Antianginal Drugs

foreign what's up Ninja nerds in this video today we're going to be talking about anti-angional medications before we get started if you guys benefit from this video it makes sense it helps you please support us in the best way that you can do this by hitting that like button commenting down the comment section and most importantly subscribe also down in the description box we have links below to our website where you guys can check that out we've got some great notes some great illustrations that I think will be very helpful to follow along with during this video so let's get started talking about the anti-angels but in order for us to do that we have to build a very basic Foundation a slight talk about angina itself so what is angenance the patient's got the chest pains right they got a lot of chest pain and the reason I have this chest pain is usually a two point reason one is they got some type of plaque within their coronary vessels the vessels that actually Supply The myocardium of the heart and so if we were to take a piece here's a blood vessel here's The myocardium of the heart now if somebody has a particular occlusion or a plaque so here is this kind of like plaque within the coronary vessel this is going to reduce the perfusion of oxygen to these myocardial cells so the oxygen delivery to these cells here this is going to be your myocardium cells there is a reduction of oxygen to these tissues now that's the problem really when it comes down to coronary artery disease or angina we'll talk about the different types of angina but one one of the reasons is that there's plaque here or there's spasm of the vessel and the basic concept here that this is reducing the O2 Supply to The myocardium right whether they're do we do to a intense spasm of the vessel or a plaque within the vessel wall so because of that there can be a reduction in oxygen supply to The myocardium now that's one particular reason the next thing is if you have reduced oxygen supply obviously depending upon the degree of reduction in oxygen supply the patient can start to have a lot of ischemia to The myocardium and whenever they have ischemia to The myocardium this may precipitate a chest pain what can be potentially even worse though for some of these patients obviously if the plaque is really really big or it's completely occluding The Vessel there's almost no oxygen supply the ischemia infarction will ensue but if patient doesn't have a significant plaque let's say that they have some type of plaque but it's not completely occluding the actual entire coronary Lumen what happens is they may be okay they may not have a lot of chest pain at rest but whenever they start to exert themselves maybe this is physically or maybe there's a lot of emotional stressors going on in their life and what happens is their sympathetic nervous systems on overdrive their heart muscles working hard the heart's beating faster whatever it may be there's an exertional component now that heart muscle is going to have to beat faster and it's going it's going to have to beat a lot faster it's going to have to pump a lot harder and so because that the workload or the demand now is going to be a lot higher so these myocardial cells if they start increasing their work they start utilizing more oxygen to make ATP to contract and work harder what happens then as a result they increase their O2 demand and that really becomes a problematic issue because when you have a mismatch here where there is a reduction in O2 Supply and an increase in oxygen demand now The myocardium isn't getting the blood flow that it needs and because it's not getting the blood flow it's not getting the oxygen and if it has to beat harder and contract harder and beat faster now it's not getting the amount of oxygen that it needs in the ischemia can get worse and this can lead to infarction for some patients so that's the basic concept of angina is it's really these two particular things that can lead to the ischemic heart disease or coronary artery disease now there's different types of angina what are those let's say here we have one patient they have a stable coronary plaque right and so because of the stable coronary plaque they do have some perfusion to The myocardium so there is a reduction in oxygen supply in this particular scenario but it's not as terrible right they're still able to get some oxygen to The myocardium but for whatever reason the patient decides to increase their oxygen demand so they're exerting themselves their hearts beating faster their hearts Contracting harder they're going to consume more oxygen here's the mismatch that mismatch will start leading to ischemia beginning to ensue and that ischemia will then start to precipitate a form of chest pain which is the the terminology that we're utilizing with angina but the question is what type of angina this is whenever there's a stable plaque that's reducing supplied the patient exerts themselves and now they start having anginal chest pain this type here is a very specific type that we call stable angina so this is a stable angina so this is a type of angina where the patient has some type of stable plaque that's actually present but whenever they exert themselves that they have an increase in O2 demand their ischemia gets worse so these patients angina is increased ischemia or chest pain with exertion so that's usually the classical presentation for stable angios that's one type this is going to be the one that we're going to see very very commonly that we're going to try to treat patient has a known history of coronary artery disease whenever they exert themselves walking upstairs you know doing some type of yard work whatever it is that's the classic presentation I'm like man I'm having a lot of chest pain another type that actually has nothing to do with the plaque it's actually due to vasospasm so in this situation the patient is having some type of intense vasospasm and whenever they have this Intense vasospasm or the actual blood vessels intensely vasoconstricting it decreases the actual coronary Lumen size and now because of that you're not getting as much oxygen to The myocardium so what's the problem here there is a reduction in O2 Supply and this can lead to ischemia so the muscle is not getting enough oxygen to be able to form its particular functions it's because of that ischemia these patients May develop a type of chest pain but the chest pain is due to a vasospasm not a plaque and that's the key here what type of chest pain is this that actually can come about for these patients but it's due to vasospasm this is actually called Prince metals or variant angina or vasospastic angina Prince Metals is the common terminology that you may see though so just realize that so Prince Metals angina is due to vasospasm usually this is not due to a coronary plaque you usually see this in younger females who smoke who maybe have migraine history they take triptans or they utilize cocaine things of that nature that's usually the more common thing and usually this is a chest pain so they have an ischemic chest pain that is usually worse in early a.m so in the early mornings these patients tend to have some of this vasospasma occurring more commonly it can occur late at night but again remember the patient profile again we've talked about this in the coronary artery disease or ischemic heart disease lecture so go see that if you want more details but that's the basic concept here and if for these patients it really has nothing to do with exertion it's just again happens to be the vasospasm of the blood vessel all right the next disease here this is a patient who has a plaque but what happens is this plaque is somewhat unstable and with the instability of the plaque it may rupture our fissure and then you can form a clot on top of that plaque so it includes the actual vessel Lumen pretty significantly so in this situation for stable there was a minor reduction O2 Supply in this one there's a significant reduction in O2 supply enough to cause pretty decent ischemia to the actual myocardium and all for these patients is they don't really need an increase in O2 demand if they did it will obviously worsen their actual ischemia but for these patients there really isn't this need for any kind of o2 demand O2 demand really is not the issue here if there is an increase in O2 demand you can definitely bet so I'll put like a little arrow here if there is an increase in O2 demand if there is an increase in O2 demand this definitely will worsen the ischemia for certain and definitely precipitate the chest pain but this is one of the interesting types of engine where they have such a significant reduction O2 Supply that this will cause a chest pain for these patients but this chest pain is interesting because they don't necessarily need to be exerting themselves to have this type of chest pain because there is such a significant reduction in O2 Supply so since that's the primary problem here this is a chest pain that we don't see with exertion and this is called unstable angina it's unstable because the plaque is unstable it likely ruptured or fissured and created a clot on top of that that caused a subtotal occlusion of the coronary Lumen and so because of that this is ischemia that can occur to The myocardium without exertion and that's a pretty interesting concept they don't necessarily need an increase in O2 demand if it is present guess what it will certainly worsen the ischemia much much more but this is one of the classic presentations for an unstable angina now with that being said the other two are very very similar let's quickly go through these the next one here very very similar they also can fissure this plaque or rupture their plaque so it's an unstable plaque and it forms a pretty significant occlusion here within this actual Lumen to the point where the ischemia is so bad so there's such a significant reduction in O2 Supply and this is maybe over a certain period of time what starts to happen is you get ischemia in the outer parts of the muscle so out here you start seeing ischemia but then the inner blood vessels because what happens is these actual these uh coronary vessels what they do is they give off like little Feeder vessels that go deep into The myocardium so imagine here there's like a little Feeder vessel and it goes deep into The myocardium the ones that actually get the most damage is the ones farthest away from the Lumen here from that big coronary vessel so what happens is you see ischemy in the outer parts of the muscle the external parts and then you start seeing infarction death