Irritable Bowel Syndrome: Management Strategies *ACPE-Accredited*

(upbeat music) - Hello, hello, welcome back, everyone, to the core console's RX podcast, my co-host, Colt Swanson, with me as always. Colt, what's up, man? - Doing good, Mike. - Can't complain, how about you? - Good, good, can't complain either. - Just definitely excited about jumping back on another episode of the podcast with you, man. So it was a good time. I wish it was a little bit earlier, like back in the good old days. But I remember, sometimes you get a record at 10 p.m. - I think last time we were on, I was talking about how excited it was for both season and I'm already just so sad about what happened. - Are you? - Yeah, we lost, I think we've lost two games since I last, we last recorded, so. - Now I'm scared. - That's unfortunate. - Well, it's all up from here probably, unless you lose more games, I guess. - Yeah. - And I guess that would be further down, but I've gotten used to it. - It's all good. You know, at least dude, you got your pharmacy career to be excited about, not come with. Yeah, there's, you know, what them had their losses. Or something, something like that. - Dude, so I was listening to one of our old episodes, trying to find a password or something that somebody said we didn't record. And I was just headed on the beginning, and it was just our normal, like what we're doing now. And I was in a hurry and I was trying to find it. I was like, yeah, shut up, just get to the freaking thing. And I was like, oh, this must be what people think when they're annoyed and annoyed. - Get to the password. - Or you're thinking you get to the beginning, yeah. - Yeah, like so I can like start like, trying to like go through and figure out where it works. I knew roughly where the password was, but. - Did you, exactly. - Did we record the password? - Yeah, I figured, I just remember thinking like, an email like that part of me is like, oh, we must have forgotten. But then I'm also like, well, we probably would have gotten a lot more emails if we actually forgot the password. - Yeah, more than one. - So it's an episode from 20 episodes ago. And it's one email, like it's in there, dude. Feel real confident about that one. - Right. - Good. - Speaking of passwords. Guess what a good idea is. - You're gonna give it now. - That would be hilarious. - No, I'm not gonna give it yet. - But it is an accredited episode. We're gonna be talking tonight about irritable bowel syndrome, IBS. And this is an accredited episode with thanks to our friends over at FreeCE.com. They've been partnering with us for quite a while. And so, hopefully by this point, you kind of know the typical spiel that I give. But if you're a member of FreeCE.com and you have their unlimited membership, you get all of our episodes that are accredited, included in that membership. And so, I mean, there's probably what, 60 something episodes on there now, 70, I don't know. But there's a bunch. And you basically listen very carefully because not only wanting to absorb the information, but we give you a super secret password at some point during this and take that password, enter it into FreeCE's website underneath this particular episode, under the list of all the episodes that we have on there. And you'll have a 10 question multiple choice test. Pass that and you get your one hour of continuing education credit, which is good for pharmacists and registered nurses. And so, it's a great way of getting your required CE while not sitting in a boring classroom and all that. Although, you may be saying somewhere else more comfortable, but still bored, that's, you know, we'll try our best to avoid that. But if you're not a member of FreeCE, definitely encourage you to check them out. They have all kinds of great learning opportunities on their website, not just our podcast episodes, but monographs and live sessions, panel discussions, all kinds of good stuff. So, big thanks to our friends over at FreeCE and been really grateful to them for continuing to partner with us and be able to bring you guys content like this. Or at least, you know, content that we would have hopefully tried to bring, but then now it's credited and probably more valuable. So, all that being said, with jumping to irritable bowel syndrome, this is a topic we haven't talked about in a while, and there's not a ton of, like, or any, like, you know, practice changing guidelines, but there's a couple new statements out from the AGA and all that, so we'll kind of look through that stuff and see what's new. - Yeah, let's do it. So, irritable bowel syndrome or IBS, we'll call it throughout the episode. It's a group of functional bowel disorders in which abdominal discomfort or pain is associated with defecation or a change in bowel habits. It's more common to affect women, prevalence is greater than women. About 50% of people with IBS report symptoms beginning before the age of 35 years old, so usually it's a bit on the younger spectrum. The development of symptoms in people older than 40 doesn't exclude IBS, but if you have somebody like that, it would probably prompt a closer look at some other underlying organic ideology. - Yeah, and like Cole mentioned, it's kind of the umbrella term, if you will, so the symptoms can vary depending on which sort of subtype you have, but some universal kind of habits, they're, you know, symptoms that you would present with. Like, Cole said, altered bowel habits, typically going to kind of have a post-prandial urgency, that's pretty common. And, you know, patients may have constipation, predominantly diarrhea, or kind of an alternation between the two, which would be, you know, like mixed symptoms. But the big sort of homework symptom is that abdominal pain. It's kind of like this diffuse pain without radiation, and it's kind of commonly seen lower abdomen, specifically the left lower quadrant. Patients may also experience abdominal bloating, abdominal distension, and then other GI issues as well. You know, they can have dyspepsia, there can be nausea, vomiting as well. But those symptoms are kind of, you know, seen regardless of which subtype they have, they're going to have that sort of abdominal pain and discomfort that goes along with the universal symptoms as they are referred to. - There are some features of these symptoms that might not be consistent with IBS, and so patients have these features, would probably warrant further investigation. I mentioned the onset being in middle or older age. If the patient has acute symptoms, it may not necessarily be, because IBS is usually characterized by it being a chronic disorder. Progressive symptoms, nocturnal symptoms, anorexia or weight loss, fever, rectal bleeding, painless diarrhea, which I wish, well, no, I won't say what I was going to say, and gluten intolerance. - Just shows your maturity in how you've grown now. - I know. - 'Cause I feel like you would have shared that. - Yeah. - It seemed like there was some golden now. I've learned. - That story. - I've learned to watch my mouth, so. - It's good. - It's still working on myself. - It is incredible to get better. - It's incredible the things that you say that are repeated like verbatim. - You have to. - And somehow, it'd be like, you know, diarrhea, and that's the word that they will then be saying. I'm like, "All the words I've said to you today, "that's the one year." He just happened to like, "Why is that? "How does that happen?" It's very strange. But, it's good that you mentioned the symptoms that are not consistent with IBS. 