Drugs for Heart Failure

foreign what's up Ninja nerds in this video today we're going to be talking about the drugs that are utilized in heart failure and there is so many of them and we're going to go through these in a systematic process okay but before we get started if you guys like this video you benefit from it you really learn a lot please support us and the way that you can really do that is by hitting that like button commenting down in the comment section and please also subscribe if you guys really want some great notes some illustrations

so you can follow along with me during this lecture because there's a lot to go over go down the description box below we got a link to our website where we have all these notes and illustrations you can check out all right without further Ado let's start talking about the drugs utilizing heart failure in order to really go through these drugs that are utilized in heart failure we have to understand the basic pathophysiology of heart failure okay so the reason why I think we need to talk about the pathophysiology of heart failures one it helps

us to understand the disease and what parts of the disease we're trying to treat but on top of that it really helps with the mechanism of action and some of the adverse effects and what's the best indications for this drug so there's a lot of things I think they can come from the benefit of discussing that so let's talk about that when a patient has heart failure there's obviously when we talk about heart failure there's two kind of like determinants of heart failure that looks at the ejection fraction and the ejection fraction is just basically

the percentage of blood that you're ejecting out of the heart compared to how much blood you have in The ventricle okay so whatever the volume is that you had in your ventricle the amount that you pump out that fraction that you pumped out is your ejection fraction and that can really be an important concept and so we can use heart failure in two different terminologies and that can be what's called so heart Fair can be divided into what's called a heart failure with a reduced ejection fraction and heart failure with a preserved ejection fraction half

ref and half path regardless of the type of heart failure these patients oftentimes have a decrease in cardiac output that's the same concept with heart failure is that regardless of the type of hefra half path these patients have a decreased cardiac output so the amount of blood so if we kind of take into consideration here here's their left ventricle the blood that they are pumping out of their left ventricle into their systemic circulation is less so this right here is going to be a decrease in their cardiac output that's the common theme between these two

types of heart failure regardless and left heart failure is the one that we're going to primarily focus on because the more common one and the one that actually has lots of complications so a patient has a decrease in cardiac output from their left ventricle what's the problem with that well generally you guys should know that there's a formula that comes with cardiac output and that is that blood pressure so your blood pressure is dependent upon your cardiac output times your systemic vascular resistance so let's say for example this patient has a constant systemic vascular resistance

but their cardiac output drops if cardiac output drops then what we can surmise from that is that it's going to also drop the blood pressure so because of that there's special receptors that are meant to pick up changes and pressure and they're located in these you know these sinuses so you have what's called your carotid sinuses and aortic sinuses and basically they pick up this change in pressure and whenever the pressure is actually low due to a reduction in cardiac output so what happens is this reduction in cardiac output leads to a reduction in blood

pressure and that really hammers on these types of baroreceptors and they really start to become in a way changed or modulated by this change in blood pressure what happens is this tells these baroreceptors to send signals to the medulla and it tells the medulla hey blood pressure be blood pressure be low out here my friends well I don't like it so what happens is when the blood pressure is low these Barrel receptors so what we're going to do is we're going to work on these things called Barrow receptors they'll be activated and they'll send signals

to our medulla now in the medulla there's going to be the cardiac kind of acceleratory centers and the cardiac inhibitory centers in the basal motor Center basically the cardiac and the vasomotor centers the centers that go to the heart and go to the blood vessels right when we activate this puppy what we do is we activate the sympathetic nervous system so now the sympathetic nervous system becomes activated and we increase the sympathetic outflow so we're going to increase the activity of the sympathetic nervous system what's the problem with that when you increase the sympathetic nervous

system that increases the release of norepinephrine and epinephrine onto three particular places so now we're going to do is we're going to increase the release of norepinephrine and then you also should know that whenever norepinephrine is released it may also be accompanied by another particular molecule made by our Adrenal medulla called epinephrine and so there may be an increase in norepinephrine as well as epinephrine now once these molecules are released and this is all due to the patient who has heart failure they're not generating a good cardiac output so it's activating these baroreceptors they're telling

the central nervous system hey blood pressure's low increase your cardiac acceleration and increase the squeeze of the blood vessels and we'll talk about the last thing that it does when it increased the norepinephrine release this acts on the heart and it acts on two components of the heart and really what I want you to know is it acts on very special receptors present on the heart these receptors that are present on the heart I really need you to remember this are called your beta 1 receptors and when you act when norepinephrine acts on the beta

1 receptors on the nodal cells it'll really jack up the patient's heart rate right that's one thing in an attempt to try to increase cardiac output and increase blood pressure on top of that it'll also try to work on the beta 1 receptors on the contractile myocardium and try to increase contractility because if I increase contractility I'll increase stroke volume and increase cardiac output that may sound good that's a compensation mechanism that the patients try to develop in response to their low cardiac output unfortunately it doesn't actually lead to any beneficial Improvement of cardiac out

but it actually can worsen the patient's disease now the question that you may have is how in the heck would me increasing the heart rate increase in the contractility be a problem over time chronic patients who are tachycardic and are constantly having to squeeze that myocardium constantly that's a problematic issue what does it really do well the problem with this is is that an increase in heart rate and contractility over a consistent amount of time is going to just consume tons and tons of oxygen so it increases the demand of oxygen that's a problematic issue

that's going to weaken The myocardium over time if it's having to constantly consume oxygen the other thing is if your heart rate is beating at a crazy fast rate do you think you get any time for diastole not really and you know what's the problem with diastole diastole is the time where the coronary arteries are perfusing blood to The myocardium all right so the other thing here is not only are you going to consume tons of oxygen trying to be able to get this heart to beat faster and contract harder but you're going to keep

it in having this constantly fast heart rate what that does is that really decreases the diastolic process and when you decrease the diastole time periods whenever you decrease diastole the time frame that time frame that you're in diastole you reduce coronary artery perfusion so you reduce coronary perfusion oh my gosh if I'm not giving my myocardium blood flow all right and I'm also causing it to work harder can you imagine how that would be a terrible situation over time that's going to put a lot of strain on that poor heart and that's going to weaken

it over time so this combination of an increased O2 demand decreased diastolic time period reducing coronary perfusion these are the things that actually leads to further weakening of the heart and further you know actual disease process the next concept that actually comes in here is that norepinephrine also acts on other receptors present on Our arteries this is going to be an artery so one of these arterial systems here and then it also acts on the veins so this would be of this venous system here now on these we're also going to have receptors but this

is a very important receptor that you need to remember so it was beta 1 on the heart this is going to be Alpha One receptors on the arteries and veins now why is that beneficial well if I have norepinephrine act on the alpha interceptors in the artery what that's going to do is that's going to squeeze the living crap out of the artery if the arteries squeezing the vasoconstrict what that does that increases your systemic vascular resistance if you increase systemic vascular resistance do you think that makes it easier for the heart to be able

to pump blood in order to get blood out of the left ventricle into the arteries do you think it's going to be easier you're going to face more resistance no because you're facing more resistance the afterload is going to go up so when there's increased systemic vascular resistance you jack up the patients after load why is that a problem now you're making it harder for the blood that's supposed to go from the left ventricle into the arterial system you're making it more difficult so what it has to do to compensate is it has to get

thicker to get stronger and so it undergoes something called left ventricular hypertrophy that's a problematic issue because you're going to lead to this heart having to work harder and you're going to cause to undergo remodeling processes which is dangerous to the heart increases mortality over time the other thing is it's also going to act on the veins and it's going to squeeze the veins so it's going to undergo Vino constriction so for this one it's going to go undergo Vaso constriction and then here it's going to undergo Vino so let's actually put this here make

