Oct 26, 2021
Classroom Lecture Cardio Pharmacology Part 2 of 3
The Classroom Cardio Lecture Part 2 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 2. We’ll go over hypertension agents, then heart failure agents and thirdly dyslipidemia agents. So with the hypertension agents, we’re first going to go over a little bit about what’s normal and what’s abnormal. So normal, we expect to see a systolic somewhere below 120, diastolic below 80. And again, hypertension, hyper meaning high, tension is the pressure within a blood vessel so high pressure within the blood vessel and what we want to do is we want to clarify or classify what those numbers mean. So if the blood pressure is elevated a little bit, we just say literally it’s elevated or then we have stage one hypertension, stage two or if it’s really high we’re in hypertensive crisis.
So how common or how prevalent is hypertension in the United States? 85 million Americans have hypertension and it’s associated with many other issues including heart disease like heart failure, heart attack or myocardial infarction, antenna pectoris, kidney disease and stroke. So that leaves the question, how do we treat hypertension? So what we want to do is look on the left-hand side you can see elevated versus stage one versus stage two and we start with non-drug therapy lifestyle changes throughout. Can the patient lose weight? Can they improve their aerobic activity? Can they change their diet? Can they reduce their sodium intake? Can they moderate alcohol?
On the right side, we have drug therapy which gets more aggressive as we go through starting with maybe a calcium channel blocker or thiazide diuretic or an ACE inhibitor or ARB. Once we get to stage two we start thinking two drugs combination from them and then maybe thinking loop diuretic potassium sparing diuretic beta blockers alpha one blocker alpha two ant alpha two agonist all of these trying to reduce that blood pressure.
So we’ll start by talking about some of the drugs themselves. The beta receptor antagonists or the beta blockers there’s two different kinds of beta receptor beta one and beta two because you have one heart and two lungs that’s often a mnemonic to remember okay well beta one is with the heart and beta two is of the lungs. So when you activate a beta-1 receptor in the heart you increase heart rate rhenium production is likely and so we’re going to get this increase in blood pressure if you activate beta 2 you’re bronchodilating or opening up the smooth muscle.
So this is what happens when we activate them so what happens when we block them? Well if we were to block beta 1 in the heart we would actually decrease heart rate and if we were to block beta 2 then we actually vasoconstrict.
So when we see in the next slide about the drugs that also affect beta 2 then we want to be careful with asthmatics. So let’s look at these three generations first generation propranolol which is brand enderol it’s non-selective for beta 1 and beta2 that means that while it does lower the heart rate unfortunately it can in asthmatics cause a bit of bronchoconstriction.
Second generation was an improvement on that where atenolol metoprolol tartrate metoprolol succinate are selective for beta-1 so they just reduce the heart rate and you think well that solves it but it doesn’t because what happens is the body will vasodilate or vasoconstrict and vasoconstrict to increase blood pressure against this decreased heart rate.
So the third generation was supposed to solve that so something like carvedilol or co-reg is a selective beta-1 blocker and alpha-1 blockage as well and what we have with this means that not only are we affecting the heart and reducing the heart rate but we’re also taking care of that response or that vasoconstriction that the body would normally do and hopefully maintaining blood pressure reduction.
A common adverse drug reaction for all of them is of course bradycardia. We can reduce the heart rate too much so bradycardic is a heart rate under 60."
"So, the beta blockade is thought to stop region production in the RAS system or the Renin-Angiotensin Aldosterone System. It creates limited vasodilation, they decrease the heart rate to lower the blood pressure and again the body vasoconstricts to keep the blood pressure up and then the alpha one blockage prevents the vasoconstriction to create the best BP outcomes with that third generation. But we still want to be careful, we don’t want to use those non-selective beta blockers in COPD or asthmatic patients because of the smooth muscle constriction causing exacerbations.
