DIP Episode 61 - Cardiac Pharmacology Part 2

Okay, welcome to the 61st episode of the Divine Intervention Podcasts. My name is Divine. I am a PGY1 a transitional year resident, I'm ultimately going into Reology and in today's podcast we're going to continue cardio pharmacology. In the previous podcast I believe this is that was episode 55, if I'm not mistaken, yep. In episode 55 I sort of leave the groundwork and I talked about the and that groundwork lecture is probably important. So I highly recommend before you study this one, listen to the first episode because there's a lot of like cardio, there's a lot of cardio physiology and like electronics I discuss that would really help you understand this lecture. So I highly highly recommend, go back and listen to that one first. Okay, so we finished the Class 1 Ontario mix. So we're going to jump to the Class 1 entire it makes, right? And the Class 1 entire it makes, right? You know that they're the bit of blockers. Okay, they're the bit of blockers. They all end in all long, right? And again, the way these drugs work is they block better one receptors and by blocking these receptors, right? They basically flattened phase 4 of the pacemaker potential and think about it. If you flattened phase 4 of the pacemaker potential, right? You know that you're decreasing heart rate. But in addition to doing that, you also, these drugs also decrease contractility, right? So again, please don't forget, right?

This is something that you should hopefully know from biochemistry and for himself biology, right? That your bit of one receptor is GS coupled, right? So ultimately GS, when it's activated, it leads to more calcium in the sacroplasmic reticulum, right? Because you activate, I didn't leave it. I didn't leave it. Cyclists, you convert ATP to excuse me to cyclic AMP. And then that cyclic AMP will activate protein kinase A. And then that protein kinase A can force for relate to an enzyme known as phospholamban. When phospholamban is phosphorylithid, it becomes inactive so that you can actually pump calcium out of the out of the sacroplasmic reticulum in cardiac myocytes so that you can have a calcium contraction. Although in addition to that, you also have some more stuff with like getting calcium into the cell from extracellular sources in cardiac muscle. I believe I either talked about that in the previous podcast, or I'll discuss it at some point in the future. So more calcium, its contractility in cardiac myocytes. That's the big thing you want to take away. And if you activate beta one receptors, you get more contractility. But if you block beta one receptors with beta blockers, right, you have less contractility. So beta blockers, right, in effect, they are negative I know tropes because they decrease cardiac contractility and they are also negative chronotropes because they decrease the heart rate.

So what are some other key things you want to know about the beta blockers, right? So the first thing you want to know is that they prolonged the PR interval, right? Because remember, the PR interval on an EKG presents conduction between the H and the ventricles, right? So that's down the AV node. So if you're a negative chronotrop, right, if you basically slow down phase for the pacemaker potential, which is also the potential that operates in the AV node, right, you prolong the PR interval, okay? You prolong the PR interval. And then don't forget that your beta blockers, right? Like perprano, for example, is actually used to treat thyroid storm because it inhibits that 5 prime diode in ease, right? That helps you convert T4 to T3 in the periphery, right? In fact, perprano law is the first drug, very high. It's the first drug that you're supposed to give in the setting of thyroid storm. And then remember that you can also give beta blockers to patients with block coma. I talked about this in the neuro pharmacology podcast, right? Because by blocking beta receptors, you decrease the synthesis of VK assume and that helps you lower in chocolate pressures. And then don't forget that you can also use beta blockers for migraine prophylaxis. You don't use them in the acute phase of migraines. That's what tripthan is at 4, okay?

But in if a patient has, let's say more than like eight migraine episodes per month, that sort of qualifies them for taking a chronic migraine prophylaxis and beta blockers like perprano law, good for those purposes. And then don't forget in the realm of psychiatry, perprano law can also be used to treat acathesia, okay? So that feeling like those people like their bodies are like moving, they cannot be like piece up and down patients that are on anticycotics, you can actually use perprano law for those purposes. And then please do not forget as well. You do not want to give perprano law in the setting of acute CHF exacerbation, right? Because if you decrease the contractile power of the heart in the CHF exacerbation, you can through those people into like overt cardiogenic shock and that would obviously not be a good thing, okay? But if a patient has chronic CHF, beta blockers have actually been shown to improve survival. Although it's not all beta blockers, there's three that have been studied and shown to improve survival. And it's actually high up to know those ones. That's metoprolol, carvedilol, and bisoprolol, okay? So metoprolol, carvedilol, and bisoprolol. Just remember biochemistry, so there's a B, a C, and an M in biochem. And that helps remember bisoprolol, carvedilol, and metoprolol as the drugs that have been shown to improve survival in heart failure that are beta blockers. There are other drugs that are like experimental lactic and the works.

