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ototoxicity

drug induced ototoxicity

introduction

  • many drugs have the potential to cause ototoxicity and depending upon the drug and circumstances, it may be reversible or irreversible, and it may be primarily cochleotoxic (causing deafness) or, as with gentamicin, primarily vestibulotoxic.
  • individual susceptibility to drug-induced ototoxicity seems highly variable, but some predisposing factors have been identified:
    • renal failure
    • advancing age
    • prior or concomitant therapy with other ototoxic drugs
    • fever
    • dehydration
    • possibly hereditary factors, and noise exposure
  • ototoxicity may contribute to, or exacerbate presbycusis (deafness of aging)

examples

aminoglycosides

  • all the aminoglycoside antibiotics can potentially cause severe, irreversible ototoxicity
  • they appear to cause generation of reactive free radical oxygen species within the cochlea that trigger downstream mechanisms leading to cell death
  • various protective agents, including antioxidants (e.g. aspirin, L-carnitine, ascorbic acid), have shown promise in protecting the inner ear from damage in experimental animals
  • may occur after parenteral administration, aerosolisation, topical use, wound or cavity irrigation or otic administration
  • can cause permanent bilaterally severe, high-frequency sensorineural hearing loss and temporary vestibular dysfunction.
  • seem to enhance the ototoxic effect of noise and vice versa
  • neomycin is the most cochleotoxic aminoglycoside
  • gentamicin is more vestibulotoxic than cochleotoxic, hence its use in severe Meniere's disease
    • recent concerns from severe ototoxicity even from a single dose has led to a general reduction in use

other antibiotics

  • erythromycin can produce a dose-dependent, usually reversible, bilateral hearing loss, frequently associated with tinnitus, usually at high serum levels such as with doses > 4g/d or in those with liver/renal disease.
  • doxycycline and minocycline have been associated with tinnitus
  • minocycline is also potentially dose-related vestibulotoxic:
    • 11-14% incidence at 50mg bd
    • 60-77% incidence at 100mg bd
    • risk is 2-3x higher in women
  • polymixin B

analgesics

  • salicylates such as aspirin are well known to cause hearing loss and tinnitus in acute toxicity (eg. doses > 4g aspirin/day)
    • in the absence of pre-existing hearing loss, salicylate typically causes bilateral mild-to-moderate hearing loss, which may be flat or more pronounced at high frequencies.
    • hearing loss is almost always reversible within a few days of drug discontinuation.

diuretics

  • loop diuretics such as frusemide / furosemide / Lasix can produce a dose-related, usually reversible ototoxicity, primarily affecting patients with renal impairment (typically involving 160 to 800 mg/day of frusemide)
    • hearing loss occurs most frequently at middle and high frequencies
    • loop diuretics act on the ion and water balance of the stria vascularis, causing oedema of tissue and temporary loss of function
    • main danger of loop diuretics probably lies in their ability to potentiate the ototoxicity of aminoglycosides

cytotoxics

  • cisplatin is the most ototoxic drug among the chemotherapeutic agents and this is irreversible

other drugs

  • many other drugs may cause ototoxicity, in particular:
    • quinine and chloroquine
    • topical chlorhexidine to ear
    • mercury - recognised in the 11th century
    • arsenicals of the early 20th century
    • desferrioxamine

references

  • Peterson, Gregory. 'What's that?: I can't understand you…' - drug-induced Ototoxicity in the elderly. Australian Pharmacist, Vol. 30, No. 11, Nov 2011: 916-918
ototoxicity.txt · Last modified: 2013/09/27 18:23 (external edit)