Let’s talk a little bit about heart failure and the pathology to start. So cardiac output can’t provide enough oxygen needed by the tissues and something we maybe forget is that the heart pumping in the heart sending blood to the tissues, it’s also sending blood to itself. So if the body can’t get enough oxygen, it might also not get enough oxygen. So we are going to classify it based on the overall effect of failure on the left hand side we have systolic heart failure, a reduced ejection fraction HFREF and the heart cannot pump well enough. On the right hand side we have diastolic heart failure so you’ve got preserved ejection fraction and the heart can’t fill enough with enough blood. So a little bit different but what’s going on with systolic is the heart can’t pump enough and then the diastolic his heart can’t fill with enough blood and the systolic is more common and this is the heart failure we’ll talk about in these slides where the ejection fraction is the percentage of blood left in the ventricle after contraction.
So, the five-year mortality rate is 50 percent and the most common cause is coronary artery disease then hypertension. So let’s look at the cardiac output factors where we have the coupling factors preload how much blood is left in the left ventricle before contraction then afterload what kind of squeeze is required to push blood into the aorta and then the cardiac factors myocardial contraction how powerful that squeeze is and then heart rate how fast the squeeze is.
So when we talk about endogenous compensatory factors for heart failure we’re talking about an increase in preload more blood in the ventricle increase in after load, the peripheral vascular constricts to keep pressure up myocardial contraction decreases and heart rate increases to try to keep blood moving through the tissues.
So, heart failure medication increases the cardiac output. So let’s look at some of the medicines. The RAZ inhibitors are RAAS, The ACE inhibitors are the first line treatment for heart failure they decrease preload and afterload through vasodilation these include Enalapril and Lysinopril. ARBs there’s not as much clinical trial data as an ACEI and should be reserved for patients who can’t tolerate them but really, one caveat is that if you get that ACE inhibitor-induced cough then we would switch someone to an ARB or a Sartan taking the last letters of Losartan Homosartan or Valsartan so ACE inhibitors are Prils ARBs are Sartans.
Another thing with heart failure is getting some of the salt water and blood volume off so Furosemide is brand Lasiks Spironolactone is Aldactone and what we do is we can decrease venous pressure and preload it allows the heart to pump more efficiently because we’re just taking off some of that fluid that would be going into the heart and it just couldn’t handle as much so any diuretic can really be used but loop and aldosterone antagonists are most common big drug reaction that would be electrolyte imbalance that comes from especially Furosemide which is hypokalemia or too little potassium and then Spironolactone too much potassium.
And then also with Spironolactone, we have gynecomastia. In heart failure with beta blockers only a few have shown benefit but it’s valuable to kind of think about why would something that slows heart rate be helpful for someone that has a heart that’s not doing its job well Metoprolol succinate and Carvedilol both will reduce heart rate until decreased heart rate interferes with daily activities what we’re saying is that you decrease heart rate a little bit so that heart can better fill.
So if a heart’s beating so fast that it can’t fill then it’s being inefficient but if it’s so slow that it doesn’t get its job done then it’s also not good so we want to be somewhere in middle adverse drug reactions of course within beta blocker we worry about bradycardia and then beta blockers are notorious for causing fatigue.
Another drug for heart failure is cardiac glycoside Digoxin or Linoxin in 90s this was drug to use but since it’s fallen out of favor it has electrical and mechanical effects to increase cardiac output and we’ll see those in next slide but it has very narrow therapeutic index which means that if you go too low it’s not effective and if you go too high it’s toxic so we want to be very careful about being between that 0.5 nanograms per milliliter to 0.9 nanograms per milliliter it’s indicated for heart failure and atrial fibrillation and adverse drug reactions dysrhythmias at very high levels nausea and vomiting can happen as well it isn’t used first line anymore it only helps with symptoms.
"There’s no mortality benefit plus there’s a lot of monitoring involved. So again, I’m going to show you how this works mechanically in just a second but heart failure and Digoxin are not the best friends that they were before. So we begin and we look at the Sodium Potassium ATPase pump and the Sodium Calcium exchanger and what we’re really trying to do is get calcium to help with the force of contraction. So we exchange sodium for potassium then Digoxin comes in have more sodium.
