DIP Episode 10 - Comprehensive GI Pharmacology

Welcome. My name is Divine. I am a fourth-year medical student. Today's podcast, this will be episode 10. We'll be talking about GI pharmacology. This should basically be a comprehensive GI pharmacology review. Okay. So without wasting so much time, let's go ahead and get in gear. So let's discuss the laxatives. Okay. GI form is relatively straightforward. So the first laxative will discuss is calcium carbonate. Okay. So calcium carbonate obviously causes diarrhea. Okay. But they are just certain high yield things you want to know about this. First thing is calcium. If you go back to your college chemistry, calcium is in group two of the periodic table. So it's di-veilant. And there is this drug that is a bacterostatic 30s inhibitor that binds di-veilant ions really well. I hope you're thinking about it recycling. So in general, if a person is taking a tetracycline, you want to avoid a di-veilant containing laxative or GI active agent like calcium carbonate. And because calcium carbonate contains calcium, right, you can cause hypercalcemia. So hypercalcemia is one of the antecedents of the milk alkalisendrum. That's why if you're taking too much calcium carbonate or if you're taking too much vitamin D, you can get milk alkalisendrum. Milk alkalisendrum has two parts of it. There is the part where you hypercalcemia because you're taking a very heavy calcium load. You can also get a metabolic alkalosis because you're taking a very heavy bi-carb load in calcium carbonate. Okay.

So something to keep in mind. Now, calcium carbonate is a basic salt. So it has like basic properties. So this is again thinking back to college chemistry. We don't need to go hardcore here, but it's a basic salt. So because it's a basic salt, it has the ability to neutralize acid. So that's why you can use this to treat peptic ulcer disease. Although I'll just tell you right now, essentially, everyone gets a PPI for peptic ulcer disease. No one really uses these salts anymore. So you can use it to treat peptic ulcer disease. The only problem is once you stop the acidity comes right back. So rebound hyperacidity is a very high yield side effect of calcium carbonate. And remember that when an acid reacts with a carbonate, it produces carbon dioxide as a byproduct. So the thing is, is there a part of your GI tract that has a lot of acid? Well, your stomach. So if you expose your stomach to a lot of calcium carbonate, you make a lot of carbon dioxide and you get all this bloating, bloating, you get gas and stuff like that. And just as an aside, remember that you can give a calcium derivative like calcium gluconate as one of the treatments for hyperkelimia. Right. So remember in hyperkelimia, you can get like a picked T-waves. You can get a YQR. So if you want to protect the myocardium, you can give a calcium carbonate. Now, the next GI active agent I'll talk about is aluminum hydroxide. Think of this drug as being a constipationist. Okay. So it causes constipation.

And because aluminum is a 3 plus iron, it can bind phosphate. Remember, phosphate has a 3 minus iron. So it binds it really well. So this drug can actually cause a hypophosphatemia. And while we're on the topic of hypophosphatemia, we can basically discuss a refidant syndrome. Right. So if we give you an example question about a person that has been anorexic for a long time and then they suddenly eat a lot of food to replenish their stores, the thing is that consumption of food is a very powerful stimulus for insulin release and insulin as a general principle sends a lot of electrolytes into cells. So it can send phosphate into cells and you can get a very severe hypophosphatemia, which can cause a lot of systemic, systemic presentations. So that's just something to keep in mind. Another application of insulin driving things into cells is in the treatment of hypercalemia. Right. So insulin increases the activity of the sodium potassium ATP is pump. So if a person is hypercalemic, you give them insulin, but remember to also add on glucose so they don't get hypo glycemic. You give them insulin, you increase the activity of that sodium potassium ATP is pump. Remember that that pump drives pumps to three sodiums out and puts two potassiums in. So it puts potassium into the cells. Okay. So that's a kind of redistributive mechanism. Now the next GI active agent I'll talk about is magnesium hydroxide.

