Drug-nutrient
interactions of folate
Several folate antimetabolites are used clinically, as cancer
chemotherapy (e.g., methotrexate), and as antibacterial (trimethoprim) and
antimalarial (pyri-methamine) agents. Drugs such as trimethoprim and pyrimethamine
act by inhibiting dihydrofolate reduc-tase, and they owe their clinical
usefulness to a con-siderably higher affinity for the dihydrofolate reduc-tase
of the target organism than the human enzyme; nevertheless, prolonged use can
result in folate deficiency.
A number of anticonvulsants used in the treatment of epilepsy,
including diphenylhydantoin (phenytoin), and sometimes phenobarbital and
primidone, can also cause folate deficiency. Although overt megalo-blastic
anemia affects only some 0.75% of treated epileptics, there is some degree of
macrocytosis in 40%. The megaloblastosis responds to folic acid sup-plements,
but in about 50% of such patients treated with relatively high supplements for
1–3 years there is an increase in the frequency of epileptic attacks.
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