Phenobarbital: A Long-Acting Barbiturate with Anticonvulsant Properties
Phenobarbital is a long-acting barbiturate that functions as a central nervous system (CNS) depressant, primarily used as an anticonvulsant for seizure disorders and as a sedative-hypnotic agent. 1, 2
Mechanism of Action
- Acts at the gamma-aminobutyric acid (GABA) receptor complex in the CNS 2, 3
- Produces inhibitory effects by:
- Prolonging and potentiating the action of GABA on GABA(A) receptors
- Directly activating GABA(A) receptors at higher concentrations
- Blocking AMPA/kainate receptors
- Inhibiting glutamate release through effects on calcium channels 3
Clinical Classifications and Uses
Primary Uses
- Long-term anticonvulsant for generalized tonic-clonic and cortical focal seizures 1
- Emergency control of acute convulsive episodes including status epilepticus, eclampsia, meningitis, and tetanus 1
- Sedative for anxiety-tension states, hyperthyroidism, and essential hypertension 1
- Short-term hypnotic for insomnia (effectiveness diminishes after 2 weeks) 1
- Preanesthetic medication 1
Pharmacokinetic Properties
- Classification: Long-acting barbiturate 2
- Half-life: 80-120 hours in adults, longer in neonates (103-141 hours) 2, 4
- Metabolism: Primarily hepatic via CYP2C9, with minor metabolism by CYP2C19 and CYP2E1 4
- Elimination: Approximately 25% excreted unchanged in urine 4
- Volume of distribution: 0.25-1.2 L/kg 2
- Protein binding: 20-60% 2
Clinical Considerations
Dosing
- Anticonvulsant loading dose: 20 mg/kg intravenously 4
- Maintenance dose: 3-4 mg/kg orally 4
- Therapeutic range: 10-25 mg/L for anticonvulsant activity 2
- Potentially toxic levels: >50 mg/L may induce coma; >80 mg/L may be fatal 2
Adverse Effects
- CNS depression: Sedation, drowsiness, impaired coordination 2
- Respiratory depression: Most serious potential adverse effect, especially at high doses 5
- Cardiovascular depression: Can cause hypotension at higher doses 5
- Paradoxical reactions: Occasionally observed, particularly in children 2
Special Populations
- Elderly: More susceptible to respiratory depression and prolonged sedation; require lower initial doses 5
- Hepatic impairment: Dose reduction required due to reduced clearance 5
- Pediatric use: Indicated as both anticonvulsant and sedative 1
Clinical Advantages and Limitations
Advantages
- Long half-life provides smooth withdrawal transition in detoxification 5
- Effective for emergency control of seizures 1
- Cross-tolerance with benzodiazepines at GABA receptors 5
Limitations
- Risk of respiratory and cardiovascular depression 2, 5
- High abuse potential 6
- Tolerance develops to sedative-hypnotic effects (but not to lethal toxicity) 2
- Has been largely replaced by benzodiazepines for sedative-hypnotic uses 7
Monitoring
- Respiratory rate, oxygen saturation, and level of consciousness 5
- Serum drug levels when used as anticonvulsant 2, 4
- Cardiovascular parameters, especially when used at higher doses 2
Phenobarbital remains a valuable medication for seizure disorders worldwide despite newer alternatives, primarily due to its efficacy, long half-life, and established safety profile when properly monitored 7.