Current pharmaceutical design
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Postoperative nausea and vomiting (PONV) are distressing and frequent adverse events of anesthesia and surgery, with a relatively high incidence after laparoscopic cholecystectomy. Numerous antiemetics have been studied for the prevention and treatment of PONV in patients scheduled for laparoscopic cholecystectomy. Traditional antiemetics, including anticholinergics (e.g., scopolamine), antihistamines (e.g., dimenhydrinate), phenothiazines (e.g., promethazine), butyrophenones (e.g., droperidol), and benzamide (e.g., metoclopramide), are used for the control of PONV. ⋯ The efficacy of a combination of serotonin receptor antagonists (ondansetron and granisetron) and droperidol is superior to monotherapy with a serotonin receptor antagonist or droperidol. Similarly, adding dexamethasone to ondansetron or granisetron improves antiemetic efficacy in PONV. Knowledge regarding antiemetics is necessary to completely prevent and treatment of PONV in patients scheduled for laparoscopic cholecystectomy.
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Spinal cord injuries (SCI) result in a devastating loss of function below the level of the lesion in which there are variable motor recoveries and, in the majority of cases, central neuropathic pain syndromes (CNP) develop several months to years following injury. Unfortunately, the study of chronic pain after SCI has been neglected in the past due in part to the lack of good animal models but largely due to the clinically held dogma that CNP is not a real phenomenon and is psychogenic in nature rather than based on described pathophysiological mechanisms. The purpose of this article is to offer standardized terminology of pain, insight into animal modeling issues of CNP, descriptions of current clinical therapies and to discuss the pathophysiological mechanisms that provide the substrate for CNP that will lead to innovative new therapies. It is hoped that this information will give insight for research strategies as well as better care not only of SCI individuals, but is generalizable to many other CNP syndromes.
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In most mammals purine degradation ultimately leads to the formation of allantoin. Humans lack the enzyme uricase, which catalyzes the conversion of uric acid to allantoin. The resulting higher level of uric acid has been hypothesized to play a role as an antioxidant. ⋯ The mechanisms by which MSU crystals lead to an acute inflammatory arthritis are under investigation and current knowledge is reviewed here. Treatment of gout includes management of acute flares with anti-inflammatory medications such as non-steroidal anti-inflammatory drugs or corticosteroids and long term management with urate-lowering therapy when indicated. Future directions in the treatment of gout, in part guided by a better understanding of pathophysiology, are discussed.
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Opiates lack potent analgesic efficacy in neuropathic pain although it is now generally accepted that the poor effect of these drugs reflects a reduction in their potency. Reduction of morphine antinociceptive potency was postulated to be due to the fact that nerve injury altered the activity of opioid systems or opioid specific signaling. ⋯ Opioid peptides biosynthesis and opioid receptors density in the nociceptive pathways and their functions change under various conditions associated with neuropathic pain following damage to the spinal cord and injury of peripheral nerves. Identification of a role of opioid systems in neuropathic pain and molecular and cellular mechanisms underlying these processes are of importance to understanding of the opioid action in neuropathic pain that will hopefully facilitate development of therapeutic strategies in which effectiveness of opioids in alleviation neuropathic pain is increased.
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Levosimendan is a new calcium sensitizer developed for the treatment of congestive heart failure. Experimental studies indicate that levosimendan increases myocardial contractility and dilates both the peripheral and coronary vessels. Its positive inotropic effect is based on calcium-dependent binding of the drug to cardiac troponin C. ⋯ The most common adverse events associated with levosimendan treatment are headache and hypotension, as a likely consequence of the vasodilating properties of the compound. In conclusion, levosimendan offers a new effective option for the treatment of acutely decompensated heart failure. Unlike traditional inotropes, levosimendan seems also to be safe in terms of morbidity and mortality.