The consequences of a slow or fast metabolism
Michel Cameron, Assistant Director of Pharmacogenetics at Biron, explains that “when a pill is swallowed, it dissolves in the body to produce its effect. It is then metabolized, i.e. transformed by our enzymes (mainly located in the liver) to assist in activating and eliminating it, as the case may be.” However, in some people, these enzymes can be defective.
For the enzyme that metabolizes codeine, CYP2D6, approximately 3% of individuals in Canada are ultra-fast metabolizers and approximately 6% are slow metabolizers.
|Drug type||Metabolism type||Effect|
|Codeine||Slow||The level of codeine in the blood is high while the level of morphine remains low = little or no desired effect (the drug may be inactive)|
|Codeine||Fast||Codeine levels drop rapidly while morphine levels rise sharply = morphine-induced toxicity (risk of apnea, coma, or even cardiorespiratory arrest)|
These figures also vary depending on ethnic origin. For example, fast metabolizers account for about 8% of the North African population. Taking a drug can therefore have radically different consequences depending on the case.
Benefits of pharmacogenetics in choosing a treatment
Not every person reacts the same way to a drug. The same dose may work well for one person and not so well for another, and may even cause serious side effects. This highly specific reaction to treatments is closely linked with our DNA.
Pharmacogenetics, a word that combines pharmacology (the study of drugs) and genetics, studies the influence of our genes on our response to medications. The aim is to improve the efficacy of treatments and the safety of patients.
The test involves taking a simple saliva sample (which requires no special preparation) and observing the enzymes responsible for metabolism.
A drug is a molecule that the body perceives as a foreign substance, a threat to be eliminated. About thirty types of enzymes are responsible for this mission of metabolization, and each one has its preferences based on the molecules to process. As a result, the mobilized enzymes vary depending on the drug. Our metabolism may then react slowly to certain classes of drugs and quickly to others.
Various avenues to explore through pharmacogenetics
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- P. Gravel. “À chaque métabolisme sa médication,” November 2008, https://www.ledevoir.com/societe/sante/214915/a-chaque-metabolisme-sa-medication.
- Milosavljevic et al. “Association of CYP2C19 and CYP2D6 Poor and Intermediate Metabolizer Status With Antidepressant and Antipsychotic Exposure: A Systematic Review and Meta-analysis,” March 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702196/.
- Kelly et al. “More Codeine Fatalities after Tonsillectomy in North American Children,” April 2012, https://pubmed.ncbi.nlm.nih.gov/22492761/.
- M. Lhermitte, D. Allorge, F. Broly. “Le polymorphisme génétique des enzymes du métabolisme des médicaments. Une opportunité pour un traitement individualisé,” January 2006, https://www.academie-medecine.fr/le-polymorphisme-genetique-des-enzymes-du-metabolisme-des-medicaments-une-opportunite-pour-un-traitement-individualise/.
- Health Canada. “Summary Safety Review - Codeine-containing products - Further Assessing the Risk of Serious Breathing Problems in Children and Adolescents,” July 2016, https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/safety-reviews/summary-safety-review-codeine-prescription-products-cough-further-assessing-risk-serious.html.