Anti Seeizure Drugs

Question 1

Phenytoin

Answer 1

• anticonvulsant effective in the treatment of grand mal (tonic-clonic) seizures, partial seizures, and status epilepticus.
• inhibits abnormal electrical activity of the brain by blocking voltage-gated sodium channels in neurons.

Phenytoin has a narrow therapeutic index with a number of potential adverse effects:

1. Phenytoin toxicity is mainly characterized by CNS manifestations. Its effect on the cerebellum and vestibular system can cause ataxia and nystagmus.
2. Long-term therapy with phenytoin may cause gingival hyperplasia, coarsening of the facial features, and hirsutism.
3. interferes with the metabolism of folic acid and may cause megaloblastic anemia.
4. induces the P450 cytochrome oxidase system. It increases the metabolism—and therefore decreases the blood level—of many medications.
5. If taken during pregnancy, phenytoin may cause fetal hydantoin syndrome.

ADR: Gingival hyperplasia- It occurs in 50% of patients who have had 3-4 months of phenytoin therapy - mechanism of this side effect is associated with increased expression of platelet-derived growth factor (PDGF).

When gingival macrophages are exposed to increased amounts of PDGF, they stimulate proliferation of gingival cells and alveolar bone. Gingival hyperplasia may regress after discontinuation of phenytoin.