of The myocardium towards the inner part and so here you're going to start seeing infarction and that's the problem so you have ischemia in the outer parts and infarction in the inner parts and so because of this they start leaking certain particular molecules into the bloodstream and you know what these molecules are these are called troponins these are called troponins they often tend to be positive in this patient population so they have such a significant reduced O2 Supply again it doesn't need to have an O2 demand for these patients to really cause ischemia that's not necessary but again you can bet on it that if this patient did particularly exert themselves which would be absolutely catastrophic for them if they did happen to exert themselves and increase their O2 demand you can imagine that this will cause a very very profound ischemia and a very profound increased risk of infarction now because they have ischemia and even infarction and death of the tissue this type of chest pain is very unrelenting and very intense so they can have chest pain but because these patients actually infarct their tissue this is called a myocardial infarction but here's one of the big things it didn't fart the entire myocardium so because of that due to the EKG changes when you do an EKG on these patients they don't have this classic ST segment elevation those are more depressions or t-wave inversions non-specific so we call this type of angina in a non-st segment elevation myocardial infarction but it's the same concept they can have ischemia but they also will have some degree of infarction of their myocardium without exertion and that is a scary finding for these patients okay and so that's the big thing so when you look at these patients EKG if you were to get an EKG of both of these patients these two patient populations here for the nstemi and the unstable angina they may have particular findings such as St depressions or T wave inversions so you may see things like St depressions and T wave inversions but you will not see any type of what St elevations and so that's pertinent for patients who have unstable angina and patients who have nstemi's all right the last patient population here that can also exhibit angina is these ones are the worst case scenario the patient has a plaque right it's unstable ruptures fissures and now worst case scenario a clot forms on top of this unstable plaque and causes 100 occlusion because of that let's make it even more severe here there is a significant reduction in O2 Supply to pretty much no O2 supply to the actual myocardium that means none of the blood flow so if I were to draw like those feeders coming off here that are supposed to go and Supply this myocardium from the external and internal part it's all gone so there's going to be complete infarction of The myocardium this is going to be all jacked up because of that these these patients will bump their troponins pretty significantly so these troponins will be pretty elevated or positive like an in stemi one of the big differences though for these patients is that they will have something called s t segment elevations so if you were to look at these patients EKGs you would notice that they would have these ST segment elevations on their EKG and that is one of the big particular findings that you'll notice with this one so since they actually infarct their tissue they have an ST segment elevation these are a very specific type of again anginal presentation it's called a stemi ace ST segment elevation myocardial infarction and these patients have infarction of their myocardial tissue which causes their chest pain and they do not need this to happen with any exertion this can happen at rest and so I think that deserves a very particular terminology to discuss here let's do this here in pink that these three particular types unstable angina and stami and stemi are part of something called acute coronary syndromes an acute coronary syndromes again this will be unstable angina and stemi and even a patient who has a stemi these are the three presentations of acute coronary syndrome and this is different from unstable I'm sorry from stable angina that these patients with acute coronary syndrome can present with a type of ischemic chest pain or pain due to infarction of The myocardium without any exertion that can occur at rest whereas those with stable it primarily occurs with exertion or emotional stress or something that causes an increase in heart rate an increase in contractility of the heart which causes it to consume more oxygen increase demand and then cause this significant mismatch that is the key here so when we talk about patients who have angina you understand the different types of angina you understand the basic pathophysiology all we can do is for these patients is figure out a way that we can reduce their O2 demand that might help a little bit and is there a potential way that we may be able to kind of increase coronary perfusion somehow if we can without having to go in there and remove the plaque that would be medical therapy that we should try to utilize for these patients so now let's talk about those medical therapy options that we can give to patients who are presenting with a classic stable angina or the prince Metals angina or one of the acute coronary syndromes let's get into it so now the first category of drugs that we should talk about that are utilized in patients who have angina is going to be beta blockers these are very good first-line prophylactic medications so a patient comes in and they're having chest pain right and the acute anginault phase this is not the first Lyme medication that you're going to give immediately it's a medication that you'll give a little bit later okay and we'll talk about with the treatment algorithm we'll go through this repetitively so you guys will remember how to approach a patient who comes in with angina now what are the beta blockers that we should actually remember because there's a very particular set of them that we have to remember the first ones that I want you to remember that are really good is going to be metoprolol metoprolol is probably going to be the more commonly utilized one so that would be one the other one that you could probably consider here is Atenolol I would say the last line one that you could give because it's not necessarily a singular cardio selective beta blocker or beta one blocker it would be propanolol so I actually want to put a little kind of asterisk next to propanolol just so that you guys remember that this one has beta 1 and beta 2 activity whereas metoprolol and Atenolol those would be more particularly focused on beta 1 activity now with these drugs the basic concept it's not hard to imagine here is that they are beta 1 blockers on the heart that's what we're focusing on is the beta 1 receptors in the heart so if we were to take the two different types of myocardial cells here so here you're going to have the nodal system so here we're gonna have our nodal cells we're going to zoom in on one of those nodal cells and then you're going to have also the other part which is the contractile portion the ones that actually squeeze and push blood out of the heart so we have the nodal cells like your essay node AV node bundle of his purkinje system bundle branches all that stuff like that and then the ones that are the contractile cells on their cell surface they have very specific types of receptors what are these receptors they're called these ones here are called beta 1 receptors now what happens is whenever the beta 1 receptors are acted on by things like norepinephrine or epinephrine which is released by our sympathetic nervous system they act on the nodal cells to increase heart rate increase the cardiac output for the contractile cells increase contractility squeeze more blood out and increase cardiac output when we give these drugs like metoprol atenolone propanolol what they're doing is they're binding onto the beta-1 receptors and they are inhibiting the effect of epinephrine norepinephrine so they will inhibit the nodal cells and the contractile cells and the subsequent result here for the nodal cells is that you're going to block the effect of the what's called chronotropic or dromotropic action so therefore you're going to decrease the patient's heart rate why is that important I'll get to in just a second the other thing is that they can block the contractile cardiac cells and so because of that that will decrease the contractility of the heart now if I decrease the contractility and I decrease the heart rate so contractility will determine what it determines a patient's stroke volume so that will drop heart rate determines cardiac output so what I'll see as an effect here is that I will decrease the patient's stroke volume which will decrease their cardiac output if I decrease their heart rate that'll decrease their what cardiac output this will decrease cardiac output now here's what I want you to think about if you decrease cardiac output you decrease the volume of blood that the heart is having to push out every minute that means that that heart doesn't have to work as hard to push as much volume of blood out of the heart that decreases the cardiac work if I decrease my cardiac output the overarching theme Here is that I'm going to decrease the work that the heart has to do and if I decrease cardiac work I'm going to decrease oxygen consumption to buy the actual heart muscle cells the nodal cells and the contractile cells they're not going to have to use as much oxygen to generate Action potentials and to generate contractility and if I reduce oxygen consumption I'm going to reduce O2 demand remember I told you what the basic pathophysiological principle behind this is is that you have a plaque here or vasospasm and it's reducing oxygen supply the problem is is that if you have a reduced O2 Supply and the demand is increased you create a significant mismatch which worsenschemia or can significantly worsen ischemia for the acute coronary syndromes so my job here is to give a drug that actually will restore this balance because what's the imbalance here there's a reduced O2 Supply and there is a increased O2 demand which part am I utilizing to inhibit this process I'm going to inhibit the increase in O2 demand because it is the combination of these two particular things that creates the increased risk of ischemia so if I do this if I reduce O2 demand I will reduce the ischemia that are the ischemic chest pain that these patients may experience so that's why these drugs are good now only downside that you have to be considering