'Cause, you know, while there is sort of this criteria and, you know, diagnostic tools and things that have come and been developed and published, a lot of times we kind of look at IBS to sort of a diagnosis of exclusion. And so, you know, having the signs and symptoms of a point you away from IBS is very important as well. But we do have what's called the Rome IV criteria and this is sort of like the official diagnosis, if you will. Although, like I said, a lot of times it's based on sort of, you know, symptomology, history, all that. But the Rome IV criteria in order to get a diagnosis of IBS, it requires that a patient has basically had recurrent abdominal pain on average, at least one day per week, during the previous three months. And that pain has to be associated with two or more of the following three things. Either related to defecation, you know, maybe increased or unchanged by defecation. Or it can be associated with a change in stool frequency. Or thirdly, it can be associated with a change in stool form or appearance. So, as to have pain at least one day per week, previous three months and two of those three that I just mentioned in order to meet the Rome criteria for IBS. And then like I mentioned, you have to kind of sub-categorize it based on their predominant symptom. You know, constipation being one and so patients are obviously going to have abnormal bowel movements that usually result in constipation. IBS with diarrhea or IBSD, the patient symptom is predominantly diarrhea, as you can imagine. And then we also have mixed IBS or IBSM and unclassified IBS as well, where, you know, I guess she is not quite sure what's the ex going on. But I do really wonder how, like, what is, what is it? Oh, it seems like it's either going to be, they have like the Bristol types have like different, I don't know, they kind of expound on the specifics of the consistency, the consistency of the appearance, all that stuff. And so I just, I don't understand how there, it could be unclassified. What is the alternative to all of the descriptions that they get? It doesn't really make much sense to me. I mean, I was trying to be funny, but at the same time, I mean, if you think about like most of the ICB 10 codes, there's usually an unspecified option. I don't know in there. Instantly just somebody looking at the toilet. I mean, I got no idea. Like just looking back at the chart, looking back and just, yeah, I got no idea. I got unclassified. That's unclassified. You have to put this in our files. But you brought up that tool that is very useful, where the Bristol types, where you obviously have this illustration of what you'd expect the consistency to kind of look like. And in fact, if you look at this diagram where it's got this triangle, it's like a right triangle with Bristol types one and two being sort of the first, I guess, upper left quadrant, if you will. Not that you can-- it's not the right terminology for a triangle, but you know what I mean. And that's the IBS constipation. And then the stool gets more loose and runny, if you will, as it gets into the lower right quadrant. And then IBS unclassified. It just literally doesn't have any pictures of feces. So again, maybe it's just like-- It's honest. Yeah, but it's sort of-- I don't think I've actually seen anybody listed that on there. I've seen mixed, for sure. But I don't think I've ever seen IBSU on anybody's chart that I can think of. Have you? No. Maybe it's like a not even a real term. We've just kind of been repeating it. I guess. But yeah, if you really need to check out that chart, you can find it pretty easily. But I think most of us can kind of use some-- We know the deal. Use some imagination and kind of put somebody in each category. But yes, it is important to know, obviously, because the treatments are very different, depending on whether you're treating diarrhea or constipation, which we'll obviously go into. Yeah. As far as the workup for patients with IBS, the American College of Gastronology Guidelines from 2020 gave a few updates at that time. One, in particular, for patients with IBS, with diarrhea symptoms, serologic testing can be performed to rule out celiac disease. Also, for those patients, you can check a fecal calprotectin or fecal lactoferin. And a c-reactor protein should be checked even in the absence of alarm features, I presume, to rule out other underlying inflammatory disorders. They recommend against routine stool testing for interic pathogens, colonoscopies, and patients younger than 45 if they don't have any other warning signs or indications for colonoscopy, or routine food allergy screening, separate from celiac disease. Yeah. And kind of looking at some of those, the testing, and, you know, those inflammatory markers, specifically in diarrhea is the predominant symptom. I think the thought is that sometimes IBS is the diagnosis the patient gets when in reality, it's actually inflammatory bowel disease because that abdominal pain, constipation, diarrhea can also be found in IBD, along with, obviously, a lot of other symptoms and whatnot. But there have been some studies they kind of showed a delayed diagnosis of IBD because patients are misdiagnosed with IBS because of their symptoms. And obviously, the delay in treatment of IBD can lead to fistula formation and, you know, the likelihood of surgery and all that. And so some of those markers have been shown to be beneficial in kind of making that differential diagnosis. The AGA, I'm called, I mentioned the ACG, but the AGA actually put out what they call a quality indicator development report that they published this year, 2025. And it basically just gives some quality measures or indicators that you can kind of utilize to see how well you're managing your IBS patients. And one of the things that they also brought up was the same kind of testing that the ACG had done previously. Specifically, it's with patients with diarrhea, celiac, you know, disease, and ruling out that. If there's any, seems to be any kind of gluten intolerance, they also echo the fecal calprotectin. And they all agree that the colonoscopy is not warranted unless they meet some kind of other criteria for an early then recommended colonoscopy. And