Magnesium hydroxide is a laxative, it's not a constipationist like aluminum hydroxide. Okay. But remember again, this is a divalent ion. Magnesium is element 12 in the predictability in group two. So again, you want to avoid this with tetracycline. And basically the way magnesium works is it's not easily absorbed in the GI tract. So it just stays in the GI tract and because it's a two plus ion, it's super osmoticly active. So you get an osmotic diarrhea with magnesium hydroxide. Okay. Now other laxatives, there's stuff like docolax and colis and sena. These are terms you hear in the hospital, but I'm going to largely skip those. They really show up on exams. Now the constipationist we've talked about we said aluminum hydroxide causes constipation as a side effect. So usually for person has bad bad bad diarrhea, right? Other constipationists you can use like mu opioid receptor agonists. So you can use drugs like lopera mite, diphenoxylate. These drugs they both act that mu opioid receptors. So you can use them to treat to treat diarrhea. Okay. You can use them to treat diarrhea. So one thing I'll just go ahead and see here is that if you're taking opioids, let's assume you're using opioids, you never develop tolerance to constipation or mailsis. Okay. You never develop tolerance to those things. For other things with opioids, you can get tolerance, but not for mailsis and constipation. Remember, mailsis is pupillary construction.

But just as an aside, remember that there's actually one opioid that has my dry acids as a side effect, not mailsis. Okay. This opioid can also cause a serotonin syndrome. It's my parody. Okay. My parody is one of those opioids that for some reason they love to give to people with pancreatitis because the Bosrero here in hospitals is that it prevents us from being able to use it as a filter of odispasm. It so happens that my paridine has a serotonergic properties. So you don't want to combine it with another serotonergic agent because you can get a serotonin syndrome. But in addition, my paridine also has mosquito receptor blocking activity. So because it blocks mosquito receptors, instead of causing meiosis, it can actually cause my dry acids. Now, so we're done with the drugs that you could use to treat constipation because they have the areas of side effect, or the drugs used to treat the area because they have constipation as a side effect. So now let's talk about the anti-medics. Okay. The anti-medics. The anti-medics, these are drugs that you give to prevent vomited. You can get MSS in many contexts on your exam. One context could be in the with a person that's getting chemotherapy for cancer. That's one group. Another group can be a diabetic that has a diabetic gastroparesis. Those people tend to get a lot of vomited because the foe just hanging around in the agitract, so that activates a few receptors here and there.

So let's talk about some of these drugs that could be used to treat vomited. The first group I'm going to talk about is on Dancer Tron. Okay. On Dancer Tron is a serotonin receptor antagonist. Okay. It's a 5-HT3 receptor antagonist and the primary use is for chemotherapy, associated with MSS. Okay. And remember that if I mean many chemo drugs cause MSS, but the big, big one you won't remember for your test at a platinum analogue, especially since platen. Okay. Especially since platen. So Dancer Tron works that way. Metoclopromide dumpery don. They are also antimerics. Okay. They block dopamine D2 receptors. Remember you find these receptors in the chemo receptor triggers in the area post-trauma. Okay. So by blocking those receptors you actually make a person not vomit. Okay. And remember that with metoclopromide dumpery don't you want you want to be careful with the extra pyramidal side effects because you're essentially giving people an anti-psychotic when they take a metoclopromide dumpery dump. No one uses dumpery dump in the US. It's not approved by the FDA in the US. And the thing is you may be like, ah, divine. All these receptors are really hard to remember. Let me just show you tell you this. Basically if you block any receptor of notes that's tested on exams in the chemo receptor trigger zone you can treat MSS, right. So we said that oh, on Dancer Tron is a serotonin receptor. So 5 HT3 receptor antagonist, 5 HT3, right. 5 hydroxychryptophan.

Serotonin is derived from triptophan. Metoclopromide dumpery don't we said the block dopamine D2 receptors. Another receptor you can block is the neuroclineine one receptor with drugs like a prepetent and for a prepetent. Okay. So those are drugs that are anti-emetics. So any receptor you block you can block serotonin with on Dancer Tronon block dopamine with dumpery dona metoclopromide or you can block neuroclineine one receptors with a prepetent or for a prepetent. Okay. Now one last thing is steroids. Remember that steroids they do actually increase your secretion of acid. So one of the effects in addition to the like the cushion goid facies and all that fun stuff you get with steroids. Steroids actually increase acidity. So peptic ulcer disease is actually a classic side effect of prolonged steroid use. In fact, if they describe a person that has been on long-term steroids and they have epigastric pain, think about a peptic ulcer disease. So if a person needs to be on steroids chronically, let's assume they have like rheumatoid arthritis or some kind of autoimmune disease and you want to place them on chronic steroids, you actually need to prophylax them with two high-yield medications. The first high-yield medication you want to prophylax with is a PPI to reduce the secretion of acid and you also want to prophylax those people with a best phosphonate. Okay. So that because remember steroids are associated with osteoporosis. Okay.