And then that sodium exchanges for calcium and then we see that the muscle cell will work. So this is it in words but Digoxin binds to Sodium Potassium ATPase, increases the sodium levels, sodium leaves the cell by the Sodium Sodium Calcium exchange increasing calcium levels. Calcium is used by the myocardial cell to increase the contraction strength. So how does it work electrically? So it slows down conduction velocity from the SA node to the AV node and there’s more time in between contractions allowing more time to fill.
And the heart rate decreases a bit so we can see this in the slide where we have heart failure with no Digoxin and this happens very quickly and then we have it with the jocks and it slows down a little bit allowing the heart to fill. Once we have medication effects on cardiac output we decrease preload and with ACEs and ARBs and diuretics afterloads with the ACEs and ARBs myocardial contraction can increase with Digoxin and then heart rate can go down a bit with Digoxin and Beta Blockers to help make the filling more efficient and cardiac output better.
So again preload decreased less blood fills the heart each time after load decreased it’s easier to get pump that blood out of the heart because we’re not pushing into as much pressure. The contraction is increased, we get more squeeze to pump the blood and the heart rate’s decreased more efficient blood pumping.
So dyslipidemia is dis meaning bad and then lipid so we’re in some way the lipids are just not working the way that they should so VLD or the levels aren’t so VLDL is a very low density lipoprotein it’s all about transporting triglycerides from the liver to the tissues. LDL is low density low lipoprotein so this is where the liver goes to the tissues this is the bad cholesterol.
And then the HDL is the high density lipoprotein that transports cholesterol from the tissues back to the liver this is the good cholesterol. So what’s the big deal? Well high triglyceride levels for example are associated with coronary artery disease and plaques. The treatment for lipid disorders usually it’s not dictated by blood levels anymore but hypertriglyce hypertriglyceridemia is an exception.
And we begin when triglycerides are greater than 500 milligrams per deciliter. So one example is Phenofibrate or Tricor it causes creation of more Lipoprotein Lipase breaks down triglycerides in liver so VLDL levels decrease less triglycerides for them to transport. So when do we use this? Hypercholesterolemia, Hypertriglyceridemia, and then mixed Dyslipidemia as well.
Now we might see some abdominal pain, back ache, abnormal liver function tests but when you think Phenofibrate think triglycerides. But what’s it look like when you’ve got too much cholesterol? Well you start with a normal artery but then you get this damage maybe it’s from smoking maybe it’s harding out arteries and then you get this fatty streak.
And then this fibrous cap comes on top and then cap ruptures and we see a thrombus and that occludes or blocks area. So again a normal artery everything moves smoothly number two excessive lipids accumulate form a fatty deposit called a fatty streak. The streak is covered by fibrous tissue in body and then cap ruptures and clotter thrombus forms.
And if it breaks off it can end up in smaller vessels cause thromboembolisms and so forth. So how do we treat it on left side? We have non-drug therapy so we decrease fat fatty acids cholesterol in diet try to get weight loss of 10 smoking cessation controlled hypertension on right side we have drug therapy.
And statins are definitely mainstay so HMG Koi Reductase inhibitors and we dose it based on cardiovascular risk other disease states rather than saying okay your LDL is this or your LDL is that two examples are Atorvastatin Rosuvastatin Lipitor Crestor HMG CoA is enzyme responsible for creating cholesterol in hepatocytes statins inhibit HMG CoA decrease cholesterol production.
So indications Hypercholesterolemia Hypertriglyc Ceridemia mixed Dyslipidemia famous reactions are muscle pain or Rhabdomyolysis tender tendon rupture so Rhabdo is where you kind of dissolve muscle muscle pain or Myopathy will usually precede it but that’s very serious condition uh maximum LDL lowering in four to six weeks but some results uh you can in two uh grapefruit juice any SIP three A4 inhibitors cause levels of statins to build up so we want to be careful about that.
And then it’s dosed in evening generally as most cholesterol is made overnight though Atorvastatin is one of those that doesn’t necessarily have to follow that rule. And if you were wondering what HMG Co-A stands for it stands for three Hydroxy III Methyl Glutaral Coenzyme A but most important thing to know is it’s involved in cholesterol it’s enzyme responsible for creating cholesterol in liver.
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