Opioid-Induced Constipation: Pathophysiology & Disease Burden

David Wang, MD: Hello, and thank you for joining this Peer Exchange titled, “Management of Opioid-Induced Chronic Constipation.” Opioid-induced constipation [OIC] is a common adverse effect in patients undergoing long-term opioid therapy. Peripherally acting mu opioid receptor antagonists [PAMORAs] have an important place in the treatment of refractory OIC when traditional laxatives have not resulted in effective laxation. Our discussion today focuses on the need to understand how and when to best use these medications for the different indications in patients with advanced illness or chronic noncancer-related pain.

I am Dr David Wang, a palliative and emergency medicine specialist at Scripps Health in San Diego, California. Joining me today are Dr Stephen Anderson, an attending physician in emergency medicine at MultiCare Auburn Medical Center in Auburn, Washington; Dr Jeffrey Fudin, a clinical pharmacy specialist in pain management at the Stratton VA Medical Center in Albany, New York, an adjunct associate professor at the Albany College of Pharmacy and Health Sciences in Albany, New York, and the CEO of Remitigate, LLC, in Delmar, New York; Dr Richard Rauck, the president of the Carolinas Pain Institute and past president of the World Institute of Pain, the pain fellowship site director at Wake Forest School of Medicine, and the medical director at The Center for Clinical Research in Winston-Salem, North Carolina; Theresa Mallick-Searle, a nurse practitioner in the Division of Pain Medicine at Stanford Health Care in Stanford, California; and Brett Snodgrass, a palliative medicine clinical coordinator at Baptist Memorial Health Care and the owner and president of BBS Health Education, Inc, in Memphis, Tennessee.

Thank you all so much for joining us. Let’s begin. To start, Rick, I’d like to turn to you and ask you, can you tell me a little about the pathophysiology of opioid-induced constipation.

Richard Rauck, MD: Well, David, really in the simplest terms, you can think of OIC coming about from new activation of the opioid receptor. However, instead of thinking about it in the brain, where we knew the mu receptor provides analgesia when it’s activated, in the gut it produces constipation. And really what happens with activation of that receptor are 4 things, is how I think of it. One, it has negative effects on the pyloric and anal sphincters. Secondly, it decreases peristalsis in the gut. Thirdly, it increases absorption fluid from the gut, so it makes the stool harder. And fourth, it decreases secretions from the lumen of the gut too. Really, that’s the way it works. There’s nothing magical about the activation. We’re still talking about the same receptors really that provide analgesia in 1 place and in another place produce constipation.

David Wang, MD: Certainly, many people in the United States have chronic conditions that result in them using opioids and being at risk for opioid-induced constipation. Steve, tell me a little about the patient population that is most likely to be burdened with this.

Stephen Anderson, MD, FACEP: Well, we understand that opioids have been the hallmark for pain management for thousands of years. So for acute pain, that’s 1 question, postsurgical post trauma. What we’re really trying to talk about are the very real population that struggles with general chronic pain conditions. Those can be severe arthritis or other modes along those lines.

Cancer pain is a very special group that we’ll talk about today, particularly around palliative care needs and things along those lines. Anytime some of the risk factors for this exist, such as chronic immobilization; people who are bedbound, etc, are certainly at risk for this; and autoimmune disorders. I briefly alluded already to things like rheumatoid arthritis, which cause inflammatory components of all sorts.

Jeffrey Fudin, BS, PharmD, DAIPM, FCCP, FASHP, FFSMB: Steve, I’ve got a question. In the hospital setting, would you see PAMORAs, which we’re going to talk about later today, utilized in an inpatient setting for a short stay compared with chronic pain? For example, if a patient comes in for a Whipple procedure, and they’re there for several weeks, would you see that as a need to treat constipation and get the patient out of the hospital sooner?

Stephen Anderson, MD, FACEP: Well, working out of the emergency department, I can say that I do see people who are chronically on PAMORAs. I can stay that occasionally we start them in the emergency department now, where we didn’t even have this in our toolbox a few years ago. But once they’re admitted to the hospital, I think that there’s certainly a place for this. But we’re going to talk a little later about the whole toolbox and how you progress through it to prevent it from occurring.

David Wang, MD: Let’s talk a little about how this actually affects people’s lives and the symptom burden it causes. Brett, can you tell me a little about the patients who have this and what their life looks like living with this?

Brett B. Snodgrass, FNP-C, CPE, FACPP, FAANP: David, obviously we know it’s a problem. We oftentimes know that it’s an inverse correlation. As constipation increases, what we get is patients having less of a quality of life. When they begin using any treatments that are available to them, then they have to wait around and wonder when they’re going to have a bowel movement. So it really does change things.

Also, you could think economically that maybe they’re not going to work because they’re also having this constipation, they don’t feel good. So it changes economically. It really can affect the society in all reality. But we know that the quality of life changes. And with symptoms, what does it look like? That’s the key, because a lot of patients don’t even know—when we say the word constipation—truly what it is. And what we see is patients describe to us as straining to have a bowel movement. They describe to us incomplete evacuation: they get done, and they don’t feel like they went. All of those are triggers for us in assessing it, first off. As we’ll talk about moving forward, it truly affects patients’ quality of life. Cancer does, pain does, but then of course some of the adverse effects associated do as well.

Stephen Anderson, MD, FACEP: You know, Brett, I’ve got a really skewed view. The emergency departments are there 24-7-365 for when you need us, but sometimes it’s sort of a failure of the system when you have to land in the emergency department for your abdominal pain that could have possibly been recognized as you’re going to head down this pathway if you don’t address it. Time in the emergency department, I hope, is successful after you’re done. But nobody really wants to be there because of this.

Jeffrey Fudin, BS, PharmD, DAIPM, FCCP, FASHP, FFSMB: Brett, you mentioned a number of the issues with patients, but there’s also the anxiety associated with a patient who takes laxatives and keeps taking more laxatives, and now they’re fearful of leaving the house because they’re afraid they’re going to sort of have an explosion when they leave.

Brett B. Snodgrass, FNP-C, CPE, FACPP, FAANP: Exactly.

Jeffrey Fudin, BS, PharmD, DAIPM, FCCP, FASHP, FFSMB: I’ve seen a lot of patients anxious about that.

Brett B. Snodgrass, FNP-C, CPE, FACPP, FAANP: Going back to your point, oftentimes they don’t have the conversation with the provider. But also on our side, the providers aren’t having this conversation, so they wind up in your neck of the woods.

Stephen Anderson, MD, FACEP: I don’t like to admit the fact that a work-up in the emergency department is frequently more expensive than recognizing the problem prophylactically in the doctor’s office. But the simple fact is, if we get the CT [computed tomography] scans and other things like that for abdominal pain, it is more expensive.

Transcript edited for clarity.