Current pharmaceutical design
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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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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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Hypertension is the most common medical disorder during pregnancy. Approximately 70 percent of women diagnosed with hypertension during pregnancy will have gestational hypertension-preeclampsia. The term gestational hypertension-preeclampsia is used to describe a wide spectrum of patients who may have only mild elevation in blood pressure to those with severe hypertension with various organ dysfunctions (acute gestational hypertension, preeclampsia, eclampsia, and the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). ⋯ Treatment of mild gestational hypertension with antihypertensive medications has not been shown to improve outcome, however, in cases of severe disease treatment has been shown to be beneficial. The purpose of this review is to discuss the different treatment modalities used in the hypertensive disorders of pregnancy. Management strategies will not be discussed.
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Subtypes of tetrodotoxin resistant voltage-gated sodium channels are involved in the development of certain types of neuropathic pains. After nerve injury hyperexcitability and spontaneous firing develop at the site of injury and also in the dorsal root ganglion cell bodies. This hyperexcitability results at least partly from accumulation of sodium channels at the site of injury. ⋯ Its use is limited by the fact that it cannot be administered orally. An oral local anesthetic type sodium channel blocker, mexiletine is an antiarrhythmic agent that is effective in neuropathic pain. However, effective doses may be difficult to achieve because of adverse effects.
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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.