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Antiepileptic Medications During Pregnancy
Antiepileptic Medications During Pregnancy
during Pregnancy
>Pathophysiology
>Paroxysmal dosorder of the CNS
>Abnormal neuronal discharge with or without loss of consciousness
>Two broad categories of epileptic syndrome:
-Partial seizure
-Generalized seizure
<Partial seizure>
-15% of all seizure
-Trauma, abscess, tumor, or perinatal factors
>Causes of Seizures:
-Trauma
-Alcohol- and other drug-induced withdrawals
-Brain tumors
-Biochemical abnormalities
-Arteriovenous malformation
Epilepsy during Pregnancy
>Carbamazepine
-Relatively slow absorption
-70~80% protein binding to albumin
-Main route of elimination : Hepatic metabolism
-Drug levels and bioavailability tend to be lower in pregnancy
-Carbamazepine-10,11-epoxide: increase during pregnancy
impaired conversion of carbamazepine
increased carbamazepine metabolism
>Phenytoin
-Highly bind to protein(90~93%)
-Main route of elimination : Hepatic metabolism
-8-hydoxylation: substantial increased during
pregnancy increased clearance rate and
consequently decreased serum concentration
fall in total serum phenytoin concentration
cause lack of seizure control
>Phenobarbital
-Sedation and impaired cognitive function
-High oral bioavailability(90%), protein-bound(50%)
-Induced hepatic microsomal oxidative enzymes
-Main route of elimination : Hepatic metabolism
-Long elimination half life
>Valproic acid
-Rapidly absorption
-Highly protein-bound to plasma albumin(88~92%)
-Pharmacokinetics limitation by:
1)large fluctuation in the concentration–time profile
2)wide therapeutic index
3)concentration-dependent protein binding
-Dose adjustments during pregnancy
>New antiepileptic drug
:Topiramate, Felbamate, Oxcarbazepine, Gabapentin,
Vigabatrin, Lamotrigine
-no antifolate effects
-no arene oxide metabolites
-no effects on the cytochrome P-450
enzyme system
-Eliminated from the body through
renal clearance
3. Genetic predisposition
:Decreased epoxide hydrolase activity
Teratogenic effects of antiepileptic drugs
Department of Clinical Neuroscience, KarolinskaInstitutet, Stockholm, Sweden
>Preeclampsia
>Postpartum hemorrhage
>Postpartum depression
>Increased cesarean section rate
>Nonproteinuric hypertension
>Increased incidence of labor induction
>Developing a seizure disorder of epileptic mother’s children
Preconceptional counseling
>Adverse outcome of an epileptic women’s pregnancy depends on:
-AED-induced teratogenecity
-Patient’s genetic disposition
-Serverity of patient’s convulsive disorder