Current pharmaceutical design
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Patients with nonvalvular atrial fibrillation (AF) and risk factors for stroke need anticoagulation to avoid thromboembolic complications. Vitamin K antagonists (VKAs) are an established pharmacological group the use of which is recommended by guidelines. ⋯ New oral anticoagulants are intended to replace warfarin, being at least as safe and effective, and lacking some of the disadvantages of VKAs. Clinical data for dabigatran, rivaroxaban, apixaban and edoxaban, and other new drugs, are discussed in this article with special focus on their use in nonvalvular AF.
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Wnt/β-catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/β-catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, β-catenin, serves several cellular functions. ⋯ However, β-catenin levels and their effects on transcriptional programs are also influenced by multiple other factors including hypoxia, inflammation, hepatocyte growth factor-mediated signaling, and the cell adhesion molecule E-cadherin. The broad implications of Wnt/β-catenin signaling in development, in the adult body and in disease render the pathway a prime target for pharmacological research and development. The intricate regulation of β-catenin at its various locations provides alternative points for therapeutic interventions.
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Chronic pain is usually treated with pharmacological measures using opioids alone or in combination with adjuvant analgesics that play an important role in the treatment of pain not fully responsive to opioids administered alone, especially in neuropathic, bone and visceral colicky pain. The important part of the chronic pain treatment is the appropriate use of non-pharmacological measures along with psychosocial and spiritual support. Opioids may be administered by different routes; the most common and most convenient for majority of treated patients are oral and transdermal. ⋯ Recently, more patients have been treated with short-acting opioids for breakthrough pain with sublingual, buccal and intranasal routes of opioid administration that may provide efficacy superior to oral and comparable to intravenous routes. Alternative routes comprise rectal, inhaled and topical administration of opioids. This article discusses various routes of opioid administration.
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Management of pain, agitation, and delirium is a complex process requiring a multimodal approach to optimize patient outcomes. Dexmedetomidine is a centrally acting alpha-2 agonist with sedative and analgesic properties that has demonstrated efficacy in managing pain, agitation, and delirium in a variety of critically ill patient populations. ⋯ However, dexmedetomidine therapy has also been associated with adverse cardiovascular events including hypotension, bradycardia, and asystole. The clinical pharmacology, therapeutic efficacy, safety considerations, controversies, and future directions of dexmedetomidine therapy in the ICU setting will be discussed.
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Cardiac events occur in 1% to 5% of patients undergoing non-cardiac surgery. Myocardial ischemia and nonfatal myocardial infarction constitute the most significant risk factors for mortality and cardiovascular morbidity, in patients with coronary artery disease. Perioperative b- blockade has been reported to reduce the risk of perioperative cardiac complications. ⋯ However, patients with extensive preoperative ischemia were at high risk of perioperative cardiac complications, despite b-blocker therapy. Conversely, perioperative b-blocker therapy did not reduce the incidence of cardiac complications in patients without clinical risk factors. While, the safety and effectiveness of perioperative b-blockers in intermediate-risk patients, still remain a debatable issue.