Development of peripheral opioid antagonists' new insights into opioid effects.
ABSTRACT The recent approval by the US Food and Drug Administration of 2 medications--methylnaltrexone and alvimopan--introduces a new class of therapeutic entities to clinicians. These peripherally acting mu-opioid receptor antagonists selectively reverse opioid actions mediated by receptors outside the central nervous system, while preserving centrally mediated analgesia. Methylnaltrexone, administered subcutaneously, has been approved in the United States, Europe, and Canada. In the United States, it is indicated for the treatment of opioid-induced constipation in patients with advanced illness (eg, cancer, AIDS) who are receiving palliative care, when response to laxative therapy has not been sufficient. Alvimopan, an orally administered medication, has been approved in the United States to facilitate recovery of gastrointestinal function after bowel resection and primary anastomosis. Clinical and laboratory studies performed during the development of these drugs have indicated that peripheral receptors mediate other opioid effects, including decreased gastric emptying, nausea and vomiting, pruritus, and urinary retention. Laboratory investigations with these compounds suggest that opioids affect fundamental cellular processes through mechanisms that were previously unknown. These mechanisms include modifications of human immunodeficiency virus penetration, tumor angiogenesis, vascular permeability, and bacterial virulence.
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ABSTRACT: Background and aims. Postoperative pain control is extremely important for both patients and surgeons; in this context, long-acting local anesthesia can play an important role after open reduction of maxillofacial fractures. The purpose of this study was to evaluate the effect of bilateral mental nerve block with bupivacaine on postoperative pain control in mandibular symphyseal fractures. Materials and methods. Fifty patients with pure mandibular symphyseal fractures were studied in two control and study groups. In contrast to the control group, the study group received bilateral mental nerve block with bupivacaine postoperatively. Patients were examined in relation to pain severity and opioid analgesic drug need sequences. Results. The study group needed significantly less opioid than the control group (P<0.01, U=141). The control and study groups were different in first opioid administration time. The control and study groups received first opioid dose in 0-2 and 2-4 hours, respectively. Conclusion. Bilateral mental nerve blocks with bupivacaine can reduce opioid analgesic need and it has a positive effect on postoperative pain control in mandibular symphyseal fractures.Journal of Dental Research, Dental Clinics, Dental Prospects 09/2014; 8(3):172-5. DOI:10.5681/joddd.2014.031
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ABSTRACT: Pain is a hallmark of sickle cell disease (SCD) and its treatment remains challenging. Opioids are the major family of analgesics that are commonly used for treating severe pain. However, these are not always effective and are associated with the liabilities of their own. The pharmacology and multiorgan side effects of opioids are rapidly emerging areas of investigation, but there remains a scarcity of clinical studies. Due to opioid-induced endothelial-, mast cell-, renal mesangial-, and epithelial-cell-specific effects and proinflammatory as well as growth influencing signaling, it is likely that when used for analgesia, opioids may have organ specific pathological effects. Experimental and clinical studies, even though extremely few, suggest that opioids may exacerbate existent organ damage and also stimulate pathologies of their own. Because of the recurrent and/or chronic use of large doses of opioids in SCD, it is critical to evaluate the role and contribution of opioids in many complications of SCD. The aim of this review is to initiate inquiry to develop strategies that may prevent the inadvertent effect of opioids on organ function in SCD, should it occur, without compromising analgesia.01/2015; 2015:1-10. DOI:10.1155/2015/540154
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ABSTRACT: Although opioids offer potent analgesia for severe acute and chronic noncancer pain, adverse gastrointestinal effects potentially undermine their clinical utility. In particular, between 40% and 95% of patients develop opioid-induced constipation (OIC). Therefore, there is a consensus that patients should commence laxatives at the start of opioid therapy and continue throughout treatment. Nevertheless, laxatives are not routinely coprescribed with opioids. Even when concurrent laxatives are prescribed, approximately half the patients treated for OIC do not achieve the desired improvement. Moreover, laxatives do not target the underlying cause of OIC (opioid binding to the μ -receptors in the enteric system) and as such are not very effective at managing OIC. The failure of lifestyle modification and laxatives to treat adequately many cases of OIC led to the concurrent use of peripherally acting opioid antagonists (such as methylnaltrexone bromide and naloxone) to reduce the incidence of gastrointestinal adverse events without compromising analgesia. Judicious use of the various options to manage OIC should allow more patients to benefit from opioid analgesia. Therefore, this paper reviews the causes, consequences, and management of OIC to help clinicians optimise opioid analgesia.Gastroenterology Research and Practice 05/2014; 2014:141737. DOI:10.1155/2014/141737 · 1.50 Impact Factor