Time Stamps

  • 02:26 Pearl 1: High-Yield Reversible Causes of Constipation
  • 09:03 Pearl 2: Deep Dive into Fiber, Hydration and Bulk-Forming Laxatives
  • 15:06 Pearl 3: Osmotic and Stimulant Laxatives
  • 25:39 Pearl 4: Suppositories and Enemas
  • 34:05 Pearl 5: Opioid Induced Constipation

CME-MOC

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Show Notes

Pearl 1: High-Yield Reversible Causes and Complications of Constipation

    • There are two types of constipation: 
      • Primary constipation/Chronic idiopathic constipation: diagnosed using the Rome IV criteria 
        • Patients must have two or more of the following for the last 3 months with symptom onset at least 6 months prior to diagnosis:
          • Straining during more than ÂŒ (25%) of defecations
          • Lumpy or hard stools more than ÂŒ (25%) of defecations
          • Sensation of incomplete evacuation more than ÂŒ (25%) of defecations
          • Sensation of anorectal obstruction/blockage more than ÂŒ (25%) of defecations
          • Manual maneuvers to facilitate more than ÂŒ (25%) of defecations (e.g., digital evacuation, support of the pelvic floor)
          • Fewer than three SBM per week
          • Loose stools are rarely present without the use of laxatives
          • Insufficient criteria for irritable bowel syndrome
      • Secondary constipation: which can be remembered using the mnemonic LMNOP
    • Lifestyle: 
      • Patients who are bedbound or immobile, those with eating disorders and those with low fiber and water intake are at a higher risk of constipation
    • Metabolic: 
      • Hypercalcemia, hypokalemia, hypomagnesemia and hypothyroidism can contribute to constipation
    • Neurologic: 
      • Ensure that patients with neurologic dysfunction (e.g. spinal cord defects, history of CVA, dementia, Parkinson disease, multiple sclerosis) have aggressive bowel regimens on admission
    • Obstructive:
      • Consider structural causes of constipation including anal or intestinal strictures and obstructive tumors
    • Pharmacologic
      • Prescribed medications which are common offenders are antipsychotics, anticholinergics, narcotics, calcium channel blockers, tricyclic antidepressants
      • Over-the-counter medications including iron supplements, aluminum containing drugs, calcium supplements, antacids and antihistamines

Pearl 2: Deep Dive into Fiber, Hydration and Bulk-Forming Laxatives

    • Fruits vs Psyllium
      • Dried plums or prunes have been shown to be more effective for reducing constipation that psyllium 
      • Kiwi may slightly increase stool frequency compared to psyllium
    • Fiber Supplementation (Psyllium, methylcellulose)
      • Mode of action: increases stool weight which can reduce transit time, increase water collection and bacterial mass from fermentation
      • Although there is evidence showing that soluble fibers (E.g. psyllium, inulin, oatmeal) improve constipation, the evidence for insoluble fiber (E.g. wheat bran) is inconsistent.  
      • Psyllium should be taken at least 2 hours before or after other medications (e.g. levothyroxine, calcium supplements, zinc supplements) as it can reduce their absorption
    • Hydration 

Pearl 3: Osmotic and Stimulant Laxatives

Pearl 4: Suppositories and Enemas

    • Suppository vs enema 
      • A suppository is a small solid capsule and an enema is a liquid medication
    • Types of enemas 
      • Osmotic enemas: sodium phosphate enema, glycerine enema, lactulose enema
      • Lubricating enemas: mineral oil enema
      • Hypotonic enemas: tap water enema, soap sud enema
    • Considerations
      • Sodium phosphate enemas can cause electrolyte abnormalities, especially in elderly patients and those with renal dysfunction 
      • Mineral oil enemas require patient retention
      • Discuss what is most comfortable for the patient
      • Discuss timing and preparation with your nursing colleagues

Pearl 5: Opioid Induced Constipation

    • Mode of action of opioids: act on the mu opioid receptors which cause inhibition of GI motility and water secretion and absorption in the GI tract resulting in constipation. 
    • Transdermal formulations of opioids are shown to have less incidences of opioids induced constipation in comparison to oral
    • Peripherally acting mu opioid receptor antagonists (PAMORAs)

Transcript

Dr. Shreya P. Trivedi: Welcome to the Core IM 5 Pearls Podcast, bringing you high-yield evidence-based pearls. Today, we’re talking about constipation. I’m Dr. Shreya Trivedi. And I’m joined by

Dr. Kalaila Pais: Hi! I’m Dr. Kalaila Pais, an Internal Medicine resident at Beth Israel Deaconess Medical Center. And this an interesting topic because i can’t say there is one particular specialty that owns the constipation treatment topic. Is it GI? Is it the internist who treats it everyday? Is it the nurses administering these bowel regimen PRN and giving enemas? Or is the pharmacist on the team? 

Dr. Shreya P. Trivedi: Yeah so we actually sat down with all of them and why don’t we let them introduce themselves. 

Dr. Alan Lee: My name is Alan Lee. I’m an assistant professor in the division of GI at the University of Michigan.