with these drugs is that because they have the capability of reducing the patient's heart rate what's an adverse effect with that my friends for this one of the adverse effects that you need to watch out for is bradycardia it can drop the patient's heart rate which could potentially make them a little bit bradycardic the other thing is that it reduces contractility if you reduce contractility just make sure that you're careful because this could cause hypotension that could lead to shock so be very very cautious especially if the patient has what's called decompensated heart failure wouldn't want to give that drug because these patients with decomposated heart failure are already cardiac output dependent you drop their cardiac output even more you can put them into a shock state the other things that you want to be careful with these drugs is that because especially for Panama when you look at the actual smooth muscle in the bronchial tree this has lots of beta 2 receptors lots of beta2 receptors so if you're giving Propranolol that's the more likely one to hit the beta 2 receptors so when it hits the beta tube receptors on the actual bronchial smooth muscle it's going to block it what is the beta-2 receptors naturally do if epinephrine norepinephrine work on them they cause bronchodilation you're going to block that effect so you're going to cause bronchoconstriction bronchospasm and so because that if you inhibit the beta 2 receptors you lead to Broncho spasm and that can definitely be worse and you'd probably want to avoid these drugs and patients who have what who have some type of COPD have some type of asthma because it potentially could exacerbate that situation since these are diseases of bronchospasm okay and again be more leery I'm going to put that pink kind of asterisk here that you're going to see that's more likely with Propranolol or very high doses of metoprolol and Atenolol okay the next concept here as you know when patients have very like here we're going to put like a little G there this is glucose this is glucose when patients have low blood glucose levels so they have hypoglycemia so here we're going to have hypo glycemia when patients are hypoglycemic what this does is this actually helps to activate glucagon release and activates our sympathetic nervous system so what it should do naturally is it should stimulate the sympathetic nervous system and the sympathetic nervous system will respond and say oh dang glucose is low I gotta alert the patient let them know that their glucose is low and will increase their heart rate it'll cause them to become more sweaty or diaphoretic and cause a lot of other potential features that make you aware of your hypoglycemia if you give a beta blocker what you're doing is you're blunting the actual sympathetic reflex so you're inhibiting this sympathetic reflex with beta blockers and so because of that you could actually have the patient develop what's called hypo glycemia on awareness and so with that being said I would just be careful of this and patients who have some type of underlying diabetes unless it's the last option for this patient but this is the things that I want you to know for beta blockers big thing to take away patients who have angina the basic pathophysiological principle here is that they have a reduced O2 Supply whether it be spasm or plaque if they have an increase O2 demand they're exerting themselves they're emotionally distressed what will it do it will increase the ischemia to the heart even if this is a response to their underlying disease process and they have to work harder now to be able to generate more forces to pump more blood out the whole process is if I give these drugs they're going to reduce the demand they're going to reduce the ischemic chest pain and potentially improve the patient's angina okay now that we've hit that what I want to do is I want to take a particular situation patient comes in they're having anginal chest pain and maybe they were exerting themselves maybe they weren't exerting themselves what's the first line and then how does beta blockers fit into this let's talk about that all right so patient comes in they're having anginal chest pain the classic anginal chest pain if that happens what's the actual treatment process well the first thing is you should do is we're going to talk about these about two parts from now there's another drug class we'll talk about but we're going to use something called nitroglycerin so nitroglycerin is a pretty good like short acting medication that'll be great in patients with acute anginal attacks after that then the prophylactic therapy that you'll add on next is going to be your beta blocker category so that's how you want to remember a patient comes in acute anginal attack give them Nitro to be able to reduce their actual oxygen demand significantly maybe even improve some of the O2 Supply we'll talk about how they do that later then prophylactically for their anginal chest pain to reduce demand consistently throughout their days continue to use a beta blocker on a daily basis now the other thing that you want to remember because there's a lot of drugs that we're going to go over actually I'd say like there's mainly like four categories of drugs so the question that you have to be able to ask yourself is what if they have other comorbidities which one of these maybe is the best particular scenario well generally beta blockers will be the first prophylactic therapy now it also would be super beneficial to do a beta blocker if the patient also has some type of post Mi so maybe they have a coronary artery disease history and they've already had a PO their post Mi this is a good drug because it's been shown to reduce mortality in these patient populations and reduce cardiac remodeling as well the other one is hypertension this may be potentially beneficial now things that you'd want to be very cautious of or avoid is impatients who have some type of COPD or asthma and we know why because it causes a pretty significant bronchospasm and then maybe be cautious in patients who have diabetes mellitus why because it can cause hypoglycemia unawareness so these are the ways that you want to think about it what is beta blockers doing they're reducing O2 Demand by dropping heart rate dropping contractility because of that the decent prophylactic medications and angina especially if the patient is post Mi or has hypertension be very cautious and avoid in COPD asthma as well as in diabetes and then again understand that the first prophylactic dedication after patients are acutely treated for the other anginal attack with nitroglycerin okay now let's go to the second category of drugs that are used in angina all right engineer so now we're going to move on to the next part which is calcium channel blockers now there's two categories of calcium channel blockers believe it or not that it can be utilized in angina you have your non-dihydropedian calcium channel blockers and your dihydropyridine calcium channel blockers and we'll talk about their utilization but both of them are actually decently good so your non-dehydro period and calcium channel blockers are going to be Verapamil so I want you to remember that one varapa mill and then the other one is called diltiazem now these have two mechanisms of action and we'll talk about those actually I guess you could even say technically three mechanisms of action but the basic concept of patients who have some underlying type of angina is is again this one's the key interesting component this can be used in your stable angina again it will talk about it's more of a second line prophylactic medication but they can be utilized but they've actually been more preferred in patients who have Prince metals or vasospastic antenna they're actually more preferred now when you have some type of again here's this point here they have some type of Vaso spasm we know that this is going to reduce oxygen supply if they have some type of plaque here this is going to reduce O2 Supply so regardless the whole concept of the pathophysiology here is that you're reducing O2 Supply to The myocardium and if for whatever reason you increase the oxygen demand to Hearts working harder either as a reflex or because you're exerting yourselves we know that this is going to precipitate some type of ischemia that can worsen the patient's chest pain whether this be due to vasospasm or whether it be due to a plaque again we've just shown that these drugs actually tend to be more beneficial and the vasospastic cause but either way it can be utilized in both now how do they actually help with again inhibiting this increase in O2 demand and by reducing O2 demand and then reducing ischemia well it's the same as the beta blockers it literally is take some of the nodal cells so the Estee nodal cells Abu nodal cells bundle of His bundle branches all that stuff zoom in on one of those cells and then the contractile ones zoom in on that one they don't have beta receptors but what they do have on them is these little receptors here these little channels I guess I should actually say and these are called your calcium channels so these are called your calcium channels now these calcium channels naturally what they're going to do is they allow calcium to come into the actual nodal cell and so calcium should be able to enter into the nodal cell and if calcium enters into the nodal cell should increase Action potentials increase the heart rate increase the cardiac output that's the whole concept here if it goes into the contractile Cell It's supposed to be utilized to bind on with the myofilaments induced in a more powerful contraction increase contractility increase drug volume cardiac output well now what I'm going to do is I'm going to give a drug like arapamil a goodizam that'll block these non-dihydropyridine calcium channels prevent calcium entry if you inhibit calcium entry into the nodal cells it's not going to be utilized to depolarize the nodal cells and so it'll drop the patient's heart rate which will drop the patient's cardiac output on top of that if I don't have calcium coming into the contractile cells they're not going to be able to generate the same powerful contraction so I'm going to decrease contractility pretty significantly if I decrease contractility what I'm going to do is I'm going to drop the patient's stroke volume and then I'm going to drop their cardiac output if I drop the cardiac output I drop the cardiac work if I drop the cardiac work then now the heart's not having to work as hard to pump this larger volume of blood out of the heart what's going