Which of the following symptoms may occur with a phenytoin level of 32 mg/dl?
A. Ataxia and confusion
B. Sodium depletion
C. Tonic-clonic seizure
D. Urinary incontinence
Correct Answer: A. Ataxia and confusion
A therapeutic phenytoin level is 10 to 20 mg/dl. A level of 32 mg/dl indicates toxicity. Symptoms of toxicity include confusion and ataxia. The neurotoxic effects are concentration dependent and can range from mild nystagmus to ataxia, slurred speech, vomiting, lethargy and eventually coma and death. Paradoxically, at very high concentrations, phenytoin can lead to seizures.
Option B: Like all toxicologic exposures, the nature of the toxicity depends on fundamental pharmacologic principles: the route of exposure (oral versus parenteral), duration of exposure (acute overdose versus chronic), dosage, and the nature of metabolism (or deficiency thereof). Phenytoin displays its main signs of toxicity on the nervous and cardiovascular systems. Overdose on oral phenytoin causes mainly neurotoxicity and only very rarely causes cardiovascular toxicity.
Option C: Symptoms correlate well with the unbound plasma phenytoin concentration. However, this laboratory value is seldom obtained. Seizures are very rare and usually occur at very high serum concentrations. The presence of seizures in a patient with suspected phenytoin overdose should prompt the search for other coingestants.
Option D: Phenytoin does not cause urinary incontinence. Incontinence may occur during or after a seizure. Kidney disease can also lead to hypoalbuminemia as well as uremia which decreases the percentage of bound phenytoin in the plasma. Malnutrition, malignancy, and pregnancy are other causes for phenytoin toxicity in a patient on chronic therapy without any changes in dose.
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