Principles in cochlear toxicity.
The hair cells of the cochlea (neuroepithelium) represent the primary target in most drug-induced ototoxic adverse effects on hearing (e.g. aminoglycoside antibiotics). To what extent an exogenically-induced morphologic damage to hair cells is reversible is not known. In aging structurally altered hair cells can persist for years likewisely not any longer participating in sensory transduction as the hair cells degenerate, secondary changes occur in the spiral ganglion cells and the neuronal pathways. Following heavy metal poisoning an adverse effect is observed on both central and peripheral innervation of the cochlea and only minor primary changes occur in the receptor cells. The link between function and morphology in the cochlea is very obvious regarding the high and middle frequencies with a distinct tonotopic localisation whereas for low frequencies (below 1 khz) such a specific morphologic correlation is lacking. Ototoxic effects primarily affecting the source for the production of endolymph, i.e. the stria vascularis, become manifest at all frequencies and at a rather early stage. Independent of type of substance penetrating into the inner ear, the substance has a considerably slower elimination rate as compared with all other compartments in the body. The toxicity of the drugs seems to be more related to its tissue binding capacity and saturation of receptor sites than related to the concentration of the drug in endo-or perilymph.
D000367:Age Factors; D000617:Aminoglycosides / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000633:toxicity; D000962:Antimalarials / Q000633:toxicity; D000970:Antineoplastic Agents / Q000633:toxicity; D003054:Cochlear Implants; D004232:Diuretics / Q000633:toxicity; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D004622:Embryo, Mammalian / Q000187:drug effects; D004710:Endolymph / Q000032:analysis; D005334:Fever / Q000150:complications; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000628:therapy; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000150:complications; D007700:Kinetics; D007759:Labyrinth Diseases / Q000139:chemically induced* / Q000473:pathology; D008670:Metals / Q000633:toxicity; D051381:Rats; D012459:Salicylates / Q000633:toxicity; D013316:Stria Vascularis / Q000187:drug effects
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000962:Antimalarials; D000970:Antineoplastic Agents; D004232:Diuretics; D008670:Metals; D012459:Salicylates