Oct 25, 2021
Classroom Lecture Cardio Pharmacology Part 1
The Classroom Cardio Lecture Part 1 of 3, you can complete the quizzes here https://residency.teachable.com/p/mobile
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Auto Generated Transcript:
Okay, welcome to cardiovascular pharmacology. We're going to do a hemodynamics review or an overview first, and then we'll talk about diuretics, the RAS system (Renin-Angiotensin-Aldosterone System), and then calcium channel blocking agents. So, let's start off with the cardiovascular system and just an overview of what we have going on.
So, the first thing is, what is the responsibility of the cardiovascular system? We want to distribute and transport these nutrients and oxygen to the tissues, but we also want to get rid of wastes and get them out of the body. And then there's homeostasis. Homeostasis is really just keeping things normal. Stasis means to stay in one place. So, thermoregulation, immune system distribution, hormone communication, all of these things are the responsibility of the cardiovascular system.
What are the components of this system? So, the first is the pump or the heart, and then obviously it circulates blood through the system, and then it has these three levels of vessels. So we have the distribution vessels with the arteries, the exchange vessels with the capillaries, and we'll see how depending on what area of the body we're in, those are more or less important, and then collection vessels, which are the veins.
It's important to know where the blood is distributed in what quantities. So when we're talking about the pulmonary system, only a very small amount of the blood is in the pulmonary system, and it's not as much of a pressure system either because it's just not that far from the heart; the lungs and the heart are right next to each other. Seven percent of the time or seven percent of that blood distribution is in the heart, and then 84 percent is throughout the body. In a 70-kilo male, you're talking about 5.6 liters, something like that, of circulating blood.
What is the blood made of? So there are three large components or our main components: the white blood cells and platelets (white blood cells usually help with immune function, platelets help if there's some kind of injury or bleed), and the red blood cells oxygenate, and then the plasma as well.
There's not a ton of math that we go over, but this is one important equation, and it's more important really to understand it rather than numerically, but understand what's going on. So, the cardiac output or the rate of blood flow out of the heart is equal to the heart rate times the stroke volume. Let's take each of those in turn.
So, cardiac output, how much blood flow is getting out of the heart. If there's just a little bit of blood flow, then we don't oxygenate enough, and if there's too much, then we might be trying to make up for some issues other places where the body's just not getting enough oxygen.
The heart rate: there are a couple of ways to control that, and we'll talk about those a little bit later. But just think about it this way: if you increase the heart rate, you're going to get more oxygenation as you go, and then if you decrease the heart rate, you're going to get a little bit less. So, there are some times when you're running or doing something active, you want to have a higher heart rate, and then there are times when you want it lower.
Stroke volume is another component, which is each time the heart pumps, how much volume is actually getting out in each heartbeat. And sometimes when the heart rate is too high, it just doesn't have time to fill, and if it doesn't have time to fill, then it's very inefficient. So sometimes we'll use medications that will actually slow down the heart, allow it to fill properly, and that will actually create a better cardiac output.
There are a number of factors that we talk about, and we start with coupling factors and cardiac factors. The coupling factors, we begin with preload (how much blood is in the left ventricle before the contraction), and then afterload (the squeeze required to push the blood into the aorta, and it has to be a lot of pressure to get it all the way through the body).
The cardiac factors include myocardial contraction (how powerful does it contract), and heart rate (how fast that squeeze is), and all of this adds up to the cardiac output. So, when we're talking again about preload, we're filling the ventricles before the contraction, and then with the afterload, we're seeing how much pressure does it take to get into the systemic circulation. Some factors that can affect this, for example, if someone is fluid overloaded, then it's going to take a lot more pressure to get into that space than if there isn't.
When we think of blood pressure, arterial blood pressure, we again divide it into systolic pressure versus diastolic pressure, and that's really what is going to cause this blood pressure cuff to take the measurement. Systolic on the top, diastolic on the bottom. So you see as you pump through, the blood goes out, and we go systolic, diastolic, and then we get the blood flow.
Diuretic agents: So, let's first talk about the processes involved, then we'll make a map of the nephron that hopefully will help you learn this spatially.
The kidney function is divided into three different processes. There's filtration where you clean things out, filter the fluids. You reabsorb it, so maintaining the balance, don't keep from losing those electrolytes, and then secreting or removing metabolic waste. And a lot of times when we think of kidneys, we're just thinking of getting rid of the urine, getting rid of the waste, but really there are three major processes, the nephron, and that's what this is. It's a picture of the nephron going from the glomerulus on, and we're going to call the glomerulus in the top left. You have millions of nephrons in your kidney, so again, this is huge blown up out of scale, but you start with the glomerulus.
