Consequences of psychophysiological stress on cytochrome P450-catalyzed drug metabolism

Konstandi, Maria, Johnson, Elizabeth O. and Lang, Matti A. (2014) Consequences of psychophysiological stress on cytochrome P450-catalyzed drug metabolism. Neuroscience and Biobehavioral Reviews, 45 149-167. doi:10.1016/j.neubiorev.2014.05.011


Author Konstandi, Maria
Johnson, Elizabeth O.
Lang, Matti A.
Title Consequences of psychophysiological stress on cytochrome P450-catalyzed drug metabolism
Journal name Neuroscience and Biobehavioral Reviews   Check publisher's open access policy
ISSN 0149-7634
1873-7528
Publication date 2014-01-01
Year available 2014
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.neubiorev.2014.05.011
Open Access Status Not Open Access
Volume 45
Start page 149
End page 167
Total pages 19
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon
Language eng
Subject 2802 Behavioral Neuroscience
2805 Cognitive Neuroscience
3206 Neuropsychology and Physiological Psychology
Abstract Most drugs are metabolized in the liver by cytochromes P450 (CYPs). Stress can modify CYP-catalyzed drug metabolism and subsequently, the pharmacokinetic profile of a drug. Current evidence demonstrates a gene-, stress- and species-specific interference in stress-mediated regulation of genes encoding the major drug-metabolizing CYP isozymes. Stress-induced up-regulation of CYPs that metabolize the majority of prescribed drugs can result in their increased metabolism and consequently, in failure of pharmacotherapy. In contrast, stress-induced down-regulation of CYP isozymes, including CYP2E1 and CYP2B1/2, potentially reduces metabolism of several toxicants and specific drugs-substrates resulting in increased levels and altered toxicity. The primary stress effectors, the adrenergic receptor-linked pathways and glucocorticoids, play primary and distinct roles in stress-mediated regulation of CYPs. Evidence demonstrates that stress regulates major drug metabolizing CYP isozymes, suggesting that stress should be considered to ensure pharmacotherapy efficacy and minimize drug toxicity. A detailed understanding of the molecular events underlying the stress-dependent regulation of drug metabolizing CYPs is crucial both for the design of new drugs and for physiology-based pharmacokinetic and pharmacodynamic modeling.
Keyword Adrenergic receptor
Cytochrome P450s
Drug metabolism
Glucocorticoids
Stress
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2015 Collection
National Research Centre for Environmental Toxicology Publications
 
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