basically, there's been some studies showing that colonoscopy doesn't, the findings are low compared to patients without IBS, you know, findings are low and patients compared to those who do not have IBS. And so what's the point of all the extra cost and all that, if we're not really going to find anything, is why they recommend against it, not necessarily that it's going to be harmful, but it might be harmful to your pockets, you know, as far as the costs and all that. And there's always complications. - Yes. So of course, with these patients, it would make sense that there may be some recommended diet changes or restrictions, in particular, they recommend excluding gas producing foods. So examples would be like those FODMAPs foods that we've talked about before. It's an acronym meaning low fermentable oligo dye in mono-saccharides and polyols. Of course. - Of course, lack, yeah, of course. Obviously I'm going to buy another. Avoiding lactose and gluten can help in patients where that might be a problem. Wheat, rye, onions, pistachio, milk, ice cream, apples, watermelon, sorbitol, manitol, containing foods, sorbitol, manitol, every time I hear that, I think of the gummy bear issue. And dude, I will tell you, it took me way too long to understand this, but pistachios, when I, especially if they don't have seeds on them, it's just way too easy. But even when they do have seeds on them, I can put down some pistachios. - Yeah, they're delicious. - Those things mess me up in a painful way. - No. And I did not understand it until, I mean, after having it happen a few different times, but I totally resonate with the pistachio recommendation. - That's good. - Well, we had that to confirm then. - Yeah, tell you what folks. - You heard of one example, it's true. - No, it's true. - It's also good to consider an impure trial of lactose-free diet. Dude, I'll tell you what, another story. When I was a kid, I was probably elementary school. I was having some IPS-related issues. And so the doctor recommended that basically, just saying cut out lactose and just see what happens. So I did. And I remember having like the lactate ice cream, which I thought was just the best tasting ice cream ever. So I was pretty happy about it. And I did it for a summer. And then I think we just got kind of lax on it. And then I just started drinking dairy again and stuff. And it resolved, which was interesting. - You beat it. - Another case study there, I beat it. - And then the case study of just perseverance. He just powered through the lactose. It is kind of like a slap in the face that's like, hey, you know that one substance that we give all mammalian babies, yeah, you can't have it. Your body's not good at digesting it. - You can't do that. - You can have it, but you're gonna have diarrhea, yes. - It makes me feel for people before there were alternative options. I mean, my goodness when they had babies, you know, like the lactose-free, like formula, I suppose and all that. It's got to have been rough. - Yeah, a lot of things rough back then, I think. I imagine. - Yeah. - I don't think it would have done well. I don't think it would have fared too well. - No, I would not. - Yeah, I would not have. - Just not having air conditioning would have done me. - Oh, that would have been done. - It would have been like, well, I'm 28. I'm like, oh man. (laughing) Anyways, gluten can potentially alter bowel barrier functions in patients with IBS, with diarrhea. Evidence for non-celiac gluten sensitivity, contributing to IBS, though, is kind of conflicting. One study, one made analysis, concluded that bifidobacterium and phantus may help alleviate some symptoms of IBS. It seems like bifidobacterium tends to be the probiotic that has like, if anything, it seems to like pop around as the one that's beneficial. This was from the 2009 American Journal of Gastroenterology, but the, for example, the 2020 ACG guidelines recommend against the broad use of probiotics in this instance. So thanks to keep in mind. - Well, and that AGA paper that came out this year does have a whole section on non-pharmacologic management. And one of the things they do kind of go into is the dietary modifications and they talk about decreasing phadmap intake. But they do mention a lot of the other stuff you said as well. But the phadmap diet in particular was something they kind of went into more detail than I had seen previously. And they also mentioned that there's other international guidelines as well like the British Society of Gastroenterology, Canadian Association of Gastroenterology. They all kind of suggest this limited trial of low phadmaps or at least increasing soluble fiber intake and all that. But the evidence to kind of support the phadmap diet is relatively low certainty. And patients are potentially at risk for developing malnutrition and potentially even like eating disorders, things like that, especially if there's any kind of like underlying psychiatric disorder or anything. Patients who have food insecurities, they're probably not going to be good candidates for the low phadmap diet. So it's definitely not just for everyone. You do need to kind of take into account patients, socioeconomic and other behavioral health, potential comorbidities. But they talk about the diet is sort of carried out in this stage. They call it a stage manner of phadmap restriction. So four to six weeks, and what happens is they kind of do this gradual takeaway and then gradual reintroduction of individual phadmaps over six to 10 weeks. And the diet is sort of like personalized, if you will, based on the symptom and the relation to certain individual phadmaps. So they do it in a more like stepwise approach to sort of try to really identify if they're specific phadmaps that are the culprit or causing bigger problems. So I thought that was kind of interesting. And they do definitely go into checking for gluten and tolerances and all that and stuff as well, especially if diarrhea is the predominant symptom. But the other thing that they kind of go into on top of the diet is the importance of the brain gut interaction with being a major component of IBS pathogenesis. And so they do talk about the importance of cognitive behavioral therapy. They also talk about gut-directed hypnotherapy and just kind of go through some of the evidence to support those. They do obviously acknowledge that there's not a plethora of those type of therapists just available. And so getting patients plugged into those type of therapy sessions can be somewhat challenging, especially in more rural areas or, I don't even know, in Charlton, I'd be curious to see if we even have somebody around here that's kind of specializes in that. I have to look. I imagine bigger cities and stuff is probably a lot more prevalent. But definitely not your typical therapist that you can find them relatively easily. So definitely