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

3. Outer Ear, Middle Ear
& Inner Ear
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4. Ototoxic Drugs
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 Antibiotics
 Loop diuretics
 Nonsteroidal anti-inflammatory drugs
 Antimalarial drugs
 Antineoplastic drugs
 Miscellaneous

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
Dr Udai Bhan Yadav 5

6. Aminoglycosides
Cochlear toxicity
Amikacin, kanamycin, neomycin, netilmicin
Vestibular toxicity
Streptomycin, gentamicin, sisomycin
Can occur simultaneously
Dr Udai Bhan Yadav 6

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
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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

13. How to avoid ototoxicity ??
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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

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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24. Topical Antimicrobials
Polymixin B (Brummett)
Chloramphenicol (Patterson)
Neomycin (Brummett)
Gentamicin (Webster)
Ticarcillin (Jakob)
Vasocidin (Brown)
Ciprofloxacin (Lenarz)
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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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28. Thank YouThank You
Dr Udai Bhan Yadav 28