DIP Episode 73 - Endocrine Physiology and Pharmacology Part 2 (Final Part)

Okay, welcome. My name is Divine. I am a PGY1 resident, going to a radiology, and currently my transitional year. And this is the 73rd episode of the Divine Intervention Podcast. And today we're going to be finishing up endocrine physiology and pharmacology. Okay, this is the second part, this is the final part. So let's go ahead and begin. We stopped at mid-forming yesterday. Let's jump on to the sofonial ears. Right, so the first thing I want to do is list some biochem about ground. Right, so the thing is remember that we have glue two receptors on the surface of on the surfaces of pancreatic bitter cells. Right, those glue two transports. Remember they are bi-directional. Remember the bi meaning two and glue two being like bi-directional. Right, so glucose comes in through that transporter convert it to glucose six, we'll see by glucose kinase. Right. And remember it's actually kind of high you to know this for step one that glucose kinase is not feedback inhibited by glucose six force feed unlike the case that obtains for hexokinase. And then you produce ATP ultimately and then that ATP closes potassium channels. Right, remember potassium is an intracellular ion, right. So the gradient for potassium is normally to go out of a cell. But if you close that potassium channel with ATP then potassium doesn't go out of the cell depolarizes. When you get that depolarization calcium comes into the cell and then that triggers insulin release from vesicles.

So the thing is how do these are so-foneal erias work? These so-foneal erias work by basically replicating the effect of ATP. Okay, they block those potassium channels so that the cell depolarizes and then you squared out more insulin. There are also some drugs known as make lead nights, right. So drugs like repaglinite and anteglyneite, they basically do the same thing, but they are shorter acting than the regular guiding variety so-foneal erias. So what are the two kinds of so-foneal erias? They're actually first-generation so-foneal erias, so these include drugs like clopropamide. In fact, basically all of them end in amide for the purposes of your USML. So there's clopropamide and there's toburamide. Toburamide is probably not much you need to know about it, but for clopropamide, it's actually very high to know that clopropamide causes an increased release of EDH. So clopropamide can actually cause EDH. It can cause like a central SIDH if you may. Okay, so hopefully you can reason through that. Those people have a high urinose molality, but a low serenose molality, right. So you have like a uvolymic hyposmolar hyponitrimia if you may. Okay, and the way you will treat that ideal, right, is to give a... you can give an EDH receptor antagonist, right. So like tovaptan, konivaptan and stuff like that. But also think about it, right. You could also try to bring in a drug that has nephrogenic diabetes in sepidosis and side effects to reverse that SIDH, right.

So you can give a tetracycline like the mechylocycline, okay. You can use that to basically... the mechylocycline causes nephrogenic guia, so you can use that side effects to your benefit. And then we have the second generation sulfonioureus. They all have like glee in their names, right. So like gliburide, glipeside, glimepride. Again, same mechanism of action, you probably want to know the side effects, right. So like gliburide is nephrotoxin. Just remember, gliburide, and it's like urine, like urine in it. So that helps you think of the kidneys. Glipeside, right. So lipid, like glipi, sounds like liver, okay. So it's hepatotoxic. Glipeside is hepatotoxic, and then we have glimepride. Now, the general side effects of sulfonioureus, you probably want to keep in mind, right. Stuff like hypoglycemia, especially like the first generation agents, they have a very high risk of hypoglycemia. They can also cause weight gain because think about it, right. Insulin is a growth factor. Insulin helps you star fat, right. So if you're increasing the release of insulin, you technically get fat, okay. So that's how these sulfonioureus cause a weak gain. And sulfonioureus literally have sulfur in their name, so the associated with sulfur allergies, okay. And remember that if a person is taking a sulfoniourea, they are insulin and the CPAP type levels will actually be elevated, okay. So if a person has like weepos symptoms and you're like, oh, is it an insulinoma that's causing this?

