Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast Narrator - ? 00:11 is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk. Episode 114 Dr. Khyati Patel 00:33 I'm your co host, Dr. Kane, and I'm Dr. Patel, and today we are going to talk about nutritional and pharmacologic consequences of bariatric surgery. The title of our episode is what else to lose besides weight, nutritional and pharmacologic consequences of bariatric surgeries. So the essence of this episode is to highlight some of the important nutritional deficiencies that can occur, some of the pharmacologic changes that can occur post surgery, particularly pharmacokinetic and dynamic changes that affect these patients and will require pharmacist interventions on coming up with dosing regimens, as well as providing some pkpd changes related interventions. Dr. Sean Kane 01:19 And you know as Dr. Patel before you kind of propose this episode, I didn't even really fully realize that there are different kinds of bariatric surgeries, and depending on the surgery that could potentially dictate, you know, how severe the risk of nutritional deficiencies are. So I think that there's a lot in this episode to unpack. Dr. Khyati Patel 01:37 Yeah, no, that's absolutely right. And the world of bariatric surgery is evolving. So we have different type of bariatric surgeries, but at the same time, the research behind what surgery can cause, what type of risk and what type of pharmacologic changes is still also emerging. So the information we have today is what we know so far. Well, why Dr. Sean Kane 01:57 don't we at least start with kind of obesity and who potentially could get surgery. And based on BMI, obesity is defined as a BMI above 30, but I would assume that not everyone with a BMI above 30 can qualify for bariatric surgery if they want it. So who among the people who are classified as being obese then can qualify for bariatric surgery? Dr. Khyati Patel 02:18 You know, watching one of those shows like 90210, you know, you might think that these surgeries are benign and, you know, are occurring left and right, but that's not true. These are by no means benign surgeries, and therefore we have to weigh the risk versus the benefit. And so, so far, the medical community sees that if the BMI is above 40, these are the patients we call morbidly or extremely obese would be qualified, or if they have BMI of 35 with at least one comorbidities. These are metabolic type comorbidities, such as having diabetes, high blood pressure, maybe a heart disease. There is some evidence that at lower BMI between 30 and 34 and and a half patients with diabetes or those who have metabolic syndrome can benefit. This benefit. Really was looking at the type of micro and macro vascular outcomes that can be prevented if a patient with diabetes went under a bariatric surgery. For example, Dr. Sean Kane 03:20 Dr. Patel, as I understand it, even that lower category of BMI, 30 to 35 if they try a lot of different stuff and it doesn't work, they potentially could be indicated for surgery. Then Is that correct, Dr. Khyati Patel 03:30 correct surgery is kind of like the tier step approach here. You have to try lifestyle modification that includes diet, exercise and behavioral modifications, and then pharmacologic options, and if you fail, you know, all of that, then we can consider surgery. Dr. Sean Kane 03:51 So in terms of surgery, as I mentioned at the beginning, I didn't really appreciate that there's so many different kinds of surgeries out there, and it's really everything from, you know, something like gastric banding, which I was a little bit more familiar with, all the way to pretty invasive, you know, resection of different portions of the GI tract. So Dr. Patel, could you just walk us through kind of the differences between some of the most common kinds of surgeries that are out there for bariatric surgery. Dr. Khyati Patel 04:15 They are divided into, like, four main types of surgery. But then if you look at those four surgeries, theoretically, they're into two different categories, and we're going to use these definitions throughout the rest of the recording. So we're going to define that there is restrictive surgery, and there is malabsorptive surgeries, and there's hybrid surgeries that include restriction as well as malabsorption theory in it. So the restrictive surgeries are basically, you're restricting the amount of calories being absorbed, restricting the amount of gastric space, basically, and so gastric banding and sleeve gastrectomy are considered the restrictive kind and sleeve. Gastrectomy is the most common weight loss procedure out of all four performed. And then moving on to the Hybrid Type, which includes the restrictive as well as malabsorptive approach, are the Roux-en-Y gastric bypass, where, again, the Roux limb, depending on how much of the limb you're bypassing can also differ in terms of all these nutritional deficiencies and the amount of weight loss we see. So for example, if it's a proximal Roux bypass, then it's about two thirds of small intestine allowed for the absorption versus distal, which is preferred for those who need a lot more weight loss has even smaller proportion of small intestine that's left for absorption of caloric nutrition and Dr. Sean Kane 05:51 Dr. Patel, what you're