Emma Louis, B.S. & Komal Sharma, MS, MBA
Pharmacogenomics: Transforming Pain Management Through Precision Medicine. Have you ever wondered why different painkillers work better for some people than others? While some find relief with over-the-counter medications, others require stronger prescription interventions, with highly variable results. This variability is partially driven by differences in genetic makeup, an area explored through pharmacogenomics (PGx). By transforming our understanding of how genetics affects both drug metabolism and drug action, PGx enables the potential for personalized pain management plans.
Genetic variants influence how a drug is processed by the body. PGx provides insights into how genetic variation influences pharmacokinetics, or how a drug is processed by the body. For example, polymorphisms in the CYP2D6 gene significantly affect response to opioids like codeine and tramadol, which require activation by the CYP2D6 enzyme. Poor metabolizers may experience inadequate relief, while ultra-rapid metabolizers face a higher risk of toxicity and respiratory depression (Crews, 2021). NSAIDs are also affected by genetics; CYP2C9 poor metabolizers can have 40–60% higher exposure to drugs like ibuprofen and celecoxib, increasing the risk of adverse drug events due to slower clearance (Theken, 2020).
Certain polymorphisms predispose patients to sub- or supra-therapeutic drug response. PGx also informs how genetic differences impact pharmacodynamics, or how well a drug produces its intended therapeutic effects. Variants in the OPRM1 gene, which encodes the μ-opioid receptor, affect opioid binding and responses (Crews, 2021). For NSAIDs, certain PTGS2 polymorphisms (encoding COX-2) have been shown to reduced anti-inflammatory efficacy, whereas IL1B variants (pro-inflammatory cytokine) may increase the risk of gastrointestinal side effects (Theken, 2020). The Clinical Pharmacogenetics Implementation Consortium recognizes these pharmacodynamic variations in their guidelines, which provide clinicians with clinically actionable insights for optimal therapeutic outcomes (Owusu, et al. 2017).
PGx can prevent opioid-related harm. A report from 2020 indicates that 10.7% of U.S. adults aged 20 and over had used at least one prescription opioid in the past month between 2015 and 2018. This usage was found to rise with increasing age (Hales, 2020). Despite this widespread use, PGx testing for opioid metabolism remains rare in clinical practice. Wider adoption of PGx could help clinicians tailor pain management regimens more precisely, reducing the likelihood of both ineffective treatment and opioid-related harm.
As genotyping becomes more accessible and integrated into clinical workflows, PGx-guided pain management is positioned to become a standard practice of care.
Learn more about UGenome’s Personalized Medication Service, ProPEx, or contact UGenome. You can also find case studies for UGenome’s bioinformatics services Metabolite Identification, Bone Metastasis Risk Analysis in Breast Cancer, Survival Analysis with gene signatures in cancer
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