AED - Anti-epileptic drug

THERAPEUTIC SERUM (BLOOD) LEVEL - the concentration of medication in the blood to prevent seizures without causing toxicity.

LINEAR PHARMACOKINETICS - the way a drug dose produces an increase in serum level when the level is therapeutic. Linear means that, for phenytoin (Dilantin) as an example, at a level of 15 a 100 mg dose produces an increase of 1 mg/liter or 1 microgram/milliliter in the blood level to a level of 16, and a 200 mg dose produces an increase of 2 micrograms/milliliter to a level of 17. Dilantin has linear pharmacokinetics up to a serum level of 20 micrograms/milliliter.

NONLINEAR PHARMACOKINETICS - the way an additional dose produces an unexpectedly large increase in serum level when the level is higher than therapeutic. At a level of 25, an additional 100 mg of Dilantin may increase the level to 28 rather than to 26.

TITRATION - adjustment of dosage to obtain best serum level to get efficacy (seizure control) with the least side effects

BENEFIT/RISK RATIO - the comparison of the benefits of using a drug to the risk. For example, in patients with intractable complex partial seizures who are not candidates for surgery, Felbatol may have a favorable benefit/risk ratio. Although Felbatol can rarely cause severe problems with the blood and liver, the risk of uncontrolled seizures is worse. Another example is epilepsy surgery. Although there is a risk of complication of 1%-2% with epilepsy surgery, in patients with intractable complex partial seizures, surgery has a favorable benefit risk ratio, since the cure rate, for temporal lobectomy - 85% seizure free and 97% marked reduction of seizures, outweights the risk of complication, since with ongoing complex partial seizures, there is a greater than 5% risk of injury.

AM SERUM TROUGH LEVEL - Blood level taken in the morning before medications. The lowest level which a patient usually experiences in the day since no drug has been taken all night and the level at which the patient is most vulnerable to breakthrough seizures.

LENNOX-GASTAUT SYNDROME - a severe, common form of epilepsy which usually consists of multiple, difficult to control seizure types, slow generalized spike and wave on EEG (2 cycles per second), usually developmental delay. Of note is that 10% of patients do not have developmental delay.

MONOTHERAPY - The use of one anti-epileptic medication to control seizures. This is preferred since usually with the standard AEDs, efficacy does not add with the addition of another AED, but toxic side effects do. Therefore, the best benefit/side effect ratio has been obtained with monotherapy.

POLYTHERAPY - The use of more than one medication to control seizrues.

RATIONAL POLYTHERAPY - The use of more than one AED to control seizures in a rational, state-of-the-art approach which selects two AEDs with different mechanisms of action. Thus, the efficacy of each drug adds with the other to produce a greater overall efficacy. This was not true with most of the standard AEDs in the past, but is becoming more useful with the newer AEDs. Examples of rational polytherapy are Dilantin and Neurontin.

STEADY STATE - A condition where the AED has reached a stable blood level so that if the person continues to take the same dose each day the level will stay the same. With most AEDs steady state blood levels occur after five half lives.

HALF LIFE - The time it takes for the blood level to decrease by half after a drug is stopped. Therefore, if an AED which has a half life of 24 hours is stopped and the blood level at that time is 20, in 24 hours the level will decrease to 10. (The level then will decrease to 5 in 48 hours, 2.5 in 72 hours, 1.25 in 96 hours, etc.)

WITHDRAWAL SEIZURES - When some AEDs are withdrawn abruptly, seizures can occur as a result. The following AEDs cause withdrawal seizures when the drug is abruptly withdrawn: barbiturates (phenobarbital, Mysoline, Mebarall) and benzodiazepines (Klonopin, Ativan, Valium, Tranxene). Some of the newer AEDs can cause withdrawal seizures if stopped faster than 1-2 weeks: Neurontin and Lamictal. The following drugs do not cause withdrawal seizures: Tegretol, Dilantin, Depakote. However, in someone who has been controlled on these AEDs, when the AEDs are stopped abruptly, there may be unmasking of seizures. Therefore we very gradually taper patients off the barbiturates and benzodiazepines over six months and taper off Neurontin and Lamictal over several weeks. When we switch patients over to a different drug we can taper Dilantin, Depakote and Tegretol within a week. Note these times are when adjusting or changing over to a new medication. If a patient is coming off medication after being seizure-free for two years, we taper barbiturates and benzodiazipines over six to nine months and with the other medications over 2-3 months or longer. This is done because of the risk of unmasking a flurry of seizures (status epilepticus).