Ans. D: N significant interaction with warfarin Barbiturates stimulates hepatic microsomal catabolism of warfarin Phenobarbital/ Phenobarbitone It is a barbiturate It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. The World Health Organization recommends its use as first-line for paial and generalized tonic-clonic seizures (those formerly known as grand mal) in developing countries. It is still commonly used to treat neonatal seizures. Phenobarbital is indicated in the treatment of all types of seizures except absence seizures. Sedation and hypnosis are the principal side effects (occasionally, they are also the intended effects) of phenobarbital. Central nervous system effects like dizziness, nystagmus and ataxia are also common. In elderly patients, it may cause excitement and confusion while in children, it may result in paradoxical hyperactivity. Another very rare side effect is amelogenesis imperfecta Contraindication: Acute intermittent porphyria, oversensitivity for barbiturates, prior dependence on barbiturates, severe respiratory insufficiency and hyperkinesia in children The principal mechanism of action of barbiturates is believed to be their affinity for the GABAA receptor (Acts on GABA : BDZ receptor Cl- channel complex). GABA is the principal inhibitory neurotransmitter in the central nervous system (CNS). Barbiturates bind to the GABAA receptor at the alpha subunit, which are binding sites distinct from GABA itself. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. In addition to this GABA-ergic effect, barbiturates also block the AMPA receptor, a subtype of glutamate receptor. Phenobarbital has an oral bioavailability of approximately 90%. Peak plasma concentrations are reached 8 to 12 hours after oral administration. It is one of the longest-acting barbiturates available - it remains in the body for a very long time (half-life of 2 to 7 days) and has very low protein binding (20 to 45%). Phenobarbital is metabolized by the liver, mainly through hydroxylation and glucuronidation, and induces many isozymes of the cytochrome P450 system. Cytochrome P450 2B6 (CYP2B6) is specifically induced by Phenobarbital It is excreted primarily by the kidneys Phenobarbital markedly reduces effect of warfarin