Current pharmaceutical design
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In patients with stable and unstable coronary disease and those undergoing coronary stenting, the activation of platelets plays a central role in the occurrence of major thrombotic events such as death, myocardial infarction and stent thrombosis. Antiplatelet therapy for primary and secondary prevention of thromboembolic events is a cornerstone for the management of these patients and for many years the cyclooxygenase-1 (COX-1) inhibitor aspirin and the second generation thienopyridine clopidogrel which targets the ADP P2Y12 receptor on platelets served as the main antiplatelet agents for these indications. Clopidogrel in particular is very efficient in reducing ischemic cardiovascular events but exposes patients to an increased risk of bleeding. ⋯ As a result clopidogrel's long lasting monopole as the only antiplatelet agent in patients undergoing coronary stenting is currently challenged by the newer P2Y12 blockers such as prasugrel and ticagrelor, which provide a stronger and more consistent inhibition of platelets. In the setting of acute coronary syndromes, this more potent platelet inhibition led to less thrombotic events with these newer agents, but at the cost of a higher bleeding risk. This review provides an overview of the indication, dosage and duration of clopidogrel therapy and discusses its role in light of the recent introduction of newer P2Y12 receptor antagonists, the combination with newer oral anticoagulants such as dabigatran, apixaban and rivaroxaban as well as the emerging use of platelet function testing in clinical practice.
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Though general anesthetics have now been used clinically for well over a century, both their mechanisms of action as well as the nature of any potentially neurotoxic side effects remain elusive. With roughly 234 million people undergoing surgery each year worldwide, it remains imperative that any potentially deleterious effects of anesthetics be investigated and addressed. The issue of anesthetic- induced neurotoxicity in certain subsets of patients has continued to garner attention over the past decade, as more pre-clinical and clinical studies released are suggesting that inhalational and intravenous anesthetics may both cause and mitigate existing significant neuropathology. ⋯ Furthermore, retrospective studies continue to allude to the potential effects of surgery and anesthesia on cognitive trajectory, and more specifically, post-operative cognitive dysfunction (POCD) in the elderly. Studies to date regarding both of these clinical topics, however, are fraught with confounders, and many are underpowered statistically. The aim of this review is to examine the current data (both pre-clinical and clinical) on anesthetic-induced neurotoxicity and argue that further data are needed to either support or refute the potential connection between anesthetics and neurotoxicity.
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Review Randomized Controlled Trial
Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers.
Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately. ⋯ In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.
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Increasingly more Americans are being diagnosed with diabetes mellitus, and the number of those using the continuous subcutaneous insulin infusion pump (CSII), commonly known as the insulin pump, is on the rise. Although evidence is lacking on how best to manage insulin pump patients perioperatively, several individual or institutional approaches have been developed. Here we propose a comprehensive algorithm for perioperative glycemic management in insulin pump patients undergoing noncardiac surgery. Where applicable, we discuss the rationale behind the algorithm.
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The cornerstone of treating patients with shock remains as it has for decades, intravenous fluids. Surprisingly, dosing intravenous fluid during resuscitation of shock remains largely empirical. ⋯ However, overzealous fluid resuscitation has been associated with increased complications, increased length of intensive care unit (ICU) and hospital stay and increased mortality. This review focuses on methods to assess fluid responsiveness and the application of these methods for goal directed fluid therapy in critically ill and peri-operative patients.