Unknown Speaker 00:00 Hi, welcome Speaker 1 00:07 to Rosalind Franklin University, College of Pharmacy top 200 drugs podcast. Speaker 2 00:12 This podcast is produced by the pharmacy faculty members to supplement study material for students learning the top 200 drugs we're hoping that our real life clinical pearls and discussions from practicing pharmacists will help you study for your next drug quiz. Speaker 3 00:28 And now on to the show. Welcome to week nine of Rosalind Franklin University's top 200 drugs podcast spring edition. I'm your co host, Dr. King, Speaker 4 00:39 I'm Dr. Weatherton. I'm Dr. Patel and I'm Dr. Mitchner. Speaker 3 00:42 This week, we're talking about a number of different gastrointestinal agents. We're going to start with methotrexate or Rheumatrex. Speaker 4 00:49 Methotrexate has an interesting mechanism of action. It's kind of the enemy of a certain substance. Speaker 3 00:55 Is that? Right? That's true. So it's kind of the the arch rival of folic acid, or folate. So the way it works is it binds to the same enzyme that folate binds to, but instead of doing anything, it just stays bound to that enzyme and doesn't let it work at all. Speaker 4 01:08 And I understand that that sort of inhibits DNA production, and it keeps immune cells and others from replicating. Is that right? Yeah. Speaker 3 01:16 So the enzyme is called dihydrofolate reductase, and it's responsible for a lot of things in the body, but the main thing is maintenance and replication of DNA, which is kind of important for cells. Speaker 5 01:28 So what are we going to use this medication for? Dr. Weatherton? Speaker 4 01:31 It's got a lot of uses. It's got some uses in inflammatory bowel disease and psoriasis, also less commonly in certain cancers, but it's real claim to fame is in rheumatoid arthritis, where it's very handy in the treatment. Unknown Speaker 01:45 So I guess the brand name Rheumatrex Makes sense. Speaker 3 01:48 So how is Rheumatrex, or methotrexate, given to patients? Speaker 4 01:52 Generally, it's dosed by mouth or parenterally, meaning subcutaneously or intramuscularly. For these indications, it's generally not used in IV forms. That's usually for cancer. Dr. Patel, how often is methotrexate dosed? Speaker 5 02:06 So methotrexate actually is dosed on a weekly basis. A patient will take this medication just once a week. Speaker 3 02:13 Gosh, I can imagine that some pretty severe adverse drug events could happen if a patient took it daily instead of weekly, right? Speaker 4 02:19 Well, there are reports of people dying due to drug accumulation and toxic side effects. Patients who are taking their weekly dose on a daily basis have died. So as a pharmacist, anytime you see methotrexate dose to anything other than weekly, you need to be calling the doctor to be sure that that's what they Speaker 3 02:35 really want. What are some of the side effects that we can see with methotrexate? It seems like because it can inhibit DNA repair and DNA synthesis, that we could probably see some pretty bad side effects Speaker 4 02:44 from it. That's correct. One of the first things I think of are fast replicating cells, such as immune cells, which is really how this drug works. It inhibits white blood cell and other production, but we can see decreased production of other blood cells as well as decreased repair of gastrointestinal mucosal cells leading to mucosal ulcers and other uncomfortable toxicities. Speaker 3 03:06 And of all the drugs that I know about, this is probably the one that has the most boxed warnings on it. It has everything from acute renal failure, myelosuppression or bone marrow suppression, fatal rash like a Stevens-Johnson rash, diarrhea, stomatitis, hepatotoxicity, new cancers like lymphomas, opportunistic infections, pneumonitis. And I'm not even done with the whole list. Speaker 4 03:28 Whoa, this drug is really toxic. Why the heck do we use a drug that's so toxic? Unknown Speaker 03:33 Because it's freaking awesome for rheumatoid arthritis, Speaker 6 03:36 and patients have limited choices. Sometimes, when they have rheumatoid arthritis, they're in such horrible pain that they really need treatment, and so this is the treatment that might work for them. Speaker 5 03:45 And given all those box warning, I'm assuming this drug is pregnancy category x, right? Speaker 3 03:50 Oh, yeah. And actually, I learned something new today, that methotrexate actually has a mortality benefit for RA or rheumatoid arthritis. Is that? Right? Dr. Weatherton, yeah, Speaker 4 03:59 patients with