Okay, ACE inhibitors, you can also throw that into that path. Okay, so now we've talked about the class one terryd mix. Let's jump to the class four. Okay, we'll talk about class three in a bit. Your class four agents are your non-dihydropyredine calcium channel blockers. Okay, so this group includes drugs like Verapamele and delta-ism. Okay, these non-dihydropyredine calcium channel blockers, they're cardiovascular, right? The block L type, okay, calcium channels. Why do you think I'm going through the trouble of seeing L type calcium channels? Because it so happens that there are drugs that block T type calcium channels, right? Use those drugs for the treatment of absente seizures like ethylsoxamide. Okay, so please do not confuse the T type calcium channels that are blocked by ethylsoxamide with the L type calcium channels that are blocked by your non-dihydropyredine calcium channel blockers. Okay, those are your class four and terryd mix. Okay, so these drugs, again, by blocking calcium channels, the decrease heart rate and the decrease contractility. Again, I talked about why that will be the case in episode 55. Now, again, you do not want to give these drugs in the setting of a CHF exacerbation. Okay, and again, since these drugs decrease heart rate, they're negative chronotropes and since they decrease contractility, they're negative I-notropes. Okay, now what can I use these drugs for?

We can use them for AFIP, okay, because again, by decreasing heart rate, you can use them in a rate control strategy for AFIP. And then you can also actually use these drugs in the treatment of variant angina. Previously, it was known as Prince Medals angina, right? So the classic presentation of this is, say, for example, you have a smoker, comes in with chest pain and he says, oh, the chest pain is worse at night, blah, blah, blah. And then you check the troponins and it's elevated. You can even see like ST elevations on an EKG and they're like, oh, no, let's take this present to the cath lab. They go to the cath lab and you're like, wait, these persons coronary vessels are clear. Okay, think about variant angina. And it classically shows up in young people on exams, right? It's a kind of visospastic disease, right? So basically, if you want to fix this problem, you want to give a drug that causes visodilation, right? Like a non-dihydroperidine calcium channel blocker like Vera Pamell and they'll tie a zel. And just while we're on this topic, right, to probably want to avoid giving like triptans to these people, right, to pay patients with a Prince Medals angina, because remember that triptans, right, they, the serotonin receptor agonists, they cause a viso-construction, right? So they are bad for people that have visospastic disease like Prince Medals angina.

And other unusual step one scenario would be a patient that has a history of crest scleroderma, like a Reynolds phenomenon, like the R in crest. Again, Reynolds phenomenon sort of goes along with like visospasin. So you want to avoid triptans in those people. And then another group of people you want to avoid triptans, it will be people that have us that are taking serotonergic medication, right? So like like a like a SSRI or an SNRI or whatever, you can actually trigger serotonin syndrome in those people, right? Because so much triptans has serotonin receptor agonist activity. And then also people that have Prince Medals angina, or people that have Reynolds phenomenon, you actually want to avoid, at least avoid a non-selective beta blocker. Because think about the beta-2 receptors when you activate them, you cause visodilation. So if you blocked those beta-2 receptors, you will get viso-construction, right? And that would not be a good thing, right? So non-selective beta blockers are probably not a great idea for patients with Prince Medals angina or patients with Reynolds phenomenon. Okay, now while we're on this topic, I just want to go ahead and talk about this drug, Ergonovine. Ergonovine is an Ergot, it's like an Ergot derivative, but think of it basically as a viso-constructor, okay? And the thing is, but it's not a great viso-constructor, but it does a fair amount of viso-construction, right? But why am I harping about Ergonovine?

