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April 15, 2019 – Dr. Kelly Diehl talks about gastric acid secretion issues in dogs and cats with Dr. Katie Tolbert, Clinical Associate Professor of Medicine at Texas A & M University College of Veterinary Medicine and Biomedical Sciences. Dr. Tolbert also discusses her Morris Animal Foundation-funded work to evaluate the effectiveness of a commonly prescribed drug for chronic kidney disease in cats.

00:18 Dr. Kelly Diehl: Welcome to Fresh Scoop, episode seven: Understanding Control of Gastric Acid Secretion in Dogs and Cats. I'm your host, Dr. Kelly Diehl, Morris Animal Foundation's Interim Vice President of Scientific Programs. And today, we'll talk to Dr. Katie Tolbert, Clinical Associate Professor of Medicine at Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, and a Morris Animal Foundation funded researcher. For those of you who may be new, Fresh Scoop is the monthly podcast of Morris Animal Foundation, the largest non-profit Foundation in the world dedicated to funding studies that find solutions to serious health threats in animals. Founded in 1948 by Dr. Mark Morris Sr., a veterinarian, we've invested more than $126 million in more than 2,600 studies that have improved and protected the health of companion animals like cats, dogs, and horses, as well as wildlife. In each episode, we feature one of the researchers we fund or one of our staff members, discussing their work in advancing animal health.

01:23 DD: Whether you're a practicing veterinarian, technician, or student, or just an animal-loving science geek, Fresh Scoop is the podcast for you. Okay, onto today's show. Today, we welcome Dr. Katie Tolbert, Clinical Associate Professor of Medicine at Texas A&M University, College of Veterinary Medicine and Biomedical Sciences. Dr. Tolbert completed her veterinary degree in small animal medicine and surgery internship at the University of Georgia. She then did her small animal internal medicine residency at North Carolina State University before pursuing a PhD in Comparative Medical Sciences from there as well. And Katie is a Foundation-funded researcher with a special interest in gastrointestinal diseases. Her most recent grant with us was focused on evaluating a commonly prescribed drug, Omeprazole, for chronic kidney disease in cats. And Katie, thanks for joining us today.

02:19 Dr. Katie Tolbert: Yeah, I'm happy to be here.

02:20 DD: So, to start with, before we get into your grant with the foundation, can you tell us a little bit about yourself and your background beyond what I just... All that formal stuff I just did?

[chuckle]

02:32 DT: Yeah, so like you said, I'm a small animal internist, so I practice small animal medicine on dogs and cats. And then I also have a laboratory, basically, in concert with the gastrointestinal laboratory at Texas A&M, which is great because it really provides both support, mentorship support from people who have been doing gastroenterology for decades and then also has a wide recognition with both veterinarians and clients alike, which really helps when we're doing things like clinical trials.

03:09 DD: Great. To dive down a little bit more, I know you've been doing GI stuff for a long time, but can you tell everyone why you chose to focus on stomach acid secretion in dogs and cats and the regulation of that?

03:26 DT: Yeah, that's a great question. I think for me, medicine... I consider myself a bit of a generalist when I'm practicing medicine. I like everything, including endocrinology and respiratory disease and everything. And so, I think sometimes what happens, you know how it is when you're a student, you are wide-eyed and bushy-tailed, and the direction that you take oftentimes is influenced by the people that surround you. So, I had really great professors in the area of gastroenterology which first stimulated my interest. And then when I was a resident at NC State, I was working with an investigator, her name is Sally Bissett, and she was actually the first one that really was interested in looking at acid suppressants in dogs and cats. And so, she got me onto this, and then just developed my interest even more.

04:10 DD: Okay. So, as a former practitioner, I know that we use a lot of these drugs for acid control a lot, but can you... I know there's still some issues. Can you review some of the big questions that remain unanswered about gastric acid manipulation really, in dogs and cats?

