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Pharmacogenomics opioid

Brett Morgan, Edwin N Aroke, Jennifer Dungan
The field of pharmacogenomics seeks to identify the impact of genetic variants on drug dosing, response, metabolism, and safety outcomes. The narrow therapeutic indices for anesthesia drugs, variability of patient responses to anesthesia, and the risks associated with surgery make anesthetics and the perioperative period prime targets for pharmacogenetic research. Anesthesia providers strive to optimize anesthesia delivery and patient outcomes and to specifically reduce anesthesia-related risks and negative outcomes...
January 2017: Annual Review of Nursing Research
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...
November 17, 2016: Anesthesia and Analgesia
Meghan MacKenzie, Richard Hall
PURPOSE: Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. SOURCE: We selected relevant literature to illustrate the important concepts contained within. PRINCIPAL FINDINGS: Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach...
October 17, 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
Flavia Franconi, Ilaria Campesi
Sex is one of several factors influencing pharmacological responses, but research on its effects on pharmacokinetics and pharmacodynamics, although emerging remarkably, remains poor and contains many methodological issues. In this review, the current state of knowledge about sex differences in pharmacokinetics and some hints to pharmacogenomics were evaluated. Moreover, considering that many pharmacological responses are monitored through biomarkers, the influence of sex on some biomarkers has been reported...
October 3, 2016: Current Medicinal Chemistry
Khuthala Mnika, Gift D Pule, Collet Dandara, Ambroise Wonkam
Sickle cell disease (SCD) is a blood disease caused by a single nucleotide substitution (T > A) in the beta globin gene on chromosome 11. The single point mutation (Glu6Val) promotes polymerization of hemoglobin S (HbS) and causes sickling of erythrocytes. Vaso-occlusive painful crises are associated with recurrent and long-term use of analgesics/opioids and hydroxyurea (HU) by people living with SCD. The present analysis offers a state-of-the-art expert review of the effectiveness of pharmacogenomics/genetics of pain management in SCD, with specific focus on HU and opioids...
October 2016: Omics: a Journal of Integrative Biology
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
D Kringel, A Ultsch, M Zimmermann, J-P Jansen, W Ilias, R Freynhagen, N Griessinger, A Kopf, C Stein, A Doehring, E Resch, J Lötsch
Next-generation sequencing (NGS) provides unrestricted access to the genome, but it produces 'big data' exceeding in amount and complexity the classical analytical approaches. We introduce a bioinformatics-based classifying biomarker that uses emergent properties in genetics to separate pain patients requiring extremely high opioid doses from controls. Following precisely calculated selection of the 34 most informative markers in the OPRM1, OPRK1, OPRD1 and SIGMAR1 genes, pattern of genotypes belonging to either patient group could be derived using a k-nearest neighbor (kNN) classifier that provided a diagnostic accuracy of 80...
May 3, 2016: Pharmacogenomics Journal
Flaminia Coluzzi, Robert Taylor, Joseph V Pergolizzi, Consalvo Mattia, Robert B Raffa
BACKGROUND AND OBJECTIVES: Achieving good clinical practice in the use of opioids as part of a comprehensive pain management regimen can face significant challenges. Despite guidelines from governmental and pain society/organization sources, there are still significant hurdles. A review of some basic tenets of opioid analgesia based on current published knowledge and experiences about this important healthcare imperative is warranted. CONTENT: Consistent with guidelines, the literature supports using the lowest total opioid dose that provides adequate pain control with the fewest adverse effects...
May 2016: Brazilian Journal of Anesthesiology
Greta M Palmer
Pain management in the paediatric acute care setting is underutilised and can be improved. An awareness of the analgesic options available and their limitations is an important starting point. This article describes the evolving understanding of relevant pharmacogenomics and safety data of the various analgesic agents with a focus on agents available in Australia and New Zealand. It highlights the concerns with the use of codeine in children and discusses alternative oral opioids. Key features of oral, parenteral, inhaled and intranasal analgesic agents are discussed, as well as evidence supported use of sweet tasting solutions and non-pharmacological interventions...
February 2016: Journal of Paediatrics and Child Health
Hsin-Chou Yang, Shih-Kai Chu, Chieh-Liang Huang, Hsiang-Wei Kuo, Sheng-Chang Wang, Sheng-Wen Liu, Ing-Kang Ho, Yu-Li Liu
Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers...
March 2016: PLoS Genetics
R D Holmes, A K Tiwari, J L Kennedy
Placebo effect research over the past 15 years has improved our understanding of how placebo treatments reduce patient symptoms. The expectation of symptom improvement is the primary factor underlying the placebo effect. Such expectations are shaped by past experiences, contextual cues and biological traits, which ultimately modulate one's degree of response to a placebo. The body of evidence that describes the physiology of the placebo effect has been derived from mechanistic studies primarily restricted to the setting of pain...
