Curative effects of Dhatryadi ghrita bioactive extracts on ethanol withdrawal syndrome in Wistar rats

2020 ◽  
Vol 16 ◽  
Author(s):  
Rashmi Saxena Pal ◽  
Amrita Mishra

Background: Alcohol withdrawal syndrome leads to irritability, aggressiveness, body posture and motor abnormalities, sensory hyper reactivity and changes in various enzyme levels. Dhatryadi ghrita penetrates the blood- brain barrier to decrease the cravings for alcohol in this syndrome. Objective: To evaluate the effect of alcoholic extract of Dhatryadi ghrita on alcohol withdrawal syndrome in Wistar rats. Material & Methods: A liquid diet with 7.2%, v/v ethanol was administered to the Wistar rats for 21 days. Control group animals received saline and normal diet. After alcohol withdrawal, rats were examined at 6th and 24th hour for anxiety and hyper locomotor activity as major withdrawal signs. Anxiety due to ethanol withdrawal was tested with the help of elevated plus maze, light and dark models. The hyper locomotor activity was assessed using Actophotometer. The hepatic enzymes level was determined with the help of the Bio-chemical Analyzer. Ghrita extract (100, 200,300 mg/kg, oral) were administered to different groups and diazepam as standard (2 mg/kg, i.p) were administered to the treatment group animals 30 minutes before alcohol withdrawal estimation. Drug treatment was administered 30 minutes before the second observation at the 24th hour. Results: Findings from the present study revealed that Ghrita extract treatment at doses 100, 200 and 300 mg/kg, oral in ethanol-dependent rats had a significant protective effect on signs and symptoms of ethanol withdrawal in alcohol-dependent rats. Conclusion: Dhatryadi extract acts effectively for the treatment of alcohol abstinence syndrome. The extract treat¬ment has beneficial effects on ethanol withdrawal depressive-like behavior in rats.

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052091005
Author(s):  
Yun Song ◽  
Xiaobin Xue ◽  
Haibin Han ◽  
Cuiluan Li ◽  
Jia Jian ◽  
...  

Objective To compare the efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with diazepam against diazepam alone for treatment of acute alcohol withdrawal syndrome (AWS). Methods In this double-blind randomized sham-controlled trial, men with acute AWS were randomly allocated to either a group treated with TEAS combined with diazepam (n = 57) or a control group treated with sham TEAS combined with diazepam (n = 60). Treatment was performed at four acupoints twice a day for 14 days. The Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar), visual analogue scale (VAS), Pittsburgh Sleep Quality Index (PSQI) and modified Epworth Sleepiness Scale (mESS) were used to evaluate treatment efficacy. Results All scores improved significantly in both groups during the trial. CIWA-Ar scores were lower in the TEAS group than in the control group from day 3 until the end of observation. VAS and mESS scores were also lower in the TEAS group than in the control group on day 7. VAS and PSQI scores were lower in the TEAS group on day 14. Conclusion Combining diazepam with TEAS may result in milder AWS symptoms than diazepam alone, improve sleep quality and reduce sleepiness.


2021 ◽  
Vol 11 (7) ◽  
pp. 919
Author(s):  
Ijasul M. Haque ◽  
Akhilesh Mishra ◽  
Bhupinder Singh Kalra ◽  
Shalini Chawla

