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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.
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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.
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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% ...