Or is it injecting insulin that is causing this? So I deal with those in a sulfoniourea. Basically, what you do is you check the insulin and CPAP type levels. If a person has an insulinoma, both will be elevated because the insulin is coming from the body. If the person is injecting a sulfoniourea, they are insulin and CPAP type will both be elevated as well, right. Because sulfonioureus increase the endogenous release of insulin, right. Although there's like a blood test known as a secretogoc screen that you can basically use to detect a sulfoniourea. But if a person is injecting insulin, the insulin that's sold in pharmacies, right, those not have CPAP type in it. So the insulin will be high, but the CPAP type will be low almost like undetectable. That basically tells you that, okay, this person is basically creating their own symptoms, so like a factitious disorder, sort of business. Now, the next drugs I'll talk about are the thiozolybine dions or the TZ Ds. So the drugs in this class include drugs like they are all like glitter drugs, right. So like Rosaglida zone, Pyroglida zone, Troglida zone, Troglida zone, I think that has been discontinued. It can cost you to check basically. So how do these drugs work? These drugs work by activating an enzyme known as P-PAR gamma. So think of gamma gene, gamma G for glucose, right. So don't confuse this with your fibrate stone that are anti-lippid medications that work by activating P-PAR alpha, okay.

So these drugs are P-PAR gamma activators. So you may wonder, define how does this help with a blood glucose issue. So, okay, let me explain. At least this is for me like reading the literature, right. So this is probably not something I'm going to worry too much about for step one, but just for the purposes of understanding, right. So the thing is free fatty acids are actually the activators of P-PAR gamma, right. So let's assume you have a lot of free fatty acids hanging around in the body. Your body will want to try to store some of those free fatty acids as fat, right. So those free fatty acids actually activate P-PAR gamma and P-PAR gamma actually makes you store more of those free fatty acids as fat in adipose cells, okay. And the thing is think about it, right. If you are storing a lot of your free fatty acids, then the only source of energy available for you, at least for the most part, is glucose. So you burn out more glucose and that will decrease blood glucose levels, okay. So this is one potential mechanism behind these drugs being good for diabetics, okay. Because you're basically giving something that activates receptors that are activated by free fatty acids for you to store more fat. If you store more fat, they are less available for energy. If they're less available for energy, you burn up your glucose, okay. There's many more mechanisms, there's probably even on discovered mechanisms, well, this is one that I saw hyalurithane in the literature.

Now, what are the side effects of these TZ Ds, right. So they cause weight gain, again, the story more free fatty acids. So you should potentially be able to cause a weight gain with that. These drugs are also hepato toxic, and the thing is they actually contraindicated in patients with CHF. So here's why. So the thing is in the collecting duct of the nephron, they actually p-part gamma receptors. And the thing is when you activate these p-part gamma receptors, you actually cause an increase in sodium reabsorption. And as you increase in sodium reabsorption, you will in effect also increase water reabsorption, so you get fluid retention. And the thing is if you have CHF, you're not very good at handling excess fluid, okay. So you can basically throw these patients into a CHF exacerbation sort of deal. Okay. So that's like the probably the biggest side effect you want to keep in mind with your thiozolydean dions. And these drugs actually also have a suffer allergy, right. So thiozo, right. So thio, thio. If you remember from organic chemistry in college, thio, right. Those are hydro groups. Now the next groups I'll talk, drug class I'll talk about are the GOP1 agonists. So, so your GOP1 agonists, right. So basically GOP1 is something known as an increase in, right. An increase in is just basically something that increases your endogenous release of insulin. From the beta cells of the pancreas, whenever you have like high blood glucose levels.

In general, if your blood glucose is like low or it's normal, your creatins will not do anything. Okay. They basically only work when your blood glucose is high. So why is this important for our purposes? The thing is, in creatins, they are actually meeting the GI tract. We actually have creatins in our body. And the thing is they are meeting the GI tract in response to an oral glucose load. Okay. So the thing is in general, if you give a person IV glucose, you actually do not release more creatins in general in general. Okay. Not that's not a hard target, but in general, and this for purposes of your USML is in general in response to an IV glucose load, you actually not release creatins. So what does this tell you? This tells you a very high yield testable concept for the USML step one exam. If a person takes oral glucose, they actually release more insulin than if a person takes IV glucose. Okay. Oral glucose causes an inc- like a higher faster, like I guess like a greater release of insulin, actually a faster release of insulin because you're also releasing creatins as you expose that glucose to the GI tract. And in creatins, again, increase the endogenous release of insulin. Now, one of the higher you think you want to know about GLP1 is that you can break it down to inactive metabolites to you can break like an in-critin, right? Or I guess like GLP1, for example, to inactive metabolites with an enzyme known as DPP4. I believe that stands for dipeptidopeptidysfor. Okay.