So let's talk about the drugs that suppress acids. I so they use that steroid story to introduce this concept. But before we can do that, I think we should spend some time doing some quick physiology to understand the mechanisms behind acid secretion. So one thing that can increase acid secretion is acetylcholine. Okay. So acetylcholine can very easily act on mascarinic M3 receptors. I remember that's GQ that's GQ coupled. So you can act on mascarinic M3 receptors on the surfaces of parietal cells and that makes you make more acid. Alternatively, your parasympathetic nervous system can also make something known as gastrin-releasing peptide. If I just said that it releases gastrin releasing peptide, what do you think GRP does? It makes your G cells release gastrin. Okay. That's kind of obvious. So it makes your G cells release more gastrin and just as a quick aside, remember if you have a gastrinoma that has an association with the Zollinger-Elicent syndrome. Okay. Which can be a component of MEN1. Okay. MEN1. Now gastrin does many things. Gastrin comes from G cells like I said. It can directly activate parietal cells through the CCKB receptor. Okay. The colicis-to-kining B receptor that makes you make more acid. Alternatively, gastrin can also activate enterochromophine like cells. Okay. ECL cells to produce more histamine. Okay. And that histamine can act on H2 receptors on the surfaces of parietal cells, which GS Copold. Okay.

To increase the activity of adenylate cyclase and release more acid. Okay. So basically one construct you sort of want to get in your brain is that an increase in cyclic AMP or increased activity of adenylate cyclase causes more acid secretion. Okay. And just as a weird hematology time here, one thing I want you to think about is many people that have the myeloprolypharative disorders, right? So those people tend to get an increase in all their blood cell lines, right? So their red cells increase in number, their platelets increase in number, their white cells increase in number. One high yield cell that increases in number is the Besophilts. Those Besophilts can actually secret histamine, right? So if a Besophil degranolite, you can release histamine into the circulation. That histamine can go and act on H2 receptors on the surfaces of parietal cells and cause peptic ulcer disease. So if they give you a question about epigastric pain in a person with a history of some kind of myeloprolypharative disorder like polycythemia vera or CML or essential thrombocytosis, I mean essential thrombocytemia really want you to think about, I really want you to think about Besophilts, secreting histamine and causing a hyperacidity. So again, histamine, we said it increases acid secretion, it comes from ECL cells and terochromophine-like cells, okay? Those cells in the stomach secret histamine, that histamine activates parietal cells through H2 receptors, okay?

And you make more acid that way. Prostaglandins on the other hand, they actually cause a decrease in acid secretion, okay? So the Prostaglandin receptors you find on the surfaces of parietal cells, they actually GI coupled, okay? So they decrease the activity of adenylates cyclase, they decrease the production of cyclic AMP, and in so do you decrease the release of acid, okay? So as a quick time here, if a person is taking aspirin, okay? For like chronic osteoarthritis, remember, aspirin is an irreversible Cox-1 and 2 inhibitor. So when you inhibit that, you make less Prostaglandins. So if you went ahead and gave a person a Prostaglandin analogue, like mesoprostol, PGE1 analogue, you can reduce, you can sort of profileux against aspirin-induced peptic ulcer disease. And somatosatin also decreases acid secretion, it basically decreases secretion of anything notable in the body, okay? And parietal cells, right? They're the cell of the hour, they're the big cells that secret acid, and they use a hydrogen potassium antipoder. So they pump hydrogen into the lumen of the stomach and bring potassium into the cell. And that should make sense, right? Because you're trying to maintain electro neutrality. If you release a positive charge from a cell, you also want to bring a positive charge into the cell to sort of balance charges, okay? And remember that these protons that are secreted from the cell, they don't just come out from thin air, okay?

