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https://www.readbyqxmd.com/read/29149154/philosophical-issues-and-psychological-variables-that-influence-the-determination-of-opioid-effectiveness-a-narrative-review
#1
Daniel Michael Doleys
BACKGROUND: The prescribing of opioids in the chronic pain setting is often based on the pharmacodynamics, pharmacokinetics, and pharmacogenetics of the drug obtained during development and clinical trials. However, the effectiveness of opioids varies widely and often appears to bear no relationship to the aforementioned variables. The impact of philosophical issues and psychological factors on determining how clinically effective opioid therapy is has often been over looked. OBJECTIVES: This manuscript provides a selective review and narrative summary of the philosophical issues and psychological factors which can influence opioid effectiveness...
November 2017: Pain Physician
https://www.readbyqxmd.com/read/29145602/genotype-based-selection-of-treatment-for-patients-with-advanced-colorectal-cancer-seticc-a-pharmacogenetic-based-randomized-phase-ii-trial
#2
A Abad, E Martínez-Balibrea, J M Viéitez, V A Orduña, P García Alfonso, J L Manzano, B Massutí, M Benavides, A Carrato, M Zanui, J Gallego, C Grávalos, V Conde, M Provencio, M Valladares, R Salazar, J Sastre, C Montagut, F Rivera, E Aranda
Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC. Patients and methods: This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms...
November 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29138287/clopidogrel-carboxylic-acid-glucuronidation-is-mediated-mainly-by-ugt2b7-ugt2b4-and-ugt2b17-implications-for-pharmacogenetics-and-drug-drug-interactions
#3
Helina Kahma, Anne M Filppula, Mikko Neuvonen, E Katriina Tarkiainen, Aleksi Tornio, Mikko T Holmberg, Matti K Itkonen, Moshe Finel, Pertti J Neuvonen, Mikko Niemi, Janne T Backman
The antiplatelet drug clopidogrel is metabolized to an acyl-β-D-glucuronide, which causes time-dependent inactivation of CYP2C8. Our aim was to characterize the UDP-glucuronosyltransferase (UGT) enzymes that are responsible for the formation of clopidogrel acyl-β-D-glucuronide. Kinetic analyses and targeted inhibition experiments were performed using pooled human liver and intestine microsomes (HLM and HIM, respectively) and selected human recombinant UGTs based on preliminary screening. The effects of relevant UGT polymorphisms on the pharmacokinetics of clopidogrel were evaluated in 106 healthy volunteers...
November 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29137046/multiple-adverse-drug-reactions-and-genetic-polymorphism-testing-a-case-report-with-negative-result
#4
Ana Lucía Arellano, Marta Martin-Subero, Mar Monerris, Adrián LLerena, Magí Farré, Eva Montané
RATIONALE: Defects in drug metabolic pathways could explain why some patients have a history of multiple adverse drug reactions (ADR); therefore we aimed to analyze genetic polymorphisms in a patient with multiple ADR related to drugs with a common hepatic metabolic pathway through CYP2D6. PATIENT CONCERNS: We report a patient with psychosis and hypertension related to amitriptyline, tramadol, and duloxetine within a 2-year period. INTERVENTIONS AND OUTCOMES: A pharmacogenetic test was performed to assess the causative role of the CYP2D6 enzyme, but did not demonstrate a metabolic deficiency...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29136278/a-critical-appraisal-of-pharmacogenetic-inference
#5
REVIEW
R A J Smit, R Noordam, S le Cessie, S Trompet, J W Jukema
In essence, pharmacogenetic research is aimed at discovering variants of importance to gene-treatment interaction. However, epidemiological studies are rarely set up with this goal in mind. It is therefore of great importance that researchers clearly communicate which assumptions they have had to make, and which inherent limitations apply to the interpretation of their results. This review discusses considerations of, and the underlying assumptions for, utilizing different response phenotypes and study designs popular in pharmacogenetic research to infer gene-treatment interaction effects, with a special focus on those dealing with of clinical effects of drug treatment...
