Role of Adenosine A1 and A2A Receptors in the Alcohol Withdrawal Syndrome

Introduction. Bromdihydrochlorphenylbenzodiazepine is the Russian original tranquilizer which widely using in psychiatry, narcology, neurology and general medicine. Particularly, that drug prescribing for patients with alcohol withdrawal syndrome (AWS). Isoenzyme CYP2C19 takes part in metabolism of the most of benzodiazepines, so the gene CYP2C19 might be included into pharmacogenetics study of bromdihydrochlorphenylbenzodiazepine. There was no study of CYP2C19 polymorphisms as biomarkers of bromdihydrochlorphenylbenzodiazepine’s safety. Methods. 102 male patients with non-comlicated AWS (F 10.3 by ICD-10) were involved into the study. During 6 days of dynamic observation each participant was prescribed bromdihydrochlorphenylbenzodiazepine (Phenazepam). 5 ml of venous blood was collected from each participant for genotyping. 38 participants were added Pagluferal (contains phenobarbitalum, natrium coffeine-benzoate, bromisoval, papaverine) and/or Carbamazepine. Blood samples were analyzed to detect the CYP2C19*2 (rs4244285), *3 (rs4986893) и *17 (rs12248560) polymorphisms. Safety of therapy was evaluated with UKU Side Effects Rating Scale. Data analysis was performed with SPSS Statistics 21.0. Results. Carriers of CYP2C19*2 GA+AA genotypes compared to GG homozygous significantly more often had such adverse effects as «Polyuria/polydipsia» in mean grade of penetration (33,3% vs 9%, p=0,016) and “Palpitations/Tachycardia” (16,7% vs 3,8%, p=0,018). Observed relationship between «Polyuria/polydipsia» and CYP2C19*2 GA+AA genotypes was confirmed in the subgroup “Combined pharmacotherapy” (37,5% vs 0%, p=0,006). CYP2C19*17 polymorphism in tendency to significance was associated with less frequent AE «Polyuria/polydipsia» among patients taking bromdihydrochlorphenylbenzodiazepine as monotherapy carriers of allele T had that AE in 16,9%, and CC homozygous in 24,2% (p=0,067). Conclusion. Significant associations between CYP2C19*2 polymorphism and several AE in patients with alcohol withdrawal syndrome taking bromdihydrochlorphenylbenzodiazepine. Substantial role of CYP2C19*17 as predictor of AE associated with bromdihydrochlorphenylbenzodiazepine was not confirmed. Gene CYP2C19 is the sufficient biomarker of bromdihydrochlorphenylbenzodiazepine’s safety profile and needs further research.

Download Full-text

Evaluating the Use of Phenobarbital for the Management of Alcohol Withdrawal Syndrome in Psychiatric Inpatients

Journal of Pharmacy Practice ◽

10.1177/0897190018822561 ◽

2019 ◽

Vol 33 (4) ◽

pp. 477-480

Author(s):

Erin Waldee ◽

Stephanie V. Phan

Keyword(s):

Alcohol Withdrawal ◽

Withdrawal Syndrome ◽

Vital Signs ◽

Alcohol Withdrawal Syndrome ◽

Psychiatric Inpatients ◽

Signs And Symptoms ◽

Altered Mental Status ◽

Treatment And Prevention ◽

Appropriate Therapy

Objectives To describe the potential role of phenobarbital as appropriate therapy in the treatment and prevention of alcohol withdrawal syndrome (AWS) among medically cleared psychiatric inpatients. Methods This was a single-center, retrospective, observational study of adult patients admitted to the psychiatric unit and administered phenobarbital for the treatment or prevention of AWS. Changes in vital signs and signs and symptoms of AWS were observed to assess the safety and efficacy of phenobarbital. The primary outcome was safety of phenobarbital for AWS as measured by change in the respiratory rate (RR). Results A total of 122 patients were included in the study. There were no significant changes in RR among patients who received phenobarbital for AWS. Significant reductions in blood pressure and heart rate were observed. Of patients with documented signs and symptoms of AWS upon admission, 94% had improvement in the signs and symptoms during phenobarbital therapy. Approximately 12% of patients had documented sedation or altered mental status during phenobarbital therapy. No patients required transfer to a medical or critical care unit. Conclusions Phenobarbital was safe, not leading to severe adverse effects or requiring a higher level of care, and efficacious for the prevention and treatment of AWS in this cohort of psychiatric inpatients.

Download Full-text

The Role of Diazepam Loading for the Treatment of Alcohol Withdrawal Syndrome in Hospitalized Patients

American Journal on Addictions ◽

10.1111/j.1521-0391.2013.00307.x ◽

2013 ◽

Vol 22 (2) ◽

pp. 113-118 ◽

Cited By ~ 24

Author(s):

Andrew J. Muzyk ◽

Jonathan G. Leung ◽

Sarah Nelson ◽

Eric R. Embury ◽

Sharon R. Jones

Keyword(s):

Alcohol Withdrawal ◽

Withdrawal Syndrome ◽

Alcohol Withdrawal Syndrome ◽

Hospitalized Patients

Download Full-text

Adjunctive Phenobarbital for Alcohol Withdrawal Syndrome: A Focused Literature Review

Annals of Pharmacotherapy ◽

10.1177/1060028021999821 ◽

2021 ◽

pp. 106002802199982

Author(s):

Julie A. Murphy ◽

Brittany M. Curran ◽

William A. Gibbons ◽

Holly M. Harnica

Keyword(s):

Patient Care ◽

Alcohol Withdrawal ◽

Withdrawal Syndrome ◽

Data Extraction ◽

General Medicine ◽

Alcohol Withdrawal Syndrome ◽

Data Synthesis ◽

Study Selection ◽

Before And After

Objective: To review the literature describing the use of adjunctive phenobarbital in the treatment of severe alcohol withdrawal syndrome (AWS). Data Sources: PubMed and EMBASE were searched using the following terms: phenobarbital, adjunct, refractory or treatment resistant, severe or complicated, and alcohol withdrawal delirium or alcohol withdrawal seizures. Study Selection and Data Extraction: The search was limited to randomized controlled trials (RCTs) and cohort studies published in English. Data Synthesis: Seven studies were identified in the emergency department (ED; RCT, n = 1; cohort, n = 2), general medicine ward (cohort, n = 1), and intensive care unit (ICU; cohort, n = 3) settings. For all studies set in the ED and general medicine ward and for 1 ICU study, phenobarbital plus symptom-guided benzodiazepine therapy was compared to symptom-guided benzodiazepine monotherapy. The other 2 ICU studies examined adjunctive phenobarbital before and after implementation of a protocol, meaning patients in both arms could have received phenobarbital. Overall risk of bias across all studies was low to moderate. Relevance to Patient Care and Clinical Practice: The specific role of adjunctive phenobarbital in AWS is not clear because a majority of studies are retrospective cohorts with varying primary outcomes in different patient care settings. Conclusions: In the ED and general medicine ward, phenobarbital demonstrated benzodiazepine-sparing effects. In the ICU, when a protocol guides phenobarbital use, the need for mechanical ventilation may be reduced. Adjunctive phenobarbital was well tolerated. Because of study limitations, it is challenging to provide specific recommendations for adjunctive phenobarbital use in severe AWS.

Download Full-text