Which antiepileptic drug causes gingival hyperplasia as a dose-dependent adverse effect and requires monitoring of serum levels for therapeutic drug monitoring?

Explanation

## Phenytoin: Gingival Hyperplasia and Therapeutic Drug Monitoring ### Gingival Hyperplasia **Key Point:** Phenytoin causes gingival hyperplasia in 20–30% of patients, a dose-dependent adverse effect that is one of its most distinctive side effects. #### Mechanism - Overgrowth of gingival connective tissue (fibroblast proliferation) - Increased collagen synthesis - Exacerbated by poor oral hygiene - Reversible upon drug discontinuation (though may require surgical correction if severe) #### Management - Meticulous oral hygiene - Regular dental care - Switching to alternative antiepileptic if severe ### Therapeutic Drug Monitoring (TDM) | Parameter | Value | |-----------|-------| | **Therapeutic range** | 10–20 μg/mL (or 40–80 μmol/L) | | **Half-life** | 24 hours (but dose-dependent due to saturation kinetics) | | **Protein binding** | 90% | | **Metabolism** | CYP2C9, CYP2C19 (saturation kinetics at therapeutic doses) | **High-Yield:** Phenytoin exhibits **Michaelis–Menten (saturation) kinetics** at therapeutic doses, meaning small increases in dose can cause disproportionate increases in serum levels. This necessitates careful TDM. **Mnemonic:** **PHENYTOIN** side effects = **P**oor gingival health, **H**irsutism, **E**xfoliate dermatitis, **N**ystagmus, **Y**ellow discoloration (teeth), **T**remor, **O**steodystrophy, **I**ncoordination, **N**europathy. **Clinical Pearl:** Gingival hyperplasia is virtually pathognomonic for phenytoin among antiepileptics and should alert the clinician to check compliance and serum levels. [cite:KD Tripathi 8e Ch 12]