Pharmacotherapy
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Percutaneous mechanical circulatory support (MCS) devices, including the intraaortic balloon pump, Impella, and TandemHeart, are often used for hemodynamic support in the setting of refractory cardiogenic shock. The thrombotic and bleeding complications associated with these devices is well recognized, and the Impella and TandemHeart devices have unique anticoagulation considerations that may influence patient outcomes. Both devices typically require use of a heparinized purge solution in combination with intravenous unfractionated heparin, thereby providing multiple sources of heparin exposure. ⋯ This review provides an overview of percutaneous MCS devices commonly used in the acute management of left ventricular failure, with an emphasis on pharmacologic considerations. We review recent evidence and guidelines and provide recommendations for appropriate use of anticoagulation during device support. Approaches to managing heparinized purge solutions, monitoring, and the utility of nonheparin anticoagulants are also provided because high-quality evidence in the literature is limited.
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The history of capital punishment in the United States is long and controversial. In many cases, lethal injection has brought medical personnel, ethically and professionally charged with preserving life, into the arena of assisting the state in taking life. U. ⋯ Others have resorted to using compounding pharmacies and enacting tougher execution secrecy laws to protect the identities of those involved in the process. Professional organizations representing health care team members, including nursing, medicine, and pharmacy, among others, have roundly denounced the medicalization of capital punishment. Legal challenges continue to mount at all levels, leading to an uncertain future for lethal injection.
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Pharmacologic options for venous thromboembolism (VTE) prophylaxis are often limited in critically ill patients due to thrombocytopenia and multisystem organ dysfunction. Fondaparinux offers potential advantages in the critically ill; however, it is currently contraindicated in severe renal dysfunction (SRD). We evaluated anti-factor Xa levels in critically ill patients with SRD who were receiving an extended interval dosing regimen of fondaparinux for VTE prophylaxis. ⋯ In critically ill patients with SRD, an extended interval fondaparinux dosing regimen of 2.5 mg every 48 hours for VTE prophylaxis achieved peak and trough anti-factor Xa levels similar to those reported in noncritically ill patients with normal renal function receiving once-daily fondaparinux. This regimen offers an alternative for patients with SRD when heparinoids must be avoided.
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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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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.