Opioid-induced bowel dysfunction

Opioid analgesics are commonly prescribed for moderate to severe pain. Opioids exert effects via receptors in the central and enteric nervous systems. Thus, central opioid analgesia can be limited by side effects involving the gastrointestinal tract, particularly by gastrointestinal motility delay. Opioid-induced bowel dysfunction is commonly treated with bulking agents, stimulant laxatives, lubiprostone, and tegaserod (removed from the market in March 2007). However, these treatments' efficacy in opioid bowel dysfunction has not been proven. Recent research has focused on developing peripheral μ opioid antagonists such as methylnatrexone and alvimopan. These drugs selectively block μ opioid receptors in the enteric nervous system without penetrating the blood-brain barrier and can avert adverse gastrointestinal symptoms of opioids without reducing central analgesia. Methylnaltrexone and alvimopan also reduce hospitalization duration in surgical patients with postoperative ileus. A second line of research has focused on peripheral κ opioid agonists that modulate nociception in the enteric nervous system without producing central nervous system side effects. Asimadoline and fedotozine reduce nociceptive reflexes caused by gut distention and improve pain symptoms in patients with irritable bowel syndrome. ADL 10-0101 (Adolor Corp., Exton, PA) is another peripheral κ opioid agonist that lowers pain scores in patients with chronic pancreatitis. Although peripheral κ opioid agonists are promising, clinical studies are needed to assess their efficacy in treating opioid-induced bowel dysfunction.