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Pharmacological Research Aug 2019Natural products have represented attractive alternatives for disease prevention and treatment over the course of human history and have contributed to the development... (Review)
Review
Natural products have represented attractive alternatives for disease prevention and treatment over the course of human history and have contributed to the development of modern drugs. These natural products possess beneficial efficacies as well as adverse efffects, which vary largely among individuals because of genetic variations in their pharmacokinetics and pharmacodynamics. As with other synthetic chemical drugs, the dosing of natural products can be optimized to improve efficacy and reduce toxicity according to the pharmacogenetic properties. With the emergence and development of pharmacogenomics, it is possible to discover and identify the targets/mechanisms of pharmacological effects and therapeutic responses of natural products effectively and efficiently on the whole genome level. This review covers the effects of genetic variations in drug metabolizing enzymes, drug transporters, and direct and indirect interactions with the pharmacological targets/pathways on the individual response to natural products, and provides suggestions on dosing regimen adjustments of natural products based on their pharmacokinetic and pharmacogenetic paratmeters. Finally, we provide our viewpoints on the importance and necessity of pharmacogenetic and pharmacogenomic research of natural products in natural medicine's rational development and clinical application of precision medicine.
Topics: Biological Products; Biological Transport; Humans; Pharmacogenetics
PubMed: 31129178
DOI: 10.1016/j.phrs.2019.104283 -
Therapeutic Drug Monitoring Apr 2021Drug-induced hematological disorders constitute up to 30% of all blood dyscrasias seen in the clinic. Hematologic toxicity from drugs may range from life-threatening... (Review)
Review
Drug-induced hematological disorders constitute up to 30% of all blood dyscrasias seen in the clinic. Hematologic toxicity from drugs may range from life-threatening marrow aplasia, agranulocytosis, hemolysis, thrombosis to mild leukopenia, and thrombocytopenia. Pathophysiologic mechanisms underlying these disorders vary from an extension of the pharmacological effect of the drug to idiosyncratic and immune-mediated reactions. Predicting these reactions is often difficult, and this makes clinical decision-making challenging. Evidence supporting the role of pharmacogenomics in the management of these disorders in clinical practice is rapidly evolving. Despite the Clinical Pharmacology Implementation Consortium and Pharmacogenomics Knowledge Base recommendations, few tests have been incorporated into routine practice. This review aims to provide a comprehensive summary of the various drugs which are implicated for the hematological adverse events, their underlying mechanisms, and the current evidence and practical recommendations to incorporate pharmacogenomic testing in clinical care for predicting these disorders.
Topics: Biomarkers; Drug-Related Side Effects and Adverse Reactions; Hematologic Diseases; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 33235023
DOI: 10.1097/FTD.0000000000000842 -
Current Drug Metabolism 2016Human genome sequencing highlights the involvement of genetic variation towards differential risk of human diseases, presence of different phenotypes, and response to... (Review)
Review
Human genome sequencing highlights the involvement of genetic variation towards differential risk of human diseases, presence of different phenotypes, and response to pharmacological elements. This brings the field of personalized medicine to forefront in the era of modern health care. Numerous recent approaches have shown that how variation in the genome at single nucleotide level can be used in pharmacological research. The two broad aspects that deal with pharmacological research are pharmacogenetics and pharmacogenomics. This review encompasses how these variations have created the basis of pharmacogenetics and pharmacogenomics research and important milestones accomplished in these two fields in different diseases. It further discusses at length their importance in disease diagnosis, response of drugs, and various treatment modalities on the basis of genetic determinants.
Topics: Animals; Biomedical Research; Dose-Response Relationship, Drug; Humans; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomic Variants
PubMed: 27494310
DOI: 10.2174/1389200217666160804150959 -
Current Opinion in Lipidology Dec 2016Randomized clinical outcome trials are costly, long, and often yield neutral or modestly positive results, and these issues have impeded cardiovascular drug development... (Review)
Review
PURPOSE OF REVIEW
Randomized clinical outcome trials are costly, long, and often yield neutral or modestly positive results, and these issues have impeded cardiovascular drug development in the past decade. Despite the significant reduction of cardiovascular morbidity and mortality with statins, substantial residual risk of major cardiovascular events remains. This could be because of the difficulty of demonstrating benefits of new drugs in addition to the current standard of care in unselected populations as well as the interindividual variability in drug response. Pharmacogenomics is a promising avenue for the development of novel or failed drugs and for the repurposing of other medications.