saying with that is that you're basically bypassing portions of the GI tract with a malabsorptive approach, and that There's less kind of surface area in that GI tract to absorb those nutrients, and the intent is to reduce the absorbed calories, but potentially you could also reduce the absorption of, you know, nutritional components that are important for health. Then, right? Absolutely. Dr. Khyati Patel 06:16 And here we're talking mainly about the proximal small intestine area that's what's you know, responsible for nutrition as well as some of the medication absorption. So that, therefore, knowing and understanding you know how these surgeries are performed is helpful in understanding what would be its impact on the absorption of various items. And then last but not the least, is, again, a hybrid type of surgery. It's restrictive and malabsorptive at the same time, which we call it, biliopancreonic diversion, with or without duodenal switch. If you ever look up the picture of this particular surgery, the image looks really complicated, but basically what they do is they separate out the flow of food from the gastric pouch, and then the flow of bile and all the pancreatic juices that are needed in order to digest and by separating, we're basically minimizing the their interaction and minimizing the absorption of the caloric nutrition. So this, this, in a nutshell, is the biliopancreatic diversion, with or without duodenal switch. Now, if you're looking at literature, there's going to be various different acronyms being used for them, so it's very important if you see a patient's chart saying they underwent a bariatric surgery, make sure you know what type of surgery they've gone through, because, depending on that, their needs for either medication changes or nutritional interventions are going to be different. Dr. Sean Kane 07:50 Now from a nutrition standpoint, one thing that I thought was interesting, that I learned is that, you know, obviously after the surgery, these patients are at risk for an inadequate amount of micronutrients and even macronutrients, but really, nutritional deficiencies are fairly common even before these patients have surgery. So for example, vitamin D, iron B, 12, thiamine, these are micronutrients that occasionally are actually at low levels even before these patients have surgeries, let alone after. I thought that was interesting, because, you know, these patients have lots of body mass. You'd assume that they have lots of nutritional intake that would give them these micronutrients. But that actually is not the case in a lot of these patients. Dr. Khyati Patel 08:30 Yeah, that's absolutely right. And therefore, they go through a very rigorous pre surgery protocol where there are, you know, interacting with all these medical professionals, they're being screened for all these nutrition deficiencies. They're being taught how to eat right. But some of the possible reasons for having these type of deficiencies in the pre surgical state could be a poor dietary choices. Maybe they're eating dense caloric items, but they're not as nutritious in terms of the various minerals and the vitamins and things like that. There's other proposed mechanisms saying there is, you know, altered overgrowth or alteration in the GI flora, especially under the intestine. So the absorption of some of these nutrition is different because of the altered flora. And then another possible mechanism is obviously decrease transport protein, because obesity increases the inflammation, and the inflammation kind of changes these transport proteins. And then, as Dr. Sean Kane 09:29 you mentioned, Dr. Patel, it's pretty important that if a patient has pre existing nutritional deficiencies that you probably want to get those fixed before you then give them a surgery that's going to potentially worsen those nutritional problems. Dr. Khyati Patel 09:42 Yeah, identify those first, treat them. You know, acutely as well as you know, have a chronic plan, because knowing that they're going to go under a surgery, it's only going to worsen that problem. Dr. Sean Kane 09:54 And it should make sense to the listeners that between the two like broad categories of surgeries, which. Malabsorptive and restrictive, that the malabsorptive type surgeries are going to be more profound in terms of causing more nutritional deficiencies down the road, because we're literally bypassing or preventing absorption of these nutrients, as opposed to restriction, where most of the mechanism is just decreasing the size of the stomach and how much food will fit in the stomach comfortably for that patient. Dr. Khyati Patel 10:23 Other reasons, if you're talking about physiologic changes that can happen due to these surgeries are, you know, the GI pH changes, so gastric pH, as well as the intestinal pH, is altered. As we talked about how malabsorptive procedures worked, the absorption area is reduced. Patient's ability to intake food is reduced, right? So that, and again, depends on after surgery, what type of foods are they going to eat that's going to suffice the nutritional needs banding procedures, the adjustable gastric banding procedures, can induce vomiting in patients. So whatever intake they have of nutrients may come out because they're frequently vomiting and then rapid, extreme weight