Psychophysiological stress: a significant parameter in drug pharmacokinetics

Abstract

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.

Gut Reactions: Breaking Down Xenobiotic–Microbiome Interactions

“…Stress is known to impact on host xenobiotic metabolism, particularly via induction of hepatic drug-metabolizing enzymes possibly mediated by glucocorticoids or noradrenaline (Konstandi, 2013;Pantelidou et al, 2017). Gut microbiome alterations are frequently reported in stressrelated disorders such as depression, anxiety, and irritable bowel syndrome (Rajilic-Stojanovic et al, 2015;Foster et al, 2017).…”

The Effect of Chronic Treatment with Lurasidone on Rat Liver Cytochrome P450 Expression and Activity in the Chronic Mild Stress Model of Depression

“…2014; Tank and Lee Wong, 2015;Faron-Górecka et al, 2016;Rossetti et al, 2016). The aforementioned CMS-evoked physiopathologic changes in the concentrations of peripheral glucocorticoids, catecholamines, and cytokines affect hepatic signaling pathways mediating the regulation of CYP (Konstandi, 2013). Glucocorticoids are known to have complex (direct and/or indirect), mostly positive effects on the expression/activity of rat hepatic CYP2B (Waxman et al, 1990), CYP2C11 (Iber et al, 1997), and CYP3A (Huss and Kasper, 2000).…”

“…Glucocorticoids are known to have complex (direct and/or indirect), mostly positive effects on the expression/activity of rat hepatic CYP2B (Waxman et al, 1990), CYP2C11 (Iber et al, 1997), and CYP3A (Huss and Kasper, 2000). However, these effects may be modified by catecholamines (adrenaline, noradrenaline) acting positively via hepatocyte a 1 and b 1/2 adrenergic receptor through the cAMP response element-binding protein pathway, but negatively via pancreatic b 2 receptor through the insulin pathway (Konstandi, 2013) on CYP expression (Konstandi, 2013). Moreover, CMS-induced immune disturbances that lead to elevation of plasma proinflammatory cytokines (interleukin-6, tumor necrosis factor-a, and tumor necrosis factor-g) may additionally diminish enzyme expression (Zidek et al, 2009;Jiang et al, 2014).…”

“…Stress, depending on its nature, intensity, and duration, produces multiple changes in the functioning of the monoaminergic systems, and thus it may affect the central neuroendocrine and autonomic regulation of liver function and CYP expression (Carrasco and Van de Kar, 2003;Uyama et al, 2004;Kot et al, 2013;Chmielarz et al, 2015). Psychotropic drugs that act on monoaminergic receptors or transporters in the brain and periphery affect the endocrine and immune systems (Jaber et al, 1994;Rane et al, 1996;Raap and Van de Kar, 1999;Drzyzga et al, 2006;Capuzzi et al, 2017;Köhler et al, 2017) and thus may also influence the liver function and CYP regulation, independently of their direct action on the monoaminergic and other receptors present in the liver (Daniel, 2005;Ruddell et al, 2008;Zidek et al, 2009;Wójcikowski and Daniel, 2011;Konstandi, 2013;Kot and Daujat-Chavanieu, 2016).…”

Морфология Печени Крыс В Условиях Острого Эмоционально-Болевого Стресса На Фоне Введения Дельта-Сон Индуцирующего Пептида

“…В частности печень, которой принадлежит уникальная роль в регуляции постоянства внутренней среды организма, обладает высокой чувствительностью к действию стрессорных раздражителей на организм [9,20]. Так, в условиях стресса изменяется метаболизм печеночных ферментов, принадлежащих к семье цитохрома Р450 (CYP) [15], развиваются стеатоз и неалкогольная жировая болезнь печени, увеличивается содержание триглицеридов, общего холестерина, уровней ИЛ-6 и ФНО в печени [16], может запускаться апоптоз гепатоцитов за счет увеличения экспрессии Fas-рецепторов и усиления миграции натуральных киллеров в печень [12]. При этом нарушение функционального состояния печени в дальнейшем способно оказывать значительное негативное воздействие на весь организм [18].…”