scholarly journals IMPACT OF CYP3A5, CYP2C9, CYP2C19, AND CYP2D6 POLYMORPHISMS ON PHENAZEPAM SAFETY IN PATIENTS WITH ALCOHOL WITHDRAWAL SYNDROME

2018 ◽  
Vol 73 (3) ◽  
pp. 206-214 ◽  
Author(s):  
D. V. Ivashchenko ◽  
K. A. Ryzhikova ◽  
Zh. A. Sozaeva ◽  
Y. A. Pimenova ◽  
E. A. Grishina ◽  
...  
Keyword(s):  
Adverse Reaction ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Haplotype Analysis ◽  
Rating Scale ◽  
Venous Blood ◽  
Alcohol Withdrawal Syndrome ◽  
Pharmacogenetic Study ◽  
Increased Risk ◽  
Icd 10

Introduction: Phenazepam is the Russian original benzodiazepine tranquilizer. We conducted first pharmacogenetic study on Phenazepam’s safety in patients with alcohol withdrawal syndrome. Isoenzymes CYP3A4, CYP3A5, CYP2C9, and CYP2C19 are involved into benzodiazepine tranquilizers’ metabolism.Aim: To determine predictive value of CYP3A5, CYP2C9, CYP2C19, and CYP2D6 genetic polymorphisms and their haplotypes for adverse reaction risk associated with the treatment with phenazepam.Materials and methods: The study enrolled 102 male patients with non-comlicated alcohol withdrawal syndrome (F10.3 by ICD-10) who entered the study group in 24 hours after the admission to hospital and was administered Phenazepam for 6 days. Therapy safety was evaluated with UKU Side Effects Rating Scale on the 6th day of treatment. 5 ml of venous blood was collected from each participant for genotyping to detect CYP3A5*3, CYP2С9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2C19*17, and CYP2D6*4 polymorphisms by real-time polymerase chain reaction. Haplotype analysis was performed by SNPStats online-tool. Statistical analysis was made in SPSS Statistics 21.0.Results: In overall sample (n=102) CYP2C9*3 increased risk of «Increased duration of sleep» (OR 1.46; 95% CI 1.11−1.9; p=0.037) and «Constipation» (OR 13.1; 95% CI 1.44−119.2; p=0.02). The following results in subgroup «Phenazepam’s monotherapy» (n=64) were observed: CYP3A5*3 increased global severity of adverse drug reactions according to patient’s opinion (OR 2.79; 95% CI 1.26−6.22; p=0.031); CYP2C9*3 led to «Increased duration of sleep» (OR 1.57; 95% CI 1.14−2.17; p=0.034). Haplotype CYP3A5*3-CYP2C19*2-CYP2C19*17 (G-G-T) was associated with increased risk of «Concentration difficulties (OR 2.86; 95% CI 0.96−8.50; p=0.061).Conclusion: The study findings confirmed that CYP2C9*3, CYP3A5*3, and CYP2C19*2 polymorphisms can decrease the phenazepam safety rate in patients with alcohol withdrawal syndrome. The result of haplotype analysis revealed that only CYP3A5*3-CYP2C19*2-CYP2C19*17 (G-G-T) can be used as a significant predictor of adverse reaction to phenazepam.

Pharmacogenetic evaluation of adverse events’ risk in patients with alcohol withdrawal syndrome taking bromdihydrochlorphenylbenzodiazepine: The role of CYP2C19 gene polymorphisms

2017 ◽  
Vol 1 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Dmitriy V. Ivashchenko ◽  
Kristina A. Ryzhykova ◽  
Zhannet A. Sozaeva ◽  
Mikhail S. Zastrozhin ◽  
Elena A. Grishina ◽  
...  
Keyword(s):  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Rating Scale ◽  
Venous Blood ◽  
General Medicine ◽  
Alcohol Withdrawal Syndrome ◽  
Cyp2c19 Gene ◽  
Icd 10 ◽  
Rating Scale Data

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.

scholarly journals A NEW RATING SCALE FOR THE ASSESSMENT OF THE ALCOHOL-WITHDRAWAL SYNDROME (AWS SCALE)