this look nice and pretty so you're going to vasoconstrict the artery and that's going to be due to stimulation of the alpha 1 receptors and then on the veins you're going to produce Vino constriction and if you Vino constrict what you do is you squeeze blood up from the veins into the heart and so what that does is that increases your venous return if you increase venous return you increase preload that means that the amount of blood that's going to the heart is increased that means if the heart is already weak okay the heart's already

weak and it's already having a difficult time being able to accommodate the volume inside of it because it's not pumping as much blood out if you're not getting as much blood out where do you think it's going to go it's going to stay in the heart so it's already congested now you go ahead and try to fill it with more blood that it can't already tolerate guess what it's going to have to do to accommodate that volume of blood the extra volume it's going to have to dilate and so this may trigger what's called left

ventricular dilation so this is a problematic issue in this disease so you can see why this is a problematic thing it may be helpful because what your body is trying to do is squeeze the vessels to try to increase your blood pressure because your blood pressure is low it may squeeze the veins to increase preload increase cardiac output to increase your blood pressure because your blood pressure is low but at the end of the day it actually may cause more problems over time the next thing is it can actually act on the kidneys too so

whenever this low cardiac output drops your pressure activates your baroreceptors activates your sympathetic nervous system causes increased heart rate contractility vasoconstricts of the arteries Vino constricts for the vein system the other thing it does is it acts on the beta 1 receptors on the JG cells of the kidney so what are the receptors here this is the beta 1 receptors on the JG cell so I'm going to kind of like put these cells right here what are these cells here called These are called the J G cells when the JG cells are stimulated what they

do is they start to pump out a particular molecule you know what that molecule is called they actually start to make a molecule called renin renin then converts a molecule called angiotensinogen made by the liver into what's called Angiotensin one and then Angiotensin 1 is then later converted via an enzyme called Ace so we'll put this on here Ace it helps to convert Angiotensin 1 into Angiotensin two Angiotensin II though is a son of a gun and this thing likes to cause a lot of problems you know what it actually can do Angiotensin II can

act on all of these different areas here it can act on your systemic arteries it can act on your venous system it can also increase the production of ADH by the posterior pituitary and increase aldosterone production from the adrenal cortex and it can also act on the efferent arterial on these receptors here and cause what's called efferent arterial vasoconstriction there's a lot of different things that are going to happen here when it acts on Angiotensin II receptors it stimulates ADH production it acts on the arteries this is going to be an artery here my friends

and it's also going to act on the Angiotensin II receptors on the veins here my friends and what's the overarching thing that's going to come out of this it's going to act on the artery and it's going to make this artery squeeze like a son of a gun it's going to increase systemic vascular resistance it's going to increase afterload and on top of that you're going to increase left ventricular apertrophy because if the the pressure that the left ventricle has to overcome is higher then it's going to have to get thicker and stronger to generate

a higher pressure to push blood out of it into the arteries and so it has to thicken and hypertrophy which is problematic if you squeeze these Angiotensin II receptors on the veins so this is Angiotensin II receptor this is an Angiotensin II receptor you're stimulating these on the vein it's going to squeeze the vein that's going to increase your venous return that's going to increase your preload that's going to cause The ventricle to have more volume that it can already tolerate because it's not getting blood out so it's going to have to dilate and this

will increase the risk of left ventricular dilation the other thing is that if you have ADH and aldosterone that are increased you're going to stimulate the production of ADH you're going to stimulate the production of aldosterone these are going to go to the kidneys you know what they're going to do to the kidneys they're going to have you retain more sodium and water so less sodium and water are actually going to be lost into the urine and you're going to have more retention of sodium and water so I'm going to have more sodium and more

water that is retained so because of that what's that going to do to my blood volume if I have more sodium and water in my bloodstream I'm going to increase my blood volume guess what that's going to do that's going to increase preload have your ventricles contain more fluid than they already can are manage and so they're going to have to dilate it's why this is a problematic issue it's of a gun on top of that it also acts on the Angiotensin II receptors that are present here on the e-fan arterials so when your blood

pressure is low you're obviously because the patient's cardiac output's low because their Heart's Not generating a good enough ejection fraction or it's not filling properly that's the big difference between a preserved ejection fraction is it's usually due to decreased filling and then usually heart failure where the reduced ejection fraction is you have a decreased systolic function so you're in other words there's a weakening of The myocardium whereas this problem it's a decrease in the filling during diastole so that's why sometimes we actually refer to a half-peff as your diastolic types of dysfunction of heart failure

whereas the hefref is usually more of the systolic dysfunction in heart failure but either way your cardiac output is low your blood pressure drops these mechanisms are all trying to increase your blood pressure the problem is that when your blood pressure is low you don't perfuse kidneys and what Angiotensin II kind of tries to help with is to say okay if I'm not perfusing my kidneys and I'm not going to make good urine I'm not going to get rid of waste products Etc so I got to try to help the kidneys but it actually causes

undue harm to it so what it does is it tries to squeeze these efferent arterials so blood is supposed to go in via the affering material into the glomerulus and then generally you'll have a filtration process and it'll leave via the efferent arterial if I clamp down on this efferent arterial am I going to get blood to leave it the glomerulus no what's going to happen now is the glomerulus is going to start having a larger volume of blood and now the blood that's supposed to be leaving the glomerulus it doesn't exit as well what

happens to the pressure inside of this glomerulus now because when I vasoconstrict this thing I'm going to inhibit the exit of blood out of the glomerulus now the glomerular blood pressure is going to increase so my glomerular blood pressure is going to increase and this causes three problematic issues one is it's going to nicely help to increase the GFR so you're trying to make urine that's a good thing you're trying to clear creatinine you're trying to make urine you're trying to get rid of waste products the negative side effects though of this is that when

you increase the pressure you cause more proteins to leak out okay which is a problematic issue so you increase what's called proteinuria and then on the last thing is imagine this you know I'm trying to like just blow these glomeruli up that pressure is going to damage the glomerular basement membrane it's going to have to like thicken to be able to accommodate this high pressure when you put a particular membrane exposed to high pressure eventually it's going to have to accommodate what does it do it thickens why is this a problem if I thicken the

glomerular basement membrane I'm trying to protect my glomerulus if you thicken it and then you cause yourself to lose protein guess what that does that increases the progression or the risk of what's called chronic kidney disease problematic thing right so when we talk about patients who really have heart failure the basic pathophysiology is their cardiac outputs drop whether they're having systolic dysfunction or diastolic dysfunction they're not getting blood out of their heart that leads to a drop in blood pressure according to this formula when you drop blood pressure you activate baroreceptors activates your sympathetic outflow

tract they activate beta receptors and Alpha receptors increase your heart rate contractility increase the con the actual constriction of Our arteries and veins and then activate the renin angiotensinaldosterone system okay and that will lead to constriction of artery constriction of veins it'll also cause you to retain more sodium and water and on top of that try to be able to maintain some good urine output but it actually can worsen your kidney disease you know what else is really interesting JG cells not only respond to the sympathetic reflex so there's two reflexes here one is you

can stimulate the JG cells via The beta-1 receptors the next thing is that when you have a reduction in cardiac output you don't perfuse the kidneys as well that can also be a stimulus so the JG cells can be stimulated by two particular reasons one is sympathetic outflow via the beta 1 receptors and the second one is they can directly be stimulated by low perfusion pressure so when our cardiac output drops it's going to drop yes the blood pressure and guess what that means that the perfusion to the kidneys is reduced and so the kidneys

are going to be like hey man the blood pressure's low we're not perfusing me I got to increase my blood pressure so what do I do what does it do you want to do me it increases your Angiotensin II process to try to increase your blood pressure and help you to make urine so you see why that's a protective reflex the cool thing about this concept is we can give drugs to really block the beta receptors and we can give drugs that maybe even have if they're beta blockers they maybe have a little bit of