loss could also complicate the picture here. Dr. Sean Kane 11:09 Then, of course, you know, even if you kind of have a plan to treat or prevent a nutritional deficiency, if the patient is not adherent to their regimen, then they're potentially going to have problems. Potentially dosing can be an issue here. So it's important that these aren't your typical like one multivitamin a day, and you're good to go for some of these deficiencies. You actually have to give these patients quite a bit from a dosing perspective, and if you underdose them, then again, you potentially will not have a good outcome in terms of preventing or treating a nutritional deficiency, and Dr. Patel, as I understand it. You know, it's not as simple as just giving one nutrient to treat nutritional deficiency. Some sometimes these can actually be related to each other. Is that correct? Dr. Khyati Patel 11:53 That's correct. A good example would be, you're treating somebody with iron and they're not responding. We got to have to check make sure that their copper is okay, because if they're if they are deficient in copper, then they may not respond to iron treatment either. And then, you know, high doses or use of antacids would also impair copper and zinc absorption, and that could lead to those deficiencies as well. So there are some other factors that could play a big role here. Dr. Sean Kane 12:21 Of course, patients can have symptoms of nutritional deficiencies, but oftentimes nutritional deficiency symptoms are manifested when these get pretty severe. So ideally you want to catch these either preventatively, where you recognize that a patient has kind of a sub clinically low level of nutritional component, or, you know, catch it before the patient starts having symptoms. Many of these micronutrients, you'll be able to either get serum levels of them. There's biomarkers. Going to be screening for these before the procedure and then on a regular basis after the procedure. So examples could be checking vitamin D levels, ALK, fast, Pth, getting a DEXA scan, looking for vitamin D deficiency. As an example, all of those are going to be related to vitamin D deficiency, looking at biomarkers, or literally, vitamin D levels, to assess whether a patient may be deficient for vitamin D, Dr. Khyati Patel 13:15 identifying them before the procedure, and then having a game plan on how we're going to approach it. It's definitely a lot better. And these tests are going to be done in the pre state, but they also will be done in the post state. Some patients may not have deficiencies in the pre surgical state, but may develop thereafter. So the clinical practice at the bariatric centers will be to monitor some of these markers on a routine basis. That might not be the case for general population who doesn't undergo this type of surgeries. You know, there is a always we say prevention is better than cure. Across the board, the bariatric surgery centers and patients who go under these surgeries should be given multivitamin dosing, and that's across the board for prevention, for restrictive surgeries, the common approach is to provide vitamins that contain about 100% of recommended daily dose of at least two thirds of the nutrients. So if you get a bottle of multivitamins, and you take a look at the table of contents, what's included. It's usually like two tables, because there's just so much in it. So as long as you're looking at that list and two thirds of the ingredients says 100% Daily Value meant that means that that vitamin is good for somebody for prevention, who is underground, one of these restrictive procedures, as we laid out earlier, though, for the malabsorptive procedure, the risk of deficiencies are higher. And so here we're going to consider the vitamins that contain 200% of the recommended daily dose of the two thirds of the nutrients that are listed on the product. Now it could be that, it could be one. 100% of the recommended daily dose, and they just take it twice to meet the 200% requirement. But this is the generalized approach that's recommended for post biotic surgery patients. That's something like, you take a medication off because, you know, maybe their blood pressure is getting better, or their blood sugar is getting better, but then we're adding a medication on board preventatively for the rest of their life, Dr. Sean Kane 15:23 and of course, after a surgery, because, you know, this is a pretty serious gi surgery, these patients may have issues breaking down tablets. So ideally you want to provide this multivitamin as a liquid or a chewable formulation, at least in the post op period until the patient is stable and you think that things have healed up enough that they'll reliably be able to break down that tablet of a multivitamin? Dr. Khyati Patel 15:47 Yeah, I mean, you know, we take our regular patients, they come to pharmacy desk and we they say, Oh, this pills are so big, you know, I'm gonna do the gummy vitamins, or, you know, something that I can chew down easily, the size of a solid formulation, solid tablet or pill formulation that these patients can take shouldn't be bigger than your regular chocolate m&ms, okay? And that's even after that immediate post period. Until then they're they're going to use the liquid and chewable formulations. Dr. Sean Kane 16:20 