November 14, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/29134625/the-pharmacogene-variation-pharmvar-consortium-incorporation-of-the-human-cytochrome-p450-cyp-allele-nomenclature-database
#6
Andrea Gaedigk, Magnus Ingelman-Sundberg, Neil A Miller, J Steven Leeder, Michelle Whirl-Carrillo, Teri E Klein
The Human Cytochrome P450 (CYP) Allele Nomenclature Database, a critical resource for the pharmacogenetics and genomics communities, has transitioned to the Pharmacogene Variation (PharmVar) Consortium. In this report we provide a summary of the current database, provide an overview of the PharmVar consortium, and highlight the PharmVar database which will serve as the new home for pharmacogene nomenclature.
November 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29120908/patients-beliefs-about-medicine-are-associated-with-early-thiopurine-discontinuation-in-patients-with-inflammatory-bowel-diseases
#7
Mark M T J Broekman, Marieke J H Coenen, Geert J Wanten, Corine J van Marrewijk, Wietske Kievit, Olaf H Klungel, André L M Verbeek, Dennis R Wong, Piet M Hooymans, Henk-Jan Guchelaar, Hans Scheffer, Luc J J Derijks, Marcel L Bouvy, Dirk J de Jong
BACKGROUND: Patients' beliefs about medicine may either reflect the necessity for treatment or concerns regarding the treatment. We explored the extent to which these beliefs have an effect on thiopurine metabolite levels and premature discontinuation in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: Patients enrolled in the 'Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory Bowel Disease Clinics' (TOPIC) trial were asked to complete the Beliefs about Medicine Questionnaire (BMQ) 4 weeks after thiopurine initiation...
November 8, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29117660/nebivolol-induced-hyperkalemia-case-report
#8
Karmela Altabas, Velimir Altabas, Tonko Gulin
In this article, we document a conclusive case of nebivolol-induced hyperkalemia for the first time in the known medical literature. Hyperkalemia is associated with serious conditions such as cardiac arrhythmias and sudden cardiac death. Nebivolol was not known to cause hyperkalemia, and this event is not listed in its summary of product characteristics (SmPC). For older beta blockers, hyperkalemia is recognized as a rare adverse event linked to cytochrome P450 2D6 (CYP2D6) polymorphism and poor drug degradation...
December 2016: Acta Clinica Croatica
https://www.readbyqxmd.com/read/29117017/race-ethnicity-difference-in-the-pharmacogenetics-of-bilirubin-related-atazanavir-discontinuation
#9
Paul Leger, Sanika Chirwa, Jacinta N Nwogu, Megan Turner, Danielle M Richardson, Paxton Baker, Michael Leonard, Husamettin Erdem, Lana Olson, David W Haas
BACKGROUND: Atazanavir causes plasma indirect bilirubin to increase. We evaluated associations between Gilbert's polymorphism and bilirubin-related atazanavir discontinuation stratified by race/ethnicity. PATIENTS AND METHODS: Patients had initiated atazanavir/ritonavir-containing regimens at an HIV primary care clinic in the southeastern USA, and had at least 12 months of follow-up data. Metabolizer group was defined by UGT1A1 rs887829 C→T. Genome-wide genotype data were used to adjust for genetic ancestry in combined population analyses...
November 6, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/29115880/treatment-response-heterogeneity-in-asthma-the-role-of-genetic-variation
#10
Susanne J H Vijverberg, Niloufar Farzan, Elise M A Slob, Anne H Neerincx, Anke H Maitland-van der Zee
Asthmatic patients show a large heterogeneity in response to asthma medication. Rapidly evolving genotyping technologies have led to the identification of various genetic variants associated with treatment outcomes. Areas covered: This review focuses on the current knowledge of genetic variants influencing treatment response to the most commonly used asthma medicines: short- and long-acting beta-2 agonists (SABA/LABA), inhaled corticosteroids (ICS) and leukotriene modifiers. This review shows that various genetic variants have been identified, but none are currently used to guide asthma treatment...
