Marklet

medical presentation

Phenytoin Overview

Introduction

Phenytoin is a hydantoin derivative widely used as an antiepileptic drug in the management of various seizure disorders.

Mechanism of Action

  1. 1Primary action involves the selective blockade of voltage-gated sodium channels in neuronal membranes.
  2. 2Slows the rate of recovery of sodium channels from inactivation, suppressing high-frequency repetitive neuronal firing.
  3. 3Exerts membrane-stabilizing effects across the central nervous system.

Clinical Uses

  1. 1Management of generalized tonic-clonic seizures.
  2. 2Treatment of focal (partial) seizures.
  3. 3Prevention and treatment of seizures occurring during or following neurosurgery.
  4. 4Management of status epilepticus (typically following initial benzodiazepine therapy).

Pharmacokinetics

  1. 1Absorption: Variable oral absorption rate dependent on formulation and patient factors.
  2. 2Distribution: High plasma protein binding, primarily to albumin (approximately 90–95%).
  3. 3Metabolism: Hepatic metabolism via cytochrome P450 enzymes (CYP2C9 and CYP2C19) exhibiting saturable (Michaelis-Menten) kinetics at therapeutic concentrations.
  4. 4Excretion: Excreted primarily as inactive metabolites in the urine via glomerular filtration and active tubular secretion.

Adverse Drug Reactions (ADR)

  1. 1Common effects: Nystagmus, ataxia, slurred speech, dizziness, and cognitive impairment.
  2. 2Long-term effects: Gingival hyperplasia, hirsutism, peripheral neuropathy, and osteomalacia.
  3. 3Idiosyncratic reactions: Hypersensitivity syndrome, Stevens-Johnson syndrome, hepatotoxicity, and blood dyscrasias (e.g., agranulocytosis).

Drug Interactions

  1. 1Enzyme induction: Phenytoin is a potent inducer of hepatic CYP enzymes (CYP3A4, CYP2C9, CYP2C19) and UGT, potentially reducing the efficacy of co-administered drugs such as oral contraceptives and warfarin.
  2. 2Plasma concentration modifiers: Drugs that inhibit CYP2C9/CYP2C19 (e.g., amiodarone, fluconazole) can increase phenytoin levels and toxicity.
  3. 3Protein-binding displacement: Agents like valproic acid can displace phenytoin from plasma proteins, transiently altering free fraction levels.

Safety Note

Consult current prescribing information and a qualified healthcare professional for complete dosing, monitoring, and safety guidelines.