Pharmacogenetics of Lethal Opioid Overdose: Review of Current Evidence and Preliminary Results from a Pilot Study-Reference-Cited by-同舟云学术

Pharmacogenetics of Lethal Opioid Overdose: Review of Current Evidence and Preliminary Results from a Pilot Study

Published:2023-05-30 Issue:6 Volume:13 Page:918
ISSN:2075-4426
Container-title:Journal of Personalized Medicine
language:en
Short-container-title:JPM

Author:

Magarbeh Leen¹²^ORCID,Gorbovskaya Ilona²³,Wells Richard⁴,Jhirad Reuven⁴,Le Foll Bernard¹²⁵⁶⁷⁸⁹¹⁰¹¹^ORCID,Müller Daniel J.¹²⁵⁶

Affiliation:

1. Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada

2. Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada

3. Factor-Inwentash Faculty of Social Work, University of Toronto, Toronto, ON M5S 1V4, Canada

4. Office of the Chief Coroner and Ontario Forensic Pathology Service, Toronto, ON M3M 0B1, Canada

5. Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada

6. Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada

7. Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1V7, Canada

8. Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada

9. Acute Care Program, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada

10. Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada

11. Waypoint Research Institute, Waypoint Centre for Mental Health Care, Penetanguishene, ON L9M 1G3, Canada

Abstract

There has been a worldwide substantial increase in accidental opioid-overdose deaths. The aim of this review, along with preliminary results from our pilot study, is to highlight the use of pharmacogenetics as a tool to predict causes of accidental opioid-overdose death. For this review, a systematic literature search of PubMed® between the time period of January 2000 to March 2023 was carried out. We included study cohorts, case–controls, or case reports that investigated the frequency of genetic variants in opioid-related post-mortem samples and the association between these variants and opioid plasma concentrations. A total of 18 studies were included in our systematic review. The systematic review provides evidence of the use of CYP2D6, and to a lower extent, CYP2B6 and CYP3A4/5 genotyping in identifying unexpectedly high or low opioid and metabolite blood concentrations from post-mortem samples. Our own pilot study provides support for an enrichment of the CYP2B6*4-allele in our methadone-overdose sample (n = 41) compared to the anticipated frequency in the general population. The results from our systematic review and the pilot study highlight the potential of pharmacogenetics in determining vulnerability to overdose of opioids.

Funder

CAMH-AHSC AFP Innovation fund

Publisher

MDPI AG

Subject

Medicine (miscellaneous)

Link

https://www.mdpi.com/2075-4426/13/6/918/pdf

Reference49 articles.

1. Ahmad, F., Rossen, L.M., and Sutton, P. (2023, March 17). Provisional Drug Overdose Death Counts. National Center for Health Statistics, Available online: https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.html.

2. Federal, Provincial and Territorial Special Advisory Committee on the Epidemic of Opioid Overdoses (2023, March 17). Opioid-and Stimulant-Related Harms in Canada. Available online: https://health-infobase.canada.ca/substance-related-harms/opioids-stimulants/.

3. Canadian Centre on Substance Abuse and Addictions (2020). Perscription Opioids (Canadian Drug Summary).

4. Changing patterns in opioid addiction: Characterizing users of oxycodone and other opioids;Sproule;Can. Fam. Physician,2009

5. The neurobiology of opioid dependence: Implications for treatment;Kosten;Sci. Pr. Perspect.,2002