is specialized cognitive behavioral therapy. But it can definitely improve symptoms, especially using it in conjunction with medication options. So we didn't want to go into a bunch of detail with that primarily just because we didn't really focus on it when we were prepping. But I definitely encourage you to check that out, especially the hypnotherapy. I need to look into that one myself. Because apparently there's some evidence, but it seems I'm always skeptical on the hypno stuff. Do they like wave a watch in front of your belly button or something? I don't know. That's what I mean. I feel like the second somebody's trying to hypnotize me, I'm going to be like, in my head, I'm going to be thinking that the dude from Star Wars, where he's like, "My tricks don't work on me." I'm like, no way, dude, you're not fooling me with that watch. But anyways, the non-pharmacologic interventions are definitely important and at least kind of given the groundwork of long-term treatment, if you will. Yeah. But let's talk about treatments, and we'll separate them into the predominant symptoms of constipation diarrhea. And that way we can kind of look at the different treatment options, and then we'll bring it back home with the universal symptoms and things. But constipation seems like a good one to start with, because we got a little bit more variety in our treatment options. Diary has been really lacking in new FDA-approved treatments for quite some time. I know. 10 years since we've had an IBS for diarrhea drug approved. We had two-- Together on diarrhea. Two in 2015, and then nothing ever since. Like unbelievable. You never know where you'll be when diarrhea hits. Was that a commercial or something? Because I feel like that was something people said a lot when I was like a teenager. I don't remember. It sounds like it could be. It could be a pep-to-bez malcommercial. It could have been something you and your friends thought was hilarious as I could have been. Yeah, it's anybody's guess at this point. It's likely the latter. So let's talk about constipation and what we can do for that. So first, we'll talk about polyethylene glycol. 3350 branded as mirrorlax, for example. It's an osmotic laxative. It's dosed 17 grams of powder and on the standard dosing powder bottle, that would be one cap full of powder. Mixing to 4 to 8 ounces of water, juice, soda, coffee, or tea. I don't know if I would do that with coffee. It just doesn't sound appetizing to me. I just like to get such a wide variety of potential beverages. I know, I do it at whatever. I have not done it myself. Yeah, brother, I've had some people including my wife swear that they can taste something. And I'm like, I don't know, maybe. I mean, it would really have to dissolve well, you know. I don't have a lot of experience. But I'm sure people can speak to it. Lots of dreamy trials in our cells. See what happens to you. Yeah, that doesn't say that. Yeah, I'm taking one idea. Yeah, we'll call that plan B. The AGA 2022 guidelines, do you recommend it, but with a low certainty of evidence? What they're doing, the medication, its mechanism, is it's causing fluid to be drawn into the bowel loom in through osmosis, which distends the colon and increases peristalsis. The onset of action is typically 24 to 96 hours. It does come along with some potential adverse effects, abdominal cramps, diarrhea, dyspepsia, nausea, for example. Yeah, and I think the ACG didn't really-- in their 2020 guidelines didn't really mention Miralax, probably if I'm going to cause it a potential treatment option. And so this was kind of an update when the AGA brought it up, but they do specify it's obviously for very mild symptoms. But much more gentle on your system is for as long-term control versus like an over-the-counter stimulal accident. We don't want to go that route if we can help it. The fiber intake is important, like we've talked about, or the increase in fiber intake. But there's also obviously fiber-based supplements as well, and essentially bulk-forming agents. The AGA-2022 guidelines don't really make mention of these. We're mentioning older, previous guidelines, things like the metamusyl or cilium, calcium, polychromic, carbophyll, which is like a fiber con, methyl cellulose, which is like what's in citric cell. The bulk-forming agents sound counterintuitive. But what actually is happening is it creates this gel-like matrix in the stool, and allows the stool to soak up fluid. And it adds bulk, which then can make that process of peristols. It's a little bit easier, more to push through, I guess. But if the patient has any sort of signs of fecal impaction, GI obstruction, or probably even a history of those, you do want to use some caution and make sure that you're not potentially worsening a problem. Onset of action, it varies depending on the patient, but it's usually 12 to 72 hours. It's kind of what we're thinking is for a symptom improvement. And because it's very easy for fiber to bind to and inhibit the absorption of other medications and other supplements and whatnot, it's usually something that should be taken two hours before after other medications. And you do have to make sure that you're adequately hydrated, drinking lots of fluids in order for it to work properly. And adverse effect wise, pretty mild for the most part, to increase gas production, maybe some bloating. But in more rare cases, can cause things like bowel obstruction and some serious issues. So not the best option by any means, and really not even something that has any great evidence in IBS, but it is still out there. And you'll see patients use it once in a while. Yeah, there's a few studies. For example, a 2011 systematic review showed no beneficial effect for bulking agents over placebo and improving abdominal pain. 2020 study showed slight improvement with a psyllium. 2008 study showed no benefit with brand, which is great. 