Patients with alcohol use disorder experience alcohol withdrawal syndrome due to the sudden cessation of alcohol. This study was designed to evaluate the protective effect of Ashwagandha and Brahmi on alcohol withdrawal in rats. Thirty rats of either sex were taken and randomly divided into 6 groups (n = 5). Their normal diet was replaced by a modified liquid diet (MLD). Ethanol was added gradually except in the MLD group for a period of 21 days and withdrawn suddenly. Four treatment groups were administered Ashwagandha (3.75 mg of withanolide glycosides per kg body weight), Brahmi (10 mg of bacosides per kg body weight), Ashwagandha + Brahmi (3.75 mg withanolide glycosides + 10 mg bacosides per kg body weight) orally and diazepam (1 mg/kg body weight, i.p.) 45 min before alcohol withdrawal. Rats were assessed for behavioural changes (agitation score and stereotypic behaviour), anxiety and locomotor activity at 2nd and 6th hours of alcohol withdrawal. Pentylenetetrazol (PTZ) kindling seizures were assessed at 6th hour of alcohol withdrawal. Ashwagandha and Brahmi alone and in combination significantly reduced the behavioural changes in alcohol withdrawal rats at 2nd hour and their combination in 6th hour. Ashwagandha and Brahmi suppressed PTZ kindling seizures effectively and improved locomotory activity at 2nd hour and 6th hour of alcohol withdrawal. Reduction in anxiety was significant among Ashwagandha at 2nd hour and the combination group at 2nd and 6th hour. The results were comparable to diazepam. Ashwagandha and Brahmi have beneficial effects in controlling the behavioural changes, anxiety and seizures in alcohol withdrawal symptoms in rats and improved locomotory activity.


Author(s):  
М.С. Застрожин ◽  
А.С. Сорокин ◽  
Т.В. Агибалова ◽  
И.А. Бедина ◽  
Е.А. Гришина ◽  
...  

