Target Audience:

Who should attend:

• Clinical faculty from the University of Pittsburgh School of Pharmacy
• Clinical staff pharmacists employed by the University of Pittsburgh Medical Center and deployed throughout the hospital campus in unit based roles and centrally in the department of pharmacy's main pharmacy
• Student pharmacy interns currently working within the department of pharmacy
• Certified Pharmacy Technicians

Abstract
Over 14 million adults, 18 and older, have alcohol use disorder (AUD) in the United States.¹ About 50% of people with AUD will experience symptoms of alcohol withdrawal syndrome (AWS) upon cessation of alcohol use.2 Alcohol enhances the inhibitory effects of gamma-aminobutyric acid (GABA) at the GABAA receptor and decreases the excitatory response of glutamate at the n-methyl-D-aspartate (NMDA) receptor. Chronic alcohol consumption leads to compensatory downregulation of GABAA receptors, decreased GABA release, upregulation of NMDA receptors, and increased glutamate production. Abrupt cessation of alcohol consumption results in brain hyper-excitability due to the increased presence of glutamate and NMDA receptors in the brain. Symptoms of alcohol withdrawal can vary in patient presentation and severity. Mild symptoms may include insomnia, mild anxiety, and gastrointestinal upset, while more severe symptoms may include visual or auditory hallucinations, seizures, or delirium tremens.²

The preferred treatment agents for AWS are benzodiazepines as this class has demonstrated to be safe and effective for preventing and treating seizures and delirium.2 Benzodiazepines bind to the GABAA receptor, independent of the GABA-binding site, and augment the inhibitory effect of GABA. Although benzodiazepines are first line in AWS, they do present limitations such as the dependence of GABA, an unpredictable pharmacokinetic/pharmacodynamic profile, and the increased risk of respiratory depression and delirium. Phenobarbital has shown to be an attractive alternative to benzodiazepines given its independent action on GABAA receptors, predictable pharmacokinetics/pharmacodynamics, and favorable safety profile. During this presentation, we will evaluate the evidence of phenobarbital use in AWS, comparing it with the standard of care, benzodiazepines. Phenobarbital is a reasonable treatment option for monotherapy and as an adjunctive agent in specific patient populations in AWS.

Educational Objectives:

Upon successful completion of this continuing pharmacy education program, the participant should be able to:

• Describe the pathophysiology and the associated complications of alcohol withdrawal syndrome (AWS)
• Discuss three studies that assess the use of phenobarbital (PHB) in AWS.
• Identify an appropriate treatment option for an AWS patient

Pharmacy Continuing Education Credits This program is sponsored by the University of Pittsburgh Center for Continuing Education in the Health Sciences. The University of Pittsburgh Center for Continuing Education in the Health Sciences is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a Provider of continuing pharmacy education. The assigned universal program number(s) is JA4008223-0000-23-088-H01-P.  This module is a webcast of an ACPE approved live presentation. The minimum credit awarded for this module (1 contact hour) is determined by the length of the entire live presentation inclusive of the post-test.

Suggested Additional Reading:

1. American Society of Addiction Medicine. Alcohol Withdrawal Management (Version 1.2020). https://www.asam.org/docs/default-source/quality-science/the_asam_clinical_practice_guideline_on_alcohol-1.pdf?sfvrsn=ba255c2_2. Accessed February 22, 2021.
2. Schmidt KJ, Doshi MR, Holzhausen JM, Natavio A, Cadiz M, Winegardner JE. Treatment of Severe Alcohol Withdrawal. Ann Pharmacother. 2016;50(5):389-401. doi:10.1177/1060028016629161
3. Tidwell WP, Thomas TL, Pouliot JD, Canonico AE, Webber AJ. Treatment of Alcohol Withdrawal Syndrome: Phenobarbital vs CIWA-Ar Protocol. Am J Crit Care. 2018;27(6):454-460. doi:10.4037/ajcc2018745
4. SAMHSA. 2019 National Survey on Drug Use and Health (NSDUH). Table 5.4A—Alcohol Use Disorder in Past Year among Persons Aged 12 or Older, by Age Group and Demographic Characteristics: Numbers in Thousands, 2018 and 2019.
5. Wood E, Albarqouni L, Tkachuk S, et al. Will This Hospitalized Patient Develop Severe Alcohol Withdrawal Syndrome?: The Rational Clinical Examination Systematic Review. JAMA 2018; 320:825.
6. Bayard M, McIntyre J, Hill KR, Woodside J Jr. Alcohol withdrawal syndrome. Am Fam Physician. 2004;69(6):1443-1450.
7. Dixit D, Endicott J, Burry L, et al. Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients. Pharmacotherapy. 2016;36(7):797-822. doi:10.1002/phar.1770
8. Phenobarbital. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com.  Accessed February 22, 2021
9. Hammond DA, Rowe JM, Wong A, Wiley TL, Lee KC, Kane-Gill SL. Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review. Hosp Pharm. 2017;52(9):607-616. doi:10.1177/0018578717720310
10. Rosenson J, Clements C, Simon B, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med. 2013;44(3):592-598.e2. doi:10.1016/j.jemermed.2012.07.056
11. 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.
12. Nisavic M, Nejad SH, Isenberg BM, et al. Use of Phenobarbital in Alcohol Withdrawal Management - A Retrospective Comparison Study of Phenobarbital and Benzodiazepines for Acute Alcohol Withdrawal Management in General Medical Patients. Psychosomatics. 2019;60(5):458-467.