'Cause I don't like brand. What is brand? Brand flakes, you know, those just-- - Brands definition, I guess brand is a brand, right? I guess it's probably a brand, a big grain. - Yeah, it's just like whole grain, it's like a whole grain cereal flakes with no just good taste, no show, no nothing good in it, you know, by my perspective. Nothing unhealthy in it, it's just like straight up, I presume like whole grain flakes that you eat. - Oh, there's nothing good to it. Well, how come Google AI then says it contains essential vitamins minerals to your fiber? They can be added to cereal, smoothies, and all kinds of baked goods. - What is this garbage? - I'm sure that's-- - That's AI's response, that's why you gotta use chat GPT or Gemini or something a little bit better. - I need my added sugars in my cereal. And I'm gonna get it from fiber rich outer coding serial grains. - Yeah, give me my look at charm, give me my brand. - So one prescription medication that's available is amatiza, a little bit per stone. It is a chloride channel activator that acts locally on the apical membranes of intestinal epithelial cells to increase fluids accretion and improve fecal transit. The FDA approved, it is FDA approved for IBS with constipation in women 18 years and older. It's approved for the treatment of-- - Any pathic-- - Any pathic-- - A video with pathic constipation in all adults. It's not been compared directly with other treatment options and it does have a recommendation that it needs to be administered with food. - And now we'll say this is my just more to sense, but I guess with some data to back it up. But amatiza's one that I kind of think of as being a little bit more of a wimpy or, you know, still prescription strength medication. So it's better than the over the counter stuff, obviously. But something I would consider a more wimpy medication in this space as far as some of the others that we're about to talk about. And, you know, the indication for women 18 years and older, there's plenty of off-label use in males 'cause like calls it, it's already approved for idiopathic constipation of different dose for all adults. So, you know, you can use it in men off-label. But there's a few different studies that were involved with, you know, it's approval and then I'll give you my anecdotal evidence after this. But there was a 12 week study that showed 18% overall response compared to 10% with placebo. And those benefits, you know, if you can call them that, persisted or even increased, I would hope so, an 8% difference, or increased at the 52 week mark, you know, follow-up. The 2012, the guidelines changed the definition, and as far as a response when it comes to like IBS constipation studies. And so they went and did a post hoc analysis, reviewed the original data. And based on the new definition, new criteria, now the results showed 24% improvement and 13% in placebo. So, a little bit more impressive, I guess. But also still not like anything. I'm like over the moon excited about. And the other kind of downside to amatizes that the symptom relief is not usually instance. And in fact, it can take at least a month to start really seeing like improvement. And so giving patients kind of a realistic, you know, timeline so that, you know, they stay on the medication and don't quit it after a few days and their symptoms aren't improving. Adverse effects wise, it's pretty well tolerated. You know, anything that is used to treat constipation obviously can push things too far in the other direction. So, it can cause diarrhea, some nausea, headache. And then the other thing to keep in mind is it can cause hypokalemia. So, it is something that if a patient's on other, you know, potassium wasting meds, you probably need to use a little bit more caution. Maybe some closer monitoring, at least when getting them on this medication, but I was anecdotally, this is the one that I feel like patients, if their symptoms are pretty, you know, intense, the other newer agents that we're about to talk about tend to do a lot better. Amatize, it seems to not be as effective, but on the flip side, the patients who have like very sensitive stomachs and like any of the newer medications just automatically cause, you know, the diarrhea and other GI side effects. I mean, those patients I actually had good success with amatize, because it's not as intense, but it is enough for them to, you know, alleviate their symptoms. So, just throwing that out there, it's not like I have a ton of experience with it, but it definitely run into that situation a few different times. So, I've seen them kind of play out in clinical practice. Those less than great, you know, impressive study results. Right. Before we move to the next one, you want to do the password? Yeah, I guess it's a good password time. So, we really want to, you know, put our heads together and we're like, what was something really elaborate that we can come up with? And we couldn't think of anything cool. So, we're just going to go with IBS 25. I'm sure some of you already guessed that. And, you know, Kudos to you. Should've done like Fod Mappers or something, something fun like that. That is good. Well, next time this is Fod Mappers, and like three years we'll do that. But it's too late now. We've already said IBS 25 and we can't go back 'cause we'll cause mass confusion. So, IBS, and that's capital already did, honestly. Yeah, that's true. Capital IBS and the number is 25. And make sure you enter that, you know, on FreeCe's website, there'll be a list of all of the accredited podcast episodes. Find this episode and then I'll be your password to get access to that post activity, multiple choice tests. Good luck to all of you taking it and I hope you get your one hour of continued education credit. I think you guys can nail it, I'm sure. If you don't, it's probably 'cause you just gave up on the test. Yeah, yeah. All right, let's give back to it. The next class are Guantalite cyclase agonists. There's two of them currently have to be approved. Lenzes, which is Lanacletide and Trulance, which is Placanetide, or I guess is I pronounce it. They increase chloride and bicarbonate secretion into the intestinal lumen. They do have a box warning related to death due to dehydration that was seen specifically in animal studies. They recommend avoiding the use in pediatric patients in particular. Lenzes must be kept in the original container. I'm sure any retopharmacist that one is Ganya. It's Ganya before. And they have some administration instructions. Take Lenzes 30 minutes before breakfast on an empty stomach. And but Trulance can be taken with or without food. It doesn't matter. And if you take Lenzes with breakfast, especially like a nice fatty breakfast, get your sausage and turkey bacon and eggs. The odds of diarrhea are strong to quite strong. And so if you have a patient. Yeah, strong to almost 100% certainty. And if you have a patient who is complaining of diarrhea, excessive diarrhea, do double check how they are taking it. Because it does make a pretty bit difference with Lenzes in particular, that 30 minute window. But making sure you take it on an empty stomach is very important for minimizing the GI upset after taking it. So I've also seen that one play out pretty significantly. And then sometimes you just have to back the dose off a little bit. But Lenzes, definitely a good option. Trulance, also very good. And there's some, a couple of different studies that were involved with getting both of the FDA approved. There was one that was looking at Lenzes versus placebo. And it showed significant reduction in symptoms with the treatment arm. With a number needed treat for the primary compositive, only six. The statistical difference from placebo was actually reached by the end of week one. And so you have a much better onset of action and symptom relief time compared