Antiepileptics

Definition

Antiepileptic drugs are medicines that reduce the frequency of epileptic seizures.

This class of drugs includes some drugs that have other uses as well. Phenobarbital is a barbiturate. Barbiturates were once widely used as sleeping pills and are still used in anesthesia for surgery. Clonazepam, clorazepate, and diazepam are members of the benzodiazepine group of drugs and are best known for their use as tranquilizers. Phenytoin is used both to control epileptic seizures and to control irregular heart beats.

Description

There are several different types of epilepsy. Different drugs work best on different types of epilepsy. Following is a list of some of the drugs and their uses:

• topamax (Topiramate), keppra, and ACTH: for infantile spasms (IS)
• ativan: for status epilepticas
• phenobarbital: widely used for tonic-clonic but effective in all forms of epilepsy
• phenytoin (Dilantin): used in tonic-clonic and psychomotor epilepsy
• ethosuximide (Zarontin): used to treat absence seizures
• methsuximide (Celontin): used to treat absence seizures
• zonisamide (Zonegran): used to treat partial seizures
• clonazepam (Klonopin): a benzodiazepine, used to treat absence, myoclonic, and akinetic seizures
• clorazepate (Tranxene): a benzodiazepine used to treat partial seizures
• diazepam (Valium): a benzodiazepine used for treatment of status epilepticus but effective against all forms of epilepsy
• primidone (Mysoline, Myidone, Sertan): useful for tonic-clonic, psychomotor, and focal epilepsy
• valproic acid and sodium valproate (Depakene, Depakote): used to treat all types of generalized seizures
• carbamazepine (Carbatrol, Tegretol): used in treatment of tonic-clonic, mixed, and psychomotor seizures
• felbamate (Felbatol): used primarily in adults but may be used to treat seizures associated with Lennox-Gastaut syndrome
• oxcarbazepine (Trileptal): for treatment of complex-partial, simple-partial, and focal seizures
• lamotrigine (Lamictal): used primarily in adults to treat simple and complex partial seizures but may be used to treat seizures associated with Lennox-Gastaut syndrome in children

General use

Although epilepsy is a collective term for a variety of different types of seizures, all forms of epilepsy start with a random discharge of nerve impulses into the brain. Antiepileptic drugs act by either raising the seizure threshold or by limiting the spread of impulses from one nerve to another inside the brain. As of 2004 the exact mechanism of action is not understood, but there are theories about how some of these drugs work.

Phenobarbital appears to act by slowing down all parts of the brain.

Hydantoins, the class that includes phenytoin, mephenytoin, and ethotoin, seem to work by reducing the flow of sodium into and out of nerve cells. This makes the cells less likely to send out spontaneous impulses, which are the beginning of an epileptic seizure.

Succinimides (ethosuximide, methsuximide, phensuximide) elevate the seizure threshold and make it harder for a nerve impulse to spread from one nerve to another.

Zonisamide may work in a manner similar to the hydantoins, by restricting sodium flow, but some studies contradict this theory.

Benzodiazepines may work by stimulating some brain chemicals that normally slow down nerve function, but the exact mechanism is not known.

Felbamate is similar to the tranquilizer meprobamate (Equanil, Miltown) and may work by blocking the effects of some of the brain chemicals that stimulate the nervous system.

Precautions

Antiepileptic drugs have a large number of side effects and possible adverse effects. To work best, the blood levels of drugs must be kept within a fairly narrow range. Patients should be seen by a qualified physician on a regular basis and, if required, have their blood tested routinely. Too high a blood level of these drugs is likely to cause toxic reactions, while a level that is too low may lead to seizures.

Side effects

Most anticonvulsant medications cause some drowsiness and stomach upset. The following list gives some of the common adverse effects of the various classes of drugs. Parents should consult specific references for more comprehensive lists.