Now, the drug names you want to know that your GLP1 are going to say drugs like exenatide, lyraglutide. These drugs, again, right? They increase the endogenous release of insulin, right? So that sort of helps if a person is a diabetic. Now, one, two actually you need to know two key things with these drugs. One is that lyraglutide has actually been approved by the FDA for weak loss. So if you notice, many of these diabetes drugs, right? So I said, for example, that metformin is weak neutral, but your softener, your ears and your TZ Ds can cause weak gain. Lyraglutide, your GLP1 agonist for the most part can cause weak loss. Okay. Now, another high thing you want to know is that if a person, and I see this as like a classic step one question, if a person has a history of an MEN syndrome, okay, especially like MEN2 or ER2 B, or they have any history of medallary thyroid cancer, you do not want to give them these GLP1 agonists. Why is that the case? The thing is this has not necessarily been replicated in humans, but if I'm remembering correctly, there have actually been some rat studies that show that whenever rats were exposed to these GLP1 agonists, they actually had an increase in incidence of medallary thyroid cancer. So this is one of those bizarre things you want to keep at the back of your mind. Now, the DPP4 inhibitors, right? You probably already know how they work. I just told you that GLP1 is broken down to inactive metabolites by DPP4.

So if you're a drug that you want that was for diabetes, right? You would rightly want to inhibit DPP4 because if inhibited DPP4, your GLP1 levels will go up, right? Your GLP1 will persist. And if you persist, again, you will increase the endogenous release of insulin and voila, all your diabetes problems go away. So these drugs, the increased levels of increase in creatins because they inhibit DPP4 and the all-ending glyptin, right? So the thing is these diabetes drugs, they look like a pain, but they're actually not that bad because many of them have a common-word root or something, right? So these drugs, your DPP4 inhibitors, they all end in glyptin, right? So like aloe glyptin, lina glyptin, sacsaglyptin, cedar glyptin, okay? And then the next drug class I'll talk about, they're your alpha glucosides inhibitors, right? So the thing is alpha glucosides is basically a brush border enzyme that helps you break down like, by sacrating the GI tract to monosaccharides, right? The thing is your GI tract, at least at the level of the genon for the most part, only has the ability to reabsorb monosaccharides, okay? Your brush border does not reabsorb dysaccharides, okay? So the thing is if you gave a drug that inhibited alpha glucosides, which is a brush border enzyme, you will not break down dysaccharides to monosaccharides, you have a persistence of dysaccharides, they will not be reabsorbed, and that way you basically prevent the prosprndial, right?

So like just after you eat the prosprndial rice in a presence of blood glucose levels, because you're not reabsorbing that glucose, at least most of it, right? Because most extent has a dysaccharide, so you just put it out, you just basically put out the glucose, and the classic drugs you want to know here are drugs like acarbols, okay? Acar, BOSE, and miglitol, right? Immiglitol is MIGLI, TOL. So these drugs, again, the inhibitor of the glucosides, you don't break down your dysaccharides, they sting the GI tract, and then you pop them out, but you can already begin to envision a potential problem with these drugs, right? So the thing is if the dysaccharide sting the GI tract, right? Your bacteria and your GI tract are going to have a field day, with those with those dysaccharides, right? So these drugs cause a lot of like bloating, a lot of diarrhea, a lot of gassing, it's just one of those things, I feel like that side effect is limiting for a lot of patients, I mean I personally have never seen a patient on any of these alpha glucosides inhibitors. And as I'm rolling into the next drug class and since we're talking about the GI tract, I guess it's probably prudence to mention that. In the GI tract, we actually have a transporter that helps us to absorb sodium and glucose, right? So it's a kind of secondary active transport, right?