They actually come from carbonic and hydrates. Carbonic and hydrates splits carbonic acid into H plus and bicarb in the parietal cell. So the H plus goes towards the lumen. The bicarb goes out the bizel side of the cell. And because bicarb has a negative charge, right? You want to, again, maintain electro neutrality. So only you do that is you're bringing chloride, okay? So you're dumping bicarb into the bloodstream, you're bringing chloride into the cell. So you actually get hypochlorimic as you're digesting food because remember in the process of food digestion, you're making more acid. And you also get an metabolic alkalosis with that because you're dumping bicarb into the cell. So you get a hypochlorimic metabolic alkalosis with food digestion, although it's a transient effect. Okay, so the blood pH increases when you're digesting food, okay? Something to keep in mind. And just real quick, again, remember that if you make autoantibodies against parietal cells, that's a pernicious anemia, right? So those people will get a megaloblastic anemia because they are not making intrinsic factor. An intrinsic factor is like the body for B12 to be reabsorbed in the terminal alien. So now that we've talked about all this physiology, it's much easier to know what the drugs do, okay? So the first drug class will talk about the histamine-heat-stermin-heat-stereceptor blockers, okay? These drugs all end in tedin.

So drugs like rhanitidine, nizzatidine, symetidine, they work by blocking histamine-heat-stereceptors, okay? So the receptors that these drugs work on should be found on the surfaces of parietal cells, okay? Step one and board exams. The occasionally you'll have to just see if you really know where these receptors are, okay? The histamine-heat-stereceptors are found on the surfaces of parietal cells, okay? So these drugs, the suppress acid secretion. The big thing you want to know about them in addition to the arol, as histamine-heat-stereceptor blockers, is you want to remember symetidine, okay? Symetidine is actually an intrusion receptor antagonist, so it can actually cause a gynecomastia as a side effect because it's that estrogen testosterone ratio is still tilting you more towards a hyperestrogenic state if you think in terms of ratios. And it's also an inhibitor of cytochrome P450, so just another thing to keep in mind with symetidine. Okay, so they can easily test that in the context of a person getting drug toxicity or drug that's metabolized by your Cp450 system, you can get more side effects because your boost drug levels with symetidine. Now, the next drugs that block acid secretion are the PPI's, okay? The Prudome Pumbin inhibitors, the all-end in presol, so these are drugs like Esomepersol, Pantopersol, Lansopersol, Omeprzol, you get the drift.

These drugs basically work by irreversibly inhibiting the hydrogen Potassium Antipoder on the surface of parietal cells, okay? So they are the most powerful acid suppressants, okay? So by blocking that anti-poder, you do not secret hydrogen ions into the lumen of the stomach, okay? So these drugs, they have many side effects, okay? And in fact let's talk about them one by one. One side effect they have is that they can cause a vitamin B12 deficiency. So what's the mechanism behind that? The mechanism behind that is that, let's think of this for a second, right? So we know that there are certain cells in the GI tract known as chief cells, okay? Chief cells, they make Pepsinojin. That Pepsinojin, it's a Zymogen form of the enzyme, it needs to be converted to the active form Pepsinojin, okay? To go from Pepsinojin to Pepsin, you need acid to make that happen, the acidity of the stomach, okay? And then that Pepsin can help you cleave vitamin B12 from animal protein. Remember vitamin B12 is derived primarily from meat, from animal protein, okay? So if you're taking a PPI, right? You suppress acid secretion, you have less conversion of Pepsinojin to Pepsin, so you cleave less vitamin B12 from animal protein, so that B12 just stays sequestered in animal protein and you don't have a chance to reabsorb it, okay? So that is how you can get vitamin B12 deficiency with the intake of a proton pump in inhibitors.

So they can cause a B12 deficiency and they actually increase your risk of certain infections, right? So like the increase your risk of C-deficulinitis because again, the acidity of your stomach is quite good at killing of C-deficulinitis. Alternatively, they also increase your risk of aspiration pneumonia again. That acidity of your stomach has an antibacterial function, so if that antibacterial function is gone, okay? And imagine let's assume you're an alcoholic, you drink too much booze because you're celebrating that you matched into residency or that you crush step one so you pass out on the ground or something and then you vomit and then you aspirate your secretions and let's assume you're taking a PPI for some bizarries and because you have a stress ulcer from being stressed from studying for step one, okay? That perfect storm can increase a person's risk of aspiration pneumonia, okay? So just things to keep in mind with PPI's. Another thing is these PPI's, they do have some ability to block potassium channels, okay? And I mean like this is more teleological explanation but think about it. If something has the ability to block a hydrogen potassium pump, it should make sense that it could potentially like do something to potassium channels, okay?