Harping about Ergonovine because it's actually used in the provocative test for variant angina, right? So the thing is for normal people, you give them like a low concentration of Ergonovine, they don't get viso-spasm from that, right? But if a patient has very sensitive coronary vessels that are prone to viso-spasm, aka a patient with variant angina, you give them that low concentration of Ergonovine, they can actually get viso-construction, and that can help you confirm the diagnosis of variant angina. I mean, obviously you'd want to do this kind of test in a cath lab, right? In case they get like a true MI from you giving them the Ergonovine so that you can intervene pronto, right? So you can actually use Ergonovine as a provocative test for variant angina. Now, let's jump to the class three antirithmics, okay? Class three antirithmics. These are the potassium channel blockers, right? So the key drugs here, drugs like amyotirone, dronatorone, sotilol, Ibutalide, the fetilide, the opotassium channel blockers, right? So again, please listen to episode 55, many things I will say you will not make sense without listening to that episode. But basically, these drugs because they block potassium channels, right? For reasons I described in the previous podcast, they prolong the QT interval, right? So if you prolong the QT interval, right? Obviously, it can cause a torsad the point, which is clearly not a good thing. So let's talk about some of these drugs, right?

So the poster child here is amyotirone, right? So amyotirone, yeah, it's a potassium channel blocker, it's a class three antirithmics. But the thing is amyotirone does pretty much every other thing, that all the other antirithmics do. It blocks sodium channels, it blocks beta receptors, it also blocks calcium channels as well. So basically, amyotirone is a class one, two, three, and four antirithmics, right? So it will prolong the PR interval, like your beta blockers do. It will widen the QRS complex, like your sodium channel blockers do. It will prolong the QT interval because it's a potassium channel blocker. And it will decrease your heart rate because it's a beta, it has beta blocking activity, right? So basically, if you get a step one question that talks about an antirithmics that just basically scrolls up the entire ecaging, you really want to think about a patient that is on amyotirone. And one high-yield thing you want to know about amyotirone is that it contains iodine, right? I mean, if you even look at the name amyotirone, the iodone, there's literally like iodine in its name. So that helps you remember that it contains iodine. And why is that important? The thing is because it contains iodine, it can play into certain phenomena that I'll probably discuss in the future endocrinology podcast, right? So from endocrine, right? There is something known as the Yod-Biz-Dal Phenomenon.

The Yod-Biz-Dal Phenomenon is basically a phenomenon that describes a patient becoming a hyperthyroid when they get an iodine load, sorry, an iodine load, right? So they get iodine, especially in people that have like a history of iodine deficiency. You give them an iodine load and they can make a ton of thyroid hormone and they can become hyperthyroid. That's actually what's known as the Yod-Biz-Dal Phenomenon. Alternatively, there are also certain people that you give an iodine load to and that actually suppresses the synthesis of thyroid hormone. That's something known as the wolf chikof Phenomenon. And the wolf chikof Phenomenon or effect taking together with the Yod-Biz-Dal Phenomenon, those things basically describe how amyotirone could potentially cause hyper and hypothyroidism, right? So classically, before a patient started on amyotirone, you check PF Ts, you check LF Ts, and you check TF Ts. TF Ts stand for thyroid function tests because amyotirone can cause hypo or hyperthyroidism. You check PF Ts because amyotirone can cause pulmonary fibrosis, okay? So you obviously want to measure like the FVV1 and stuff like that before you place people on amyotirone. Another thing you also have to check out the LF Ts, right? So the thinnest amyotirone is like very lipid soluble so you can actually collect in the liver so it's hepato toxic, okay? So for those reasons, you obtain LF Ts, PF Ts, and TF Ts, okay? And don't forget the other drugs that can cause pulmonary fibrosis, right?

So drugs like like Bliomisin, or Busofan, or amyotirone, or like methyltricsate, and also the antibiotic that's used for UT Is, like for cystitis and females, nitrofyrantuin, I think it's known as macrobid, that also does cause pulmonary fibrosis, although that's pretty rare. Okay, now other things with amyotirone, right? So I mean, if I don't know how it is with high school, I'm in this country, but I did go to high school in Nigeria, and I do remember in high school, we did a certain experiment where we take starch and add iodine, if you add iodine to starch, well, voila, the starch turns blue because you have like some kind of weird reaction going on. So, same thing with amyotirone, amyotirone contains iodine. Well, guess what you'll find in your skin? Collagen, collagen is a kind of sugar. So guess what? That collagen in your skin reacts with the iodine in amyotirone, and boom, your skin turns blue. So amyotirone can actually cause blue skin, okay? So you can cause like blue skin, you can even have like blue tears on amyotirone, okay? So you're sort of keep that at the back of your mind. Contrast this with like methemoglobinemia. I talked about that in the biochem review video, where you basically have like blue lips. You don't have like generalized blue all over your body. And then the last class three drug I'll talk about is pseudolol. This occasion usually shows up on exams. Soolol, I mean, block spitter receptors, right?