Dr. Taylor Thompson: I’m Taylor Thompson. I’m currently a clinical assistant professor at West Virginia University School of Pharmacy and School of Medicine. I practice in outpatient family medicine within the family medicine residency.

Jack Sibilia: My name’s Jack Sabilia. I’m a registered nurse.  I’m the unit-based educator there.

Dr. Shreya P. Trivedi: So lets get into it, Test yourself by pausing after each of the 5 questions!

Dr. Kalaila Pais: Remember the more you test yourself, the deeper your learning gains.

Dr. Shreya P. Trivedi: Pearl 1: High-yield reversible causes of constipation. What are some of the common, intervenable causes of constipation? 

Dr. Kalaila Pais: Pearl 2: Fiber, hydration and bulk forming laxatives. Which type of fiber is more helpful for constipation? And is more hydration really better?

Dr. Shreya P. Trivedi: Pearl 3: Osmotic and Stimulant Laxatives. What makes you pick one vs. the other? 

Dr. Kalaila Pais: Pearl 4: Suppositories and Enemas. What are the differences between suppositories and enemas?

Dr. Shreya P. Trivedi: Pearl 5: Opioid-Induced Constipation. What are some of the best practices when it comes to opioid induced constipation? 

PEARL 1: HIGH YIELD REVERSIBLE CAUSES OF CONSTIPATION

Dr. Kalaila Pais: I think the first big question I had was, how do we even define constipation? Is there a specific number of bowel movements per day? Is it the hardening of stool or increased straining? 

Dr. Shreya P. Trivedi: Yeah, all good questions and I think the textbook definition is that it is abnormal for someone to have three bowel movements or fewer in a week.  But practically speaking, it honestly comes down to what is normal for the patient. Either way, when we see someone who has it, it’s really about us putting our investigating hat on to rule out secondary causes! They are so common. Kalaila, why don’t you tell our listeners about the mnemonic you made to help you bucket these causes? 

Dr. Kalaila Pais:I would love to! So to try to keep all of the things that contribute to constipation straight in my head, I came up with the mnemonic : LMNOP  which stands for Lifestyle, Metabolic, Neurologic, Obstructive, Pharmacologic. 

Dr. Shreya P. Trivedi: Nice we will go through each in super speed but I think it is so valuable to review since if you catch a secondary cause, you might not have to reach for some of the medications we are going to touch in pearls 3 and 4. So first up with L lifestyle, what should we dig into here?

Dr. Kalaila Pais: So for lifestyle, I’m thinking about if patients are moving or eating enough. This is especially true in our patients who are more bedbound or having low fiber diets

Jack Sibilia: With constipation, I personally like to do more of a less is more. And I have seen a lot of the time people with just getting up and moving, you start to see something, even if it’s more like it starts off small and then it starts going gradually until the point where they’re starting to have more regular bowel movements.

Dr. Shreya P. Trivedi: Yep I do love when that does the trick. But I would be remiss to say that as an internist I’m always thinking about #multifactorial contributors. So, I’m always thinking about other things going on, especially metabolic insults.  So lets dig into the M of the mnemonic – metabolic. 

Dr. Kalaila Pais: So when I am admitting someone for constipation, I’m keeping a close eye on 3 electrolytes: calcium, potassium and magnesium. So with calcium, I know that elevated calcium levels affect the nervous system and smooth muscle, and so what happens in the gut? Hypercalcemia slows things down in the gut

Dr. Shreya P. Trivedi: Yeah so there is one more mechanism for calcium at play! I remember having a patient with primary hyperparathyroidism with elevated calcium levels and she was just peeing a ton and getting more dehydrated in this vicious constipation cycle. Turns out high calcium levels impair the kidneys ability to concentrate the urine. So that dehydration wont help the constipation a bit.

Dr. Kalaila Pais: And then with the K and Mg I’m looking for those levels that are appreciably low in a patient with constipation.  Low K can mess up GI smooth muscle function and low magnesium can cause muscle spasms.

Dr. Shreya P. Trivedi: No fun! I think the other important metabolic insult to keep in mind is the thyroid. Especially if you see a TSH >10 mIU/L, then hypothyroidism might be at play.

Dr. Kalaila Pais: Okay, let’s move on to the N in the mnemonic for neurologic disorder. So, when you are taking care of a patient with MS, Parkinson’s, dementia or spinal cord dysfunction,you need to make sure they have a strong bowel regimen from the get go since they are at a higher risk of constipation

Dr. Shreya P. Trivedi: O in the mnemonic is for obstruction so things that may be a little more obvious, like colon cancer, fissures and stricture. These will definitely impact the stool moving forward.  

Dr. Kalaila Pais: And finally, the one we think about the most in internal medicine, the P is for pharmacologic, 

Dr. Alan Lee: So tricyclic antidepressants, antispasmodics, these are some of the medications that we commonly will see. Calcium channel blockers are another common class of medications. Patients who are on antipsychotics have a lot of constipation, and that actually is a very tough group of patients to manage. So we can see that as unfortunately a pretty common cause for constipation. And then I think one of the medication classes that we’re seeing more and more as being associated with constipation are these GLP one analogs that people are using for diabetes as well as the treatment of obesity.