So this transporter is known as the sodium glucose linked transporter, because literally it takes advantage of the gradient energy of sodium to bring glucose against this concentration gradient into the entire site, okay? And in the GI tract for the most part, the sodium glucose linked transporter we have is known as SGLT1. In fact, while on this topic, remember if a person has like a color, right? You're told to give them something called ORT, like my Nigerian friends will probably know of ORT as like OR Royhydrician therapy. It's usually when you have like really, really bad diarrhea in Nigeria, right? So basically it's a salt sugar solution. The reason you give that salt sugar solution is that by giving salt and sugar, you increase the activity of that sodium glucose linked transporter, because that is basically the only transporter that can help you retain like sodium and glucose and fluid, right? Because wherever sodium goes, water would technically follow, okay? That's the only like that's like the major transporter system that is not knocked out by the color of toxin, okay? So that's why OR Royhydrician therapy contains like a nice concentration of salt and sugar. So that leads us to our next diabetic drug class. In fact, probably it's actually the last group. They have the SGLT2 inhibitors. I said SGLT1 is found in the GI tract. Remember GI, the I in GI like a one, okay? And then we have the SGLT2 inhibitors.

The SGLT2 inhibitors, again, they are easy to remember because they all end in flosing, right? So like can I get flosing, the pagly flosing and pagly flosing, they all inhibit the transporter SGLT2, because that SGLT2 transporter in the proximal convoluted tubule helps you reabsorb sodium and glucose, right? It basically it's a glucose transporter, but it uses the gradient energy of sodium, just like we have in the GI tract. So the thing is, if you inhibited that transporter, you will not reabsorb glucose and then you basically waste the glucose in the urine. And by doing that, if you have peanut glucose, then it's not coming into your blood, right? So that way you decrease your glucose levels. But again, what there are bugs that leave in your urinary tract, right? And you'll have like a banquet when you expose them to all that glucose, right? So SGLT2 inhibitors can generally cause UT Is. They can actually cause very serious genital urinary infections. And I mean if a person has bad kidneys, obviously, don't want to give these drugs, right? They are contrary to it. In patients with in patients with with a renal dysfunction, okay? In fact, like think the classic infection that they get on examples is like a candida, like a candida infection, okay? Remember, there are some other things that increase your risk of a candida infection, right? If you're diabetic, that's one. And by basically the same path of his, I explain as I explain for the SGLT2 inhibitors.

And also for a person has HIV, that increases your risk of having candida vaginitis. And then another classic scenario for a person having candida vaginitis on MBM Es is if a person recently just took like a broad spectrum antibiotic, taking a broad spectrum antibiotic actually does increase your risk of candida vaginitis. Okay, so let's then, I guess talk about some quick adrenal and growth hormone and pharmacology and then we'll round this up. This should be a short report, Kaz, that yesterday I hope. So, adrenal pharmacology, right? So again, let me just lay down some physiology first. So, classic disease that's discussed in under the adrenal gland is Adescent disease, right? Basically it's an autoimmune attack against like the person's adrenal cortex, right? So that's why it's called a primary adrenalin sufficiency. The thing is, the adrenal gland has three regions, right? And actually the histological structure of the adrenal gland is very high yield to know for the USMMS. They will classically give you an image that sort of shows like the different parts like the glomerulosa, fasciculata, and reticularis, through the adenomidol and then you have to basically pick out one region. So, I remember the glomerulosa is on the outside, it's the outermost, right? It makes outosterone and then we have the fasciculata that's on the inside, that's in the middle, produces glucocoricoids and then we have the reticularis that is the innermost, that produces sex steroids, right?

So like GFR, you've probably heard of this in the morning that it's like the glomerulosa mix, salt, the fasciculata mix, sugar, the reticularis mix, sex, right? So like salt, sugar, sex, the deeper you go, the sweeter it gets, kind of bizarre in the morning there, but it's actually pretty effective. So, I just thought I should mention that so it's something to know for you, exam, right? But adescent disease, that's basically where a person has a primary adrenalin sufficiency. And in general, the way you treat adescent disease, right, you can give synthetic glucocoricoids, right? Remember your steroids, basically work by inhibiting a phospholipids H2. I've talked about that pathway multiple times in many different podcasts. I believe I discussed it also in the pulmonary pharmacology podcast, right? So, drugs like dexamethosone or prednisolone, right? Those drugs are very good glucocoricoids and you can use them to treat primary adrenalin sufficiency. Classically, right, if a person has a primary adrenalin sufficiency, I mean, sorry, if a person is taking a glucocoricoid, they are right, with their white blood cell count will go up, right? Because remember steroids cause a demarcination of your neutrophils, right? So all the white cells, you'll see them in the bloodstream, but they don't necessarily go to their, go to the site of infection, right? Because again, you're getting a demarcination if you make, that's the mechanism you want to know.

