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ORGANIZATION OF CLASS

This class of drugs, often called anticonvulsants, does not lend itself to the type of organization used in many other chapters. Here we need to consider the disease to be treated.

Epilepsy is a chronic disorder characterized by recurrent episodes in which the brain is subject to abnormal excessive discharges (seizures) synchronized throughout a population of neurons. The seizures themselves have been classified to assist with demographics and treatment. The accompanying table provides a simplified seizure classification scheme.

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Seizure Type Clinical Manifestations
I. Partial (focal, local)  
 A. Partial simple Focal motor, sensory, or speech disturbance. No impairment of consciousness.
 B.Partial complex  
 C. Partial seizures with secondary generalization Dreamy state with automatisms. Impaired consciousness.
II. Generalized seizures  
 A. Generalized convulsive (tonic-clonic, grand mal) Loss of consciousness, falling, rigid extension of trunk and limbs. Rhythmic contractions of arms and legs.
 B. Generalized nonconvulsive (absence, petit mal) Impaired consciousness with staring and eye blinks.

Notice that some of these seizures do not involve muscle jerking or convulsions. In particular, absence seizures are called nonconvulsive. Technically, this would make the name anticonvulsants inaccurate, but it is often used to designate this class of drugs.

Now that we have defined the types of seizures we want to control, we can start examining the drugs. To simplify this organization, let’s consider which drugs are used for which types of seizures. There is not 100% agreement on which is the best drug in each category, so do not be bothered by discrepancies between textbooks.

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Focal Seizures Conventional Drugs More Recent Drugs

Simple focal

carbamazepine

brivaracetam

Complex focal

phenytoin

eslicarbazepine

 

valproate

gabapentin

Focal with second generalization

carbamazepine

phenobarbital

phenytoin

primidone

valproate

lacosamide

lamotrigine

levetiracetam

perampanel

rufinamide

tiagabine

topiramate

zonisamide

Generalized Seizures
Absence

ethosuximide

valproate

clonazepam

lamotrigine
Myoclonic

valproate

clonazepam

levetiracetam
Tonic-clonic

carbamazepine

phenobarbital

phenytoin

primidone

valproate

lamotrigine

levetiracetam

topiramate

First, notice all the overlap; that is, drugs are used for more than one seizure type. Valproate is used for all types of seizures, and lamotrigine is used for all except one (check which one!).

IMPORTANT DETAILS ABOUT THE MOST IMPORTANT DRUGS

VALPROATE is associated with elevated liver enzymes, nausea and vomiting, and weight gain. It can also produce a tremor.

Valproate may produce fatal hepatic failure. This is most common in children under the age of 2 years who are taking more than one antiepileptic drug. The hepatotoxicity is not dose related; it is considered to be an idiosyncratic reaction. Valproate is also teratogenic, producing neural tube defects.

CARBAMAZEPINE causes autoinduction of its own metabolism.

Carbamazepine is metabolized by the liver and over a period of several weeks induces the ...

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