to like amities. I mean, at least based on the studies, obviously, it's not fair to compare them like that. But whatever, one study in particular showed that there was a continued benefit from that initial portion of the study that continued benefit at the six month mark. And obviously that's encouraging, especially since some of the IBS studies that were done earlier were much shorter in length. And then with Trulance, it was also compared to placebo. And it showed significant reduction in symptoms with a number needed treat of nine. And again, statistical difference from placebo was reached by the end of week one. And so if you look at the AGA 2022 guidelines, they do recommend Lens S with higher certainty of evidence compared to Trulance. So the high certainty with Lens S and moderate certainty with Trulance. But essentially, that's because Lens S has one extra randomized control trial. It's got four compared to three done with Trulance. And it's just shown improvement in all end points with those four studies. So it gets a higher level of quality. And I will say I do tend to probably use Lens S more often if I'm dealing with these. But if you've done either option Trulance or Lens S and one of them did not work, it is perfectly fine to do a trial of the alternative agent in the same class, even though they're technically same class of medication, same mechanism. Some patients do respond better to one over the other. And before insurance companies will pay for the next drug in our lineup, a lot of times we'll want you to have tried Lens S and Trulance. And the two times that I've gotten this next drug, we're going to talk about approved. I had to verify the patient had tried both of those drugs. So food for thought, for those of you who are dealing with prior authors and stuff, throw that out there. Yeah, I'm sure that's going to pop up with these. Another class of medication are sodium hydrogen exchanger three medication. It's abbreviated as NHE3. But Ibserella is the drug to napenore. Yeah, to napenore. It acts locally to reduce sodium absorption from the small intestine and colon reducing sodium absorption leads to increasing intestinal lumen, water secretion, and accelerating the intestinal transit time. It also has a box warning for risk of serious dehydration in pediatric patients. So that's significant. And so I'm going to consider. But it has other normal adverse effects related to risk for diarrhea, dizziness, and abdominal distension. If you-- if I had no idea what the plan was today, and you said, hey, your only hint is that you're going to use the word accelerating fecal transit time, at least three times. So I'd say, well, it's got to be podcast day. Who do you think a card was that on? Yeah, because that's the only time I think of that's going to happen. Ibserella is very expensive. So I think it's like $1,500 for a 30-day supply last time I checked. And so this is typically going to be more of your last line after you've kind of gone through the lenses, trulance, probably even amatiza. But at least trulance and lenses for a lot of the insurance companies before they're willing to fork over that kind of money. But it's the newest kid on the block. And I will say I only had one patient that I worked with that had tried everything for constipation was on multiple over-the-counter products. Not to much work in. And I talked to the attending. I was working under and asked about this drug. And he's like, yeah, he's looking up on up-to-date as I'm talking about it. And he's like, dude, it sounds great. Let's try it. And the patient was thrilled with the results. I got it approved and it was really cool to see. She was super, super excited. I was like, yes. We basically gasped for entriologists. Look at us go. But yeah, I was shocked at how expensive it was because it was around 1,500, I believe. Not a cheap drug to get your hands on. But no, not for that. But yeah, so we'll come back to some augmentation options with dealing with these patients when we get through the diarrhea symptomology. But there's a lot less treatment options when it comes to IBS with diarrhea. And we were calling out we're joking about earlier. I mean, there hasn't really been a new drug approval since 2015. And our options are very limited. There is a couple things in the pipeline that are showing some promise. But nothing that has been approved in the last few years. So we'll start off with if the patient is very mild symptomology, diarrhea, being the predominant one, lupyrmide, which is just over the counter, brand name, amodium AD. I'm sure we've all seen this at some point in time. The 2022 AGA guidelines do recommend. Lupyrmide is a treatment option for mild IBS with diarrhea. However, they do say that it's very low certainty evidence. Mechanistically, lupyrmide is going to directly work on the intestinal muscles. And it works through the opioid receptors. And basically, this inhibits parastelosis prolongs transit time, reduces fecal volume, and also increases viscosity, and diminishes fluid and electrolyte loss. And from my dosing perspective, the suggested dosing, two milligrams, 45 minutes before a meal on a regular schedule for regular schedule doses, with a max of 16 milligrams per day. And then if it's more acute diarrhea, then you can do that 4 milligram loading dose followed by a 2 milligram dose after each loose stool thereafter. As far as evidence to back it up, systematic reviews have shown lupyrmide is superior to placebo, although, again, the quality of that evidence is not super impressive. It is effective at decreasing stool frequency, as well as consistency, and not necessarily symptoms of bloating or abdominal discomfort. So it's helping with the stool consistency itself. But lots of other symptoms they can go on answered. So interestingly, it also has abuse potential, which you wouldn't really think of for a diarrhea medication. But patients have used OTC lupyrmide to self-treat the symptoms of opioid withdrawal, or to achieve euphoric effects of opioid use, something to keep in mind. It has a box warning for cases of cardiac issues, torsade de puentes, cardiac arrest, and death. So clearly, abusing it would be not particularly safe. It does have some contraindications. You shouldn't take it if you have bloody diarrhea with a high fever, and has some other adverse effects related to abdominal cramping, constipation, nausea, and QT prolongation. So patient has other meds that can prolong the QT interval, and low magnesium, other risk factors for torsades, and especially if they're taking really high doses. That patients have-- there's been a lot more case reports than you'd probably think of patients actually overdosing on lupyrmide. I know that was something I looked into years ago, and I was shocked that that was an actual thing that was going on. But the bloody diarrhea had obviously been a