Oct 27, 2021
Classroom Lecture Cardio Pharmacology Part 3 of 3
The Classroom Cardio Lecture Part 3 of 3, you can complete the quizzes here https://residency.teachable.com/p/mobile
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Auto Generated Transcript:
Welcome to Cardiology Pharmacy Part Three. The topics we’re going to cover include Angina Pectoris agents, Anticoagulating and Anti-Platelet agents, and then MI or Myocardial Infarction agents. So let’s start with Angina Pectoris or pain in the chest.
So the pathology behind Angina or Angina begins with this pain behind the sternum and it starts pretty rapidly. Usually it’s caused by some kind of atherosclerosis from coronary artery disease but at rest the heart receives as much oxygen as needed for the contraction and so there’s an oxygen demand that meets oxygen supply and so we can represent this by a scale and this scale is even there’s no tipping of demand or no tipping of supply when exerted the heart needs to have more oxygen to be able to contract more and a healthy heart increases the supply as needed so the demand goes up the supply goes up no problem the scales are still where they need to be.
So this isn’t a problem where we do have a problem is when the heart doesn’t get the oxygen it wants it causes a pain beneath the sternum sometimes this pain will radiate to the left shoulder and arm and it will eventually reach the jaw so when oxygen demand exceeds oxygen supply and we have coronary artery disease in this exertion then we have an imbalance.
So we’re going to look at the cardiac output factors, the preload, the afterload, the myocardial contraction and the heart rate. So let’s start with the preload again that’s how much blood in the left ventricle is there before contraction, the afterload is the squeeze required to push the blood into the aorta so what’s going on afterwards, the myocardial contraction is how powerful the squeeze is and the heart rate is how fast the squeeze is.
So, the more the heart works, the more oxygen it needs and treatment involves decreasing how much the heart needs to work or getting it more oxygen. So again less demand it needs less oxygen or getting more oxygen more supply all Angina types are caused by a lack of oxygen and the treatments entail decreasing myocardial oxygen requirements so if we’re decreasing cardiac output we can decrease oxygen demand.
But let’s first take a look at classifications or the three types of Angina there’s Chronic Stable Angina which is Exertional Angina and the cause is usually Coronary Artery Disease or CAD there’s Variant Angina or Vasospastic literally a vessel and the cause is Coronary Artery Spasm and then there’s Unstable Angina where we have severe Coronary Artery Disease with clots or blockage that’s unpredictable and that’s a medical emergency so again Chronic Stable Variant or Unstable.
One medication we can use are Nitrates so with Chronic Stable or Variant Nitroglycerin brand Nitrostat causes vasodilation of the veins by directly acting on the vascular smooth muscle. The vasodilation decreases the preload so if there’s less preload there’s going to be less oxygen demand or the vasodilation can decrease spasms but it doesn’t decrease oxygen demand what it does is it increases oxygen supply.
And you can imagine this that when you have a vessel and it’s spasming it’s obviously not a nice smooth flow of blood and oxygen but when that spasm goes away we get that smooth flow again as we’re looking at beta blockers we see that with Chronic Stable Angina we can use Propranolol brand Enderol Metoprolol Tartrate Metoprolol Succinate Toprol XL and we can decrease heart rate and contractility so slower heart rate weaker pumping less work for heart causes decreased oxygen demand again sometimes compensatory reaction of heart is to increase heart rate to point that it’s difficult to fill.
And if we can slow that heart rate then we can create this lesser demand with Variant we don’t use beta blockers they don’t help at all with vasospasm so when you’re thinking about Variant we’re thinking okay well maybe I can use Nitrate or maybe I can use Calcium Channel Blocker which is next one we’ll talk about.
So Diltiazem brand Cartazam or Verapamil brand Kalin both dilate arterioles decrease heart rate contractility so this results in decreased afterload so less afterload decreased oxygen demand.
"If we want to think back to just basic physiology where calcium is so important in muscle contraction and by blocking that calcium we’re in a way decreasing the heart rate, decreasing that contractility because we affect it. We can also with variant angina induce relaxation of the spasms and cause an increased oxygen supply. So again, the two that work for variant are calcium channel blockers and nitro and for chronic stable we have calcium channel blockers, beta blockers and nitro.
Nitroglycerin can be given via different routes: sublingual tablets which is the most common and fastest outside of IV works in about three minutes and it’s an oral spray, transdermal patches as well. And then the adverse drug reactions as you would expect if you’re going to rapidly vasodilate something you can get orthostatic hypotension and orthostatic quite literally means ortho standing straight static and standing so straight standing hypotension is a rapid loss of blood pressure and then headache again from that vasodilation.
The way that we deal with someone who’s having a painful chest or having this angina and has to take a nitro pill is that if it doesn’t go away after five minutes take another tablet and call 9-1-1. The chest pain that doesn’t respond to a nitrate may be an MI or heart attack. Male patients cannot take nitrates with the PDE5 inhibitors those are the Viagra Cialis or Sildenafil as it were due to the hypotension interaction.
Okay so now we move on to anticoagulants, antiplatelets, Anoxiparon, Heparin, Warfarin, Dabigatran and Clopidogrel. The coagulation cascade is something we’re going to overview but because it all kind of meets in one place we’re going to see how it’s relatively straightforward as what we want to affect. The interaction between the different proteins or factors cause fibrin to be deposited at the end a tissue injury site and the proteins have been named long time ago and they were named as Roman numerals so factor VI is factor six and so forth.
And they were numbered based on the discovery not their function so the cascade doesn’t follow a numerical order if you’re wondering why it doesn’t go one two three or something like that. And what we’re doing is we’re going from an inactive protein to an active protein and we represent this by VII so the inactive protein 7 becomes active protein 7A.