RECENT FINDINGS
Several variants were identified in genes that were associated with the effects of statins on plasma lipids. Genomic studies of mutations in genes that encode drug targets have the potential to inform on the link between drug therapy acting on those targets and clinical outcomes. Recently, ADCY9 gene variants were shown to be significantly associated with responses to dalcetrapib in terms of clinical outcomes, atherosclerosis imaging, cholesterol efflux, and inflammation, which provided support for the conduct of a new prospective clinical trial in a genetically determined population.
SUMMARY
Pharmacogenomics hold great potential in future lipid trials to decrease failure rates in drug development and to identify patients who will respond with greater benefits and smaller risk.
Topics: Clinical Trials as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipid Metabolism; Pharmacogenetics; Precision Medicine; Treatment Outcome
PubMed: 27676198
DOI: 10.1097/MOL.0000000000000351 -
Expert Review of Pharmacoeconomics &... Dec 2017Pharmacogenomic testing has the potential to greatly benefit patients by enabling personalization of medication management, ensuring better efficacy and decreasing the... (Review)
Review
Pharmacogenomic testing has the potential to greatly benefit patients by enabling personalization of medication management, ensuring better efficacy and decreasing the risk of side effects. However, to fully realize the potential of pharmacogenomic testing, there are several important issues that must be addressed. Areas covered: In this expert review we discuss current challenges impacting the implementation of pharmacogenomic testing in the clinical practice. We emphasize issues related to testing methods, reporting of the results, test selection, clinical interpretation of the results, cost-effectiveness, and the long-term use of pharmacogenomic results in clinical practice. We identify opportunities and future directions to facilitate clinical implementation. Expert commentary: Several key elements are necessary to optimally integrate pharmacogenomic testing into clinical practice. Collaborative efforts among laboratories are needed to improve standardization of testing and reporting of the results. Clinicians need educational opportunities to improve understanding of which test to order and how to interpret the results. The electronic health records and other clinical systems need to improve their storage of the pharmacogenomics test results and interoperability to facilitate the use of clinically actionable results to improve patient care.
Topics: Cooperative Behavior; Cost-Benefit Analysis; Drug-Related Side Effects and Adverse Reactions; Electronic Health Records; Humans; Patient Care; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 28949250
DOI: 10.1080/14737167.2017.1385395 -
Clinical Pharmacology and Therapeutics May 2018A number of barriers exist for adoption of pharmacogenomics into practice. Physicians, pharmacists, and nurses report limited knowledge about pharmacogenomics and its...
A number of barriers exist for adoption of pharmacogenomics into practice. Physicians, pharmacists, and nurses report limited knowledge about pharmacogenomics and its use in patient care. Lack of pharmacogenomics education curricula as part of professional schools or postgraduate training programs has been reported as a potential cause. Understanding pharmacogenomics is further complicated by a complex and nonstandard lexicon, limited medication guidelines, rapidly changing evidence, and insufficient awareness of test availability and utility.
Topics: Curriculum; Education, Pharmacy; Health Knowledge, Attitudes, Practice; Humans; Patient Care; Pharmacists; Pharmacogenetics; Physicians; Professional Role
PubMed: 29417560
DOI: 10.1002/cpt.1019 -
American Journal of Health-system... Dec 2016The development and implementation of a multidisciplinary pharmacogenomics clinic within the framework of an established community-based medical genetics program are... (Review)
Review
PURPOSE
The development and implementation of a multidisciplinary pharmacogenomics clinic within the framework of an established community-based medical genetics program are described.
SUMMARY
Pharmacogenomics is an important component of precision medicine that holds considerable promise for pharmacotherapy optimization. As part of the development of a health system-wide integrated pharmacogenomics program, in early 2015 Northshore University Health-System established a pharmacogenomics clinic run by a multidisciplinary team including a medical geneticist, a pharmacist, a nurse practitioner, and genetic counselors. The team identified five key program elements: (1) a billable-service provider, (2) a process for documentation of relevant medication and family histories, (3) personnel with the knowledge required to interpret pharmacogenomic results, (4) personnel to discuss risks, benefits, and limitations of pharmacogenomic testing, and (5) a mechanism for reporting results. The most important program component is expert interpretation of genetic test results to provide clinically useful information; pharmacists are well positioned to provide that expertise. At the Northshore University HealthSystem pharmacogenomics clinic, patient encounters typically entail two one-hour visits and follow a standardized workflow. At the first visit, pharmacogenomics-focused medication and family histories are obtained, risks and benefits of genetic testing are explained, and a test sample is collected; at the second visit, test results are provided along with evidence-based pharmacotherapy recommendations.
CONCLUSION
A multidisciplinary clinic providing genotyping and related services can facilitate the integration of pharmacogenomics into clinical care and meet the needs of early adopters of precision medicine.
