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Ototoxicity


      a silent hazard
Definition

 –   Damage to the cochlea or vestibular
     apparatus from exposure to a chemical
     source.
 –   The sources may include the drugs consumed
     by the patient on therapeutic or non
     therapeutic purposes and also the compounds
     present in the environment.
Ototoxic drugs

-   Aminoglycosides
-   Diuretics
-   Antimalarials
-   Anticancer drugs
-   Analgesics
-   Miscellaneous
High risk groups

-   Patients having impaired renal function.
-   Elderly patients(age above 65 yrs).
-   Patients simultaneously receiving other ototoxic
    drugs [aminoglycosides when concomitantly
    used with diuretics have synergistic ototoxicity].
-   Patients who have genetic susceptibility to these
    group of drugs.
-   Patients under prolonged treatment.
Aminoglycosides

-   Streptomycin, Gentamicin, Tobramycin, Neomyc
    in and Kanamycin.
-    Cochlear toxicity:
    Neomycin, Kanamycin, Amikacin.
-   Vestibular toxicity: Gentamicin, Streptomycin
-   Pathogenesis: Selectively destroy outer hair
    cells, they even destroy inner hair cells.
-   Symptoms: hearing loss, tinnitus, vertigo
Normal inner ear hair cells   Damaged inner ear hair cells
Diuretics

-   Furosemide and Ethacrynic acid (loop diuretics)
-   Known to cause edema and cystic changes in
    stria vascularis of cochlear duct.
-   The edema is caused due to blockage of Na+ &
    Cl- ions transport.
-   Effect: mostly reversible but permanent damage
    may occur.
Antimalarials

-   Quinine & Chloroquine
-   Ototoxic effect is due to vasoconstriction in the
    small vessels of the cochlea and stria vascularis.
-   The effect is reversible which generally appears
    on prolonged medication, but deafness is
    permanent with chloroquine.
-   Congenital deafness and hypoplasia of cochlea
    have been reported in children whose mothers
    received these drugs during pregnancy(1st
    trimester).
Anticancer drugs

-   Nitrogen
    mustards(Cyclophosphamide, Ifosfamide), Cispla
    tin, Carboplatin can cause cochlear damage.
-   Ototoxic effect is due to outer hair cell
    degeneration leading to high frequency sensory
    neural hearing loss.
Analgesics

-   NSAIDS like Salicylates, Indomethacin, Phenyl
    butazone, Ibuprofen.
-   Ototoxic effect is reversible and is due to
    interference at enzymatic level.
-   No structural damage hence normal
    histology(no hair cell loss)
-   Site of lesion testing indicates cochlear
    involvement.
-   Symptoms: tinnitus and b/l hearing loss
    particularly affecting higher frequencies.
Miscellaneous

-   Desferrioxamine: Iron chelating substance.
-   It causes high frequency sensory neural hearing
    loss.The effect is permanent but rarely reversible.
-   Cases of deafness have been reported with
    Erythromycin, Ampicillin, Propanalol, Propyl
    thiouracil, Phenytoin, Barbiturates, Hexadimethi
    ne bromide, Dantrolene, OCPs.
-   Alcohol, tobacco and marijuana also cause
    damage to inner ear.
Chemicals classes:
- Gas(Carbon monoxide)
- Heavy metals(lead, arsenic, mercury)
- Organic solvents(carbon disulfide, styrene, xylene
  and toluene).
Topical drugs

-   Topical ear drops used in the treatment of otitis
    externa may be absorbed from the round and
    oval windows into the fluids of inner ear leading
    to ototoxicity.
-   Chlorhexidine which was used in the
    preparartion of ear canal before surgery has also
    been blamed for such deafness.
Investigations

-   Monitoring drug concentrations in the body.
-   PTA
-   Caloric test
-   Electrocochleography
-   Oto-acoustic emission
-   BERA(brain stem evoked response audiometry)
Management

-   Early recognition and discontinuation of drugs.
-   Hearing aid in cases of severe hearing loss.
-   Tinnitus treated by mild hypnotics.
-   Disequilibrium should be treated with
    reassurance and regular physiotherapy including
    vestibular exercises, wearing of soft thick padded
    shoes, avoidance of walking in darkness and
    unnecessary head movement.
Abhilash

