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细胞色素 P450 在心理应激下某些抗抑郁药和抗焦虑药代谢中的作用。

The role of cytochromes P450 in the metabolism of selected antidepressants and anxiolytics under psychological stress.

机构信息

Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

出版信息

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2022 May;166(2):140-149. doi: 10.5507/bp.2022.019. Epub 2022 Apr 12.

Abstract

In today's modern society, it seems to be more and more challenging to cope with life stresses. The effect of psychological stress on emotional and physical health can be devastating, and increased stress is associated with increased rates of heart attack, hypertension, obesity, addiction, anxiety and depression. This review focuses on the possibility of an influence of psychological stress on the metabolism of selected antidepressants (TCAs, SSRIs, SNRIs, SARIs, NDRIs a MMAs) and anxiolytics (benzodiazepines and azapirone), as patients treated with antidepressants and/or anxiolytics can still suffer from psychological stress. Emphasis is placed on the drug metabolism mediated by the enzymes of Phase I, typically cytochromes P450 (CYPs), which are the major enzymes involved in drug metabolism, as the majority of psychoactive substances are metabolized by numerous CYPs (such as CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2A6, CYP2D6, CYP3A4). As the data on the effect of stress on human enzymes are extremely rare, modulation of the efficacy and even regulation of the biotransformation pathways of drugs by psychological stress can be expected to play a significant role, as there is increasing evidence that stress can alter drug metabolism, hence there is a risk of less effective drug metabolism and increased side effects.

摘要

在当今的现代社会,应对生活压力似乎越来越具有挑战性。心理压力对情绪和身体健康的影响可能是毁灭性的,而压力的增加与心脏病发作、高血压、肥胖、成瘾、焦虑和抑郁的发生率增加有关。这篇综述重点探讨了心理压力对某些抗抑郁药(三环类抗抑郁药、SSRIs、SNRIs、SARIs、NDRIs 和 MMAs)和抗焦虑药(苯二氮䓬类和阿扎吡隆)代谢的影响的可能性,因为接受抗抑郁药和/或抗焦虑药治疗的患者仍然可能会受到心理压力的影响。重点放在由 I 相代谢酶(通常为细胞色素 P450 [CYPs])介导的药物代谢上,这些酶是参与药物代谢的主要酶,因为大多数精神活性物质都被许多 CYP 代谢(如 CYP1A2、CYP2B6、CYP2C19、CYP2C9、CYP2A6、CYP2D6、CYP3A4)。由于关于压力对人类酶的影响的数据极为罕见,因此可以预期心理压力对药物疗效的调节甚至对生物转化途径的调节将发挥重要作用,因为越来越多的证据表明压力可以改变药物代谢,从而存在药物代谢效果降低和副作用增加的风险。

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