DIP Episode 152 - Comprehensive USMLE Renal Pharmacology 4 (Final Part)

Okay, welcome. My name is Divine. This is episode 152 of the Divine Intervention Podcasts. And in this podcast, I'll be completing, in fact, I'll be tightly in this podcast, the comprehensive USMLA RINAL from Ecology 4 Podcasts. This will complete the series for RINAL from Ecology with reference to the USMLA step one example. And I think with this, I'm certain, I'm almost uncertain that I've covered, essentially, of the pharmacology in first data. I have podcasts for essentially every system of pharmacology. So let's go ahead and jump right into it. I want to make this podcast real short. So last podcast we stopped, you know, by talking about the Thaisites, right? So essentially, I stopped at the distal completed tubial. So now I'm going to jump to the collecting duct, right? I'm essentially working through the transporters, right? So if you get to the collecting duct, we know we have the principal cell, right? And we know that on the basal surface, like the blood surface of the principal cell, we have like the sodium potassium ETP's pump, again, like I said, that brings three sodiums out of the cell and takes into potassiums. And then on the urine side, we have something called an inek channel, okay, that brings sodium into the cell. And then we have a romkey channel on the, on the urine side as well that helps with excreting potassium ions.

Essentially, the thing that happens is when sodium ions come in through the inek channel, a negative charge is created in the urine side. And that drops potassium out through the romkey channel, right? That is why whenever you have our doster and doing its job, remember our doster and activates that inek channel, you'll help you reabsorb more sodium, you'll create more negative charge on the urine side. And that will draw out more potassium. Now it's high up to know some drugs that work along this axis. We have like a familiar edentrium term, they block that inek channel, right? So they essentially keep sodium on the urine side, right? So that will draw water in the urine. That's why those drugs are diuretics. So though they are not super powerful diuretics. And these drugs, right? Because again, by blocking that inek channel, you're not creating that negative charge that draws out the potassium through that romkey channel. The thing that effectively happens is that these drugs they help you demicure it in potassium. So they cause hyperchylemia, okay? So that's a big thing you want to keep at the back of your mind with these drugs. And it's actually high up to know that these drugs are used to amener edentrium during the inek channel blockers. They are used to treat nephrogenic diabetes in sypedas that arises from lithium use. Or repeat that again, they are used to treat nephrogenic diabetes in sypedas that are arises from lithium use.

The thing is if you think back to your college courses, maybe I don't know like Gen Chem. And I say this because I do a ton of people for Gen Chem and O Chem. The thing is in general chemistry, if you remember lithium is a group one element, right? It has one electron in its atom shell kind of like sodium and zwak, right? Sodium, although lithium I believe is like a lemon, three sodium is a lemon, but they are both in group one, right? So if sodium can go through a channel, you better believe that lithium can go through that channel. So the thing is lithium actually uses that inek channel to gain access to the principle cells of the collecting duct and it messes up the signal lachar skid of ADHD, right? So the thing is if you wanted to prevent lithium from causing that nephrogenic di, you want to go ahead and give something that blocks that inek channel so that it doesn't gain entry, right? So that's where it drops like a millerite and triumphant urine coming to play. And you should also remember drugs like spurnolato and eplereinone, right? They also essentially work at the level of the principle cell of the collecting duct because the outdo-stron receptor antagonists, right? So by blocking out those sort of receptors, you decrease the activation of that inek channel, right? So again, you ultimately have hyperchylemia because again, like I said, you're not creating that negative charge that draws out potassium.

So you get hyperchylemia and also by blocking out those sort of receptors, you also create a metabolic alkalosis, right? Because the sorry, a metabolic acidosis, whoops, a metabolic acidosis. And because if you think about it, right? That if you look at the upper intercalated cells of the distal nephron, those are for intercalated cells. They have proton pumps on the urine side and the typical side. And those proton pumps are activated by our doster. So whenever a person, whenever a person is on an outdo-stron receptor antagonist, like spurnolato and eplereinone, that alpha intercalated cell proton pump wouldn't work as well. So those people will retain protons, right? So they'll have a metabolic acidosis, okay? So in general, you want to be able to group the side effects of these diuretics nicely, right? It spans all the way from you're getting very ready like thiazides and lube diuretics that have the combination of hypochylemia and metabolic alkalosis to acerazolomide or dorsolomide, your carbonych and hydrazine inhibitors that give you a combination of hypochylemia and metabolic acidosis. And then all the way to the outdo-stron receptor antagonist, like spurnolato and eplereinone, that have the combination of metabolic acid doses and hypochylemia, right? And the metabolic acidosis to be most specific is a non-anion gap metabolic acidosis and to be more specific, it's a type 4 RTA.

