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Current Neuropharmacology 2016There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in... (Review)
Review
There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs. Although many classes of epigenetic drugs are being investigated, at present most attention is being paid to two classes of epigenetic drugs: drugs that inhibit DNA methyltransferase (DNMTi) and drugs that inhibit histone deacetylase (HDACi). This paper discusses the potential use of epigenetic drugs in the treatment of MS, focusing on DNMTi and HDACi. Preclinical drug trials of DNMTi and HDACi for the treatment of MS are showing promising results. Epigenetic drugs could improve the clinical management of patients with MS.
Topics: Animals; Clinical Trials as Topic; Epigenesis, Genetic; Histone Deacetylase Inhibitors; Humans; Multiple Sclerosis; Pharmacogenetics
PubMed: 26813117
DOI: 10.2174/1570159x13666150211001600 -
Pharmacogenetics and Genomics Mar 2014The number and use of pharmacogenetic tests to assess a patient's likelihood of response or risk of an adverse event is expanding across medical specialties and becoming... (Comparative Study)
Comparative Study Review
The number and use of pharmacogenetic tests to assess a patient's likelihood of response or risk of an adverse event is expanding across medical specialties and becoming more prevalent. During this period of development and translation, different approaches are being investigated to optimize delivery of pharmacogenetic services. In this paper, we review pre-emptive and point-of-care delivery approaches currently implemented or being investigated and discuss the advantages and disadvantages of each approach. The continued growth in knowledge about the genetic basis of drug response combined with development of new and less expensive testing technologies and electronic medical records will impact future delivery systems. Regardless of delivery approach, the currently limited knowledge of health professionals about genetics generally or PGx specifically will remain a major obstacle to utilization.
Topics: Electronic Health Records; Evidence-Based Medicine; Genetic Testing; Humans; Pharmacists; Pharmacogenetics
PubMed: 24384556
DOI: 10.1097/FPC.0000000000000028 -
Pharmacogenomics Jul 2021Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare... (Review)
Review
Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare professional and student education is strong and there are multiple opportunities in the state for learners to gain workforce skills and develop advanced competency in PGx. Implementation planning is occurring at several organizations and others have incorporated structured utilization of PGx into routine workflows. Laboratory-based and translational PGx research in Minnesota has driven important discoveries in several therapeutic areas. This article reviews the state of PGx activities in Minnesota including educational programs, research, national consortia involvement, technology, clinical implementation and utilization and reimbursement, and outlines the challenges and opportunities in equitable implementation of these advances.
Topics: Biomedical Research; Education, Pharmacy, Graduate; Health Personnel; Humans; Minnesota; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 34137665
DOI: 10.2217/pgs-2021-0058 -
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 -
Clinical Pharmacology and Therapeutics Sep 2021Pharmacogenetics (PGx) seeks to enable selection of the right dose of the right drug for each patient to optimize therapeutic outcomes. Most PGx focuses on... (Review)
Review
Pharmacogenetics (PGx) seeks to enable selection of the right dose of the right drug for each patient to optimize therapeutic outcomes. Most PGx focuses on pharmacokinetics (PKs), due to our relatively advanced understanding of the genes involved in PKs and the causative effects of variants in those genes. Genetic variants can also affect pharmacodynamics (PDs), but relatively few PGx-PD associations have been identified. This is partially due to a more limited understanding of the relevant genes and the consequences of genetic variation, but is also due in part to the potential confounding of PK variability in assessments of clinical outcomes that have a contribution from both PKs and PDs. For example, it is challenging to confirm the effect of mu opioid receptor (OPRM1) genetic variation on opioid response due to the contribution of CYP2D6 genotype to bioactivation of some opioid drugs (i.e., codeine and tramadol). The objectives of this mini-review are to describe several recent efforts to discover and validate PGx-PD that disentangle the influence of PK variability and propose potential approaches that could be used in future PGx-PD analyses. We use the effect of OPRM1 genetics on opioid response to illustrate how these analyses could be conducted and conclude by discussing how PGx-PD could be translated into clinical practice to improve therapeutic outcomes.
Topics: Analgesics, Opioid; Genetic Variation; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Receptors, Opioid, mu
PubMed: 34043820
DOI: 10.1002/cpt.2312 -
Discovery Medicine Aug 2011Inter-individual variation in drug response and adverse drug reactions (ADRs) are well known in medicine. This individual variation in drug response could be at least,...
Inter-individual variation in drug response and adverse drug reactions (ADRs) are well known in medicine. This individual variation in drug response could be at least, in part, due to genetic diversity among individuals. Although substantial studies that connect genetic variants to inter-individual variation in drug response have been documented in several diseases such as cancer and heart diseases, such studies are slowly progressing in ophthalmology. In recent years, advancement in technologies has led to the identification of genes associated with several eye disorders. At the same time, some small-scale studies have demonstrated the association of various genotypes or haplotypes with response to drug therapies. However, its integration into clinical practice in ophthalmology is not possible at present. This is because there are many challenging questions that remain to be addressed. For instance, in the case of complex disorders a single gene study is not enough. Multiple genes, environmental factors, multiple single nucleotide polymorphisms (SNPs), and rare or low frequency variants may contribute to the disease and they must be considered. The functional aspects of many genetic variants are not known. This raises questions of their biological importance and their clinical usefulness. In addition, there are legal, ethical, and social issues that need to be regulated. Moreover, physicians and patients must be educated about the limitation and sensitivity of genetic testing. At present pharmacogenetic studies in ophthalmology are still in their infancy and do not suggest that a pharmacogenetic basis of drug development in ophthalmology is a concept that can yield immediate results, but can become a reality in the future. In this article an attempt has been made to summarize some of the recent small-scale pharmacogenetic studies on two major eye disorders, age-related macular degeneration (AMD) and glaucoma.
Topics: Genetic Predisposition to Disease; Glaucoma; Humans; Macular Degeneration; Ophthalmology; Pharmacogenetics
PubMed: 21878193
DOI: No ID Found -
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 -
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 -
BMJ (Clinical Research Ed.) Apr 2000
Review
Topics: Drug Hypersensitivity; Forecasting; Genome, Human; Humans; Pharmacogenetics; Polymorphism, Genetic
PubMed: 10753155
DOI: 10.1136/bmj.320.7240.987 -
Genes Sep 2022Since the beginning of pharmacology, several variations in responses to drugs have been recorded [...].
Since the beginning of pharmacology, several variations in responses to drugs have been recorded [...].
Topics: Humans; Pharmacogenetics
PubMed: 36140743
DOI: 10.3390/genes13091575