A 35-year-old woman on valproate for epilepsy develops tremor, weight gain, and hair loss. These adverse effects are most likely related to which mechanism?

• A Inhibition of histone deacetylase causing epigenetic changes
• B Interference with zinc-dependent enzymes involved in keratinocyte proliferation ✓
• C Inhibition of carnitine transport leading to mitochondrial dysfunction
• D Blockade of thyroid hormone synthesis causing hypothyroidism

Explanation

Valproate-induced alopecia is linked to zinc chelation by valproate metabolites, impairing zinc-dependent enzymes in the hair follicle. Weight gain is mediated by appetite stimulation through increased GABA-B signaling. Tremor results from enhanced GABAergic inhibition in the cerebellum. Selenium deficiency and carnitine depletion occur with long-term valproate use but are linked to hepatotoxicity, not alopecia primarily.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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