Expert Perspectives in the Management of Opioid Induced Constipation - Episode 8
William F. Peacock, MD; Conar Fitton, MD; and Neel Mehta, MD, review the rationale for the use of μ-opioid receptor agonists for the treatment of opioid-induced constipation.
William F. Peacock, MD: What’s the rationale for using μ [opioid μ receptor] agonists for opioid-induced constipation?
Neel Mehta, MD: The μ receptor is involved in pain, and treatment of pain involves opioids at times. Activity on a μ receptor then triggers the pain relief that we’re hoping for. But the μ receptor isn’t present only in the nervous system. It’s also present in other areas, including the gut. The activity there unfortunately leads to what Conar was eloquently talking about in terms of the development of constipation.
If we could find a molecule or drug that acted on that particular aspect without reversing the analgesia in the ED [emergency department] with Narcan, how well suited could that be? This takes the miracle that you just talked about and adds another thing to it. That methyl group prevents the crossing of the blood brain barrier of naltrexone to keep people with their analgesic, have pain relief, and reverse the constipation adverse effect. This has been proven in many studies, where you don’t see any change in pain scores or any signs of significant withdrawal when patients were given this drug compared with placebo. That’s what I try to highlight. I say, “These are the 3 or 4 mechanisms of why you’re having constipation, and this class of medication has been useful in reversing that.”
Conar Fitton, MD: What Neel said is such a key point, too. Going back to what patients understand and the percentage of what we say that’s understood, we try to say it in layman’s terms, but they aren’t going to hear the whole mechanism. They’re going to hear, “This is why the other ones didn’t work, and the doctor was able to tell me why.” But if you don’t tell them that it isn’t going to affect their pain relief, they won’t take it if they think that it’s going to somehow block their ability to get relief from their chronic pain.
The other thing, too, which I highlight anecdotally from giving someone a subcutaneous injection in the office 1 time, is that while it may not work in 60 seconds, the data are pretty impressive with how fast it can work. A lot of the data were looking at what percentage of patients will have bowel movements within a 4-hour period. If you look at it more closely, a significant percentage of the patients who responded were having them within 2 hours, and a significant percentage of patients have them within 30 minutes.
We use the subcutaneous methylnaltrexone in our hospital the most frequently, and I warn the nurses that after you give this, you have to be ready, especially if someone just had surgery and can’t be very mobile. The patient will oftentimes have a bowel movement within 30 minutes, and they’re going to need help. Or it can happen within 2 hours. Although it may not be 60 seconds, it’s a very effective way to reverse that mechanism on the gut for a significant percentage of patients.
William F. Peacock, MD: The mechanism of action of methylnaltrexone is such a cool story of designer medication manipulation. You take a drug that worked well for what it did, and now it can’t get in the brain, so it takes care of only the colon. It’s the best thing ever.
Conar Fitton, MD: It’s competitive antagonism of the same receptor, patients can understand that. You don’t have to get too pharmacologic. They’ll understand when you talk to them about that. Hopefully that will increase compliance.
William F. Peacock, MD: I’ve told them, “We’re going to put your colon into narcotic withdrawal,” and they think that’s cool.
Neel Mehta, MD: That’s interesting. We all have a story from perhaps early in our careers of using subcutaneous methylnaltrexone and having our office never be the same.
Conar Fitton, MD: That’s correct.
William F. Peacock, MD: There are several of these drugs in this class. Methylnaltrexone has a home in the ED because, like you said, a majority of patients will be able to defecate within an hour. We published a trial about a year ago. In that trial, 61%, which is a big number when you consider this disease, had a rescue-free laxation. They went to the bathroom on their own, did their business, and were done. That’s good, because the 4-hour number is the ED number for: “I have to decide whether to discharge you or admit you. But after 4 or 5 hours, I can’t have you hanging out in the ED.” A drug that works with that speed is an ED drug.
Transcript Edited for Clarity