So if they have some potassium channel blocking activity and as we'll discuss when we get to the entire rhythmics, you can already begin to imagine that this can cause a by blocking potassium channels, you can prolong the QT interval and you can get a torsad the point, okay? So that's something you want to keep in mind with PPI's. Don't just prescribe PPI's like candy to your patients in the future. And just as a real quick review, remember that there are many other causes of a prolonged QT interval, right? So any notable electrolyte anomaly that has hypo in the name can all cause a QT prolongation, right? So like hypochylemia, hypochalcemia, hypochymizemia, those all cause QT prolongation that can cause torsad the point and can die, okay? And remember the way you treat the torsad is with with magnesium, okay? Remember torsad the point is a polymorphica ventricular tachycardia. And a mild side effect as well, this is quite low yield but it's something that is definitely testable is that PPI's they can actually increase your risk of osteoporosis. Okay, now real quick though before we dump these PPI's in the context of hypochylory, your PPI's can actually be a constant length of triple therapy, okay? For Hpylory, okay? So remember the triple therapy is a clarythromycin, okay? That's a macrullid, that's a 50s inhibitor, a moxicillin, okay? Remember that's a penicillin, so it inhibits transpeptidase and then a PPI, okay?

So you can remember cap for that, that's a nice no money for that. So PPI's you can actually use them for Hpylory. And one unusual step, one question you could get is a person that you suspect they have Hpylory and they about to come into the hospital for testing, or I guess the physician's office for testing. And the ask, which of the following drugs should be stopped or whatever? Okay, you want to go ahead and stop the PPI because again remember PPI's have activity against Hpylory. Okay, and then also don't forget that PPI can also be used in quadruple therapy, okay? For Hpylory, right? So remember quadruple therapy, you have a macrullidazole, you have this smooth subcellicylate, we'll talk about that in a bit, you have tetracycline, so again remember those are your butterstatic 30s inhibitors and then you have your PPI's as well. And don't forget that Hpylory is silversteam positive and it's a u-reus positive bug, okay? Being u-reus positive is what makes it a recavoc on your stomach because by having expressed a lot of u-re's you can basically neutralize a ton of the acid that's secreted by your parietal cells. Now just a grab bag of other drugs and conditions that relate to GRI from Acology, so don't forget Orlis that, okay? So remember to break down triglycerides, you need lipase, if you don't have lipase activity you don't break down triglycerides and you basically just poop them out. So that's how a drug like Orlis that works.

Orlis that is a lipase inhibitor, so by inhibiting lipase you don't break down triglycerides, you just basically poop them out, okay? Now gastroperesis, basically it's something that you will classically test on exams in the context of a diabetic. And if a diabetic has gastroperesis, right? So things are not moving through the GRI tract, you want to try to give them things that can make the GRI tract move, okay? So the thing is your parasympathetic system, right? So think of yourself as resting and digesting. Imagine yourself like just sitting on a restroom and reading a newspaper, not worrying about the worries of a med student like step one or step two CK. So you sit down, you're resting, digesting, you're pooping, right? That's a relaxed state, that's a parasympathetic state. So I'm just using that to help you remember that, sitting down on a, I mean that, sorry, I'm using that to remind you that your parasympathetic system makes things move through your GRI tract. So if a person had a gastroperetic disorder, one way you can treat that is to give something that activates a parasympathetic effect. So one thing you could do with that is you could give a direct Moschronic receptor agonist, okay? So drugs that fall under this purview include drugs, things like Bethanychol. Bethanychol is a Moschronic agonist, so you can use that to treat gastroperesis, but you can also use Bethanychol to treat post-surgical ilias, okay?

Because again, by activating Moschronic receptors, you increase flux through the G-I tract. Another thing you can do to boost the parasympathetic effect is to inhibit acetylcholine esterase, right? So remember that acetylcholine esterase breaks down acetylcholine. So if you inhibit acetylcholine esterase, your acetylcholine levels build up, okay? And you can increase flow through your G-I tract. So that's how drug like Nio-Steaming works, okay? Nio-Steaming, you can also use that, like I mentioned, for Bethanychol to treat post-op ilias. Now, if you remember for your studies of micro-pharmacology and we'll have a series of podcasts on that in the future, but you probably learned that macrolids have G-I upset as a side effect, right? So remember your macrolids are your 50s inhibitors that inhibit translocation and their bacterial static in general and use them to treat atypical causes of pneumonia like microplasma, chlamydia, and ligenella, right? So your macrolids, they have G-I upset as a side effect and you may have wondered what's the mechanism behind that? The thing is there is a receptor in the G-I tract known as motillin, okay? Motillin receptor. Motillin receptor is respond to motillin, okay?