So, Dr. Patel, you know, prevention is obviously ideal, but sometimes prevention isn't enough, either because of under dosing, the wrong formulation, the patient's non compliant for whatever reason. Unfortunately, these patients are at risk for a whole host of nutritional deficiencies. And you know, this could be a one hour talk on its own, so we're not going to go into great depth on each potential deficiency, but I think it's worth kind of a good overview of what are some of the more common ones, and how would you actually treat some of those more common deficiencies? Dr. Khyati Patel 16:49 Yeah, so like you said, Dr. Kane, we're going to focus on the common ones, and that starts out with some of the water soluble vitamins like thiamine, vitamin b1, the rate of post op deficiency is as high as 49% and somebody who has thiamine deficiencies can present with wet or dry beriberi‑type symptoms, so muscle weakness, convulsions, tachy or bradycardia, lactic acidosis. They could even develop signs of Wernicke's encephalopathy. So kind of affects the CNS system in terms of confusion, ataxia or nystagmus. So in addition to somebody who's taking those multivitamins, as we laid out for prevention, additional thiamine supplementation might be needed. This could be given separately as a thiamine, for example, 100 milligrams per day, if they're aggressively vomiting for, you know, up to two weeks. For people who have like Wernicke encephalopathy, they are going to need higher doses. So we kind of call this quote, unquote treatment doses. They're going to be needed to treat immediately with IV doses, and they might be put on higher po doses. I'm talking about 30 milligrams, you know, twice daily thereafter for chronic use, yeah. Dr. Sean Kane 18:06 And for the listeners, anyone who's kind of treated an alcohol withdrawal patient, this is a very common additive that is given preventatively to prevent wernickes and alcohol withdrawal patients, or even for treatment if wernickes is suspected, for patients, I think one thing to really drive home here is that if you truly think the patient has the thiamine deficiency, especially something like wernickes, you must give IV therapy to those patients, and then once they stabilize, at least after several days, that's when you would potentially give them oral therapy at higher doses, and then down the road, drop them down to a more reasonable dose. But this is very, very common in that alcohol withdrawal patient probably patient population, and also pretty common you set up to about 50% of these bariatric surgery patients may be deficient in thiamine. Doesn't mean that they'll progress to where to keys, but they will need additional supplementation. Right? Dr. Khyati Patel 18:56 Another water soluble vitamin is cobalamin, vitamin B, 12, and the rate of deficiency post op could range from 35 to 62% so like after two years, it could be up to 62% after fires, it decreases a little bit up to 35% again, these patients may come with symptoms of anemia, pernicious anemia. They may have neuropathic symptoms, depression or dementia. Again, these patients would need additional supplementation on top of the multivitamins, either via po and if they're not responding to the PO therapy, they may even need intramuscular injections. Again, example is 1000 micrograms per month, or even 3000 micrograms every six months, such higher doses. Dr. Sean Kane 19:43 And you know, this is kind of a hotter topic, with, you know, for example, Metformin potentially causing vitamin B 12 deficiency, chronic PPI therapy or other acid suppression therapy causing B 12 deficiency. So again, we see this in other areas, but we definitely can see this as well in. In bariatric surgery patients. Dr. Khyati Patel 20:02 Interestingly enough, you mentioned Dr. Kane about vitamin B 12 deficiency in people taking PPI as bariatric surgery patients after the surgery are able to get off of some of the medications because of the increased heartburn and dyspepsia related complaints, there actually have been increased use of PPIs and other antacids in this patient population. So perhaps the vitamin B12 deficiency is coming from the surgical interventions, but it could be coming from co‑existing use of PPI as well. Dr. Sean Kane 20:35 So then our next one is folic acid deficiency. And again, people are going to be familiar with folic acid, because this is something for pre and postnatal care to prevent neural tube defects in kids or in infants. But again, we also see deficiencies ranging from about 10 to 40% and post bariatric surgery patients symptoms are anemia would be the main one that comes to my mind. But we can also see fatigue, palpitations, and then again, we mentioned the risk in pregnancy. So certainly, if someone had bariatric surgery and they want to become pregnant, this would be a very notable thing to look into. Supplementation wise, the doses here are fairly similar to what you would see for women of childbearing age in terms of the typical dose that we're giving, and this is going to be for several months after the surgery to kind of make sure that we give them a sufficient amount of folic acid to prevent or to treat a deficiency. Dr. Khyati Patel 21:30 The next one, that's a bigger one, is iron deficiency. And I tell you, the reason I am passionate about is