And one higher thing to actually know, because it's something that always bogged me is that why will a person has have a eosynophilia in adolescents disease? The thing is, in adolescents disease, right, you have a primary adrenalin sufficiency. So you're not me longer making glucocoricoids. One of the functions of glucocoricoids is that they cause hipoptosis of eosynophils. So think about it. If you have a steroid deficiency, it's like a glucocoricoid deficiency, it's not longer making glucocoricoids, right? So you're no longer causing hipoptosis of eosynophils. So your eosynophil count goes up, okay? That's why eosynophilia is one clinical finding or gets lab finding in the setting of adolescents disease. Now, if a person has adolescents disease, right, and you're giving them a ton of steroids, right? So remember, there are certain bad things that can happen when you take steroids. I've already highlighted most of these. You can have like the buffalo hump, right? Remember that your protease inhibitors, that's a HIV drug class. I talked about that in micro-phomacology, can also cause a buffalo hump, right? So like the fatta redistribution, your steroids, if you take them for a long time, they can also cause a purple striate, right? Because steroids basically destroy connective tissue. You can also get osteoporosis if you take steroids, right? So if a person is on chronic steroids, you need to place them on this phosphon, it's a very classic USMLE exam question.

And then, under thing steroids do is they also increase the secretion of gastric acid, right? So if a person is on chronic steroids, you also need to place them on PPI, right? Because PPI's, right? They can basically steroids, if you take them for long enough, you can begin to get like peptic ulcer disease. And then don't forget that steroids can cause hipostunicrosis. Contrast that with this phosphon is that can cause jaw osteonecrosis. Now, what are the other things we use steroids for besides like adrenally primary adrenally insufficiency, right? So I already talked about a thyroid storm yesterday, because remember steroids have the ability to inhibit the five prime, five prime guio-dines, right? That conversity photo-T3, so you can use them for a thyroid storm. And another thing is thyroid storm is actually, at least there are some studies that sort of show that people in thyroid storm may actually have like an adrenally insufficiency. So giving steroids basically, it's that adrenally insufficiency. Another high-eof thing is if a person has severe sepsis and you're giving them like a lot of fluid replicion, you're giving them a ton of antibiotics and they're not really responding, you can also add on steroids at that point. I mean, if you've also given them pressures, if you've also given them pressures, after that you then can add a glucocoricoid. And then steroids, right? You can use them for asthma, right?

Like in health cortical steroids, for like mild asthma, and then pill steroids, if a person has like very severe, like persistent asthma. And then, so basically if you have like daily continuous asthma symptoms, you need to be placed on oral steroids. And then steroids, you can also give like a stress dose of steroids, right? Classicly on exams, you'll be on a person that has been on steroids for like a long period of time for like an autoimmune disease or some kind of rheumatologic disease. And then they get sick or they need surgery, right? So you have like an increased metabolic demand for steroids. So the the normal, like the normal dose of steroids, you give them, we will not cut it. So usually for those people, you give them like a higher than normal dose of steroids. So you give them like a stress dose of a glucocoricoid, so sort of give them, give them over that increase the metabolic that constitutes like being in line for surgery or being like severely ill. And then in terms of mineralocoricoid, right? The synthetic one you want to know about is flu drug cortisol. For a person who has primary adjournal insufficiency, they need like glucocoricoid replenishment, which you can use like a dexamethylzone or prednisolone or whatever for. But you they also need mineralocoricoid replenishment. And you can do that with flu drug cortisone. Very high you to know that.

