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Pharmacogenomics of pain

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https://www.readbyqxmd.com/read/28930612/genetic-addiction-risk-score-gars-%C3%A2-a-predictor-of-vulnerability-to-opioid-dependence
#1
Kenneth Blum, Amanda L C Chen, Panayotis K Thanos, Marcelo Febo, Zsolt Demetrovics, Kristina Dushaj, Abraham Kovoor, David Baron, David E Smith, Alphonso Kenison Roy Iii, Lyle Fried, Thomas J H Chen, Edwin Chapman, Edward Modestino, Bruce Steinberg, Rajendra D Badgaiyan
The interaction of neurotransmitters and genes that control the release of dopamine is the Brain Reward Cascade (BRC). Variations within the BRC, whether genetic or epigenetic, may predispose individuals to addictive behaviors and altered pain tolerance. This discussion authored by a group of concerned scientists and clinicians examines the Genetic Addiction Risk Score (GARS), the first test to accurately predict vulnerability to pain, addiction, and other compulsive behaviors, defined as Reward Deficiency Syndrome (RDS)...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28901847/micrornas-to-monitor-pain-migraine-and-drug-treatment
#2
Luca Gallelli, Erika Cione, Maria Cristina Caroleo, Marco Carotenuto, Pasqualina Lagana, Antonio Siniscalchi, Vincenzo Guidetti
Migraine is a prevalent neurovascular disorders with a complex pathophysiology and therapeutic options characterized by important side effects or problems related to drug abuse. No specific biomarkers are recognized to be univocal for this subclinical condition, yet. In this concern microRNAs have been suggested as potentially useful screening/diagnostic tool, and research is underway to recognize the most effective candidate(s). microRNAs, able to regulate immune and neuronal processes are herein reported for both, mice models with multiple induced pain conditions and human subjects...
September 12, 2017: MicroRNA
https://www.readbyqxmd.com/read/28891702/pharmacokinetics-of-a-sustained-release-formulation-of-meloxicam-after-subcutaneous-administration-to-hispaniolan-amazon-parrots-amazona-ventralis
#3
David Sanchez-Migallon Guzman, Michael H Court, Zhaohui Zhu, Noémie Summa, Joanne R Paul-Murphy
Meloxicam has been shown to have a safe and favorable pharmacodynamic profile with individual variability in Hispaniolan Amazon parrots (Amazona ventralis). In the current study, we determined the pharmacokinetics of a sustained-release formulation of meloxicam after subcutaneous administration to Hispaniolan Amazon parrots. Twelve healthy adult parrots, 6 males and 6 females, were used in the study. Blood samples were collected before (time 0) and at 0.5, 1, 2, 6, 12, 24, 48, 72, 96, and 120 hours after a single dose of the sustained-release meloxicam formulation (3 mg/kg SC)...
September 2017: Journal of Avian Medicine and Surgery
https://www.readbyqxmd.com/read/28854576/genetics-of-age-related-macular-degeneration-amd
#4
Margaret M DeAngelis, Leah A Owen, Margaux A Morrison, Denise J Morgan, Mingyao Li, Akbar Shakoor, Albert Vitale, Sudha Iyengar, Dwight Stambolian, Ivana K Kim, Lindsay A Farrer
Age-related macular degeneration (AMD) is a progressive blinding disease and represents the leading cause of visual impairment in the aging population. AMD affects central vision which impairs one's ability to drive, read and recognize faces. There is no cure for this disease and current treatment modalities for the exudative form of the disease require repeated intravitreal injections which may be painful, are incompletely efficacious, and represent a significant treatment burden for both the patient and physician...
August 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28853040/state-of-the-art-management-of-acute-vaso-occlusive-pain-in-sickle-cell-disease
#5
REVIEW
Latika Puri, Kerri A Nottage, Jane S Hankins, Doralina L Anghelescu
Acute vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD). Multiple complex pathophysiological processes can result in pain during a VOC. Despite significant improvements in the understanding and management of SCD, little progress has been made in the management of pain in SCD, although new treatments are being explored. Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of treatment of VOC pain, but new classes of drugs are being tested to prevent and treat acute pain...