So and then one drug, I mean it's used more to treat gout, but I just want to mention is that I'm talking about Reno. The thing is you should not forget that prebenicid, right? It's a drug that you can use to treat gout in people that are under excretors. Essentially inhibits the reabsorption of ureac acid in the proximal convolut tube, right? So it essentially increases the renal expression of ureac acid. Now, so let's continue this, let's continue at the discussion of the you know distal nephron, right? So continue with the principal cell another receptor you'll find there's you know the idiot receptor. The idiot receptor we actually find it for the most part on the blood side, right? It should make sense that it should be found on the blood side right? Because if that receptor responds to anti-diarrytic hormone, which is which is a hormone, right? And hormones by definition travel in the blood stream, right? So the idiot receptor, the visopressin vitro receptor you find on the blood side, right? And remember that that visopressin vitro receptor is a G protein coupled receptor. It's a GS, it's a G stimulatory coupled receptor. So it actually responds to a denilite to it actually works through like a denilite site, please, right? So the thing that happens is when idiot binds to its receptor, it ultimately through its signaling cascade, it leads to the insertion of acoper in two receptors, acoper in two channels on the urine side.

And that helps you reabsorb more water at the principal cell. But also remember that one thing EDH encourages is, it encourages the reabsorption of urea. Remember I said this in the last Rino pharmacology podcast that urea actually contributes quite significantly to the medallary concentration ingredient that helps you reabsorb water. So you should hopefully, right, not forget that small cell lung cancer, right? Is associated with like SIDH, right? So those people as a primary or plastic phenomenon in small cell lung cancer, you make a crap term of EDH, study each increases water reabsorption in the urine, right? So those people have like hypo or smaller urine and they will have hyper, sorry, they will have hypo or smaller blood and hyper or smaller urine, right? Because they are concentrating, they are urine like real well, concentrating the urine real, real well. So the thing is, if for example a person had SID in general, the way you treat it is with like fluid restriction. But if they were asking you about pharmacology on the mbimics exam, right? You want to consider giving people those people ED receptor antagonists, right? So drugs like a honeyvaptan, they are all vaptans. So drugs like honeyvaptan and tow vaptan, they are ED receptor antagonists, right? So they will essentially prevent that increased water reabsorption that you get with EDH access. And then it's also high yield to know that a carbamazepine, right?

carbamazepine, it's an anti-pileptic, it works as a sodium channel blocker, it's used to treat like Tidlero, I'm so like a trigeminal ranger, but the high yield thing you also want to know about it is it's associated with the development of SIDH. Your early generation of sulfonial urias, right? Like tubular mites and clopropomide, those also associated with the development of SIDH. And then your SSR Is, right? Your SSR Is also have a stronger risk of a person developing a SIDH with those. And then don't forget the mechalus cyclones, since we're talking about the principal cell of the collecting duct. I remember the mechalus cyclones attached to a cyclone anti-biotic, right? So it's like a 30s, but you're static anti-biotic. You can actually use this to reverse SIDH, right? Because it causes nephrogenic diabetes in sypitalus as a side effect, right? So you essentially use the side effect to treat SIDH. And then one thing I want to go ahead and say is that remember I said that if a person has nephrogenic diabetes in sypitalus that arises from lithium toxicity, you can treat it with an inept channel blocker like a milleride or triumetric. Here's one thing you want to keep at the back of your mind. If a person, because many, I mean many people, you know, you're learning many, many med schools that, oh, to treat nephrogenic diabetes in sypitalus, you can use a thiazide diuretic. That is absolutely true. That is the right thing to do.