So as we look at the pathways there’s extrinsic and intrinsic and the way that we measure them is by the prothrombin time for the extrinsic pathway or the PTT or the for the intrinsic pathway. So what we’re looking at is two different ways to get to this thrombin and fibrin and what we want to look at is where do the medications that we use what factors do they affect? So all these factors become targets for medications when we try to stop coagulation PTT and PT become important when we want to monitor how well the anticoagulation is working.
So Warfarin, we see is going to work on 9A10A 7A and then eventually Thrombin2A. The bigotran goes right to 2A and Heparin low molecular weight Heparin 10A and Thrombin2A. So when we’re looking at these, we’re going to start linking all the pathways together and we see the common middle where factor 10A or XA in the Roman numerals links both pathways together and becomes an efficient way to stop coagulation.
So anticoagulation, the Vitamin K antagonists Warfarin brand Coumadin it was developed as a rodenticide by Wisconsin Alumni Research Foundation and you see WHARF W-A-R-F which is beginning of name in 1950s. And rodenticide is something that kills rats and it prevented regeneration of Vitamin K epoxide Vitamin K used to create factors further down cascade it’s used by factors 7A 9A 10A and Thrombin which is 2A.
It’s a bit of a delayed onset five to seven days and it’s inappropriate for emergencies so dose changes take seven to fourteen days to take effect monitoring INR or International Normalized Ratio that’s marketer of time to coagulation so most patients have INR of two to three if lower than two to three increase dose or higher than two to three decrease dose.
And obviously it depends on patient depends on condition that trying prevent adverse drug reactions."
"If we have high drug levels we could have hemorrhage or bleeding, bruising, bloody stools all of these different things. There are many interactions with Warfarin and we’ll go over just a few with this pop-up. So green leafy vegetables have Vitamin K and this interacts with Warfarin and then several of the SIP 450 enzymes work on Warfarin as well so a lot of drugs change the metabolism.
So Coumarin was discovered in cattle that died of hemorrhagic disease after eating spoiled sweet clover and it was refined and developed into Warfarin is how we put this all together. Okay well that’s Warfarin in a nutshell this is an oral anticoagulant let’s look at something that’s an IV anticoagulant the Heparins both inhibit factors 10A and Thrombin 2A and are equally effective.
There’s Unfractionated Heparin which is given by injection only given in the hospital and requires extensive monitoring it’s relatively cheap but being in the hospital is not. Then there’s Low Molecular Weight Heparin LMWH or An Oxaparin which is brand Lovenox it’s injection only and it’s given in the hospital and at home there’s no monitoring required it’s quite expensive but not as expensive as being in the hospital so the choice is to take someone from Heparin in the hospital they both start with H and then go on to An Oxiparin.
Now as we look at the anticoagulants and one of the newer ones Debigatran brand Pradaxa it’s an oral direct Thrombin inhibitor it’s quite expensive but it doesn’t require monitoring. We do have adverse drug reactions like hemorrhaging, bleeding, bruising, bloody stools and while it doesn’t require monitoring not having monitoring also says that we may not know how the patient is doing as well as if we did when we had Warfarin.
So the anticoagulants work on the coagulation cascade usually we’re talking about the larger vessels but if you’re talking about a high speed vessel like an artery arteriole then we’re talking about platelets and the first antiplatelet we’ll talk about is Clopidogrel brand Plavix. So Glycoproteins 2B and 3A act as hands on the platelets grabbing more and sticking them together Clopidogrel prevents the hands from opening up grabbing more platelets to form a clot.
So what indications do we have Myocardial Infarction or MI Cerebrovascular Cerebrovascular Incident Percutaneous Coronary Intervention and then the ADR is just like with Warfarin just like with Heparin and Oxaparin and Bigatran hemorrhage or bleeding are always possible.
So looking at MI or Myocardial Infarction we’re going to talk a little bit about this and just just a heart attack so an infarct is tissue death due to the lack of oxygen coronary artery supply the oxygen to the myocardial tissues blood flow stopped usually by some kind of narrowing or blockage and then the myocardial tissue stops receiving oxygen.
So if the heart stops receiving oxygen that’s obviously a very bad thing for the patient what we can see is that when we have this blockage it’s going to stop what’s going distal to it or what’s going after the blockage and that’s going to be really really difficult for the patient because these vessels are very tiny and we don’t necessarily think of we think of the heart giving blood to the body but we forget the blood still has to give blood to itself so if it can’t do that then how does it pump the blood there that’s why a heart attack is so such a concern.
So, the two types ST Elevated Myocardial Infarction are STEMI it’s the more common uh myocardial tissue death and it releases cardiac Troponins One and T these are the best markers to see if someone had a heart attack and then the treatment we’ll discuss next. The Non-ST Elevated Myocardial Infarction NSTEMI is less common, The Troponins are also released but The ECG is going to show different rhythms. The treatment’s not covered in this lecture but let’s look at what The Elevated S STEMI rhythm looks like next to a normal heart rhythm.
So The Elevated rhythm you’re going to see here and that’s contrasted to The Normal ST Segment that we see here so The ST Segment is after The Ventricles contract and are recharging electrically for The Next Contraction. So what do we do to treat an MI? Well uh we used to have this acronym called MONA where you have Morphine for pain relief Oxygen to reduce The Infarct size Nitroglycerin to decrease preload and afterload into vasodilate and then Aspirin to be chewed to prevent platelet aggregation but The Guidelines are currently under review they’re going to be updated soon but often Beta Blockers are used instead of Nitroglycerin slow down The Heart allow it to fill because one of The Responses of The Heart is to start beating very fast because it’s noticing that it’s not getting oxygen to itself.
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