title: Pharmacogenetics of opiates in clinical practice: the visible tip of the iceberg.
abstract: Opioids are the cornerstone of analgesic therapy and are used as a substitution therapy for opiate addiction. Interindividual variability in response to opioids is a significant challenge in the management of pain and substitution. Therefore, treatment with opioids requires a careful individualization of dosage to achieve an appropriate balance of efficacy and adverse effects and, consequently, avoid toxicity, particularly respiratory depression, sedation and for some, cardiac ventricular fibrillations. Many studies have investigated the association between genetic factors and the variability of response to opioids. Variants in genes encoding proteins implied in opioid pharmacokinetics (absorption, distribution, metabolism, excretion and toxicity), together with those implied in opioids direct and indirect pharmacodynamics (genes of opioid receptors and monoaminergic systems), are the most studied. Many association studies have not been replicated. The purpose of this article is to summarize pharmacogenetic data associated with some opioids frequently encountered in managed care settings.
authors.affiliation: Laboratoire de Pharmacologie Clinique et Pharmacocinétique, Faculté de Pharmacie, Université Saint Joseph, Beyrouth, Liban, Lebanon.
authors.forename: Aline
authors.initials: A
authors.lastname: Hajj
authors.forename: Lydia
authors.initials: L
authors.lastname: Khabbaz
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.forename: Katell
authors.initials: K
authors.lastname: Peoc'h
mesh_terms: D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D056726:Genetic Association Studies; D006801:Humans; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects; D018847:Opioid Peptides / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D059408:Pain Management; D010597:Pharmacogenetics; D011957:Receptors, Opioid / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine; D008691:Methadone