An epileptic patient on long-term phenytoin therapy develops coarse facial features, gum hypertrophy, and hirsutism. Blood levels are within the therapeutic range. These effects are best explained by which pharmacological property of phenytoin?

• A Direct stimulation of fibroblast proliferation independent of plasma levels ✓
• B Induction of hepatic CYP enzymes increasing collagen synthesis
• C Dose-dependent blockade of voltage-gated sodium channels in connective tissue
• D Inhibition of folate absorption leading to megaloblastic overgrowth

Explanation

Gingival hyperplasia, hirsutism, and coarsening of facial features are idiosyncratic cosmetic adverse effects of phenytoin that occur at therapeutic plasma levels and are not strictly dose-dependent. They are thought to arise from phenytoin-stimulated fibroblast proliferation and altered collagen metabolism in peripheral tissues. These effects are particularly problematic in young female patients.

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

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