rheumatoid arthritis are at higher risk of dying of cardiovascular disease because of the long term inflammation that they have, but patients who get methotrexate and respond to it have a more normalized risk of cardiovascular disease. Speaker 3 04:12 So moving on to our second agent. The generic name is allopurinol and the brand name is Zyloprim. So how Unknown Speaker 04:18 does this medication work? Dr. Michener, Speaker 6 04:20 so it inhibits xanthine oxidase, and that's the enzyme that is responsible for converting both hypoxanthine to Xanthine into uric acid, and it also reduces the production of uric acid without disrupting the production of very important purines. Speaker 4 04:36 And why do we care about how much uric acid is in the body? What happens if there's too much Unknown Speaker 04:40 kidney stones Speaker 5 04:42 correct, the uric acid crystals are not water soluble, so if the concentration rises above certain normal levels, they can precipitate and cause an inflammation into the joints, and that's called gout. So what's this drug used for? So like we said, it. Used for prophylaxis. It is also used for, as Dr. Michener said, and the management of renal calculi, basically renal stones and in some patient who has elevated uric acid levels, mainly in patients who have cancer. Speaker 3 05:16 So how is this drug available? So I typically see it as oral tablets, but I believe it also comes as an IV solution, Speaker 4 05:22 and I understand that titration scheme is because we're trying to avoid Allopurinol hypersensitivity syndrome, which is often accompanied by a very severe rash. So what are some other side effects that we see with Allopurinol? When I think of allopurinol, I think that when we start it, we start messing with the uric acid levels in the body, and we can cause an acute gout attack, so it's often started with another medicine to prevent gout attacks, like Colchicine. Also, we can see diarrhea, nausea and potentially increased liver function tests. Speaker 3 05:51 It's kind of interesting. You'd think that it would actually prevent or stop gout attacks from starting, but as it turns out, when you start the medication, you're at higher risk for gout attacks than when you weren't on the medication. Speaker 4 06:01 Yeah, it's pretty counterintuitive. So the next drug on the list that we're going to talk about is mesalamine, which goes by many different brand names, including Pentasa, Asacol and Lialda. Speaker 3 06:12 So I bet I can guess why some of the brand names are the way that they are. Take your best guess. Dr. Kane, so Pentasa, pent meaning five Assa, like aspirin, Asa, right? Speaker 4 06:23 These are amino salicylic acids, so it's close, but not exactly the same. Speaker 3 06:28 And then Asacol Certainly from the area that it works in, right? Yeah, the colon. Now, what do you think they got Lialda from? You got me there? Yeah, I don't Speaker 4 06:37 know either. So you mentioned that this drug works in the colon, and that it's kind of an anti inflammatory drug. What the heck is it used for? Speaker 3 06:45 So I think commonly it's used for ulcerative colitis, but in some circles it's also used for Crohn's disease, which is a similar disease process. Speaker 4 06:53 I understand that these these medications, we don't really understand their mechanism of action. Is that right? Dr. Patel, Speaker 5 07:00 that is quite correct. They are mediating the immune response that is causing the Ulcerative Colitis and Crohn's, mostly by local inhibition of prostaglandins and also inhibiting the TNF and interleukins, which are responsible for the inflammatory reactions in the body. Speaker 4 07:18 So you mentioned that these drugs work locally, and I just wanted to point out that all the brand names that you see here are mesalamine, but they're in some fancy extended release tablet, and the reason for that is so that mesalamine can get all the way to the end of the colon where it may need to work. What kind of dosage forms do we have with mesalamine? There are many oral dosage forms, like the three that we're talking about today, pentasa, colon, lialda, since it's used for colonic difficulties, suppositories and enemas are also available. The suppositories Canasa and the enema is Rowasa. Is there anything we need to know about the different oral Unknown Speaker 07:53 dosage forms? They're Speaker 5 07:54 taken with different frequencies, as Dr. Weatherton earlier mentioned, they're formulated in different release forms. So Asacol and Pentasa is usually taken three to four