Phenytoin exerts its therapeutic effects primarily through its action on voltage-gated sodium channels in the brain. Its key mechanisms include:

1. Sodium Channel Blockade:
   • Phenytoin stabilizes neuronal membranes by binding to and inhibiting voltage-gated sodium channels in their inactivated state.
   • This prevents the repetitive firing of action potentials, which is crucial in controlling seizure activity.
2. Calcium Channel Modulation:
   • Phenytoin also inhibits T-type calcium channels, which play a role in thalamocortical circuitry involved in absence seizures.
3. Neurotransmitter Modulation:
   • By reducing the release of excitatory neurotransmitters like glutamate, phenytoin further contributes to its anticonvulsant effects.
4. Membrane Stabilization:
   • Phenytoin’s ability to stabilize neuronal membranes makes it effective in preventing the spread of abnormal electrical activity in the brain.

Phenytoin is approved for a variety of clinical conditions, including:

1. Epilepsy:
   • Treatment of generalized tonic-clonic seizures (grand mal seizures).
   • Focal (partial) seizures with or without secondary generalization.
   • Prevention and treatment of seizures during or after neurosurgery or traumatic brain injury.
2. Status Epilepticus:
   • Intravenous phenytoin is used as a second-line treatment for status epilepticus (after benzodiazepines).
3. Off-Label Uses:
   • Trigeminal neuralgia (in cases where carbamazepine is not tolerated).
   • Cardiac arrhythmias (due to its membrane-stabilizing effects).

The dosage of phenytoin varies depending on the indication, patient age, and clinical response. The following dosing guidelines are based on the British National Formulary (BNF) and clinical pharmacology references:

1. Epilepsy:
   • Adults: Start with 3–4 mg/kg/day in divided doses, increasing gradually to a maintenance dose of 200–500 mg daily.
   • Children: Start with 5 mg/kg/day in divided doses, adjusted based on response and tolerability.
2. Status Epilepticus:
   • Adults: 15–18 mg/kg intravenously at a rate not exceeding 50 mg/minute.
   • Children: 15–20 mg/kg intravenously at a rate not exceeding 1–3 mg/kg/minute.

Important Considerations:

• Phenytoin has non-linear pharmacokinetics, meaning small dose increases can lead to disproportionately large increases in plasma levels. Therapeutic drug monitoring is essential to maintain plasma levels within the therapeutic range (10–20 mg/L).
• Dose adjustments may be necessary for patients with hepatic or renal impairment.
• Phenytoin is available in oral tablets, capsules, and intravenous formulations.

Phenytoin is associated with a range of side effects, some of which can be serious. Common side effects include:

1. Central Nervous System:
   • Dizziness, drowsiness, ataxia, and nystagmus.
   • Cognitive impairment and behavioral changes.
2. Gastrointestinal:
   • Nausea, vomiting, and constipation.
3. Dermatological:
   • Skin rashes, which may progress to severe reactions like Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).
4. Hematological:
   • Megaloblastic anemia due to folate deficiency.
   • Leukopenia and thrombocytopenia.
5. Other:
   • Gingival hyperplasia (overgrowth of gum tissue).
   • Hirsutism (excessive hair growth).

Serious Side Effects:

• Cardiovascular: Hypotension and arrhythmias with rapid intravenous administration.
• Hepatotoxicity: Elevated liver enzymes and, rarely, severe liver damage.
• Teratogenicity: Phenytoin is associated with fetal hydantoin syndrome, characterized by craniofacial abnormalities, developmental delays, and congenital heart defects.

Phenytoin requires careful monitoring and adherence to specific precautions to ensure patient safety:

1. Therapeutic Drug Monitoring:
   • Regular monitoring of plasma phenytoin levels is essential to avoid toxicity or subtherapeutic levels.
2. Pregnancy and Lactation:
   • Phenytoin should be used during pregnancy only if the potential benefits outweigh the risks. It is excreted in breast milk, so breastfeeding is generally not recommended.
3. Elderly Patients:
   • Lower doses may be required due to increased sensitivity to side effects.
4. Hepatic and Renal Impairment:
   • Dose adjustments are necessary for patients with impaired liver or kidney function.
5. Suicidal Risk:
   • Like other anticonvulsants, phenytoin may increase the risk of suicidal thoughts or behavior.

Phenytoin has a high potential for drug interactions due to its metabolism via cytochrome P450 enzymes (primarily CYP2C9 and CYP2C19) and its ability to induce hepatic enzymes. Key interactions include:

1. CYP2C9/CYP2C19 Inhibitors:
   • Fluconazole and amiodarone can increase phenytoin levels, increasing the risk of toxicity.
2. CYP2C9/CYP2C19 Inducers:
   • Rifampin and carbamazepine can decrease phenytoin levels, reducing its efficacy.
3. Other Anticonvulsants:
   • Valproic acid can increase phenytoin levels by displacing it from protein binding sites.
4. Oral Contraceptives:
   • Phenytoin reduces the efficacy of hormonal contraceptives by increasing their metabolism.
5. Other Interactions:
   • Warfarin: Phenytoin can alter anticoagulant effects.
   • Theophylline: Phenytoin can reduce its levels.

Phenytoin is the generic name for this medication. It is marketed under various brand names, depending on the country and manufacturer. Some examples include:

• Epanutin (a well-known brand in the UK and other regions).
• Dilantin (a widely recognized brand in the United States).
• Phenytek (extended-release formulation).