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Phenobarbital for Alcohol Withdrawal Masterclass

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  1. Pathophysiology and Assessment of Acute Alcohol Withdrawal Syndrome
  2. Pathophysiology
  3. Pharmacology and Pharmacokinetics of Common Medications
  4. Phenobarbital Pharmacology
  5. Clinical Literature
Lesson 4 of 5
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Phenobarbital Pharmacology

Riszel January 14, 2022

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


  • 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. 


  • 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


  • 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

AgentRoutes of AdministrationDoseOnset(minutes)Metabolism
LorazepamPO, IV, IMIV 1-4 mg q 5-15 minIV: 15-20Hepatic (inactive)
DiazepamPO, IV, IM,rectalIV: 5-10 mg q 10-15 minutesIV: 2-5Hepatic (active)
ChlordiazepoxidePOInitial: 50-100 mg qMax 300 mg per 24 hrOral: 30-120Hepatic (active)
PhenobarbitalPO, IV, IM10 mg/kg or 130-260 mgIV: 5Oral: 30Hepatic (inactive)
DexmedetomidineIV0.1-0.7 mcg/kg/hrIV: 15-30 Hepatic (inactive)
KetamineIV,IM,PO,IN0.15–0.3mg/kg/hrIV: 1-5Hepatic (active)