Author: Jeffrey A. Gudin
Constipation happens universally in patients who are prescribed opioids. I’ve met a handful of patients over the years that don’t develop constipation from opioids and I always think the same thing. You’re not taking your drug. That’s how universal constipation is associated with opioids. Just as we have opioid receptors in the central nervous system we also have them in the peripheral nervous system, the myenteric plexus, which is scattered all throughout the intestines. When opioids bind to the receptors in the periphery like in the gut, they have a number of physiological effects. They slow down motility. The mass of stool stays still and gets bigger over time. More water is sucked out of the stool, out of the lumen and into the vascular of the intestines. So the stool gets more difficult to pass, causing constipation. Until now none of the agents that we used really targeted the cause of opioid induced constipation, the opioid receptor.
But a relatively new class of drug called PAMORA (peripherally acting mu-opioid receptor antagonist) have really revolutionized the way we treat opioid induced constipation. They only work in the periphery, they unblock those receptors in the GI tract, they help recovery of motility, they help recovery of fluid enhancement of the bulk of the stool. But the benefits of only working in the periphery are that they don’t enter into the central nervous system so they don’t cause any type of opioid withdrawal and most importantly, they don’t take away from the analgesic benefits of the original opioid.
Up until now the only agent we’ve had available is an injectable subcutaneous form of naltrexone called methylnaltrexone. But there are some oral agents that have been developed which are hopefully close to approval so that patients will not have to inject themselves over time to treat the side effects of their analgesics.