So it will obviously prolong the PR interval, okay? So now that I'm done with the mainstream antirithmics, let me just say a few words about some other drugs here and there that are sort of like discussed along with antirithmics. The first one I'll discuss is amyotirone. So amyotirone is kind of sketchy, but there's the belief that a denocene activates potassium channels, right? So think about this. Potassium is primarily in intracellular iron, right? Because remember the sodium potassium ATP is pump takes three sodiums out of the cell and brings two potassiums in. So potassium is primarily an intracellular iron. So if you activate potassium channels, right? Potassium will flow down its gradient from inside the cell to outside the cell. And if potassium is living in the cell, you will clearly get a membrane hyperpolarization. So if you hyperpolarize the cell, you basically prevent the transmission of action potentials, okay? And you also again prevent the firing of of cells, right? So what do we use a denocene for? We use it. We use a denocene for so a denocene, right? So what do we use a denocene for? We use it for superventricular tachycardia. Remember superventricular, superventricular. They are coming from above the ventricles, above the perkyngi system. So with a superventricular tachycardia, be a white complex or a narrow complex tachyorythmia. Well, I hope you are saying narrow complex tachyorythmia, okay?

If you have an arrhythmia that comes from above the perkyngi system, it's going to be narrow complex, okay? So SVT is a narrow complex tachyorythmia. So think about it if a patient has like an SVT, right? Like superventricular tachycardia. If that SVT is transmithed across the AV node to the ventricles, you can go from ventricles that are bidding just fine to VTAC, right? And the thing is VTAC is not good, right? People actually like die from VTAC, right? So the thing is if a patient had an SVT, you want to try to block the AV node as quickly and as promptly as possible, right? So the thing is you can give a denocene to make this happen, right? Because again, by hyperpolarizing the cell, action potentials will stop traveling, okay? You basically shut down the heart for literally a denocene transiently stops the heart, okay? And that helps you break the SVT. Many times you can break the SVT for you. And I mean usually they give it in three doses, they give like six milligrams, if that doesn't break the SVT, they give 12 milligrams, if that doesn't work, they give 12 milligrams to break an SVT. But in addition to being used for SV Ts, a denocene also has other uses, especially like its analogs. They are certain adenosine analogs, the all-end in like Osen, right? So like, Appadenosine, I think that's spelled as APADNOSN, okay? So like, Appadenosine, Rigadenosine, those are adenosine derivatives, and they are used for cardiac stress tests.

In fact, they are used for like pharmacological cardiac stress tests. And the principle, they work by something known as the coronary steel principle. I believe I've discussed that in a previous podcast, but I'm going to describe it again here since I'm talking about cardiology. So I guess I might as well do the discuss it here, right? So the thing is, because of the mechanism of action of adenosine causing hyperpolarization of cells, it can actually cause a visual dilation, okay? So why is this important? Think about it. If a patient has coronary artery disease, right? They have stenosis of the coronary vessels. The thing is, if you have stenosis of a coronary vessel, the way your body responds is to maximally dilate that vessel, okay? Is to maximally dilate that vessel. So let's assume you then took adenosine, or its analogs, like Appadenosine or Rigadenosine, right? The other coronary vessels, the patient has that are hopefully not stenosed. You dilate those vessels. But the thing is, when you give Appadenosine, for example, you dilate the vessels that are not stenosed, but the vessel that is already stenosed, right? The stenosed vessel is already maximally dilated. So it cannot dilate any further. So because the other surrounding vessels dilate, right? Obviously, blood flow will increase, it will increase in these newly dilating vessels.

And because blood flow is increasing in these newly dilating vessels, you then have less blood flow through the stenose coronary vessel that is already maximally dilated. So you effectively still in blood from that maximally dilated stenosed coronary vessel, okay? And if you send less blood through this again, maximally dilated stenose coronary vessel, you'll ultimately be in a situation where that part of the heart begins to freak out, right? Because like, oh no, I'm getting less blood, right? So if you have like a positive test, or you see like, and if I mean, if that myocardium is suffering, right? You'll begin to see like EKG changes, or the patient can begin to say, oh no, my chest hurts. And then you know that's a positive cardiac stress test, okay? That's test that's based on the coronary steel principle. I mean, alternatively, you could also, for this like visual dilation business, you can give a diperedomal. Diperedomal is a, is a forceful diesterase inhibitor. And if you inhibit a forceful diesterase, that will increase the amount of cyclic AMP in smooth muscle. And actually, increasing cyclic AMP in smooth muscle causes visual dilation, okay? Cause is visual dilation. So you can use diperedomal. It's an anti-plitlet drug. You can use it actually to cause the same visual diletry effect in the coronary steel principle, just as you can use an adenosina analog as well.

