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Pharmacogenomics of pain

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https://www.readbyqxmd.com/read/27861439/trends-in-tramadol-pharmacology-metabolism-and-misuse
#1
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
https://www.readbyqxmd.com/read/27798813/economic-evaluation-of-a-pharmacogenomics-test-for-statin-induced-myopathy-in-cardiovascular-high-risk-patients-initiating-a-statin
#2
Dominic Mitchell, Jason R Guertin, Ange Christelle Iliza, Fiorella Fanton-Aita, Jacques LeLorier
BACKGROUND: Statins are the mainstay hypercholesterolemia treatment and reduce the risk of cardiovascular events in patients. However, statin therapy is often interrupted in patients experiencing musculoskeletal pain or myopathy, which are common in this patient group. Currently, the standard tests for diagnosing statin myopathies are difficult to interpret. A pharmacogenomics (PGx) test to diagnose statin-induced myopathy would be highly desirable. METHODS: We developed a Markov state model to assess the cost-effectiveness of a hypothetical PGx test, which aims to identify statin-induced myopathy in high-risk, secondary prevention cardiovascular patients...
October 31, 2016: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27696737/highly-polygenic-architecture-of-antidepressant-treatment-response-comparative-analysis-of-ssri-and-nri-treatment-in-an-animal-model-of-depression
#3
Karim Malki, Maria Grazia Tosto, Héctor Mouriño-Talín, Sabela Rodríguez-Lorenzo, Oliver Pain, Irfan Jumhaboy, Tina Liu, Panos Parpas, Stuart Newman, Artem Malykh, Lucia Carboni, Rudolf Uher, Peter McGuffin, Leonard C Schalkwyk, Kevin Bryson, Mark Herbster
Response to antidepressant (AD) treatment may be a more polygenic trait than previously hypothesized, with many genetic variants interacting in yet unclear ways. In this study we used methods that can automatically learn to detect patterns of statistical regularity from a sparsely distributed signal across hippocampal transcriptome measurements in a large-scale animal pharmacogenomic study to uncover genomic variations associated with AD. The study used four inbred mouse strains of both sexes, two drug treatments, and a control group (escitalopram, nortriptyline, and saline)...
October 1, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27662648/pharmacogenomics-in-pain-treatment
#4
Ana M Peiró, Beatriz Planelles, Gabriella Juhasz, György Bagdy, Frédéric Libert, Alain Eschalier, Jérôme Busserolles, Beata Sperlagh, Adrián Llerena
The experience of chronic pain is one of the commonest reasons for seeking medical attention, being a major issue in clinical practice. While pain is a universal experience, only a small proportion of people who felt pain develop pain syndromes. In addition, painkillers are associated with wide inter-individual variability in the analgesic response. This may be partly explained by the presence of single nucleotide polymorphisms in genes encoding molecular entities involved in pharmacodynamics and pharmacokinetics...
September 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27636225/an-expert-review-of-pharmacogenomics-of-sickle-cell-disease-therapeutics-not-yet-ready-for-global-precision-medicine
#5
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
https://www.readbyqxmd.com/read/27388970/the-role-of-cytochrome-p450-pharmacogenomics-in-chronic-non-cancer-pain-patients
#6
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
https://www.readbyqxmd.com/read/27139154/emergent-biomarker-derived-from-next-generation-sequencing-to-identify-pain-patients-requiring-uncommonly-high-opioid-doses
#7
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
https://www.readbyqxmd.com/read/27108830/good-clinical-practice-guide-for-opioids-in-pain-management-the-three-ts-titration-trial-tweaking-tailoring-transition-tapering
#8
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
https://www.readbyqxmd.com/read/27062626/pain-management-in-the-acute-care-setting-update-and-debates
#9
REVIEW
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
https://www.readbyqxmd.com/read/27060151/a-genome-wide-association-study-identifies-a-novel-locus-for-bortezomib-induced-peripheral-neuropathy-in-european-patients-with-multiple-myeloma
#10
Florence Magrangeas, Rowan Kuiper, Hervé Avet-Loiseau, Wilfried Gouraud, Catherine Guérin-Charbonnel, Ludovic Ferrer, Alexandre Aussem, Haytham Elghazel, Jérôme Suhard, Henri Der Sakissian, Michel Attal, Nikhil C Munshi, Pieter Sonneveld, Charles Dumontet, Philippe Moreau, Mark van Duin, Loïc Campion, Stéphane Minvielle
PURPOSE: Painful peripheral neuropathy is a frequent toxicity associated with bortezomib therapy. This study aimed to identify loci that affect susceptibility to this toxicity. EXPERIMENTAL DESIGN: A genome-wide association study (GWAS) of 370,605 SNPs was performed to identify risk variants for developing severe bortezomib-induced peripheral neuropathy (BiPN) in 469 patients with multiple myeloma who received bortezomib-dexamethasone therapy prior to autologous stem cell in randomized clinical trials of the Intergroupe Francophone du Myelome (IFM) and findings were replicated in 114 patients with multiple myeloma of the HOVON-65/GMMG-HD4 clinical trial...
