What are the uses of Phenytoin (antiepileptic drug)?

Uses of Phenytoin

Phenytoin is primarily indicated for the treatment of generalized tonic-clonic seizures, partial seizures with or without generalization, and convulsive status epilepticus, but is no longer considered first-line therapy for most seizure disorders due to its adverse effect profile.

Primary Indications

Seizure Management

• Generalized tonic-clonic seizures (formerly known as grand mal seizures) 1
• Partial seizures (simple partial, complex partial, and secondarily generalized) 1, 2
• Status epilepticus (emergency treatment) 3
• Prevention of seizures during neurosurgery 3
• Short-term intravenous substitution when oral phenytoin administration is not possible 3

Mechanism of Action

Phenytoin works by:

• Inhibiting the spread of seizure activity in the motor cortex 1
• Promoting sodium efflux from neurons 1
• Stabilizing neuronal membranes against hyperexcitability 1
• Reducing posttetanic potentiation at synapses 1
• Reducing activity in brain stem centers responsible for tonic-clonic seizures 1

Clinical Considerations

Efficacy and Limitations

• Therapeutic serum levels range between 10-20 mcg/mL 1
• Plasma half-life averages 22 hours (range 7-42 hours) 1
• Steady-state levels achieved after 7-10 days of therapy 1
• Exhibits saturable metabolism (non-linear pharmacokinetics) at higher doses 1, 4
• 90-95% protein bound in plasma 4

Important Limitations and Adverse Effects

1. Not recommended for prophylaxis of post-traumatic seizures

   • Guidelines do not support routine use for primary prevention of post-traumatic seizures 5
   • If prophylaxis is needed in high-risk TBI patients, levetiracetam is preferred over phenytoin 5

2. Not recommended for seizure prophylaxis in aneurysmal subarachnoid hemorrhage

   • Potentially harmful for seizure prophylaxis in aSAH 5
   • Associated with poorer cognitive outcomes 5

3. Significant adverse effects:

   • Hypotension and cardiac dysrhythmias with IV administration 6
   • "Purple glove syndrome" with IV administration 6
   • Gingival hyperplasia, coarsening of facies, and hirsutism with long-term use 7
   • Phenytoin encephalopathy (cognitive impairment and cerebellar syndrome) 4
   • Severe thrombocytopenia (rare but potentially life-threatening) 8
   • Various cutaneous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis 7

Current Place in Therapy

Status Epilepticus

• Traditionally used after benzodiazepines for status epilepticus 5
• Success rate of approximately 56% in terminating status epilepticus 5
• Alternative agents with better safety profiles are now available:
  • Valproate (88% success rate, fewer hypotensive events) 5
  • Levetiracetam (44-73% success rate, minimal adverse effects) 6

Specific Patient Populations

• Intellectual disability: Not recommended due to susceptibility to balance disturbances and cognitive dysfunction 4
• Brain tumor patients: Caution due to risk of severe thrombocytopenia 8
• Pregnancy: Associated with fetal hydantoin syndrome 7

Monitoring Requirements

• Serum level monitoring recommended 5-7 half-lives after treatment initiation or dosage change 1
• Trough levels provide information about clinically effective range and confirm compliance 1
• Peak levels indicate threshold for dose-related side effects 1
• Regular monitoring of complete blood count due to risk of thrombocytopenia 8
• Monitoring of cognitive function during long-term therapy 4

Phenytoin remains an effective antiepileptic medication but requires careful patient selection and monitoring due to its complex pharmacokinetics and potential for significant adverse effects. Newer antiepileptic drugs with better safety profiles are generally preferred for most indications.