Pregnancy And anti epileptic drugs

-the incidence of cleft palate with mothers taking Dilantin: 2-5%

-the incidence of cleft palate in normal pregnancy (no drugs): 0.5%

-Lidocaine + epi pregnancy category: B

-Dilantin pregnancy category: D

Pregnancy categories range from A (being absolutely safe, there are no drugs that are absolutely safe for pregnant women to take) to B (practically no risk) to C to D to X (being absolutely contraindicated for pregnant women because of proven harmful effects to the baby). When you see a drug that is a “D” that means that there’s lots of evidence, in humans that the drug should be avoided. So clearly, the court found that the cleft palate was not from using lidocaine judiciously, but from use of Dilantin.



Epilepsy is the third most common neurologic disorder. Epilepsy is diagnosed as a discreet clinical event, accompanied by an abnormal electrical discharge in the brain. Not all seizures indicate epilepsy; if you O.D. your pt with lidocaine you can induce seizures. Provoked seizures are less predictive than epilepsy. As soon as you see any excitation, be aware that you can quickly provoke a seizure disorder.



If you had to get a med consult, it would only be to determine whether or not the pt is controlled. The neurologist would probably say they have some generalized seizures, either myoclonic, tonic-clonic, tonic, clonic, atonic, or absence. Absense refers to a peculiar seizure in which a pt just stares blankly into space, not thrashing around, but it is a seizure and is diagnosed by that behavior and an EEG. Partial seizures are less likely to be encountered because they’re minor.


Goals of therapy for epileptics include: eliminating seizures or reducing seizure frequency as much as possible, avoiding acute and chronic side effects of therapy (almost impossible to do, ie. Dilantin pts may show some or all side effects associated with use), maintaining or restoring normal psychosocial/vocational adjustment (basically ensuring quality of life as much as possible).




If we understood the etiology of disease better, we could treat epileptics better. All drugs that we’re discussing today are CNS depressants and decrease neuronal firing. Two neurotransmitters prevalent in human brains, Glutamate and Aspartate, clinically cause excitation, so these are nice targets for drugs. However, maybe pts have seizures because they lack inhibitory neurotransmitters, such as GABA. This theory was used in developing Neurontin (gabapentin) as a drug. But alas, gabapentin doesn’t work that way… its anti-epileptic properties have nothing to do with GABA receptors. So although it’s a good rational, it just didn’t pan out the way they planned.



Keppra is a newer agent, not discussed in the book. It is an anti-epileptic drug for the treatment of seizures in adults. The exact anti-epileptic effect is unknown. Protection against secondarily generalized activity from focal seizures induced by two chemoconvulsants that induce seizures (ie. lidocaine overdose) was observed. Keppra is rapidly and almost completely absorbed, and is not affected by food; good bioavailability, low protein binding. The drug is metabolized by the cytochrome system p450 enzymes. Metabolites are inactive. Clinical trials say that you control between 20-40% of pts. This is the newest and preferred agent of neurologists now, probably because of lack of interactions with other drugs.



Gabapentin is an amino acid, an analog of GABA that is effective against partial seizures. Originally planned as a spasmolytic (smooth muscle relaxing agent), it was found to be more effective as an anti-epileptic drug… it was a serendipitous discovery.



Gabapentin is unbound in plasma proteins. NSAIDS have a very high affinity for serum albumin, any drug bound to these proteins will have a drug interaction. Gabapentin’s mechanism of anti manic properties is not known. It is used as adjunctive therapy in the treatment of partial seizures; not monotherapy.


Adverse effects of Gabapentin include fatique, somnolence, dizziness, ataxia and nystagmus. From these effects we can see that this is a CNS depressant.



Felbamate (Felbatol) was popular a few years ago, but with chronic use was found to cause aplastic anemia (bone marrow suppression) and severe hepatitis at unexpectedly high rates, and so has been relegated to a third-line drug for refractory cases. Despite the seriousness of the adverse effects, approximately 10,000-15,000 pts in the USA remain on the med. So neurologists must weigh the risks involved, this drug is expensive because of the blood monitoring that must be involved.



According to published and unpublished reports, Valproic Acid (Depakene) may produce teratogenic effects in the offspting of human females receiving the drug during pregnancy. The dilemma is this: the mother must be controlled because if she gets seizures during pregnancy there is an even greater risk for the child than the teratogenic possibilities from taking the drugs to control her.

Category: Pharmacology Notes