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American Journal of Health-system... Dec 2016The current state of pharmacogenomics education for pharmacy students and practitioners is discussed, and resources and strategies to address persistent challenges in... (Review)
Review
PURPOSE
The current state of pharmacogenomics education for pharmacy students and practitioners is discussed, and resources and strategies to address persistent challenges in this area are reviewed.
SUMMARY
Consensus-based pharmacist competencies and guidelines have been published to guide pharmacogenomics knowledge attainment and application in clinical practice. Pharmacogenomics education is integrated into various pharmacy school courses and, increasingly, into Pharm.D. curricula in the form of required standalone courses. Continuing-education programs and a limited number of postgraduate training opportunities are available to practicing pharmacists. For colleges and schools of pharmacy, identifying the optimal structure and content of pharmacogenomics education remains a challenge; insufficient numbers of faculty members with pharmacogenomics expertise and the inadequate availability of practice settings for experiential education are other limiting factors. Strategies for overcoming those challenges include providing early exposure to pharmacogenomics through foundational courses and incorporating pharmacogenomics into practice-based therapeutics courses and introductory and advanced pharmacy practice experiences. For practitioner education, online resources, clinical decision support-based tools, and certificate programs can be used to supplement structured postgraduate training in pharmacogenomics. Recently published data indicate successful use of "shared curricula" and participatory education models involving opportunities for learners to undergo personal genomic testing.
CONCLUSION
The pharmacy profession has taken a leadership role in expanding student and practitioner education to meet the demand for increased pharmacist involvement in precision medicine initiatives. Effective approaches to teaching pharmacogenomics knowledge and driving its appropriate application in clinical practice are increasingly available.
Topics: Education, Pharmacy; Humans; Patient Care; Pharmaceutical Services; Pharmacogenetics; Students, Pharmacy
PubMed: 27864206
DOI: 10.2146/ajhp160104 -
The Pharmacogenomics Journal Jun 2021The outbreak of Coronavirus disease 2019 (COVID-19) has evolved into an emergent global pandemic. Many drugs without established efficacy are being used to treat... (Review)
Review
The outbreak of Coronavirus disease 2019 (COVID-19) has evolved into an emergent global pandemic. Many drugs without established efficacy are being used to treat COVID-19 patients either as an offlabel/compassionate use or as a clinical trial. Although drug repurposing is an attractive approach with reduced time and cost, there is a need to make predictions on success before the start of therapy. For the optimum use of these repurposed drugs, many factors should be considered such as drug-gene or dug-drug interactions, drug toxicity, and patient co-morbidity. There is limited data on the pharmacogenomics of these agents and this may constitute an obstacle for successful COVID-19 therapy. This article reviewed the available human genome interactions with some promising repurposed drugs for COVID-19 management. These drugs include chloroquine (CQ), hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir (LPV/r), atazanavir (ATV), favipiravir (FVP), nevirapine (NVP), efavirenz (EFV), oseltamivir, remdesivir, anakinra, tocilizumab (TCZ), eculizumab, heme oxygenase 1 (HO-1) regulators, renin-angiotensin-aldosterone system (RAAS) inhibitors, ivermectin, and nitazoxanide. Drug-gene variant pairs that may alter the therapeutic outcomes in COVID-19 patients are presented. The major drug variant pairs that associated with variations in clinical efficacy include CQ/HCQ (CYP2C8, CYP2D6, ACE2, and HO-1); azithromycin (ABCB1); LPV/r (SLCO1B1, ABCB1, ABCC2 and CYP3A); NVP (ABCC10); oseltamivir (CES1 and ABCB1); remdesivir (CYP2C8, CYP2D6, CYP3A4, and OATP1B1); anakinra (IL-1a); and TCZ (IL6R and FCGR3A). The major drug variant pairs that associated with variations in adverse effects include CQ/HCQ (G6PD; hemolysis and ABCA4; retinopathy), ATV (MDR1 and UGT1A1*28; hyperbilirubinemia; and APOA5; dyslipidemia), NVP (HLA-DRB1*01, HLA-B*3505 and CYP2B6; skin rash and MDR1; hepatotoxicity), and EFV (CYP2B6; depression and suicidal tendencies).
