False statement regarding phenytoin is: March 2007
Ans. D: Follows zero order kinetics at lower doses Phenytoin acts to dampen the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage gated sodium channels. Absorption of phenytoin by oral route is slowit is widely distributed in the body and 80-90% bound to plasma proteins. Phenytoin is metabolized in liver by hydroxylation and glucuronide conjugation. The kinetics of metabolism is capacity limited; changes from first order to zero order over the therapeutic range-small increments in dose produce dispropoionately high plasma concentrations. The plasma half life (12-24 hours) progressively increases (upto 60 hours) when plasma concentration rises above 10 microgram/ ml as metabolizing enzyme gets saturated. Aside from seizures, it is an option in the treatment of trigeminal neuralgia as well as ceain cardiac arrhythmias. At therapeutic doses, phenytoin produces horizontal gaze nystagmus At toxic doses, patients experience sedation, cerebellar ataxia, and ophthalmoparesis, as well as paradoxical seizures. Idiosyncratic side effects of phenytoin, as with other anticonvulsants, include rash and severe allergic reactions. Phenytoin causes a reduction in folic acid levels, predisposing patients to megaloblastic anemia. Folic acid is presented as polyglutamate in foods, it is then conveed into monoglutamates by intestinal conjugase. Phenytoin acts by inhibiting this enzyme therefore causing folate deficiency. Phenytoin is a known teratogen. The syndrome consists of craniofacial anomalies (broad nasal bridge, cleft lip and palate, microcephaly) and a mild form of mental retardation (average IQ=71).This syndrome resembles the well-described Fetal Alcohol Syndrome and has also been called the "fetal hydantoin syndrome." Phenytoin may accumulate in the cerebral coex over long periods of time, as well as causing atrophy of the cerebellum when administered at chronically high levels. Despite this, the drug has a long history of safe use and it is a common "first line of defense" in seizure cases. Phenytoin has been known to cause Drug-induced Lupus. Phenytoin has been associated with drug induced gingival enlargement (hyperplasia) in the oral cavity probably due to folate defiency. Patients whose epilepsy is treated with drugs face about twice the risk of suicidal thoughts compared to placebo-takers Phenobarbitone competitively inhibits phenytoin metabolism, while by enzyme induction both enhance each other's degradation. Phenytoin induces microsomal enzymes and increases degradation of steroids (failure of oral contraceptives), digitoxin, doxycycline, theophylline.
Is highly protein bound
Half life decreases with decreasing dose
Microsomal enzyme inducer
Follows zero order kinetics at lower doses