alpha blocking activity so we'll talk about that drug category the beta blocker category and they may be helpful in this particular situation we can give drugs that inhibit the renin angiotense and aldosterone system and they may be able to inhibit all this negative processes you know what else there's interesting things about you know when the poor heart is super weak right it's struggling it's struggling to get out blood and all it's doing is it's just filling and filling and filling it's stretching more than the waistbands of my sweatpants on Thanksgiving day and what happens is

as it stretches and stretches and stretches because of why when a patient has a low cardiac output you're going to increase the What's called the volume of blood in the heart right so there's increased volume in the left ventricle so because of that I'm not getting blood out of the heart it's going to stay in the heart and this is going to be kind of like an overload or like a congestion of the ventricles you know what this does this this screams it's like the waistband they're screaming right and what happens is this ventricle myocardium

says man I can't tolerate all this volume we got to get rid of this volume and so what it does is it stimulates the ventricular myocardium and it starts pumping out a very interesting molecule you know what this molecule is called it's called B in P being brain nature peptide you know what brain nitratic peptide does it's actually really cool it just goes and opposes Angiotensin II so all the Angiotensin II effects that we just talked about BNP will inhibit that so wouldn't it be really cool if I had a drug category that would work

in some way to increase BMP absolutely and we'll talk about that drug category there is a drug category that can work to increase BMP because the problem is when the ventricles are overloaded they try to increase the production of the BMP and then think about why is this kind of cool why is this a cool concept if I increase BMP I'm going to inhibit Angiotensin too now think about all the downstream effects of that if I inhibit Angiotensin II I reduce my afterload and I reduce the thickening of The myocardium I reduced venous return reduce

preload now reduce the dilation of The myocardium again this is preventing remodeling of the heart I inhibit ADH and aldosterone so I reduce sodium and water retention which reduces blood volume preload you know what else here is if a patient has all this like high blood volume they also can increase the risk of Edema right because you're having a lot of like venous congestion and that can really cause edema if I do that I actually cause them to pee out sodium and water so I dilate their arteries I dilate their veins I cause them to

pee out sodium and water so they don't retain it reducing their edema and their preload and their dilation and I also inhibit the efferential Ethan arterial vasoconstriction which reduces proteinuria and reduces thickening of the GBM so that's a really cool concept but that's the big thing so we've talked about a couple drugs how they can really Target them we'll get into more detail we talked about the beta blocking system with maybe some that have a little bit of alpha blocking activity we talked about the Rand and angiotensinaldostron system Inhibitors we talked about the drugs that

maybe we'll be able to increase the BMP process and inhibit the random angiotensinaldosterone system there's some other drugs that we'll have to talk about and these are really interesting and we'll talk about them a little bit later but we might have drugs that don't work on the alpha-1 receptor or the uh directly they may actually work on the smooth muscle itself of the veins and the arteries and dilate them we'll talk about those later these are called direct acting vasodilators so in other words they don't work to block The alpha-1 receptors they don't have a

very specific receptor they just dilate arteries directly and we'll talk about those a little bit later the other problem here is when a patient has less cardiac output right so you have a reduction in cardio Capital yes a lot of volume can stay in the heart but you know what eventually this poor ventricle it's going to be able to not hold on to much more volume and so what happens is if it can't hold on to much more volume where is it going to start going into the left atrium and then it's going to back

up into the pulmonary venous circulation if it backs up into the pulmonary venous circulation what's that going to lead to pulmonary edema if I start causing fluid to accumulate here in the actual lungs I'm going to start causing pulmonary edema and this is due to high Venus there's lots of venous congestion so my pulmonary venous system is going to start becoming congested with flu because I can't get the dang fluid out of my heart so it's going to start backing up you know what else if the patient has terrible sided right heart failure right maybe

the left heart's causing the left heart to fail okay because if you're not getting blood out of the left heart it's going to back up into the right heart and the right heart will start feeling if that starts failing it only can hold on to so much of this fluid that it starts backing up and starts going into the jugular veins causing them to distend or back up into the inferior vena cava and then what will that do if it starts blocking up in an inferior vena cava and starts going into that those poor those

poor feces they're going to get all kinds of swollen and if they get swollen this can lead to peripheral edema so that's an important concept to understand so again I want you to understand if a patient has a low cardiac output yes they may congest their heart increase their BMP production but if they also have a lot of volume in their heart eventually it's going to start backing up into their venous circulation if it backs up into their pulmonary venous circulation it'll cause pulmonary edema if it backs up into the lower extremity circulation it'll cause

peripheral edema so these are possibilities that you can see with a lot of venous congestion and you know what I could do to actually reduce venous congestion we'll talk about this a little bit later diuretics when diuretics come in guess what they do they rip sodium and water out into your urine they reduce your blood volume they reduce your Prelude so they reduce the more volume inside of the heart they reduce venous congestion and they help to reduce some of the pulmonary edema and peripheral or lower extremity pitting edema that's a cool concept now the

next thing I have to talk about here is if a patient has a reduction in cardiac output what's another particular problem why is this such a bad thing well we know that it could actually cause congestion pulmonary and systemic venous congestion but if I don't push blood out of the heart I know that it'll drop the patient's blood pressure and cause all these compensation mechanisms but what I'm really trying to get at is what's the problem with me not getting blood out of the heart why don't perfuse and what's that decrease in perfusion look like

let's come down and talk about that so that's that that's the concept right the patient is not pushing blood out of their left ventricle so if I'm not getting blood out of my left ventricle I'm not feeling my arterial tree so my systemic arterial tree is not being filled with blood so if there's a reduction in cardiac output there's technically a reduction in your perfusion pressures right which we can actually refer to as the mean arterial pressure right and so we can kind of say that the patient isn't perfusing if you don't perfuse then you

don't deliver blood to very important organs and what could this potentially look like well one thing is it could literally put the patient into fulminant like cardiogenic shock so the worst case scenario the worst case scenario here is if the patient's cardiac output is so dang low that they're barely getting any blood out of their heart their mean arterial pressure and perfusion pressure could drop so low that it puts the patient into something called cardiogenic shock and this is a terrible situation right very high mortality rate with this type of situation here so this would

be a very sad type of situation here that you don't want to see and we'll go over how you would really identify and manage this a little bit later but the other concept here is that we don't perfuse let's say that the perfusion isn't as bad where you're actually at risk of like cardiogenic shock and then that can lead to like multi-system organ failure and obviously death but if you don't profuse things like the skin then you got skin you get like cool uh pale skin right so if you go and you actually try to

you know look at the patient's skin maybe they have modeling of their skin maybe it's very cold to the touch maybe it's very pale because they're not perfusing that extremity that's a problem on top of that if you don't perfuse the kidneys then you lead to a decrease in the actual urination right so you're not going to perfuse those and then you increase the risk of an acute kidney injury that's terrible who wants to end up with not being able to make urine and end up with an acute renal failure that's a problematic issue the

other thing is if I don't deliver oxygen so if I don't perfuse I don't deliver oxygen to other organs especially my skeletal muscles imagine having your skeletal muscles not having oxygen if I don't give my poor skeletal muscles oxygen what's going to happen to them one of the big things is that they're going to become weak and this really causes the patients to develop like fatigue so you can become disc on exertion you can become super fatigued just like walking a little bit a couple steps this can be really problematic issues here so we really

want to be able to think about if the patient isn't perfusing this is the terrible situation that we could potentially see so how do I actually go about managing these patients we'll talk about that a little bit later whenever you have a problem who a patient's becoming super congested and they're having a decreased perfusion that's an acute heart failure that we have to be able to recognize and we'll talk about that a little bit later but we talked about drugs that block the beta their beta blockers running Angiotensin system Inhibitors drugs that increase the BMP

