Which of the following mechanism is mainly responsible for gentamicin induced ototoxicity?

GENTAMICIN It was obtained from Micromonospora purpurea in 1964; has become the most commonly used aminoglycoside for acute infections. The propeies of gentamicin including plasma tY=2 of 2-4 hours after i.m. injection are the same as described above for streptomycin, but there are following differences: (a) It is more potent (MIC for most organisms is 4-8 times lower.) (b) It has a broader spectrum of action: effective against Ps. aeruginosa and most strains of Proteus, E. coli, Klebsiella, Enterobacter, Serratia. (c) It is ineffective against M. tuberculosis, Strep. pyogenes and Strep. pneumoniae, but inhibits many Strep. faecalis and some Staph. au reus. (d) It is relatively more nephrotoxic Ototoxicity This is the most impoant dose and duration of treatment related adverse effect. The vestibular or the cochlear pa may be primarily affected by a paicular aminoglycoside. These drugs are concentrated in the labyrinthine fluid and are slowly removed from it when the plasma concentration falls. Ototoxicity is greater when plasma concentration of the drug is persistently high and above a threshold value. The vestibular /cochlear sensory cells and hairs undergo concentration dependent destructive changes. Amoglycoside ear drops can cause ototoxicity when instilled in patients with perforated eardrum; contraindicated in them. ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:721