Pharmacogenetics of Opiates in Clinical Practice: the Visible Tip of the Iceberg

Abstract

Opioids are the cornerstone of analgesic therapy and are used as a substitution therapy for opiate addiction. Interindividual variability in response to opioids is a significant challenge in the management of pain and substitution. Therefore, treatment with opioids requires a careful individualization of dosage to achieve an appropriate balance of efficacy and adverse effects and, consequently, avoid toxicity, particularly respiratory depression, sedation and for some, cardiac ventricular fibrillations. Many studies have investigated the association between genetic factors and the variability of response to opioids. Variants in genes encoding proteins implied in opioid pharmacokinetics (absorption, distribution, metabolism, excretion and toxicity), together with those implied in opioids direct and indirect pharmacodynamics (genes of opioid receptors and monoaminergic systems), are the most studied. Many association studies have not been replicated. The purpose of this article is to summarize pharmacogenetic data associated with some opioids frequently encountered in managed care settings.

KEYWORDS::

• association study
• methadone
• morphine
• opiates
• OPRM1
• pharmacogenetic
• polymorphisms

Acknowledgements

The authors would like to thank INSERM, Université Paris Descartes and Université Paris Diderot (all France) and the research committee of the Université Saint Joseph (Lebanon) for funding our research on opiates.

Financial & competing interests disclosure

The authors have received funding from INSERM, Université Paris Descartes and Université Paris Diderot (all France) and the research committee of the Université Saint Joseph (Lebanon) for their research on opiates. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors have received funding from INSERM, Université Paris Descartes and Université Paris Diderot (all France) and the research committee of the Université Saint Joseph (Lebanon) for their research on opiates. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.