Dr. Shreya P. Trivedi: I have to say the pharmalogic bucket is my favorite one! I love thinking about if nifedipine or verapamil may play a role and transitioning them to another medication or lower the dose. I really appreciated hearing from our pharmacist discussant that even over-the- counter meds that can contribute to constipation. 

Dr. Taylor Thompson: Yeah, I think there are actually a lot of over the counter things that can cause constipation that might not be on the med list in the chart. So asking about aluminum-containing drugs like antacids, calcium supplements, like a lot of antacids. So Tums, depending on what kind of tums they’re taking, those things can cause constipation. And we might not even know that patients are taking a ton of Tums at home, so asking about that. Over-the-counter iron supplements can cause a lot of constipation. Over-the-counter antihistamines, especially things like Benadryl that can cause constipation. Anything anticholinergic. 

Dr. Kalaila Pais: Okay that is really humbling and honestly has motivated me to do a better job of asking my patients about their use of over the counter medications, especially tums, iron supplements or benadryl. 

Dr. Shreya P. Trivedi: Since we came to the end of the mnemonic and just say out loud if none of these secondary causes of constipation, we do have to think about if primary or idiopathic constipation is at play. This is basically due to pelvic outlet obstruction or slow transit, but that is beyond the scope of our episode today

Dr. Kalaila Pais: Right so to summarize what I’m taking away from this pearl is when I’m seeing a patient with constipation to think through the helpful LMNOP mnemonic for secondary causes: L for lifestyle asking about how much they’ve been moving,  how much water they’ve been drinking, ask about their diet and get a sense of how much fiber they are taking in, M for metabolic, so looking at high calcium and low Mg and low K levels, or a high TSH that could be contributing, N for neurologic disease, O for obstruction and P, everyone’s favorite, for pharmalogic

Dr. Shreya P. Trivedi: Yeah! And looking at the med rec to see if the timeline for when starting either an antipsychotic, antidepressants, Ca Ch blockers, antispasmodics or opioids may be at play, and also ask them about OTCs like tums or iron supplements that might be impacting things. 

PEARL 2: DEEP DIVE INTO FIBER, HYDRATION AND BULK-FORMING LAXATIVES

Dr. Shreya P. Trivedi: Ok let’s say there may or may not be a clear offending cause, our patients still need relief – so let’s get into different constipation treatments and start off with some of the easier, or more first-line things like fiber, dig into hydration more and bulk forming laxatives! 

Dr. Kalaila Pais: I don’t know about you Shreya, but I spend a lot of time telling my patients to increase their fiber intake. 

Dr. Shreya P. Trivedi: Yeah same, especially if the constipation is mild to moderate, they don’t have a lot of symptoms. Sure, let’s do a trial of fiber supplementation with psyllium or methylcellulose. It is low-risk, low-cost and easily accessible, a win to try. 

Dr. Kalaila Pais: And it’s great when it works. The way it works is basically forming a gel-like matrix around the stool. This bulks up and softens the stool because it increases stool weight and water retention.

Dr. Shreya P. Trivedi: So psyllium or methylcellulose affects the stool only and has no effect on colonic activity.

Dr. Alan Lee: There’s been a number of systematic reviews and meta-analyses that have shown benefit with fiber for the treatment of chronic idiopathic constipation. I think one thing to realize is that most of these meta-analyses have shown benefits specifically for soluble fiber, and that includes things like psyllium, but not necessarily with insoluble fiber like bran.

Dr. Shreya P. Trivedi: ah so not all fiber supplementation is the same! Insoluble fiber like wheat bran might actually make constipation worse and you really want to reach for the more soluble fibers like psyllium or my favorite, oats.

Dr. Kalaila Pais: And when counseling patients to take more fiber, I actually did not realize this until researching for this podcast that there is an FDA recommendation to take psyllium 2 hours before or after other medications to avoid med interactions. 

Dr. Taylor Thompson: The one thing with the fiber agents like psyllium and Methylcellulose is they might reduce absorption of some of your other medications. So for example, if you’re on Synthroid, for example, and you’re also taking fiber, there may be recommendations to separate the fiber from other medications.

Dr. Kalaila Pais: In addition to the thyroid medication our pharmacist just mentioned, fiber binds to other meds like calcium in antacids, magnesium and zinc. So really maybe advise patients to take synthroid first thing in the morning and then fiber a few hours apart from other supplements.  

Dr. Alan Lee: The other things that I’ll tell patients when I start them on fiber is that fiber can worsen GI symptoms, especially as they’re ramping up, particularly symptoms like bloating and abdominal pain. So my general advice when I start patients on fiber is to start low. So, they could start at three to four grams of fiber per day and then increase their dose slowly over time for a goal of about 20 to 30 grams of fiber per day. And this total includes both dietary as well as supplemental fiber intake. And this may take weeks for patients to get up to that goal. 