Topics: Antiviral Agents; COVID-19; Drug Repositioning; Genome, Human; Humans; Multidrug Resistance-Associated Protein 2; Pharmacogenetics; COVID-19 Drug Treatment
PubMed: 33542445
DOI: 10.1038/s41397-021-00209-9 -
Biomedicine & Pharmacotherapy =... Jun 2022Mendelian randomization (MR) is an epidemiological method that uses genetic variants to proxy an exposure predicting its causal association with an outcome. It occupies... (Review)
Review
Mendelian randomization (MR) is an epidemiological method that uses genetic variants to proxy an exposure predicting its causal association with an outcome. It occupies a valuable niche between observational studies and randomized trials. MR applications expanded lately, facilitated by the availability of big data, to include disease risk causation prediction, supporting evidence of prior observational data, identifying new drug targets, and drug repurposing. Concurrently, the last decade witnessed the growth of pharmacogenomics (PGx) research as a cornerstone in precision medicine. PGx research, conducted at discovery and implementation levels, resulted in validated PGx biomarkers and tests. Despite many clinically relevant PGx associations that could be translated into clinical applications, worldwide implementation is lagging far behind. The current review examines the intersection zones between MR and PGx research. MR can provide supporting evidence that allows generalizing PGx findings supporting its implementation. Interchangeability, PGx research can fuel MR studies with libraries of genetic variants of validated biological relevance. Furthermore, PGx and MR exhibit a synergistic relationship in drug discovery that can accelerate identifying new targets and repurposing old drugs. Interdisciplinary research applied by PGx researchers, epidemiologists with MR experience, and data scientists' collaborations can unlock unforeseen opportunities in accelerating precision medicine acquisition.
Topics: Drug Discovery; Mendelian Randomization Analysis; Pharmacogenetics; Precision Medicine
PubMed: 35429744
DOI: 10.1016/j.biopha.2022.112952 -
Pharmacogenomics Feb 2021Pharmacogenetics represents a major driver of precision medicine, promising individualized drug selection and dosing. Traditionally, pharmacogenetic profiling has been... (Review)
Review
Pharmacogenetics represents a major driver of precision medicine, promising individualized drug selection and dosing. Traditionally, pharmacogenetic profiling has been performed using targeted genotyping that focuses on common/known variants. Recently, whole-genome sequencing (WGS) is emerging as a more comprehensive short-read next-generation sequencing approach, enabling both gene diagnostics and pharmacogenetic profiling, including rare/novel variants, in a single assay. Using the example of the pharmacogene , we demonstrate the potential of WGS-based pharmacogenetic profiling as well as emphasize the limitations of short-read next-generation sequencing. In the near future, we envision a shift toward long-read sequencing as the predominant method for gene diagnostics and pharmacogenetic profiling, providing unprecedented data quality and improving patient care.
Topics: Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Whole Genome Sequencing
PubMed: 33517770
DOI: 10.2217/pgs-2020-0155 -
Clinical Pharmacology and Therapeutics Nov 2019
Topics: Databases, Genetic; Decision Support Systems, Clinical; Electronic Health Records; Humans; Leadership; Pharmacogenetics; Pharmacogenomic Variants; Precision Medicine
PubMed: 31498426
DOI: 10.1002/cpt.1600 -
Human Genetics Jun 2022Pharmaceutical companies have increasingly utilized genomic data for the selection of drug targets and the development of precision medicine approaches. Most major... (Review)
Review
Pharmaceutical companies have increasingly utilized genomic data for the selection of drug targets and the development of precision medicine approaches. Most major pharmaceutical companies routinely collect DNA from clinical trial participants and conduct pharmacogenomic (PGx) studies. However, the implementation of PGx studies during clinical development presents a number of challenges. These challenges include adapting to a constantly changing global regulatory environment, challenges in study design and clinical implementation, and the increasing concerns over patient privacy. Advances in the field of genomics are also providing new opportunities for pharmaceutical companies, including the availability of large genomic databases linked to patient health information, the growing use of polygenic risk scores, and the direct sequencing of clinical trial participants. The Industry Pharmacogenomics Working Group (I-PWG) is an association of pharmaceutical companies actively working in the field of pharmacogenomics. This I-PWG perspective will provide an overview of the steps pharmaceutical companies are taking to address each of these challenges, and the approaches being taken to capitalize on emerging scientific opportunities.
Topics: DNA; Genomics; Humans; Pharmaceutical Preparations; Pharmacogenetics; Precision Medicine
PubMed: 34081195
DOI: 10.1007/s00439-021-02282-3 -
Nucleic Acids Research Jan 2022Cancer pharmacogenomics studies provide valuable insights into disease progression and associations between genomic features and drug response. PharmacoDB integrates...