to happen now well then I'm going to decrease O2 consumption and then subsequently if I decrease O2 consumption I'm going to reduce O2 demand and that is how we're going to help with this patient who has some type of angina whether it be vasospastic or again whether it be due to a plaque that's within the vessel wall now that is the basic concept of how these drugs are actually working the non-dihadropyridine types but they have two more mechanisms of action what I want us to do is we have the arterial system here coming from the left heart so here's going to be the heart here obviously a left ventricle will pump blood out into the aorta and into the systemic circulation right now what I want to do is I want to take a piece of the arterial smooth muscle cells and zoom in on this then what I want to do after that is I want to take a piece of this myocardium here I want to take a piece of The myocardium in the coronary vessel and then zoom in over here okay so we're going to look at two different diagrams here on the arterial smooth muscle cell here within the actual systemic vasculature there is calcium channels okay there is calcium channels these calcium channels have a dihydropyridine type of molecule associated with it so they're called dihydropyridine calcium channels again the basic concept for these is that what do they allow to come in they allow calcium to come in and when calcium comes into these actual smooth muscle cells what is it supposed to do induce contraction of the arterial smooth muscle cell and that'll cause vasoconstriction and increase afterload and make more work for the left ventricle to pump putt out that sounds not very helpful so what if I give a drug that'll inhibit these dihydropyridine calcium channels if they inhibit them you inhibit calcium entry if I inhibit calcium entry into the arterial smooth muscle cell what am I going to do I'm going to cause vasodilation if ivasodilate I reduce afterload if I reduce afterload I reduce left ventricular work which reduces O2 consumption and what is that going to do that's going to reduce O2 demand oh my gosh that that's actually pretty straightforward then right so that would be one benefit then so this is another benefit here to me reducing the oxygen Demand by just causing vasodilation of the arterial system and that will actually make left ventricle a lot easier to pump blood out then it's not gonna have to work so hard to push it against a higher pressure that's beneficial okay well here's one of the things Verapamil and dothiazem not only can they do the blockage of the non-dehydropodium calcium channels on the actual heart muscle they can also do this on the arterial smooth muscle so you do have particular drugs Verapamil will actually be better so if I had if we look at it here Verapamil and deltiazem if I were to actually compare here how they work on these actual these channels here these dihydropriating calcium channels the Verapamil is going to have a more profound vasodilatory effect in comparison to diltiazem on the arterial smooth muscle cells the true drugs that are actually going to be more powerful here at the arterial smooth muscles within the systemic circulation are the dihydropyridine calcium channel blockers these are the ones that are truly going to be the best and working here on the arterial smooth muscle cells and inhibiting them allowing calcium in therefore allowing them to vasodilate reduce afterload reduce work on the left ventricle reduce consumption of oxygen oxygen demand this drug category for the dihydropyridines is going to be two particular drugs amlodipine and another one called nifedipine nifedipine and this is actually going to be the more preferred utilization within this category nifedipine all right we have now dihydropated calcium channel blockers will inhibit the arterial smooth muscle cells when the systemic vasculature so will Verapamil detoxin but Verapamil more powerful than diltiazem varapamil deltaism will also drop heart rate and contractility the dihydropedic calcium channels will not be able to do this on the heart okay that's important to remember there's one more function that the non-dihydropyridines and the dihydroperating calcium channel blockers have in comparison to each other this next thing is we have to zoom in on this portion here so now I'm looking here at the actual myocardium so here's our one this is The myocardium and here is the coronary artery now this coronary artery is an intense vasospasm it is an intense Vaso spasm if it's an intense vasospasm we're reducing the coronary perfusion to The myocardium leading to ischemia so because of this this is so small of a lumen that this will precipitate ischemia to The myocardium leading to chest pain what I'm going to do is is guess what on these actual coronary arteries just like this the smooth muscle cells guess what they have calcium channels so if I were to actually take a piece out of this coronary artery and look at the smooth muscle cell here's a coronary artery smooth muscle cell if I would actually take a piece out of this one and zoom in on it here this is what you're going to see and then again on that is going to have what calcium channels what type of calcium channels will you see here my friends you'll see the dihydropyridine calcium channels on these coronary artery smooth muscles and so what's going to happen is if you give them something like amlodipine or nifedipine or verapamilitizen what is it going to do generally calcium is supposed to enter into these and if calcium enters in That's supposed to cause this muscle too contract and then cause reduced coronary perfusion if I give them these particular drugs amlodipine to pedophene nifedipine for optomets better than diltiazem it'll inhibit calcium entry into this coronary artery smooth muscle cell and then what's that going to do that's going to reduce the vasospasm it's going to inhibit the vasospasm so there was vasospasm going on here right let's actually write this down Vaso spasm this was vasospasm here which was precipitating reduced coronary perfusion causing ischemia when I give drugs like amlodipine nifedipine varapamil deltiazem it'll inhibit the calcium entry into the coronary artery smooth muscle cells that will inhibit the vasospasm it'll open up this vessel a lot more so because it's going to vasodilate if it vasodilates now I'm going to increase the perfusion to the coronary myocardium and inhibit ischemia wow that's actually pretty interesting when you think about that so again what I want you to take away from this is Verapamil and deltaism their primary function is working on the cardiac tissue they drop heart rate and contractility which drops cardiac output but they do have two other functions but not as powerful they can reduce the actual vasoconstriction of their arterial smooth muscle cells within the systemic vasculature reduce afterload reduce heart on the work on the left ventricle they also can reduce vasospasm of the coronary arteries improving coronary perfusion and decreasing ischemia the dihydroperating calcium channel blockers amlodipine in the nifedipine they're going to be more powerful and cause two particular functions one is they inhibit calcium entry into their arterial smooth muscle cells in the systemic vasculature reduce afterload reduce left ventricular work and they cause vasodilation of the vasospastic coronary arteries improving coronary perfusion and inhibiting ischemia this is what I want you to remember for these particular drugs let's also put this one here we're just going to create like a little it'll also perform that function okay wrap Mill dataism can do all three functions more powerful on the ones above amylodipine nifedipine are going to be more powerful for the ones here on the bottom okay now that we've discussed this particular action here what I need to do now is I want to talk a little bit about how these actual drugs potentially can cause some adverse effects it's not hard to imagine that the varapodiacin what would their adverse effect be we don't even need to really kind of be too crazy about it what is one of the adverse effects it can cause a reduction in heart rate so watch out for any bradycardia it also can reduce contractility so you better be darn careful in patients who have heart failure do not give this medication because it can drop their contractility make them hypotensive and put them into cardiogenic shock the other adverse effect here that you have to watch out particularly with the dihydropyridine calcium channel blocker so with these the one of the big things that you want to watch out for is that they reduce the systemic vasculature so what do they do they reduce systemic vascular resistance and then drop the blood pressure one of the big things with this is that this is going to cause a reflex tachycardia so watch out for this is a potential adverse effect that you can see with the dihydropyridine calcium channel blockers they also may cause a little bit of vasodilation of the cerebral vessels which may cause headache so watch out for that as well but again big big adverse effects of what job for Verapamil to tiazem watch out for bradycardia cardiac that can cause hypotension even cardiogenic shock if they have decompensated heart effects or avoided in those patient populations and then the dihydropyridines again they can cause a reflexive tachycardia because they actually will drop your systemic vascular resistance one last thing is that these drugs the dihydropedic calcium channel blockers they have been shown to be able to increase the risk of mortality in very specific patients patients who have coronary artery disease and have had a recent Mi so particularly post Mi this has been shown to potentially increase mortality so you should be very very careful and patients who have some type of postmi avoiding these medications because there has been some literature of the show that they can actually increase mortality okay now that we got the calcium channel blockers kind of in our head okay we know that these are way better at treating what type of true angina the prince Metals the vasospastic engine is what they're really good at that's going to be the best thing they're not as good at treating more of the stable angina unstable angina Etc if a patient comes in and they're presenting with angina how are we going to treat them well we already know we hit them with Nitros then first line prophylactic is beta blockers then what how do we fit in the next part let's talk about that all right my friend so now when we talk about patients who come in with anginal chest pain again