And motillin is endogenously secreted in the G-I tract, mix a G-I tract, sort of move a lot, but the thing is you could give an exogenous motillin receptor and agonist, sorry, motillin receptor agonist like erythromycin and by activating those receptors you make your G-I tract more tired, okay? So by increasing flow through your G-I tract you can use a motillin receptor agonist like erythromycin to treat ilias and also diabetica gastroparesis. And the next drug I'll talk about that you can use for gastroparesis works with a certain construct and this construct, I just want to introduce it now, I'll develop this construct further when we talk about psychiatric pharmacology. But basically this construct is that low levels of dopamine, so just remember it for now, we'll talk about this some more later, but low levels of dopamine equals high levels of acetylcholine, low levels of dopamine equals high levels of acetylcholine, okay? So if you memorize this construct, the thing you want to remember is that if you blocked dopamine receptors, your levels of acetylcholine will go up, okay? So metoclopromycin is a drug that could also be used for the erythromycin because by blocking dopamine receptors it increases your levels of acetylcholine and that increases flow through your G-I tract, so metoclopromycin is a prokinetic agent, okay? Now, last series of conditions I'll mention in the context of G-I farm, first it will be a hepatic insect fallopathy, okay?

So remember if a person has liver disease, they have an ammonia problem because the urea cycle is not working, so one way you could sort of deal with this ammonia problem is to try to trap it in the G-I tract, okay? You can try to pull out the ammonia, so how can you do this? The thing is ammonia is reabsorbed in the G-I tract, but ammonium is not, okay? Because it's an ionic compound, so it's not reabsorbable, so lactic acid can, remember it's an acid, right? So it can protonate ammonia, make it into ammonium, you don't reabsorb it and you poop it out. So how can you make lactic acid? You can make lactic acid from compound known as lactulose, okay? Lactulose, your GI flora converted to lactic acid, that lactic acid goes ahead and protonate ammonia, mix ammonium, it's an ionic non-resorbable compound, so you poop it out in the G-I tract, okay? Second way you can also deal with the ammonia problem is you could say, you know what? Let me try to decrease the potential sources of ammonia, because the thing is it's not just a diet, containing protein that gives us an ammonia load, you can actually also get an ammonia load from the bugs in your GI tract, your GI flora do make ammonia, so one thing you can do is just to kill all of them, okay? So one way you can kill off all your GI flora is with a drug known as refaxamine, okay? Refaxamine, it rarely sounds a lot like rye fanpine, okay? They actually have a very similar mechanism of action.

Refaxamine is an RNA polymerase inhibitor, okay? So it kills off your GI flora, you kill off a source of ammonia production and you could potentially relieve the symptoms, the person gets in the context of hepatic and cephalopathy. And just remember real quick that tips procedures, right? So this is classically done by IR, tips procedure is I think that stands for trans hepatic, no, trans joggola, intra hepatic, porous systemic shunt, okay? So basically it's just a conduit to create between your hepatic and porous veins to acutely decrease the porous pressures, if you think about it, if you make that conduit, you're basically bypassing your liver, you're bypassing the metabolic effects of the liver, so tips procedures actually increase your risk of hyperamonemia and hepatic and cephalopathy. But again, you want to use a tips procedure for prison has high porous pressures and they have like really bad side effects from that like esophageal viruses. Okay, now another grab bad GI condition is a polystatic autoimmune problem, so you get an example question about a lady in her 40s that has a lot of paritis, okay? And she has direct hyperbiliarobinemia, what are you thinking about? Well, I hope you're thinking about primary bilayer colangitis, this was previously known as primary bilayer cirrhosis, okay? Remember the association with antimidocondyl antibodies, the pathophysiologies, you're basically making auto antibodies against intra hepatic bowel dots.

