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How Seizure Medications Work

by Julie A. Murphy, PharmD, BCPS

Seizures happen when neurons fire abnormally and there is a breakdown of the processes that would normally block this abnormal firing.  The excitability can spread locally (focal seizure) or widely (generalized seizure).  The symptoms that a patient experiences are determined by the origin of the seizure (focal versus generalized).

A correct diagnosis of a patient’s seizure type is needed to select the best antiepileptic drug (AED) therapy.  Not all AEDs work on all types of seizures.  Sometimes, an AED can make seizures worse. Various diagnostic tests and a correct description of the seizure itself are needed for an accurate diagnosis.  Some parts of the seizure that are important to note are behavior before and after the seizure, movement of the eyes or head to one side, loss of consciousness, loss of bowel or bladder function, and the length of the seizure.  A patient and/or caregiver should keep a seizure diary to record events.

The overall goal of AED therapy is to improve the patient’s quality of life.   AEDs can help the patient to be free of seizures.  The hope is that this is done with few, if any, side effects.  Different AEDs can do this in different ways. 

First, some AEDs block channels that are used to spread electrical impulses.  Carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenytoin, topiramate, and zonisamide block sodium channels.  Ethosuximide, gabapentin, and pregabalin block calcium channels.  Ezogabine stabilizes potassium channels.

Second, some AEDs control seizures by increasing the action of a neurotransmitter called gamma-aminobutyric acid (GABA) in the brain. By increasing GABA, rapid-fire electrical signals that can cause seizures are slowed down.  Phenobarbital and tiagabine work in this way.  Similarly, valproic acid and vigabatrin will block the breakdown of GABA.

Finally, there are some AEDs that work by multiple mechanisms.  Lacosamide blocks sodium channels and stabilizes hyperexcitable neuronal membranes.  It is thought that levetiracetam may block calcium channels, increase the effect of GABA, and bind to proteins that effect neurotransmitter release.  Felbamate may adjust GABA receptors and block sodium and calcium channels.

The seizures of about 65% of patients with epilepsy can be controlled with one AED.  Often times combination therapy will be necessary.  This will increase the risk of side effects and cost to the patient.  Therapy should not be considered ineffective unless the patient has experienced some concentration-dependent side effect with continued seizure activity.  The most common reason for treatment failure is when the patient does not take the medicine.  About 60% of patients do not take the AED as prescribed.  The more complex the regimen, the more likely a patient is to not take his or her AED.

A patient with the diagnosis of epilepsy should work with the physician to find an AED regimen that is effective for his or her specific seizure type and causes minimal, if any, side effects.

Dr. Murphy is an Associate Professor for the Division of Pharmacy Practice at St. Louis College of Pharmacy.  She is a clinical pharmacist with the Mercy Family Medicine program with Mercy Hospital St. Louis.