1997 ◽  
Vol 32 (6) ◽  
pp. 753-760 ◽  
Author(s):  
T. WETTERLING ◽  
R.-D. KANITZ ◽  
B. BESTERS ◽  
D. FISCHER ◽  
B. ZERFASS ◽  
...  
Keyword(s):  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Rating Scale ◽  
Alcohol Withdrawal Syndrome

scholarly journals DEVELOPMENT OF A RATING SCALE TO PREDICT THE SEVERITY OF ALCOHOL WITHDRAWAL SYNDROME

2006 ◽  
Vol 41 (6) ◽  
pp. 611-615 ◽  
Author(s):  
TILMAN WETTERLING ◽  
BERNHARD WEBER ◽  
MARKUS DEPFENHART ◽  
BARBARA SCHNEIDER ◽  
KLAUS JUNGHANNS
Keyword(s):  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Rating Scale ◽  
Alcohol Withdrawal Syndrome

Influence of oxygen therapy methods in comprehensive treatment on cognitive functions at correction of alcohol withdrawal syndrome

2020 ◽  
Vol LII (2) ◽  
pp. 52-58
Author(s):  
Dmitry A. Kopytov ◽  
Il’ya V. Bychenko ◽  
Andrej V. Kopytov
Keyword(s):  
Cognitive Impairment ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Hyperbaric Oxygenation ◽  
Alcohol Withdrawal Syndrome ◽  
Comprehensive Treatment ◽  
Mental Performance ◽  
Icd 10 ◽  
Clinical Verification ◽  
Research Criteria

Aim.Based on the application of methods of normoxic therapeutic compression and hyperbaric oxygenation incombination with pharmacotherapy for the relief of cognitive impairment in alcohol withdrawal syndrome (AWS), to evaluate the effectiveness of their use to optimize the treatment process. Methods.160patients with AWS were examined: 62people underwent hyperbaric oxygenation and 56normoxic therapeutic compression sessions along with symptomatic pharmacotherapy, 42with drugs in accordance with medical care protocols. To assess the severity of the manifestations of AWS, the CIWA-A scale was used. Diagnosis and clinical verification of the diagnosis of alcohol dependence was carried out in accordance with the research criteria of the ICD-10 and AUDIT. To study cognitive impairment, the Schulte table technique was used. Results.The use of the method of normoxic therapeutic compression in the complex treatment of AWS increases the mental performance after the first day of therapy by 4.6times, after the third day of therapy, 3.18times, after the seventh day of therapy, 3.25times, compared with drugs. Conclusion.Oxygen therapy methods in combination with pharmacotherapy should be used when stopping cognitive impairment in alcohol withdrawal syndrome, which will increase the effectiveness of treatment and avoid possible cognitive impairment in pharmacotherapy.

Treatment of the Acute Alcohol-Withdrawal Syndrome

1958 ◽  
Vol 19 (1) ◽  
pp. 118-124 ◽  
Author(s):  
Lincoln Godfrey ◽  
Martin D. Kissen ◽  
Thomas M. Downs
Keyword(s):  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome

scholarly journals Should the CIWA-Ar be the standard monitoring strategy for alcohol withdrawal syndrome in the intensive care unit?

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tessa L. Steel ◽  
Shewit P. Giovanni ◽  
Sarah C. Katsandres ◽  
Shawn M. Cohen ◽  
Kevin B. Stephenson ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome ◽  
Patient Characteristics ◽  
Response To Treatment ◽  
Alternative Measure ◽  
Icu Patients ◽  
Verbal Responses

Abstract Background The Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) is commonly used in hospitals to titrate medications for alcohol withdrawal syndrome (AWS), but may be difficult to apply to intensive care unit (ICU) patients who are too sick or otherwise unable to communicate. Objectives To evaluate the frequency of CIWA-Ar monitoring among ICU patients with AWS and variation in CIWA-Ar monitoring across patient demographic and clinical characteristics. Methods The study included all adults admitted to an ICU in 2017 after treatment for AWS in the Emergency Department of an academic hospital that standardly uses the CIWA-Ar to assess AWS severity and response to treatment. Demographic and clinical data, including Richmond Agitation-Sedation Scale (RASS) assessments (an alternative measure of agitation/sedation), were obtained via chart review. Associations between patient characteristics and CIWA-Ar monitoring were tested using logistic regression. Results After treatment for AWS, only 56% (n = 54/97) of ICU patients were evaluated using the CIWA-Ar; 94% of patients had a documented RASS assessment (n = 91/97). Patients were significantly less likely to receive CIWA-Ar monitoring if they were intubated or identified as Black. Conclusions CIWA-Ar monitoring was used inconsistently in ICU patients with AWS and completed less often in those who were intubated or identified as Black. These hypothesis-generating findings raise questions about the utility of the CIWA-Ar in ICU settings. Future studies should assess alternative measures for titrating AWS medications in the ICU that do not require verbal responses from patients and further explore the association of race with AWS monitoring.

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