Phenytoin
Phenytoin is used orally for the prevention of generalized (grand mal) and partial complex seizures. Intravenous phenytoin is used to treat status epilepticus and occasionally as an antiarrhythmic agent. Oral formulations include suspensions, capsules, and tablet preparations. The brand Dilantin Kapseals exhibits delayed absorption characteristics not usually shared by generic products.
Mechanism of toxicity. Toxicity may be caused by the phenytoin itself or by the propylene glycol diluent used in parenteral preparations. (To make it soluble for IV use, phenytoin must be dissolved in 40% propylene glycol and 10% ethanol at pH 12.)
Phenytoin suppresses high-frequency neuronal firing, primarily by increasing the refractory period of voltage-dependent sodium channels. Toxic levels usually cause CNS depression.
The propylene glycol diluent in parenteral preparations may cause myocardial depression and cardiac arrest when infused rapidly (>40–50 mg/min [0.5–1 mg/kg/min]). The mechanism is not known. The injectable form of phenytoin also is highly alkaline and can cause tissue necrosis if it infiltrates (“purple glove syndrome”).
Fosphenytoin, a water-soluble prodrug, does not contain the propylene glycol diluent and does not cause these toxic effects. As a result, it can be given at rates twice as fast as those for phenytoin. It does not appear to provide faster times to peak plasma phenytoin concentration or to result in fewer adverse effects compared with phenytoin.
Pharmacokinetics.
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