Введение: Имплементация систем поддержки принятия решений, способных формировать рекомендации по выбору лекарствен- ного средства и его дозы в соответствии с результатами фармакогенетического тестирования, является актуальной задачей, так как решение ее позволит повысить эффективность терапии и снизить риск развития нежелательных лекарственных реакций.Материалы и методы: В исследовании принимал участие 51 пациент (21 - основная группа, получавшая назначения в соответ- ствии с рекомендациями, основанными на результатах фармакогенетического тестирования, а 30 - группа сравнения, получавшая назначения без них) мужского пола с синдромом отмены алкоголя. Для оценки эффективности и безопасности терапии синдрома отмены алкоголя, которую осуществляли с использованием бензодиазепинового транквилизатора феназепама (бромдигидрохлор- фенилбензодиазепина), а также стандартной дезинтоксикационной и витаминотерапии, применялись международные психоме- трические шкалы и шкалы оценки выраженности нежелательных реакций. Определение полиморфизмов генов CYP2D6*4 (1846G>A, rs3892097), CYP2C19*2 (681G>A, rs4244285), CYP2C19*3 (636G>A, rs4986893), CYP2C19*17 (-806C>T, rs12248560), CYP3A5*3 (6986A>G, rs776746) и ABCB1*6 (3435C>T, rs1045642) осуществлялось методом полимеразной цепной реакции в реальном времени с аллель-специфиче- ской гибридизацией. Интерпретацию результатов фармакогенетического тестирования осуществляли с использованием свободно распространяемого программного обеспечения PharmacoGenomeX2 (www.pgx2.com).Результаты: Получены статистически значимые различия в количестве баллов по всем психометрическим шкалам у пациентов основной группы и группы сравнения. Например, по шкале оценки тяжести синдрома отмены алкоголя к 3-му дню исследования количество баллов в основной группе составляло 13,5 [11,2; 16,0], а в группе контроля - 18,0 [17,0; 22,0] (p < 0,001); к 5-му в основ- ной группе - 6,5 [4,2; 8,0], в группе контроля - 15,0 [14,0; 16,0] (p < 0,001). По шкале безопасности UKU также была получена стати- стически значимая разница. К 3-му дню исследования количество баллов по шкале UKU в основной группе составило 6,0 [5,0; 7,0], а в группе контроля - 7,0 [6,0; 8,0] (p = 0,030); к 5-му дню разница возрастала. В основной группе - 5,5 [3,0; 9,0], в группе контроля - 14,0 [12,0; 19,0] (p < 0,001). Группы были репрезентативны (при включении в исследование разница в количестве баллов отсутствовала). Выводы: Персонализация дозы лекарств в соответствии с фармакогенетическими алгоритмами у пациентов с синдромом отмены алкоголя, способна снизить риск развития нежелательных реакций и фармакорезистентности, что позволяет рекомендовать исполь- зование фармакогенетических систем поддержки принятия решений для подбора дозы лекарств. Introduction: Implementation of the clinical decision support systems capable of forming the recommendations on drug and dose selec- tion according to the results of pharmacogenetic testing is an urgent task. Fulfillment of this task will allow increasing the efficacy of ther- apy and decreasing the risk of undesirable side effects.Materials and methods: The study involved 51 patients (21 - the main group receiving appointments in accordance with the recommenda- tions based on the results of pharamogenetic testing, and 30 - the comparison control group receiving appointments without them) male with alcohol withdrawal syndrome. In order to assess the effectiveness and safety of alcohol withdrawal syndrome, which was performed with the benzodiazepine tranquilizer of phenazepam (bromodihydrochlorophenylbenzodiazepine), as well as standard detoxification and vitamin therapy, international psychometric scales and scales of assessment in expressions of adverse reactions. Genotyping Determination of genetic polymorphisms CYP2D6*4 (1846G>A, rs3892097), CYP2C19*2 (681G>A, rs4244285), CYP2C19*3 (636G>A, rs4986893), CYP2C19*17 (-806C>T, rs12248560), CYP3A5*3 (6986A>G, rs776746) and ABCB1*6 (3435C>T, rs1045642) were realized using real-time polymerase chain reaction with allele specific hybridization. Interpretation of the results of pharmacogenetic testing was carried out with the help of free soft- ware PharmacoGenomeX2 (www.pgx2.com)Results: Statistically significant differences in the number of scores for all psychometric scales in the patients of the main group and the comparison group were obtained. For example, on the scale of assessing the severity of alcohol withdrawal syndrome by the 3rd day of the study, the score in the main group was 13.5 [11.2; 16,0], and in the control group - 18,0 [17,0; 22.0] (p <0.001); to the 5th in the main group - 6.5 [4.2; 8.0], in the control group - 15.0 [14.0; 16.0] (p <0.001). On the UKU security scale, a statistically significant difference was also obtained. By the 3rd day of the study, the UKU score in the main group was 6.0 [5.0; 7,0], and in the control group - 7,0 [6,0; 8.0] (p = 0.030); by the 5th day the difference increased. In the main group, 5.5 [3.0; 9.0], in the control group - 14.0 [12.0; 19.0] (p <0.001). The groups were representative (when included in the study, the difference in the number of points was absent).Conclusion: Personalization of the dose of drugs in accordance with pharmacogenetic algorithms in patients with alcohol withdrawal syn- drome, can reduce the risk of unwanted reactions and pharmacoresistance, which allows to recommend the use of pharmacogenetic deci- sion support systems for drug dosage selection.


2021 ◽  
Vol 25 (4) ◽  
pp. 605-609
Author(s):  
Y. V. Volkova ◽  
S. S. Dubivska ◽  
A. V. Omelchenko-Seliukova ◽  
O. V. Biletskyi