drugs that help to reduce venous congestion a lot of the pulmonary and peripheral edema effects there's also drugs that we'll talk about a little bit later that I can actually directly stimulate the heart and try to get it to squeeze more and push more blood out especially utilize when patients are in cardiogenic shock or refractorate a lot of the other therapies that we'll talk about we'll talk about positive inotropic agents a little bit later but I think the the big question is is like if a patient has these problems that we've discussed so we we

listed a lot of things here so whenever a patient has heart failure whether this be due to heart failure with reduced ejection fraction or preserved there's just a lot more data on the reduced ejection fractions that's why we talk about that one a lot but in general we know that the patient has a decreased cardiac output and all of these compensation mechanisms that we saw so then this leads to all those compensation mechanisms and what were some of those compensation mechanisms it was increasing heart rate increasing contractility what was the basic concept though if I

if I had a patient who I was increasing their heart rate and I was increasing their contractility why is that a bad thing I already told you that this is going to lead to an increase in O2 demand because I'm going to have this poor muscle beating fast Contracting hard utilizing oxygen that's a problem and it's already weak and on top of that I'm going to decrease coronary perfusion so now I'm not going to give the dang muscle the oxygen that it needs and give it the blood flow that it needs that's a problematic issue

on top of that you can have patients who have a lot of left ventricular hyperch if you do excessive afterload and you can have patients that have an increased left ventricular dilation due to lots of preload and being over volume congested this situation here where you have a patient who has an increase in heart rate increase contractility a lot of left ventricular dilation left ventricular hypertrophy all of these things what they really do to a patient is they really just collectively increase the patient's mortality this all increases mortality and also increases the morbidity so one

of the things that I need to be able to think about is how can I treat patients to help them reduce their mortality and reduce their morbidity what are the drugs that are really really good at reducing the left ventricular hypertrophy left ventricular dilation reducing contractility reducing the heart rate and which will provide some actual true benefit to the patient and then which are one of the other ones that I can really add on as a symptom control and then what's the drugs like I have no other option I'm refractory at this point and to

all the other medications I just need something to help them the best I can we're going to go through each one of these and we're going to start with the beta blockers were they going to go to the drugs that actually inhibit the rain and Angiotensin aldosterone system then we're going to go into the drugs that increase BMP then we're going to go into the drugs that actually reduce the actual venous congestion then we'll go into some other refractory drugs so drugs that usually are going to be utilized in patients who are refractory to a

lot of therapies like I have a braiding digoxin a lot of other positive ionotropes so let's actually go through these systematically step by step talk about those drugs what do they do in a Teensy bit more detail and then what are some of the indications for them in adverse drug reactions let's get into it all right so now we're going to move into this first category the beta blockers now beta blockers there's a bunch of different types of these we're really only going to talk about just a few that have actually been shown to be

beneficial and reduce mortality in patients who have CHF now what are some of these beta blockers all right the first one is the selective beta blockers in other words they only block the beta 1 receptors on the heart and on the JG cells of the kidney what are those this is going to be metoprolol which is a very commonly utilized one but I want to add on here metoprolol there's two different types there's tartariat which is really good in patients who have hypertension and then there's succinate and succinate which is more kind of like an

extended release it's actually been shown to be more like Superior to tartarian patients who have heart failure so here's how I remember metoprolol succinate is good in patients whose Hearts suck it's just how I remember it so when you think about metoprolol think about metoprolol succinate it's better and then the other one that may be utilized but is less you know effective I would say is bisoprolol and then the next thing is you have another drug that has beta 1 blockade but it also blocks The alpha-1 receptors that are present on the arteries in the

venous system and this one's actually been shown to be very very good and this is called Carvedilol so Carvedilol so don't forget about these drugs now what I really want you to take away is that these drugs have the ability to reduce mortality that's huge so these are a reduction in mortality these types of drugs here which is a great great drug that you want to put your patients on now what do they do okay it's we've already talked about this so we should be very very quick all they do is again all of them

are going to block The beta1 receptors that are present on the nodal system so the AV node essay node all that kind of stuff like that they work on those beta 1 receptors so in other words if I give these drugs they're going to bind onto the beta 1 receptors on the nodal cells and on the contractile cells and what are they going to do they're going to block them so because of that generally whenever epinephrine norepinephrine is supposed to work on these we're going to block that okay so you're not going to be able

to get that effect so generally when narpinephrine hit the beta 1 receptors it increased heart rate in this situation we're going to decrease heart rate on the contractile cells it was supposed to increase contraction on this situation here we're going to decrease the contractility boom and by doing that by reducing the heart rate reducing the contractility you reduce that constant oxygen demand and consumption and you actually allow for better coronary perfusion because you prolong the heart rate so if you slow down the heart rate you actually allow for a longer diastolic filling process and that's

beneficial so this is one particular way that you can see potential benefit here so again I want you to remember that in this particular situation just to make this a little bit more pretty here again we are going to decrease contractility and we're also going to reduce heart rate the other concept here is that you also are going to have JG cells and those JG cells that are located on the kidney are also going to have what type of receptors on them they're also going to have beta 1 receptors and so since they have beta

1 receptors you're going to give these drugs and they're going to block those beta 1 receptors that are present on the on the JG cells of the kidney if I block the beta 1 receptors that are present on these cells what do I do I reduce the renin production so therefore I'm going to inhibit the renin Angiotensin aldosterone system all the negative connotations that we saw with Angiotensin II such as increasing resistance increasing venous return causing again problems with increase in ADH and aldosterone causing the increase in the efferent arterial vasoconstriction we're going to inhibit

that process so that's a pretty cool concept just they're not going to be as powerful as the Director in energy tense and aldosterone Inhibitors so that's the concept here now the Carvedilol we can add one more thing on so Carvedilol is really cool so this is only going to be applicable to the Carvedilol so on the venous smooth muscle cells what we're doing is I'm taking a piece of the venous smooth muscle cell and I'm zooming in on it here and I'm taking a piece of the arterial smooth muscle so and I'm zooming in on

it here on these receptors we have Alpha One receptors when you give a drug like Carvedilol it's the only one out of these beta blockers that are going to have the ability to bind onto the alpha-1 receptors and normally when norepinephrine wants to bind onto these what does it want to do it wants to act on the arteries to cause vasoconstriction increase the semifascular resistance and increase afterload if I give this drug to actually block The alpha-1 receptors it will reduce what the systemic vascular resistance that will reduce afterload and that will reduce the left

ventricular hypertrophy and that's a beneficial concept for the venous smooth muscle what am I going to do I'm actually going to do what in this situation let's actually go this way so with the venous smooth muscle cells if I actually inhibit them I'm going to lead to a decrease in what I'm going to lead to a decrease in the preload because I'm in a vino dilate I'm not going to venous constrict so I'm not going to push as much blood up into the heart now if I reduce preload what's that going to do that's going

to reduce the left ventricular dilation and that's a potential benefit so you see how when I give beta blockers the primary beta 1 blockers like metoprolol bisoprolol and then Carvedilol has beta 1 blocking it's going to reduce heart rate reduce contractility and inhibit the rain angiotensinaldosta system but Carvedilol the only one has Alpha One blocking activity so it'll block the actual norepinephrine on the Alpha interceptors and the veins reduce venous constriction reduce preload reduce the dilation effects you're not going to have as much volume going into the heart and it's also going to relax the

arteries which reduces the resistance in the afterload and has The ventricle not have to thicken to accommodate to that that's a cool concept all right now with that being said why would I give these drugs what is the benefit of a beta blocker they're great in heart failure with a reduced ejection fraction right so if a patient has heart failure with a reduced ejection fraction these are pretty decent drugs now if a patient has heart failure with reduced ejection fraction and on top of that their post Mi because what we know is when patients are

