
Mode of Action
- Enhances the binding of GABA to the receptor and through increasing the duration of GABAA-mediated inhibitory currents
- Barbiturates at high concentrations may also be GABA mimetic and inhibit stimulatory AMPA Glutamate receptors

Dose
- Weight-based and fixed doses
- IV: 65 to 260 mg of phenobarbital up to 10-20 mg/kg
- Oral: 60 mg 4 times daily on day 1, followed by 60 mg 3 times daily on day 2, 60 mg twice daily on day 3, and 30 mg twice daily on day 4.
PK/PD
- Onset: IV: 5 min, Oral: ≥60 minutes
- Duration: 6-12 hours
- Half-life: 80-120 hours
- Peak effect: CNS depression: ≥15 minutes
- Metabolism: Substrate of CYP2C19, CYP2C9, and CYP2E1 (minor); weak CYP450 inducer
- Elimination: 25-50% eliminated unchanged in the urine
- Therapeutic Blood levels: 15-40 ug/mL
Adverse Effects
- Hypotensive
- Respiratory depression
- Ataxia
- Lethargy
Pearls
- Predictable pharmacokinetics: blood levels correlate we to clinical and toxic clinical response
- Wide therapeutic index as dosing for alcohol withdrawal (5-10 mg/kg) rarely is enough to cause blood level concentrations >30 ug/mL and most CNS adverse effect occur around 60+ ug/mL
- Same dosing of the drug in IV, IM, and PO formulations
- Compatible with NS, D5W, and LR
Warning with loading doses in patients that are hypotensive and received large doses of benzodiazepines
Agent | Routes of Administration | Dose | Onset(minutes) | Metabolism |
Lorazepam | PO, IV, IM | IV 1-4 mg q 5-15 min | IV: 15-20 | Hepatic (inactive) |
Diazepam | PO, IV, IM,rectal | IV: 5-10 mg q 10-15 minutes | IV: 2-5 | Hepatic (active) |
Chlordiazepoxide | PO | Initial: 50-100 mg qMax 300 mg per 24 hr | Oral: 30-120 | Hepatic (active) |
Phenobarbital | PO, IV, IM | 10 mg/kg or 130-260 mg | IV: 5Oral: 30 | Hepatic (inactive) |
Dexmedetomidine | IV | 0.1-0.7 mcg/kg/hr | IV: 15-30 | Hepatic (inactive) |
Ketamine | IV,IM,PO,IN | 0.15–0.3mg/kg/hr | IV: 1-5 | Hepatic (active) |