Effects of CYP2C19*17 genetic polymorphisms on plasma and saliva concentrations of diazepam in patients with alcohol withdrawal syndrome

2022 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Valentin Yurievich Skryabin ◽  
Mikhail Zastrozhin ◽  
Marco Torrado ◽  
Elena Grishina ◽  
Kristina Ryzhikova ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome

Effects of CYP2C19*17 Genetic Polymorphisms on the Steady-State Concentration of Diazepam in Patients With Alcohol Withdrawal Syndrome

2020 ◽  
pp. 001857872093175
Author(s):  
Valentin Yurievich Skryabin ◽  
Mikhail Zastrozhin ◽  
Marco Torrado ◽  
Elena Grishina ◽  
Kristina Ryzhikova ◽  
...  
Keyword(s):  
Steady State ◽  
Genetic Polymorphisms ◽  
Adverse Drug Reactions ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Steady State Concentration ◽  
State Concentration

Background: Diazepam is one of the most widely prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS), which includes the symptoms of anxiety, fear, and emotional tension. However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions, reducing the efficacy of therapy. Aim: The purpose of our study was to investigate the effects of CYP2C19*17 genetic polymorphisms on the steady-state concentration of diazepam in patients with AWS. Materials and Methods: The study was conducted on 50 Russian male patients suffering from the AWS. For the therapy of psychomotor agitation, anxiety, fear, and emotional tension, patients received diazepam in injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time polymerase chain reaction. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Therapeutic drug monitoring (TDM) was performed using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 − 806C>T genotypes: (*1/*1) −12.0 [−15.0; −8.0], (*1/*17+*17/*17) −7.0 [−14.0; −5.0], P < .001, as well as the results of TDM: ( CC) 250.70 [213.34; 308.53] ng/mL (*1/*17+*17/*17) 89.12 [53.26; 178.07] ng/mL, P < .001. Conclusion: Thus, our study enrolling 50 patients with AWS, showed the effects of CYP2C19*17 genetic polymorphisms on the efficacy and safety rates of diazepam. Furthermore, we revealed the statistically significant difference in the levels of plasma steady-state concentrations of diazepam in patients carrying different genotypes.

How do CYP2C19*2 and CYP2C19*17 genetic polymorphisms affect the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome?

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Valentin Yu Skryabin ◽  
Mikhail S. Zastrozhin ◽  
Marco V. Torrado ◽  
Elena A. Grishina ◽  
Kristina A. Ryzhikova ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Safety Assessment ◽  
Alcohol Withdrawal Syndrome ◽  
Efficacy And Safety ◽  
Psychometric Scales ◽  
Therapy Efficacy ◽  
Scale Scores ◽  
Male Patients

Abstract Background Diazepam is one of the most commonly prescribed tranquilizers for therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on its efficacy and safety. The objective of our study was to investigate the effect of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy and safety of diazepam in patients with AWS. Methods The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Results Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 681G>A (CYP2C19*2, rs4244285) genotypes: (CYP2C19*1/*1) −8.5 [−15.0; −5.0], (CYP2C19*1/*2 and CYP2C19*2/*2) −12.0 [−13.0; −9.0], p = 0.021. The UKU scale scores, which were used to evaluate the safety of therapy, were also different: (CYP2C19*1/*1) 7.0 [6.0; 12.0], (CYP2C19*1/*2 and CYP2C19*2/*2) 9.5 [8.0; 11.0], p = 0.009. Patients carrying different CYP2C19 –806C>T (CYP2C19*17, rs12248560) genotypes also demonstrated differences in therapy efficacy and safety rates. Conclusions Thus, the effects of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy of diazepam were demonstrated.

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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