Drug Groups

approved

Description

An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [PubChem]

Indication

For the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.

Pharmacology

Phenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. Phenytoin acts to dampen the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells. It lacks the sedation effects associated with phenobarbital. There are some indications that phenytoin has other effects, including anxiety control and mood stabilization, although it has never been approved for those purposes by the FDA. Phenytoin is primarily metabolized by CYP2C9.

Toxicity

Oral, mouse: LD₅₀ = 150 mg/kg; Oral, rat: LD₅₀ = 1635 mg/kg. Symptoms of overdose include coma, difficulty in pronouncing words correctly, involuntary eye movement, lack of muscle coordination, low blood pressure, nausea, sluggishness, slurred speech, tremors, and vomiting.

Affected Organisms

Biotransformation

Primarily hepatic

Absorption

Bioavailability 70-100% oral, 24.4% for rectal and intravenous administration. Rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours.

Half Life

22 hours (range of 7 to 42 hours)

Protein Binding

Highly protein bound, 90%

Elimination

Most of the drug is excreted in the bile as inactive metabolites which are then reabsorbed from the intestinal tract and excreted in the urine. Urinary excretion of phenytoin and its metabolites occurs partly with glomerular filtration but, more importantly, by tubular secretion.

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