I think one of the big big things to be able to remember here is that these drugs the calcium channel blocker category regardless of which one they are just really good at that vasospastic or Prince Metals angina this is really the the preferred indication of these drugs all right but it's one of the types of engine that we did discuss but there is some benefit to it in patients who have some type of plaque within their vessels just make sure that they haven't had a recent in mind okay but patient has angina they come in what do you first give them sublingual nitroglycerin because it's short acting it's going to be the first one then after that is a prophylactic therapy first line is going to be beta blockers now if the patient still has refractory so if they're refractory to the above therapy so they're still having refractory angina despite the utilization of acute nitroglycerin and beta blockers then what you do is you have one of two options you can do a calcium channel blocker whether it be the non-dihydropyridines or the dihydropyridines or you can do what's called nitrates and that's the next drug category that we'll talk about here in a second the long-acting nitrates now if you're going to be giving a patient a calcium channel blocker what would make it a little bit more preferable one is that it's a vasospastic angina that's one particular reason but the other thing is does the patient have underlying hypertension if they have hypertension these drugs actually may make them a little bit more preferable especially especially the dihydropyridine calcium channel blockers may make this a little bit more favorable the other thing is that in patients who have underlying diabetes and patients who have underlying COPD or asthma this will not cause bronchospasm this will not cause hypoglycemia unawareness so it may be pretty beneficial in those situations who maybe can't tolerate a beta blocker so in this situation think about this it may be beneficial in COPD and Asthma where they weren't able to so they had they weren't able to take a beta blocker so then you can give them a calcium channel blocker in the same way they have diabetes so they have increased risk of hypoglycemia unawareness they couldn't tolerate the beta blocker then you can go with a calcium channel blocker but again one of the big things that you have to be aware of is just do not give this to patients who are post am I there is an increase mortality with these particular drugs reason why not completely understood but again something that you should potentially avoid okay so when we're talking about calcium channel blockers again we have the two particular categories just so you know the dihydropyridine and the non-dihydropyridine they're good more preferable and the vasospastic prince Metals angina but can be used in stable angina or the Q coronary syndromes again you want to be very careful though with these agents if you're going to use them you use them after you've already tried a beta blocker in the patient's refractory to it or maybe they won't be able to tolerate a beta blocker for some particular reason generally you still can give it in these particular situations just you know but if you're going to give a calcium channel blocker it may be beneficial if the patient has hypertension diabetes and COPD which they can't tolerate a beta blocker or again diabetes or COPD asthma that they can't tolerate a beta blocker calcium channel blocker may be more preferred but if they're post Mi do not give them this because there's an increased risk of mortality because you may drop their pressure and put them in a cardiogenic shock okay that discusses this option let's move into the next option which we haven't discussed but we've mentioned it kind of briefly the nitroglycerin and then the other ones which are your long-acting nitrates which we're going to talk about now here the isosorbide so this is your long acting ones whereas nitroglycerin is going to be more of the short acting one but let's talk about the category of drugs called nitrates now all right so next category nitrates now nitrate's actually pretty cool pretty beneficial in these patient populations so again basic concept I want you guys to just keep this pathophysiological principle is actually probably one of the simplest ones in medicine thank goodness but again there's a coronary plaque it's reducing oxygen delivery to The myocardium so again we got that basic concept that there's a reduction in O2 Supply and if there is an increase in O2 demand this mismatch is the problem with this disease it leads to ischemia which precipitates worsening chest pain so how do we treat these patient populations it's really interesting so what I want to do is is because these drugs don't actually drop heart rate they don't drop contractility and they don't even really dilate your arterial smooth muscle cells within the systemic circulation they have two primary functions so beta blockers they reduce heart rate contractility that was their mechanism of action the calcium channel blockers that all of them actually if you think about it well particularly the non-dehydropyridine they reduce heart rate to reduce contractility but they also systemic vasodilation coronary artery vasodilation for the dihydropyridines it was systemic vasodilation and arterial coronary arterial vasovilation for these drug categories they don't really have any effect on the systemic arterial system the heart rate the contractility they really work on veins and the coronary arteries that's it so what do they do first so let's focus here on the veins so here this is going to be the venous circulation the big veins I'm going to zoom in on one of these actual venous smooth muscle cells and show you how nitrates actually work so nitrates are pretty cool so what the nitrates do is so here we're going to have this nitrate drug category and we'll talk about these in just a second what they do is they get taken up into this venous smooth muscle cell once they do that they release a molecule from their structure called nitric oxide the nitric oxide will then stimulate a very special type of enzyme here called guanol cyclase guanolocyclase will then take a molecule called GTP and convert it into cyclic GMP cyclic GMP will then activate something called protein kinase G and then protein kinase G will act on with acting what's called myosin light chain phosphatase and what it'll do is it'll act on this enzyme phosphorylated and when it's phosphorylated it's not able to allow for the contraction of the cardiac muscle I'm sorry the sub I'm sorry the smooth muscle cell it's going to inhibit the smooth muscle cell contraction if you inhibit the smooth muscle cell contraction why is that potentially beneficial so what am I going to do I'm going to cause inhibit smooth muscle contraction if I inhibit smooth muscle contraction particularly within the veins within the veins what's the overarching concept here I'm going to cause Vino dilation if I cause Vino dilation I will reduce preload if I reduce preload I reduce stroke volume if I reduce stroke volume of reduced cardiac output if I reduce cardiac output I reduce what oxygen consumption or cardiac work there's less volume that the heart has to pump out now and so it's going to reduce oxygen consumption and then subsequently if I reduce oxygen consumption I'm going to reduce O2 demand and if I do this where I actually reduce the O2 demand I may reduce the ischemia so the basic concept with these actual nitrates is that they cause a very profound Vino dilation of larger veins which is going to reduce the return of blood back to the right heart this is inhibited you inhibit the actual return of blood to the actual heart why is that potentially beneficial because you reduce the massive volumes that can be returned which reduces preload stroke volume and now you're not going to have to pump as much volume of blood out of the heart that's less work that it's got to do that's the benefit behind this now with that being said Vino dilation does come with some particular risk that you have to be careful of if a patient has a right ventricular myocardial infarction so their right ventricle is already jacked up okay it's not pumping blood from the right heart to the left heart so with a right ventricular Mi if a patient has some type of damage here to their right ventricle it's not pushing blood out via the pulmonary circulation and it's not giving blood to the left heart so because of that with a right ventricular Mi the downside is that it's going to reduce the left ventricular preload and then subsequently the cardiac output and then drop the patient's blood pressure If you that you give a nitrate then you reduce their preload even more you reduce the left ventricular cardiac output even more and you drop their blood pressure even more so with a right ventricular Mi be very careful do not give nitrates because of why it can significantly drop the patient's blood pressure so be careful if a patient has a right ventricular mind don't give them a nitrate because you can drop their preload if the right ventricles are not squeezing blood out and now it has no volume to squeeze you're not going to give anything to the left heart the left heart's not going to get any love and the blood pressure is going to tank another thing is don't give this drug with another drug that has a similar type of activity so I would probably avoid giving this drug in patients who are on what's called phosphodastrase five Inhibitors and these are the you know medications for the raw you know the Viagra or the tadal philosophyll I would be careful with those why because what these drugs do is they also work too and increase your cyclic GMP within what the actual venous smooth muscle cells and if they do that what are they going to do if you increase the GMP you're going to inhibit smooth muscle cells even more you're going to cause more profound Vino dilation and more profound venon dilation is going to produce preload and reduce significant Venus return to the heart and make the patient's blood pressure tank so because of that this also will lead to hypotension so one of the potential contraindications is patients who may have an increased risk of hypotension with pde5 Inhibitors and right ventricular Mis be careful the other thing that I would also be careful with is whenever you Vino dilate guess what else you do you reduce preload stroke volume cardiac output and what's that potential downside to that is this may drop blood pressure during positional changes and because of that what this may look like is when a patient's