Effect of genetic factors on opioid action

Opioid administration is a mainstay of anesthetic practice both for treating acute perioperative pain and for chronic pain syndromes. Growing pharmacogenetic data make it evident that many opiate-related phenomena are influenced by genetics. Genetic variation may significantly affect opiate absorption, distribution, metabolism, excretion and toxicity. We provide a current review of opiate pharmacogenetics.

Gene association studies should ideally be conducted in highly phenotyped populations of homogenous ethnic admixture with identified associations adjusted for patient demographics, risk factors and medications. Patients' phenotype responses to opiates are the result of a complex interplay between genetic and environmental variables. Although most pharmacogenetic studies to date have assessed the association between individual single nucleotide polymorphisms that exist within selected single gene regions (e.g. opioid receptor mu-1, catechol-O-methyltransferase, cytochrome P450 2D6) and opiate effects, more recent studies have begun to assess the potential influences of gene-gene interactions.

Knowledge of genetic factors that affect opioid efficacy, metabolism, and side effects have the potential for personalizing both acute and chronic pain management, and for designing more effective opiate pain medications with lower side effect profiles.