoxic effects are also seen with quinine and heavy metals such as mercury and lead.[7] At high doses, aspirin and other salicylates may also cause high-pitch tinnitus and hearing loss in both ears, typically reversible upon discontinuation of the drug.[7] The erectile dysfunction medications Viagra, Levitra and Cialis have also been reported to cause hearing loss.[13]

Mixed Exposures

Ototoxic chemicals interact with mechanical stresses on the hair cells of the cochlea in different ways. For organic solvents such as Toluene, styrene or xylene, the combined exposure with noise increases the risk of hearing loss in a synergistic manner [14] Heavy metals, ashpyxiants and endocrine disruptors have a variety of interactions as well. Specific toxicity limits for combined exposures are not well established. However, given the potential for enhanced risk of hearing loss, the noise exposures should be kept below 85 decibels and the chemical exposures should be below the recommended exposure limits given by agencies such as OSHA, NIOSH, or ACGIH.

Symptoms

Symptoms of ototoxicity include partial or profound hearing loss, vertigo, and tinnitus.[7]

Treatment

No specific treatment is available, but immediate withdrawal of the drug may be warranted in cases where the consequences of doing so are less severe than the consequences of the ototoxicity.[7]

References

  1. ^ Dobie RA, Black FO, Pezsnecker SC, Stallings VL (March 2006). "Hearing loss in patients with vestibulotoxic reactions to gentamicin therapy". Archives of Otolaryngology--Head & Neck Surgery 132 (3): 253–7. doi:10.1001/archotol.132.3.253. PMID 16549744. http://archotol.ama-assn.org/cgi/pmidlookup?view=long&pmid=16549744. 
  2. ^ Basile AS, Huang JM, Xie C, Webster D, Berlin C, Skolnick P (December 1996). "N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss". Nature Medicine 2 (12): 1338–43. doi:10.1038/nm1296-1338. PMID 8946832. 
  3. ^ Wu WJ, Sha SH, Schacht J (2002). "Recent advances in understanding aminoglycoside ototoxicity and its prevention". Audiology & Neuro-otology 7 (3): 171–4. doi:10.1159/000058305. PMID 12053140. http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=aud07171. 
  4. ^ Munckhof WJ, Grayson ML, Turnidge JD (April 1996). "A meta-analysis of studies on the safety and efficacy of aminoglycosides given either once daily or as divided doses". The Journal of Antimicrobial Chemotherapy 37 (4): 645–63. doi:10.1093/jac/37.4.645. PMID 8722531. http://jac.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=8722531. 
  5. ^ Tepel M (August 2007). "N-Acetylcysteine in the prevention of ototoxicity". Kidney International 72 (3): 231–2. doi:10.1038/sj.ki.5002299. PMID 17653228. 
  6. ^ Perez N, Martín E, García-Tapia R (March 2003). "Intratympanic gentamicin for intractable Ménière's disease". The Laryngoscope 113 (3): 456–64. doi:10.1097/00005537-200303000-00013. PMID 12616197. 
  7. ^ a b c d e f g h i j Roland, Peter S. (2004). Ototoxicity. Hamilton, Ont: B.C. Decker. ISBN 1-55009-263-4. 
  8. ^ Voelker JR, Cartwright-Brown D, Anderson S, et al. (October 1987). "Comparison of loop diuretics in patients with chronic renal insufficiency". Kidney International 32 (4): 572–8. doi:10.1038/ki.1987.246. PMID 3430953. 
  9. ^ a b Rademaker-Lakhai JM, Crul M, Zuur L, et al. (February 2006). "Relationship between cisplatin administration and the development of ototoxicity". Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology 24 (6): 918–24. doi:10.1200/JCO.2006.10.077. PMID 16484702. http://www.jco.org/cgi/pmidlookup?view=long&pmid=16484702. 
  10. ^ a b Hellberg V, Wallin I, Eriksson S, et al. (January 2009). "Cisplatin and oxaliplatin toxicity: importance of cochlear kinetics as a determinant for ototoxicity". Journal of the National Cancer Institute 101 (1): 37–47. doi:10.1093/jnci/djn418. PMC 2639295. PMID 19116379. http://jnci.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=19116379. 
  11. ^ Rybak LP, Whitworth CA, Mukherjea D, Ramkumar V (April 2007). "Mechanisms of cisplatin-induced ototoxicity and prevention". Hearing Research 226 (1-2): 157–67. doi:10.1016/j.heares.2006.09.015. PMID 17113254. http://linkinghub.elsevier.com/retrieve/pii/S0378-5955(06)00272-3. 
  12. ^ Hensley ML, Hagerty KL, Kewalramani T, et al. (January 2009). "American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants". Journal of Clinical Oncology 27 (1): 127–45. doi:10.1200/JCO.2008.17.2627. PMID 19018081. http://www.jco.org/cgi/pmidlookup?view=long&pmid=19018081. 
  13. ^ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109012.htm
  14. ^ name=fechter Fechter L.D. "Promotion of noise-induced hearing loss by chemical conaminants," J. Tox. Env. Health Part A. 67:727-740 (2004)

External links


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Look at other dictionaries:

  • ototoxicity — noun see ototoxic …   New Collegiate Dictionary

  • ototoxicity — See ototoxic. * * * …   Universalium

  • ototoxicity — noun Damage to the ear, specifically the cochlea and sometimes the vestibular system, by a toxin …   Wiktionary

  • ototoxicity — The property of being injurious to the ear. [oto + G. toxikon, poison] familial aminoglycoside o. inherited susceptibility to sensory hearing loss upon administration of aminoglycoside antibiotics due to a mutation in the m …   Medical dictionary

  • ototoxicity — oto·toxicity …   English syllables

  • ototoxicity — noun see ototoxic …   Useful english dictionary

  • ototoxic — ototoxicity /oh teuh tok sis i tee/, n. /oh teuh tok sik/, adj. having a harmful effect on the organs or nerves concerned with hearing and balance. [1950 55; OTO + TOXIC] * * * …   Universalium

  • Vancomycin — Drugbox IUPAC name = unable to be assigned width=300 CAS number=1404 90 6 ATC prefix=A07 ATC suffix=AA09 ATC supplemental=ATC|J01|XA01 PubChem=14969 DrugBank=APRD01287 C=66 | H=75 | Cl=2 | N=9 | O=24 molecular weight = 1449.3 g.mol 1… …   Wikipedia

  • Netilmicin — Systematic (IUPAC) name (2R,3R,4R,5R) ​2 ​{[(1S,2S,3R,4S,6R) ​4 ​amino ​3 ​{[(2S,3R) ​3 ​amino ​6 ​(aminomethyl) ​3,4 ​dihydro 2H ​pyran ​2 ​yl]oxy} ​6 ​(ethylamino) ​2 ​hydroxycyclohex …   Wikipedia

  • Cisplatin — Systematic (IUPAC) name (SP 4 2) diamminedichloridoplatinum …   Wikipedia


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