What's important is that you have the afferent arteriole and then the efferent arteriole and capillaries in between. And that's really unusual because generally you say artery, capillary, vein. In this case, by having a high-pressure system, that means that if something is a bit closer to the glomerulus, then there's going to be more diuresis, and if it's further, there's going to be less.
Let's first get the map of the tubule transport system, starting with the proximal convoluted tubule or the PCT. Just as if someone is in close proximity to you, that means it's close to you or proximal. We go down the loop of Henle, then up the thick ascending limb, and that's where one of our most common diuretics, furosemide, works. We get to the distal convoluted tubule, just again the word distant means far, so it's far from the glomerulus, and then the collecting tubule and collecting duct.
But let's overlay this with some pressures, watch water permeability to better understand how this works. So we have very high water permeability or a diuretic effect starting with the glomerulus and going into the proximal convoluted tubule. Then when we go into the loop of Henle, we're still pretty high. As we get to the distal convoluted tubule, not as much, and then it's a bit variable when you get to the collecting tubule.
What we want to do is we want to replace these very high, high, low, and variable with drug names. So, mannitol, which is here at the proximal convoluted tubule or the PCT, is the one that's going to have the most diuresis, and we use this when we're talking about something like intracranial pressure.
Furosemide as the loop of Henle, and that's something we're talking about like CHF (congestive heart failure). HCTZ, maybe some blood pressure issues. Triamterene, spironolactone, really more valuable for maintaining potassium than they are for anything else.
When we look at mannitol, we're expanding the systemic plasma volume, forcing the kidneys to filter a lot faster, and then sodium and water are not reabsorbed in the PCT. The urine volume increases, really reducing intracranial pressure. That's one of the issues but also reducing intraocular pressure. On the adverse drug reaction side, we have headache, nausea, vomiting, electrolyte imbalances, dehydration, but usually, this is some kind of medical emergency that you'd have to use something like osmitrol.
Talking about furosemide or Lasix, we're preventing sodium from being reabsorbed in the loop of Henle. The water follows the sodium and causes increased urine formation. We're really talking about maybe pulmonary edema or other edemas that we would have throughout the body, sometimes congestive heart failure is a cause. Adverse drug reaction, so hypokalemia, we lose potassium, electrolyte imbalances, so mention the potassium but also magnesium, and then ototoxicity where we might have some issues with hearing.
The thiazide diuretics, hydrochlorothiazide (brand Microzide), they prevent sodium from being reabsorbed into the distal convoluted tubule. Water follows sodium and causes this increased urine formation. Some of the indications we'd have would be hypertension. Someone just becomes hypertensive; they might use hydrochlorothiazide or heart failure. Adverse drug reactions just like furosemide, we lose potassium, so hypokalemia, potassium, magnesium, and then in some cases, increased cholesterol levels.
The next one are the potassium-sparing diuretics, so spironolactone, brand Aldactone, this aldosterone antagonist. If you think a little bit about what aldosterone does, it helps you better know what spironolactone does. So aldosterone normally causes sodium and water to be retained, and the body holds onto it. If you hold onto sodium and water, you increase blood pressure, and that's what the body wants to do if the blood pressure is too low. But if spironolactone is blocking aldosterone, now we release this sodium and water, and now we decrease blood pressure. But again, while the indications are hypertension, heart failure, hyperaldosteronism, what we're really trying to do is often hold onto potassium to counteract either furosemide or hydrochlorothiazide's hypokalemic effect. Adverse drug reactions, so hyperkalemia, gynecomastia, metabolic acidosis, those are some of the adverse drug reactions.
Okay, the potassium-sparing diuretics move on to triamterene, which is often paired with hydrochlorothiazide as a combination. So triamterene blocks sodium resorption in the collecting duct and the distal convoluted tubule. Water, again, follows sodium into the urine, so we would see this with hypertension and edema, but again, compared to furosemide, hydrochlorothiazide, it is certainly nowhere near the amount of diuresis. Adverse drug reactions include hyperkalemia and then certainly electrolyte imbalances, but now we're going the other way, just as with spironolactone, we're holding on to the potassium rather than getting rid of it.
Next slide is the renin-angiotensin-aldosterone system or the RAAS system, taking the R, the A, the A, and the S, and we'll talk about a few medications here. So the RAAS system is meant to maintain fluid and salt in the body, regulate blood pressure, and there are two main enzymes that are involved, and it'll be critical in understanding how the medications work and knowing how this very straightforward RAAS system works.