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Ototoxicity

  • 1. Ototoxicity a silent hazard
  • 2. Definition – Damage to the cochlea or vestibular apparatus from exposure to a chemical source. – The sources may include the drugs consumed by the patient on therapeutic or non therapeutic purposes and also the compounds present in the environment.
  • 3. Ototoxic drugs - Aminoglycosides - Diuretics - Antimalarials - Anticancer drugs - Analgesics - Miscellaneous
  • 4. High risk groups - Patients having impaired renal function. - Elderly patients(age above 65 yrs). - Patients simultaneously receiving other ototoxic drugs [aminoglycosides when concomitantly used with diuretics have synergistic ototoxicity]. - Patients who have genetic susceptibility to these group of drugs. - Patients under prolonged treatment.
  • 5. Aminoglycosides - Streptomycin, Gentamicin, Tobramycin, Neomyc in and Kanamycin. - Cochlear toxicity: Neomycin, Kanamycin, Amikacin. - Vestibular toxicity: Gentamicin, Streptomycin - Pathogenesis: Selectively destroy outer hair cells, they even destroy inner hair cells. - Symptoms: hearing loss, tinnitus, vertigo
  • 6. Normal inner ear hair cells Damaged inner ear hair cells
  • 7. Diuretics - Furosemide and Ethacrynic acid (loop diuretics) - Known to cause edema and cystic changes in stria vascularis of cochlear duct. - The edema is caused due to blockage of Na+ & Cl- ions transport. - Effect: mostly reversible but permanent damage may occur.
  • 8. Antimalarials - Quinine & Chloroquine - Ototoxic effect is due to vasoconstriction in the small vessels of the cochlea and stria vascularis. - The effect is reversible which generally appears on prolonged medication, but deafness is permanent with chloroquine. - Congenital deafness and hypoplasia of cochlea have been reported in children whose mothers received these drugs during pregnancy(1st trimester).
  • 9. Anticancer drugs - Nitrogen mustards(Cyclophosphamide, Ifosfamide), Cispla tin, Carboplatin can cause cochlear damage. - Ototoxic effect is due to outer hair cell degeneration leading to high frequency sensory neural hearing loss.
  • 10. Analgesics - NSAIDS like Salicylates, Indomethacin, Phenyl butazone, Ibuprofen. - Ototoxic effect is reversible and is due to interference at enzymatic level. - No structural damage hence normal histology(no hair cell loss) - Site of lesion testing indicates cochlear involvement. - Symptoms: tinnitus and b/l hearing loss particularly affecting higher frequencies.
  • 11. Miscellaneous - Desferrioxamine: Iron chelating substance. - It causes high frequency sensory neural hearing loss.The effect is permanent but rarely reversible. - Cases of deafness have been reported with Erythromycin, Ampicillin, Propanalol, Propyl thiouracil, Phenytoin, Barbiturates, Hexadimethi ne bromide, Dantrolene, OCPs. - Alcohol, tobacco and marijuana also cause damage to inner ear.
  • 12. Chemicals classes: - Gas(Carbon monoxide) - Heavy metals(lead, arsenic, mercury) - Organic solvents(carbon disulfide, styrene, xylene and toluene).
  • 13. Topical drugs - Topical ear drops used in the treatment of otitis externa may be absorbed from the round and oval windows into the fluids of inner ear leading to ototoxicity. - Chlorhexidine which was used in the preparartion of ear canal before surgery has also been blamed for such deafness.
  • 14. Investigations - Monitoring drug concentrations in the body. - PTA - Caloric test - Electrocochleography - Oto-acoustic emission - BERA(brain stem evoked response audiometry)
  • 15. Management - Early recognition and discontinuation of drugs. - Hearing aid in cases of severe hearing loss. - Tinnitus treated by mild hypnotics. - Disequilibrium should be treated with reassurance and regular physiotherapy including vestibular exercises, wearing of soft thick padded shoes, avoidance of walking in darkness and unnecessary head movement.