地西泮诱导后对麻醉苏醒的影响及其与 CYP2C9、CYP2C19 和 CYP3A4 基因多态性的关系

T. Mittal, VK Badhe, DS Divekar Badhe, P. Ahluwalia, Balraj Mittal, Rama Mittal
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引用次数: 0

摘要

简介和目标:苯二氮卓常用作静脉注射麻醉剂的辅助剂。地西泮的剂量因所需终点的不同而有很大差异。这种个体间药物反应差异背后的原因是由基因决定的酶活性改变。我们评估了使用两种不同剂量地西泮诱导麻醉后患者的苏醒时间,并评估了苏醒时间与药物代谢物 CYP2C19、CYP2C9 和 CYP3A4 基因的基因多态性之间是否存在相关性。研究方法研究对象为随机选择的 40-60 岁择期手术成年患者,并预先设定了纳入和排除标准。患者被分为两组,第一组接受 0.2 毫克/千克地西泮,第二组接受 0.3 毫克/千克地西泮。手术后的唤醒时间由录音机播放标准口令后确定。在实施麻醉前,采集 3 毫升乙二胺四乙酸(EDTA)血液。结果两组患者的苏醒时间在 8-18 分钟之间没有差异。相比之下,CYP2C9 2、CYP2C9 2 和 CYP2C9 2 的患者需要更长的时间才能醒来,但这种关联在统计学上并不显著。然而,CYP2C9 2 和 2 C9 3 以及 CYP3A4 基因型对苏醒时间没有影响。结论该试验研究表明,2C19 2 基因型的患者服用地西泮的苏醒时间更长,而 2C19 2 基因型的患者具有慢代谢表型。然而,在临床应用之前,这项研究需要在更大样本量下重复进行,以得出明确的结论。缩写:BDZ-苯二氮卓;EDTA-乙二胺四乙酸;GA-全身麻醉 关键词地西泮;出现;基因多态性;药物遗传学 引文: Mittal T, Badhe V. Mittal T, Badhe V. Mittal T, Badhe V:Mittal T, Badhe VK, Badhe DSD, Ahluwalia P, Mitta Bl, Mittal R. 地西泮诱导后对麻醉苏醒的影响及其与 CYP2C9、CYP2C19 和 CYP3A4 基因多态性的关联。 Anaesth.DOI: 10.35975/apic.v28i1.2380 收到:2023 年 7 月 20 日;审阅:收稿日期:2023 年 7 月 20 日;审稿日期:2023 年 12 月 07 日;接受日期:2023 年 12 月 07 日:接受:2023 年 12 月 07 日
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect on emergence from anesthesia following induction with diazepam and its association with CYP2C9, CYP2C19 and CYP3A4 gene polymorphisms
Introduction & Objectives: Benzodiazepines are commonly used as adjuvants to IV anesthetic agents. Diazepam dosage varies widely depending on the desired endpoints. The rationale behind such inter-individual variability in drug responses has been attributed to genetically determined alterations in the enzyme activities. We assessed the emergence time in patients after induction of anesthesia with two different doses of diazepam and evaluated if any correlation exists between the emergence time and genetic polymorphism in drug metabolizers CYP2C19, CYP2C9, and CYP3A4 genes. Methodology: The study was conducted on randomly selected adult patients scheduled for elective surgery between 40-60 y of age with predefined inclusion and exclusion criteria. The patients were distributed into 2 groups, with group 1 receiving 0.2 mg/kg and group 2 given 0.3 mg/kg diazepam. Wake-up time after surgery was determined after a standardized verbal command played by a tape-recorder. Three ml blood in Ethylenediaminetetraacetic acid (EDTA) was collected before administering anesthesia. Results: Wake-up time between 8-18 min did not vary between the two groups. Comparatively persons having 2C19 2 took longer time to wake-up but this association was not statistically significant. However, CYP2C9 2 and 2 C9 3 and CYP3A4 genotypes had no influence on wake-up time. Conclusion: The pilot study suggests the emergence time from diazepam is longer in patients having 2C19 2 which confers slow-metabolizer phenotype. However, this study needs to be replicated in larger sample size to arrive at definitive conclusions before clinical applications. Abbreviations: BDZ- benzodiazepine; EDTA- Ethylenediaminetetraacetic acid; GA-General Anesthesia Key words: Diazepam; Emergence; Gene Polymorphism; Pharmacogenetics Citation: Mittal T, Badhe VK, Badhe DSD, Ahluwalia P, Mitta Bl, Mittal R. Effect on emergence from anesthesia following induction with diazepam and its association with CYP2C9, CYP2C19 and CYP3A4 gene polymorphisms.  Anaesth. pain intensive care 2024;28(1):126-138. DOI: 10.35975/apic.v28i1.2380 Received: July 20, 2023; Reviewed: December 07, 2023; Accepted: December 07, 2023
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