18 - Ototoxicity

Question 1

What is tinnitus? What is the mechanism?

Answer 1

• Result of trauma, disease, or xenobiotic toxicity
• Mechanism unknown (central involvement)
• Hair cell dysfunction (central neurotransmission)

Question 2

What drugs can cause tinnitus?

Answer 2

• Streptomycin, neomycin, indomethacin, doxycycline, furosemide, heavy metals, and high dose caffeine
• Typically salicylates and quinine

Question 3

Describe audiometry and what each level corresponds to

Answer 3

• Threshold = minimum effective sound capable of evoking a hearing sensation 50% of the time
• 0 dB = normal
• 10-20 dB = mild hearing loss
• 21-40 dB = moderate loss
• > 40 dB = severe loss

Question 4

What are symptoms of vestibular dysfunction?

Answer 4

• Light-headedness, headache, whirling sensation

- Pt may display nystagmus, ataxia, unsteady gait and posture

Question 5

Which drugs cause reversible hearing loss?

Answer 5

• Diuretics (acetazolamide, furosemide) -> physiologic dysfunction, loss of hair cells, and edema at stria vascularis
• Inhibition of potassium pump and G protein associated w/ adenylcyclase => decreased potassium activity in the endolymph amd decreased endocochlear potential
• Salicylates
• Erythromycin
• Quinine
• Phosphodiesterase-5 inhibitors

Question 6

Describe salicylates ototoxicity

Answer 6

• Generally mild
• Mechanism unclear -> effect on prostaglandin synthesis may interfere w/ Na+K+ATPase pump function at stria vascularis => decrease in cochlear blood flow => reversible decrease in outer hair cell turgor secondary to membrane permeability changes
• Reversible 24-72 h after d/c of the drug
• Hearing loss typically bilateral and symmetrical

Question 7

Dose of salicylates required to cause ototoxicity

Answer 7

• Dose dependent
• Daily doses > 2.7 g are associated w/ increased ototoxicity
• Doses > 4 g/day produce tinnitus in 50% of px and hearing loss in ~25% of px

Question 8

Describe erythromycin ototoxicity

Answer 8

• Mechanism unclear (effects on central auditory pathways)
• Bilateral impairment of hearing at all frequencies associated w/ slurred speech, double vision, and confusion
• PO, IV, IP (dialysis px), topical administration to the ear

Question 9

Risk factors for erythromycin ototoxicity

Answer 9

• High doses w/ renal or hepatic failure
• IV administration
• Age
• Use w/ other ototoxic agents
• Use w/ inhibitors of erythromycin metabolism

Question 10

Dose of erythromycin required to cause ototoxicity

Answer 10

• PO doses > 4 g/day

- Dose < 2 g/day has been associated w/ ototoxicity in renal or hepatic failure

Question 11

Describe phosphodiesterase-5 inhibitor ototoxicity

Answer 11

• Sudden hearing loss (very rare)
• Unilateral, first 24 h
• Causality not confirmed

Question 12

Which drugs cause irreversible hearing loss?

Answer 12

• Aminoglycosides

- Cisplatinum

Question 13

Which aminoglycosides are the most ototoxic?

Answer 13

• Neomycin

- Kanamycin

Question 14

Mechanism of aminoglycoside ototoxicity

Answer 14

Binding to hair cell membrane => membrane disruption, loss of electrolytes, loss in enzyme function, and inhibition of protein synthesis

Question 15

Risk factors for aminoglycoside ototoxicity

Answer 15

• Severity of illness (hydration state, organ failure)
• Pre-existing hearing loss
• • Previous exposure to AGs
• Duration of therapy
• Peak-trough variation
• Other ototoxic drugs (synergistic effects w/ loop diuretics)
• Pre-existing renal failure
• Age, noise exposure, previous ear infection
• Genetic predisposition (cochlear toxicity)

Question 16

Describe cisplatinum ototoxicity

Answer 16

• Clinically apparent hearing loss noted in 50% of px receiving doses of 50-100 mg/m2
• Damage to outer hair cells and stria vascularis
• Usually bilateral
• Cochlear and vestibular sx (2-5 days after 1st or 2nd dose)