04:33 DT: Yeah, there's really so many, which is why it's a good field for me to be in, because there's so many questions that we have. And one of the biggest problems that we have is that there are really so few studies in dogs and cats, and obviously, Morris Animal Foundation is trying to change that, but so few studies to understand, first of all, why ulcers develop in a dog and cat, and what conditions cause the development of gastric stomach ulcers in dogs and cats, and what are the best treatments for those. So, we have, literally, a handful of studies that really even embark on that. And so, what happens a lot of times is that some of these drugs that we use to treat these conditions, namely, things like Prilosec and Pepcid, they're available over the counter.

05:18 DT: And so one of the problems that we have is that clients sometimes are like, "Well, my dog is vomiting, my cat is vomiting, or my dog's not eating, and so I can give this medication because it works for me," and we don't know that that's actually the case. And the other thing that we have is a lot of dogma that's applied from human medicine to veterinary medicine, which we know is really inappropriate. So, for example, in humans, chronic kidney disease can cause ulceration, and in dogs and cats, we're finding that that actually may not be the case. So, we really need to do these studies to really understand what is the best way to treat ulcers in dogs and cats, and when should we treat them.

05:53 DD: Okay, so before we dive, that was a good lead-in to your research that we recently funded, but most of our audience is veterinarians, but we do have some donors out there, and so, could you give us all a review, just very quickly, on the types of acid blockade drugs that we have available to us, and a little, really quick summary of how they work?

06:20 DT: Yeah, sure. So gastric acid production is stimulated by different hormones. And so, the drugs that we have available to us can act on those hormones or can act actually on the acid-producing protein itself. And so, we can use things like, for example, histamine 2 receptor antagonist, so that's like the Famotidine or Pepcid, and that blocks histamine which is a potent stimulus for gastric acid secretion. Or we can use something called a proton-pump inhibitor like Prilosec, or Omeprazole, or Nexium, also known as Esomeprazole, and those will basically block acid secretion at the acid-producing protein itself. And then, I guess the other thing that I should mention is there's also something called antacids, and those basically just don't do anything for acid production, but they kind of neutralize the acid that you have in your stomach. So, an example of that would be Maalox.

07:18 DD: Right, or TUMS, right? because I think...

07:19 DT: Yes, exactly.

07:21 DD: I think sometimes our... At least our clients know those very well too, right?

07:26 DT: Yeah, yeah, exactly.

07:27 DD: They're kind of old-fashion ones. As you led into it before, let's talk a little bit about the latest research grant you had looking at Omeprazole's use in cats. So, for everyone out there, can you tell us the basics of your grant, just the hypothesis and your methodology and what you were interested in?

07:49 DT: Yeah, absolutely. Let me just give a bit of background first. If you were to pick up a textbook on small animal internal medicine and you looked up stomach ulcers and what causes stomach ulcers in the dog and cat, one of the things that you would find is that chronic kidney disease is listed as a condition that causes that. And not quite sure where that came from, but it's something that's just sort of been passed down to generations. In fact, I remember that when I was in vet school, learning that, that that was one of the conditions that causes ulcers. One of the problems that we have, especially in cats, is that it can be really difficult to pill a cat. And so, when we recommend treatments for cats and dogs obviously, we want to make sure that they're really appropriate and it's reasonable to put the cat or dog through pilling them for that particular medication. And so, I got to talking a little bit more with some anatomic pathologists about ulcers and dogs and cats with chronic kidney disease, and they said, "You know what, we actually don't see that ever in dogs and cats that have chronic kidney disease, unless there's another reason why they might have ulcers." And so, we're like, "Oh, that's interesting."

08:52 DT: And so, one of the first studies that we did, which was funded by the ACVIM Foundation was we looked to see if the stomach pH of cats with chronic kidney disease differs from age-matched healthy cats. Because sometimes what happens is if you have a really acidic stomach, which was suspected to be the case in chronic kidney disease, you could develop ulcers. And so, we were like, "Let's just start with that and see if that's something that could be a problem or not." And so, when we did that study, we were surprised to find, actually, no, that that's not the case, that cats don't have acidic stomachs when they have chronic kidney disease compared to healthy cats. And so, when we talked to veterinarians, they said, "Well, we understand that's the case, but we still feel like acid suppressants such as Omeprazole provide a benefit to cats. It seems to stimulate their appetite and reduce vomiting." And so that's what this study is really about.

