The use of antiepileptic drugs (AEDs) in pregnancy always presents challenges to doctors and their patients as it may have deleterious effects on the developing embryo. Which antiepileptic should be prescribed to epileptic pregnant women? The choice drug is one that is effective, safe and free from foetal toxicity. No antiepileptic is both ideal and safe.
Monotherapy is preferred when managing patients with epilepsy, given similar efficacy and superior tolerability compared to polytherapy for most patients, especially those with newly diagnosed epilepsy who are not refractory to other treatments.
Owing to the decreasing popularity of first-generation AEDs in women of child-bearing age, the use of second-generation AEDs is steadily growing. More monotherapy data on common novel AEDs other than lamotrigine are now urgently needed, particularly on levetiracetam, which is developing into a first-line drug in the treatment of epilepsy.
Although the safety profile of lamotrigine (LTG) appears favorable during pregnancy, its use in young females is complicated by its pharmacokinetic interactions with endogenous end exogenous estrogens.
Lamotrigine has been increasingly prescribed for women with epilepsy who are of childbearing age, while data on other new AEDs, especially levetiracetam, have been accumulating.
Levetiracetam (LEV) is a broad-spectrum antiepileptic drug which is currently licensed in the United States and the United Kingdom and Ireland for use as adjunctive treatment of focal-onset seizures and myoclonic seizures or generalized tonic-clonic seizures, occurring as part of generalized epilepsy syndromes.
This study aimed to evaluate and compare the teratogenic effect of the second generation antiepileptic drugs (lamotrigine and levetiracetam) on normal adult female albino rats, in order to find out the safest and the least teratogenic one of them.
Sixty female albino rats and thirty male rats were used in this study. The female rats were virgin, close to 120 days of age as possible and their weight ranged from 180-200 gm. The males were of the same range of weight and age. Each 2 females were placed over night with one male. If the vaginal smear in the following morning contained sperms, that day was considered as day zero of gestation.
Pregnant rats divided into 3 groups, the 1st group is the control group that received only the vehicle, the 2nd and the 3rd group were administered a single daily oral doses that equivalent to therapeutic human dose of laomtrigine and levetiracetam respectively from 7-15 gestational days.
The fetuses of the pregnant mothers were obtained by caesarian operation at the 20th day of gestation. Fetuses randomly picked up from each pregnant female, dehydrated, fixed by immersion in 95% ethyl alcohol and were used for skeletal visualization by Alizarine red stain. The rest of fetuses were placed in Bouin’s solution and were used for razor sections as well as histological sections after external examination.
The results of the present study revealed that LTG induced severe maternal toxicity in the form of death of two dams and a significant decrease in body weight, food and water consumption. While LEV treated groups showed minimal maternal toxicity manifested by significant decrease in percentage of increase of maternal body weight during 3rd week of gestation.
The results of the present study revealed that the post implantation losses and resorption sites were high among LTG treated group with significant decrease in numbers of viable fetuses. While post implantation losses and resorption were high among LEV treated group with decrease in numbers of viable fetuses.
As regard the weight, crown-rump length, biparietal diameter and head length of the fetuses, this study revealed that both treated groups have a significant difference in comparison to the control. With more affection of LTG treated group than LEV treated group. Hematomas were detected in LTG treated group, while not observed in LEV treated groups.
By staining the skeletons of the rat fetuses by alizarine red stain, it revealed that both treated groups have teratogenic effects on the fetal bones. These effects were more extensive in LTG treated group especially on skull, vertebrae and hind limb, while sternum were more affected in LEV group.
Gross anomalies were present in both treated groups. The anomalies found in LTG treated groups were dilatation of both lateral ventricle, while in LEV group, were malformed lung, heart with large hematoma, hemorrhagic liver spots and shrunken stomach.
Histopathological examination of internal organs detected the following: dilated lateral and forth ventricles, unilateral cleft palate, cerebral cortex vacuolations, less clearly defined plexiform layer of the cortex, degenerated vertebral bodies, undifferentiation between gray matter and white matter of spinal cord, degeneration of the cartilage of the trachea, enlarged distorted kidney in LTG treated group. While in LEV treated group the histological sections revealed that there were liver affection in the form of dilation and congestion of central vein, cavitation of the liver, diffuse necrosis and loss of architecture of the liver tissues.
Lastly we can conclude that both antiepileptic drugs included in this study were teratogenic in variable degrees. But the new antiepileptic drug LEV appears to be less teratogenic than the old one LTG.
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