Lecture 20 - Eye & Ear Toxicity Flashcards
define ototoxicity
functional impairment and cellular degeneration of the tissues of the inner ear
purpose of cochlear fluids
- conduct sound waves to the hair cells
- provide nutrients and remove waste
- control pressure
- maintain electrochemical gradient
Describe tinnitus
- result of trauma, disease or xenobiotic toxicity
- MOA unknown
- hair cell dysfunction
- streptomycin, neomycin, indomethacin, doxycycline, ethacrynic acid, furosemide, heavy metals and high dose caffeine
What is tinnitus typically caused by?
salicylates and quinine
Describe presbycusis
hearing loss
-common in the elderly (atrophy of the basal end of organ of Corti, loss of hair cells, stiffening of basilar membranes, vascular changes)
Describe symptoms of vestibular dysfunction
- lightheadedness
- headache
- whirling sensation
- patient may display nystagmus, ataxia, unsteady gait and posture
What drugs can cause reversible hearing loss?
Diuretics (acetazolamide, furosemide, bumetanide, ethacrynic acid): physiologic dysfunction, loss of hair cells and edema at the stria vascularis
Inhibition of potassium pump and G protein associated with adenylcyclase - decreased potassium activity in the endolymph and decreased endocochlear potential
-Salicylates, Erythromycin, Quinine, PDE5 inhibitors
Describe the reversible hearing loss caused by salicylates
- generally mild
- MOA unclear - effect on PG synthesis may interfere with the Na+, K+ ATPase pump function at the stria vascularis - decrease cochlear blood flow - reversible decrease in outer hair cell turgor secondary to membrane permeability changes (inhibition of otoacustic emission)
When is it reversible after salicylates
24-72 hours after d/c of the drug
Salicylates - what dose causes ototoxicity
daily doses above 2.7 grams associated with increased ototoxicity
doses above 4g/day produce tinnitus in 50% of patients and hearing loss in 25% of patients
*typically bilateral and symmetrical
Describe reversible hearing loss with Erythromycin
- MOA unclear
- incidence as high as 20-30% of patients
- bilateral impairment of hearing at all frequencies associated with slurred speech, double vision and confusion
What dose of erythromycin causes ototoxicity
PO doses > 4 gram/day (2 gram / day in renal or hepatic failure)
What are risk factors for erythromycin ototoxicity
high doses with renal or hepatic failure, IV administration, age, use with other ototoxic agents, use with inhibitors of erythromycin metabolism
Describe quinines
- PG inhibition
- inhibit phospholipase A2 enzyme (converts phospholipids to arachidonic acid)
- inhibition of calcium channels
- vasoconstriction
- inhibition of potassium channel
PDE5 inhibitors and hearing loss
- sildenafil, vardneafil, tadalfil
- sudden hearing loss (very rare)
- unilateral, first 24 hours
- causality not confirmed
What drugs can cause irreversible hearing loss
aminoglycosides (gentamicin)
cisplatinum
What are some risk factors for irreversible hearing loss with aminoglycosides
- Severity of illness (hydration state, organ failure)
- Pre-existing hearing loss
- Previous exposure to aminoglycosides (it is a lifetime risk yo)
- Duration of therapy
- Peak-valley variation (extended interval dosing)
- other ototoxic drugs (synergistic effects with loop diuretics)
- pre-existing renal failure
- age, noise exposure, previous ear infection
- genetic predisposition (cochlear toxicity)
Describe cisplatinum and irreversible hearing loss
- Clinically apparent hearing loss noted in 30-70% of patients receiving doses of 50-100 mg/m2
- Damage to the outer hair cells and stria vascularis (inhibition of adenyl cyclase in the stria vascularis, inhibition of protein synthesis and formation of free radicals)
- Usually bilaterial
- Cochlear and vestibular symptoms (2-5 days after first or second dose)
What are the 2 separate vascular systems of the eye?
- Uveal blood vessels
- Retinal vessels
Where does amiodarone precipitate in the eye
cornea and lens
_____ is very rich with enzymes (so it is highly susceptible to injury)
retina or cornea
What is the cornea?
- Transparent protective membrane (must remain transparent, allows light rays to reach the retina)
- Avascular (corneal epithelium, stroma, endothelium)
What is the lens?
- Avascular and transparent
- Focus and accomodation