Review Question - QID 103003

This patient likely has phenytoin toxicity secondary to a poor diet, leading to hypoalbuminemia, and an increase in paroxetine, a P450 inhibitor. The level of her prescribed phenytoin should first be checked, then reduced.

Phenytoin toxicity can present with central nervous system signs and symptoms. These include: nystagmus, slurred speech, dizziness, diplopia, ataxia, lethargy, nausea and vomiting. If the drug is administered intravenously cardiac toxicity is also possible and may manifest with arrhythmias and hypotension. In this vignette the patient had been placed on phenytoin after her CVA secondary to seizures. She also likely has hypoalbuminemia and thus increased levels of free phenytoin. The recent increase in paroxetine also likely decreased phenytoin metabolism, increasing serum concentrations.

Roberston et al. review a case of phenytoin toxicity in an elderly patient. Phenytoin is a commonly administered drug in post-CVA patients with seizures. The pharmacokinetics of phenytoin are important to take into account in elderly patients as co-morbidities and drug interactions may predispose towards toxicity. Furthermore, phenytoin is mostly a protein bound drug in the body. In elderly patients with poor nutrition or on a drug like TMP-SMX (which can elevate bilirubin), free phenytoin must be monitored as protein bound levels of the drug are decreased.

Craig provides an overview of phenytoin pharmacology and toxicity. Phenytoin metabolism follows zero-order kinetics and has a narrow therapeutic index. Hence, if an overdose occurs, symptoms can be prolonged. Special attention should be provided when treating a patient with phenytoin in the inpatient setting. Differential diagnoses for toxicity include: drug intoxication (benzodiazepines, alcohol, lithium), hypoglycemia, Wernicke’s encephalopathy and CVA or tumor.

Incorrect Answers:
Answer 1: tPA would be appropriate if this patient were having an occlusive CVA, but her CT suggests otherwise. If stroke is still likely despite this CT scan, the time frame is such that tPA would be inappropriate regardless.
Answer 2: TMP-SMX would be the correct treatment for a urinary tract infection (UTI). While UTIs may present with altered mental status, given the constellation of signs and symptoms in this patient, such a diagnosis is unlikely
Answer 4: TPN will help improve this patient's nutritional status and likely ameliorate phenytoin toxicity over time. Decreasing the level of phenytoin is the most appropriate short term step in this patient.
Answer 5: Increasing the dose of phenytoin would only worsen the patient's condition.