going from a seated to a you know from a seated position to standing or from supine to a seated there's a quick positional change and that position will change naturally may do What it may naturally reduce their Venus return but then you Vino dilate them reduce their venous return even more and so because of that this could actually lead to ortho static hypotension so an orthostatic hypotension drop in blood pressure so watch out for that as well another potential thing that it may do is actually dilate the cerebral vessels a little bit and maybe actually bang on those pain receptors in the dura mater and cause headaches as well but again these are some of the big things that you really got to be careful with another concept here with this drug just going off of the venous smooth muscle so this is another venous smooth muscle cell so here's another venous smooth muscle cell we're zooming in on it now naturally what's really interesting about nitrates is that they really are pretty powerful and they love to again kind of increase the nitric oxide and stimulate the heck out of this one loss cyclase right and the concept behind that is again it'll take the GTP and convert it into lots of cyclic GMP that's the whole process when you give nitrates what happens is this guanolocyclase becomes desensitized all right it starts becoming desensitized with continuous usage and so because of that if the guanolas cyclase will start to become desensitized desensitized then what you see is you see a decrease in the efficacy of the drug and so because of that as you have desensitization of the guanolas cyclists from stimulating it so much it may not respond as well to exposure to nitrates the efficacy may go down so what you want to do to actually improve the sensitivity is have what's called a nitrate free interval and what that nitrate free interval will do is is it'll actually give you a time period generally like 10 to 12 hours and when you give them that 10 to 12 hour nitrate free period it'll actually inhibit that desensitization to allow for the guanol cyclase to be like okay you haven't annoyed me and nagged me enough for the past 10 to 12 hours so now I'm good you can go ahead stimulate me again I'm ready to roll so that's the whole concept is that it's just been being bugged and stimulated constantly by the nitrates you want to give these patients about a 10 to 12 hour period where they're free from nitrates so that way whenever you do that the actual guanalysis cyclase is more responsive it's ready to respond to the nitrates and again allow for the efficacy to improve so that's the whole concept is give them a nitrate free period generally the nitrates you want to give them about a 10 to 12 hour free period and that should be able to restore that sensitivity and for some patients this may be best at night when their cardiac output's already down and they're not having to do too much cardiac work that would be more for your classic coronary artery disease patients for the vasospastic or Prince Metals may actually be better to kind of have their hold their nitrates during the later afternoon because their chest pain is usually early in the morning so that might be something to consider all right so we got the basic concept of their Vino dilation how that works and some of the adverse effects from that and then the tolerance factor is a huge one to remember the next thing is that it also has another mechanism of action the next mechanism of action is that here's an arterial smooth muscle cell from a coronary vessel so what I did is I took this coronary artery here I zoomed in on one of the smooth muscle cells within this now what this does is it's the exact same concept here's this enzyme called I'm going to stimulate the heck out of it so I'm going to take a nitrate it's going to come into this coronary artery smooth muscle cell it's going to increase nitric oxide stimulate this enzyme take GTP convert it into cyclic GMP stimulate increase in protein kinase G and then work on the myosin light chain phosphatase and by doing that what it's going to do is it's going to inhibit the actual smooth muscle cell contraction if I decrease coronary artery smooth muscle cell contraction uh contraction what I'm going to do is I'm going to actually vasodilate this will work in those will cause coronary vasodilation and if I coordinate vasodilate what I'm going to do is I'm going to increase perfusion to The myocardium and improve some of the oxygen supply so that is the basic concept with nitrates so what nitrates are going to do is twofold Function One coronary artery vasodilation the other one is vino dilation of the big massive venous structures that return blood to the heart that's the concept I want you guys to know now with these drugs there's two particular categories that I want you to know one is your short acting drug category and the other one is your long acting drug categories the short acting I want you to remember something called Nitro glycerin commonly abbreviated ntg now this drug is terrible given po it it literally the first past metabolism about the liver is like 90 so like 10 of the drug will actually be utilized by the time it's done with the liver so because of that it's not good to give it that way these drugs we'd prefer to give it sublingual or as transdermal so we can give it transdermal so sometimes they put like a paste on or they put like an ointment on and these are actually the best ways because it avoids the first past metabolism effect now this is why we give it for acute anginal attacks okay the long-acting ones are going to be what's called isosorbide dinitrate and then the other one is called isosorbide mononitrate if I were to use plus signals to tell you the duration of effect here this one would be two plus the isosorbic mononitrate it actually has again with this one it actually has much more or longer duration so these are drugs that we could actually give to be able to increase again the duration of this nitrate effect so that's the concept behind these drugs so now we know the name of the drugs we know there are two mechanisms of action we know the adverse effects let's go back to the treatment algorithm because we're beating this thing like a dead horse we should know it by the end of all of this patient comes in with an acute anginal attack how do we treat them where does the long-acting nitrates short actin nitrates come into this picture all right my friend so now patient comes in acute angle attack how do we treat them acutely nitroglycerin that's why it's again it's sublingual transdermal so again this would be nitroglycerin it's going to be a cute kind of Vino dilation reducing pretty low stroke volume cardiac output and coronary artery vasodilation after that the first line prophylactic will be beta blockers this is beneficial in patients with hypertension patients who are post Mi be careful in diabetes COPD asthma again from these they're reducing heart rate reducing contractility beta blockers metoprolol atenolol and Propranolol if the patient still has refractory angina despite what we have just covered at this point then what do we move on to we can move on to the calcium channel blockers this would be beneficial if a patient has vasospastic or Prince Metals angina this is the non-dihydroperatings they reduce heart rate contractility they also can cause arterial vasodilation of the systemic artery system and coronary artery vasodilation the more potent vasodilators is the dihydropyridine such as nifedipine amlodipine they cause systemic arterial and coronary artery vasodilation which increases perfusion as well as the systemic reduces afterload reduces left ventricular work these will be beneficial patients who have underlying hypertension may be beneficial in patients who can't tolerate beta blockers and patients who have COPD asthma or diabetes avoid them post Mi because of increased mortality risk then if you don't want to do a calcium channel blocker for whatever reason such as their post Mi they just won't tolerate it for whatever reason then you can go on to another option is the long acting nitrates such as isosorbide dinitrate or isosorbide mononitrate I'll tell you though that isosorbent nitrate is going to be more commonly utilized one now in this situation when would nitrates be beneficial with other Associated comorbidities they may be more beneficial if a patient has some type of post-mi so if they're post-mi nitrates maybe not a bad idea so post to my the other thing is that these Also may be potentially beneficial and a patient who has diabetes and COPD because they don't alter the process of bronchospasm they don't have anything to do with hypoglycemia unawareness so they may be beneficial in patients who have COPD asthma again they have no effect on that process and then again they also may be beneficial in patients who have diabetes because again this will not cause no bronchospasm so that's why it may be beneficial and then again it causes no hypoglycemia on awareness so it has no effect on that so because of that again we're not going to see the type of problematic issue with these only thing I would be careful of is again they're not really good in hypertension so if you're trying to put a patient on a nitrate or has hypertension that's not really a great indication for these medications but that is the concept that I want you guys to understand so we now know the mechanism of action of these drugs we now know again the adverse effects we know how they work we know how we utilize them in patients who have angina what's a potential benefit to these again can be used post to my for symptomatic relief can be utilized because it's not going to cause any drug reactions or problems with bronchospasm or hypoglycemia awareness and these two diseases but they're not going to be great at hypertension they're just not the first line agents now that we've talked about that let's talk about the last category the refractory drug that you probably might not see very often at all renolazine all right my friends last drug is renolazine is actually pretty interesting it's kind of like a sodium channel blocker so how does a sodium channel blocker kind of like an anti-rhythmic really come in and help us out and with a patient who has angina you get whole concept of engine is you've got a patient here with a coronary plaque coronary plaque is kind of occluding the blood flow and that's reducing the oxygen supply to The myocardium so if there is a reduction in oxygen supply and a patient has an increase in demand for whatever reason this is going to create a mismatch it's