Ototoxicity DNB Theory 2018, 2016

Ototoxicity is the partial or total reduction in cochleovestibular function caused by the interaction ofchemicals, commonly therapeutic agents, with the vestibule, cochlea or the vestibulocochlear nerve.1–3 What is Ototoxicity? Classify ototoxic drugs and briefly discuss their mechanism of action in causation of ototoxicity. Q – How will you diagnose and manage a case of ototoxicity? June 2014, Dec 2013, Dec 2016, Dec 2018 Mechanism of Action of various drugs chart Ototoxicity4 Aminoglycosides4 Mechanism of action: -act on bacterial ribosomes to stop synthesis of bacterial cell protein.-bactericidal against gram-negative aerobic bacilli. Mechanism of ototoxicity (theory):-aminoglycosides form complexes with iron - free radicals - damage to outer hair cells and vestibular receptors, type I hair cells are more susceptible than type II hair cells. Histopathology (order of progression): Early damage to first row of outer hair cells beginning at basal turn of cochlea - highfrequency SNHL.Progression to apex.Second and third rows of outer hair cells.Inner hair cells May be due to genetic predispositionDamage is permanent if symptoms persist beyond 2-3 months Vestibulotoxic: Streptomycin and gentamicin-manifested by vertigo or disequilibrium-overall incidence of 15% for gentamicin Cochleotoxic: Amikacin, neomycin, kanamycin, tobramycin-onset heralded by tinnitus Agents that potentiate or synergise with aminoglycosides to cause ototoxicity:-ethacrynic acid (facilitates gentamicin diffusion into endolymph)-furosemide-cisplatin-flagyl Macrolides Ototoxicity reported mainly in pts receiving long-term, high-dose therapy such as for HIV-relatedinfections.-MOA for ototoxicity unknown.-most common manifestation is hearing loss in conversational frequencies.-hearing loss is reversible. Vancomycin Rare reports of cochleotoxicity.Tinnitus and high-frequency hearing loss. Antineoplastic Agents Cisplatin - Usually permanent hearing loss, bilateral and symmetric.High-frequency hearing loss:Histopathology: outer hair cell damage and cell loss most extensive in basal turn.-MOA for ototoxicity thought to be d/t generation of oxygen free radicals within inner ear anddepletion of glutathione in auditory hair cells.->50% receiving > 400 mg/m2 - Permanent ototoxicity. Risk factors:-high cumulative dose of cisplatin.-hx of noise exposure.-high dose of vincristine.-high dose of individual cycle than total dose.-elderly or young children. Carboplatin -79% of patients experience hearing loss.-inner rather than outer hair cells are damaged. Diuretics Furosemide and ethacrynic acid--SNHL, tinnitus and vertigo.-transient and permanent loss reported.-incidence of ototoxicity ~ 6%.-MOA: injury to stria vascularis.-disturbance of K-ion transport with subsequent reduction of endocochlear potential.-keeping the rate of continuous infusion at rates less than 15 mg/min. Salicylates Typically from high-dose aspirin therapy for arthritis.-limited to cochlea - flat, bilateral, SNHL and tinnitus.-serum salicylate levels > 30 mg/100L.-threshold shifts of 30-40 dB.-complete reversibility within 2-3 days after cessation. Ototopicals Human studies estimate incidence ~1/10 000-avoid prolonged use especially when a tympanic membrane perforation present.-avoid use in a healthy ear.-studies in guinea pigs failed to show evidence of ototoxity with topical quinolones. Protocol for patients with Ototoxicity Protocol for patients with Ototoxicity MONITORING Conventional audiometry often used.Limited by several factors (eg. patient participation, logistical impracticalities).ENG and other vestibular testing also impractical.OAEs currently being studied for monitoring ototoxicity. Preloading with glutathione and vitamin C may become standard practice to minimize ototoxicity. Cochleotoxic symptoms require regular pure tone audiometric monitoring until thresholds are stable or improve (temporary threshold shift) in order to quantify the disability. Vestibulotoxic recovery can be symptomatically monitored by out-patient assessment and if necessary quantified by ENG caloricmeasurements. Vestibulosedative medication and rehabilitation exercises, e.g. Cooksey-Cawthorne exercises,minimize morbidity and may aid symptomatic recovery by accelerating compensation ASHA classification of ototoxicity ASHA classification does not include grading, it is the only available classification emphasizing baseline evaluation and is best suited for the earliest identification of ototoxicity. Even though ASHA and AAA guidelines for monitoring of ototoxicity emphasize the significance of DPOAEs, there are no universally accepted criteria to define cochleotoxicity using DPOAEs. 1. Crundwell G, Gomersall P, Baguley D. Ototoxicity (cochleotoxicity) classifications: A review. Int J Audiol. 2016;55(2):65-74. doi:10.3109/14992027.2015.1094188 2. Rybak L, Ramkumar V. Ototoxicity. Kidney Int. 2007;72(8):931-935. doi:10.1038/sj.ki.5002434 3. Ganesan P, Schmiedge J, Manchaiah V, Swapna S, Dhandayutham S, Kothandaraman P. Ototoxicity: A Challenge in Diagnosis and Treatment. J Audiol Otol. 2018;22(2):59-68. doi:10.7874/jao.2017.00360 4. Chan Y, Goddard JC. KJ Lee’s Essential Otolaryngology, 12th Edition. McGraw-Hill Education; 2019. https://books.google.co.in/books?id=AzmbDwAAQBAJ. What is Ototoxicity? Classify ototoxic drugs and briefly discuss their mechanism of action in causation of ototoxicity. Q – How will you diagnose and manage a case of ototoxicity? June 2014, Dec 2013, Dec 2016, Dec 2018 Ototoxicity is the partial or total reduction in cochleovestibular function caused by the interaction of chemicals, commonly therapeutic agents, with the vestibule, cochlea or the vestibulocochlear nerve. Aminoglycoside, Diuretics and cisplatin are few.. Yes, for details see - https://dnbmentors.com/kb/ear-dnb-ent-questions-2010-2019/

Ototoxicity DNB Theory 2018, 2016

Mechanism of Action of various drugs chart

Aminoglycosides⁴

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Mechanism of Action of various drugs chart

Aminoglycosides​4​

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Aminoglycosides⁴