Phenytoin - Uses, Mechanism Of Action, Adverse Effects & Toxicity (Anti-epileptic Drugs)

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Phenytoin is a first-generation anti-epileptic medication used in the treatment of various types of seizures, terminal neuralgia, behavioral disorders, and status epilepticus; a condition characterized by prolonged seizures.
A seizure is a condition where there is uncontrolled, abnormal electrical activity of the brain, causing neurons to fire action potentials more frequently.
Voltage-gated membrane sodium channels of the neurons are responsible for this increased firing of nerve signals.
Phenytoin works by blocking these voltage-gated sodium channels, reducing the frequency of nerve signals.
Phenytoin can be administered orally and intravenously.
Phenytoin achieves higher concentrations in the central nervous system compared to the serum.
Therefore, it is ideal in the treatment of central nervous system disorders.
Phenytoin is metabolized by the cytochrome P450 enzyme system in the liver.
Drugs that alter the function of these enzymes affect the plasma concentrations of phenytoin.
Medications that inhibit these enzymes will increase the plasma concentrations of phenytoin.
Some of these drugs include amiodarone, cimetidine, metronidazole, chloramphenicol, sodium valproate, and sulfonamides.
By contrast, medications that induce the enzyme system will decrease the plasma concentrations of phenytoin.
Some of these drugs include rifampicin, barbiturates, theophylline, and carbamazepine.
So, individuals who are taking these medications concurrently with phenytoin require dose adjustments according to the clinical response.
Major adverse effects of phenytoin include the following.
Gingival hyperplasia.
Hypotension.
Arrhythmias.
Sedation.
Psychosis.
Megaloblastic anemia.
Steven Johnson syndrome.
Decreased bone mineral content with long-term use.
And immunoglobulin A deficiency.
Since phenytoin is a medication with a narrow therapeutic index, it is important to know the toxic effects of the drug.
Phenytoin displays its primary signs of toxicity in the nervous system and cardiovascular system.
Main central nervous system effects include nystagmus, slurred speech, tremors, hyperactivity, seizures, and coma.
In the cardiovascular system, it can cause life-threatening arrhythmias, hypotension, and cardiovascular collapse.
Finally, there is a rare condition associated with phenytoin crystallization within the circulation called “Purple Glove Syndrome”.
This condition is characterized by worsening limb edema and discoloration.
If not identified and corrected early, this can lead to life-threatening ischemia of the limb, which necessitates amputation.

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