BARBIT

Indications

• Generalized tonic-clonic seizures
• Partial seizures
• Myoclonic seizures
• Status epilepticus
• Sedation
• Management of neonatal jaundice

Dosage

Children: Dosing for children should be individualized based on age, weight, and clinical condition. Refer to the BNF for Children for specific dosage recommendations.

Adults: The usual initial dose is 60 to 120 mg orally at bedtime, with maintenance doses adjusted according to clinical response. For status epilepticus, loading doses may be higher and administered intravenously.

Mechanism of action

Phenobarbital acts on GABAA receptors, enhancing synaptic inhibition, which elevates seizure thresholds and reduces the spread of seizure activity. It may also inhibit calcium channels, leading to decreased excitatory transmitter release. The sedative-hypnotic effects are likely due to its influence on the polysynaptic midbrain reticular formation responsible for CNS arousal. Additionally, it induces glucuronyl transferase, which helps in the conjugation of bilirubin, thus lowering serum bilirubin concentrations.

Pharmacodynamics

As the longest-acting barbiturate, phenobarbital exhibits significant anticonvulsant and sedative-hypnotic effects. It modifies central nervous system activity by enhancing GABAergic transmission and affecting inhibitory and excitatory balance, particularly in regions involved in arousal and seizure activity.

Pharmacokinetics

Phenobarbital is well-absorbed after oral administration and reaches peak plasma concentrations within 2 to 8 hours. It is metabolized primarily in the liver and has an elimination half-life ranging from 79 to 120 hours, making it suitable for long-term administration. The drug is excreted mainly in urine, with a portion as unchanged drug and metabolites.

Contra-indications

• Known hypersensitivity to phenobarbital or other barbiturates
• Severe respiratory insufficiency
• Porphyria
• Severe hepatic impairment

Adverse effects

• Drowsiness
• Dizziness
• Ataxia
• Cognitive impairment
• Nausea
• Vomiting
• Hypotension
• Respiratory depression
• Dependence and withdrawal symptoms

Interactions

• May enhance the effects of other CNS depressants (e.g., alcohol, benzodiazepines)
• May reduce the effectiveness of oral contraceptives
• May alter the metabolism of anticoagulants, corticosteroids, and other drugs metabolised by the liver

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor for signs of respiratory depression, especially in elderly or debilitated patients
• Use cautiously in patients with liver impairment or porphyria

Pregnancy

Phenobarbital is classified as a Category D drug. It may cause fetal harm and is associated with risks of congenital malformations. Use only if the benefits outweigh the risks.

Breast-feeding

Phenobarbital is excreted in breast milk. Caution is recommended, and a decision should be made whether to discontinue nursing or the drug.

Storage

Store in a well-closed container at room temperature, away from light and moisture.

Formulations

• Tablets (e.g., 15 mg, 30 mg, 60 mg)
• Oral liquid (e.g., 20 mg/5 mL)
• Injection (e.g., 200 mg/2 mL)

Mechanism of action

Phenobarbital acts on GABAA receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal. /Phenobarbital/ produces anticonvulsant effects in subhypnotic doses. The drug lowers serum bilirubin concentrations in neonates and patients with congenital nonhemolytic unconjugated hyperbilirubinemia and patients with chronic intrahepatic cholestasis, presumably by induction of glucuronyl transferase, the enzyme which conjugates bilirubin. The exact mechanism(s) by which barbiturates exert their effect on the CNS, has not been fully elucidated. However, it is believed that such effects are related, at least partially, to the drugs' ability to enhance the activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the CNS, by altering inhibitory synaptic transmissions that are mediated by GABAA receptors. /Barbiturates General Statement/ Although the drugs act throughout the CNS, a site of particular sensitivity is the polysynaptic midbrain reticular formation which is concerned with the arousal mechanism. Barbiturates induce an imbalance in central inhibitory and facilitatory mechanisms influencing the cerebral cortex and the reticular formation. The significance of the effect of barbiturates on neurotransmitters is unclear. It appears that the drugs decrease the excitability of both presynaptic and postsynaptic membranes. It has not been determined which of the various actions of barbiturates at cellular and synaptic levels are responsible for their sedative and hypnotic effects. /Barbiturates General Statement/ Relatively low doses of the barbiturates depress the sensory cortex, decrease motor activity, and produce sedation and drowsiness. In some patients, however, drowsiness may be preceded by a period of transient elation, confusion, euphoria, or excitement, especially after subhypnotic doses of aprobarbital, pentobarbital, or secobarbital. /Barbiturates General Statement/ For more Mechanism of Action (Complete) data for Phenobarbital (12 total), please visit the HSDB record page.

Pharmacodynamics

Phenobarbital, the longest-acting barbiturate, is used for its anticonvulsant and sedative-hypnotic properties in the management of all seizure disorders except absence (petit mal).