this topic is because I am referred a lot of post bariatric surgery patients to come up with iron supplementation doses in my clinic. And you know, as we know, it could be done with po or IV interventions. So iron deficiencies could be as common as about 17% with restrictive and obviously higher up to 45% of those patients getting mild absorptive procedures. After two years of procedure, obviously the symptoms of iron deficiencies are going to be, you know, anemic in nature, they may have difficulty keeping a body temperature regulation. Dr. Sean Kane 22:11 I remember from Pharmacy School Dr. Patel pica would be a symptom as well, where patients may eat strange things like paint chips or dirt or things like that to try to get some iron in their diet without really realizing why they're doing it too. Dr. Khyati Patel 22:25 I think I've heard ice chips an affinity to increased use of ice chips could be one of the iron deficiency signs. Yeah, exactly. It's interesting. But prevention again, in addition to those multivitamins, the research so far says that one formulation, meaning one salt, is not better than the other, but we know that ferrous sulfate is the most common salt, and the kind of drawback here is that it needs an acidic environment. So the most of the studies in this patients have looked at Iron sulfate, 300 milligrams, you know, about two to three times per day. But we know that these patients have higher gastric pH, and so the sulfate is not going to be absorbed properly. So some studies have looked at giving iron sulfate along with vitamin C, about 250 milligram with each of the iron doses. And that helps, but they will need this dose two to three times per day, once a day is not going to cut it. And for some patients who still cannot respond with po doses, will need to be then given IV iron therapy. Dr. Sean Kane 23:31 And you know, in terms of that oral iron therapy, one thing that always comes to my mind is the risk of constipation, especially at those higher doses, patients can have some GI complaints, mostly constipation from something like that, and they can't tolerate that, then you may have to reach for that IV therapy anyway, just because of tolerability reasons. Dr. Khyati Patel 23:50 Yeah, and one of the you know, product available over the counter is slow iron, which is a slow release. But the thing is, with the pharmaco kinetic changes that have happened post surgery, most patients with bariatric procedures should not use any type of slow release or extended release formulation anyway, so we can't even recommend those to reduce some of the constipation site symptoms. So a transition from po to direct to IV supplementation would be just fine in these patients. Dr. Sean Kane 24:19 And then our next one is calcium and vitamin D. And you know, calcium deficiencies relatively uncommon, about 10% but vitamin D, you know, up to 80% and really in North America, the vast majority of people in North America have a vitamin D level that is below the normal limit. Potential complications of both of these is that you can have a low bone mineral density, which would be osteopenia or osteoporosis, at very low levels of calcium, you can have issues with muscle contractions and spasms, tingling, myalgias, potentially even depression. With vitamin D, there's a whole host of potential symptoms that go along with this. So for supplementation in post bariatric surgery, patient. Citrates preferred, although carbonate can be taken with meals if cost becomes an issue with the citrate and then also the vitamin D and for prevention, we're talking typical vitamin D doses, which would be, you know, 400 to 800 international units a day. But that could tell, as I understand it, it's a whole game changer if we're really trying to treat for vitamin D and calcium deficiency, as opposed to just preventing it. Dr. Khyati Patel 25:22 Yeah, in these patients, if they are deficient, and we're using quote, unquote, the treatment doses for both calcium and vitamin D, these are pretty higher doses, as opposed to those who haven't gone under surgeries, and we're treating them for, you know, calcium or vitamin D deficiency. If I give you an example, we know that calcium citrate provides lower elemental but here we're looking at 1200 to 1500 milligrams daily, or even up to 2400 milligrams daily, in divided doses for some of those who have gone under malabsorptive procedure, and then looking at vitamin D, these patients may need as high as 50,000 units three times a week, as opposed to non surgical patient needing vitamin D supplementation or dosing, would probably get 50,000 once a week. Dr. Sean Kane 26:10 So then you know, our next item for business is fat soluble vitamins. This would be vitamins A, D, E and K, and it really depends on the kind of procedure you see. So for vitamin A, maybe about 10% for roux and y, and then potentially up to 70% of fat soluble vitamin deficiencies can be seen with certain malabsorptive procedures. Vitamin E and K are a little bit less common in terms of deficiencies, but still is a potential concern. Specifically for vitamin A, we worry about nocturnal vision loss, so inability to see at nighttime, or difficulty seen at nighttime, we can also see hair problems and a variety of other problems as well, right? Dr. Patel, Dr. Khyati Patel 