November 8, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/29110602/pharmacometabonomics-technique-to-identify-warfarin-response-using-nuclear-magnetic-resonance-spectroscopy
#11
Abdulkader Ahmad Bawadikji, Chin-Hoe Teh, Muhamad Ali Bin Sheikh Abdul Kader, Syed Azhar Syed Sulaiman, Baharudin Ibrahim
BACKGROUND: Warfarin, an anticoagulant medication, has prescribed regularly despite of its bleeding tendency for the prevention and/or treatment of various thromboembolic conditions, such as deep vein thrombosis, and complications associated with atrial fibrillation, and myocardial infarction, but because of its narrow therapeutic window have a lot of interactions with drugs and diet. METHOD: Warfarin relies on regular monitoring of International Normalized Ratio which is a standardized test to measure prothrombin time and appropriate dose adjustment...
November 3, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29108090/characteristics-and-quality-of-oral-anticoagulation-treatment-in-pediatric-patients-in-the-netherlands-based-on-the-caps-cohort
#12
Hedy Maagdenberg, Marc B Bierings, C Heleen van Ommen, Felix J M van der Meer, Inge M Appel, Rienk Y J Tamminga, Anthonius de Boer, Anke H Maitland-van der Zee
BACKGROUND: The use of vitamin-K antagonists in pediatric patients is rare and information on quality and safety of the treatment with acenocoumarol and phenprocoumon is limited. OBJECTIVES: To assess the quality, safety and effectiveness during the first year of acenocoumarol and phenprocoumon treatment in pediatric patients in the Netherlands. METHODS: The Children Anticoagulation and Pharmacogenetics Study (CAPS) was designed as a multicenter retrospective follow-up study...
November 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29107547/camkii%C3%AE-expression-defines-two-functionally-distinct-populations-of-granule-cells-involved-in-different-types-of-odor-behavior
#13
Sarah Malvaut, Simona Gribaudo, Delphine Hardy, Linda Suzanne David, Laura Daroles, Simon Labrecque, Marie-Anne Lebel-Cormier, Zayna Chaker, Daniel Coté, Paul De Koninck, Martin Holzenberger, Alain Trembleau, Isabelle Caille, Armen Saghatelyan
Granule cells (GCs) in the olfactory bulb (OB) play an important role in odor information processing. Although they have been classified into various neurochemical subtypes, the functional roles of these subtypes remain unknown. We used in vivo two-photon Ca(2+) imaging combined with cell-type-specific identification of GCs in the mouse OB to examine whether functionally distinct GC subtypes exist in the bulbar network. We showed that half of GCs express Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα(+)) and that these neurons are preferentially activated by olfactory stimulation...
November 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29103068/antiplatelet-therapy-for-secondary-prevention-of-vascular-disease-complications
#14
REVIEW
Rahul R Goli, Mayur M Contractor, Ashwin Nathan, Sony Tuteja, Taisei Kobayashi, Jay Giri
PURPOSE OF REVIEW: Platelets are activated upon interaction with injured vascular endothelium to form a primary hemostatic plug. Pathogenic thrombosis driven by platelet aggregation can occur in the setting of vascular disease leading to ischemic events. The use of antiplatelet agents has become a mainstay for prevention of the secondary complications of vascular disease. This review summarizes seminal and recent literature related to this area. RECENT FINDINGS: Aspirin is a cornerstone of antiplatelet therapy for coronary artery disease and cerebrovascular disease for prevention of myocardial infarction, stroke, and vascular death...
November 4, 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/29100168/genetic-variants-as-ovarian-cancer-first-line-treatment-hallmarks-a-systematic-review-and-meta-analysis
#15
REVIEW
Joana Assis, Carina Pereira, Augusto Nogueira, Deolinda Pereira, Rafael Carreira, Rui Medeiros
BACKGROUND: The potential predictive value of genetic polymorphisms in ovarian cancer first-line treatment is inconsistently reported. We aimed to review ovarian cancer pharmacogenetic studies to update and summarize the available data and to provide directions for further research. METHODS: A systematic review followed by a meta-analysis was conducted on cohort studies assessing the involvement of genetic polymorphisms in ovarian cancer first-line treatment response retrieved through a MEDLINE database search by November 2016...