Annotation. Polytrauma is considered the main cause of death among people younger 45 years. Among trauma patiens 15-20% regularly take alcohol, close to 32% of patients who needed intensive therapy to alcohol withdrawal syndrome (AWS), and 5-20% of the progressed to alcohol delirium. The aim of the study is to analyze the dynamics of autoimmune response to markers of neurodestruction in the blood of patients with moderate polytrauma and alcohol withdrawal, complicated by alcohol delirium and assessment of cognitive functions depending on the method of sedation. The study involved 80 patients with moderate polytrauma with alcohol withdrawal, complicated by alcohol delirium. The median age was 45 years (39-54). Patients in Group 1 (n=40) were given dexmedetomidine as a sedation method, and in Group 2 (n=40) diazepam sedation was used according to the symptom-trigger protocol. The content of antibodies to neuron-specific enolase (NSE), myelin basic protein (MBP), total human brain antigen (THBA), S-100 calcium were determined by enzyme-linked immunosorbent assay on days 1, 3, 7 and 14 after alcohol delirium. Assessment of cognitive function was performed (after withdrawal from sedation if present) on days 4 and 14 using the Montreal Cognitive Assessment Scale (MoCa). Mathematical processing of the obtained results was performed in accordance with the generally accepted methods of statistical analysis. The critical value of the significance level (p) was taken as ≤5%. Signs, the distribution of which differed from normal, are presented in the form of Me (median), the confidence interval within the first and third quarters [QI - QIII]. To assess the causal role of various factors in the development of lesions used χ-square with the inclusion of the Yates correction and the odds ratio. In the first 24 hours after the manifestation of AD, the levels of autoantibodies in the two groups of patients did not differ significantly from the level of healthy volunteers. Estimation of the level of antibodies to the S-100B protein showed that in group 1 this indicator increased by a maximum of 24.4% and amounted to 15.8 [14.7 - 17.6], while in the second group increased by 32.6% and became 17.5 [15.3 - 19.7]. From the 7th day, the number of antibodies began to decrease in both groups and was 15.6 [13.6 - 16.8] in group 1 and 16.3 [14.1-19.2] in group 2 on the 7th day, and 14.0 [11.6 - 15.3] and 15.2 [ 13.1 - 18.3], respectively, on the 14th day after hospitalization in ICU. The level of antibodies to NSE was maximum on the 3rd day of the study and was 29.8 [28.4 - 31.8] in patients of group 1, which is higher than the initial level by 26.8%, and in patients of group 2 was 31.6 [29.5 -33.2], which exceeds baseline by 33.9% (p=0.0114 between groups 1 and 2). Subsequently, there was a decrease in the level of antibodies to NSE on the 7th and 14th day after the onset of AD, while maintaining a significant difference between the comparison groups. Antibodies to MBP did not differ between groups up to and including day 3, but were significantly higher than in healthy volunteers. On the 7th day, the level of antibodies to MBP in group 1 was 26.8 [24.4 - 28.8], which corresponded to the values of the control group, and in group 2 was 29.3 [27.7 - 31.5], which is significantly more than the first group (p = 0.0017). In the study on day 14, this trend was maintained: the level of antibodies to OBM among patients in group 2 was 28.6 [27.0 - 30.8], while in group 1 it was 26.2 [23.7 - 28.2]. Antibody levels to THBA on day 3 were significantly higher than baseline and were 30.8 [28.4 - 34.5] in group 1 and 32.7 [30.6 - 36.1] in group 2 (p=0.0056). On day 7 and day 14, the number of antibodies THBA in patients of group 1 did not differ significantly from the control group, while in patients of group 2 they were significantly higher on day 7 - 31.5 [29.4 - 34.9] and normalized on day 14. When analyzing the results of the MoCa test after eliminating the main manifestations of alcohol withdrawal syndrome (4 days after admission to ICU), the number of points in the study groups was significantly lower than the control values: in group 1 1.3 times (p <0.0001), in group 2 – 1.6 times (p<0.0001). The differences between the studied groups of patients are significant (p = 0.000087). Thus, the use of dexmedetomidine for the sedation of patients with hypertension and polytrauma reduces autumnal neurodestruction, which improves the prognosis for the restoration of cognitive function.


2019 ◽  
Vol 33 (4) ◽  
pp. 477-480
Author(s):  
Erin Waldee ◽  
Stephanie V. Phan

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.


