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Pain Research and Management
Volume 18 (2013), Issue 3, Pages 133-136
Original Article

Life-Threatening Adverse Events Following Therapeutic Opioid Administration in Adults: Is Pharmacogenetic Analysis Useful?

Parvaz Madadi,1 Johanna Sistonen,2,3,4 Gregory Silverman,5,6 Rebecca Gladdy,7 Colin J Ross,2,3 Bruce C Carleton,3,8,9 Jose C Carvalho,5 Michael R Hayden,2,3 and Gideon Koren1

1Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada
2Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
3Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
4Institute of Clinical Chemistry, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
5Department of Anesthesia and Pain Management, Mount Sinai Hospital, Canada
6Global Health and Social Responsibility Program, Department of Anesthesia, Faculty of Medicine, University of Toronto, Canada
7Department of Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada
8Pharmaceutical Outcomes Programme, British Columbia Children’s Hospital, Canada
9Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada

Copyright © 2013 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


BACKGROUND: Systemic approaches are needed to understand how variations in the genes associated with opioid pharmacokinetics and response can be used to predict patient outcome. The application of pharmacogenetic analysis to two cases of life-threatening opioid-induced respiratory depression is presented. The usefulness of genotyping in the context of these cases is discussed.

METHODS: A panel of 20 functional candidate polymorphisms in genes involved in the opioid biotransformation pathway (CYP2D6, UGT2B7, ABCB1, OPRM1, COMT) were genotyped in these two patients using commercially available genotyping assays.

RESULTS: In case 1, the patient experienced adverse outcomes when administered codeine and morphine, but not hydromorphone. Genetic test results suggested that this differential response may be due to an inherent propensity to generate active metabolites from both codeine and morphine. These active metabolites are not generated with hydromorphone. In case 2, the patient experienced severe respiratory depression during postoperative recovery following standard doses of morphine. The patient was found to carry genetic variations that result in decreased morphine efflux transporter activity at the blood-brain barrier and increased sensitivity to opioids.

CONCLUSIONS: Knowledge of the relative contribution of pharmacogenetic biomarkers and their influence on opioid response are continually evolving. Pharmacogenetic analysis, together with clinical history, has the potential to provide mechanistic insight into severe respiratory depressive events in patients who receive opioids at therapeutic doses.