But don't forget that you can also give like a better one, again, it's like the vitamin for these pharmacologic stress test, because by giving better one receptors, you stress out the heart because you're increasing heart rate and contractility. If the patient has a kind of, if a patient has a, a stenoast vessel, right? You may not be able to supply enough blood to meet those increased demands from the beta one agonist activity, so you can get a positive stress test with that. Now, one last quick thing with adenosine is that there are certain drugs that actually antagonize the activities of adenosine, right? And those are the methyl zang things, right? So like, like caffeine, right? Or fiorfel and the ophylene that's used to treat a, used to treat a COPD, right? So here's the deal. If a patient is being taken to, like a pharmacologic stress test that will use adenosine, they should probably lay off the coffee, right? And they should probably also not think that the ophylene, right? Because they will not respond to the adenosine analogs that you're giving those are stress tests, right? So that's kind of like a weird concept that will probably not show up on step one, but if it did, I can almost prognosticate that most people will get it wronged, okay? But please don't get it wrong because you listen to this podcast. Okay, and fiorfelin is a first for the history of foreign inhibitor. I believe I'll talk about that in a later podcast on our pulmonary or pharmacology.

Okay, now the next anti-rhythmic like drug, I'll discuss is a dejuoxin, right? So the juxin is a, it's floridly high, or to know everything about the juxin for your exam. If you don't know about the juxin, you should not be taking step one, okay? That was not a very good, that will not be a very good life decision. So how does the juxin work? Let's say a few things first about how myocardial cells work, right? So myocardial cells, just like pretty much every cell in the body, has, they have sodium potassium ATP spumps, right? So that gets three sodiums out of the cell brings into potassium. And then your myocardial cells actually also have something known as a sodium calcium exchanger, okay? The sodium calcium exchanger. Since sodium, I mean it's primarily extracellular, right? This sodium calcium exchangers, the next sodium calm down its gradient into the cell, okay? And then as that sodium is coming down its gradient into the cell, you use that gradient energy to pump out one calcium, right? So if every three sodiums that comes in, one calcium gets extruded from the myocardial cell. So think about it. If calcium is extruded, you have less calcium available for contractility in the cardiac myocytes. So how does the juxin play into this story? The juxin plays into this story because it inhibits the sodium potassium ATP spump. So why would this help? So think about this for a second. If you blocks the sodium potassium ATP spump, right?

Less sodium will be extruded from the myocardial cell. If less sodium is extruded from the myocardial myocytes, your intracellular concentration of sodium will rise. Now think about it. If you're interested in the concentration of sodium rises, right? The gradient that the sodium calcium exchanger uses, right? To bring sodium into the cell for you to pump out calcium in secondary active transport goes away, right? Because remember sodium mommally is primarily extracellular and then it flows down its gradient into the cell for you to pump out one calcium with the sodium calcium exchanger in the process of secondary active transport. So if you block the sodium potassium ATP spump, you're not sending sodium out of the cell. Intracidular concentration of sodium goes up. Sodium gradient basically goes away, right? So the sodium calcium exchanger stops working. And if the sodium calcium exchanger stops working, calcium will begin to build up inside the cardiac myocytes. And if calcium is building up, well, guess what? You have more cardiac contractility. Okay? So the joxin is actually a positive I-notrop. Okay? And the thing is if a patient has CHF, congestive heart failure, joxin is a great drug, right? Because I mean it's increasing your contractility. So it's increasing your stroke volume, right? So it's increasing your cardiac output, right? So increasing this contractility is amazing in the short term. It makes your symptoms of CHF feel a lot better, right?

