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  1. 1. Ototoxicity a silent hazard
  2. 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. 3. Ototoxic drugs- Aminoglycosides- Diuretics- Antimalarials- Anticancer drugs- Analgesics- Miscellaneous
  4. 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. 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. 6. Normal inner ear hair cells Damaged inner ear hair cells
  7. 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. 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. 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. 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. 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. 12. Chemicals classes:- Gas(Carbon monoxide)- Heavy metals(lead, arsenic, mercury)- Organic solvents(carbon disulfide, styrene, xylene and toluene).
  13. 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. 14. Investigations- Monitoring drug concentrations in the body.- PTA- Caloric test- Electrocochleography- Oto-acoustic emission- BERA(brain stem evoked response audiometry)
  15. 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.
  16. 16. Abhilash