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Clinical Pharmacology and Therapeutics Aug 2023Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of...
Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information. Moreover, current clinical recommendations for cardiovascular pharmacogenetics can be confusing because they are outdated, incomplete, or inconsistent. A myriad of misconceptions about the promise and feasibility of cardiovascular pharmacogenetics among healthcare providers also has halted clinical implementation. Therefore, the main goal of this tutorial is to provide introductory education on the use of cardiovascular pharmacogenetics in clinical practice. The target audience is any healthcare provider (or student) with patients that use or have indications for cardiovascular drugs. This tutorial is organized into the following 6 steps: (1) understand basic concepts in pharmacogenetics; (2) gain foundational knowledge of cardiovascular pharmacogenetics; (3) learn the different organizations that release cardiovascular pharmacogenetic guidelines and recommendations; (4) know the current cardiovascular drugs/drug classes to focus on clinically and the supporting evidence; (5) discuss an example patient case of cardiovascular pharmacogenetics; and (6) develop an appreciation for emerging areas in cardiovascular pharmacogenetics. Ultimately, improved education among healthcare providers on cardiovascular pharmacogenetics will lead to a greater understanding for its potential in improving outcomes for a leading cause of morbidity and mortality.
Topics: Humans; Pharmacogenetics; Cardiovascular Agents; Cardiovascular Diseases; Drug-Related Side Effects and Adverse Reactions; Health Personnel
PubMed: 37303270
DOI: 10.1002/cpt.2957 -
Clinical Pharmacology and Therapeutics Jan 2019Pharmacogenomics (PGx) can be seen as a model for biomedical studies: it includes all disease areas of interest and spans in vitro studies to clinical trials, while... (Review)
Review
Pharmacogenomics (PGx) can be seen as a model for biomedical studies: it includes all disease areas of interest and spans in vitro studies to clinical trials, while focusing on the relationships between genes and drugs and the resulting phenotypes. This review will examine different characteristics of PGx study publications and provide examples of excellence in framing PGx questions and reporting their resulting data in a way that maximizes the knowledge that can be built on them.
Topics: Humans; Periodicals as Topic; Pharmacogenetics; Terminology as Topic; Translational Research, Biomedical
PubMed: 30406943
DOI: 10.1002/cpt.1279 -
Drug Metabolism and Personalized Therapy Mar 2016Pharmacogenetics and pharmacogenomics (PGx) are rapidly growing fields that aim to elucidate the genetic basis for the interindividual differences in drug response. PGx... (Review)
Review
Pharmacogenetics and pharmacogenomics (PGx) are rapidly growing fields that aim to elucidate the genetic basis for the interindividual differences in drug response. PGx approaches have been applied to many anticancer drugs in an effort to identify relevant inherited or acquired genetic variations that may predict patient response to chemotherapy and targeted therapies. In this article, we discuss the advances in the field of cancer pharmacogenetics and pharmacogenomics, driven by the recent technological advances and new revolutionary massive sequencing technologies and their application to elucidate the genetic bases for interindividual drug response and the development of biomarkers able to personalize drug treatments. Specifically, we present recent progress in breast cancer molecular classifiers, cell-free circulating DNA as a prognostic and predictive biomarker in cancer, patient-derived tumor xenograft models, chronic lymphocytic leukemia genomic landscape, and current pharmacogenetic advances in colorectal cancer. This review is based on the lectures presented by the speakers of the symposium "Pharmacogenetics and Pharmacogenomics as Tools in Cancer Therapy" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society (SEFF), held in Madrid (Spain) on April 21, 2015.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Humans; Molecular Targeted Therapy; Neoplasms; Pharmacogenetics; Precision Medicine; Xenograft Model Antitumor Assays
PubMed: 26863347
DOI: 10.1515/dmpt-2015-0042 -
Clinical Biochemistry Sep 2014The experience of chronic pain is one of the commonest reasons individuals seek medical attention, making the management of chronic pain a major issue in clinical... (Review)
Review
OBJECTIVE
The experience of chronic pain is one of the commonest reasons individuals seek medical attention, making the management of chronic pain a major issue in clinical practice. Drug metabolism and responses are affected by many factors, with genetic variations offering only a partial explanation of an individual's response. There is a paucity of evidence for the benefits of pharmacogenetic testing in the context of pain management.
