Anticonvulsants, folate vitamin

Folate supplements will rectify the megaloblastic anemia of vitamin Bj2 deficiency but may hasten the development of the (irreversible) nerve damage found in B,2 deficiency. There is also antagonism between fohc acid and the anticonvulsants used in the treatment of epilepsy. 

If anticonvulsants are used, daily folate (1 mg per day) may decrease the risk of neural tube defects and vitamin K (20 mg per day) may prevent drug-induced bleeding. 

Many epileptics receiving anticonvulsants excrete increased amounts of copper and zinc in their urine. Increased serum ceruloplasmin also increases the total serum copper concentration. In 20% to 30% of epileptic children receiving anticonvulsant therapy, erythrocyte aspartate aminotransferase activity is low, indicating a lowered pyridoxal (vitamin Bg) status. In as many as 50% of the adults receiving phenytoin for some time, there will be folate deficiency, manifested by reduced erythrocyte and serum folate concentrations. The mechanism for the deficiency has not yet been established conclusively. In about 10% of adults taking phenytoin, the serum vitamin is low. 

Davis et al. found that folate was not the only B group vitamin which was reduced in patients receiving treatment with anticonvulsant drugs (D4). In a study of 68 patients suffering from severe epileptic seizures they found that 18 patients had a low folate, 10 a low serum pyridoxal, and in 15 both the folate and pyridoxal were reduced. Only two patients in this series had a reduced erythrocyte folate, and this is in accord with the infrequency with which a macrocytic anemia is seen in these patients. All the patients in this series had a normal hemoglobin concentration and a normal mean corpuscular volume. However, in a study of 75 epileptic children Maxwell (M3) found both the serum and erythrocyte folate levels to be reduced in 60% and similar observations have been made by other workers (M4, N2). 

FOLATE DEFICIENCY Folate deficiency is a common complication of diseases of the small intestine, which interfere with the absorption of dietary folate and the recirculation of folate through the enterohepatic cycle. In acute or chronic alcohohsm, daily intake of dietary folate may be severely restricted, and the enterohepatic cycle of the vitamin may be impaired by toxic effects of alcohol on hepatic parenchymal cells this is the most common cause of folate-deficient megaloblastic erythropoiesis. However, it also is the most amenable to therapy, inasmuch as the reinstitution of a normal diet is sufficient to overcome the effect of alcohol. Disease states characterized by a high rate of cell turnover, such as hemolytic anemias, also may be complicated by folate deficiency. Additionally, drugs that inhibit dihydrofolate reductase (e.g., methotrexate and trimethoprim) or that interfere with the absorption and storage of folate in tissues (e.g., certain anticonvulsants and oral contraceptives) can lower the concentration of folate in plasma and may cause a megaloblastic anemia. 

An anticonvulsant drug. Among its undesirable side-effects h that of osteomalacia. This is thought to be due to the stimulatior by the drug of hepatic enzymes which inactivate vitamin D resulting in decreased calcium absorption. Phenytoin also in terferes with folate metabolism and this may result in i megaloblastic anaemia. 

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