Dr. Shreya P. Trivedi: Yes so start slow! I also learned another lesson about fiber the hard way. When I was pregnant for the 1st time, and a bit of TMI here, but I started taking psyllium prophylactically because I thought, I’ve heard so many stories about how constipation is worse in pregnancy, so let me try to beat it. But actually, it got so much worse and created a problem I didn’t even have. All because I didn’t increase my fluid intake with that extra fiber.  

Dr. Kalaila Pais: Here you were thinking you were getting extra credit staying ahead of problems but nope. 

Dr. Shreya P. Trivedi: No good deed goes unpunished.

Dr. Kalaila Pais: Speaking of fluid, I know we counsel patients to stay hydrated, which is honestly a personal challenge for me. How much water is really needed to improve constipation? 

Dr. Alan Lee: So I think my general approach to hydration, I think this is a reasonable initial recommendation, especially in patients who aren’t consuming adequate amounts of water. So that’s about a liter and a half to two liters per day, but in patients who are already consuming adequate amounts of hydration, it’s probably not going to be a huge benefit in increasing this for patients who have chronic constipation. 

Dr. Kalaila Pais: Yes, there was a study in 1990 which compared constipation in healthy males based on fluid intake. It showed that those who took only 500cc of liquid were, of course, constipated, but those who took 2.5L really did not have more  improvement in their constipation with more water intake. 

Dr. Shreya P. Trivedi: So maybe the way to think about it is if you’ve reached 2L of water a day you’ve removed hydration being a contributor to chronic constipation and you should look for other reasons

Dr. Kalaila Pais: Okay so that fluids.  I’ve also heard that certain fruits and vegetables can prevent constipation. I have wondered if there is any evidence to it and if so which are the high-yield ones to tell patients to order for their lunch?

Dr. Shreya P. Trivedi: Or dinner.

Dr. Taylor Thompson: So dried plums or prunes appear to be more effective for reducing constipation than psyllium in adults with mild to moderate constipation. And then kiwi fruit may slightly increase stool frequency compared to psyllium in adults with chronic constipation.

Dr. Shreya P. Trivedi: Alright prunes and kiwi it is! Let’s summarize this pearl. We can emphasize to patients the importance of increased intake of soluble fiber supplementation like psyllium or methyl cellulose, oats as opposed to insoluble fibers like wheat bran. 

Dr. Kalaila Pais: And when I prescribe fiber supplementation for patients, I give them a heads up about possible bloating and abdominal pain. I tell them to take the fiber a few hours apart from other medications like synthroid or other mineral supplements  like zinc and calcium. 

Dr. Shreya P. Trivedi: And of course what i learned the hard way,  encourage that hydration! Patients who already have adequate hydration, like 2L or above of water, may not necessarily get that extra relief.  And then of course, I love telling patients to order oatmeal in the morning and then prunes and kiwis for lunch from the cafeteria. 

PEARL 3: OSMOTIC AND STIMULANT LAXATIVES

Dr. Shreya P. Trivedi: Okay, so say fiber supplementation and hydration don’t work, this is when I start thinking about medications like laxatives. I think most people break it down to osmotic and stimulant laxatives

Dr. Kalaila Pais: Yeah I’ve seen those separated out like that and i think it’s helpful to know which one falls into which bucket 

Dr. Shreya P. Trivedi: Yeah I think it’s important to keep which meds fall into which bucket because if we don’t, they might end up with a bowel regimen that all has the same mechanism 

Dr. Kalaila Pais: Yeah have definitely seen a med rec where someone was on these “aggressive bowel regimens” but was just on all osmotic laxatives again and no other medications with other modes of action. 

Dr. Shreya P. Trivedi: It would really suck if the patient is super volume down and on 3 osmotic laxatives. And just to say it out loud, there is no clear evidence to say that this approach is better than that approach. But, theoretically, to me, if one agent is maxed out, let’s try a medication in another category to see if that can move things forward. 

Dr. Kalaila Pais: Yes so to keep them all straight so the best mnemonic we came up with for the osmotic laxatives is pretty magical liquid – the p is for polyethylene glycol, m in magical for magnesium-based meds, and L in liquid for lactulose. And hopefully, just the idea of pretty magical liquid helps us remember that it is a magical liquid that contains osmotically active molecules drawing fluid into the lumen

Dr. Shreya P. Trivedi: And then for the stimulant laxatives, we’ve got Spicy Bowel Movers. S in spicy for senna and B in bowel for bisacodyl, and movers for trying to remember they work directly to stimulate the colonic neurons to move the colon. 

Dr. Kalaila Pais: Okay now that we know which one falls in which bucket, let’s actually get nuanced and think about each of the laxative buckets and their time of onset, side effects, and general patient tolerance  

Dr. Shreya P. Trivedi: Let’s get started with our osmotic laxatives. So we already learned the osmotic laxatives are polyethylene glycol, lactulose, magnesium citrate, magnesium oxide, and they work by drawing fluid into the bowel through osmosis. 

Dr. Kalaila Pais: You know what’s  interesting? Polyethylene glycol, lactulose, mag ox or mig citrate…all these medications all work in a similar way, they have different onsets of action.

