Drugs for Seizure Disorders and Epilepsy

The text spends a lot of time going through the description of epilepsy, which is measured by the EEG for partial seizures, local seizures, grand mal seizures, petit mal seizures… these are all terms that go back to the turn of the last century when electrical recording began to be used. Epilepsy is diagnosed by electroencephalogram. The goal of therapy is to manage the pts symptoms, so that they have some quality of life. Some newer drugs only control 30-40% of pts. So the search for an ideal anti-epileptic drug continues.


There is a condition known as “status epilepticus” that is life threatening! If this occurs in your dental office, you’ll need to dust off the emergency drug kit and give i.v. Valium (diazepam), immediately. It turns out that this is an obsolete drug, because the new paradigm for treating status epilepticus involves use of a benzodiazepine, and the protocol is in the handout (not text). By the way, “obsolete” only means that there is a superior drug available, not that the older drug is illegal or contraindicated.


This describes the frequencies of types of seizures that occur. 35% of seizures are complex partial (temporal lobe), 30% are grand mal (tonic-clonic). Except for status epilepticus, seizures will be self limiting.



When you’re taking your history, be sure that you understand when the pt was first diagnosed, sometimes its very early. For example, at birth a fever is often associated with seizures, mothers are taught to put their baby into a cold bath with ice and to cool the body temp so the seizure will stop. Head trauma is another indication where there is physical damage that can lead to seizures…



So infection also can cause seizures. Then there can be idiopathic seizures, where we don’t know what’s causing it.


Local anesthetic toxicity: The toxic manifestations of all local anesthetics, as you approach the maximum recommended dose (you need to know this in mg/kg weight), you can precipitate convulsions and seizures. There is no antidote to local anesthetic-induced convulsions. You can manage the symptoms, but there is no specific antidote. This is why we need to know the number of carpules, and mg/kg, that we can use in an adult.


As far as drug therapy, the real decision of the neurologist is based on the tolerability of the drug. The efficacy is sometimes low, but the decision which drug to use is based on the side effects profile, and avoiding drug interactions.


Carbamazepine (Tegretol) is an adjunct for neuropathic pain, but was developed only for epilepsy. So if your pt is taking Tegretol you must specify why they are taking it (seizures or peripheral neuropathy). Phenytoin (Dilantin) is very old. Although both of these drugs are “obsolete” compared to the newer agents, they still have some role. The newer agents, such as Valproic acid, have tremendous risk of toxicity and significant warnings which have implications in terms of dental practice.


The action of Dilantin on the Na+ channel facilitates its results. Dilantin blocks the sodium flux by blocking the channel and so prolongs the inactive state of the sodium channel. We don’t know how the newer agents work, all we know is that they control seizures.


There’s a need to monitor blood levels when a pt is taking these drugs (carbamazepine, phenytoin, ethosucimide, valproic acid). Because there is tremendous variability in bioavailability and serum levels associated with both brand name and generic Dilantin. So there are drugs that when the physician is titrating the drugs they must monitor blood levels, obviously this adds to the cost of treating a disorder.


We see that half-lives are relatively long, over 10-15 hours sustained release allows for once a day dosing. This improves compliance.



With regards to the drugs of choice, in grand mal carbamazepine, phenytoin and valproate tend to be our first choices. You’ll notice Phenobarbital here, which was used long before the other drugs, but the side effects included drowsiness, sedation and tolerance, which decreases the effectiveness over time. For partial seizures, including secondarily generalized, we have the same choice drugs. Neurologists have many choices of drugs and where they switch from one to another depends on the response of the pt.


Regarding status epilepticus, i.v. diazepam (which has many indications: anxiety, hypnotic, and parenterally anti-seizure properties) is in our emergency dentist kits. Now, Lorazepam is preferred because it is superior in efficacy.


Clinical Problems

Tegretol (Carbamazepine) can result in agranulocytosis and aplastic anemia.

Dilantin (Phenytoin) can result in gingival hyperplasia, among other things such as Hirsutism (excessive hair growth), ataxia and nystagmus (rapid movement of the eyes), plus some CNS effects which clearly limits the use of this drug.

Valproic Acid can result in liver problems.

Phenobarbital results in drowsiness, sedation, cognitive impairment, and because the liver p450 system is actually stimulated other drugs are metabolized faster.


Trade Names

A pharmacist was sued when he substituted a generic version of Dilantin when the MD ordered “do not substitute.” The pt was killed. So there’s a new law: when a generic drug is introduced, the drug company must prove efficacy.

Category: Pharmacology Notes