Introduction
• Definition
– Damage to the cochlea or vestibular apparatus from exposure to a chemical source
• Many sources
– Mercury
– Herbs
– Streptomycin (1944)
• Dihydrostreptomycin (1948)
– Gentamicin (1965)
– Others
Aminoglycosides
– 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
– Eliminated by kidney
• Cochlear toxicity
– Amikacin, kanamycin, neomycin, netilmicin
• Vestibular toxicity
– Streptomycin, gentamicin, sisomycin
• Can occur simultaneously
– 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
– Outer hair cell loss first in basal turn then to apex
– Inner hair cell loss later
• Cochlear toxicity presentation
– High frequency SNHL first, then lower frequencies to profound loss
– Not reversible
– Damage usually heralded by tinnitus
– Can be familial form of nonsyndromic HL– maternal inheritance
– Associated with mtDNA 1555A to G point mutation in 12S ribosomal RNA gene– causes increased binding to ribosome
Aminoglycosides
• Vestibular toxicity
– Assessment is difficult
– Dynamic posturography can detect
– Pathologically
• Type I hair cells more sensitive
• Cristae ampullaris then utricle and saccule
– Clinically (ambulatory vs. bedridden)
• Ataxic gait, lose balance when turning
• Bobbing oscillopsia
• Prevention
– Pharmacological
– Clinical
• 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
Macrolides
• Discovered erythromycin 1952 (McGuire)
• Mintz (1972) first report of ototoxicity
– Reversible 50-55 dB losses in two cases
• Clinically
– Hearing loss with/without tinnitus– 2 days
– All frequencies, recovery after stopping
– Rarely permanent (hepatic)
– Incidence unknown
• Mechanism unknown
• Azithromycin and clarithromycin can cause similar findings in animals
Other antibiotics
• Vancomycin
– Believed to be ototoxic (no data)
• Penicillin, sulfonamides, cephalosporins
– May have topical toxicity in middle ear
• Nucleoside analog reverse transcriptase inhibitors
– Poor study
Loop Diuretics
• 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
• Pathologically
– Edema of stria vascularis
– Ionic gradient changes
– Inhibition of adenylate cyclase and G-proteins
Salicylates and NSAIDS
• 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
Quinine
• Similar clinical findings with aspirin
• Usage up for leg cramps
• Clinically
– High-pitched tinnitus
– Reversible, symmetric SNHL
– Occasional vertigo
• Mechanism
– Decreased perfusion, direct damage to outer hair cells, biochemical alterations
Antineoplastic Agents
• 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
• Cisplatin
– Prevention
• Probenecid, WR 2721, DDTC, diuretics, calcium supplements– not effective
• L-N-acetyl-cysteine– protective in vitro
Topical Antimicrobials
• Commonly prescribed for otorrhea after tubes and CSOM
• Controversial subject
– Agents may enter middle ear and gain access to membranous labyrinth
– Animal testing reveals irrefutable evidence of severe ototoxicity
• Polymixin B (Brummett)
• Chloramphenicol (Patterson)
• Neomycin (Brummett)
• Gentamicin (Webster)
• Ticarcillin (Jakob)
• Vasocidin (Brown)
• Ciprofloxacin (Lenarz)
• Differences in humans
– Round window is not exposed
– Round window thicker
– Mucosal membrane protective
– Mucosal edema with or without exudates typically present
– Widespread usage with few side effects
• One in ten thousand
• Remains a possibility in humans
• Patient education important
• Prescribe for only necessary duration
• Avoid in healthy ear
• Caution with prexisting vestibular defects
Russell D. Briggs, M.D.
Arun K. Gadre, M.D.
