Phenytoin is a commonly prescribed antiepileptic drug. Due to its saturation (zero-order) pharmacokinetics, phenytoin carries a special risk of dose-related toxicity that is an important issue in emergency medicine.
Phenytoin blocks voltage-sensitive sodium channels in neurons. This action leads to a delay in neuronal electrical recovery from inactivation. Phenytoin's inhibitory effect is dependent on the voltage and frequency of neural cell firing by selectively blocking the neurons that are firing at high frequency. Phenytoin prevents the electrical spread of a focus of irritable tissue from entering normal tissue.
Phenytoin administration has been associated with toxic effects. Phenytoin toxicity depends on the route of administration, duration, exposure, and dosage. The route of administration is the most important determinant of toxicity. Phenytoin may be administered orally or intravenously. In addition, fosphenytoin (water-soluble phenytoin prodrug) may be administered intramuscularly
Gingival hyperplasia is the most common adverse effect (20%) seen with chronically elevated serum phenytoin concentrations but is not associated with acute toxicity.
Neurologic findings in phenytoin toxicity may include the following: Hyperreflexia or hyporeflexia Abnormal gait (bradykinesia, truncal ataxia - Ataxia is very typical with elevated phenytoin levels, and may lead to falls and consequent trauma Encephalopathy Meningeal irritation with pleocytosis Tremor (intention) Irritability or agitation Confusion Hallucinations
Others include the following: Mental status varies from completely normal to the extremes of stupor and coma, particularly if co-ingestants are present Peripheral neuropathy (long-term use) Priapism Urinary incontinence Choreoathetoid movements Dysarthria Dysphagia Seizures (rare) Death (rare)
Eye examination may reveal the following: Nystagmus (horizontal, vertical) Ophthalmoplegia Diplopia Miosis or mydriasis
Gastrointestinal/abdomen findings may include the following: Right upper quadrant tenderness Hepatomegaly Splenomegaly Nausea Vomiting Hepatitis
Fetal hydantoin syndrome Intrauterine exposure to phenytoin will cause fetal hydantoin syndrome which results in the following physical features: Broad nasal bridge Wide fontanelle Low hairline Cleft lip/palate Epicanthal folds Short neck Microcephaly Low-set ears Small or absent nails Hip dislocation Hypoplasia of distal phalanges Impaired growth Congenital heart defects
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