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INTERNATIONAL CONGRESS OF

PharmacoGenetics

• Pharmacogenetics of Opioid Analgesics: Toward Safer Pain Management

• Negar khaki ,^1,* Kiana hajavi,²
  1. Medical university and Azad university
  2. Azad university
  
  
  
• Introduction: Opioid analgesics remain a mainstay in the management of moderate to severe pain. However, significant interindividual differences in drug response and risk of adverse effects, including respiratory depression and addiction, pose ongoing challenges. Pharmacogenetics—the study of genetic variation affecting drug metabolism and response—offers promising avenues for personalizing opioid therapy. Key genetic variants in enzymes and receptors such as CYP2D6, OPRM1, and COMT are implicated in opioid efficacy and safety. Incorporating pharmacogenetic data into clinical decision-making may help optimize pain relief and minimize harm.
• Methods: This review analyzes major pharmacogenetic variants affecting opioid analgesics based on findings from published pharmacogenomic studies, clinical implementation guidelines (such as CPIC), and peer-reviewed literature. Key genes discussed include CYP2D6 (opioid metabolism), OPRM1 (μ-opioid receptor function), and COMT (pain modulation). Literature was selected to reflect both molecular mechanisms and clinical applicability in pain management.
• Results: CYP2D6 polymorphisms significantly influence the metabolism of prodrugs like codeine and tramadol. Ultra-rapid metabolizers may face toxicity due to excessive conversion to active metabolites, while poor metabolizers experience insufficient pain relief. OPRM1 A118G polymorphism affects receptor binding and analgesic efficacy, with G allele carriers often requiring higher opioid doses. . COMT Val158Met variant modulates catecholamine breakdown and endogenous pain control, influencing patient-specific opioid needs. Implementation pharmacogenetic testing has been shown to improve prescribing practices and reduce trial-and-error approaches in clinical settings.
• Conclusion: Pharmacogenetics enables a more personalized approach to opioid prescribing by accounting for genetic variability in metabolism, receptor sensitivity, and pain perception. Genotyping key genes can guide opioid selection and dosing, reducing risks and improving outcomes. As technology advances and clinical awareness grows, integrating pharmacogenetic testing into routine practice may become a cornerstone of safer and more effective pain management.
• Keywords: Pharmacogenetics, Opioids, CYP2D6, OPRM1, COMT, Personalized Medicine, Pain Management