Ototoxicity

Ototoxicity

1. Ototoxicity

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

3. 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

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

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

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

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

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

11. 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

12. 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

13. Quinine 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. 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

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

16. The End