Barbiturates cause the following side effects:

• clumsiness
• dizziness
• constipation
• depression
• faintness

Benzodiazepines cause the following side effects:

• fatigue
• abnormal behavior which can include hallucinations and agitation
• slowed breathing and slowed heart rate
• increased or decreased appetite
• rash and itching

Hydantoins cause the following side effects:

• confusion
• dizziness
• growth of the gums
• severe skin reactions
• stuttering and trembling

Succinimides cause the following side effects:

• dizziness and loss of balance
• severe skin reactions
• depression
• headache
• aggressive behavior

Valproic acid and sodium valproate cause the following side effects:

• stomach and intestinal discomfort
• weight gain or loss
• hair loss
• menstrual bleeding changes
• trembling

Interactions

These drugs have many interactions. People should consult specific references for full information regarding the interactions of all drugs that may be used to treat epilepsy.

Phenobarbital and the hydantoins have a large number of other interactions, but most of the drugs involved are not commonly used in patients under the age of 18 years. The succinimides have no significant drug interactions.

Valproic acid and sodium valproate interact with many of the other drugs used to treat epilepsy. If valproates are added to an existing anti-epileptic drug regimen or other drugs are added to a regimen that contains valproate, additional dose adjustments will usually be needed.

Cimetidine (Tagamet) increases the effects of diazepam, clonazepam, and clorazepate.

Interaction prevention

Because antiepileptic drugs have large numbers of adverse effects and drug interactions, they should be prescribed only by physicians who are experienced in their use. Parents should consult specific references for complete information on the drugs related to their child's case.

Best effects and lowest toxicity are achieved when the blood levels of these drugs are kept constant. Maintaining that constant level requires taking the drugs at the same time each day.

Excessive gum growth associated with the hydantoins can normally be prevented or minimized by good dental care.

Patients taking antiepileptic drugs should not receive additional medications without checking with a physician or pharmacist for possible drug interactions. This precaution includes over-the-counter remedies.

Parental concerns

For liquid dosage forms, parents should always use a medicinal teaspoon or calibrated teaspoon. These are designed to deliver an exact amount of medication. Household teaspoons vary in size and should not be used for measuring medication.

Different dosage forms of the same drug may vary in their onset and duration of action. This fact is particularly relevant to phenytoin, which comes in liquid, chewable tablets, short-acting capsules and long-acting capsules. Patients should not switch from one dosage form to another without consulting their physician.

Because children may not be able to describe some of the symptoms associated with some of the adverse effects of these drugs, any evidence of change in behavior or activity should be discussed with the physician who prescribed the drug.

KEY TERMS

Absence seizure —A brief seizure with an accompanying loss of awareness or alertness. Also known as a petit mal seizure.

Lennox-Gastaut syndrome —A severe form of epilepsy that is characterized by the onset in early childhood of frequent seizures of multiple types and by developmental delay.

Seizure threshold —The amount of stimulation required to induce a seizure.

Sodium —An element; sodium is the most common electrolyte found in animal blood serum.

Tonic-clonic seizure —This is the most common type of seizure among all age groups and is categorized into several phases beginning with vague symptoms hours or days before an attack. These seizures are sometimes called grand mal seizures.

See also Seizure disorder.

Resources

BOOKS

Beers, Mark H., and Robert Berkow, eds. The Merck Manual, 2nd home ed. West Point, PA: Merck & Co., 2004.

Mcevoy, Gerald, et al. AHFS Drug Information 2004. Bethesda, MD: American Society of Healthsystems Pharmacists, 2004.

Siberry, George K., and Robert Iannone, eds. The Harriet Lane Handbook, 15th ed. Philadelphia: Mosby Publishing, 2000.

PERIODICALS

Dutta, S., et al. "Divalproex-ER pharmacokinetics in older children and adolescents." Pediatric Neurology 30 (May 2004): 330–7.

ORGANIZATIONS

American Neurological Association. 5841 Cedar Lake Road, Suite 204, Minneapolis, MN 55416. Web site: <www.aneuroa.org>.

Epilepsy Foundation. 4351 Garden City Drive, Landover, MD 20785-7223. Web site: <www.efa.org>.

WEB SITES

"Epilepsy." MedlinePlus. Available online at <www.nlm.nih.gov/medlineplus/epilepsy.html> (accessed December 20, 2004).

Samuel Uretsky, PharmD