26:49 that's true, and some of the issues related to vitamin K deficiencies will be obviously, you know, the increased INR includes, you know, bleeding and bruising. Vitamin E deficiency can bring in issues such as other visual disturbances, myalgia, gait issues, muscular issues, etc, etc. Now the looking at the fat soluble vitamins, as we noted that vitamin E and K are not really the problem child. Here is the A. So a lot of the focus and recommendations are revolved around how to dose vitamin A. Some evidence suggests, you know as up to five to 10,000 units you know vitamin A daily, if patient starts to develop some of these visual changes where they can even have corneal lesions, so they will first look for these lesions, and the absence or presence of these lesions would then determine the need for some of the higher intramuscular doses for the vitamin A. Dr. Sean Kane 27:51 And it should go without saying, but we're talking fat soluble vitamins here. So unlike our water soluble vitamins, where we have a very wide therapeutic range, it's not as wide for our fat soluble vitamins. So it doesn't mean that every patient is going to get, like, the max dose of vitamin A potentially, because we could worry about toxicity if it's given at too high of a dose over too long of a period of time. So it is a concern. We still have a fairly wide therapeutic range, but not nearly as wide as our fat soluble vitamins. Dr. Khyati Patel 28:20 And then just looking at some of the rare element type deficiencies, there is, again, wide variety, but the most common ones that can occur in these patient is zinc and copper. So the rate for zinc deficiencies could be as high as 33% for a restrictive procedure, and as high as 91% for malabsorptive procedures. And as we know, zinc is a good element for all bodily functions, especially when it comes to like skin related issues. So like skin lesions, poor wound healing, dermatitis, even hair related issues, like alopecia, can occur, and then it plays a good role in immune function too. So deficiency can lead to altered immune response as well. Additional zinc supplementation is not really recommended as but as long as your multivitamin that we are dosing contains it. However, in those who have severe zinc deficiencies, we could use about eight to 15 milligrams of elemental zinc, any and all the salt forms are okay taking po because zinc and copper kind of go hand in hand, and such higher dose of zinc can lead to copper deficiency, so we have to dose about one milligram of copper per eight to 15 milligram of zinc dose. So you're adding here basically two different medications and not just one. Dr. Sean Kane 29:43 And as a good segue for copper deficiency, pretty rare with restrictive procedures, but can be up to 10 to 25% for malabsorptive procedures, symptoms are fairly generic and not really that specific. So we can see anemias, a low white blood cell count, any of the kind of. Neuro type symptoms, so neuropathies, neuropathic issues, paresthesias, again, wound healing, just like what we saw with zinc as well. And this can be given on its own, so you can have elemental copper that you take orally once a day, in a variety of different salts. And as we mentioned, if you're giving zinc treatment, you may also have to give copper to prevent copper deficiency caused by supplementing with zinc, which is kind of interesting. Then finally, for treatment of copper deficiency, we also can give this print early if we have to basically as effectively a loading regimen followed by an oral regimen after that. Dr. Khyati Patel 30:37 So as we can see, you know, there's just so many different deficiencies that these patients can develop, and we only cover like the major ones. And as we said, that these procedures are evolving and becoming more sophisticated, that we are learning more about how different procedures have different rates of deficiencies. And you know, different way of correcting the deficiencies too, Dr. Sean Kane 31:04 in addition to those nutritional deficiencies, as pharmacists, we're worried about drug therapy. I'm sure that there's going to be some changes to drug therapy in terms of its kinetic disposition as a result of bariatric surgery as well. Right? Dr. Khyati Patel 31:16 Yeah, because of all these surgical interventions there, there's a lot of PK changes that occur, kind of categorizing them in a broad categories. We're talking about reduced drug absorption. So you're, you know, when we're talking about small absorptive surgeries, we're taking out that proximal small intestine, so you're bypassing that and therefore that area which is where the drugs and nutrition is absorbed is now out. So we're talking about lower drug absorption. The other issue that can happen is altered gi pH, and here we're talking about gastric as well as duodenal pH. Usually the gastric pH increases. We are looking at decreased mucosal exposure in the GI area too, and other gastric emptying, such as dumping syndrome and things like that. Dr. Sean Kane 32:07 You know, in addition to all of those kinetic changes, we also have metabolic changes. So by avoiding certain portions of the GI tract, now you're going to have less involvement of the cytochrome P450 enzyme system and the P‑glycoprotein system as well. So potentially you're going to have a