Ototoxicity of drugs

Dr Udai Bhan Yadav MBBS,DMCH .Senior Medical officerGeneral hospital alwar rajasthan, india.

Dr Udai Bhan Yadav 1

IntroductionDefinition

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.


Outer Ear, Middle Ear & Inner Ear


Ototoxic Drugs


Antibiotics Loop diuretics Nonsteroidal anti-inflammatory drugs Antimalarial drugs Antineoplastic drugs Miscellaneous

AminoglycosidesStreptomycin, kanamycin, neomycin, amikacin,

gentamicin, tobramycin, sisomycin, netilmicinEnter into inner ear by unknown mechanism

Secreted into the perilymph by spiral ligament or endolymph by stria vascularis

Diffuse through round window membraneEliminated by kidney


AminoglycosidesCochlear toxicity

Amikacin, kanamycin, neomycin, netilmicinVestibular toxicity

Streptomycin, gentamicin, sisomycinCan occur simultaneously



Increase of 10-20 dB in thresholds of one or more frequencies

Incidence (6-13%), netilmicin lowestRisk factors

Diuretics, renal failure, prolonged treatment, old age, preexisting SNHL

Infants less affected, once daily dosing



Outer hair cell loss first in basal turn then to apex

Inner hair cell loss later


AminoglycosidesCochlear toxicity presentation

High frequency Sensorineural hearing loss (SNHL) first, then lower frequencies to profound loss

Not reversibleDamage usually heralded by tinnitus


AminoglycosidesVestibular toxicity

Assessment is difficultDynamic posturography can detectPathologically

Type I hair cells more sensitive Cristae ampullaris then utricle and saccule

Clinically (ambulatory vs. bedridden) Ataxic gait, lose balance when turning


AminoglycosidesPrevention

PharmacologicalClinical

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


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

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

MacrolidesDiscovered erythromycin 1952

(McGuire)Mintz (1972) first report of ototoxicity

Reversible 50-55 dB losses in two casesClinically

Hearing loss with/without tinnitus– 2 daysAll frequencies, recovery after stoppingRarely permanent (hepatic)Incidence unknown


MacrolidesMechanism

unknownAzithromycin and

clarithromycin can cause similar findings in animals


Other antibioticsVancomycin

Believed to be ototoxic (no data)Penicillin, sulfonamides, cephalosporins

May have topical toxicity in middle earNucleoside analog reverse transcriptase

inhibitorsPoor study


Loop DiureticsEthacrinic acid, furosemide, bumetasideClinically (6-7%)

Usually tinnitus, temporary and reversible SNHL, rare vertigo within minutes

High doses can cause permanent SNHLHighest risk– coadministration of

aminoglycosides


Loop DiureticsPathologically

Edema of stria vascularis

Ionic gradient changes

Inhibition of adenylate cyclase and G-proteins


Salicylates and NSAIDSMost common OTC drugsMechanism

Normal histology (no hair cell loss)Decreased blood flow, decreased enzymes

ClinicallyTonal, high frequency tinnitus (7-9 kHz)Reversible mild to moderate SNHL (usually

high frequency)– rarely permanent


QuinineSimilar clinical findings with aspirinUsage up for leg crampsClinically

High-pitched tinnitusReversible, symmetric SNHLOccasional vertigo

MechanismDecreased perfusion, direct damage to outer

hair cells, biochemical alterations


Antineoplastic AgentsCisplatin

Incidence is high (62%-81%)Pathologically

Outer hair cell degenerationClinically

Bilateral symmetric SNHL, usually high frequency– not reversible, cumulative

Risks factors– age extremes, cranial irradiation, high dose therapy, high cumulative dose


Antineoplastic DrugsCisplatin

Prevention Probenecid, WR 2721, DDTC, diuretics, calcium

supplements– not effective L-N-acetyl-cysteine– protective in vitro


Topical AntimicrobialsCommonly prescribed for otorrhea after

tubes and CSOMControversial subject

Agents may enter middle ear and gain access to membranous labyrinth

Animal testing reveals irrefutable evidence of severe ototoxicity


Topical AntimicrobialsPolymixin B (Brummett)Chloramphenicol (Patterson)Neomycin (Brummett)Gentamicin (Webster)Ticarcillin (Jakob)Vasocidin (Brown)Ciprofloxacin (Lenarz)


Topical AntimicrobialsRemains a possibility in humansPatient education importantPrescribe for only necessary durationAvoid in healthy earCaution with prexisting vestibular defects


Case PresentationPatients 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 sleepLong history of mild hearing loss, now worsening

alsoDenies vertigo or dysequilibriumHas prior history of significant noise exposure

(worked in factory)No recent or prior antibiotic useNo prior otologic history except mild HL


.Referrence ms Ekta yadav project on drugs

induced ototoxicity .


Thank YouThank You


Health & Medicine

Ototoxicity of drugs