August 29, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/28696420/a-cost-effectiveness-analysis-of-maternal-cyp2d6-genetic-testing-to-guide-treatment-for-postpartum-pain-and-avert-infant-adverse-events
#6
M E Moretti, D F Lato, H Berger, G Koren, S Ito, W J Ungar
Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. Pharmacogenetic testing may be a valuable tool to identify such mothers, but testing can be costly. The objective of the study was to determine the incremental costs of genotyping to avert neonatal adverse events during maternal pharmacotherapy. A cost-effectiveness analysis, using a decision model, was performed with a hypothetical cohort of prenatal subjects...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28658526/reverse-pharmacogenomics-carbamazepine-normalizes-activation-and-attenuates-thermal-induced-hyperexcitability-of-sensory-neurons-due-to-nav1-7-mutation-i234t
#7
Yang Yang, Talia Adi, Philip Effraim, Lubin Chen, Sulayman D Dib-Hajj, Stephen G Waxman
BACKGROUND AND PURPOSE: Pharmacotherapy for pain currently involves trial-and-error. A previous study on inherited erythromelalgia (a genetic model of neuropathic pain due to mutations in voltage-gated sodium channel Nav1.7) used genomics, structural modeling, biophysical and pharmacological analyses to guide pharmacotherapy, and showed that carbamazepine normalizes voltage-dependence of activation of the Nav1.7-S241T mutant channel, reducing pain in patients carrying this mutation. However, whether this approach is applicable to other Nav mutations is still unknown...
June 28, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28526150/pharmacogenomics-in-pain-management
#8
REVIEW
Ramsey Saba, Alan D Kaye, Richard D Urman
There is interpatient variability to analgesic administration. Much can be traced to pharmacogenomics variations between individuals. Certain ethnicities are more prone to reduced function of CYP2D6. Weak opioids are subject to interpatient variation based on their CYP2D6 type. Strong opioids have variations based on their transport and individual metabolism. Several cytochrome enzymes have been found to be involved with ketamine but there is no strong evidence of individual polymorphisms manifesting in clinical outcomes...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28490206/pharmacokinetics-pharmacodynamics-and-pharmacogenetics-associated-with-nonsteroidal-anti-inflammatory-drugs-and-opioids-in-pediatric-cancer-patients
#9
REVIEW
Jonathan E Constance, Sarah C Campbell, Amit A Somani, Venkata Yellepeddi, Katie H Owens, Catherine M T Sherwin
Advancing appropriate and adequate analgesic pharmacotherapy in pediatric patients with cancer is an area of clinical need. Few studies have been performed to evaluate the selection of an analgesic and appropriate dosing corresponding to analgesic effect among pediatric cancer patients. This review describes information related to pharmacokinetic, pharmacodynamic, and pharmacogenomic (when applicable) considerations for analgesics that are commonly used to manage pain experienced by pediatric patients with cancer...
July 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28486096/key-pharmacogenomic-considerations-for-sickle-cell-disease-patients
#10
Alexandra Kolliopoulou, Apostolos Stratopoulos, Stavroula Siamoglou, Argyro Sgourou, Bassam R Ali, Adamantia Papachatzopoulou, Theodora Katsila, George P Patrinos
Sickle cell disease (SCD), although a monogenic disease, exhibits a complex clinical phenotype that hampers optimum patient stratification and disease management, especially on hydroxyurea treatment. Moreover, theranostics, the combination of diagnostics to individualize and optimize therapeutic interventions, has not been firmly on the forefront of SCD research and clinical management to date. We suggest that if tailor-made theranostics in SCD is envisaged, pharmacogenomics is anticipated to be the way forward...
June 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28339912/pharmacogenomics-and-patient-treatment-parameters-to-opioid-treatment-in-chronic-pain-a-focus-on-morphine-oxycodone-tramadol-and-fentanyl
#11
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...
February 24, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/27999358/review-of-toxic-epidermal-necrolysis
#12
REVIEW
Victoria Harris, Christopher Jackson, Alan Cooper
Toxic epidermal necrolysis (TEN) is a rare but life threatening mucocutaneous reaction to drugs or their metabolites. It is characterised by widespread keratinocyte apoptosis and sloughing of the skin, erosions of the mucous membranes, painful blistering, and severe systemic disturbance. The pathophysiology of TEN is incompletely understood. Historically, it has been regarded as a drug-induced immune reaction initiated by cytotoxic lymphocytes via a human leukocyte antigen (HLA)-restricted pathway. Several mediators have been identified as contributors to the cell death seen in TEN, including; granulysin, soluble Fas ligand, perforin/granzyme, tumour necrosis factor-α (TNF-α), and TNF-related apoptosis-inducing ligand...
December 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27992298/what-is-the-future-of-pharmacogenomics-in-pain-management
#13
Ana M Peiró, César Margarit, Adrián LLerena
No abstract text is available yet for this article.
January 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/27861439/trends-in-tramadol-pharmacology-metabolism-and-misuse
#14
REVIEW
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
https://www.readbyqxmd.com/read/27798813/economic-evaluation-of-a-pharmacogenomics-test-for-statin-induced-myopathy-in-cardiovascular-high-risk-patients-initiating-a-statin
#15
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...
February 2017: 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
#16
COMPARATIVE STUDY
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)...
April 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27662648/pharmacogenomics-in-pain-treatment
#17
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
#18
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
#19
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
#20
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...
October 2017: Pharmacogenomics Journal
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