Anticonvulsant drugs

Anticonvulsant drugs inhibit neuromuscular transmission. They can be

prescribed for:
• long-term management of chronic epilepsy (recurrent seizures)
• short-term management of acute isolated seizures not caused by
epilepsy, such as seizures after trauma or brain surgery.
In addition, some anticonvulsants are used in the emergency treatment
of status epilepticus (a continuous seizure state).Treatment of epilepsy
should begin with a single drug, increasing the dosage until seizures
are controlled or adverse effects become problematic. Generally, a second
alternative should be tried as monotherapy before considering
combination therapy. Choice of drug treatment depends on the seizure
type, the drug’s characteristics, and the patient’s preferences.
Anticonvulsants can be categorized into several major classes:
• hydantoins
• barbiturates
• iminostilbenes
• benzodiazepines
• carboxylic acid derivatives
• 1-(aminomethyl) cyclohexane acetic acid
• phenyltriazine
• carboxamide
• sulfamate-substituted monosaccharides
• succinimides
• sulfonamides

Hydantoins
The two most commonly prescribed anticonvulsant drugs— phenytoin
and phenytoin sodium—belong to the hydantoin class. Other hydantoins
include fosphenytoin and ethotoin.

Pharmacokinetics
The pharmacokinetics of hydantoins varies from drug to drug. Phenytoin
is absorbed slowly after oral and IM administration. It’s distributed rapidly
to all tissues and is highly (90%) protein bound. Phenytoin is metabolized
in the liver. Inactive metabolites are excreted in bile and then reabsorbed
from the GI tract. Eventually, however, they’re excreted in urine.
Ethotoin is metabolized by the liver. Extensively protein bound, ethotoin
is excreted in urine, primarily as metabolites.
Fosphenytoin is indicated for short-term IM or IV administration.
It’s widely distributed throughout the body, is highly (90%) protein bound,
and is metabolized by the liver and excreted in urine.

Pharmacodynamics
In most cases, the hydantoin anticonvulsants stabilize nerve cells to keep
them from getting overexcited. Phenytoin appears to work in the motor
cortex of the brain, where it stops the spread of seizure activity. The
pharmacodynamics of fosphenytoin and ethotoin are thought to mimic
those of phenytoin.
Pharmacotherapeutics
Because of its effectiveness and relatively low toxicity, phenytoin is the
most commonly prescribed anticonvulsant and one of the drugs of choice
to treat:
• complex partial seizures (also called psychomotor or temporal lobe
seizures)
• tonic-clonic seizures.
The enzyme system responsible for the metabolism of phenytoin is
saturable. A change in dose can result in disproportional changes in serum
concentration. Health care providers sometimes prescribe ethotoin in
combination with other anticonvulsants for partial and tonic-clonic
seizures in patients who are resistant to or intolerant of other
anticonvulsants. Phenytoin and fosphenytoin are the long-acting
anticonvulsants of choice to treat status epilepticus after initial IV
benzodiazepines.

Drug interactions
Hydantoins interact with several drugs. Here are some drug interactions of
major to moderate clinical significance:
• The effect of phenytoin is reduced when taken with phenobarbital,
diazoxide, theophylline, carbamazepine, rifampin, antacids, and
sucralfate.
• Enteral tube feedings may interfere with the absorption of oral
phenytoin. Stop feedings for 2 hours before and after phenytoin
administration.
• The effect of phenytoin is increased and the risk of toxicity increases
when phenytoin is taken with allopurinol, cimetidine, disulfiram,
fluconazole, isoniazid, omeprazole, sulfonamides, oral
anticoagulants, chloramphenicol, valproic acid, or amiodarone.
• The effect of the following drugs is reduced when taken with a
hydantoin anticonvulsant: oral anticoagulants, levodopa,
amiodarone, corticosteroids, doxycycline, methadone, metyrapone,
quinidine, theophylline, thyroid hormone, hormonal contraceptives,
valproic acid, cyclosporine, and carbamazepine.

Adverse reactions
Adverse reactions to hydantoins include:
• drowsiness
• ataxia
• irritability and restlessness
• headache
• nystagmus
• dizziness and vertigo
• dysarthria
• nausea and vomiting
• abdominal pain
• anorexia
• depressed atrial and ventricular conduction
• ventricular fibrillation (in toxic states)
• bradycardia, hypotension, and cardiac arrest (with IV administration)
• hypersensitivity reactions.