Please don't confuse this with primary sclerosine colangitis, which has an authoritative colitis association, pi and k, okay? Where you actually make auto antibodies against the intra and extra hepatic bowel dots, okay? So in PBC, you make auto antibodies just against the intra hepatic bowel dots, in PSU you make auto antibodies against the intra hepatic and extra hepatic bowel dots. But again, because you're making auto antibodies against bowel dots, you have no problems conjugating bilayerobin, but you can get it out of the liver, okay? So you get a conjugated hyperbiliarobinemia. So in general, one way you can treat these conditions is with a drug known as orso dial, also known as orso geoxycholic acid, so you give this drug and it actually does improve survival in patients with PBC. It generally does not improve survival in PSU, but in PBC, there have been studies that show that orso dial does in fact improve survival. And then if a person has orso-relative colitis and Crohn's disease, again, another grab baggy condition, you can give steroids, you can give TNF inhibitors, we'll talk about TNF inhibitors later. You can also give a drug known as a sofa salazine, okay? They occasionally call it 5 A or 5 amino salicylic acid, okay? It's an anti-inflammatory agent, okay? Because again, it basically contains aspirin, if you may remember aspirin, actually does have anti-inflammatory properties.

So by giving an anti-inflammatory agent, you can sort of tune down the inflammation you get in UCN Crohn's. But generally on exams, sofa salazine is used primarily to treat those radiative colitis. Another grab bag, a set of GI drugs, a propramolose per anolactone, you can actually use them for chronic prophylaxis, in a person that has chronic portal hypertension and sofa geoviruses because the thing they do is that they cause plungeant viso-construction, so they decrease pressures in the portal system by someone known mechanism and you could use those as chronic prophylaxis against an esophageal bleed, although you do not want to give these, in general, you don't give these drugs acutely, the drug you give acutely first of a geoviruses is octriotide, okay? But chronic prophylaxis, you can give propramolol and aspirinolactone. And then for ulcers in the GI tract, right? So those ulcers, one thing you potentially want to do to ulcers is you want to sort of like quote them so that they heal, okay? Because if you keep exposing ulcers to the acidity of the GI tract, they don't heal in the first place. So one way you can promote ulcer healing if you make is to give a cytoprotective agent, that's the buzzword you want to recognize on exams, okay? A cytoprotective agent, you want to give drugs like bismuth, okay? Bismuth subsalicylate is a cytoprotective agent, but in addition to actually being a cytoprotective agent by codein ulcers, it also causes a constipation as a side effect.

So you can actually give it to a person that has diarrhea, right? So if you've ever heard of the drug, in modium, in modium contains bismuth subsalicylate. So you're basically using the constipation side effect to lock up your GI tract. Bismuth, remember that it also makes your stool black. It so happens that some of the bugs in your GI tract make hydrogen sulfide and bismuth can react with that hydrogen sulfide to make your stool a tari black. The other side of protective agent is sucrophate, okay? Socrophate is an aluminum containing compound sucrophate, right? So all has aluminum. It's positively charged, okay? Most ulcers are negatively charged. So you have those ionic interactions and again you basically protect ulcers, okay? You give them a chance to heal. So that is all I am going to say about GI from ecology. If you have any questions, please let me know and I hope to see my hope to see you guys in the next podcast, okay? I wish all the best and enjoy a wonderful weekend. Have a bye.

PP Is (to reduce acid secretion) and Bisphosphonates (to prevent osteoporosis).

Magnesium hydroxide.

Increased risk of Clostridioides difficile colitis (C. diff).

Mypadon (or Meperidine/Meperidone, as mentioned in the transcript context).

It acidifies the colon, trapping ammonia ($\text{NH}_3$) as non-absorbable ammonium ion ($\text{NH}_4^+$) for excretion.

Bismuth subsalicylate (or Sucrospate).

Irreversible inhibition of the $\text{H}^+/\text{K}^+$ AT Pase pump on parietal cells.

H2 receptor antagonists (e.g., Ranitidine, Cimetidine).

Reduced stomach acidity impairs pepsinogen activation to pepsin, which is necessary to cleave B12 from animal protein.

Rifaximin.

Cholinergic agonists (e.g., Bethanechol) or A ChE inhibitors (e.g., Neostigmine).

Chronic use of systemic steroids (due to increased risk of peptic ulcer disease and osteoporosis).

Irreversible inhibition of the $\text{H}^+/\text{K}^+$ AT Pase pump on parietal cells.

H2 receptor antagonists (e.g., Ranitidine, Cimetidine).

Reduced stomach acidity impairs pepsinogen activation to pepsin, which is necessary to cleave B12 from animal protein.

Rifaximin.

Cholinergic agonists (e.g., Bethanechol) or A ChE inhibitors (e.g., Neostigmine).

Chronic use of systemic steroids (due to increased risk of peptic ulcer disease and osteoporosis).