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One or more keywords matched the following properties of IMPROVING OF CARE BY REVERSAL OF OPIOID CONSTIPATION
abstract Morphine and other opioids are widely used analgesics in advanced cancer patients, and constipation is the most common treatment-associated side effect of opioid pain medications. Conventional measures for opioid-induced constipation are often insufficient, and constipation becomes a limiting factor in opioid use and opioid dose in these patients. A significant number of hospice patients receiving chronic opioids for pain would rather endure their pain than face the severe incapacitating constipation that opioids cause. Thus, opioid-induced constipation, a symptom secondary to the treatment, has a significant negative impact on the quality of life of these terminal patients. Palliative care and end of life management practices have received insufficient attention in the past, and the need to enhance palliative care of dying patients has become apparent in this country. In this proposed project, the efficacy of a novel peripheral opioid receptor antagonist, methylnaltrexone, in the treatment of chronic opioid-induced constipation, will be evaluated. Specific Aim 1 and 2 studies will utilize a clinical pharmacology approach (Phase II/III trials) to evaluate the efficacy and dose-response of intravenous and oral methylnaltrexone in reversing chronic opioid-induced gut motility changes and constipation in methadone addicts and patients with advanced malignant conditions. These trials will be randomized, double-blind, placebo-controlled studies. In these studies, the oral-cecal transit time will be measured using the lactulose hydrogen breath test, and positive laxation response and opioid analgesic effect will be evaluated. In addition, subjective visual analog scale (VAS) scores for constipation, stool frequency and consistency, and "overall well being" will be recorded. Pharmacokinetic data will also be collected. In these studies, mechanisms underlying opioid gastrointestinal pharmacology in humans, an issue that has not been addressed before, will be investigated, since translation of data from previous animal experiments to humans may be problematic due to differences in the physiology of the opioid systems. Bringing methylnaltrexone, the first selective peripheral opioid receptor antagonist, to clinical application will be a significant advance in palliative care. Successful completion of this project will lead to a number of future studies in which other applications of methylnaltrexone, as well as its mechanisms of action of both opioids and their antagonism in humans, can be explored.
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