Phenobarbital
Phenobarbital is a barbiturate that is used primarily as an anticonvulsant and sedative. It is one of the oldest antiepileptic drugs, widely used for the treatment of seizures, particularly focal and generalized tonic-clonic seizures. It is also used for sedation and in the management of withdrawal symptoms from alcohol or sedative-hypnotic drugs.
Trade Name
Phenobarbital is marketed under several trade names, including Luminal.
Chemical Properties
Chemical structure: Phenobarbital is a barbiturate, a class of compounds derived from barbituric acid.
Molecular formula: C₁₂H₁₂N₂O₃
Molecular weight: 232.24 g/mol
Solubility: Phenobarbital is moderately soluble in water and is typically administered orally in tablet or liquid form, and intravenously in emergency situations.
Biochemical Properties
Mechanism of action: Phenobarbital works by enhancing the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain. It binds to GABA receptors and prolongs the opening of chloride ion channels, resulting in neuronal hyperpolarization and reduced neuronal excitability, which helps prevent seizures. Phenobarbital also reduces the excitability of neurons by inhibiting certain excitatory neurotransmitter systems, making it effective in controlling various types of seizures.
Pharmacology
Administration: Phenobarbital is commonly administered orally in tablet or liquid form, and can also be given intravenously for acute seizure control or in hospital settings.
Bioavailability: Phenobarbital has high bioavailability, typically around 90% when taken orally.
Metabolism: Phenobarbital is metabolized in the liver by cytochrome P450 enzymes (especially CYP2C9) and is excreted primarily in the urine as inactive metabolites.
Half-life: The half-life of phenobarbital is quite long, ranging from 53 to 118 hours, depending on the individual, which allows for once or twice daily dosing in most cases.
Clinical Indications
Treat seizures: It is used for the long-term management of generalized tonic-clonic seizures, focal seizures, and status epilepticus (a prolonged seizure emergency) in both adults and children.
Sedation: It has sedative properties and is sometimes used to manage anxiety or insomnia.
Alcohol or sedative-hypnotic withdrawal: Phenobarbital can be used to help manage withdrawal symptoms from alcohol or sedative-hypnotic medications, particularly in inpatient settings.
Activate cytochrome P450 enzymes in lever.
Side Effects
Sedation and drowsiness: One of the most common side effects, especially when starting treatment or increasing the dose. It can impair the ability to drive or operate machinery.
Cognitive impairment: Long-term use of phenobarbital can cause memory problems, confusion, and difficulty concentrating.
Ataxia and coordination issues: Phenobarbital can cause motor incoordination, affecting balance and coordination.
Hypotension: IV administration can cause a drop in blood pressure, particularly with rapid infusion.
Respiratory depression: High doses or IV administration can cause respiratory depression, which can be life-threatening.
Rash: Skin rashes, sometimes severe, can occur, including the rare but serious condition of Stevens-Johnson syndrome.
Dependency and withdrawal: Long-term use can lead to physical dependence, and abrupt discontinuation may result in withdrawal symptoms such as anxiety, tremors, and seizures.
Phenobarbital is a highly effective anticonvulsant, especially in acute seizure management, but it carries a risk of significant side effects, particularly sedation and cognitive impairment, making it less suitable for long-term use in some patients. Careful monitoring is required, especially during dose adjustments or when used in combination with other CNS depressants.