The only thing is the joxin actually does not improve survival. In fact, if a mom is speaking, there's actually been studies that show an increased risk of death in patients that in some patients that take the joxin for CHF. So the joxin is good for symptoms. It's amazing for symptoms in CHF, but it actually does not improve survival in the setting of CHF. Okay, because I mean, and I mean this, why might that be the case? I guess I could offer a teleological response, right? So this is just basically what I see teleological. Something that's probably not been proven, but it makes like logical sense if you think through the physiology, right? Think about it. If you're if you're chronically increasing the contractility of the heart, right? You're chronically increasing myocardial oxygen in the mat, right? So you're stressing out those myocytes above normal, right? So they can they can get into trouble that we are probably like crop off after some time, right? I mean, think about it. If for example, someone tells you to like go work out, like lift like a hundred pound weights for like 20 hours a day, right? I mean, if you lift weights for like a couple of hours, you're probably like your muscles will like give you at some point and then you like like collapse and like die or something, right? So think of that happening to your cardiac myocytes.

If you keep working hard, working hard, working hard, because the on that the activity of a positive vinyl drop, they can crop out at some point and then the cardiac muscle dies, okay? But just that's my way of understanding why the junction is potentially not good at improving survival in the setting of chronic CHF. Okay, now another high-youth thing about the junction is that it actually has a muscaronic receptor agonist activity. Okay, so think about it. If the junction is a muscaronic receptor agonist, that will tell you that it's it gives a proper sympathetic response, right? So it basically causes an increased release of a cello calling. So it causes a proper sympathetic response. So why is that helpful? The thing is this is helpful because that will clearly again listen to episode 55. That will clearly decrease the slope of the phase four of the of the pacemaker potential, okay? So that will actually slow conduction through the AV node. So it so happens that the junction can actually be used as in a rate control strategy for AFIP because it basically works like like a beta blocker almost, right? It's slow conduction through the AV node, right? So you could technically also give the junction for like an SVT again to slow because it's slow conduction through the AV node. I mean, obviously in SV Ts you can do other things, right? Like you could give a denocene, you can try vagal maneuvers, right? I mean, why do vagal maneuvers work, right?

You press on the carotids, the bar receptors are like, whoa, way too much pressure, right? And when the send those signals to the brainstem, your brain is like, oh no, this person's blood pressure is too high. So let me send a massive, massive parasympathetic discharge, okay? And that could actually slow by sending the massive parasympathetic discharge, you slow down conduction through the AV node and you can break the SVT. Another thing you can also do is to do like a valve solver maneuver, right? If you do a valve solver maneuver, you increase intrathoracic pressures, if you increase intrathoracic pressures, that will also compress on the carotids on your bar receptors. And by compressing on those pesky bar receptors, again, you trick your brain into thinking that your, you're under like a massive sympathetic response. So your brain says, okay, let me send the parasympathetic discharge and that can also break the SVT. Another thing you can also do is to dunk the patient's head in cold water. Now that didn't come out right, you should gently lower the patient's head into cold water, okay? And that will also basically, again, trick those bar receptors, you send the massive parasympathetic discharge and you can quiet down the, you can break the SVT that way. Okay, so let's summarize a few quick things about the joxin, right? So the joxin is a negative chronotrop, okay? But it's a positive I-Notrop because of, right?

So it's a musculine receptor agonist, so it slows down the heart rate, so it's a negative chronotrop in that respect. But by inhibiting the sodium potassium ETP is pump and raising intracellular calcium, it's a positive I-Notrop, okay? So the joxin is a negative chronotrop, but it's a positive I-Notrop. Contrast that with your beta blockers that are negative chronotropes and negative I-Notropes. Be slow down heart rate, but also slow down contractility. Now, let's see a few more high-yield things about the joxin, the joxin, right? So the actually love to test these things on the USML Es, like the medicine shelf, on step two, on step three. So let's talk about this real quick. The thing is, I said that the joxin inhibits the sodium potassium ETP is pump. The thing is, it so happens that for the joxin to inhibit the sodium potassium ETP is pump, it actually binds to, uh, binds to like the potassium part of the sodium potassium ETP is pump, okay? So think about it. If a patient is hypochilimic, you're opening up more spots on the sodium potassium ETP is pump for the joxin to see it on, okay? So the thing is, the joxin hypochilimia actually works since, uh, like basically renders you most susceptible to the joxin toxicity, okay? So you may see like divine, why is this important? Well, think about it, right? Who takes the joxin for the most part? Patients with CHF, right? Well, it so happens that patients with CHF may also be taking on water pills, aka diuretics, right?