times a day, while Lialda, which is a longer release, is taken once daily. Speaker 3 08:08 Sounds like Asacol and Pentasa are really a pain in the Asacol. Speaker 4 08:13 What sort of adverse effects do these medications cause? Speaker 6 08:16 Well, they can cause headache, dyspepsia, rash and diarrhea, but more rarely, they can also be nephrotoxic and cause myelosuppression or suppression of the bone marrow. Speaker 4 08:27 And as Dr. Kane mentioned, these medications are salicylates. Are there any patients who we shouldn't use these medications in? Speaker 5 08:33 And smart enough, I'm thinking of aspirin because that's salicylic acid. Speaker 3 08:38 So our next drug class is actually a couple different drugs that we'll be talking about today. Now I'll make up a drug class as a whole called proton pump inhibitors. Speaker 5 08:47 What the heck do those do? So the proton pump inhibitors inhibit gastric acid production in your stomach, mainly by inhibiting the hydrogen potassium ATPase, which is a pump that is responsible for producing the acid. Speaker 3 09:04 So I bet we see this for things like heartburn, right? You got it. Speaker 5 09:07 And in addition to heartburn, it is also used for esophagitis prevention or treatment of gastric ulcer caused by various different reasons, such as NSAID-induced ulcers, stress ulcers, or H Pylori induced ulcers. Higher doses of PPIs are used for secretory conditions such as Zollinger-Ellison syndrome. Speaker 3 09:30 So I've heard that the Canadians have a different use for PPIs that we don't have here in the US. Is that correct? Speaker 5 09:36 Yeah, because all the nerds reside in Canada, apparently, nerds, yeah, so like there is Gerd gastric esophageal reflux disease, there is nerd, which is non erosive reflux disease. Speaker 3 09:48 So essentially, it's approved in Canada for patients who have heartburn that don't have erosive esophagitis, whereas in the US, we really in terms of its approval, it's approved for people who have esophageal problems. Speaker 4 10:00 Sounds good, eh? Hey, I guess so. Also, you guys are both nerd so when I'm at the hospital, it seems like just about everybody is on a ppi. Do these drugs have any interactions that I should be looking for? Speaker 5 10:12 So when the PPIs were introduced in the market, they were thought to be very safe medications with minimal side effects and minimal drug interactions. But obviously, over the years, the results came out, and that we see quite a few interactions, but there are a couple important interactions that we must discuss in this podcast, and that would be what Dr. Kane, Speaker 3 10:32 so the one I am tired of hearing about is clopidogrel or Plavix with omeprazole or Prilosec. Speaker 4 10:39 Oh, I've heard a lot about that one. Dr. Kane, can you refresh my memory? Speaker 3 10:43 About a decade ago, there was a study that came out of the VA that showed that patients who were on Prilosec and Plavix tended to have more myocardial infarctions than patients who were on Plavix alone. And why did they think that happened? So there is a drug interaction that in the test tube we definitely know occurs where Plavix doesn't get converted to its active metabolite. Speaker 4 11:03 And so the theory is that patients might be more susceptible to clots. Is that right? Absolutely. Speaker 3 11:09 So if you don't convert Plavix to its active metabolite because your PPI is blocking that pathway, it's like you're not taking Plavix at all. Speaker 4 11:15 And so in the clinic, when you see patients on omeprazole and Plavix are most of them dropping dead of heart attacks. Speaker 3 11:22 They are not. What do you mean? It's a very controversial topic, and unfortunately, the one study that was supposed to either prove or disprove this interaction in the clinical setting in a prospective, randomized way was underfunded, and they had to stop early. So we really don't have a firm answer for this question. Speaker 6 11:38 So what do you do for your patients in the intensive care unit after they've had a heart attack. Dr. Kane, Speaker 3 11:43 actually, our hospital just went to a different PPI called pantoprazole that, in theory, does not have this interaction with Plavix. Speaker 6 11:51 And by the way, are all PPIs created equal? As far as efficacy, yeah, Speaker 3 11:57 pretty much they are not created equal in terms of how much they cost. But as far as an efficacy standpoint, there really is no difference between any of the PPIs. That's correct. Speaking of all the PPIs, I've just gotten many emails