Dr. Taylor Thompson: So MiraLax is great, right? It’s safe for most people, but if you need something quicker, that’s going to take up to 72 hours.

Dr. Shreya P. Trivedi: Yes I guess with the amount of polyethylene glycol in typical miralax it can take up to 3 days and its funny to think a lot of the times we upregulate a patient’s bowel regime and expect that they will have a bowel movement but the end of the afternoon. But it may take a bit longer than that

Dr. Kalaila Pais: Yeah I have definitely fallen into that exact same trap. And then looking into it, lactulose works a little faster 24-48hrs. And Mg citrate is actually cited to work even faster, ranging from half an hour to 6 hours. And its cousin Mg Ox is less bioavailable than Mg citrate but still cited to work pretty fast, as quickly as 3-6 hours

Dr. Shreya P. Trivedi: Oh I’m so glad you are bringing this because sometimes i don’t know whats the best bowel regimen to reach for first, and I just put the patient on Miralax because that’s the practice pattern that’s been passed on. But maybe one way to think about it is, if I want someone to have a bowel movement faster I might want to reach for Mag ox or Mg citrate, or even lactulose

Dr. Kalaila Pais: But this is where side effects could be your tie breaker and weighing which ones have more or less side effects

Dr. Taylor Thompson: Lactulose has more bloating, and it has more flatulence. Our magnesium products can cause those electrolyte abnormalities. So avoiding those in patients with kidney dysfunction or anyone at risk of electrolyte abnormalities.

Dr. Shreya P. Trivedi: Okay to break that down, so best to avoid lactulose in patients who may already have abdominal pain, bloating or are already gassy. And just to cement why we have that side effect is, when we think about what lactulose is, it is a synthetic disaccharide and is minimally absorbed. So, when it passes down our gut, it’s our gut bacteria that ferments it, and produces a nasty gas like methane and some other things that cause all these side effects. Interestingly, though, we often use lactulose in hepatic encephalopathy. Why? Because that gas is really helpful because it brings a lower pH which traps ammonia in the gut. 

Dr. Kalaila Pais: And when we think about the magnesium side effects, many will say to ““Avoid in renal dysfunction”.” The thought is that patients with impaired renal systems may not be able to tolerate the excess Mg.  since an impaired renal system might not be able to tolerate the Mg. But, we looked into it and it’s actually controversial. More recent studies and thinking  is that giving Mg supplementation can be done safely, but with routine monitoring of magnesium levels

Dr. Shreya P. Trivedi: One last thing to close out on osmotic laxative is something that blew my mind. I was ordering Moviprep or GoLytely for a patient before a colonoscopy, it was called “PEG-3350” as the generic. and then when it hit me that Moviprep was just a larger volume of polyethylene glycol AKA PEG.

Dr. Alan Lee: So GoLytely is essentially PEG with electrolytes just in a larger volume and given over a shorter amount of time. And so basically we’re just trying to purge patients of their stool burden and trying to relieve their symptoms in a shorter amount of time. I typically wouldn’t give peg, sorry, wouldn’t give go lightly in patients who are just having run-of-the-mill constipation. So this is only in patients who are having more moderate to severe type symptoms.

Dr. Kalaila Pais: Yeah the 1st time I saw GoLytely used for severe constipation, I thought wow I cannot believe I didn’t think about that before. We use it to clean out the bowels before colonoscopies so why not use it when the team feels really stuck that nothing is moving  (pun intended) .

Dr. Shreya P. Trivedi: Okay with that, let’s transition to our stimulant laxatives? We already learned  Spicy Bowel Movers aka senna and bisacodyl. 

Dr. Kalaila Pais: And just to remind everyone, Senna and Bisacodyl have no effect on the actual stool the way that psyllium does but senna and Bisacodyl instead stimulate the colonic neurons. 

Dr. Shreya P. Trivedi: One of my favorite teaching points is to ask the team why is senna dosed at night? 

Dr. Kalaila Pais: Yeah like does it have something to do with how senna is processed at night?

Dr. Shreya P. Trivedi: Yeah, I wondered that too. Turns out that the onset of senna taking  6-12 hours  to work. People like to tell their patients to take it at night so it can take effect overnight and people can have their first bowel movement in the morning. So you can very much feel liberated to tell the patient to take it whenever unless they feel particular about having their bowels move in the AM.

Dr. Kalaila Pais: That’s good to know where the EPIC default of senna at 2100 comes from! One thing I was thinking about is how I often see senna as a daily medication but looking into the literature, it has really been tested more as a rescue laxative. 

Dr. Taylor Thompson: I think of Bisacodyl and Senna as your rescue laxatives. And the reason for that is the use for a long period of time. So beyond four weeks, there’s not really data for long-term efficacy and the efficacy of these agents will actually decrease over time if you use them chronically every single day. In my practice, I have seen you can go up to four tablets or two tablets twice a day. So 17.2 in the morning, 17.2 in the evening, and as you go up on the dose, I think that it tends to work better. We use four tablets a day. So there’s really not a ton of data for how to dose Sena, but commonly you’ll see even four tablets twice a day.