And then another adrenov drug you want to know about is co-saintrupping, COSYN, TRUP, IN, co-saintrupping, co-saintrupping is actually an ACTH analog, okay? Classically you use co-saintrupping to make the diagnosis of adicence disease, right? So primary adjournal insufficiency, because think about it. If your adrenal gland are gone, right? If you gave that person an ACTH analog, your cortisol levels would not rise, right? So basically failure of co-saintrupping, co-saintrupping is diagnostic for adicence disease, right? Primary adjournal insufficiency. And then the next adrenov ish drug I'll talk about is a drug known as miteraport, okay? So if you're doing something, this is probably where you want to pause and like really listen really closely. Because it's something that's very high-yout and it's something that they love to test because they know that people don't take the pains to like learn this one, okay? So let's talk about miteraport. How does miteraport work? The thing is miteraport is an inhibitor of an enzyme known as 11 beta hydroxylates, okay? Miteraport inhibits 11 beta hydroxylates. Well what's special about 11 beta hydroxylates? The thing is 11 beta hydroxylates does two key things that you want to know about for step one. 11 beta hydroxylates converts 11 deoxyclotico sterum to co-stero and it also converts 11 deoxyclotizone to cortisol. Now why is it important to know this? The thing is if for some reason, right?

We're doing an experiment and you inhibited 11 beta hydroxylates. Then your levels of 11 deoxyclotico sterum and 11 deoxyclotizone should rise. But your levels of cortisol should decrease because cortisol is the outgrowth of that reaction. In addition your ACTH and your CRE should also rise under those circumstances because think about it. You inhibited 11 beta hydroxylates. You're not making cortisol anymore. There is no more negative feedback at the level of the hypothalamus and the anterior pituitary, right? So your CREH and your ACTH level should rise, okay? That's the normal response. So you really want to be able to reason through like miteraport experiments to help you distinguish between like oh, a normal response or if a person had like congenital hyperagenerable hyperplegia or let's assume they have like primary adrenaline sufficiency or let's assume they have like some problem with hypothalamus or the pituitary, right? So let me give you an example, right? So let's establish a baseline, right? We said that the normal case is if you give me tyropone you kill 11 beta hydroxylates. I'm just repeating this again. Repetition always helps. Your cortisol will go down. Your 11 deoxyclical sterone will go up. Your 11 deoxyclatisol will go up. Your ACTH and CREH will go up, right? And again I already explained why that is the case. Now let's assume a person has trouble with hypothalamus or the anterior pituitary, right? And you are not making ACTH under those circumstances.

For those people, if you give them miteraport, right? Again your cortisol will go down, right? But your ACTH will not rise. Your CREH will not rise because your hypothalamus and pituitary are not working, right? Your 11 deoxyclatisol and 11 deoxyclatical sterone would not rise either, okay? So it's just one of those bizarre things you want to know. I mean if they wanted to be particularly evil in the exam you are taking and they say like, oh wait, they give you a scenario where the CREH rises, the ACTH does not. Basically the CREH rises but every other thin downstream does not rise. Then that tells you that they have a problem in the anterior pituitary. But if the CREH and everything downstream of it does not rise, that tells you the problem is likely in the hypothalamus. I mean there is one other weird scenario that could be the case but I'm not going to mention it because it will just confuse you profoundly. It's just something I don't think will ever be tested on an exam. So let's move on. But let's assume a person had like congenital adrenal hyperpleasure, right? Let's assume they have like a 21 hydroxylase deficiency, right? Or they have like a three bilahydroxy sterogyhydrogenase deficiency, right? So like a three-bidah HSD deficiency. The thing is for those people when you give them miteraport, remember that 21 hydroxylase and three-bidahydroxy sterogyhydrogenase both come upstream of 11 beta hydroxylase. So if you give those people miteraport, right?

The acortisol will decrease. I mean the acortisol will already be low from the beginning, right? So it's not a huge deal. But let's say they have like two or three percent activity remaining of 11 beta hydroxylase. You give those people miteraport, right? The acortisol will go down, right? The acrhygiene CT will actually go up, right? But the acortisol, 11 adoxycoticosterone would not rise because they have a more upstream problem in that pathway, okay? Compared to a person that for example has like a normal situation where everything is working just fine and you're inhibiting that 11 beta hydroxylase with miteraport. So I really hope you understand these experiments because it's kind of high you to know if you're confused, I will encourage you to just maybe scroll back a little, listen to it again and you should get it. And please do not confuse 11, this is a common mistake many people have treated me. Do not confuse 11 beta hydroxylase with 11 beta hydroxylosterogyhydrogenase 2. So 11 beta hydroxylase is not the same thing as 11 beta HSD2. 11 beta HSD2 exists primarily in the kidneys, okay? And the thing is the job of 11 beta HSD2 is to convert cortisol to cortisol, okay? Versus 11 beta hydroxylase that converts 11 deoxycoticosterone to 11 deoxycoticol. Okay? Why is this 11 beta HSD2 enzyme important in converting like cortisol to cortisol? The thing is cortisol has some activity, some activity, some agonist activity if you may, on mineralocorticoid receptors.