So, angiotensinogen goes through renin, and when we think of an enzyme, we usually think we're going to see an ace, and a lot of times you can have an in at the end instead of the ase, and that's what renin is. It's an enzyme that gets angiotensinogen to angiotensin one, and it's a response to low arterial pressure, low sodium, where the body's saying, "Hey, our blood pressure is a bit too low. We need to raise it. Please release renin, the enzyme." And once that enzyme goes out, then angiotensin 1 forms.
We have to go through one more step, and that next step is the angiotensin-converting enzyme, which we call ACE. So once ACE gets in there, we get the angiotensin II. So we've gone from angiotensin one, from the liver to angiotensinogen to angiotensin one to angiotensin II. Angiotensin II does two important things: it promotes sodium and water reabsorption, but it also maintains constriction of the arteries. Both things are going to increase blood pressure, which is what we want. But if you have someone who's hypertensive and you want to lower their blood pressure, well, we're going to want to block some of these pathways or some of these steps.
ACE inhibitors or ACEIs are going to block at the angiotensin-converting enzyme step, and the angiotensin II receptor blockers are going to block at the receptor, bypassing the enzyme. And these two ways of doing it are really helpful.
Let's talk about the ACE inhibitors versus the ARBs. So the ACE inhibitors like enalapril and lisinopril, enalapril's brand Vasotec, lisinopril's brand Zestril. Both of these end with "pril," that's a common suffix, and they stop the angiotensin-converting enzyme. It prevents the conversion of angiotensin I to angiotensin II, so we don't get that salt and sodium and water retention, we don't get that vasoconstriction, hopefully lowering blood pressure.
So the indications include hypertension and heart failure. Adverse drug reactions we can see hypotension, dry cough, hyperkalemia. So again, we want to be mindful. For example, if we're giving a diuretic, and that diuretic causes hyperkalemia, we could make the condition even worse. This dry cough is not something that you treat, rather you discontinue the ACE inhibitor, and you would go to the ARB, which is in the next slide.
"So, an ARB or Angiotensin II Receptor Blocker. We’re going to first go over the three examples: Losartan which is Kosar, Omasartan Benicar, and Valsartan which is Diovan. So we see the Sartan ending and that again our suffix and that again helps us know that these are ARBs. We prevent Angiotensin II from binding to sites on kidneys and arteries that causes vasodilation and prevents sodium reabsorption. Indications again are hypertension and heart failure and adverse drug reactions can include hypotension where we take their blood pressure too low and hyperkalemia again just like the ACEI. Here’s a caveat: there’s no dry cough adverse drug reaction so we may need to switch a patient from an ACE to an ARB if this presents. They should not be used together because the outcomes are no better and we can cause renal impairment as well.
Calcium blockers or calcium channel blockers, we’ll go over the two major classes. So the first class is, well let’s start with what calcium does. Calcium, we need it for smooth muscle contraction and the vasculature, the blood vessels use calcium for vasoconstriction. So if we block the calcium from entering the smooth muscles it causes vasodilation or opening up the vessels. The heart uses calcium for regulating the timing of the contraction so if we block calcium in the heart we can help reduce arrhythmias.
But let’s look at the two different categories and we use a very formal chemical class it’s either a non-dihydropyridine or a dihydropyridine. So the non-dihydropyridine is what we’ll start with: Dotism brand Cartism Verapamil brand Kalin. These block the calcium channels in the heart and blood vessels. They’re used most commonly for dysrhythmias and indications include hypertension, antonopectorus, cardiac dysrhythmias and we’ll see that that’s going to be missing from the next group of calcium channel blockers, those cardiac dysrhythmias.
Adverse drug reactions: constipation, bradycardia and why are those? So the first constipation because again just like with the muscles your body when it’s trying to use the GI system also uses calcium and if you take block that calcium it makes it harder for the GI system to do its job and get things out of the body. Bradycardia is on the other end where instead of just lowering heart rate a little bit maybe we reduce heart rate a bit too much and we make the patient bradycardic.
The other group of calcium channel blockers are the dihydropyridine so Amlodipine which is brand Norvasc, Nifedipine which is brand Procardia. You notice that the peen ending a lot of people say oh that’s a dip in blood pressure is a way to remember it. So we block the calcium channels in the blood vessels there’s no heart activity so there’s no using these for dysrhythmias and it’s most commonly for hypertension but again we see the hypertension angina pectoris as two of the indications but we don’t see, and I’ll go back to that slide, uh, the cardiac dysrhythmias that we did with the non-dihydropyridines.
Adverse drug reactions: we could get some peripheral edema again we’re vasodilating and we could get some headache again from that vasodilation.
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