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Phenytoin is a hydantoin compound related to the barbiturates that are used for the treatment of seizures. It is an effective anticonvulsant for the chronic treatment of tonic-clonic (grand mal) or partial seizures and the acute treatment of generalized status epilepticus (Table 10-1).1,2 After generalized status epilepticus has been controlled with intravenous benzodiazepine therapy and supportive measures have been instituted, phenytoin therapy is usually immediately instituted with the administration of intravenous phenytoin or fosphenytoin. Orally administered phenytoin is used chronically to provide prophylaxis against tonic-clonic or partial seizures. Phenytoin is a type 1B antiarrhythmic and is also used in the treatment of trigeminal neuralgia.

Table 10-1 International Classification of Epileptic Seizures with Treatment Recommendation

The antiseizure activity of phenytoin is related to its ability to inhibit the repetitive firing of action potentials caused by prolonged depolarization of neurons.3,4 Additionally, phenytoin stops the spread of abnormal discharges from epileptic foci thereby decreasing the spread of seizure activity throughout the brain. Posttetanic potentiation at synaptic junctions are blocked which alters synaptic transmission. At the cellular level, the mechanism of action for phenytoin appears related to its ability to prolong the inactivation of voltage-activated sodium ion channels and reduction of the ability of neurons to fire at high frequencies.

The usual therapeutic range for total (unbound + bound) phenytoin serum concentrations when the drug is used in the treatment of seizures is 10–20 μ/mL. Since phenytoin is highly bound (~90%) to albumin, it is prone to plasma protein binding displacement due to a large variety of factors. Because of this, unbound or “free” phenytoin concentrations are widely available. Although there is clinical data to support the therapeutic range for total phenytoin concentrations, the suggested therapeutic range for unbound phenytoin concentrations is based on the usual unbound fraction (10%) of phenytoin in individuals with normal plasma protein binding. Thus, the generally accepted therapeutic range for unbound phenytoin concentrations is 1–2 μg/mL, which is simply 10% ...

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