Ototoxicity

2.  Definition
 Damage to the cochlea or vestibular apparatus from
exposure to a chemical source
 Many sources
 Mercury
 Herbs
 Streptomycin
 Dihydrostreptomycin
 Gentamicin
 Others

3.  Streptomycin, kanamycin, neomycin, amikacin, gentamicin, tobramycin,
sisomycin, netilmicin
 Enter into inner ear by unknown mechanism
 Secreted into the perilymph by spiral ligament or
endolymph by stria vascularis
 Diffuse through round window membrane

4.  Cochlear toxicity
 Amikacin, kanamycin, neomycin, netilmicin
 Vestibular toxicity
 Streptomycin, gentamicin, sisomycin

5.  Cochlear toxicity
 Increase of 10-20 dB in thresholds of one or more frequencies
 Incidence (6-13%), netilmicin lowest
 Risk factors
 Diuretics, renal failure, prolonged treatment, old age, preexisting SNHL
 Infants less affected, once daily dosing

6.  Cochlear toxicity presentation
 High frequency SNHL first, then lower frequencies to profound loss
 Not reversible
 Damage usually heralded by tinnitus

7.  Vestibular toxicity
 Dynamic posturography can detect
 Clinically
 Ataxic gait, lose balance when turning
 Bobbing oscillopsia

8.  Prevention
 Consider less ototoxic drugs (netilmicin)
 Identify “high-risk” patients
 Audiogram before and weekly after starting
 ENG prior if possible
 History and physical exam daily (Romberg, VA)
 Adjust doses or switch drugs if toxic

9.  Erythromycin
 Clinically
 Hearing loss with/without tinnitus– 2 days
 All frequencies, recovery after stopping
 Rarely permanent (hepatic)

10.  Vancomycin
 Believed to be ototoxic (no data)
 Penicillin, sulfonamides, cephalosporins
 May have topical toxicity in middle ear

11.  Ethacrinic acid, furosemide, bumetaside
 Clinically (6-7%)
 Usually tinnitus, temporary and reversible SNHL, rare vertigo within
minutes
 High doses can cause permanent SNHL
 Highest risk– coadministration of aminoglycosides

12.  Most common OTC drugs in US
 Mechanism
 Normal histology (no hair cell loss)
 Decreased blood flow, decreased enzymes
 Clinically
 Tonal, high frequency tinnitus (7-9 kHz)
 Reversible mild to moderate SNHL (usually high frequency)– rarely
permanent

13.  Similar clinical findings with aspirin
 Clinically
 High-pitched tinnitus
 Reversible, symmetric SNHL
 Occasional vertigo
 Mechanism
 Decreased perfusion, direct damage to outer hair
cells, biochemical alterations

14.  Cisplatin
 Incidence is high (62%-81%)
 Pathologically
 Outer hair cell degeneration
 Clinically
 Bilateral symmetric SNHL, usually high frequency– not reversible,
cumulative
 Risks factors– age extremes, cranial irradiation, high dose therapy, high
cumulative dose

15.  Polymixin B (Brummett)
 Chloramphenicol (Patterson)
 Neomycin (Brummett)
 Gentamicin (Webster)
 Ticarcillin (Jakob)
 Vasocidin (Brown)
 Ciprofloxacin (Lenarz)