September 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27046448/epigenetic-regulation-of-g-protein-coupled-receptor-signaling-and-its-implications-in-psychiatric-disorders
#11
Shalini Dogra, Chandan Sona, Ajeet Kumar, Prem N Yadav
G protein-coupled receptors (GPCRs) act as a relay center through which extracellular signals, in the form of neurotransmitters or therapeutics, are converted into an intracellular response, which ultimately shapes the overall response at the tissue and behavioral level. Remarkably in similar ways, epigenetic mechanisms also modulate the expression pattern of a large number of genes in response to the dynamic environment inside and outside of the body, and consequently overall response. Emerging evidences from the pharmacogenomics and preclinical studies clearly suggest that these two distinct mechanisms criss-cross each other in several neurological disorders...
August 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27001122/mechanisms-of-the-placebo-effect-in-pain-and-psychiatric-disorders
#12
REVIEW
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
https://www.readbyqxmd.com/read/26995880/-optimal-treatment-for-rheumatoid-arthritis-with-companion-diagnostics
#13
REVIEW
Shunichi Kumagai
The medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introduction of biologics in addition to methotrexate, an anchor drug, has made it possible to not only suppress pain and inflammation (clinical remission), but also inhibit joint destruction (structural remission), leading to cure from the disease. Since the condition and pathology are heterogeneous among individual patients, optimal treatment for each patient based on the use of companion diagnostics is desired (precision medicine)...
November 2015: Rinsho Byori. the Japanese Journal of Clinical Pathology
https://www.readbyqxmd.com/read/26993413/-good-clinical-practice-guide-for-opioids-in-pain-management-the-three-ts-titration-trial-tweaking-tailoring-transition-tapering
#14
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
https://www.readbyqxmd.com/read/26976339/pharmacogenomics-for-personalized-pain-medicine
#15
REVIEW
Tai-Ming Ko, Chih-Shung Wong, Jer-Yuarn Wu, Yuan-Tsong Chen
Pharmacogenomics aims to unravel the way that human genetic variation affects drug efficacy and toxicity. Genome-wide association studies and candidate gene findings suggest that genetic approaches may help choose the most appropriate drug and dosage while preventing adverse drug reactions (ADRs). Pain is an unpleasant feeling that usually results from tissue damage. The management of different types of pain (acute, chronic, inflammatory, neuropathic, or cancer) is challenging. Currently, drug intervention is the first-line therapy for resolving pain...
March 2016: Acta Anaesthesiologica Taiwanica: Official Journal of the Taiwan Society of Anesthesiologists
https://www.readbyqxmd.com/read/26929662/the-pharmacogenomics-of-pain-management-prospects-for-personalized-medicine
#16
REVIEW
Sonya Ting, Stephan Schug
Pain is a common symptom that can be complex to treat. Analgesic medications are the mainstay treatment, but there is wide interindividual variability in analgesic response and adverse effects. Pharmacogenomics is the study of inherited genetic traits that result in these individual responses to drugs. This narrative review will attempt to cover the current understanding of the pharmacogenomics of pain, examining common genes affecting metabolism of analgesic medications, their distribution throughout the body, and end organ effects...
2016: Journal of Pain Research
https://www.readbyqxmd.com/read/26897853/-personalized-medicine-in-rheumatoid-arthritis
#17
REVIEW
Shunichi Kumagai
Medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introductions of biologics and methotrexate as an anchor drug have made it possible to not only suppress pain and inflammation (clinical remission), but also to inhibit joint destruction (structural remission), leading to cure of the disease. In order to achieve this target, it is the most important to diagnose RA early and promote disease remission. However, since the condition and pathology are diverse among patients, optimal treatment for each patient is desired (personalized medicine)...
October 2015: Rinsho Byori. the Japanese Journal of Clinical Pathology
https://www.readbyqxmd.com/read/26747884/sodium-channel-nav1-8-emerging-links-to-human-disease
#18
REVIEW
Chongyang Han, Jianying Huang, Stephen G Waxman
The NaV1.8 sodium channel, encoded by gene SCN10A, was initially termed sensory neuron-specific (SNS) due to prominent expression in primary sensory neurons including dorsal root ganglion (DRG) neurons. Early studies on rodent NaV1.8 demonstrated depolarized voltage dependence of channel inactivation, a slow rate of inactivation, and rapid recovery from inactivation. As a result of these biophysical properties, NaV1.8 supports repetitive firing in response to sustained depolarization. This article reviews recent studies that reveal multiple links of NaV1...
February 2, 2016: Neurology
https://www.readbyqxmd.com/read/26678969/clinical-implications-of-opioid-pharmacogenomics-in-patients-with-cancer
#19
REVIEW
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
https://www.readbyqxmd.com/read/26155821/considerations-when-using-pharmacokinetic-pharmacodynamic-modeling-to-determine-the-effectiveness-of-simple-analgesics-in-children
#20
REVIEW
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
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