October 20, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29099735/effect-of-pharmacogenetic-markers-of-vitamin-d-pathway-on-deferasirox-pharmacokinetics-in-children
#16
Sarah Allegra, Jessica Cusato, Silvia De Francia, Filomena Longo, Elisa Pirro, Davide Massano, Antonio Piga, Antonio D'Avolio
OBJECTIVES: Patients with β-thalassemia major have extremely low vitamin D levels, owing to reduced intestinal absorption, subicteric tint, and/or iron-induced higher pigmentation. We investigated whether some polymorphisms within the VDR, CYP24A1, CYP27B1, and GC genes could play a role in deferasirox pharmacokinetics in a cohort of pediatric patients. PATIENTS AND METHODS: Eighteen children with β-thalassemia were enrolled. Drug plasma concentrations at the end of dosing interval (Ctrough) and after 0, 2, 4, 6, and 24 h of drug administration were measured by a HPLC-UV method...
November 2, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/29099403/considerations-for-the-use-of-virally-delivered-genetic-tools-for-in-vivo-circuit-analysis-and-behavior-in-mutant-mice-a-practical-guide-to-optogenetics
#17
Dóra Zelena, Kornél Demeter, József Haller, Diána Balázsfi
Optogenetics was the method of the year in 2010 according to Nature Neuroscience. Since then, this method has become widespread, the use of virally delivered genetic tools has extended to other fields such as pharmacogenetics, and optogenetic techniques have become frequently applied in genetically manipulated animals for in-vivo circuit analysis and behavioral studies. However, several issues should be taken into consideration when planning such experiments. We aimed to summarize the critical points concerning optogenetic manipulation of a specific brain area in mutant mice...
December 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29099060/clinical-pharmacogenetics-of-cytochrome-p450-associated-drugs-in-children
#18
Ida Aka, Christiana J Bernal, Robert Carroll, Angela Maxwell-Horn, Kazeem A Oshikoya, Sara L Van Driest
Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug-CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs...
November 2, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29095108/pharmacogenetics-of-glatiramer-acetate-therapy-for-multiple-sclerosis-the-impact-of-genome-wide-association-studies-identified-disease-risk-loci
#19
Olga Kulakova, Vitalina Bashinskaya, Ivan Kiselev, Natalia Baulina, Ekaterina Tsareva, Ruslan Nikolaev, Maxim Kozin, Sergey Shchur, Alexander Favorov, Alexey Boyko, Olga Favorova
AIM: Association analysis of genome-wide association studies (GWAS) identified multiple sclerosis (MS) risk genetic variants with glatiramer acetate (GA) treatment efficacy. PATIENTS & METHODS: SNPs in 17 GWAS-identified immune response loci were analyzed in 296 Russian MS patients as possible markers of optimal GA treatment response for at least 2 years. RESULTS: Alleles/genotypes of EOMES, CLEC16A, IL22RA2, PVT1 and HLA-DRB1 were associated by themselves with event-free phenotype during GA treatment for at least 2 years (p f  = 0...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29091211/influence-of-abcb11-and-hnf4%C3%AE-genes-on-daclatasvir-plasma-concentration-preliminary-pharmacogenetic-data-from-the-kineti-c-study
#20
Jessica Cusato, Amedeo De Nicolò, Lucio Boglione, Fabio Favata, Alessandra Ariaudo, Simone Mornese Pinna, Federica Guido, Valeria Avataneo, Chiara Carcieri, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio
Background: Daclatasvir is an inhibitor of HCV non-structural 5A protein and is a P-glycoprotein substrate. Pharmacogenetics has had a great impact on previous anti-HCV therapies, particularly considering the association of IL-28B polymorphisms with dual therapy outcome. Objectives: We investigated the association between daclatasvir plasma concentrations at 2 weeks and 1 month of therapy and genetic variants (SNPs) in genes encoding transporters and nuclear factors (ABCB1, ABCB11 and HNF4α)...
October 1, 2017: Journal of Antimicrobial Chemotherapy
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