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Tramadol pharmacogenomics

Cathy R Fulton, Yong Zang, Zeruesenay Desta, Marc B Rosenman, Ann M Holmes, Brian S Decker, Yifei Zhang, John T Callaghan, Victoria M Pratt, Kenneth D Levy, Brandon T Gufford, Paul R Dexter, Todd C Skaar, Michael T Eadon
BACKGROUND: Tramadol and codeine are metabolized by CYP2D6 and are subject to drug-gene and drug-drug interactions. METHODS: This interim analysis examined prescribing behavior and efficacy in 102 individuals prescribed tramadol or codeine while receiving pharmaco-genotyping as part of the INGENIOUS trial (NCT02297126). RESULT: Within 60 days of receiving tramadol or codeine, clinicians more frequently prescribed an alternative opioid in ultrarapid and poor metabolizers (odds ratio: 19...
February 20, 2019: Pharmacogenomics
Keith Gray, Sanjib D Adhikary, Piotr Janicki
The field of pharmacogenomics seeks to understand how an individual's unique gene sequence can affect their response to certain drugs. It is particularly relevant in anesthesia when the interindividual response to pain medication is essential. Codeine and tramadol are prodrugs metabolized by CYP2D6, polymorphisms of which can cause dangerous or even fatal levels of their metabolites, or decrease the level of metabolites to decrease their analgesic effect. Many other opioids are metabolized by CYP2D6 or CYP3A5, of which loss-of-function variants can cause dangerous levels of these drugs...
April 2018: Journal of Anaesthesiology, Clinical Pharmacology
Vinko Palada, Mari A Kaunisto, Eija Kalso
PURPOSE OF REVIEW: The review describes recent advances in genetics and genomics of postoperative pain, the association between genetic variants and the efficacy of analgesics, and the role of pharmacogenomics in the selection of appropriate analgesic treatments for postoperative pain. RECENT FINDINGS: Recent genetic studies have reported associations of genetic variants in catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), voltage-gated channel alpha subunit 11 (SCN11A) and μ-opioid receptor (OPRM1) genes with postoperative pain...
October 2018: Current Opinion in Anaesthesiology
Renae A Lloyd, Elizabeth Hotham, Catherine Hall, Marie Williams, Vijayaprakash Suppiah
Objective: Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl. Method: A literature search of databases Medline and Embase was carried out, and studies up to April 2016 were included in this review...
December 1, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Karen Miotto, Arthur K Cho, Mohamed A Khalil, Kirsten Blanco, Jun D Sasaki, Richard Rawson
Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic potency of a given dose of tramadol is influenced by an individual's CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects...
January 2017: Anesthesia and Analgesia
Tatiana Tverdohleb, Bora Dinc, Ivana Knezevic, Kenneth D Candido, Nebojsa Nick Knezevic
INTRODUCTION: Pharmacogenomics is the field that studies an individualized treatment approach for patients' medication regimen that can impact drug safety, productivity, and personalized health care. Pharmacogenomics characterizes the genetic differences in metabolic pathways which can affect a patient's individual responses to drug treatments. AREAS COVERED: The various responses to pharmacological agents are mainly determined by the different types of genetic variants of the CYP450...
July 15, 2016: Expert Opinion on Drug Metabolism & Toxicology
Gillian C Bell, Kristine A Donovan, Howard L McLeod
BACKGROUND: Pain can be a significant burden for patients with cancer and may have negative effects on their quality of life. Opioids are potent analgesics and serve as a foundation for pain management. The variation in response to opioid analgesics is well characterized and is partly due to genetic variability. METHODS: We reviewed the results of clinical studies to evaluate the relationships between genetic variants and select genes involved in the pharmacokinetics and pharmacodynamics of opioids, with an emphasis on patients with cancer...
October 2015: Cancer Control: Journal of the Moffitt Cancer Center
Carolyn R Rohrer Vitek, Wayne T Nicholson, Cloann Schultz, Pedro J Caraballo
AIM: To assess impact and value of using clinical decision support (CDS) to drive providers toward online pharmacogenomics education. MATERIALS & METHODS: CDS was used to target prescribers of codeine/tramadol, send an educational email, display alert/inbox and provide links to an online resource. Providers were surveyed to assess impact. RESULTS: Of the methods used to target providers, educational email was more effective (7.2%). Survey response rate was 29...
2015: Pharmacogenomics
Gillian C Bell, Kristine R Crews, Mark R Wilkinson, Cyrine E Haidar, J Kevin Hicks, Donald K Baker, Nancy M Kornegay, Wenjian Yang, Shane J Cross, Scott C Howard, Robert R Freimuth, William E Evans, Ulrich Broeckel, Mary V Relling, James M Hoffman
BACKGROUND: Active clinical decision support (CDS) delivered through an electronic health record (EHR) facilitates gene-based drug prescribing and other applications of genomics to patient care. OBJECTIVE: We describe the development, implementation, and evaluation of active CDS for multiple pharmacogenetic test results reported preemptively. MATERIALS AND METHODS: Clinical pharmacogenetic test results accompanied by clinical interpretations are placed into the patient's EHR, typically before a relevant drug is prescribed...
