Opioid antagonists in the treatment of gastrointestinal motility disorders

Opioids are commonly used during anaesthesia, as part of sedative regimes in intensive care units, and for chronic pain management. However, opioids impair gastrointestinal motility by activation of intestinal p-receptors and may lead to nausea, vomiting, constipation, disturbed enteral feeding, increased gastric reflux, aspiration and nosocomial pneumonia. Different strategies may be used to selectively block the intestinal effects of opioids without interfering with the analgesic effects and to enhance gastrointestinal motility. Enteral naloxone,has a low systemic bioavailability and does not substantially affect systemic antinociception as long as hepatic first-pass capacity is not exceeded. Enteral or parenteral Methylnaltrexone does not cross the blood-brain barrier, and Alvimopan shows limited enteral absorption after enteral administration. Both mechanisms result in an inhibition of gastrointestinal opioid effects without impairment of antinociception. However, neither Methyinaltrexone nor Alvimopan are commercially available yet. Most published studies reported on enteral naloxone in chronic pain patients with opioid-associated constipation. The majority of these studies observed an increase of gastrointestinal motility parameters. In these studies, single doses below 12 mg of naloxone did not appear to cause systemic side effects or to interfere with ongoing pain management. Methylnaltrexone was successfully used to reduce constipation during methadone maintenance. In the fields of anaesthesia and intensive care, respectively, the selective gastrointestinal receptor blockade by naloxone has been investigated in only one controlled, double-blind trial so far. In critically ill patients who received fentanyl for analgesia, enteral naloxone reduced gastric reflux and the incidence of pneumonia. Postoperatively, Alvimopan has been shown to improve gastrointestinal recovery. In conclusion, selective antagonism of intestinal opioid receptors might be a cost-effective, simple - and possibly preventive - treatment of opioid-associated gastrointestinal motility disorders. To date, enteral application of naloxone is the most extensively studied strategy and currently the only available treatment option.