Drugs
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Chronic pain represents one of the most important public health problems and, in addition to classical analgesics, antidepressants are an essential part of the therapeutic strategy. This article reviews available evidence on the efficacy and safety of antidepressants in major chronic pain conditions; namely, neuropathic pain, headaches, low back pain, fibromyalgia, irritable bowel syndrome (IBS) and cancer pain. Studies, reviews and meta-analyses published from 1991 to March 2008 were retrieved through MEDLINE, PsycINFO and the Cochrane database using numerous key words for pain and antidepressants. ⋯ The efficacy of the newer serotonin and norepinephrine reuptake inhibitors is less supported by evidence, but can be recommended in neuropathic pain, migraines and fibromyalgia. To date, evidence does not support an analgesic effect of serotonin reuptake inhibitors, but beneficial effects on well-being were reported in several chronic pain conditions. These results are discussed in the light of current insights in the neurobiology of pain, the reciprocal relationship between pain and depression, and future developments in this field of research.
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*A new formulation of the nonselective NSAID diclofenac sodium suitable for intravenous bolus injection has been developed using hydroxypropyl beta-cyclodextrin as a solubility enhancer (HPbetaCD diclofenac). * HPbetaCD diclofenac intravenous bolus injection was shown to be bioequivalent to the existing parenteral formulation of diclofenac containing propylene glycol and benzyl alcohol as solubilizers (PG-BA diclofenac), which is relatively insoluble and requires slow intravenous infusion over 30 minutes. * Single-dose HPbetaCD diclofenac 3.75, 9.4, 18.75, 25, 37.5, 50 and 75 mg administered by intravenous bolus injection produced significantly greater responses than placebo for total pain relief (TOTPAR) over 6 hours or pain intensity at 4 hours in the treatment of moderate or severe postoperative dental pain in randomized, double-blind trials. HPbetaCD diclofenac 37.5 and 75 mg were similar in efficacy to intravenous bolus ketorolac 30 mg. * In a well controlled trial, single-dose HPbetaCD diclofenac 75 mg intravenous bolus injection was shown to be superior to PG-BA diclofenac 75 mg intravenous infusion with respect to TOTPAR over 4 hours, indicating faster onset of analgesia in the treatment of moderate or severe postoperative dental pain. Both HPbetaCD diclofenac and PG-BA diclofenac were superior to placebo. * HPbetaCD diclofenac was generally well tolerated during single-dose treatment of postoperative pain. The tolerability profile was similar to that of PG-BA diclofenac, but with a lower incidence of thrombophlebitis.
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The past decade has witnessed significant progress in the management of invasive aspergillosis. Potent, relatively non-toxic antifungal drugs, data on early chest CT scanning and the availability of a non-invasive diagnostic test (serum galactomannan) are the key advances; among these, the contribution of the recently available drugs is the most significant. Safer and earlier intervention resulting in reduced mortality and improved outcome is being demonstrated. ⋯ Reports of emergence of less-susceptible Aspergillus spp. during azole therapy are of concern and close monitoring is needed. Remarkably, the era of polyenes appears to be nearing the end in the therapy of invasive aspergillosis. The promise of newer classes of drugs, immune-modulating therapies and vaccines are exciting future additions to the arsenal against invasive aspergillosis.
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Sildenafil citrate (Revatio), an inhibitor of phosphodiesterase type 5 (PDE5), is approved for use in the US, Europe and other countries for the treatment of pulmonary arterial hypertension (PAH). Oral sildenafil 20 mg three times daily added to conventional background therapy was significantly more effective than placebo at increasing exercise capacity in patients with idiopathic PAH or PAH associated with connective tissue diseases or repaired congenital systemic-to-pulmonary shunts. ⋯ Sildenafil provides benefits in terms of exercise capacity when added to epoprostenol; however, these findings come from a trial that did not use the approved dosage of sildenafil. In conclusion, sildenafil is an effective oral treatment option for patients with PAH.
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Alvimopan, a trans-3,4-dimethyl-4-(3-hydroxy-phenyl) piperidine, is a selective, peripherally acting micro-opioid receptor antagonist that is available for short-term use in hospitalized patients who have undergone bowel resection. The efficacy of alvimopan in the management of postoperative ileus has been evaluated in five phase III trials; four conducted in North America and one conducted in Europe/Australasia. Patients who had undergone partial large or small bowel resection surgery with primary anastomosis were randomized to receive alvimopan 12 mg or placebo as a single oral pre-operative dose followed by twice-daily administration for up to 7 days postoperatively. ⋯ In the phase III trials conducted in North America, the time to writing the hospital discharge order was 13-21 hours sooner with alvimopan than with placebo. Alvimopan did not reduce opioid-induced analgesia and/or increase the amount of opioids administered postoperatively. Short-term alvimopan was generally well tolerated in adults undergoing bowel resection.