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Ototoxicity of drugs.
1. Dr Udai Bhan Yadav
MBBS,DMCH .
Senior Medical officer
General hospital alwar rajasthan, india.
Dr Udai Bhan Yadav 1
2. Introduction
Definition
Damage to the cochlea or vestibular apparatus from exposure to a
chemical source.
Drug ototoxicity is defined as a temporary or permanent inner ear
dysfunction after drug exposure, resulting in a hearing and/or
balance disturbance. It represents one of the main preventable
causes of deafness, an outcome that can perhaps be most directly
influenced by healthcare professionals. Although the use of
ototoxic drugs in humans should be avoided, this is not always
possible because the benefits of these drugs in combating life-threatening
diseases often outweigh the risks.
Dr Udai Bhan Yadav 2
5. 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
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7. 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
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8. Aminoglycosides
Cochlear toxicity
Outer hair cell loss
first in basal turn then
to apex
Inner hair cell loss
later
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9. Aminoglycosides
Cochlear toxicity presentation
High frequency Sensorineural hearing loss (SNHL)
first, then lower frequencies to profound loss
Not reversible
Damage usually heralded by tinnitus
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10. 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
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11. Aminoglycosides
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
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12. Risk factors for ototoxicity
Impaired renal function
Intrinsic ototoxic potential of the drug
Combination with other ototoxic drugs
Total dose and duration of therapy
Prior exposure to aminoglycosides
Prolonged exposure of inner-ear
tissues to the aminoglycoside
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13. How to avoid ototoxicity ??
Renal, auditory, and vestibular function
Assessed before, during, and following therapy
Aminoglycoside serum concentrations
Avoiding prolonged therapy and ototoxic agents
Maintain hydration, urine output, and normal serum
electrolytes
Recommend : stop the aminoglycoside at the first
sign of vestibulotoxicity
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14. 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
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15. Macrolides
Mechanism
unknown
Azithromycin and
clarithromycin can
cause similar findings
in animals
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16. 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
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17. 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
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18. Loop Diuretics
Pathologically
Edema of stria
vascularis
Ionic gradient
changes
Inhibition of
adenylate cyclase and
G-proteins
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19. Salicylates and NSAIDS
Most common OTC drugs
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
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20. 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
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21. 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
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22. Antineoplastic Drugs
Cisplatin
Prevention
Probenecid, WR 2721, DDTC, diuretics, calcium
supplements– not effective
L-N-acetyl-cysteine– protective in vitro
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23. 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
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25. Topical Antimicrobials
Remains a possibility in humans
Patient education important
Prescribe for only necessary duration
Avoid in healthy ear
Caution with prexisting vestibular defects
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26. Case Presentation
Patients presents to clinic with complaint of “ringing in
my ears”
Described as high pitched in both ears, onset was 5 days
prior and worsening, not able to sleep
Long history of mild hearing loss, now worsening also
Denies vertigo or dysequilibrium
Has prior history of significant noise exposure (worked
in factory)
No recent or prior antibiotic use
No prior otologic history except mild HL
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27. .
Referrence ms Ekta yadav project on drugs induced
ototoxicity .
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Mercury used for treatment of syphilis– vertigo, deafness, tremors
First clinical trial revealed irreversible deafness and disturbances of balance– bobbing oscillopsia
Dihydrostreptomycin 1948– much more toxic to cochlear hair cells
Can be administered several ways– all of which can produce significant ototoxicity-- parentally, topically, intratympanically, intrathecally, orally
Can be administered several ways– all of which can produce significant ototoxicity-- parentally, topically, intratympanically, intrathecally, orally
Can be administered several ways– all of which can produce significant ototoxicity-- parentally, topically, intratympanically, intrathecally, orally