And diuretics, one of their classic side effects because they make your volume down is hypochilimia, right? Because if your volume down, you'll rev up the activity of your raining and your tensing out of the dormant system, right? So diuretics cause hypochilimia. Well, if you're taking the joxin and taking a diuretic, the hypochilimia that you get from the diuretic can predispose you to getting the joxin toxicity, okay? But another weird thing, and I, um, I guess let me say some more things here before I talk about the other weird thing, right? So what are the signs of the joxin toxicity, right? So the joxin can cause yellow vision, right? So basically, they describe a patient that has heart failure and they are taking some meds for heart failure and they have like vision problems, like yellow vision, basically you want to think about the joxin toxicity, okay? The joxin can also cause like abdominal pain, right? So you can cause like some GI symptoms. The joxin actually increases the risk of erythmia, right? So you can cause early after depolarizations as I described in episode 55, right? And that can prolong the cutie interval, you're not going to to start the point and die, right? So again, that's not a, that's clearly not a, not a good thing. Now, how do you treat the joxin toxicity? You can treat the joxin toxicity with anti-dage fib fragments. I believe in the hospital of these things are known as a Digibind, okay? The Amunoklunal antibodies against the joxin, okay?

The anti-dage fib fragments. Now, what is the other weird thing I said, I would discuss about the joxin? The other weird thing is, again, it all goes back to the mechanism of action. The joxin blocks sodium potassium, the sodium potassium ETP's pump. And I said that the sodium potassium ETP's pump takes three sodium cells out of the cell and brings two potassium in. So if you blocks that pump, guess what? You will no longer be bringing potassium into the cell, right? If you no longer bring potassium into the cell, right? You can imagine that your extracellular concentration of potassium will go up. So the joxin can actually cause hyper-kilemia. So why did I say this is a weird point? It's an obvious point, it makes perfect sense, but here's where you do not want to mix things up on your test. The joxin by virtue of its mechanism of action causes hyper-kilemia. But if you are a hypo-kilemic, you are most susceptible to the joxin toxicity, as I described earlier. Do not mix those two points up. The MBMI counts on you to mix those points up. Do not be one of those people. I'll repeat it again. The joxin by blocking the sodium potassium ETP's pump causes hyper-kilemia. But for the joxin to do its job, it binds to the potassium spot on the sodium potassium ETP's pump. So if you're hypo-kilemic, they are more open spots for the joxin to bind on the sodium potassium ETP's pump. So that renders you most susceptible to the joxin toxicity. Okay.

Now, last drug I would discuss today is Ranolezine. Okay, Ranolezine is just one of these drugs that probably showed up in the last one or two iterations of first aid for step one. So it's a new drug, so it's probably high-youtunu about. Okay, so how does Ranolezine work? Ranolezine works by inhibiting something known as a late sodium channel. Okay, the late sodium channel is a channel, right? So because it's a channel, it basically lets things flow down their concentration gradient, right? So it's governed primarily by a concentration gradient. And we know that sodium is primarily an extracellular ion. So a late sodium channel will let sodium flow into the cell. Okay, so think about it. If you block these late sodium channels, less sodium is flowing into the cell. If less sodium is flowing into the cell, an extracellular concentration of sodium will decrease. If your intracellular concentration of sodium decreases, right? You're basically creating a stronger gradient for the sodium calcium exchanger that you find on the surface of cardiac mausites. If you increase that gradient, right, you'll actually pump more calcium out of the cardiac mausite. And think about it. If your pump more calcium out of the cardiac mausite, that cardiac mausite is not contracting. In fact, if it's not contracting, it's doing the opposite of contracting. It's relaxing. And if it's relaxing, that means you're basically putting that cardiac mausite into diasteli.

In fact, you're promoting something known as diastolic relaxation. In fact, if I'm not mistaken, I believe these are known as this phenomenon is known as lucitropy. Lucitropy is basically the stoically relaxation of a cardiac mausite. So, Ranozine improves the lucitropic properties of cardiac mausites. Because, again, when cardiac mausites are in a contractile state, right, gain systole, but if they're in a relaxed state, they're in diastole, right? And you may see, like, hmm, divine. Why would Ranozine help if it's promoting the stoically relaxation? Well, think about it. If you're promoting the stoically relaxation, right, you'll get more preload. If you get more preload, according to the Frankstalline principle, you get more cardiac output, right? Alternatively, think about this concept as well. If when a coronary vessel's profused, is it insistently or in diasteli? Well, hopefully you know that your coronary vessels are profused in diasteli. So, if you're promoting more the stoically relaxation, right, you're promoting more profusion of your coronary vessels because coronary vessels profuse in diasteli, right? And that can actually help relieve the symptoms of angina, okay? So, this is why Ranozine is a great drug for the treatment of angina, okay? Although, classically, for angina, use nitroglycerin, okay? And why am I harping on Ranozine? I'm harping on Ranozine because there are many wonderful things they can test about this.