Dr. Shreya P. Trivedi: And as we are going up from once a day to twice a day, what side effects should we be on the look for?

Dr. Alan Lee: I know there used to be this concern or fear that chronic use of stimulant laxatives may damage the enteric nervous system, or patients may get dependent on these, but that’s largely been shown to be false. For the stimulant laxatives, I think really abdominal cramping and pain are the side effects that I counsel patients about certainly can cause diarrhea as well.

Dr. Kalaila Pais: I also really appreciated hearing what our nursing colleagues had to say about his experience administering Senna

Jack Sibilia: Senna, you can get it as a liquid; it comes in a little Dixie cup type thing. It’s 8.6 milliliters or something like that. Very easy. You can mix it in with a lot of meds. So a lot of our confused patients or stuff like you have a patient with dementia, some sort of encephalopathy, whatever, will crush a lot of the vents and give it with ice cream, you can relatively give it and it will go unnoticed. The second you add senna to that mix, the ice cream becomes a hint of brown and it tastes gritty and very, it’s like dirt. So it’s always tricky once you start adding Senna into that mix, because they’re going to know it’s like, this is the worst ice cream I’ve ever tasted. I’m like, oh yeah, sorry, must be old. It’s our old brown ice cream that we have in the back. 

Dr. Shreya P. Trivedi: A round of applause to the nurses and the tricks that they have to pull to help patients take their meds. And so with that, why don’t we summarize all good things on osmotic and stimulant laxatives? So we learned that osmotic laxatives work by pulling water, through osmosis, into the colon and it’s really pretty magical liquids, things like polyethylene glycol, mag supplements, and lactulose. And then for the stimulant laxatives, they work by stimulating the colonic wall to move, think spicy bowel movers for senna and bisacodyl.

Dr. Kalaila Pais: And when thinking about which osmotic laxative to use, keep in mind that Miralax is generally safe and well tolerated but may take up to 72 hours to work. So we may consider some of them, like magnesium oxide or magnesium citrate if we want a faster onset of action. In terms of stimulant laxatives, senna and bisacodyl have a faster onset of action than miralax, but it has only been studied as a rescue agent for up to four weeks and anything outside of that just hasn’t been studied

PEARL 4: SUPPOSITORIES AND ENEMAS

Dr. Shreya P. Trivedi: Now onto suppositories and enemas, maybe my favorite section because I learned a ton here!

Dr. Kalaila Pais: Okay, I’m going to be honest. If you had asked me the difference between a suppository and an enema before making this episode, I would not have been able to answer. So, I really appreciate Jack’s vivid description of two, especially since he sees it all the time as a bedside nurse

Jack Sibilia: So with the suppository, you’re pretty much dealing with a medication that’s going in the rectum. We call it torpedoes. It looks like they’re these small, cylindrical white, it looks almost like a crayon-type medication. They’re very slippery. They react a lot to body heat, so once you take ’em out, you got to be relatively quick to get ’em in there, but it’s pretty much like a torpedo of medication that goes up the patient’s rectum, for lack of a better description, is what it looks like. With an enema, it’s more of we’re instilling water into the rectum to help kind of loosen up the stool. 

Dr. Kalaila Pais: Okay so the teaching point is that a suppository is a dissolvable solid tablet that is placed into the patient’s rectum vs an enema, which is the insertion of fluid into the patient’s rectum. 

Dr. Shreya P. Trivedi: And I think how Jack described it is a rule of thumb because there are so many different types out there. Another thing to keep in mind is what a patient may tolerate. Is this someone who is delirious and not able to follow instructions? Are they really going to be able to hold something in their rectum for 15 minutes? 

Dr. Kalaila Pais: But what I struggle with is knowing which suppository or enema to choose in the first place and the difference between them. There are so many out there -we have fleet enemas, water enemas, mineral oil enemas, lactulose enemas, even soap sud enemas.

Dr. Shreya P. Trivedi: And so one day I went on a crazy deep dive into this evidence-free zone of enemas and suppositories.  I didn’t understand why GI was recommended soap suds and mineral oil enema for this patient with severe constipation and fleet enema for another patient, so I thought it was worthwhile to dive into to get some clarify in this evidence-free zone.

Dr. Kalaila Pais: Let’s get into it! And maybe one way to ground us is the mechanism, and then from there it’s easier to think about our patients and what they might tolerate the best

Dr. Shreya P. Trivedi: I agree, let’s start with mineral oil enemas!  Mineral oil basically lubricates the colon. 

Dr. Kalaila Pais: Interesting! So mineral oil enemas are like greasing the tracks for the poop train, which takes time.

Dr. Shreya P. Trivedi: Yes, it feels like a “duh” now it’s an oil so mineral oil enemas basically coat the stool and colonic walls to help things slide out more easily.

Dr. Taylor Thompson: Mineral oil enemas are probably a safer option compared to some of our other enema options. I will say the mineral oil enema is a retention enema, which requires patients to hold it or retain the fluid for a bit. So the enema has time to work. 