Topics: Community Health Planning; Community Pharmacy Services; Genetic Testing; Humans; Patient Care Team; Pharmacogenetics; Precision Medicine; Professional Role
PubMed: 27864203
DOI: 10.2146/ajhp160072 -
American Journal of Health-system... Dec 2016The process and methods used by payers when evaluating coverage of personalized medicine testing are described. (Review)
Review
PURPOSE
The process and methods used by payers when evaluating coverage of personalized medicine testing are described.
SUMMARY
Personalized medicine encompasses a number of diagnostic tools that measure drug metabolism, genetic risk for disease development, and tumor type or markers that can guide oncology treatments. However, whole genome testing, tumor marker testing, and testing for drug metabolism are additional costs to the healthcare system. In order to justify these costs, payers and health technology assessment bodies must evaluate the individual tests or groups of tests on their own merits. In order for a test to be covered by payers, test developers must demonstrate clinical utility as measured by improved outcomes or well-informed decision-making. In the United States, payers generally focus on clinical benefit to individual patients and benefits to the healthcare system. Clinical benefits include improved outcomes. Benefits to the healthcare system are generally considered to be cost offsets, which may be due to reductions in the use of unnecessary interventions or to more efficient use of resources. Provider organizations have been assuming more responsibility and liability for healthcare costs through various risk arrangements, including accountable care organizations and patient-centered medical homes. Diagnostic tests that increase efficiency, reduce unnecessary interventions, and improve outcomes will be chosen by specialists in provider organizations.
CONCLUSION
For personalized medicine approaches to be adopted and covered by health plans, the methods must be shown to be analytically and clinically valid and provide clinical utility at a reasonable level of cost-effectiveness to payers.
Topics: Humans; Insurance, Health, Reimbursement; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 27864208
DOI: 10.2146/ajhp160038 -
Cardiovascular Drugs and Therapy Feb 2018There is growing interest in the use of pharmacogenomics to optimize the safety and efficacy of anticoagulation therapy. While the pharmacogenomics of warfarin have been... (Review)
Review
PURPOSE
There is growing interest in the use of pharmacogenomics to optimize the safety and efficacy of anticoagulation therapy. While the pharmacogenomics of warfarin have been well-studied, the pharmacogenomics of direct oral anticoagulants (DOACs) continue to be a fledgling, but growing, field of interest. We present a pertinent clinical review of the present state of research on the pharmacogenomics of DOACs.
METHODS AND RESULTS
The present article is a review of pertinent clinical and scientific research on the pharmacogenomics of DOACs between January 2008 and December 2017 using MEDLINE and the United States National Institutes of Health Clinical Trials Registry. Many studies have identified single-nucleotide polymorphisms (SNPs) in genes responsible for DOAC metabolism that impacted serum DOAC concentration but had uncertain clinical significance.
CONCLUSIONS
As such, there is currently no strong evidence for the use of pharmacogenomic testing in optimizing the safety and efficacy of DOAC therapy. Nonetheless, genes of interest have been identified for each DOAC that may be of potential clinical utility. Further research is currently underway to elucidate the value of pharmacogenomics in this increasingly prescribed therapy.
Topics: Administration, Oral; Anticoagulants; Biotransformation; Clinical Decision-Making; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Phenotype; Polymorphism, Single Nucleotide; Precision Medicine; Risk Factors; Treatment Outcome
PubMed: 29435777
DOI: 10.1007/s10557-018-6774-1 -
Gene Nov 2019Individual specific variable drug response against similar drugs raises a significant challenge for the effective and safe treatment of many human diseases.... (Review)
Review
Individual specific variable drug response against similar drugs raises a significant challenge for the effective and safe treatment of many human diseases. Pharmacogenomics is the branch which try to deal with these challenge by relating drug response to patient specific genome in order to better customize patient treatments. Pharmacogenomics based research focus on the whole genome, but since last few years after realizing the importance, it mainly centralized towards genes of pharmacological importance called pharmacogenes, and try to explore association between their variants and variable drug response in world's different population. This research was initiated with the resulted data from human genome based research projects and later on assisted by exome sequencing projects. Simultaneously, it was boost-up with the participation of various pharmacogenomics groups lead by PGRN. By realizing the significance of pharmacogenes, and their variant related information, in health science, scientific communities are already started to look for genes of pharmacogenomics importance with different aspect. This article aims to provide an inclusive insight on current state of knowledge of pharmacogenes, recent trends and progress in the understanding of the pharmacogenes and the implications for personalized medicine.
Topics: Genome, Human; Humans; Pharmacogenetics; Precision Medicine
PubMed: 31425740
DOI: 10.1016/j.gene.2019.144050