Toxicology – Phenytoin & Fosphenytoin Toxicity

Source

Phenytoin is an anticonvulsant used for seizure control. Fosphenytoin is a water-soluble prodrug of phenytoin that is commonly used intravenously because it is better tolerated.

Typical Presentation

A patient taking phenytoin may present with unsteady gait, slurred speech, lethargy, and altered mental status. Neurological findings usually become more pronounced as the serum concentration rises.

Clinical Features

Acute toxicity is dominated by neurological symptoms, including:

• Nystagmus
• Nausea and vomiting
• Ataxia and poor coordination
• Slurred speech
• Lethargy
• Extrapyramidal movements
• Altered mental status
• Coma in severe cases

IV phenytoin can also cause:

• Hypotension
• Ventricular dysrhythmias
• Cardiovascular collapse

Chronic therapy may be associated with:

• Gingival hyperplasia
• Coarsening of facial features
• Chronic ataxia
• Liver injury

Mechanism of Action

Phenytoin inhibits voltage-gated sodium channels in neurons, reducing repetitive neuronal firing. Excessive concentrations produce predominantly cerebellar and CNS dysfunction.

Management

Treatment is mainly supportive:

• Airway and respiratory support when necessary
• Neurological monitoring
• Cardiac monitoring after IV phenytoin toxicity
• Activated charcoal may be considered in appropriate recent oral exposures
• Manage hypotension, dysrhythmias, or other complications supportively

There is no specific antidote for phenytoin toxicity.

Key Points

• Nystagmus, ataxia, and slurred speech are classic findings of phenytoin toxicity.
• Neurological toxicity generally worsens as drug levels rise.
• IV phenytoin formulations can cause significant cardiovascular toxicity.
• Fosphenytoin is generally safer for IV administration because it does not contain the propylene glycol vehicle used in traditional IV phenytoin.
• IV phenytoin may cause severe local tissue injury, sometimes referred to as purple glove syndrome.