Clinical and experimental evaluation of some unwanted effects of sodium valproate

ABSTRACT

The aim of the present work was to evaluate some side effects induced by sodium valproate in epileptic patients. Moreover, to study the effect of the drug on brain chemical neurotransmitters, namely GABA and 5-HT to confirm its anticonvulsant effect and to exptain some of its side effects. This study was carried out in 2 parts clinical and experimental. The clinical part was done by clinical evaluation of side effects of sodium valproate on 40 epileptic patients receiving it for at least 3 months. Liver function tests and serum prolactin level were also done before and after treatment. The experimental part was carried out on 30 rats receiving the same drug, and another 30 rats as a control group. Measurements of GABA and 5-HT in different brain areas in both groups was done. Liver biopsy was taken also from both groups and examined under light microscope. The results of the study revealed that side effects appeared in 35% of patients. Weight gain [in 15%], increased appetite, gastrointestinal disturbances and tremors were the commonest side effects. But sedation, headache and skin rashes were less common. The effect of sodium valproate on hepatic enzymes showed significant [P bilirubin, SGOT and SGPT. But non-significant change [P >/= 0.05] on serum prolactin level. Moreover, sodium valproate significantly elevates GABA in different areas of brain, and 5-HT in cerebral cortex and midbrain. There was significant reduction of 5-HT level [P thalamus- hypothalamus areas. Some side effects may be dose dependant [sedation - headache - tremor], while others [rashes- nausea- heartburn- indigestion] were due to both toxic reactions and idiosyncratic reactions. The anticonvulsant effect of the drug may be due to significant elevation of both GABA and 5-HT in cerebral cortex. Moreover, sedation and weight gain may he due to elevated GABA in Cerebral cortex and midbrain, while increased appetite may be due to reduction of 5-HT in thalamus-hypothalamus