post Mi beta blockers actually have been shown to reduce mortality in that particular scenario plus if a patient has coronary artery disease so if a patient has coronary artery disease that also may be a potential benefit so if they have a heart failure with reduced ejection for Action plus or minus if they have post Mi plus or minus if they have coronary artery disease these are good situations why because in all of these they've been shown to be beneficial and potentially reduce mortality that's a good thing the other concept here of why we would want

to give this drug okay for patients is not only has it been shown to be beneficial in patients who have a reduced ejection fraction who are post to my own coronary heart disease is here's what's really interesting and I used to get really confused and this seemed to be complicated but in this patient it will eventually improve their ejection fraction so initially initially when I first when they first start the beta blocker so initially there will be an initial decrease in the ejection fraction why because when you start a beta blocker you're going to reduce

the heart rate reduce their contractility which yes in the first in the beginning so early this will actually drop their cardiac output but over time over time it will increase their cardiac output because their heart is going to start to improve it's not going to be working so hard to consume oxygen it's going to get better diastolic filling you're also going to see the benefit from this drug over time where initially you'll drop your EF but over a certain amount of time the patients will have a increase in their ejection fraction I've seen it a

lot and it's actually pretty astonishing and I think one of the bones that you'll see the most benefit from is going to be Carvedilol According to some of the studies but again metoprolol succinate is also a very very good drug so that's something to think about now one of the downsides to these drugs is thinking about the adverse effect think about it and a patient who has a who has the ability to drop their heart rate what's an adverse effect to that it can cause bradycardia so watch out for bradycardia the other thing is it

can drop your contractility so if a patient has decompensated heart failure do not give it to them hold that drug because it could potentially worse their decompensation and drop their cardiac output and put them into shock the other thing is it can hit the beta 2 receptors in the lungs and cause bronchospasm so generally whenever you act on The beta2 receptors on the bronchials they dilate if you block them you're going to spas in them the other things that generally when a patient becomes hypoglycemic um generally so whenever you become hypoglycemic you actually develop kind

of a sympathetic reflex to alert your body that you have hypoglycemia but whenever you give them a beta blocker you actually blunt that sympathetic reflex and they won't become aware they don't become tachycardic and you know they usually become diaphoretic have this sense of impending doom so they have hypoglycemia unawareness so this is an important concept to be cognizant of in these particular patients with beta blockers so again know the mechanism they reduce heart rate reduce contractility which may seem odd because you think oh they're going to drop the patient's cardiac output so they're going

to drop their blood pressure initially yes they will drop the patient's cardiac output but over time you will start to see a benefit of this drug because it's going to reduce oxygen demand it's going to reduce the actual time for it's actually going to sorry prolong diastole improve coronary perfusion and that's going to allow for the heart to heal and eventually start to regain an improvement in the EF okay so that's something to think about and it's especially good in a patient who has heart failure with a reduced ejection fraction who has post Mi so

they just had an MI or they have coronary artery disease it's been shown to be beneficial and reduce mortality in those patients so think about that just watch out for the adverse reactions and then don't forget Carvedilol is special that it blocks The alpha-1 receptors on the arteries and veins so it can also in addition to dropping the heart rate contractility it can also reduce afterload and reduce preload which is a pretty cool concept okay now that we hit the beta blockers let's go into the next category of drugs which is the drugs that inhibit

the renin angiotensinaldoctrine system so the Renaissance system Inhibitors all right so these are really good drugs and again what did I want you to know I want you to know the drugs that actually been shown to reduce mortality beta blockers happen and then as well as Roz Inhibitors so these are really good drugs to utilize in patients who have heart failure so it does reduce mortality by reducing a lot of that left ventricular remodeling decreasing the left ventricular dysfunction reducing a lot of the fibrosis inflammation of the actual myocardial tissue and again helping to improve

ejection fraction so there's three drug categories here ACE inhibitors arbs and aldosterone antagonists so ACE inhibitors these are going to be your prills so Lisinopril is a pretty good one I'm actually a pretty good fan of the captive Pro I do like that one um enalapril and then there's a lot of other ones benzopril we can just keep going just think about the pearls arbs is the next category so these are the zart hands and so um Lazar Tan's a pretty good one I'm actually a pretty big fan of valzar tan I do like this

one and then candizart tan but again the whole concept is if you're confused think about these zart hands I think is the the easy thing to remember and then the aldosterone antagonist there's a spironolactone and then another one that I've actually come to like as well if you utilize it is called eplerone so eplerone is also another decent agent so we have all these different drugs right we got the ACE inhibitors the arbs the aldosterone antagonists now how do they work we've already kind of hit that they're inhibiting the written age intensity aldosterone system but

to quickly quickly kind of recap kidneys either due to beta 1 receptor stimulation or due to a reduction in cardiac output so it's either you're pumping norepinephrine under the beta 1 receptors or your reduced cardiac output is not perfusing these JG cells and they pump out renin renin we know converts angiotensinogen into Angiotensin one and then Angiotensin 1 is acted on by an enzyme called Ace angiotensic converting enzyme and converted into angiotensin two and you have lots of this Angiotensin II and what we know is that Angiotensin II will do a couple different things we're

going to have it act on the arteries and when it acts on your systemic arteries what does it do it increases systemic vascular resistance and therefore it'll increase your afterload and therefore it's going to increase left ventricular hypertrophy so that's one concept it'll also act on the vein all right when it acts on the veins it's going to increase venous return it's going to increase preload and then it's going to cause an increase in left ventricular dilation because it's going to have to accommodate for that the other thing is that it's going to act on

increasing ADH and it's going to stimulate the production of aldosterone via the adrenal cortex and then ADH from the poster pituitary and then they're going to go to the kidney and they're going to increase the reabsorption of sodium and water if I reabsorb more sodium and water I'm going to increase blood volume and that can do two things one is it's going to increase preload and increase left ventricular dilation but it also can increase the risk of edema okay and then on top of that Angiotensin II is also going to act on the efferent arterial

squeeze the living crap out of it and then what's that going to do if it squeezes this efferent arterial it's going to cause the pressure inside of the glomerulus to increase the glomerular blood pressure will go through the roof as a result what what are the three things that happen as a result you'll increase GFR you'll also increase proteinuria and then lastly you'll thicken up that GBM because it's going to be a lot of high pressure it's going to have to accommodate okay now you're wondering how in the world do these drugs come into play

don't worry got your back Ace ACE inhibitors if I inhibit this enzyme if I give an Ace inhibitor so this will be which drugs here let's actually do them in red here so Ace Inhibitors they're going to inhibit the ace enzyme what do you do to the Angiotensin II levels you drop the angiotensin two levels if you have less Angiotensin II do you act on the arterial system no so what happens to the systemic vascular resistance it reduces what happens to the afterloe it reduces what happens to left ventricular hypertrophy it reduces does it work

on the veins and Vino constrictum no it Vino dilates them that reduces the venous return that reduces the preload and that reduces the left ventricular dilation effect does it increase ADH and aldosterone production no so it actually decreases ADH decreases aldosterone production leads to decreased sodium and water reabsorption leads to a drop in the blood volume and that will reduce preload reduce left ventricular dilation and reduce edema is it going to construct the efferent arterial no it's not going to constrict the afferent arterial it'll actually vasodilate that'll decrease the GFR which is the only downside

it'll actually decrease protein urea which is a good thing and it'll decrease the thickening of the GBM which will decrease the progression of chronic kidney disease so this will decrease chronic kidney disease these two things okay that's the concept of ace inhibitor so we just Crack the Case on that okay what about the aldosterone receptor blockers right I'm sorry the Angiotensin receptor blockers well on each one of these sites here let's do it here in Blue on the artery there's an Angiotensin II receptor on the vein there's an Angiotensin II receptor on these receptors on