contraindication, because you probably want to rule out C-DF if you're dealing with that in top of a high fever. But let's get into the little bit more efficacious medications, if you will. We have an antibiotic that is familiar to-- I'm sure a lot of you-- but Zyfaxin-- Rhyfaxin is an antibiotic that was originally used to produce hepatic encephalopathy. But it also is used for things like travelers diarrhea, and now IBS with diarrhea symptomology. And it seems to be particularly useful in patients that are having diarrhea, but also experiencing heavy bloating. And it's not like a long-term chronic medication. It's actually something that just is used to kill off and control some of the bacteria in the gut. And it's actually only a 14-day course. So they do 550 milligrams three times a day for 14 days. And think of it as a loading dose, if you will, to your treatment, because they'll use this in combination with the other med we're about to talk about another adjunct of medications that you can use for the abdominal pain and whatnot. But it is a good intro to get control of that bacterial growth, if there's signs of that, like with the bloating and all that. Adverse effects can cause peripheral dima, dizziness, headache, flatulence. So pretty well-tolerated. And the American College of Gastroenterology does suggest that the non-absorbable antibiotic or if a mixin is a good option for reducing global IBS symptoms, as well as bloating in non-constipated IBS patients. I like that. They didn't just say diarrhea. They just said non-constipated. Because it could be completely unclassified. You could, yep. It's not specific enough. It's not specific type. Unspecified. Unspecified. Another medication, vibaryzilexedoline, maybe, it is a mixed-- You're really questioning your-- No, I usually feel pretty confident about it. Usually on the last two, you're down on yourself tonight. Now, I don't feel good about that one. I'm going to say I was wrong. But it's a mixed-mew opioid receptor agonist, Kappa opioid receptor agonist that acts locally to reduce abdominal pain and diarrhea in patients with IBS. D without constipating adverse effects. It has contraindications. For instance, if a patient has had their gallbladder removed, they're not supposed to take it. If they are an alcoholic, if they have alcoholism, they shouldn't take it. They specify patients who drink more than three alcoholic drinks per day. There's potentially a risk for pancreatitis, and it has adverse effects, like constipation, nausea, abdominal pain. And upper respiratory tract infections. That's recommended to take it with food, and it is a controlled substance. So I think a C5. Is it-- I was thinking it was a C3 or 4, but I could be right. Yeah, we can Google that in a second. But I remember vividly, and almost 100% sure I've told this story on here at some point or another. But I was like 19 or 20 maybe. I was still in undergrad. I was a tech. I wasn't even an intern yet. And no, no, I couldn't have been, because it was 2015 in the skin. So I must have been-- actually, I must have been graduating, or getting close to it, actually. So my timeline's totally out that I just realized, in real time as I'm telling the story. But I don't want to lie to you guys. So I'm going to keep it honest. But I remember sitting in the pharmacy, I wasn't an actual licensed pharmacist. I do know that, because I was standing at the front counter, ringing people out and stuff. And this little lady start off very sweet, took a turn, as we found out her medication wasn't ready. And it was because she was trying to pick it up five days early, and trying to explain, well, it's a controlled substance. And she's like, what does that mean? What is a controlled substance? And she's like, well, well, controlled substance meaning that there's some abuse potential. And she goes, are you kidding me? She's like, I am so sure. There's abuse potential. She goes, this is my diarrhea medication. She just started yelling at me in front of all these people in the waiting room area, lobby, and I was just kind of like, man, can we please not shout diarrhea that loud? But she's so hostile. And then you still graduated pharmacy school and went to work for them? Yeah, I know. I was like, what am I doing? This is a terrible decision. But it's a good learning opportunity. I'll leave it at that. But Vibersie, definitely one of the more effective options that is approved for IBS of diarrhea. And for a lot of patients, unless they have any of those contraindications, a good one to consider. If all else fails, we do have a medication called Elisitron or Lotronx, which is a 5-hydroxy atryptamine three receptor, 5-HT3 antagonist. So working on serotonin receptor, 5-HT3. And it is approved for the treatment of severe IBS with diarrhea in female patients, only whose symptoms have lasted for six months and who have failed to respond to all other conventional treatment. And you may be asking yourself, why is such strict guidelines as far as who can be a candidate for this medication? Well, it's because after this medication was on the market, we started getting case reports of a causing a schematic colitis and complications of severe constipation leading to it being eventually withdrawn from the US market. And so now it is available under this restricted prescribing program. And I actually think they're doing away with that as well. So this probably won't be something that will have-- clinicians will have access to, but maybe none of the countries and stuff. So we figured we'd keep it in here and still mention it. But probably one, you won't be seeing all that often, if at all. Yeah. All right. So kind of finishing up here with IBS, global symptoms, there are some universal symptoms, like I've been saying four or five times already. Global symptoms. That's what I meant to say. Yeah, not the whole universe, just the globe. Just the globe. Just the world. I was getting way too broad. Yeah, yeah, way too big. Whole universe. Interesting medications that can be used, in particular, TCA's. Try sick, looking at it in presence. You have your tertiary amine TCA's, the L-A-VIL, doxapin, and metpermine. The secondary amine TCA's, like decypermine and nortriptoline. They block the reuptake of serotonin and norepinephrine. They also block acetylcholine and histamine receptors. And they are definitely not without their side effect profiles. And some of them can be pretty intense. And in fact, the concern, because these are meds that they use in behavioral health and things like that, obviously, things like overdose and whatnot, something that needs to be considered. And overdosing can actually cause very quickly the patient to develop these fatal arrhythmias. And so if you do have a patient that you're thinking about starting a TCA on, it's a good idea. If it's a patient who already has cardiac risk factors, or if the patient