Pharmacotherapy
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The topic of precision medicine is increasingly more prevalent in the general medical literature, with oncology research leading the way. Many factors, such as availability of targeted drugs, advances in laboratory science, and improved information systems, converged to make precision medicine research possible on a large scale at the National Cancer Institute. The resultant big data will spur new kinds of research in the decades to come, but until then, all clinicians are challenged to make sense of an overabundance of information when managing individual patients.
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Interindividual variability in response to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, with regard to both efficacy and safety is an obvious target for pharmacogenetic research. Many genes have been identified as possible contributors to variability in statin response and safety. Genetic polymorphisms may alter the structure or expression of coded proteins, with potential impacts on lipid and statin absorption, distribution, metabolism, and elimination as well as response pathways related to the pharmacologic effect. ⋯ In this review article, we provide a statin-based summary of available evidence describing pharmacogenetic associations that may be of clinical relevance in the future. Although currently available studies are often small or retrospective, and may have conflicting results, they may be useful in providing direction for future confirmatory studies and may point to associations that could be confirmed in the future when more patient outcomes-based studies are available. We also summarize the clinically relevant evidence currently available to assist clinicians with providing personalized pharmacotherapy for patients requiring statin therapy.
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Despite advances in technology and guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) that focus on how to use pharmacogene test results, hurdles remain that have delayed the widespread application of pharmacogenomics in clinical practice. These hurdles include a lack of prospective randomized controlled trials to address the utility of pharmacogenomics on clinical outcomes, what the clinical algorithm for pharmacogenomics should be, and whether pharmacogenomics is cost-effective. However, the implementation of clinical practice guidelines, such as those from professional organizations, is commonplace and often termed the application of evidence-based medicine. ⋯ Food and Drug Administration-approved labeling recommendations and the evidence supporting recommendations from CPIC. Although many clinical practice guideline recommendations are supported by the results of randomized controlled clinical trials, we cite examples of common clinical practices that are supported by levels and types of evidence similar to the evidence supporting many of the CPIC recommendations. Specifically, we discuss clinical recommendations for guidance related to drug-drug interactions, drug-gene interactions, therapeutic range selection, and dosage adjustments based on patient-specific factors within the context of a select set of cardiovascular therapeutic topics.
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Right ventricular failure (RVF) after cardiac transplant (CTX) or implantation of a continuous-flow left ventricular assist device (CF-LVAD) is associated with significant postoperative morbidity and mortality. A variety of modalities have been used to treat postoperative RVF, including management of volume status, intravenous inotropes and vasodilators, and right-sided mechanical support. Inhaled vasodilator agents are a unique treatment option aimed at minimizing systemic absorption by delivering therapy directly to the pulmonary vasculature. ⋯ Based on our assessment of the literature, we suggest that when RVF occurs in the setting of a normal pulmonary vascular resistance (PVR), traditional inotropic therapy (e.g., dobutamine) should be used. Conversely, if the PVR is elevated (> 250 dynes/sec/cm5 or 3 Wood units), or the patient has other evidence of a high right ventricular afterload (i.e., a transpulmonary gradient > 12 mm Hg), then an inhaled pulmonary vasodilator would be the preferred initial pharmacologic agent. Drug selection depends largely on the institution's capacity to safely prepare and administer the medication, along with formulary considerations, such as the high costs associated with inhaled iloprost and inhaled nitric oxide.
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Review
Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women.
Pregnant women with opioid use disorder can be treated with methadone, buprenorphine, or naltrexone to reduce opioid use and improve retention to treatment. In this review, we compare the pregnancy outcomes of methadone, buprenorphine, and naltrexone in clinical trials and discuss the potential behavioral and developmental effects of these agents seen in offspring in animal studies. Important clinical considerations in the management of opioid use disorder in pregnant women and their infants are also discussed. ⋯ Naltrexone is not a first-line treatment primarily because both detoxification and an opioid-free period are required. More research is needed to determine naltrexone safety and benefits in pregnant women. Animal studies suggest that changes in pain sensitivity, developmental processes, and behavioral responses may occur in children born to mothers receiving methadone, buprenorphine, or naltrexone and is an area that warrants future studies.