09:45 DT: That's kind of the next study that we're doing, which is a clinical trial, where we have cats that are randomized. It's a crossover study, meaning that they receive both treatments, placebo and the drug Omeprazole, that acid suppressant, the proton-pump inhibitor that I talked about. And both, ourselves are working with Dr. Jessica Quimby out of Ohio State, and the clients are blinded to what treatment is being received. And so, essentially what happens is that we follow these cats, they get the treatment for 14 days, and they undergo a rest period, and then they get the other treatment for 14 days, and we're monitoring, "Does it seem to improve their appetite? Does it seem to improve their activity? Do they seem brighter? Did they have a reduction in vomiting?" And that will really help us understand, is this really an appropriate treatment for cats that have chronic kidney disease? Is there a benefit, or should we take this off the table because it's one more medication that we're using? Which really, cats suffer an enormous pill burden with chronic kidney disease. And so, if we can take this one off the table, that would be great. So, either finding whether it would show a benefit or not is actually going to be really helpful to veterinarians who treat cats with chronic kidney disease.

10:54 DD: And what are you seeing so far with it, if you can comment on it?

11:00 DT: I can't because I'm blinded.

[chuckle]

11:01 DD: Oh, that's right. That's right.

11:02 DT: Yes. But I will say that we are about a little over halfway through. The study has gone really, really well. The owners have been really happy to help us out. They're completing a daily log to let us know what's going on. And so, I haven't looked at the results because I just don't want to even try to figure out if there's a difference, to be honest, just so I can stay blinded. And the other thing I'll say, just to plug, is that if there are any veterinarians or owners who have cats with chronic kidney disease near the college station, Raleigh, or Columbus, Ohio area, please, please contact us.

11:39 DD: Cool. So how many cats have you enrolled?

11:44 DT: I believe that we... And I need to double-check, but I believe that at this point we've enrolled about 10 cats, and I think we're looking for 16 total. So, we have about six more cats to enroll.

11:55 DD: Cool. So how has your research maybe changed the way you practice? I know this study is still in progress, but has your research made you really look at things differently?

12:11 DT: Yeah, [chuckle] yes, definitely, in a variety of ways. I guess probably the most specifically as it relates to this topic with you, when I first... My very first study, the one I mentioned with Sally Bissett and my residency, it was a comparative study looking at acid suppression in dogs. And essentially, what we were trying to do is figure out, what was the most potent acid suppressant in dogs? And what we figured out is that the proton-pump inhibitor, as expected, is more potent, so a better acid suppressant as compared to something like a histamine 2 receptor antagonist or Famotidine. And so, when I first started out, I was like, "Okay, well, we need potent acid suppression, we need to treat this for a variety of conditions." And now, more than a decade later, I'm sort of on the opposite end of the spectrum where I'm really concerned about the overuse of these medications.

12:55 DT: And now, sort of my, I guess, call-to-arms, is to try to figure out what diseases is it not appropriate for so that we can really be mindful and have a rational use of these medications. Because, certainly in humans, especially when you use these drugs chronically, they can cause some pretty serious side effects.

13:14 DD: Right. And so, I'll ask you about that, because I think the... And I'm sure you were taught the same thing I was, was there was this feeling like, "Well, that can't be that bad. They're pretty benign medications." But can you tell all of us what the... That these do have side effects and what they are.

