Phenobarbital for Alcohol Withdrawal: Difference between revisions
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# Like all barbiturates, PB is a ''sedative/hypnotic''.<ref name = "Harvey1979">Harvey SC. Hypnotics and Sedatives: The Barbiturates. In: Goodman LS, Gilman A, eds. The Pharmacologic Basis of Therapeutics. 5th ed. New York: MacMillan Publishing Co., Inc.; 1975:124-136.</ref> | # Like all barbiturates, PB is a ''sedative/hypnotic''.<ref name = "Harvey1979">Harvey SC. Hypnotics and Sedatives: The Barbiturates. In: Goodman LS, Gilman A, eds. The Pharmacologic Basis of Therapeutics. 5th ed. New York: MacMillan Publishing Co., Inc.; 1975:124-136.</ref> | ||
# PB is also classified as an ''anti-convulsant''. | # PB is also classified as an ''anti-convulsant''.<br /> | ||
::In anesthetic doses, all BBTs have an anti-convulsant effect. However, PB is the only currently produced BBT which has an anti-convulsant effect at ''sub-sedative'' doses. (Historically, two closely related BBTs [mephobarbital and metharbital] also had an anti-convulsant effect at sub-sedative doses).<ref name="Harvey1979" /> | |||
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Revision as of 22:47, 28 August 2019
Phenobarbital is a non-competitive gamma-Aminobutyric acid (GABA) agonist which is an equally effective and safe alternative to benzodiazepines (BZD) for the treatment of alcohol withdrawal syndrome (AWS).[1] Though its use for AWS has waned and consequently many clinicians are now unfamiliar with this regimen, PB has both mechanistic and pharmacokinetic properties which make it more suitable for outpatient monotherapy than BZD.
IV/IM titrated PB is the first-line outpatient medication used for treatment of AWS at the Yukon-Kuskokwim Delta Regional Hospital. Its use is favored because substantial experience has shown that it is effective, it minimizes return visits, and it eliminates the need to dispense abuse-prone medications (i.e. BZD) to abuse-prone patients while in the midst of a substance abuse crisis. Indeed, minimizing high-risk dispensing of abuse-prone medication is important for improving the health of our community.
Evidence of Effectiveness and Safety
A 2016 systematic review by Mo et al. in the Journal of Critical Care[1] concluded that "barbiturates alone or in combination with BZDs are at least as effective as BZDs in the treatment of AWS. Furthermore, barbiturates appear to have acceptable tolerability and safety profiles, which were similar to those of BZDs in patients with AWS." This review included three randomized controlled trials (RCT's) and four observational studies. While this review firmly establishes PB's similar pharmacological effectiveness compared to BZD's, only one of the included studies (an RCT by Hendey et al.[2]) focused solely upon outpatient treatment. Though its sample size was not large (25 in PB group, 19 in BZD group), Hendey et al. did report statistically nonsignificant trends toward better outcomes in the PB group.
Pharmacology
The following are the important properties of PB with regard to outpatient treatment of AWS.
Drug Class
Chemical Class
PB belongs to the chemical class barbiturate.
Clinical Class
- Like all barbiturates, PB is a sedative/hypnotic.[3]
- PB is also classified as an anti-convulsant.
- In anesthetic doses, all BBTs have an anti-convulsant effect. However, PB is the only currently produced BBT which has an anti-convulsant effect at sub-sedative doses. (Historically, two closely related BBTs [mephobarbital and metharbital] also had an anti-convulsant effect at sub-sedative doses).[3]
Mechanism of Action
- Like all barbiturates, PB's sedative/hypnotic effect occurs via noncompetitive agonism of the GABAA ion channel. Like BZDs, PB/BBT do not themselves open the channel and thus GABA is still required. PB/BBT bind at a different site than BZDs.
Dosing
Distribution
Elimination
Adverse Effects
Cautions
Contraindications
Pregnancy
Lactation
Toxicology
Authors
Andrew W. Swartz, MD
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References
- ↑ 1.0 1.1 Mo Y, Thomas MC, Karras GE. Barbiturates for the treatment of alcohol withdrawal syndrome: A systematic review of clinical trials. J Crit Care. 2016;32:101-107. doi:10.1016/j.jcrc.2015.11.022
- ↑ Hendey GW, Dery RA, Barnes RL, Snowden B, Mentler P. A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. Am J Emerg Med. 2011;29(4):382-385. doi:10.1016/j.ajem.2009.10.010
- ↑ 3.0 3.1 Harvey SC. Hypnotics and Sedatives: The Barbiturates. In: Goodman LS, Gilman A, eds. The Pharmacologic Basis of Therapeutics. 5th ed. New York: MacMillan Publishing Co., Inc.; 1975:124-136.