the posterior pituitary there's receptors for uh Angiotensin 2 to simulate ADH and to stimulate aldosterone and then here is going to be let's just actually change the color of it here is going to be a Angiotensin II receptor on the efferent arterial if I give a drug like a ARB what am I going to do and ARB is going to block Angiotensin II here at this receptor and R was going to block it here and R will block it here at the ADH it'll block it here at the aldosterone and it'll block it here at

the efferent arterial so effectively even though Angiotensin II may be present you're going to block its effect at every single one of these sites it's the exact same thing that you would get if you had less Angiotensin II so because of that you should see a drop in the resistance the afterload the left ventricular apertrophy less preload left left ventricular deletion less sodium water retention less blood volume preload less edema and dilate the efferent arterials it shouldn't thicken it should actually decrease protein area and unfortunately increase I'm sorry decrease the GFR but that's the effect

of arbs so arbs are going to be working at the receptor site okay so they're going to be working at the receptor site okay cool the last drug category is aldosterone antagonists what do you think it's going to do if I were to really zoom in on the kidney cells in the kidney cells there's a receptor so if I were to take and like zoom in on where the actual Doctrine is working here's going to be a cell here and what happens is in order for sodium and water to be reabsorbed aldosterone has to be

able to exert its effect here on this like receptor inside of the cell okay so here's aldosterone okay in order for it to exert its effects to be able to have this effect on sodium and water increasing sodium and watery absorption ADH has to bind onto this receptor to elicit this process if I give an aldosterone antagonist like spironolactone and eplerone guess what I do I block I block this aldosterone from binding to the receptor which leads to less sodium and water reabsorption drops the blood volume drops the preload drops the ventricular dilation and reduces

the edema effect this is the only one that would be for aldosterone antagonist so I'm going to put a a here okay so we see now how these drugs particularly work when would they be useful in patients who have heart failure every single patient so this is generally it's important to remember that this is going to be your first line and what I mean by first line is I'm talking very specifically your ACE inhibitors or your arbs that's very important it's one of the other you can't be on both of them but these are first

line the adoption antagonist you can already tell from the mechanism but only blocks this one part right so if it only blocks one part it's probably not as good as they snippet in the RB yeah that's probably true so because that ACE inhibitors and arbs are going to be superior and they're going to be your first line drug especially if the patient has heart failure with a reduced ejection fraction again we're coming to realize that the evidence a lot of the evidence done in the past was done on patients who had a reduced DF it's

good in patients who have a heart failure with a preserved ejection fraction as well so just realize that we just don't have enough evidence on that yet but they're good for in general a patient with a heart failure it's just we know the evidence supports reduce DF and if they have hypertension because these drugs reduce afterload what are you going to do when you reduce afterload you actually reduce blood pressure whenever you reduce resistance you actually do reduce blood pressure and so because that if I reduce resistance I will drop the patient's blood pressure because

cardiac output is dependent upon heart rate I'm sorry a cardiac so we know that sorry blood pressure is equal to cardiac output time systemic vascular resistance so if I drop a patient's resistance what am I going to do I'm going to drop there blood pressure so that's one of the cool things about this drug is it should be utilized in patients who also have hypertension which is usually a very common risk factor in etiology of heart failure anyway but that's one thing to think about we want to give ACE inhibitors or arbs their first line

in patients who have heart failure plus they have hypertension what about the arbs so I'm sorry the um aldosterone antagonist aldosterone antagonists are really an add-on therapy so they are going to be an add-on so let's actually put that here so they're an add-on therapy what does that mean generally a patient is on an Ace inhibitor or an ARB but they're still having a reduced ejection fraction okay or they're still symptomatic so if a patient has an Ace inhibitor or an ARB on and they still have a low EF and they're symptomatic then you put

them on an aldosterone antagonist okay and we'll go through this whole process step by step but again that is going to be one of the indications for the aldosterone Tigers they're not going to be first line they're generally going to be a drug that you add on to an Ace inhibitor or an ARB if the patient's still having symptomatic heart failure and on top of that they're still having a reduced ejection fraction and we'll talk later about another benefit to this drug but let's come to the next thing what is the downsides to these drugs

okay with ACE inhibitors there's one particular thing not only do they inhibit the Angiotensin II formation but you know what else they inhibit there's a molecule here called bradykinins and bradykinins are supposed to be broken down by Ace and then they usually make like this inactive metabolite but whenever you give an Ace inhibitor it actually inhibits the breakdown of bradykines the problem with that is is if you build up bradykinins guess what they do they cause a lot of vasodilation of the capillary system and they cause a little bit of increased capillary permeability you know

what the problem with that is this increases the risk of having a patient like with a dry cough and it also increased the risk of what's called angio edema and you really only see that with the ACE inhibitors so watch for that for ACE inhibitors and so now we come to this part so this part of the Cascade we see this effect with asymmeters but now we come down here so we can still see the effect of an Ace inhibitor down here and an ARB down here at this point so what you may see here

is coming to this part so ACE inhibitors will drop the Angiotensin II and then arbs will block the angiotensin two so same effect if you drop a patient's GFR does that mean what happens to their creatinine clearance it decreases because of that if you actually decrease creatinine clearance what's going to happen to the patient's creatinine it may bump so watch for an increase in creatinine for these patients as a potential complication or adverse reaction one more thing Angiotensin 2 is supposed to act on aldosterone okay axon aldosterone and so if I give an Ace inhibitor

or a given ARB either way I'm either decreasing Angiotensin to or blocking Angiotensin II so I drop the aldosterone what's the problem with that guess what aldosterone does it increases pseudonym and water retention and causes potassium excretion so what would I see as a result if I inhibit aldashrin I'm not going to reabsorb sodium in water but I'm also not going to excrete potassium what happens to the potassium in the blood it goes up so watch out here because of the effect on blocking aldosterone you can see hyperkalemia okay another thing is with aldosterone antagonists

they directly block aldosterone so you're going to reduce sodium it'll actually reduce sodium water retention but you'll also inhibit potassium excretion so potassium hyperkalemia can be seen with ACE inhibitors it can be seen with arbs and it can also be seen without aldosterone antagonists both ACE inhibitors and arbs you'll see a reduction in the GFR and an increase in the creatinine and only with ACE inhibitors will you see the angioedema and dry cough due to the increased Brady kindness okay the last thing is I would actually just add on just be careful and usually contraindicated

to give ACE inhibitors or arbs to patients who are pregnant that's another thing is that ACE inhibitors arbs they are contraindicated in pregnancy they are what's called teratogenic do not give these Sons of Guns to those patients okay we got the Raz Inhibitors down now okay now all we got to do is we got to go over the drugs that actually help to increase BMP which kind of actually indirectly block this pathway let's talk about that all right increasing DMP how do we do it well I told you that BMP is a good thing right

so when a patient has all of this excessive kind of like congestion within the heart because they have a low cardiac output they got this low cardiac output so they're just not getting blood out of their heart and so it's sitting there and stretching this poor myocardium you know like like the waistband of my sweatpants on on Thanksgiving day all right I eat baby all right what happens is your ventricular myocardium when it stretches like that it says oh my gosh I gotta start pumping out some BMP and so it increases this molecule called BMP

brain naturetic peptide what happens with BMP is we already know that it's supposed to go and work to specifically inhibit this random angiotensinaldosta system because it just blocks every site of Angiotensin II but here's the downside BMP has a very kind of like interesting Pac-Man structure that likes to break it down all right this molecule here is called nephrolysin called nepra lysine and what neprolysin does is it takes BMP and it breaks it down all right so it takes this BMP and it breaks it down into an inactive metabolite so basically it's no longer effective