On the other hand, cortisol has zero activity on mineralocorticoid receptors. So if a person had like a congenital deficiency of the 11 beta HSD2 enzyme, right? That person will have like a chronic hypertension, right? Because the thing is they have like elevated levels of cortisol and because you are getting basically like outdosterone-like effect on mineralocorticoid receptors, right? You retain sodium, you retain water, so you will be hypertensive. And those people classically will also get like a hypochalemic metabolic alkalosis because again, outdosterone has those effects, right? Because remember, outdosterone activates the inept channel that you find that the principal cell of the collecting duct, right? So as you bring in sodium through that inept channel, you create a negative charge that pulls out potassium, so you waste potassium in the urine, right? So you become hypochalemic and also don't forget that outdosterone activates that proton pump that you find that the alpha-intercalated cell of the collecting duct, the distal nephron, right? So if that proton pump if you activate it, some more, you are basically dumping more protons in the urine, right? So you become, you have a metabolic alkalosis, okay? So if a person has a congenital deficiency of 11 beta HSD2, they'll have like a hypochalemic metabolic alkalosis and they'll also have hypertension.

Alternatively, and probably the more common way to me test this on the USMLE exam is if you consume a ton of licorice, right? So licorice, at least I think that's how it's pronounced, licorice contains a ton of an acid called glyceritic acid. Glyceritic acid is a very powerful inhibitor of 11 beta HSD2, okay? So if you consume like a cropped on a licorice, the glyceritic acid and that licorice will inhibit 11 beta HSD2 and you can have like a transient rising your cortisol, which can cause mineralocodic oil like activity. So hypochalemic metabolic alkalosis with hypertension. Okay, so to round this up, probably round this up in like two minutes, let's talk about growth hormone pharmacology, right? So this one is pretty easy. For a person, it has a acromegaly. That means they have like too much growth hormone as an adult, right? If a person has a gigantism, right? It means that they have a tumor growth hormone as a kid. And the thing is, having these problems, these tumor growth hormone, you're like, oh, great, you'll make me tall. No, it's not very great. And here's why. The reasoning behind that is growth hormone causes like growth of literally a visceral organs as well. So people that have like acromegaly, they can actually die of like a heart disease, okay? They can get like a very nasty CHF. In fact, if I'm not mistaken, I believe cardiovascular disease is the most common cause of death in patients with acromegaly.

So the only time that you really give a growth hormone to people is if, for example, it's a patient with like a like toner syndrome, you can give them for like a very short period of time to make them grow or if some in like some selective cases of like growth, you can also give a growth hormone on that of circumstances. But those are things that you likely see more on a pediatric shelf than on a step one exam. So if a person has this growth hormone excess, right? How may you, how would you want to treat it? Right? So you can potentially give a chryotide, right? Chryotide is a somatosetating analog. Basically, a chryotide shuts down the production of most anti-operatory hormones, right? So you can use it to treat a growth hormone excess. Although the perfect treatment, right? If a person has like a pediatric tumor, that's making a ton of growth hormone is to do like a transphinoidolary section. Other things you can actually use a chryotide for, right? So you can actually use it to treat a viperma. Remember I said it yesterday, a viperma is a thing that can present with a WD Hase syndrome. So like watered diarrhea, hypochylemia, and acrohedria, right? So a viperma, you can actually treat that without chryotide. On chryotide, you can actually also use them to treat a prolactinomas, right? So if for example, a person has a tumor in the pediatric that is making a ton of prolactin, you can give a chryotide for that.