But if a person has an nephrogenic di and it arises from lithium use, using a thiazide diuretic is a terrible idea. That will vastly increase those people's risks of lithium toxicity. That vastly increase the risks of lithium toxicity. So you may say, okay, divine. Why is that the case? Well, let's look at this for a second. The thing is one general principle and I believe I've explained this in a in a prior podcast. One general principle is anything that increases the activity of the ring in and jutezine or dostron system will make a person have more lithium toxicity. Why is that? The thing is if if a person has a revenue of the ring in and jutezine or dostron systems, they will have a lot of activation of that in that channel. Now you'll find that the principle cell of the collecting duct. And if you result that in that channel, right, yes, you are revenue of sodium absorption, but guess what? You're also revenue of lithium absorption, okay? In general, if a dostron is working on a high level, you'll also have high level absorption of lithium, okay? So if a person is having a lot of lithium toxicity like nephrogenic di or tremors or hypothyroidism, that will be made even worse when you give a fireside, right? So again, fireside diuretics are awesome for treating nephrogenic di that arises from any other cause, but lithium toxicity. Very, very high yield to know those things. I promise you, very, very high yield to know those things. So some of you may ask, okay, divine.

So why does a fireside diuretic work for the treatment of nephrogenic diabetes and sypitus? The thing is, if a person has nephrogenic di, right? It means that they are wasting a ton of water in your urine. Well, guess what? If you, in fact, maybe let me use an analogy, I think it was really, really drive this point home, right? You really, really drive the point home. Think about it. If, for example, you know that on your way home from school, right? There's this bully, right? So imagine yourself in high school or whatever. Let's say there's this bully on your way home from school. And this person always takes 10 from you, right? Just rips you off and says, let me have your 10, right? Takes that 10 from you. Well, let me, that kind of sucks, right? But you can say, you know what? Maybe you are, let's assume this person is like a 10-foot tall bully, right? So obviously there's not much you can do under those circumstances. So you can say, okay, you know what? Instead of taking 10, is that of having 10 with me on my way home. Let me put 9.99 in my locker at school, right? And then have only one cent in my pocket. I'm still going to get bullied, but you can bully me all you want and take the one cent I have on me. There's literally nothing else I have on me. So your call, take the one cent that's fine. I don't care, right? So that's the same thing that happens when you take a thiazai diuretic.

When you take a thiazai diuretic, you know, at first, you know, you're peanut or ton, peanut or ton, peanut or ton. But it's like, hmm, okay, I'm losing a ton of volume. This is not good. I want to self-preserve. I want to preserve myself. So the thing your body does is to say, okay, you know what? If before, I used to reabsorb 67% of my sodium and water at the proximal convoluted tubule and then leave the rest for more distal parts of the nephron. Your body is like, okay, let me bump that bump that 67% to like 85, 90%. That arises because that's an adaptation to you being volume depleted from studying this thiazai diuretic, right? That is why, as time goes on, your body adapts to reabsorb in more sodium and water at earlier parts of the nephron before the bully, before the sight of action of a thiazai diuretic. That is why thiazides, if essentially by giving a thiazai diuretic, you induce the body to become more efficient with regards to sodium and water reabsorption in the nephron. That is why thiazai diuretics can be used to treat nephrogenic diabetes and sypedas. And I mean, if a person has diabetes and sypedas, obviously you can figure out why do they have this diabetes sypedas by doing something called the water deprivation test. So, you observe a person who is like, this person has a high serimosmolarity but they have a low urinous molarity. Let me bring them into the hospital and deprive them of water. You deprive them of water and you notice that crap.

This person's serimosmolarities is still rising and the urinous molarity is still low. So, that makes you worried that, okay, this person likely has diabetes and sypedas. So, the way you then figure out, okay, is it central on the phrogenic? Is you give the smoking person? The smoking person is an ADHD channel lock. So, you give the smoking person. If you notice that the serimosmolarity goes down and the urinous molarity goes up like spot neck and not going out by like 50 points, like going out by a lot, like doubly not tripling, then you know that, oh, giving ADHD fixed the problem. So, that tells you that for sure, this people have central diabetes and sypedas. But if giving the smoking person does not fix the problem, then that tells you that those patients have nephrogenic diabetes and sypedas. And obviously, you treat central diabetes and sypedas by giving what is missing. You give the smoking person. You treat the phrogenic Di by again, giving a thizide diuretic if it's caused by something other than lithium or giving an inexional blocker, like amyloidotrium terin, if it's some, if it's a nephrogenic Di from lithium toxicity. Because again, remembering nephrogenic Di, you have tons of ADHD around. So, you have very high levels of ADHD, but your body is resistant to that ADHD. And then one other thing I also want to go ahead and mention is these potassium sparing diuretics like the amyloidotrium terin or the spurnolactone clarinone. You can give those drugs.