that's what the neprolysin is going to do so the nephrolysin works in this step to be able to break down or catabolize the BMP now if I had a drug that could inhibit the nephrolysin wouldn't that be an interesting concept guess what we got one so one of the drugs that I'm going to give here is called succubitril so it's called circubatoril and one of the cool things about circuitry is circuitry is actually going to be in neprolysin Inhibitors what it's going to do is it's going to inhibit neprolysin and so in other words instead

of me breaking down BMP I'm actually going to do the other thing I'm actually going to allow for lots and lots and lots of BMP to actually accumulate because I'm going to reduce the degradation so if I reduce the degradation I'll increase my amount of BMP that I'm actually going to be having available so that's a cool concept now another thing that we can do here and it's actually been very very interesting because again this drug combo has been shown to potentially reduce mortality so that's again another benefit and a drug that we need to

be able to remember and consider for our patients because it can reduce their risk of death and you always want that another drug combo that we should give with succubital so this is actually a combo and I'll write down the name here in just a second here but it's going to be utilized to actually block or inhibit the rain adjectives on a Doctrine system you know what this drug is called we've already talked about it it's an ARB so it's an ARB and it's a very specific type of ARP this is valzartan valzartan so we

actually do a combo here and this drug combo of which you actually have that contains the neprolysin inhibitor and the ARB is actually called an a r n i so it's an Angiotensin receptor blocker with a nepalyzen inhibitor this drug is called entresto this is kind of the brand name of the drug the entresto but it's a cubitril and valzartan so it's the combo of the two all right so what's the benefit of this well with having lots and lots and lots of BMP you're going to block Angiotensin II so real quick guys here it

goes JG cells they're pumping out renin when renin is released it converts angiotensinogen into Angiotensin one Angiotensin one then is acted on by Ace and converted into angiotensin two angiotensin two can then go in act on the arteries act on the veins it can work to work uh to increase aldosterone and increase ADH release and then it also goes and tries to act on the efferent arterial and induce vasoconstriction okay when I give this drug here BMP it opposes the action of Angiotensin II so just think everything Angiotensin II does I'm going to block and

then on top of that I'm going to give an ARB so I'm going to block Angiotensin II even more so the whole concept of this drug category is to just significantly block and reduce the activity of Angiotensin II so what's the overarching theme of this succubital valzartan combo is the combo here of circuba trill so it's a cubitril and valzartan is to do what is to significantly reduce Angiotensin II activity that is the basic concept because going to inhibit the BMP from getting broken down which is going to block Angiotensin II and then I'm going

to give valzartan which is going to block Angiotensin II so everything I'm going to see here is just a significant plummeting effect opposing Angiotensin II so what I see as a result here I'm going to see on the arterial system on the systemic arterial system what I'm going to see I'm going to see a massive decrease in the systemic vascular resistance I'm going to see a massive decrease in the afterload and then on top of that I'm going to see a massive decrease in left ventricular hypertrophy that's a pretty cool concept I'm also going to

do this on the venous system if I do it on the vein I'm going to reduce venous return I'm going to reduce preload and I'm going to reduce the left ventricular dilation effect if I inhibit ADH or inhibit aldosterone production then I'm going to have less of this effect on the kidneys so I'm going to reabsorb less sodium I'm going to reabsorb less water and I'm going to pee out a ton of sodium in water so now all I'm going to do is I'm just going to urinate non-stop all the sodium and water out and

by doing that if I get rid of sodium and water I have less of this in my circulation I effectively drop my blood volume and if I drop blood volume and that drops preload and that also may help to reduce the edema I'm also going to block efferent arterial vasoconstriction so that's going to do what it's going to reduce the glomerular blood pressure which will do three things one is it'll actually decrease the GFR but it'll also reduce protein urea and reduce thickening of the GBM which will do reduce the progression of CKD do you

see why this drug is actually pretty darn cool right it's just basically kind of like a very powerful Angiotensin receptor blocker because it's really increasing the activity of BMP which is opposing the effect of Angiotensin II and then we're giving a drug that also inhibit Angiotensin to that's a really really cool concept now however it's not first line okay it's not your first line agent really it's an it's an alternative that's really what it comes down to this is not a first line agent it's really an alternative two an Ace inhibitor so it's an alternative

to if a patient is on an Ace inhibitor or or an ARB so if they're on an Ace inhibitor or narb and there's a couple or there's two particular scenarios one is their maxed on an Ace inhibitor or an ARB and they're still having a reduced ejection fraction with symptoms they're not getting any better with it they're ef's still low they're still having symptomatology associated with this then you add on this particular drug which we're going to put here as the a r and I another option is that if they have a contraindication to an

Ace inhibitor Okay then if they have a contraindication to an Ace inhibitor then you can consider putting them on and a r and I that would be the particular reasons of why we would consider this drug and it's a pretty decent drug all the interesting thing about this is that the adverse effects is pretty much the exact same as an Angiotensin receptor blocker or an Ace inhibitor so again recapping all of their primary effects here is that if you have a reduction in GFR you're going to have a increase in the crit if you also

inhibit aldosterone you're also going to see an increase in the potassium here's the other interesting thing with this drug because you're really dropping systemic vascular resistance you'll actually see more hypotension potentially a drop in blood pressure more of an actual anti-hypertensive effect and so you may see a lower like afterload you may see more significant afterload reduction which may potentially cause the patient's blood pressure to just be a little bit lower than you would see solely with an ace or an R by itself okay and then the last thing here is Believe It or Not

neprolysin guess what else it breaks down bradykinins so bradykinins are also broken down by neprolysin into these inactive metabolites but if you inhibit nepalice and guess what you do you and you actually inhibit the breakdown of bradykines which increase the Brady kindness and so that can also lead to a cough and that can also lead to potentially angioedema so also just be a little bit cautious of that okay generally these drugs are pretty well tolerated though and that's an again a consideration so usually with these drugs the common situation where you'll see it is a

patient who's been maxed on an ace inhibit or an ARB they're still not seeing the actual benefit their ef's still low they're still symptomatic you'll you can actually consider that drug if the patient has a contraindication to it again kind of the concept to think about is that oftentimes the adverse effects are pretty darn similar so that's not going to be super super a good reason it's usually going to be the prior one but if they did have some other wonky contraindication you could consider discontinuing that and then trying an arni all right that is

the concept of this particular drug category so we've gone over the beta blocker system we've gone over the drugs that inhibit the range and ran and Angiotensin aldosterone system and then we went over the drug that really helps to increase the amount of BMP that we have but also help to shut down the written Angiotensin aldosterone system now let's talk about the next drug category so this is a drug category that's really interesting so we've talked a lot about like arterial and venous dilation but we talked about it via really either the Alpha One receptors

or the Angiotensin II receptors what if it has vasodilation by no way of Alpha One receptor blocking or by no effect of Angiotensin II receptor blocking what's that drug category so now we're going to talk about is direct acting vasodilators and their potential effect on reducing mortality in a certain patient population let's get into that so we got into verbata blockers we went over the drugs that inhibit the brain Angiotensin aldosterone system and then we even went over the drugs that again helped to increase BMP and kind of put the brake takes on the Angiotensin