November 2016: Pharmacogenomics Journal
Flaminia Coluzzi, Robert Taylor, Joseph V Pergolizzi, Consalvo Mattia, Robert B Raffa
BACKGROUND AND OBJECTIVES: Achieving good clinical practice in the use of opioids as part of a comprehensive pain management regimen can face significant challenges. Despite guidelines from governmental and pain society/organization sources, there are still significant hurdles. A review of some basic tenets of opioid analgesia based on current published knowledge and experiences about this important healthcare imperative is warranted. CONTENT: Consistent with guidelines, the literature supports using the lowest total opioid dose that provides adequate pain control with the fewest adverse effects...
May 2016: Revista Brasileira de Anestesiologia
V Chidambaran, R Venkatasubramanian, X Zhang, L J Martin, J Niu, T Mizuno, T Fukuda, J Meller, A A Vinks, S Sadhasivam
Respiratory depression (RD) is a serious side effect of morphine and detrimental to effective analgesia. We reported that variants of the ATP binding cassette gene ABCC3 (facilitates hepatic morphine metabolite efflux) affect morphine metabolite clearance. In this study of 316 children undergoing tonsillectomy, we found significant association between ABCC3 variants and RD leading to prolonged postoperative care unit stay (prolonged RD). Allele A at rs4148412 and allele G at rs729923 caused a 2.36 (95% CI=1...
January 26, 2016: Pharmacogenomics Journal
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
Brian J Anderson, Jacqueline A Hannam
INTRODUCTION: Assessment of analgesic drugs includes comparative studies to other analgesics and local anesthesia blockade, number needed to treat estimates and opioid sparing descriptions. An additional methodology is to define the concentration-response relationship using pharmacokinetic/pharmacodynamic (PK/PD) modeling. AREAS COVERED: A concentration-response relationship allows analgesic effect comparison between drugs for different acute pain types. Covariates such as size, age and organ function impact greatly on PK in children...
2015: Expert Opinion on Drug Metabolism & Toxicology
Eugenia Yiannakopoulou
Variation exists in patient response on analgesic treatment in terms of efficacy and safety. This variation may be in part explained by pharmacogenomics. This paper aimed to review data on pharmacogenomics of opioid analgesics focusing on the effect of genetic variation on the efficacy and safety of these agents. Current evidence suggests that pharmacogenomics contribute to variation in efficacy and safety of opioids. However, most data come from case control studies and case reports. In addition, a recognized drawback in the field of pharmacogenomics is the common occurrence of false positive association between polymorphisms and the investigated outcome...
2015: International Journal of Genomics
Kenneth Blum, Peter K Thanos, Rajendra D Badgaiyan, Marcelo Febo, Marlene Oscar-Berman, James Fratantonio, Zsolt Demotrovics, Mark S Gold
INTRODUCTION: Addiction is a substantial health issue with limited treatment options approved by the FDA and as such currently available. The advent of neuroimaging techniques that link neurochemical and neurogenetic mechanisms to the reward circuitry brain function provides a framework for potential genomic-based therapies. AREAS COVERED: Through candidate and genome-wide association studies approaches, many gene polymorphisms and clusters have been implicated in drug, food and behavioral dependence linked by the common rubric reward deficiency syndrome (RDS)...
July 2015: Expert Opinion on Biological Therapy
Robert M Ward, Justin Stiers, Karen Buchi
Neonatal abstinence syndrome (NAS) is reaching epidemic proportions related to perinatal use of opioids. There are many approaches to assess and manage NAS, including one we have outlined. A standardized approach is likely to reduce length of stay and variability in practice. Circumcision is a frequent, painful procedure performed in the neonatal period. The rationale for providing analgesia is presented as well as a review of methods. Pharmacogenomics and pharmacogenetics have expanded our understanding of diseases and their drug therapy...
April 2015: Pediatric Clinics of North America
S Sadhasivam, X Zhang, V Chidambaran, J Mavi, V Pilipenko, T B Mersha, J Meller, K M Kaufman, L J Martin, J McAuliffe
Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year because of opioid-induced respiratory depression (RD) in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy...
October 2015: Pharmacogenomics Journal
S Sadhasivam, V Chidambaran, X Zhang, J Meller, H Esslinger, K Zhang, L J Martin, J McAuliffe
Opioid-related respiratory depression (RD) is a serious clinical problem as it causes multiple deaths and anoxic brain injuries. Morphine is subject to efflux via P-glycoprotein transporter encoded by ABCB1, also known as MDR1. ABCB1 polymorphisms may affect blood-brain barrier transport of morphine and therefore individual response to its central analgesic and adverse effects. This study aimed to determine specific associations between common ABCB1 genetic variants and clinically important outcomes including RD and RD resulting in prolonged stay in hospital with intravenous morphine in a homogenous pediatric surgical pain population of 263 children undergoing tonsillectomy...
April 2015: Pharmacogenomics Journal
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