DESIGN AND METHODS
We reviewed the literature between 2000 and 2013, and references cited therein, using various keywords related to pain management, pharmacology and pharmacogenetics.
RESULTS
Opioids continue to be the mainstay of chronic pain management. Several non-opioid based therapies, such as treatment with cannabinoids, gene therapy and epigenetic-based approaches are now available for these patients. Adjuvant therapies with antidepressants, benzodiazepines or anticonvulsants can also be useful in managing pain. Currently, laboratory monitoring of pain management patients, if performed, is largely through urine drug measurements.
CONCLUSIONS
Drug half-life calculations can be used as functional markers of the cumulative effect of pharmacogenetics and drug-drug interactions. Assessment of half-life and therapeutic effects may be more useful than genetic testing in preventing adverse drug reactions to pain medications, while ensuring effective analgesia. Definitive, mass spectrometry-based methods, capable of measuring parent drug and metabolite levels, are the most useful assays for this purpose. Urine drug measurements do not necessarily correlate with serum drug concentrations or therapeutic effects. Therefore, they are limited in their use in monitoring efficacy and toxicity.
Topics: Adjuvants, Pharmaceutic; Analgesics, Opioid; Chronic Pain; Drug Interactions; Humans; Pain Management; Pharmacogenetics
PubMed: 24912048
DOI: 10.1016/j.clinbiochem.2014.05.065 -
Annual Review of Genomics and Human... Aug 2022Pharmacogenomic testing can be an effective tool to enhance medication safety and efficacy. Pharmacogenomically actionable medications are widely used, and approximately... (Review)
Review
Pharmacogenomic testing can be an effective tool to enhance medication safety and efficacy. Pharmacogenomically actionable medications are widely used, and approximately 90-95% of individuals have an actionable genotype for at least one pharmacogene. For pharmacogenomic testing to have the greatest impact on medication safety and clinical care, genetic information should be made available at the time of prescribing (preemptive testing). However, the use of preemptive pharmacogenomic testing is associated with some logistical concerns, such as consistent reimbursement, processes for reporting preemptive results over an individual's lifetime, and result portability. Lessons can be learned from institutions that have implemented preemptive pharmacogenomic testing. In this review, we discuss the rationale and best practices for implementing pharmacogenomics preemptively.
Topics: Genotype; Humans; Pharmacogenetics; Precision Medicine
PubMed: 35537468
DOI: 10.1146/annurev-genom-111621-102737 -
Journal of Human Genetics May 2020Increasing enthusiasm for clinical pharmacogenetic testing and the availability of pharmacogenetic-based guidelines indicate that pediatricians will increasingly be...
Increasing enthusiasm for clinical pharmacogenetic testing and the availability of pharmacogenetic-based guidelines indicate that pediatricians will increasingly be expected to interpret and apply pharmacogenetic test results into medical care. Previous studies have identified a lack of knowledge on pharmacogenetics across many physician specialties; however, this has not been systematically assessed among pediatricians. To evaluate pediatrician knowledge, attitude, and educational interest in pharmacogenetics, we surveyed physician cohorts from both the United States (U.S.) and Japan. A total of 282 pediatricians (210 from the U.S. and 72 from Japan) participated in an anonymous survey (online or hardcopy) on pharmacogenetics knowledge, perception, and education. Over 50% of all respondents had >10 years of clinical experience and >75% had some prior education in genetics. However, <10% felt they were familiar with pharmacogenetics, which was very consistent with <20% of the U.S. pediatricians correctly responding to a codeine/CYP2D6 pharmacogenetics knowledge question and <10% of U.S. pediatricians being aware of the Clinical Pharmacogenetics Implementation Consortium (CPIC). Despite being generally unfamiliar with pharmacogenetics, >80% of all respondents indicated that implementation of clinical pharmacogenetic testing will improve efficacy and safety, and that pediatricians should be capable of applying this testing to their practice. Moreover, the majority (83.1%) were interested in educational opportunities on pharmacogenetics, particularly on result interpretation and therapeutic recommendations. Taken together, these data indicate that although practical knowledge of pharmacogenetics among pediatricians in the U.S. and Japan is currently very low, their interest in clinical pharmacogenetics and related education is high, which will likely facilitate future implementation.