about a year ago saying that there was a new black box warning added to all of them. What was that about? Dr. Patel? Speaker 5 12:16 recent warning that you're talking about, Dr. Weatherton, was that PPIs are associated with the C diff, which is basically an organism which causes severe watery diarrheas. I've been hearing about this, and the physician also asked me on rounds, but I don't know what clinical evidence that's there that constitutes this warning. Speaker 4 12:38 So Dr. Kane in the hospital, does every patient on a PPI end up getting C diff? They do not. Speaker 6 12:44 Well, why not? If it causes C diff, then why isn't it something to be C Speaker 3 12:49 So normally, I'm a big advocate of the FDA. I think that they do really good work, and it's really important work, but in this case, I think they really dropped the ball by putting a black box warning on all PPIs for potentially causing C diff. The data is from retrospective trials, where they take a bunch of patients and then they see which ones got PPIs and which ones didn't. Obviously, the people who get PPIs tend to be sicker, tend to be in the hospital more statistically, they try to correct for all the differences between the two groups, and they come out with people who take PPIs tend to get a little bit more C diff, even after they adjust for factors like how severely ill different patient groups are, Speaker 4 13:25 and so in the end, they're erring on the side of better to be safe than sorry. I suppose Speaker 3 13:30 they are, but my concern is that it scares the crap out of patients. Have you seen providers stop prescribing PPIs because of this? Some people do choose to use h2 blockers. But in general, patients who are on PPIs have very difficult time getting off PPIs because they can develop tolerance, and when you pull it away, they can have a withdrawal syndrome. Speaker 6 13:50 But on the other side of it, I'd like to know, Dr. Kane, would you say that the PPIs are probably overused anyway, in the hospitalized setting, Speaker 4 13:59 they absolutely are over utilized. So I understand there's some interesting things that we need to know about dosing for the PPIs before we move on to specific agents. What's the Dilly with that? Speaker 5 14:09 So these agents reach the maximum effect within one hour after taking the first dose. Most of the time, these agents are taken once a day, so they should be taken before breakfast in the morning. But if the agent, the PPIs, are given two times a day, they should be taken before meals. Speaker 4 14:25 Now, does it matter if you take it with a meal or just in the morning? Yeah, it does. These agents can only bind to and turn off proton pumps that are on and working. So you should give the drug 30 minutes to an hour before a meal, so that it has a chance to get absorbed, and then the meal is taken, and that turns on the proton pumps. So what's the first agent on the list here? Speaker 3 14:46 So the first agent is s, omeprazole or Nexium. Now that Speaker 4 14:50 sounds a lot like another agent I know of, called omeprazole. Are they related? Speaker 5 14:54 You got it the Nexium or s? Omeprazole is basically s isomer of the omeprazole. It is more expensive than omeprazole, and unlike omeprazole, this one is only available by prescription. So you're talking about mucha mula, the S stands for scam. Speaker 3 15:10 I get GERD just thinking about how much heartburn I'm going to have at the drug counter. With that price, I Unknown Speaker 15:15 get nerd. Speaker 3 15:17 How is Nexium or esomeprazole available? So we have the standard delayed release capsule, which many of the PPIs come as a delayed release we also have granules for suspension, and then also an IV product that we can give in the hospital. So for people who can't swallow, what can we do with the capsules? Speaker 6 15:33 You can open the capsules and you can put them into applesauce, and the granules can be dissolved in water. Speaker 4 15:39 So the next agent on the list is pantoprazole or protonix. How am I supposed to remember what protonix does and what its generic is? Speaker 3 15:47 They both start with P and protonix. Proton is in the name, just like a proton pump inhibitor, Unknown Speaker 15:53 and it nixes it right, absolutely stops it Speaker 5 15:55 from pumping, just like the Nexium. The Protonix is also available in delayed release tablet granules for suspension and IV solution. The only difference with the granules here is it must be taken with applesauce or apple juice. It should not be combined with