Although I will see that the first line treatment for prolactinoma on exams is a dopamine agonist, right? So like bromocryptin or cabregulin, cabregulin is actually preferred over bromocryptin, has a better side effect profile. And then if a person also has a syvajovaricis, you can actually place those people on a chryotide as well. Because a chryotide causes something known as a splanchonic viso-construction, so that can decrease the portal pressures and help people present that has a syvajovaricis. And then I guess another treatment for a levetate growth hormone is to give a drug known as pechvisomant. Pechvisomant is a growth hormone receptor antagonist. You can actually use it to treat a chromaegany. So here is one classic thing your friends at the endemic can do to you on an exam with pechvisomant. One classic question that you could ask is what happens to your levels of growth hormone when a person takes pechvisomant? Well your growth hormone levels will increase because you're not getting your growth hormone effect. So growth hormone is around it, just cannot act that it's your receptor. That's one. Second potential question is to ask you what will be true of your IGF1 levels if you're taking pechvisomant? Well your IGF1 levels should be low because if you block growth hormone receptors, you will not make IGF1. Another classic USL-MLA question. In fact, this will be like a particularly tricky one.

A particularly tricky question will be what kind of like where is the site of action of pechvisomant in the body? The thing is the site of action of pechvisomant. I can envisage when people are choosing like brain or something ridiculous. Pick liver as you answer because remember IGF1 is actually made in the liver. So growth hormone travels in the circulation gets to the liver, acts on growth hormone receptors and then you produce that IGF1 from the liver. So the site of action of pechvisomant is actually the liver. I guess another classic, I guess like peripherally related question on exams, right? Is to ask what kind of receptors will be found on like a fiochromocytoma or I guess another way you can read it is like an adrenaline cell. It will be a nicotinic acetylcholine receptor, right? Because remember your adrenaline dollar, right? Is a modified postganglionic sympathetic neuron, basically, okay? So just one of those weird things, those chromafin cells, just those weird bizarre things that you don't think about much. They probably want to keep in mind for the purposes of your of your USML Is. And then the last drug I'll talk about is a drug known as a tesamoreline. Tessamoreline is a growth releasing hormone analog, okay? So it's like a GHRH analog. You basically use it for like HIV relief, a catexia, okay? It can basically like sort of like slow down at the loss of fat in these in those in that patient population. So that's where I'm going to stop today.

And again, my usual message at the end, I offer one and one tutoring for the USML Is step one, step two CK, step two CS and step three exams, okay? And I also prepare people for the internal medicine, intranin exam, and internal medicine board exam actually. And I also prepare applications, like for ERAS and AMCAS, because I have a lot of experience with that. I do more interviews and whatnot. So if you need help with any of those things, or if you bizarrely have like a relative that is taking organic chemistry, that also needs help with that, I do also offer one and one tutoring for those. So and we show the best, have a wonderful rest of your day. And God bless, I'll see you in the next podcast. Thank you.

Oral glucose causes a greater/faster endogenous release of insulin because it exposes the glucose to the GI tract, which also stimulates incretin release (GLP-1).

The gliptins (e.g., sitagliptin, alogliptin).

They block ATP-sensitive potassium channels on pancreatic beta cells, preventing K+ efflux, leading to depolarization and subsequent insulin release.

TZ Ds because they increase sodium reabsorption in the collecting duct, causing fluid retention and exacerbating CHF.

Eosinophilia, because glucocorticoids normally cause apoptosis of eosinophils.

Cosyntropin (synthetic ACTH).

Glomerulosa (outermost) $\rightarrow$ Mineralocorticoids (Aldosterone); Fasciculata (middle) $\rightarrow$ Glucocorticoids; Reticularis (innermost) $\rightarrow$ Sex steroids.

Metyrapone.

Hypertension, hypokalemia, and metabolic alkalosis (due to mineralocorticoid excess effect).

Acarbose, Miglitol.

The liver (where it blocks GH receptors and prevents IGF-1 synthesis).

Both Insulin and C-peptide levels.

CRH rises, but ACTH does not rise when Metyrapone is given.

Glomerulosa (outermost) $\rightarrow$ Mineralocorticoids (Aldosterone); Fasciculata (middle) $\rightarrow$ Glucocorticoids; Reticularis (innermost) $\rightarrow$ Sex steroids.

Metyrapone.

Hypertension, hypokalemia, and metabolic alkalosis (due to mineralocorticoid excess effect).

Acarbose, Miglitol.

The liver (where it blocks GH receptors and prevents IGF-1 synthesis).

Both Insulin and C-peptide levels.

CRH rises, but ACTH does not rise when Metyrapone is given.