going to make the heart not get blood and then have to work harder without less blood and it's going to precipitate ischemia how in the world is a Reynolds thing going to help out with this okay on the actual contractile myocardial cells there is sodium channels okay and what happens is on these channels we have this this sodium channel it's called a late inward sodium Channel and what happens is generally this channel will open up and allow for sodium to enter in when sodium enters into this actual cell what happens is then the concentration of sodium increases when it comes in Via this sodium Channel when it enters into the cell now what happens is the sodium concentration is going to be lower outside of the cardiac myocyte and then the higher inside of the cardiac myocyte so then the sodium is going to be utilized via this next transporter to pump sodium out and then subsequently bring another molecule in and this is going to be calcium calcium is then going to be utilized to work to stimulate the actual myofilaments to induce contraction of The myocardium now why is that potentially a problem so now this contractile cell will induce an intense contraction and this contraction will be sustained especially during diastole okay so especially during diastole what happens is ischemia patients who have some type of ischemic ischemic heart disease really accelerates the activation of this late inward sodium Channel and causes lots of sodium influx lots of calcium to move in Via this sodium calcium exchanger and cause increased contraction that's sustained and especially during diastole now that is an interesting concept why if this muscle is firing and it's Contracting intensely especially during the diastolic process during diastole your heart is supposed to get more blood flow that's really when the coronary perfusion is supposed to occur but in this situation who in patients who have some type of ischemic heart disease what we see is that this ischemia will increase contraction so it'll increase the stimulation of contraction of The myocardium what that's going to do is if that's going to cause the actual wall tension to increase especially during diastole so it's going to increase what's called your diastolic wall tension it's going to increase your diastolic wall tension since this muscle is going to be contracting so powerfully the tension that you're going to actually experience within that actual left ventricular wall is going to increase especially during diastole when you have that that diastolic wall tension goes up it's also going to increase the left ventricular in diastolic pressures as well so you're going to have an increase in diastolic wall tension and an increase in the diastolic pressures why is that problematic the reason why that's problematic is that if your tension is higher what it's going to do is Imagine here you have these coronary vessels let's actually get rid of some of these Plus hours here's going to be these coronary vessels that give feed into The myocardium when you have all of this tension what you're doing is you're squeezing and clamping down so if the diastolic wall tensions high if the left ventricular in diastolic pressure is high this is pushing and squeezing on these micro vessels of the coronary circulation now you're not going to get any coronary blood supply to The myocardium and that's going to worsen the ischemia right so you see how this is a problematic thing that it's just going to be this vicious cycle so this is going to compress the micro vessels so this leads to micro vascular compression and what that does is that worsens oxygen delivery and on top of that if you increase contraction increase wall tension increase left ventricular and diastolic pressure all of these three things are increasing your actual O2 demand so this right here is increasing O2 demand this is problematic right this is very problematic so imagine now I give the drug reynoldazine renolazine is going to inhibit this inward sodium Channel sodium will not be brought in let's do it in a different color sodium will not be brought in to the actual cardiac muscle cell so you're going to inhibit sodium entry if sodium is not in then we don't have the actual gradient to push sodium out and bring calcium in so then this exchange process will be inhibited less calcium will come in to the actual cardiac muscle cell less calcium means less contractility if I decrease the contraction of the actual cardiac muscle cell I'll decrease the sustained diastolic contraction what will that look like now so if I give renolazine now ischemia so I'm going to have a patient who has ischemia of their myocardium with renolazine the this one was without renolazine so this one is without renolazine what would this look like now to give it a different color here with reynoldsing what you're going to do is is you're actually going to inhibit or decrease the contraction of The myocardium that's going to reduce the O2 demand now the heart's not going to have to work as hard to pump blood out and also we'll do what subsequently if I decrease contraction that's sustained into diastole I'm going to decrease the diastolic wall tension so the tension within the actual ventricular walls during diastole is decreased subsequently if the tension on the wall is decreased the left ventricular end diastolic pressure will also be decreased if that's the case I'm going to have these micro vessels that are actually coming into The myocardium there's going to be less compression so if the actual left ventricular and diastolic pressure naturally and is in the diastolic wall tension is lower there's going to be less compression of the micro vessels if there's less compression of the microvasculature the coronary microvasculature why is that potentially beneficial microvasculature compression I'm not going to squeeze those small coronary arteries and that's going to improve the O2 delivery and that is going to help to do what I'm going to help too fix the O2 Supply so I'm actually going to inhibit the low O2 Supply and I'm going to decrease the increase in O2 demand and improve coronary perfusion by having less microvascular compression less diastolic wall tension less left ventricular and diastolic pressure all by inhibiting these late inward sodium channels within the contractile myocardial cells that's pretty interesting now this is the last line drug it's not a drug that we're going to give first because it comes with relative risk one of those is that there's a lot of drug interaction so you know your cytochrome p450 system so cytochrome p450 system so when we take particular drugs and we metabolize them right so here it's metabolized this has lots of drug interactions so significant drug interactions I would actually really really remember that there is an increasing risk of drug interactions here the other thing that would also be an adverse effect of this drug so one is a pretty profound drug interactions the other thing is that it prolongs the depolarization phase okay potentially a parts of the depolarization phase it's going to alter it so whenever well in general sodium channel blockers they can actually do something very interesting so sodium channel blockers when you look at the phases we'll talk about this in the anti rhythmic lectures but there has this ability to be able to prolong the QT interval which increases the risk of what's called torsods to points so because of that that is another adverse effect that you really want to be careful with but this is pretty common because this is a sodium Channel blocker so because it is a sodium channel blocker it's going to have this ability to prolong the QT interval and increase the risk of tors odds into points so watch out for that with renaultine so renolazine has the ability to inhibit late inward sodium channels inhibit sodium calcium exchange less calcium less contraction less contraction that's sustained during diastole especially that's going to reduce contractility of the actual myocardium reducing oxygen demand it's going to reduce the diastolic wall tension reduce the left ventricular and diastolic pressures less compression of the small microvasculature of the coronary circulation therefore we're going to have more oxygen distribution to the actual myocardium therefore we're going to have the ability to help minorly increase the O2 Supply and then decrease the O2 demand helping to reduce the degree of ischemia watch out for drug interactions and QT prolongation now how does this last algorithm fit in with reynoldsing so a patient comes in they have an acute angle attack how do we treat them nitroglycerin so given the nitroglycerin that's going to be the acute phase after that what's the first prophylactic medication beta blockers nitroglycerin again then first prophylactic medication beta blockers if they have refractory I'm just going to put these threads here inadequate relief despite the beta blocker then what do we do calcium channel blocker or another option would be long-acting nitrates Okay then if there's still refractory to all of these therapies then you give them ranolazine and that is how we will treat a patient with angina right now another potential benefit to renolazine since it is the last line medication is it may also be beneficial if the patient has some type of underlying arrhythmia if they have an underlying arrhythmia this is a sodium channel blocker so it may be potentially beneficial so watch for that but again now we know beta blockers reduce heart rate contractility reduce O2 demand calcium channel blockers the non-dihydropodium reduced heart rate contractility reduce O2 demand they also cause systemic arterial vasodilation reducing after the reducing oxygen demand they also do what reduce the revaso spasm and they actually can cause coronary artery vasodilation improving coronary perfusion nitrates what do they do they Vino dilate reduce preload stroke volume cardiac output and then reduce O2 demand but they also provide coronary artery vasodilation and lastly renolazine reduces inward sodium channels and then reduces sodium calcium exchange reduces contractility of The myocardium which reduces O2 demand it also reduces the contractility that's sustained during diastole which reduces diastolic wall tension reduces left ventricular and diastolic pressures which has less compression of the microvasculatures coming off of the coronary vessels and improves oxygen delivery and again treats ischemia Within These patients of angina again but it's last line now that we know this we've covered all of them let's do some questions now and some cases