decrease in metabolism, especially first pass metabolism of these drugs that would normally be metabolized more had you not had that bariatric surgery, Dr. Khyati Patel 32:34 some of the enterohepatic circulation is affected, and that's where the SIP enzyme disturbances come in play, and Dr. Sean Kane 32:42 then, of course, altered bioavailability. And that should make sense, that the bioavailability for these patients is going to be reduced compared to someone who did not have gastric bypass surgery. So it's going to depend on the lipophilicity of the drug and how it's metabolized and things like that, and where it gets absorbed. But potentially this could have a significant impact on how much of that drug is absorbed, just like you know, the intent of the surgery, which is to impact how much how many calories get absorbed, it can also impact drug as well. Dr. Khyati Patel 33:12 And so kind of diving a little bit more specific to the kind of concerns that pharmacists might be consulted for, for these patients, would be dosage form. So as kind of we alluded earlier, immediately post surgery for up to two months. I guess this is patient dependent, but in generally, up to two months, patients should be considered and given liquid and crushed, chewable or open capsule type formulations over the you know, the solid pill or capsule forms. The alternatives to this could be sublingual, intranasal, rectal, sub cube and transdermal. These are okay, too. One thing to keep in mind about the liquid formulations that they should be free of any sugar that is non absorbable. So things like mannitol, sorbitol, honey, fructose corn syrup, because all that can lead to dumping syndrome. Dumping syndrome is basically patient presents with like nausea, pain, diarrhea, sweating, tachycardia, fainting, and this could be anywhere between 30 minutes of ingesting some of these items to up to three hours after, and we definitely don't want patients to have this, so kind of have to come up with formulations that don't contain this, you know. So that definitely takes an investigative hat. Dr. Sean Kane 34:34 Then in addition to that, as we kind of already mentioned several times, is enteric coded and extended release. Products are really to be avoided, and you should be using that immediate release product or other dosage forms. And hopefully it makes sense that you know if the extended release or enteric code of products are supposed to release when they pass after an acidic environment and into a basic environment, that change in pH is potentially not going to occur. As it would normally in someone who didn't have bypass surgery. So changes in pH, and just in terms of transit time in general, all of those are going to be impacted by that surgery. So really, you should be selecting immediate release products, as opposed to extended release or enteric code of products for these patients. Dr. Khyati Patel 35:17 And then there are medications that require our GI pH to be a little bit more acidic for the absorption. The example of these drugs are some of the anti epileptics like carbamazepine or phenytoin, some of the anti‑infectives such as cefuroxime or ketoconazole, and even other vitamins and supplements, as we kind of talked about earlier, these all need acidic environment we now have gone through the, you know, gi pH changes, and we talked about how these patients use PPI at a higher level too, which further changes the gastric pH two. And so this all can lead to decreased bioavailability of these items. Now, what can we do for some of these neurotherapeutic drugs, such as phenytoin, and we have to, you know, make sure that we're monitoring them closely and then adjusting the doses as necessary. And then for vitamins and supplements, as we talked about earlier, additional supplementation is considered. Dr. Sean Kane 36:12 And then, of course, it goes without saying, you know, we know that we're going to have altered PK in these patients. So any drug that is going to have a narrow therapeutic window. This would be anything from warfarin, like you mentioned already, Dr. Patel, to many immunosuppressants, to digoxin, anything that you're drawing a drug level for probably falls in this category, because you know you're going to have altered PK in these patients. You absolutely have to monitor them more closely. You're going to expect changes to occur, and you're going to expect to likely have to make dosage adjustments as a result of those PK changes. So close monitoring is going to be really important, and that's probably one area where pharmacists can really shine. Here is that these patients no longer are kind of the typical population estimate. You're really going to have to individualize care for these patients because of these PK changes. Dr. Khyati Patel 37:04 So one of the things that you mentioned was warfarin. It's a narrow therapeutic window type drug in patients who are post bariatric surgery. We're going to probably consider empiric dose reduction and closer INR monitoring these patients require lower doses anytime, immediately after surgery. Up until about six months, studies have shown, again, when I say studies, these are pretty limited studies with small patient population, but whatever evidence that we have has shown that after six months, patients are able to go back