The effect and clinical consequences of hypoxia on cytochrome P450, membrane carrier proteins activity and expression
Bibliographic record
Abstract
INTRODUCTION: Chronic pulmonary disease and heart failure reduce drug clearance and consequently enhance adverse drug reactions. The mechanisms of action underlying the regulation of cytochrome P450 (CYP) isoforms and membrane carrier proteins by hypoxia, and the clinical consequences of the regulation of CYP by hypoxia, alone or combined with other conditions have been elucidated in the last decades. Overall, a reduced drug clearance appears to be associated with hypoxemia. AREAS COVERED: In this review, the mechanisms of action underlying hypoxia-induced regulation of CYP enzymes are discussed. The authors also revise the effects of hypoxia on serum mediators, signal transduction pathways, orphan nuclear receptors, transcription factors and post-transcriptional mechanisms regulating CYP and membrane carrier proteins expression. Additionally, the paper also discusses the clinical repercussions of hypoxia-induced changes in CYP and membrane carrier proteins activity. EXPERT OPINION: Acute systemic hypoxia down-regulates selected CYP isoforms and up-regulates CYP3A4 and P-glycoprotein, changing the metabolic clearance of drugs and endogenous compounds biotransformed by these isoforms as well as the kinetics. In patients with acute hypoxia, the dosage of drugs, biotransformed by CYP isoforms, may need to be adjusted. Tissue hypoxia enhances the expression of efflux membrane carrier proteins, increasing the probability of drug resistance.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".