Phenytoin therapy may lead to which of the following:

Ans. (d) Folic acid deficiencyRef. KDT 6th ed. 404-405* Phenytoin is a major epileptic drug which is effective for treatment of partial seizures and generalized tonic- clonic seizures and in the treatment of status epilepticus.* MOA: Phenytoin blocks voltage-gated sodium channels by selectively binding to the channel in the inactive state and slowing its rate of recovery.* It follows zero order kinetics.* It can also be used as an anti-arrhythmic drug (class lb) for the treatment of digitalis induced arrhythmia.* Use of phenytoin during pregnancy can cause Fetal hydantoin syndrome characterized by: hypoplastic phalanges, cleft lip, cleft palate and microcephaly. It occurs due metabolite of phenytoin, arene oxide.* Phenytoin decreases folate absorption and increases its excretion - Megaloblastic anemia.* Prolonged use of phenytoin can result in gingival hyperplasia (gum hypertrophy).* It can inhibit the insulin release and can cause hyperglycemia.* Other adverse effects on long-term use include: Hirsutism, coarsening of facial features, megaloblastic anemia (treated with folic acid), vitamin D deficiency (rickets and osteomalacia), vitamin K deficiency, hyperglycemia (due to inhibition of insulin release), hypersensitivity.