Dr. Shreya P. Trivedi: Okay so it may take some time to work, but what’s not to love about a little extra lubrication here and there! 

Dr. Kalaila Pais: Now onto fleet enema, aka sodium phosphate enemas. 

Dr. Shreya P. Trivedi: What is it? It is basically mixing water and salt, so like a saline solution, pulling in water, making it easier for stool to pass.  

Dr. Taylor Thompson: Sodium phosphate hypertonic enemas. So you’ll commonly see these be referred to as fleet enemas, but a lot of the fleet enemas do have phosphate in them. They are effective and smaller volumes are often required. But I will say the fleet phosphate enemas often cause electrolyte abnormalities. So a lot of my geriatric pharmacist friends really dislike the fleet enemas because they can cause serious electrolyte abnormalities. So I try to avoid those in our older adults and in patients with kidney disease.

Dr. Kalaila Pais: And just for a bit of background, the phosphate in the enemas is absorbed from the GI tract. However, in patients with kidney dysfunction or dehydration, this phosphate can overwhelm the body’s ability to remove excess phosphate, leading to high phosphate levels and low calcium levels. 

Dr. Shreya P. Trivedi: So if you have a patient with CKD with phosphate that is already elevated, maybe stay away from fleets or sodium phosphate enemas. 

Dr. Kalaila Pais: Another enema or suppository that works similarly are glycerin suppositories 

Dr. Shreya P. Trivedi: so, Glycerin enemas also work by pulling water into the colon to soften stools. 

Dr. Kalaila Pais: Yep! And can you guess how lactulose enemas work? 

Dr. Shreya P. Trivedi: Probably also a similar mechanism. Lactulose we already mentioned, is a synthetic disaccharide, so via osmosis, just like the  PO version, draws water into the colon 

Jack Sibilia: So lactulose enemas, it’s similar, but it’s not as much as a tap water, but it’s still a significant amount of liquid. And you can always tell one of our lactose enema, there’s a specific smell. If someone’s on lactose, you can walk on the floor and you could pick out the room in a second, especially if they’re on a lactose enema. It’s like, yeah, there’s no question of it. 

Dr. Shreya P. Trivedi: Oh! That is good to know! There is a particular smell from time to time. I’ll have to ask a nurse if that is c. diff smell or lactulose enema smell

Dr. Kalaila Pais: Haha yes okay so to recap so far. We have mineral oil enema, which are well tolerated and basically lubricate the stool and walls of the colon to get things moving. And then there are all the enemas that work by pulling in water from the body into the colon to soften up the stools. These are Fleet enema, glycerin enemas, and lactulose enemas.

Dr. Shreya P. Trivedi: Great and I really appreciate thinking about the mechanism because after thinking about what a patient can tolerate and worrisome side effects, then I think it’s thinking about what are the different enemas and mechanisms are that I can pair together when someone is really clogged up with constipation. 

Dr. Kalaila Pais: Yep and one last group of enemas to close out: hypotonic enemas like tap water and soap suds. Because these have a lower osmolarity compared to the surrounding tissues, water moves from the enema solution into the colon and this increases stool volume which stimulates peristalsis. Soap suds, they have an added mechanism in that they irritate the colon which also helps in stool evacuation

Dr. Shreya P. Trivedi: So to summarize, mineral oil enemas are non-irritating but it can be difficult to ask patients to hold it in their rectum for long periods of time. The tap water enemas are also pretty well tolerated. The phosphate enemas should be used in caution in elderly patients and those with kidney disease. And then as you just mentioned Kalaila, the soap sud enemas cause colon irritation to evacuate the stool but anecdotal well tolerated.

Dr. Kalaila Pais: One last thing and I promise this last thing, let’s hear from Jack to hear about the nursing perspective on administration of these enemas. 

Jack Sibilia: Fleet or a mineral oil type enema actually comes in a little squirt bottle. It has a little tip and you put it in and you just squeeze the whole bottle and it goes in. With a tap water or soap suds. It looks almost like a tube feed bag, so you put it with warm water, you fill it up, you put it on an IV pole, and then same mechanism, you go into the rectum. The tricky part is having it stay in because you’re instilling about a thousand like a liter of fluid sometimes into these patients and depending on the patient’s condition, this is more of a gown up type situation a lot of the time because it can go in and sometimes it just comes right back out and it becomes a mess very quickly. I can’t stress it enough: Pre-planning this is a big thing. If it ever gets ordered toward the end of shift or even at nighttime, it’s probably not going to get done until the morning. Just because it is intensive a little bit, especially if you have someone who can’t walk and is bed bound, they’re going to be, they’re hard to turn. They have a broken leg. There’s all these things going on where this enema is just going to cause it’s going to be a mess. You’re going to spend probably two hours in these rooms with some of these patients just for the cleanup after.

Dr. Kalaila Pais: Wow, that is really eye-opening for me. So many times, I have just clicked the order button and it seems as though the medications are magically given. But we have so many blindspots about what our colleagues may have to experience to give these medications  at the bedside. 