on patients who have angina all right so let's do some question so here we have which one of the following best describes stable angina so it's a plaque stable plaque they have reduced oxygen supply at The myocardium if there's an increase in demand or exertion or anything like that it's going to worsen the patient's ischemia so which one of these kind of supports that answer excuse me so angina occurs more frequently or with or with progressively less exercise or stress than before no that doesn't make that goes completely opposite angina is due to spasm of coin that's vasospastic angina due to increased myocardial demand which is reproducible and relieved by rest or nitroglycerin that's the answer so it's a patient who's having more demand and if you have them chill out rest calm down or give them Nitro to reduce preload and coronary vasodilate they will improve so it's definitely C and angina pain accompany by increasing serum biomarkers of myocardial necrosis no there's no troponin leak at all remember that I told you that's only with the acute coronary syndromes all right beautiful that should be see okay next one which medication should be prescribed to all angina patients to treat an acute attack I always told you that the first one has to be nitroglycerin so it always should be sublingual you can do a spray in the mouth and then if that doesn't work then you can do nitroglycerin patches so they can do potentially it's more like a paste actually like a paste or an ointment but they can put a patch over it but generally it's going to be nitroglycerin sublingual tablet or spray it's always going to be first line which are the following instructions important to communicate to a patient receiving a prescription for nitroglycerin apply the patch at onset of anginal symptoms for quick relief yes that's necessary that could be true remove the old patch for after 24 hours of use and immediately apply the next patch to prevent any breakthrough not necessarily do not use sublingual Nitro in combination with the patch that's definitely something you probably shouldn't do oh this is what we talked about the Whiteboard have a nitrate free interval to 10 to 12 hours every day to prevent the development of nitrate tolerance it has to be that that's always something that you should communicate to these patients to have a 10 to 12 hour free period without nitrate so reduce the kind of excessive stimulation of this guanola side glaze and improve and restore sensitivity okay 64 year old man prescribed a tenal which is a beta blocker and sublingual Nitro which is the again nitroglycerin after his recent hospitalization for unstable angina so an acute query syndrome which of the current medication should be discontinued remember I told you sublingual Nitros can cause intense hypotension in patients with a right ventricular Mi or they're taking some other medication that increases cyclic Gene PA like a pde4 inhibitor so the lexiled NFL Viagra so get away from that which will find correctly ranks the calcium channel blockers from most active on The myocardium to most peripherally active so in other words you want the drugs that are going to be non-dihydroperating calcium channel blockers those drop heart rate drop contractility that's going to be the ones that act in the heart and the dihydro period in calcium channel blockers those are going to be the ones that work on the peripheral vessels so if we're going off of that it should always be the Verapamil deltiazem should be more on the heart so those should be up front so right here and then nifedipine or amlodipine would be the peripherally active ones so it should be B 76 year old man with uncontrolled hypertension is experiencing typical engine of chest pain that is relieved with rest and sublingual Nitro he has a high blood pressure 178 over 92 a low heart rate so he has bradycardia which is the most appropriate therapy for his angina at this time so remember I told you it always nitroglycerin first and then a beta blocker what if they have a particular contraindication to a beta blocker such as their bradycardic probably wouldn't want to give that in this patient population why because if you give them a beta blocker you're going to drop their heart rate even more so I'd probably stay away from a beta blocker that goes to the next option so the next option is if you can't tolerate a beta blocker then it's a calcium channel blocker or a long-acting nitrate so we don't even have a nitrate option in here so that's not the case either so it's going to be a calcium channel blocker now which ones actually are the ones that drop your heart rate Verapamil deltiazam so I can't give these as well because this will drop the patient's heart rate and make them bradycardic so I can't give arapa milk because it's a non-dihydropyridine they can't give them a taupe these two will drop the heart rate even more they both can be used in hypertension but which one's even better in hypertension because it peripherally vasodilates and loaded paint so amlodipine is the other calcium channel blocker the dihydropyridine calcium channel blocker that will be good in this particular scenario because it treats hypertension just can't do a beta blocker because why the patient already has bradycardia can't do the non-dihydropyridine because they have bradycardia so it should be amlodipine all right 65 year old male experiences uncontrolled anginal attacks the limit is ability to household chores he's adherent to his maximized dose of beta blockers with a low heart rate and a low blood pressure he's unable to tolerate an increase in isosorbidden nitrate due to headache which is the most appropriate addition to his antiaginal therapy so if he has an acute attack he uses Nitro he's been on prophylactic beta blocker he's been maximized the next option is a calcium channel blocker or isosorbide dinitrate or mononitrate one of the long active nitrates they use long-acting nitrates patient must not be able to tolerate a calcium channel blocker so again it's either one or the other a long-acting nitrate or a calcium channel blocker they're on a long-acting nitrate so the long-acting nitrate has been maximized they have no other benefit now they're still having refractory angina what's the last line medication that we add reynoldazine beautiful 60 year old man with ischemic heart disease complains of angina pain that has been progressively worse over the past 30 minutes despite the use of nitroglycerin which is the following is the best course of action so this is a person having again progressively worsening anginal chest pain they definitely likely have are having some type of Mi whether it's an end stemi a again a stemi or maybe even an unstable angina these patients yes you can initiate metoprolol but they're likely probably having an active Mi so I wouldn't even bother initiating metoprolol for this person they're likely going to need the most important thing they've probably ruptured that plaque and they're at high risk of a complete occlusion to their myocardium and at this point I say that they need to get a catheterization to go in and actually open up that vessel so they need to go to the Ed immediately it's likely that they're having an acute coronary syndrome metoprolol could be initiated post um kind of catheterization but right now they're likely having some type of acute coronary event they got to go to the Ed which is correct regarding anti-anginal therapy in patients with heart failure where the reduced DF will beta blockers have an associate have been associated with a reduced mortality that's always the case beta blockers ACE inhibitors arbs are always associated with reduced mortality so I know that's the answer then diode repeating calcium channel blocker should be avoided yeah you really should be careful with these again we know that patients who have heart failure with a reduced DF or post Mi there has been associated with an increased mortality so yeah I probably wouldn't do that one beta blockers with intrinsic sympathomatic activity or Isa are preferred over those without Isa no any kind of intrinsics and pathomagnetic activity is definitely going to put a lot of strain on the heart so no that's not the best option and the non-dehydroperating calcium channel blocker should be used in patients with heart failure with a reduced EF fraction who cannot tolerate beta blockers no because it drops their pressure drops their cardiac output the answer is a beta blockers okay 45 year old woman with type 1 diabetes has been diagnosed with Prince metals and you know which the lung is correct regarding management of angina and this patient well first off Prince battles always responds good to calcium channel blockers and we've seen that patients who respond better on these calcium channel blockers actually respond much better to the dihydropyridine calcium channel blockers than the non-dehydroperating calcium channel blockers so that's one concept here so looking at these answers I gotta find the one that actually kind of tells or supports that answer beta blockers are the treatment of choice but should be avoided because of her diabetes again you can still get beta blockers of patients have diabetes but beta blockers are not the treatment of choice in patients with Prince Metals it's always going to be calcium channel blockers Nitro is not beneficial for this type of angina that's not necessarily true Nitro can be beneficial for any kind of antigenous she should be counseled to take nitroglycerin before physical activity to prevent symptoms no felodipine will be more effective than Verapamil well philodipine in general is a calcium channel blocker so is Verapamil but in this patient right here felodipine is a dihydroperating calcium channel blocker like amlodipine like nifedipine so it is going to be a very good drug so either one of those would be a good drug but definitely yes felodipine will be more beneficial than Verapamil that's just what the literature shows that dihydropyridine calcium channel blockers are superior than the non-dihydropyridine and vasospastic or Prince Metals angina so it should be D all right my friends that covers all of the cases and the questions that we talked about with anti-anginal medications I hope it made sense I hope that you guys enjoyed it and as always until next time [Music] foreign [Music]

Channel: Ninja Nerd

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Keywords: Ninja Nerd Lectures, Ninja Nerd, Ninja Nerd Science, education, whiteboard lectures, medicine, science

Id: kVGbMnSaI_g

Length: 84min 17sec (5057 seconds)

Published: Fri Oct 21 2022