One they can test about how you promote the aestolic relaxation. Another thing is they can test it in the context of the joxine, right? Like a compare and contrast kind of question. Because remember, the joxine, I said that the joxine, if you sort of skip back a few minutes, it raises your intracellular sodium so that decreases the extrusion of calcium from a cardiac myocyte versus Ranozine that causes less sodium to go into the cardiac myocyte. So it decreases intracellular sodium so that increases the gradient for the sodium calcium exchanger. So it decreases intracellular calcium and basically promotes the aestolic relaxation, right? So it's kind of like the opposite of the way the joxine works, although the target many different things, okay? And another reason why Ranozine may be good for angina, right, is because by promoting the aestolic relaxation, right? It's decreasing my acardioloxygen demand, right? So if your heart does not have to work as hard, right? Then you would not need as much blood supply to meet the demands of the heart, right? So you probably will stop having angina of symptoms with that, okay? Although I guess one weird thing is super low yield, you probably never see this on a test, but Ranozine also actually blocks potassium channels, okay? So you can cause cutie prolongation, right? So it has some like some class three anti-rhythmic effects. So I think this has gone on for a long enough, so I'm going to stop here.

I am unfortunately not yet done with cardiac pharmacology, so we have another podcast, but I think with the other podcast we'll probably be able to finish cardiac farm or maybe like in two podcasts, because I'll also have to talk about like the anti-lippid medications and all that stuff. And before I sign off, I just want to mention that I offered tutoring, private tutoring for the USMLE step one, two, and three exams, okay? I offer for like step two C, can step two Cs, and I also do like application advising, right? So if you're applying to med school or you're applying to residency, I do application advising, and yeah, I can help you put together very solid application for med school and for residency. So if you know anyone that needs any of those services, feel free to reach out, divine intervention podcasts at gmail.com, or you can use the contact, whatever thing at the top of my website. So I wish all the best. I hope you enjoy this podcast. I will try as much as possible to keep making more. If you notice, I haven't done anyone since October 29th. I've been on a medicine rotation in residency, and you know how medicine rotations go. So, but I'll try to make some more in the next few days, and I wish you the best. Hopefully the liquor's win tonight. So have a wonderful rest of the day. God bless. I'll see you next time.

They are negative chronotropes (decrease heart rate) and negative inotropes (decrease contractility).

Metoprolol, Carvedilol, and Bisoprolol (M-C-B mnemonic).

Triptans are serotonin receptor agonists that cause vasoconstriction; CC Bs like Verapamil/Diltiazem promote vasodilation.

Beta-blockers decrease contractility, which could precipitate overt cardiogenic shock in an acutely failing heart.

It inhibits the Na+/K+-AT Pase pump, leading to increased intracellular calcium and enhanced myocardial contraction (positive inotropy).

Adenosine or its analogs (e.g., Appadenosine), which cause profound vasodilation.

Metoprolol, Carvedilol, Bisoprolol.

Amiodarone (due to risk of thyroid dysfunction/pulmonary fibrosis).

Prolongation of the QT interval, increasing the risk of Torsades de Pointes.

Ranolazine.

M-C-B (Metoprolol, Carvedilol, Bisoprolol).

Digoxin toxicity.

Digoxin increases intracellular Ca++ (positive inotrope); Ranolazine promotes diastolic relaxation by increasing the Na+ gradient for Ca++ extrusion.

Metoprolol, Carvedilol, Bisoprolol.

Amiodarone (due to risk of thyroid dysfunction/pulmonary fibrosis).

Prolongation of the QT interval, increasing the risk of Torsades de Pointes.

Ranolazine.

M-C-B (Metoprolol, Carvedilol, Bisoprolol).

Digoxin toxicity.

Digoxin increases intracellular Ca++ (positive inotrope); Ranolazine promotes diastolic relaxation by increasing the Na+ gradient for Ca++ extrusion.