13:33 DT: Yeah, so the side effects that we know of are most commonly reported in humans. And I have to be a little bit careful because causation does not obviously... Association does not mean causation, I should say. So, the unfortunate thing about a lot of the studies in humans is sometimes it's very difficult to tease out, is Omeprazole just associated with these side effects because they're used in people that are already predisposed to these side effects, or does it actually induce or cause these side effects? So, I'll just put that disclaimer out first. But some of the biggest things that we see in terms of what we're worried about potentially is, with long-term use, things like osteoporosis and pathologic fractures. So, for example, one of the biggest reasons why I worry about it in chronic kidney diseased cats is they're already predisposed to having osteopenia as a result of their chronic kidney disease.

14:25 DT: So, if this drug causes that too, then that's certainly problematic. Some other things that I worry about are things like, it increases your risk of certain GI infections such as Clostridium difficile. It potentially increases your risk for nosocomial pneumonia. So, if you're in the hospital and you're already sick, and then you're getting a lot of acid suppression, one of the things that stomach acid does for you is it actually prevents bacteria that enters your stomach into getting anywhere else, because it kind of kills that bacteria. And so if you take that defense mechanism away, and then you get colonized, your stomach gets kind of covered with this nasty bacteria that you might pick up in the hospital, and then you just happen to aspirate while you're in the hospital because you're debilitated and you're lying around, then you can get a really, really bad pneumonia.

15:16 DT: And that's one of the ones I'm really actually worried about in dogs and cats, specifically, in our hospital. Something that I'm really interested in studying is, does it potentially increase your risk or maybe worsen pneumonia in the hospital if you're given acid suppressants?

15:33 DD: And that actually makes me think of another question that I was going to ask you, so thanks for the lead-in, which is, I think a lot of us out there have been trained, for sure me, to acid suppress dogs that are in danger of aspirating. Right? Because the theory is, well, maybe it's not so acidic if they have trouble, and it sounds like maybe we're not thinking right. So, what do you do now, as a clinician, what do you tell veterinarians who may call for a consult about when you really should be reaching for some kind of gastric acid suppressor, and when maybe you shouldn't?

16:14 DT: Yeah, so the biggest thing for me is, do you have documented or suspected GI bleeding, or do you have documented or suspected esophagitis? If you have those things, then I think acid suppressants are reasonable. If you don't have those things, for example, you're just like, "Well, this dog has CKD, or this dog is vomiting, or this cat has liver dysfunction," but no evidence really that the patient has GI bleeding, or has inflammation in their esophagus, then it's really not appropriate to use those drugs, and potentially really increases the risks of side effects.

16:52 DD: Okay, so it sounds like your recommendation is really quite focused now on when you would recommend these. Just really quickly, because you mentioned dogs and cats, are the recommendations different between dogs and cats, whether it's medication used or diseases you may think about treating?

17:15 DT: I would say the development of ulceration is certainly more of a concern in dogs compared to cats, although it's still a concern in cats. But typically, when we see upper GI ulceration, so I mean basically the stomach and the first part of the small intestine or the duodenum, we think about things like cancer. So basically, my top three differentials, if I see upper GI bleeding in a cat, is cancer, cancer, cancer, versus in the dog, I think more things can potentially cause it. In the dog, I think about more like, certainly cancer, but non-steroidal drug administration, which we see as a more common... It's obviously more commonly used in dogs and definitely more commonly causes GI ulceration in dogs. And then things like Addison's disease or severe systemic illness sometimes can do that as well. So, it's just that we see it more commonly in the dog, I think, than the cat.

18:11 DD: So, thinking about what we were just talking about, what do you think right now, and I know your research isn't done, is the take-home message? If you were to talk to veterinarians and owners, what would you want them to know about these drugs?

18:30 DT: Yeah, I think probably for veterinarians specifically, because this really should be, honestly, even though it's available over the counter, it should be prescribed by a veterinarian. So, clients should not use these drugs without consult of their veterinarian. And so, I would speak more to the veterinarian. It's really more to think about why you're using it. If you're using it for, because you suspect or you document upper GI ulceration, that's completely appropriate.

