A 60-year-old woman on chronic high-dose aspirin for rheumatoid arthritis develops tinnitus and altered mental status. Her serum salicylate level is elevated. The mechanism of salicylate-induced neurotoxicity (salicylism) is primarily:
- A Direct GABA-A receptor antagonism causing seizures
- B Uncoupling of oxidative phosphorylation and stimulation of the respiratory centre leading to mixed respiratory alkalosis and metabolic acidosis ✓
- C Serotonin syndrome from enhanced 5-HT release
- D Inhibition of vitamin K epoxide reductase causing cerebral microbleeds
Correct answer: B. Uncoupling of oxidative phosphorylation and stimulation of the respiratory centre leading to mixed respiratory alkalosis and metabolic acidosis
Explanation
Salicylate uncouples oxidative phosphorylation in mitochondria, increasing oxygen consumption and CO2 production, which stimulates the medullary respiratory centre causing hyperventilation and respiratory alkalosis. Simultaneously, metabolic acidosis develops from accumulation of lactic acid and ketoacids. This mixed acid-base disturbance with direct CNS toxicity produces tinnitus, confusion, and altered consciousness. Options A, C, and D describe toxicities of other agents.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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