Genetic and metabolic factors cause painkillers to have different effects on people
Extensive scientific literature confirms that genetic and metabolic factors—such as variations in drug-metabolizing enzymes and receptors—significantly alter how individuals respond to painkillers and analgesics.
The retrieved papers consistently support the claim that genetic polymorphisms (e.g., CYP2D6, CYP2C9, UGT2B7) and metabolic profiles cause inter-individual differences in the efficacy, pharmacokinetics, pharmacodynamics, and side-effect profiles of painkillers like opioids, NSAIDs, and tramadol. There are no refuting studies in the provided set.
Martin da Silva I, Plaza-Díaz A, Ruiz-Ramos J, Juanes-Borrego A, Riera P. The Role of Pharmacogenetic Biomarkers in Pain.. 2025. https://doi.org/10.3390/biomedicines13081935
Substantial evidence indicates that genetic variants in genes such as CYP2C9 and CYP2D6 significantly influence patient responses to analgesics and pain management.
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Scuteri D, Kodounis M, Katsuki M, Bezgal B, Bednarczyk N, Alevetsovitis SK, Wołos J, Henriques M, Pinheiro TA, MaassenVanDenBrink A, Lampl C. Pharmacological mechanisms underlying neurovascular alterations related to resistant and refractory migraine: CGRP pathways and beyond.. 2026. https://doi.org/10.1186/s10194-026-02395-y
Genetic and epigenetic modifications contribute to inter-individual variability in pharmacokinetics and pharmacodynamics regarding analgesic drug responses.
Bhuchakra HP, Balasubramanian S, Nair AG, Marcos I, Falconett VC, Falcon D, Bari AA, Sadhasivam S. Personalized Perioperative Opioid Strategies in Children: Focus on Methadone, Pharmacogenomics and Prevention of Persistent Postoperative Opioid Use.. 2025. https://doi.org/10.3390/children12121660
Pharmacogenomic-guided opioid prescribing and variants in genes like CYP2D6 and OPRM1 help tailor dosing to individual metabolic profiles for improved efficacy.
Breaux AM, Von-Koeller-Jones BM, Dufour SI, Drinkard J, Moore P, Griffin P, Shekoohi S, Ahmadzadeh S. Comparison of Pecto-Intercostal Fascial Block Vs Transversus Thoracic Plane Block and Their Pharmacogenomics for Pain Management After Sternotomy in Cardiac Surgery: A Narrative Review.. 2026. https://doi.org/10.2147/jpr.s599378
Pharmacokinetic, pharmacodynamic, and genetic factors contribute to variability in analgesic response and pain management strategies.
Elshaikh RH, Babker AM, Hussein SE, Ahmed KAM, Sah AK, Alfeel AH. Pharmacogenomics and Opioid Efficacy in Sickle Cell Disease.. 2026. https://doi.org/10.3390/medicina62010172
Polymorphisms in metabolic enzymes like CYP2D6 and UGT2B7 modify the pharmacokinetics and pharmacodynamics of opioids, altering pain relief.
Lauschke VM, Ingelman-Sundberg M. The evolving landscape of pharmacogenomics: Current achievements and future directions.. 2026. https://doi.org/10.1016/j.pharmr.2026.100122
Pharmacogenomics investigates how inherited and acquired genetic variation shapes drug efficacy and toxicity across various therapeutic areas including pain management.
Gürbüz E, Elfiky AA, Ök N, Köseler A. The Effect of <i>CYP2D6</i> Gene Polymorphism on Tramadol Efficacy in Total Knee Arthroplasty.. 2026. https://doi.org/10.21873/invivo.14273
The CYP2D6 genotype directly influences tramadol efficacy and side-effect profiles, demonstrating that genetic factors alter painkiller effects.
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