18:52 DT: If you're using it for something else, like vomiting or appetite stimulation, there are other drugs that are much more effective for those conditions than things like proton-pump inhibitor. So, if you have vomiting, I would suggest that you use an antiemetic. If you want an appetite stimulant, then use a drug that's marketed for appetite stimulation. So, reach for those other drugs that make more sense to use in those situations rather than of trying to use proton-pump inhibitors for a variety of things, which is not so appropriate.

19:19 DD: So that's good advice, because I think it's really different. I'm getting older, I hate to admit it, but I think that's really different than what we were trained to do that, again, these were fairly benign, they did all those mystical things, like make animals feel better, I think [chuckle] is a lot of times...

19:38 DT: I think the other problem is we have those anecdotal situations, right? We all have those anecdotal cases where a patient was vomiting. We gave them Prilosec, and they stopped vomiting. So now, every patient who's vomiting gets Prilosec, which is not really appropriate, but I can see where that comes from.

19:53 DD: Right, right, exactly. So, we were talking about this, and you were talking about this before, some of the big research questions and questions that still really need to be answered, that there's no good data or really good controlled studies to support the use or not use of these drugs. Looking ahead, pie in the sky, kind of your wishes, where do you think your research focus is going to be over the next few years? What questions would you like to tackle based on what you know now?

20:27 DT: Yeah, I think it's kind of some of the things that we've been alluding to. Really for me, now my focus is really defining the appropriate use of these drugs. And so, I'm very interested in investigating diseases such as chronic kidney disease, such as liver failure, such as pancreatitis, to see if these drugs are appropriate for those conditions or not. And then, again, another thing that we kind of talked about, looking for side effects of the long-term use of these drugs so that... Maybe there is an indication. You have a patient that has a slow-growing gastric tumor that seems to alter it, and you feel like the patient needs a potent acid suppression. Are there things that we can do to mitigate some of those side effects? Maybe it causes, I don't think so, but maybe it causes vitamin deficiencies, and so, should we be supplementing vitamins in those particular cases? So, all of the studies that I really want to do have kind of immediate clinical application so that we can direct how we treat these patients appropriately.

21:29 DD: That sounds really interesting. I know that, as a veterinarian, I know the folks listening, both veterinarians and cat and dog owners probably, can take a lot from our discussion because I think you're right about it's no fun giving pills to, especially cats, and to cut something out that's ineffective, I think, would make a lot of owners happy. And for those of us on the, as you know, answering the phone with my cat spitting out the pills, you always feel bad doing that. So, I think that sounds really interesting. Well Katie, thanks so much for joining us today.

22:11 DT: Yeah, thank you so much, Kelly, I appreciate the opportunity.

22:15 DD: Yeah, you answered all of my questions and telling us about this issue. I think it's a really... Seems like it's becoming a very popular subject at the conferences that I've been to and revisiting, as you said, what has become dogma in veterinary practice with maybe not all the science behind it. So, I'm going to look forward to see what happens with your [chuckle] study when it all flushes out. I think that's...

22:42 DT: Me, too. I'm looking forward to it as well. [chuckle]

22:44 DD: I think it'll be really great for folks. So again, thank you so much for joining us. I know you have to run off, so I appreciate you carving out the time.

22:53 DT: Yep, absolutely Kelly, I'm happy to do it.

22:55 DD: Alright, take care, Katie.

22:57 DT: Okay, bye.

22:58 DD: Bye. That does it for this episode of Fresh Scoop. Once again, thanks to Dr. Katie Tolbert for joining us. We'll be back with another episode next month that we hope you'll find just as informative. The science of animal health is ever-changing, and veterinarians need cutting-edge research information to give their patients the best possible care, and that's why we're here. You can find us on iTunesSpotifyGoogle Play Music, and Stitcher. To learn more about Morris Animal Foundation's work, again, go to morrisanimalfoundation.org. There, you'll see just how we bridge science and resources to advance the health of animals. You can also follow us on FacebookTwitter, and Instagram. I'm Dr. Kelly Diehl, and we'll talk soon.