on their pre surgery doses. So that's one of the examples to tell you how these changes affect some of the high risk medications. Dr. Sean Kane 37:45 Dr. Patel. In my head, I'm thinking, all right, if I don't want to mess with all that Warfarin stuff, can I just give them a doac instead? But now I'm wondering, well, with all these changes, do we really even know how a doac would perform in a patient with bariatric surgery? Dr. Khyati Patel 37:59 You bring up a really good point. These drugs are not studied in patients who have gone under bariatric procedures. We do know that rivaroxaban and edoxaban get absorbed in that proximal small intestine, and so if they've gone through that duodenal switch, and you know, diversion, then there you go. They may not be absorbed reliably, and we may not get the anticoagulant effect that we need. Apixaban, theoretically, is absorbed in the colon, so we can say that the absorption is not occurring. However, we don't have a pixabane put to test to say that it doesn't produce additional, you know, thromboembolic events in these patients. And then last but not the least, Dabigatran should probably avoid it at best, because these patients, as is, would have symptoms of dyspepsia, heartburn and indigestion, and we know that Dabigatran increases this risk, especially in GI banding type procedures. We definitely should avoid dabigatran, and in some isolated cases, of those who have gone under when bypass, we've seen actually failure reports so patients ended up having thromboembolic events. But again, this data is pretty small, but that again, tells us that we have very low evidence for doac use in this patients. Dr. Sean Kane 39:21 Yeah, so as kind of annoying as it might be to even transition a doac patient to warfarin, that's probably the right answer in this patient population, because at least with warfarin, you can get an INR, you can adjust your dose, you can follow these patients, so close monitoring is possible. Whereas with a doac, you have one dose, you're stuck with that dose, and there's no way to get a blood level to really see if they're over under anticoagulated, you're kind of stuck. So potentially, Warfarin has a lot of advantages in that patient population. Unknown Speaker 39:49 That's absolutely right, yep. Dr. Sean Kane 39:52 Well, in terms of some key concepts from today, I mean, as we mentioned at the very beginning, this is a very involved, very complex topic. In terms. Terms of some of the key concepts that I think the listener should take home, one would be, yes, bariatric surgeries do provide a lot of health benefits in addition to weight loss, just in terms of comorbidity reduction, so helping with diabetes and hypertension and things like that, however, long term consequences like nutritional deficiencies and other health conditions because of those nutritional deficiencies, that's a big concern, that pharmacists potentially can play a big role in either preventing or treating these nutritional deficiencies. Dr. Khyati Patel 40:29 And if you're a part of a team that's taking care of those patients, you know, we want to make sure that we're monitoring for these deficiencies before they go under knife, correct them, if possible, beforehand, and then, obviously, after the procedures too, we're going to have to implement some routine laboratory testing for these patients. Dr. Sean Kane 40:49 Yeah, and you know, yes, these patients are going to get a multivitamin. And that is, like, kind of the obvious thing. But sometimes these patients are going to need additional supplementation for prevention. And then if they need treatment, where we identified that they currently have a nutritional deficiency, it's really important to distinguish that the dosing regimen and sometimes even the product itself, in terms of what you're giving them, maybe even parenteral therapy could be considered and really drawn. The distinction between prevention and treatment is really important for these patients. Dr. Khyati Patel 41:19 Yep, and some of these surgery can result into big time PK changes. Here we're talking about altered gi pH, reduced absorption area, as well as changes in some Metabolic Enzymes, which would lead to alteration in drug properties, such as drug absorption, bioavailability, drugs metabolism and these changes really should be kept in mind and guide the current medication changes, as well as selection of medications and formulations for future recommendations. Dr. Sean Kane 41:52 Well, Dr. Patel, I think that wraps up episode 114 quite nicely. If the listeners want to go to our website, they can see show notes from today. That's HelixTalk.com we're also on Twitter at HelixTalk, where we release clinical pearls from all of our episodes historically that kind of get dripped over time. So if you want to get a pearl every now and again, you're welcome to follow us there and again. We love the five star reviews. If anyone has any episode suggestions, you can email us or leave us a shout out on iTunes, and we're happy to read those as well. So with that, I'm Dr. Kane Dr. Khyati Patel 42:24 and I'm Dr. Patel, and as always, study hard and stay safe. Narrator - Dr. Abel 42:29 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there Narrator - ? 42:40 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.