fenobarbital

Fenobarbital (international spelling of phenobarbital) is a long-acting barbiturate used primarily as an anticonvulsant and sedative. First synthesized in the early 20th century, it remains on the World Health Organization’s list of essential medicines for management of seizures, including neonatal convulsions and certain generalized and partial epilepsies.

Pharmacologically, fenobarbital enhances the inhibitory effects of gamma-aminobutyric acid (GABA) at GABAA receptors by prolonging chloride channel opening, which reduces neuronal excitability. It is well absorbed orally and can be given intravenously or intramuscularly. The drug has a long and variable half-life (often measured in days), is metabolized in the liver, and is a potent inducer of cytochrome P450 enzymes, producing numerous drug interactions.

Therapeutic monitoring is common; typical serum therapeutic ranges are cited around 15–40 µg/mL. Common adverse effects include sedation, cognitive impairment, ataxia, and tolerance with long-term use. Dependence and withdrawal are concerns; overdose can cause profound respiratory depression and coma. Fenobarbital can precipitate porphyria attacks and has teratogenic risk; it crosses the placenta and is secreted in breast milk.

Because it alters metabolism of other drugs (e.g., reducing effectiveness of some anticoagulants and oral contraceptives), clinicians consider interactions and alternatives when prescribing. In many countries it is a controlled substance and its use has declined in favor of newer antiepileptics with more favorable safety profiles.