February 2014: Journal of the American Medical Informatics Association: JAMIA
Mindy Cohen, Senthilkumar Sadhasivam, Alexander A Vinks
PURPOSE OF REVIEW: This review will discuss the most recent developments in pharmacogenetics of commonly used perioperative medications, new collaboration networks in the field of personalized medicine, and future clinical implications of pharmacogenetics. RECENT FINDINGS: Evidence now suggests that pharmacogenetics has a role in the effects of analgesic, sedative, beta-blocker, local anesthetic, antiemetic, and obstetric medications. Variants in the μ opioid receptor gene change the analgesic effects of morphine...
August 2012: Current Opinion in Anaesthesiology
Markus R Meyer, Hans H Maurer
Pharmacologic and toxic effects of xenobiotics, such as drugs of abuse, depend on the genotype and phenotype of an individual, and conversely on the isoenzymes involved in their metabolism and transport. The current knowledge of such isoenzymes of frequently abused therapeutics such as opioids (oxycodone, hydrocodone, methadone, fentanyl, buprenorphine, tramadol, heroin, morphine and codeine), anesthetics (γ-hydroxybutyric acid, propofol, ketamine and phencyclidine) and cognitive enhancers (methylphenidate and modafinil), and some important plant-derived hallucinogens (lysergide, salvinorin A, psilocybin and psilocin), as well as of nicotine in humans are summarized in this article...
February 2011: Pharmacogenomics
Inger Johansson, Magnus Ingelman-Sundberg
Individual susceptibility to environmental, chemical, and drug toxicity is to some extent determined by polymorphism in drug-metabolizing enzymes, in particular the cytochromes P450 (CYPs). This polymorphism is in particular translated into risk differences concerning drugs metabolized by the highly polymorphic enzymes CYP2C9, CYP2C19, and CYP2D6, whereas CYP enzymes active in procarcinogen activation are relatively well conserved without important functional polymorphisms. Examples of drug toxicities that can be predicted by P450 polymorphism include those exerted by codeine, tramadol, warfarin, acenocoumarol, and clopidogrel...
March 2011: Toxicological Sciences: An Official Journal of the Society of Toxicology
A Eichhorn, J Barth
This casuistic reports on a 59-year-old pain patient taking normal dosage Tramadol as analgetic drug, who suffered from chronic dizziness leading to immobilisation for more than 9 months. On admission to inpatient rehabilitation Tramadol was removed in exchange for morphine sulphate with the unexpected result of a prompt and lasting stop of dizziness. A molecular-genetic investigation showed a duplication in the CYP2D6 gene. This genetic situation caused a quick metabolizing-status for substances dependent on CYP2D6 like Tramadol, which is a prodrug...
December 2010: Die Rehabilitation
Paul J Jannetto, Nancy C Bratanow
AIMS: The use of medication in pain management currently involves empirical adjustment based on observed clinical outcome and the presence of adverse drug reactions. In this study, pharmacogenomics and therapeutic drug monitoring were used to evaluate the clinical effectiveness of genotyping chronic pain patients on analgesic therapy. It was hypothesized that patients who have inherited polymorphisms in CYP2D6 that make them poor or intermediate metabolizers of opioid medications would have higher steady-state concentrations of those opioids and may be more likely to experience adverse drug reactions...
July 2009: Pharmacogenomics
Burkhard Madea
One of the problems in the diagnosis of the cause of death in cases of sudden death, especially in infancy, is the rapidity of death and that the morphological correlates of the underlying diseases and cause of death may be scarce or even completely missing. This is especially true for functional disorders causing death (e.g. arrhythmias) or cases where death occurs in an initial stage of disease with still lacking morphological findings (e.g. myocarditis). Molecular pathological techniques, which were initially of great importance for identification, today contribute also to the determination of the cause and manner of death, especially in cases, where classical methods do not reveal a clear anatomical cause of death...
April 2009: Legal Medicine
B J Anderson, G M Palmer
Growth and development are two linked processes that distinguish children from adults. The use of size as the primary covariate during pharmacokinetic (PK) analyses allows exploration of the effects of age. Allometric scaling models have assisted understanding of the developmental clearance changes in common analgesic drugs such as paracetamol, morphine, tramadol and local anaesthetics agents. Single nucleotide polymorphisms (pharmacogenomics [PG]) and their impact on hepatic drug metabolism for opioids, tramadol, non-steroidal anti-inflammatory drugs (NSAIDs) and drug receptor responses are increasingly reported...
August 2006: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Brian J Anderson, Greta M Palmer
PURPOSE OF REVIEW: This review explores progress in developmental pharmacokinetics, pharmacogenomics and formulations of analgesic agents, and discusses potential implications for pain therapy. RECENT FINDINGS: Characterization of the developmental pharmacokinetics of morphine, tramadol, paracetamol and nonsteroidal anti-inflammatory drugs has improved dosing in children. Oral sugar solutions have replaced the brandy/sugar pacifier and are effective for single painful events in neonates...
June 2006: Current Opinion in Anaesthesiology
Thomas C Kupiec, Vishnu Raj, Nicole Vu
Pharmacogenomics is the study of the linkage between an individual's genotype and the disposition of drugs in the body. The first association between adverse drug reactions and inherited variations was recognized in the 1950s, and since then, pharmacogenomics has come a long way. The importance of pharmacogenomics is accentuated by the incidence of adverse drug reactions, which may account for hospital expenditures of up to 5.6 billion dollars annually. Interindividual variations in drug metabolism are often the result of genetic variants or genetic polymorphisms, and polymorphisms have been known to alter the relationship between dose and plasma drug concentration...
March 2006: Journal of Analytical Toxicology
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