any other foods. Speaker 4 16:13 And you can remember that because protonix and pantoprazole have two peas and applesauce does too. Are there any generics available for pantoprazole? Speaker 5 16:22 Yeah, both the tablets and the IV solutions are available generics. Speaker 4 16:25 So what's the next agent on the list? Rabeprazole or AcipHex? Is there anything different about this drug than any of the other? PPIs really, Speaker 5 16:34 not really. The only different thing is that there's only one formulation available, which is the delayed release tablets, the AcipHex Sprinkle, which are the capsules, were approved in March 2013 but they're not available in the market for sale yet. Speaker 3 16:52 So kind of changing gears away from our PPIs, we have a another agent called sucralfate, or Carafate. I understand this drug is used for ulcers as well, right? Speaker 5 17:01 Yes, and the treatment and prevention of the ulcers, Dr. Weatherton and Speaker 4 17:05 we learned that PPIs work by decreasing the acid in the stomach. How does sucralfate work? Speaker 5 17:09 So basically, sucralfate forms a viscous protective layer over the GI tract, and so all the acid cannot penetrate the mucosa and cause any damage. Speaker 3 17:20 So in the same vein of it binding to the GI mucosa, it can also bind to a lot of different drug we see physical, chemical drug interactions, where it binds to different drugs if they're given too close together. How can we avoid that? So if we just take whatever drug we need to take a couple hours before sucralfate, we should be good to go. Speaker 4 17:37 Now I see a certain ingredient in sucralfate, and it leads me to believe that there's constipation associated with the drug. What ingredient Am I thinking of? Aluminum? That's right, that's the classic side effect of aluminum containing compounds. And indeed, we do see constipation with sucralfate. What other things do we see? We might Speaker 6 17:56 actually see something called a bezoar when medications collect in a patient's intestines, a bezoar might actually form where the medications get backed up. Speaker 3 18:05 The other thing with this medication, particularly in patients who have very bad renal function, is we can see some aluminum toxicity, because aluminum, if it is absorbed, is eliminated renally. How is this medication dosed? Speaker 5 18:18 So unlike the proton pump inhibitors, which are just taken once a day. This medication should be taken for the treatment of ulcer about four times a day. So imagine spacing the medication four times a day and spacing other medication two hours apart. Speaker 3 18:32 Feel like you need a job just dosing your medications at that point. I think I'd rather take a ppi. I agree. So the other thing to note about sucralfate or Carafate, is that it comes as a suspension and a tablet, and it makes sense that we wouldn't have an IV form of it because it works directly on the GI mucosal. Speaker 5 18:50 So moving on to the last drug that works in the GI system, we have dicyclomine, brand name Bentyl. So can you tell us? Dr. Weatherton, what dicyclomine, or Bentyl, Speaker 4 19:01 is dicyclomine is used for its anticholinergic properties, and essentially it slows down the secretion and the muscle contractions within the GI system and helps with some symptoms of irritable bowel syndrome. Speaker 3 19:15 So I was aware of this drug as a capsule, but I was surprised to find that it actually has an im injection tablet and even a syrup. What sort of Unknown Speaker 19:22 patients wouldn't we want to use this medication? Speaker 5 19:24 Or just like any medications that are used in irritable bowel syndrome, we don't want to use the medication if patient has known or suspected gi obstruction. A patient has a ulcerative colitis flare or severe level of ulcerative colitis, a patient has reflux, esophagitis, obstructive uropathy, glaucoma, patients with myasthenia gravis, breast feeding or infants less than six months. A lot of these contraindications come from the nature of the drug itself, because it is an anticholinergic, so they aggravate certain conditions. Such as obstructive uropathy or glaucoma. Speaker 3 20:02 And I think by now, based on the previous drugs that we've had in the podcast, we could probably predict a lot of the adverse effects, like urinary retention, constipation, dry mouth, dry eyes, blurry vision, all of those things are the anticholinergic properties at its best. You got it. Dr. Kane, now the next agent we're going to talk about is gas x, or Mylicon, and the generic