Topics: Adult; Female; Health Knowledge, Attitudes, Practice; Humans; Japan; Male; Middle Aged; Pediatricians; Pharmacogenetics; United States
PubMed: 31983733
DOI: 10.1038/s10038-020-0723-0 -
Trends in Pharmacological Sciences Oct 2022Recent advances in next-generation sequencing (NGS) have resulted in the identification of tens of thousands of rare pharmacogenetic variations with unknown functional... (Review)
Review
Recent advances in next-generation sequencing (NGS) have resulted in the identification of tens of thousands of rare pharmacogenetic variations with unknown functional effects. However, although such pharmacogenetic variations have been estimated to account for a considerable amount of the heritable variability in drug response and toxicity, accurate interpretation at the level of the individual patient remains challenging. We discuss emerging strategies and concepts to close this translational gap. We illustrate how massively parallel experimental assays, artificial intelligence (AI), and machine learning can synergize with population-scale biobank projects to facilitate the interpretation of NGS data to individualize clinical decision-making and personalized medicine.
Topics: Artificial Intelligence; High-Throughput Nucleotide Sequencing; Humans; Machine Learning; Pharmacogenetics; Precision Medicine
PubMed: 36008164
DOI: 10.1016/j.tips.2022.07.002 -
Dialogues in Clinical Neuroscience Dec 2014Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect... (Review)
Review
Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.
Topics: Antipsychotic Agents; Biomarkers; Humans; Pharmacogenetics; Precision Medicine; Psychotic Disorders
PubMed: 25733959
DOI: 10.31887/DCNS.2014.16.4/jpouget -
Pharmacogenomics Jan 2018To date, antiretroviral therapy is highly effective in HIV-affected patients, but the individualization of such a life-long therapy may be advised. This review briefly... (Review)
Review
To date, antiretroviral therapy is highly effective in HIV-affected patients, but the individualization of such a life-long therapy may be advised. This review briefly summarizes the main factors involved in the potential personalization of antiretroviral treatment. Relevant articles in English were identified by PubMed and recent congresses' abstracts. Foremost influences concerning pharmacodynamics, therapeutic drug monitoring, pharmacogenetics, comorbidities, immune recovery and viral characteristics affecting the healthcare of HIV-positive patients are listed here. Furthermore, pharmacoeconomic aspects are mentioned. Applying pharmacokinetic and pharmacogenetic knowledge may be informative and guide the better choice of treatment in order to achieve long-term efficacy and avoid adverse events. Randomized investigations of the clinical relevance of tailored antiretroviral regimens are needed in order to obtain a better management of HIV/AIDS-affected patients.
Topics: Anti-HIV Agents; Economics, Pharmaceutical; HIV Infections; Humans; Pharmacogenetics; Precision Medicine
PubMed: 29202676
DOI: 10.2217/pgs-2017-0123 -
Methods in Molecular Biology (Clifton,... 2022Pharmacogenetic testing in patients with cancer requiring cytotoxic chemotherapy offers the potential to predict, prevent, and mitigate chemotherapy-related toxicities.... (Review)
Review
Pharmacogenetic testing in patients with cancer requiring cytotoxic chemotherapy offers the potential to predict, prevent, and mitigate chemotherapy-related toxicities. While multiple drug-gene pairs have been identified and studied, few drug-gene pairs are currently used routinely in the clinical status. Here we review what is known, theorized, and unknown regarding the use of pharmacogenetic testing in cancer.
Topics: Humans; Neoplasms; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 36068461
DOI: 10.1007/978-1-0716-2573-6_4