1980 ◽  
Vol 14 (3) ◽  
pp. 213-215 ◽  
Author(s):  
D. G. Lambie ◽  
R. H. Johnson ◽  
M. E. Vijayasenan ◽  
E. A. Whiteside

The value of sodium valproate in the management of patients during withdrawal from alcohol dependence has been assessed. Alcoholic inpatients were randomly allocated to two groups — one treated with sodium valproate and the other acting as a control. All patients received multivitamins and fluid and electrolyte replacement, and some received chlormethiazole or other tranquillisers. Treatment with sodium valproate (1200 mg daily) was continued for one week. The occurence of seizures and other withdrawal symptoms (tremulousness, nausea, sweating, disorientation) were noted daily. Forty-nine episodes of withdrawal have been included in the trial — 22 in the sodium valproate group and 27 in the control group. Five patients, all in the control group, had seizures. Other withdrawal symptoms disappeared more quickly in the sodium valproate group even though fewer patients were receiving chlormethiazole.


2020 ◽  
Vol 71 (1) ◽  
pp. 19-26
Author(s):  
Enrico Marinelli ◽  
Renata Beck ◽  
Antonio Malvasi ◽  
Alfredo Fabrizio Lo Faro ◽  
Simona Zaami

AbstractGamma-hydroxybutyrate (GHB) is a central nervous system depressant primarily used as a recreational drug of abuse, but also for the treatment of narcolepsy with cataplexy in adult patients and as an adjuvant for control of alcohol withdrawal syndrome. The main aim of this review is to summarise updated knowledge about GHB pharmacokinetics and pharmacodynamics, acute poisoning, and clinical features of GHB withdrawal syndrome, its diagnosis and medical treatment. The most common clinical signs and symptoms of acute poisoning include sleepiness to deep coma, bradycardia, hypotension, and respiratory failure. Therapy is essentially supportive and based on continuous monitoring of vital signs. GHB withdrawal syndrome shares patterns with other withdrawal syndromes such as alcohol withdrawal and is sometimes difficult to distinguish, especially if toxicological tests are GHB-negative or cannot be performed. There are no official detoxification protocols for GHB withdrawal syndrome, but its therapy is based on benzodiazepine. When benzodiazepine alone is not effective, it can be combined with barbiturates or antipsychotics. Information about abuse and distribution of GHB and its precursors/analogues among the general population is still limited. Their prompt identification is therefore crucial in conventional and non-conventional biological matrices, the latter in particular, to clarify all the issues around this complex molecule.


2022 ◽  
Vol 8 (1) ◽  
pp. 1-6
Author(s):  
Rana Shahabi ◽  
◽  
Mohammad Rostampour ◽  
Behrooz Khakpour ◽  
Bahram Soltani ◽  
...  

Background: Along with industrial development and the increasing social complexity of societies, anxiety is one of the most prevalent psychological disorders. Medicinal plants are considered as an enrichment source of ingredients with biological activity. Objectives: The aim of this study was to evaluate the anxiolytic effect of Anethum Graveolens seed (AGS) and the possible involvement of Gamma-Aminobutyric Acid (GABA)-ergic system in the AGS effect. Materials & Methods: In the present experimental study, 64 female Wistar rats were divided into eight groups and received various concentrations of hydroalcoholic extract of AGS. To measure the level of anxiety, an elevated plus maze was used in a way that the animal’s head turned to an open arm. Prior to the injections of AGS extract, the GABA receptor antagonist was used. The results were analyzed by one-way analysis of variance using IBM SPSS v. 16. Results: Dose-response experiments showed that the AGS extract significantly decreased the anxiety indices compared to the control group (P<0.05). To analyze locomotor activity, our data showed that AGS extract at 0.1, 1, and 10 mg/kg could significantly increase locomotor activity compared to the control group (P<0.001). Pentylenetetrazol (PTZ (+extract significantly decreased the anxiolytic effect of AGS extract (P<0.01). Conclusion: Considering the anti-anxiety effects of AGS extract and a reduction in this effect caused by PTZ, part of the anti-anxiety effect of extract might be assumed via its interaction with GABA-ergic receptors. Further experimental trials; however, are required for the establishment of the anti-anxiety impact of AGS.


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