is simethicone. What is a medication called gas X used for I really don't know. I know it's over the counter, but I'm not sure. Speaker 7 20:33 I'm so sorry, you guys. I'm so sorry you need to take some gas X, as Speaker 4 20:39 Dr. Mitchell eloquently pointed out, gas X is used for intestinal gas or bloating. Speaker 3 20:45 How does it work? So basically, gas X will reduce the surface tension of bubbles which turn into gas, and by reducing that surface tension, it makes the bubbles go away in the GI tract, or at least that's what we think. It's a really old medication. So we actually don't have a lot of good data that actually shows that it does anything at all. Speaker 4 21:03 We do, however, know that it's not really absorbed systemically. Is that right? Yep. Speaker 3 21:08 So it pretty much just stays in the GI tract and works to reduce as many bubbles as it can find. Speaker 4 21:14 I feel much better now. How is this medication supplied? Speaker 5 21:18 It's available over the counter as chewable tablets, soft gels, suspension and, interestingly enough, orally disintegrating strips. So the Speaker 3 21:27 next medication I actually have very little experience with is called pyrantel or Pin-X is the brand name. Pin-X. Speaker 4 21:34 I'm thinking pin worms, round worms, hook worms, if you've got worms, Pin-X is for you. How does it work? Speaker 5 21:43 This medication is an anthelmintic Which works by releasing acetylcholine and inhibiting the cholinesterase. It also acts by depolarizing the neuromuscular blocker and thus paralyzing the helminths. So it basically paralyzes the worms. Speaker 3 21:59 The way the worms stay in your body is they basically chomp onto your GI tract and don't let go. So you can imagine, if we paralyze the worm, its jaw isn't going to be able to hold on to your GI tract anymore, and it will just pass right on through. And that's Speaker 4 22:12 indeed, what it does. I've used this medicine to treat worms in my cat, and you can expect about a day after you dose the medicine to see the worms come out. Speaker 3 22:20 Ew, what kind of adverse effects might we expect from something like pyrantel or Pin-X? Speaker 4 22:27 It's fairly well tolerated, but patients might see some abdominal pain or nausea, vomiting and diarrhea, headache or dizziness. To me, all of that is a small price to pay for not having worms. Speaker 3 22:39 So moving on to a much more palatable agent, lactase enzyme, or Lactaid is our final over the counter product. Normally, when I see ase on an enzyme, it means it chops something up. Is that what this one does? Yes, it does. What does it chop up some Unknown Speaker 22:53 milk. So it chops up lactose Speaker 5 22:55 plainly used in patient who has lactose intolerance, and patients might be complaining of symptoms such as, you know, diarrhea, nausea, vomiting, cramps, bloating and gas. Speaker 3 23:05 How is this available? So it comes over the counter as a capsule tablet, chewables, which would be nice for a meal and then also a liquid. So to review the medications that we discussed for week nine, they were methotrexate or Rheumatrex, Unknown Speaker 23:20 Allopurinol or Zyloprim Speaker 5 23:22 mesalamine, which has various different brand names, such as Pentasa, Asacol or Lialda. Unknown Speaker 23:28 And then we talked about Esomeprazole or Nexium, Unknown Speaker 23:31 then pantoprazole or Protonix, rabeprazole or AcipHex. Speaker 5 23:35 We moved on to sucralfate or Carafate, Unknown Speaker 23:38 dicyclomine or Bentyl. Speaker 3 23:40 Then our over the counter products included simethicone, which is Gas-X or Mylicon Speaker 6 23:48 and pyrantel or Pin-X. Speaker 5 23:52 And the last one on the list was lactase enzyme, which is sold as Lactaid. Speaker 3 23:56 So that concludes week nine of University's top 200 drugs podcast, spring edition. I'm your co host, Dr. King, Unknown Speaker 24:03 Dr. Mitchener, Dr. Patel and Unknown Speaker 24:05 Dr. Weatherton. Study hard. Speaker 1 24:10 This has been an educational production by the Rosalind Franklin University, College of Pharmacy. Speaker 3 24:14 This podcast is copyright Rosalind Franklin University of Medicine and Science. Speaker 1 24:19 No participants have any conflicts of interest to disclose. This podcast is for educational purposes only and is not intended to treat a particular patient. This information should not be used in lieu of the judgment of a healthcare provider. The theme music for this podcast is an excerpt of Metro Mix by Sea Salt released under Creative Commons. You.