A cohesive overview of the classes of agents used to treat patients with opioid-induced constipation.
David Wang, MD: We certainly talked a lot about how to diagnose this important underrecognized issue and the nuance of approaching the conversation and involving the entire interdisciplinary team. I'd like to shift our focus now and talk about the treatment options for opioid-induced constipation [OIC]. I'll start, Rick, by turning to you and asking you to give us a sense of the environment treatment landscape.
Richard Rauck, MD: Thanks, David. We already talked a little about lifestyle changes. I'm going to skip over that, the increased fluids that are really important still. Of the 3 things I think of, at least the classes of how to approach this, the first is simple over-the-counter/OTC drugs. I think it was brought out earlier, and it's fair. Several comments that were made by my fellow panelists that if you have a really high bowel function index, maybe these aren't going to work. There are patients for whom OTCs do work, and even patients who are on opioids. Obviously we haven't had peripherally acting mu-opioid receptor antagonists (PAMORAs) that long. During my practice and lifetime, OTCs are what we often had to do, and they do work in some folks. Some people will tell you that has taken care of it.
I do think in a lot of our patients it's appropriate to start with those drugs. Also, those drugs we know; they've been around a long time. There are many of them in the class. Senna is one. Bisacodyl is another. Sometimes it's worth trying a couple in the class, because not all patients respond the same, in my experience.
The second thing is what I'll call secretagogues, and those are drugs that are really lubricants, and lubiprostone fits into that, a very good drug in that way. It does not work directly on the receptor for opioid-induced constipations. I think we have to be clear that while it can help, it's, again, not a direct antagonist to the problem of opioid-induced constipation.
And then certainly the other class of drugs, at least when the OTCs fail for me, or maybe a secretagogue in addition, are the PAMORAs. PAMORA is an acronym that stands for peripherally acting mu receptor opioid antagonist. Those drug are the new ones that have come about, and they are peripherally restricted, that specifically reverse the effects we started the whole conversation with, and it happens when the mu opioid receptor is activated in the gut.
I know we'll talk more about those, but they have been very effective. I think the reason is that they attack the problem at the source, which is what the opioid does when it negatively impacts the mu receptor in the enteric plexus of the gastrointestinal tract.
David Wang, MD: Jeff, as our pharmacology expert, do you have anything to add to that?
Jeffrey Fudin, BS, PharmD, DAIPM, FCCP, FASHP, FFSMB: Yes, I think it's important that we recognize that the PAMORAs, and actually the secretagogues as well, are not laxatives. They are not laxatives, right? That's important. They are more for prevention. Of the secretagogues, the lubiprostone is the only one of the two of them that actually has an FDA approval for OIC.
As Rich pointed out, they do not work specifically at this site of the problem. That doesn't mean they won't work. I mean, lubiprostone is a chloride channel 2 agonist, and it will cause lubrication. But the problem is actually caused by the opioid combining with the mu receptor, and the PAMORAs specifically have a higher finish for that receptor and prevent the opioid from binding. To me that makes a lot of sense pharmacologically. There are not a lot of drugs that are really sort of an antidote to a problem. And that is the case here. It actually blocks the problem from happening. I think that's really important. We'll talk a little later about the specific differences among the PAMORAs.
Richard Rauck, MD: I think I'd add to that, Jeff, as we said, it's not that these don't always exist completely separate from one another. Sometimes when the PAMORAs may not be as effective as we hope, we don't realize that there is this underlying idiopathic component. Sometimes we want to combine lubiprostone with a PAMORA. I don't think we do that routinely. I don't think we need to routinely, but certainly that has helped me with some of the really refractory cases. Also, it just points that you can use these, even OTCs and PAMORAs, together occasionally when one isn't enough.
Stephen Anderson, MD, FACEP: From a simple clinician's point of view, I have to say, I think it's absolutely fascinating that they're peripheral blockers; that this has nothing to do with blocking the central mu receptor, so it doesn't get in the way of pain management. We'll talk about that in a little bit.
To me, that's fascinating that the pharmacologist can figure out how to do that.
David Wang, MD: A very important point to make, Steve. Thank you.