Invited Speaker Abstracts

Abstract

The immense potential of translating pharmacogenetics into clinical practice in pain medicine coexists with many questions and challenges, due to the complexity of pain multifaceted phenotype nature. What we have witnessed in the past decade, however, is a breathtaking acceleration in understanding human genetic diversity as the result of a technological revolution. The sequencing of genome and other technological advances have revealed the extent of diversity and the relative contribution to predict drug outcomes and adverse effects, of genetic and nongenetic factors, including age, concomitant therapy or drug interactions. Overall, there are now several examples in which interindividual differences in opioid pharmacologic effect and safety, are due to sequence variants in genes involved with pharmacokinetics and dynamics response that encoding drug targets (mu-opioid receptor, MOR-1), transporters (substrates of P-glycoprotein, ABCB1) or cytochrome P450 enzymes (ultrarapid and poor metabolism, CYP2D6). Genomic variants of CYP2C9 and CYP2C8 genes influence NSAIDs' blood concentrations and side effect profile. Overall, the level of evidence linking genetic variability to codeine, tramadol, hydrocodone, oxycodone and tricyclic antidepressants response and metabolic profiles is strong; however, this information is probably of limited use to most physicians and patients. On the other hand, predicting analgesic response to morphine based on pharmacogenetic testing continue being more complex; probably phenotypes are also affected by rare SNPs, structural variants or epigenetic mechanisms modifying genes expression including covalent DNA modifications (methylation), DNA-packaging histones (e.g., deacetylation or phosphorylation) or regulatory non-coding RNA molecules (microRNAs). Opportunities (knowledge networks, electronic health record (HER) database and biobanks, drug developments, therapeutic decision support tools) and challenges (understanding probabilities, managing expectations, involvements of stakeholders, cost) are greats. Thus, the transition to a new era of genome informed medical care will need a team approach incorporating medical and genetics professionals, ethicists, and health-care delivery organisations because requires an oversight system that ensures the accuracy and discriminatory use of genetic information. References: 1. Ashley, E, Butte A, Wheeler M et al. Clinical assessment incorporating a personal genome.