Dr. Shreya P. Trivedi: Yeah, this is why I love this podcast because we really are able to get different perspectives from our healthcare professionals.

PEARL 5: OPIOID INDUCED CONSTIPATION

Dr. Shreya P. Trivedi: If you remember from pearl one, P stood for pharmacologic causes of constipation. One of the most common and notoriously difficult types to treat is opioid induced constipation. 

Dr. Kalaila Pais: Let’s think about how opioids can contribute to constipation. There are two big ways. One is slowing down the GI tract and 2 is impairing sphincter tone, is slowing down the GI tract and impairing sphincter tone. And then on top of that, opioids also reduce biliary and pancreatic secretion also messing up digestion and drug absorption. 

Dr. Shreya P. Trivedi: I definitely don’t think about the digestion and drug absorption. Say the patient still needs opioids (and is maxed on all the other good things) and you are thinking about how to prevent the constipation. 

Dr. Alan Lee: There is a study that suggested that transdermal formulations of opioids actually had less incidences of opioid induced constipation compared to oral administration of equivalent doses of morphine. 

Dr. Kalaila Pais: So I was relieved  to learn there are some lateral moves we can make where we can change to other opioids that cause less constipation 

Dr. Shreya P. Trivedi: Transdermal patches! Ah, so good! I feel like I think of transdermal for oncology patients with cancer pain but good to know this trick and would have to reach out to pharmacy or the pain service to help with the best titration plan

Dr. Allen Lee: Another example would be tapentadol, which is a mixed mu opioid agonist also a norepinephrine reuptake inhibitor. There is some data to suggest that it may have fewer side effects compared to traditional opioids.

Dr. Shreya P. Trivedi: Well what do we do when those aren’t an option?

Dr. Allen Lee: And then I think in patients who are still struggling despite some of these pragmatic changes, then we have a specific algorithm for opioid induced constipation. So typically we’ll use our traditional over-the-counter laxatives, so things like osmotic laxatives, stimulant laxatives, et cetera. And then if patients fail two of these types of laxatives, then we start thinking about prescription laxatives, specifically these PAMORAs, which are these peripherally acting mu opioid receptor antagonists. And so these are medications that block the actions of opioids in the gut specifically, but they don’t cross into the central nervous system, and so they don’t affect pain management.

Dr. Shreya P. Trivedi: So Dr Lee is describing the PAMs or PAMORAs – most common being methylnaltrexone which can actually come as both an oral and subcutaneous injection. 

Dr. Kalaila Pais: One thing I have to reassure patients about is that methylnaltrexone does not affect the pain relief patients feel from opioids. 

Dr. Taylor Thompson: And these work better for people who have been on opioids for at least four weeks. So patients treated with opioids for less than four weeks might actually have less of a response to our mu opioid antagonist, and it’s recommended to actually stop treatment with our other maintenance laxatives prior to starting the opioid antagonist. And then if they don’t get relief from the opioid antagonist, we can reinitiate our other therapies. 

Dr. Shreya P. Trivedi: So methylnaltrexone  targets the gut which is my area of concern, but still maintains the systemic effects of opioids they are on! But how effective is it in really relieving constipation? 

Dr. Kalaila Pais: It is actually really effective and methylnaltrexone is dose dependent. So give you a patient 1mg methylnatlrexone, on average there will be relief around 48 hours. But if you give them 5mg or greater, there is relief in a whooping 1.26 hours. 

Dr. Shreya P. Trivedi: What a win. What’s the catch?

Dr. Alan Lee: I think these PAMORAs certainly have a pretty high rate of side effects. So depending on the literature, it’s like 15 to 30% of patients will have adverse side effects. I think abdominal pain is typically the most common side effect from these PAMORAs, but diarrhea is definitely up there. So yes, that is a negative potential downside with these PAMORAs.

Dr. Shreya P. Trivedi: Its humbling to hear that some of these medications for constipation may make things like abdominal pain worse, which patients may already be feeling from their constipation.

Dr. Kalaila Pais: Yes so much to think about when thinking about constipation and this abdominal pain. Let’s do a quick recap. So, the peripheral mu receptor antagonists or PMRAs like methylnaltrexone are medications that can be used for opioid induced constipation in patients who have failed a typical laxative trial. 

Dr. Shreya P. Trivedi: The utility of the drug is targeting the action of the opioids on the gut without decreasing opioids system effects, particularly pain relief.

Dr. Kalaila Pais: Some side effects of the medication includes abdominal pain and diarrhea and so if your patient is unable to tolerate PMORAs, consider alternative medications like transdermal patches.

Dr. Shreya Trivedi: That is all for today, thank you so much for listening. If you have ever gotten any value from the podcast, please please please share this with at least one other colleague who might also get something out of the episode

Dr. Kaliala Pais:  Thanks to our reviewers for this podcast. Thank you to Dr. Jesse Powell for the accompanying graphics. This episode was made as a part of the Digital Education Track at BIDMC.

Dr. Shreya Trivedi: Opinions expressed are our own and do not represent the opinions of any affiliated institutions.

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