Cancer pharmacogenomics studies provide valuable insights into disease progression and associations between genomic features and drug response. PharmacoDB integrates multiple cancer pharmacogenomics datasets profiling approved and investigational drugs across cell lines from diverse tissue types. The web-application enables users to efficiently navigate across datasets, view and compare drug dose-response data for a specific drug-cell line pair. In the new version of PharmacoDB (version 2.0, https://pharmacodb.ca/), we present (i) new datasets such as NCI-60, the Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) dataset, as well as updated data from the Genomics of Drug Sensitivity in Cancer (GDSC) and the Genentech Cell Line Screening Initiative (gCSI); (ii) implementation of FAIR data pipelines using ORCESTRA and PharmacoDI; (iii) enhancements to drug-response analysis such as tissue distribution of dose-response metrics and biomarker analysis; and (iv) improved connectivity to drug and cell line databases in the community. The web interface has been rewritten using a modern technology stack to ensure scalability and standardization to accommodate growing pharmacogenomics datasets. PharmacoDB 2.0 is a valuable tool for mining pharmacogenomics datasets, comparing and assessing drug-response phenotypes of cancer models.
Topics: Databases, Genetic; Genomics; Humans; Pharmacogenetics; Pharmacogenomic Testing; Software
PubMed: 34850112
DOI: 10.1093/nar/gkab1084 -
Nurse Education Today Jun 2024Pharmacogenomics is the bioscience investigating how genes affect medication responses. Nurses are instrumental in medication safety. Pharmacogenomics is slowly being... (Review)
Review
BACKGROUND
Pharmacogenomics is the bioscience investigating how genes affect medication responses. Nurses are instrumental in medication safety. Pharmacogenomics is slowly being integrated into healthcare, and knowledge and understanding of it is now pertinent to nursing practice.
PURPOSE
This paper aims to map the scholarly literature on pharmacogenomics in relation to nurses.
METHODS
A scoping review was conducted in four databases: CINAHL, Embase (Ovid), ProQuest Health and Medicine and PubMed using the search terms pharmacogenomic*, pharmacogenetic*, PGx*, and nurs*, resulting in 263 articles of which 77 articles met the inclusion criteria.
FINDINGS
Most articles (85 %, n = 65) were non-empirical and 12 presented empirical data (15 %, n = 12). The articles were USA-centric (81 %, n = 62) and represented a broad range of nursing specialties.
CONCLUSION
The majority of scholarly literature on nurses and pharmacogenomics is narrative reviews. Further empirical research is warranted to investigate nurses' current knowledge levels and potential involvement with pharmacogenomics in clinical practice.
Topics: Humans; Pharmacogenetics; Nurses
PubMed: 38484442
DOI: 10.1016/j.nedt.2024.106153 -
Pharmacotherapy Sep 2017Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as... (Review)
Review
Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African Americans and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarin-related adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype-guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry. Despite differing frequencies of variants by race/ethnicity, most evidence in diverse populations evaluates variants that are most common in populations of European ancestry. Algorithms that do not include variants important across race/ethnic groups are unlikely to benefit diverse populations. In some race/ethnic groups, development of race-specific or admixture-based algorithms may facilitate improved genotype-guided warfarin dosing algorithms above and beyond that seen in individuals of European ancestry. These observations should be considered in the interpretation of literature evaluating the clinical utility of genotype-guided warfarin dosing. Careful consideration of race/ethnicity and additional evidence focused on improving warfarin dosing algorithms across race/ethnic groups will be necessary for successful clinical implementation of warfarin pharmacogenomics. The evidence for warfarin pharmacogenomics has a broad significance for pharmacogenomic testing, emphasizing the consideration of race/ethnicity in discovery of gene-drug pairs and development of clinical recommendations for pharmacogenetic testing.
Topics: Anticoagulants; Ethnicity; Humans; Pharmacogenetics; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Warfarin
PubMed: 28672100
DOI: 10.1002/phar.1982 -
Dialogues in Clinical Neuroscience Dec 2014It is timely to consider the ethical and social questions raised by progress in pharmacogenomics, based on the current importance of pharmacogenomics for avoidance of... (Review)
Review
It is timely to consider the ethical and social questions raised by progress in pharmacogenomics, based on the current importance of pharmacogenomics for avoidance of predictable side effects of drugs, and for correct choice of medications in certain cancers. It has been proposed that the entire population be genotyped for drug-metabolizing enzyme polymorphisms, as a measure that would prevent many untoward and dangerous drug reactions. Pharmacologic treatment targeting based on genomics of disease can be expected to increase greatly in the coming years. Policy and ethical issues exist on consent for large-scale genomic pharmacogenomic data collection, public vs corporate ownership of genomic research results, testing efficacy and safety of drugs used for rare genomic indications, and accessibility of treatments based on costly research that is applicable to relatively few patients. In major psychiatric disorders and intellectual deficiency, rare and de novo deletion or duplication of chromosomal segments (copy number variation), in the aggregate, are common causes of increased risk. This implies that the policy problems of pharmacogenomics will be particularly important for the psychiatric disorders.
Topics: Humans; Pharmacogenetics; Public Policy
PubMed: 25733960
DOI: 10.31887/DCNS.2014.16.4/egershon