is over the age of 50, that you get a baseline EKG, just to make sure that there's no arrhythmias going on that the patient's unaware of. As far as the kind of common side effects, orthostasis is a big one. They can be problematic for several reasons, including obviously our geriatric patient population, increasing fall risk, and all that. Anticholinergic effects are pretty substantial with this class of medications. Some being worse than others. It can cause they can have vivid dreams, weight gain, sedation, sweating. And as a general rule of thumb, the tertiary amines tend to be more likely to cause side effects, or at least more intense side effects. So this can come to as an advantage in the case of IBS with diarrhea, in particular, amitryptaline has pretty intense anticholinergic effects. We just compared to the other members of the TCA class. And so the guidelines do kind of bring up if the patient needs something for global symptoms, you know, the pain and abdominal cramping and all that. But the diarrhea is their predominant symptom. You may be able to use that anticholinergic effect of the amitryptaline to your advantage in that case. And maybe improve the stool consistency along with the global symptoms. So amitryptaline could be utilized in that case to do an advantage, but definitely something you need to be aware of as far as the difference in side effect profiles between the different drugs, right? The TCA's are recommended in terms of guidelines by the 2020 ACG guidelines and the 2022 AGA guidelines. The ACG guidelines recommend against the use of anti spasmodics. So those would be like hypsymine, dichylamine, for example. The AGA guidelines recommend the use of anti spasmodics, but they give it a low certainty of evidence. It's a more recent guideline, 2022. Hypsymine, I know they're not going to, yeah. Hypsymine, like I mentioned, is an anti spasmodic. It's usually dose 0.125 to 0.25 milligrams orally or sublingually three or four times a day is needed. Does have some adverse effects associated with it anticholinergic adverse effects, tachycardia, abdominal pain. Dicyclamine, which is bento, is dosed 20 milligrams four times a day. You should avoid the use in patients with ulcerative colitis because of the increased risk for toxic mega colon. And it has other adverse effects related to anticholinergic effects as well as anxiousness. And I think the 2020 the ACG guidelines did sort of make a note that they didn't bring up like Dicyclamine or Hysemin, or didn't include those as part of the recommendations because the one, the low quality of evidence, or low certainty evidence, but also there does tend to be a kind of a pattern where a patient gets started on these and they just keep getting refilled with large quantities and see if patients are getting these big quantities of Dicyclamine or Hysemin for like a year and no one's sort of re-evaluated. And I think that kind of all goes back to making sure that the patient doesn't have other kind of like underlying inflammatory issues going on or some more severe that the meds covering up and you don't actually do further work up. So again, some debate there, but they can be effective as needed for patients that are dealing with those global symptoms. Again, global symptoms, not universal. All right, let's bring it home and talk about kind of a big summary, patients IBS, categorizing them based on obviously their symptomology, but all of these patients could at least somewhat benefit from some of the non-pharmacologic interventions that we talked about whether it's on the behavioral health side, the cognitive behavioral therapy or hypnotherapy, or on the diet side with the fiber intake or you know, fog map restriction and all that. And then when we're actually coming up with maintenance medications for the primary symptomology you know, we were looking at either constipation or diarrhea. If it is constipation and it's considered very mild in severity, then we may be able to get away with you know, an osmotic laxative like mirror lax. And then you know, we typically will consider you know, there's some sort of a TCA or anti spasmodic when it comes to abdominal pain, the global symptoms. If we get into the realm of, you know, moderate severity to severe, you know, we're thinking about more of our secreted dogs like the amatiza, the lens S, the trulance or our new kid in the block, Isabella. And we kind of want to work our way through, you know, the newer or the older agents first and then Isabella would be kind of the last one to go with and of those just because of the way insurance coverage and all that stuff is going to go. On the diarrhea side of things, lapyramide can be utilized if it's again, very mild symptomology. There's also some data with like bile acids, questions as well, like well call. Same thing with the abdominal pain, global symptoms, you can use anti spasmodics, TCA's potentially. But first line treatment often times if there's bloating and some of those type of symptoms, we'll do a 14 day course of Zyfaxin. And then Vibersi is one of the, you know, prescription options that you can do long term. And then again, we have our TCA's for like global symptoms, but with diarrhea, specifically maybe consider amatryptoline 'cause you can kind of use the anti-colonurgic effects to your benefit. If the symptoms of abdominal pain, psychological symptoms aren't improving with treatments or, you know, improvement of, you know, overall stool frequency and all that, then considering switching, you know, to another TCA or if, you know, they're already taking a TCA and it's no improvement in that SNRI or cognitive behavioral therapy, like brain gut, behavioral therapies, basically CBT, hypnosis and all that. So there you have it. That's our breakdown or summary, if you will. And IBS is hopefully going to have some new meds on the horizon over the next couple of years. So I'm sure we'll be doing another episode, you know, God willing at that point and cover all those new and improved treatment options. More poop talk. Yep. As everyone looks forward to, do you have anything else you want to go through with this? It's all I got, man. Well, we appreciate all of you listening. I always want to remind you that if you do want more structured style, you know, content and, you know, lectures with PowerPoint slides and all that good stuff, check out our Patreon, patreon.com/coreconseltarex. And we have lots of different clinical therapy lectures on there with slidesets that you can download along with it. Some practice, like, board type questions that go along with some of the disease states that are talked about. And it's fairly cheap, you know, as far as reviews of photocotherapy goes. I think you can get a year's access, you know, and download all the slidesets and all that for like $33 or something. 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