Current pharmaceutical design
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Opioids induce respiratory depression via activation of μ-opioid receptors at specific sites in the central nervous system including the pre-Bötzinger complex, a respiratory rhythm generating area in the pons. Full opioid agonists like morphine and fentanyl affect breathing with onset and offset profiles that are primarily determined by opioid transfer to the receptor site, while the effects of partial opioid agonists such as buprenorphine are governed by transfer to the receptor site together with receptor kinetics, in particular dissociation kinetics. Opioid-induced respiratory depression is potentially fatal but may be reversed by the opioid receptor antagonist naloxone, an agent with a short elimination half-life (30 min). ⋯ Such agents include ampakines and serotonin agonists which are aimed at selectively enhancing central respiratory drive. A novel approach is aimed at the reduction of respiratory depression from opioid-activation of (micro-)glia cells in the pons and brainstem using micro-glia cell stabilizers. Since this approach simultaneously enhances opioid analgesic efficacy it seems an attractive alternative to the classical reversal strategies with naloxone.
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Review
Prevention of non-immune mediated transfusion-related acute lung injury; from blood bank to patient.
Transfusion-related acute lung injury (TRALI) is a severe form of pulmonary insufficiency induced by transfusion. TRALI is the leading cause of transfusion-related death, and is caused by the infusion of either anti-leukocyte antibodies in plasma containing blood products or neutrophil priming substances that accumulate during storage of cellular blood products. ⋯ In this review, the accumulation of these different substances during storage, as well as their mode of action in inducing TRALI are discussed. In addition, different improvements in current blood banking procedures to prevent TRALI due to these non-immune mediators will be proposed.
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The alpha-2 agonist dexmedetomidine is being increasingly used for sedation and as an adjunctive agent during general and regional anesthesia. It is used in a number of procedures and clinical settings including neuroanesthesia, vascular surgery, gastrointestinal endoscopy, fiberoptic intubation, and pediatric anesthesia. ⋯ However, the drug frequently produces hypotension and bradycardia, and also decreases cerebral blood flow without concomitantly decreasing the cerebral metabolic rate for oxygen. This review discusses recent advances in the use of dexmedetomidine in anesthesia and intensive care settings, as well as discuss potential problems with its use.
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Treatment of chronic lymphocytic leukemia (CLL) has recently undergone revolutionary changes. Two large randomized trials demonstrated superiority of chemoimmunotherapy combining fludarabine and cyclophosphamide with monoclonal anti-CD20 antibody rituximab (FCR) over fludarabine and cyclophosphamide (FC) alone in first line and relapse; this lead to establishment of FCR regimen as new gold standard in younger and physically fit patients. However, elderly and/or comorbid patients may not tolerate such aggressive approach due to high risk of unacceptable toxicity. ⋯ Highdose steroids combined with rituximab might be a promising in relapsed/refractory CLL but infectious toxicity is serious. Finally, ofatumumab has been recently approved for the treatment of fludarabine and alemtuzumab-refractory patients. This article provides an overview of the current and future possibilities in the treatment of elderly and comorbid patients with CLL.
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The operating room offers a unique setting where anesthetics, preoperative medications, patient comorbidities, and surgery all merge. Anesthesiologists are responsible for combining these concerns into a dependable and safe approach. From formulation to administration, enhancements in nearly every aspect of a given drug have improved the ability of anesthesiologists to accomplish this. ⋯ On May 1, 2012, a report issued by the Institute of Medicine advised the United States Food and Drug Administration to undertake a much more rigorous patient-centered effort to evaluate a drug's safety over its entire life-cycle. This recommendation is in agreement with the objectives of the Anesthesia Patient Safety Foundation. With these mutual goals shared by many stakeholders and their continued efforts, the future of the estimated 200 million global surgeries to be undertaken this year hopefully provides a safer experience while under anesthesia.