PAMORAs: What They Are, How They Work, and Why They Matter for Gut Health

When you take opioids for pain, they don’t just quiet your nerves—they slow down your gut. That’s where PAMORAs, peripheral mu-opioid receptor antagonists that block opioid effects in the digestive tract without affecting pain relief. Also known as peripherally acting mu-opioid receptor antagonists, these drugs are designed to fix one problem—constipation—without undoing the pain control you need. Unlike regular laxatives that just push things along, PAMORAs target the root cause: opioids binding to receptors in your intestines and freezing your bowel movements.

PAMORAs like methylnaltrexone, naloxegol, and naldemedine are used by people on long-term opioid therapy—whether for chronic pain, cancer, or post-surgery recovery. They’re not for occasional constipation. They’re for when your pain meds are doing their job too well, leaving you stuck. These drugs work by sitting on the opioid receptors in your gut, stopping the opioids from slowing digestion, while leaving brain receptors untouched. That’s why you don’t lose pain relief. You just get your bowels back.

They’re not magic. Side effects like abdominal pain, diarrhea, or nausea can happen. And they won’t help if your constipation comes from something else—low fiber, dehydration, or other meds. But for opioid-induced constipation, they’re one of the few tools that actually match the problem. If you’re on opioids and have been struggling with bowel issues, PAMORAs might be the missing piece. Below, you’ll find real comparisons and practical guides on how these drugs stack up against other treatments, what to watch for, and how to talk to your doctor about options that fit your life.