You can use those drugs as addon diuretics. When a patient has you know, like profound hypochylemia from Tic and a thizide, but you don't necessarily want to stop that. I mean, profound hypochylemia from taking any diuretic, but you don't necessarily want to stop that diuretic. You can add a case sparing diuretic for those purposes. And then one thing I want to say is that because by adding those drugs, right, like you're essentially using the hyperchylemia side effect of those drugs to temper the hypochylemia that arises with taking most other diuretics. And then don't forget that if you have comparing spurnolactone and a plerinone, right, spurnolactone in addition to blocking our dose-tronoreceptors, it also has the ability to block androgenoreceptors. That is why it is associated with gynecomastia as a side effect, okay? But a plerinone does not cause gynecomastia because it has no blockade at androgenoreceptors, like we have with spurnolactone. And then, remember when we have talked about how like butter syndrome involves like, almost it's almost like taking a loop diuretic and gyroman syndrome is almost like taking a thazide diuretic and those are both in herithet in autosomal recessive and fashion. The thing is, if you take, there is, and those are like loss of functional mutations, right?

So like for batters, it's a loss of functional mutation in the sodium potassium-2 chloride transport as a simporter that you'll find at the level of the thickest end and the length of the loop of Henley. Gyroman syndrome autosomal recessive inheritance, it's a loss of functional mutation of the sodium chloride simporter that you find at the level of the distal convoluted tributum. There is another disorder that is actually not a loss of functional mutation, but it's more like an activity mutation in the inek channel that we find at the principle cell of the collecting duct. That is a little syndrome, little syndrome. Little syndrome is actually in herithet in an autosomal dominant fashion. It is unlike batters and gyroman's that are inherited in an autosomal recessive fashion. It's actually in herithet in an autosomal dominant fashion. And then one thing that just dropped to my mind as I mentioned in these syndromes, gyroman syndrome can actually be a presentation on NBM exams of CPPD. The pseudo-gaute, that's something that's classically thought in most met school like rheumatology and MSK curricula. That's just one of those weird things you want to keep at the back of your mind, for example. Then these autosomal receptor antagonists, like Spirinolatrine Apparionone, they are one of the drugs that have actually been shown to improve survival in heart failure. The other drugs that also have that cling to fame as some beta blockers like Metoprolol, Carvedi-Lol and Bisoprolol.

Then your ACE inhibitors, like your Inala Preo, Captopryla, and whatnot, they've also been shown to improve survival in heart failure. Then the combination of isosobidinitrade and hydrozene, improve survival in heart failure in African-Americans. Sometimes in the hospital you hear that drug referred to as bibil. Then there's also this, when you implant a pacemaker, it also does improve survival, but in certain select patients, there's not necessarily something that'll be tested on the USM-LIS step one. That's more for the step two, CK step three, and the internal medicine abort exams. Then one thing I want to say about Spirinolatrine is that Spirinolatrine can actually be used to treat chronic, like elevated esophageal pressures, like in the setting of esophageal varices, for example. It decreases portal pressures. No one really understands the mechanism behind that, but that's something you definitely want to keep in mind. It is not used, though. I'll repeat this again because this is one thing that gives people a lot of an exams. Spirinolatrine is not used in the acute treatment of esophageal varices. For esophageal varices, acute treatment, if you're thinking from ecology, you're thinking more along the lines of optriotide. But for chronic treatment of esophageal varices, you can use Spirinolatrine. You can use a non-selective bit of blocker, like needle lo, or proprylonal lo, for example.

Then one of the things with Spirinolatrine is you can actually use Spirinolatrine to treat the hersotism that accompanies PCOS, because Spirinolatrine actually has the ability to inhibit five-hour-ferred doctors in the skin. It can inhibit five-hour-ferred doctors in the skin. By inhibit five-hour-ferred doctors in the skin, you prevent the conversion of testosterone to DHT, and that helps with hersotism that accompanies PCOS. One round about where they can test that concept is they can talk about a person that's relatively normal, like a female that's relatively normal, doesn't have high levels of testosterone or anything of that sort. Would you tell you that she has a small beard? That arises because there are certain populations that actually have genetic issues where they have increased activity or five-hour-ferred doctors. That's the way your friends at the MDME can sort of link those concepts together. I find that concept to not be in most resources you would see for people that are studying for exams, for the USM Ls especially. That's why they started to drop that in this podcast because believe it or not, it's a high-yield concept to your friends at the MDME, expect you to know for the USM Ls.

