Treatment of opioid-induced gut dysfunction

Abstract

Opioid analgesics are the mainstay in the treatment of moderate-to-severe pain, yet their use is frequently associated with adverse effects, the most common and debilitating being constipation. Opioid-induced motor stasis results from blockade of gastrointestinal peristalsis and fluid secretion, and reflects the action of the endogenous opioid system in the gut. Methylnaltrexone and alvimopan are new investigational drugs that selectively target peripheral μ-opioid receptors because they are poorly absorbed in the intestine and do not enter the brain. Clinical studies have proved the concept that these drugs prevent opioid-induced bowel dysfunction without interfering with analgesia. As reviewed in this article, opioid receptor antagonists with a peripherally restricted site of action also hold therapeutic promise in postoperative ileus and chronic constipation due to the fact that they have been found to stimulate intestinal transit.

Keywords::

• alvimopan
• constipation
• enteric nervous system
• intestinal peristalsis
• naloxone
• N-methylnaltrexone
• opioid peptides
• opioid-induced bowel dysfunction
• peripherally restricted opioid receptor antagonists
• prokinetic effects

Acknowledgements

Work in the author’s laboratory is supported by the Austrian Research Funds, the Austrian Federal Ministry of Education, Science and Culture, the Jubilee Funds of the Austrian National Bank and the Zukunftsfonds Steiermark.