University of Ioannina, School of Medicine, Department of Pharmacology , Ioannina, GR-451 10 , Greece +30 26510 07554 ;
Expert Opin Drug Metab Toxicol. 2013 Oct;9(10):1317-34. doi: 10.1517/17425255.2013.816283. Epub 2013 Jul 9.
The available evidence suggests that psychophysiological stress regulates a substantial number of factors, which in turn, can alter the pharmacokinetic parameters of a drug.
Due to the multi-factorial involvement of stress in the regulation of a drug's pharmacokinetic profile, this review has been limited to and focuses only on the impact of stress on drug metabolism. Specifically, the review presents studies which have indicated that psychophysiological stress can significantly modify the function of the major hepatic drug-metabolizing enzymes belonging to cytochrome P450s (CYP) family in a stress-specific and species-specific manner. Furthermore, the article discusses how stress related changes in CYP regulation appear to be mediated by glucocorticoids and epinephrine/norepinephrine. This can lead to an increased rate of metabolism of the majority of prescribed drugs and chemical pre-carcinogens.
Apparently, psychophysiological stress has a significant impact on some of the major drug-metabolizing enzyme systems. Therefore, stress should be considered as an important factor affecting drug metabolism and pharmacokinetics, with the potential to significantly alter the outcome of drug therapy and toxicity. Despite the fact that the majority of data come from experimental studies, it is conceivable that the elimination of stress is an essential condition in order to ensure the optimal outcome of pharmacotherapy.
现有证据表明，心理生理应激调节着大量的因素，这些因素反过来又可以改变药物的药代动力学参数。
由于应激在调节药物药代动力学特征方面的多因素参与，本综述仅限于并仅侧重于应激对药物代谢的影响。具体而言，该综述介绍了一些研究表明，心理生理应激可以以应激特异性和物种特异性的方式显著改变属于细胞色素 P450（CYP）家族的主要肝药物代谢酶的功能。此外，本文还讨论了应激相关的 CYP 调节变化如何似乎是由糖皮质激素和肾上腺素/去甲肾上腺素介导的。这可能导致大多数处方药物和化学前致癌物的代谢率增加。
显然，心理生理应激对一些主要的药物代谢酶系统有重大影响。因此，应激应被视为影响药物代谢和药代动力学的一个重要因素，有可能显著改变药物治疗的结果和毒性。尽管大多数数据来自实验研究，但可以想象，消除应激是确保药物治疗最佳结果的必要条件。
