Treatment of opioid-induced gut dysfunction.

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 mu-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.