I mean, I guess since I've talked about organic homosteia, you should hopefully also remember that same editing, remember it's a H2 receptor antagonist, it also has anti-entrogen properties so you can cause organic homosteia and remember it's an inhibitor of cytochrome P450, so you can increase the levels of many other drugs. I think I'm going to go ahead and stop here. I am officially done with Renault from Acology, and again, if you listen to all four of these podcasts, you should be a master at Renault Farm. Some people may be saying, but the one you didn't talk about is inhibitors and AR Bs and all that stuff. I talk about all those in the cardiac pharmacology podcast, so I think you should refer to those there. So hopefully you gain something for this podcast as I do at the end of every podcast. I'd offer one or one tutoring for many exams, step one, two CK, two CS, step three, the internal medicine, the internal medicine, the EBI and board exams, pre-clinical med school exams, 30-year shelf exams, and then I do this day and I call it longitudinal tutoring. So if you're first year, second year, third year, I'll tutor you for your blocks in med school or for your shelf exams, but at the same time, I tutor you for the corresponding board exam that you have coming up.

I've noticed that when the people have done that with, they have done super well on most of their shelf exams and whatnot and then those people have the role have been wildly successful on their USMLA exams because again, as we go through those blocks or those shelf exams, I tutor you for those exams specifically, but for example, say like you're 30, I tutor you for like the USMLA step two CK exam at the same time. And then if you have like a college body that needs to earn for general chemistry organic chemistry, physics, biochemistry, physiology and histology, I'd offer one or one advice in slasher tutoring for those as well. And then if you're a med student applying to residency so like an ERAS application or a college student applying to med school so on an AMCA application, I'd offer like one or one advice in slasher consulting for that. I've worked with like hundreds of people on this like rec letters, personal statements, editing applications, mocking interviews. I have done that with tons of people who begin as a role that people have worked with have been again very successful. Most people have worked with have much done to their first choice for residency. Yes, I've had some people matching the second third choices, but like 90% of the people have worked with have much have much done their first choice. So I do hope you've got something from this podcast. Please at your respective med schools, please feel free to share this podcast with people.

My goal is ultimately to have this podcast in the hands of every med student because I feel like hopefully you're getting something from it. And subscribe to the podcast and you're also welcome to subscribe to my You Tube channel. Hopefully over the next few weeks I can get this podcast on like a podcast app or and get most of the podcast over to You Tube as well. So I'll see you in the next podcast. Have a great weekend. God bless you. Thank you.

They block sodium reabsorption in the distal convoluted tubule (DCT), increasing Na+ delivery downstream.

Hypokalemia and metabolic alkalosis.

Thiazides increase proximal tubular sodium reabsorption, which increases the absorption of lithium via E NaC channels, worsening toxicity.

A mineralocorticoid excess inhibitor (MMEI) like amiloride or triamterene, as they block E NaC and prevent both Na+ and Li+ reabsorption.

Spironolactone can cause gynecomastia because it blocks androgen receptors in addition to mineralocorticoid receptors.

Vaptans (e.g., tolvaptan, conivaptan) are ADH receptor antagonists that prevent excessive water reabsorption.

Thiazide diuretics (and loop diuretics).

Na+ enters via E NaC, creating a negative charge in the lumen, which drives K+ out through ROMK channels.

Tolvaptan, Conivaptan, Vaptans (used to treat SIADH).

Autosomal dominant; it involves an activity mutation in the E NaC channel at the principal cell.

Carbonic anhydrase inhibitors (e.g., acetazolamide).

Central DI responds to ADH replacement; NDI does not respond, and requires an E NaC blocker or thiazide (if non-lithium related).

Thiazide diuretics (and loop diuretics).

Na+ enters via E NaC, creating a negative charge in the lumen, which drives K+ out through ROMK channels.

Tolvaptan, Conivaptan, Vaptans (used to treat SIADH).

Autosomal dominant; it involves an activity mutation in the E NaC channel at the principal cell.

Carbonic anhydrase inhibitors (e.g., acetazolamide).

Central DI responds to ADH replacement; NDI does not respond, and requires an E NaC blocker or thiazide (if non-lithium related).