The role of cytochrome P450 pharmacogenomics in chronic non-cancer pain patients

ABSTRACT

Introduction: Pharmacogenomics is the field that studies an individualized treatment approach for patients’ medication regimen that can impact drug safety, productivity, and personalized health care. Pharmacogenomics characterizes the genetic differences in metabolic pathways which can affect a patient’s individual responses to drug treatments.

Areas covered: The various responses to pharmacological agents are mainly determined by the different types of genetic variants of the CYP450. CYP2D6 polymorphism is well known for its variation in the metabolism of drugs from many therapeutic arenas, including some analgesic drugs such as codeine, hydromorphone, oxycodone and tramadol. Allele combinations determine the phenotypic expression, characterized as either: extensive metabolizer, intermediate metabolizer, ultra-rapid metabolizer and poor metabolizer.

Expert opinion: The Human Genome Project (HGP) revolutionized the future of medicine and the way health care providers approach individualized patient treatment, and chronic pain management is one of those areas. The key findings in the literature appear to be related to the CYP2D6 expression and its high polymorphism influencing the metabolism of opioid medications, and the impact of that on the patient’s therapeutic outcome thus exemplifying the importance of genetic testing for CYP2D6 in the process of physician therapeutic decision making.

KEYWORDS:

• Chronic pain
• cytochrome P450
• CYP2D6
• opioids
• pharmacogenomics

Article highlights

• Pharmacogenomics is the field that studies the individualized treatment for patients

• Cytochrome P450 2D6 is a major enzyme subset involved in metabolism of most of the opioid medications

• CYP2D6 has a high genetic polymorphism which underlies bimodal distribution of individuals into ultra-rapid (UM) and poor metabolizer (PM) phenotype.

• Codeine, hydrocodone, oxycodone, tramadol are opioid medications metabolized through CYP2D6

• Poor metabolizers-minimal or no therapeutic effect; ultra-rapid metabolizers-increased adverse effects.

• Genetic testing for CYP2D6 is recommended for breastfeeding mothers who are on opioid medication; who have poor responses to opioid medication on a high dose or who are on two opioids; increased adverse effects noted with a small dose of opioid.

• Oxycodone relies on CYP2D6 and CYP3A4 for its metabolism and in the presence of CYP2D6 deficiency the metabolism is shunted to CYP3A4.

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Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.