Format

Send to

Choose Destination
See comment in PubMed Commons below
Neurosci Biobehav Rev. 2014 Sep;45:149-67. doi: 10.1016/j.neubiorev.2014.05.011. Epub 2014 May 27.

Consequences of psychophysiological stress on cytochrome P450-catalyzed drug metabolism.

Author information

1
Department of Pharmacology, School of Medicine, University of Ioannina, Ioannina GR-451 10, Greece. Electronic address: mkonstan@cc.uoi.gr.
2
Department of Anatomy, University of Athens, School of Medicine, Mikras Asias 75, 11527 Athens, Greece.
3
National Research Centre for Environmental Toxicology, University of Queensland, Coopers Plains, Australia.

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.

KEYWORDS:

Adrenergic receptor; Cytochrome P450s; Drug metabolism; Glucocorticoids; Stress

PMID:
24877684
DOI:
10.1016/j.neubiorev.2014.05.011
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center