II what about the drugs that directly vasodilate the arteries in the veins okay because we've seen a lot of arterial vasodilation a lot of Vino dilation but do we have drugs that can just directly do it not via the sympathetic system or via the brain Angiotensin aldosterone system yes this is really cool so these drugs I actually do like to give it especially in patients who have like an acute heart failure this is direct acting vasodilator so there's two types one drug that dilates the arteries and then one drug that dilates the veins it's actually

a good combo to give so the arterial dilator the primary one here is going to be hydralazine so hydralazine this is a pretty cool drug and then the other one that'll dilate the venous system is going to be isosorbide dinitrate so I like to give these as a combo right so if you think about it here what we're going to do is we're going to take a venous smooth muscle cell zoom in on it and then here we're going to take an arterial smooth muscle cell and then zoom in on it what's the actual effect

here on the venous smooth muscle cell we're going to see isosorbidden nitrate what isosorbide dinitrate does is it actually gets into this venous move muscle cell and it increases the amount of nitric oxide nitric oxide then goes and stimulates this special enzyme on the venous smooth muscle cell and this is called guanola cyclase guanolocyclase then takes a molecule called GTP and converts it into cyclic GMP cyclic GMP then goes and actually inhibits an enzyme called protein it actually works on an enzyme called protein kinase G and then when protein kinase G is acted upon what

it does is it goes and inhibits some special enzymes which are like for example there's what's called myosin light chain phosphatase so it'll act on very special enzymes that will inhibit the actual contraction of the myofilaments so when I give isosorbidden nitrate it increases nitric oxide activates guanolocyclase activates the conversion of GTP to cyclic GMP increases protein kinase G which then works too it actually stimulates myosin light chain phosphatase which inhibits the actual myofilament contraction it puts it into a relaxation state so then what happens to this smooth muscle cell and the vein is it's

going to relax if I relax a venous smooth muscle cell that's going to cause Vino dilation now think about why that's pretty beneficial my friends if ivenodilate what do I do I'm going to reduce the venous return into this congested heart so I'm going to prevent this process because right now this poor heart is already squealing and it's being like bro please stop filling me up I already got way too much in my ventricles here sitting so what I'm going to do is I'm going to reduce that venous return process and so that's one potential

benefit so that would be reducing venous return which will reduce preload and that's a pretty good thing to have the other thing here is the hydralazine so hydralazine is actually pretty interesting and as well and so what hydralazine does is hydralazine doesn't play any of these games where it works to kind of increase nitric oxide it actually just directly stimulates directly stimulates this enzyme called guanolocyclase if you directly stimulate it what it does is it takes GTP and increases cyclic GMP cyclic GMP that works too stimulate protein kinase G and then what protein kinase G

does is it actually activates the myosin light chain phosphatase which will inhibit the contraction of the myofilaments and this will cause the artery to undergo relaxation this will cause vasodilation of the arterial system if you vasodilate you reduce the systemic vascular resistance and you reduce afterload and the whole concept of this is that if I reduce preload I reduce the further congestion of the heart so if I reduce preload I'm going to reduce further congestion and if I reduce afterload I'm going to allow for an increase in forward flow so really when you think about

this hydralazine is going to increase forward flow it's going to make it easier for blood to be able to get out of the left ventricle and isosorbidden nitrate is going to decrease the venous congestion if you want to think about it so it's going to decrease the overflowing of the heart with more and more blood which is a beneficial concept here and so really you would see this as a pretty decent drug now what would we actually use it though like it and when would we actually be utilized in patients who have heart failure that's

a great question so generally the indication is it is an alternative therapy so just like the drug that actually increases BMP and then you also have the combo of the ARB with it that's an alternative to alternative to an Ace inhibitor or an ARB especially if they're maxed out on that and they're having still no actual maximal benefit of it they're still symptomatic this level oef or they have a contraindication similar this is an alternative to an Ace inhibitor or an ARB and there's two particular situations one of them is if the patient has a

decreasing renal function the reason why is is ACE inhibitors and arbs they actually decrease renal function so if you put them on an Ace inhibitor and ARB and they already have decreasing renal function you'll worsen their renal function so that's why you would discontinue the ace inhibitor the RB and then put them on this combo okay so you understand it if a patient has a poor creatinine they have a very high creatinine they have worsening kidney injury and they're on an Ace inhibitor or an ARB it may be a good idea to say okay probably

hold on the acid number ARB do hydralazine or an isos orbital nitrate because that doesn't hit the kidneys as much a little bit gentler on the kidneys and so that's a good indication especially an acute heart failure this is really when I like to utilize it as a intensivist as patients who have acute heart failure they're going to have a very high risk of their kidneys getting hit pretty well and so sometimes if a patient's hypertensive and I just can't get their blood pressure under control so I used to put on ACE inhibitors or an

ARB but then a couple days later I noticed that their creatinine would jump and I would actually be kind of kicking myself in the butt so I could consider another alternative combo like hydrology and isosorbide nitrate to afterload reduce those patients and still get the same benefit to actually reduce them and to Vino dilate them get the same benefit that you would with an Ace inhibitor or an ARP okay I just wouldn't get as much of that effect on the kidneys which is a nice thing because I'm not going to inhibit the I'm not going

to work to play a role inhibiting the efferent arterial artery vasoconstriction so I'm not going to reduce the patient's GFR and increase their creatinine so you see the benefit to that the other one and I think this is important a really really important one so I actually want to really highlight this and I'm going to put it like in a and a pink here in a second but if a patient is African-American and has heart failure this is a superior drug to ACE inhibitors or arbs because patients who have heart failure generally they're running adjectives

on The Bachelor system tends to be a little bit lower in its intensity so patients who are African American and have heart failure this is going to be better so it's greater than ACE inhibitors or arbs so this is a very very important Point okay please don't forget that and the reason why I don't want you to forget that is this drug category May reduce mortality a little bit more in patients who are of African-American have heart failure so if your African-American descent have heart failure this drug category has been shown to be a little

bit more beneficial in comparison to ACE inhibitors or arbs because patients who are African-American generally are thought to have a lower renin hypertension that kind of cause so really please don't forget about that with this drug category the last thing to talk about is what are some of the adverse effects these don't hit the kidneys which is a great reason of why I would prefer these and an acute heart failure patient or an African-American patient the other thing is that it doesn't really have that many adverse effects which is kind of a nice concept here

really what you want to think about is if you Vino dilate you reduce venous return to the patient and if the patient is preload dependent so in other words they go from a seated position to a standing position or they go from a supine to a seated they quickly have these fluid shifts where Venus return naturally drops if you venodilate them you drop their Venus return even more and can drop their preload and kind of make them a little bit hypotensive and drop their kind of make them a little bit like dizzy and kind of

almost syncopize so watch out for orthostasis that you can see with Vino dilation and the other thing is when you arterial dilate and you reduce resistance you kind of create a baroreceptor reflex which actually may increase the patient's heart rate so watch out for a reflex tachycardia as well okay so in the same way that whenever you dilate the arteries it drops the resistance it drops the blood pressure that can activate those bare receptors and when you activate the baroreceptors it'll actually tell the sympathetic nervous system to increase and increase the heart rate so watch

out for that as a potential adverse effect here with these drugs okay that covers the direct acting vasodilator so up to this point we've covered drugs that have been shown to potentially reduce the mortality and heart failure what we're going to now move into is drugs that actually don't have any true benefit in reducing mortality they're more symptomatic relief they have no change in mortality or no increase in mortality really and that they may be beneficial in refractory cases but again that's going to be these last line drugs so let's talk about those now all

right next category is diuretics now we've talked up to this point about drugs that reduce mortality this one does not really reduce mortality it reduces symptoms when we talked about that in the beginning of the video where we said that it really helps to reduce the venous congestion a lot of the pulmonary edema and peripheral edema and just the volume overload States because blood isn't getting out of the heart if blood isn't getting out of the left ventricle where excuse me where is it going to go to so blood can't get out of the left

ventricle because the left ventricular cardiac output's just you know stinky guess what's going to happen it's going to back up into the left atrium and then from there it's going to act back up into the pulmonary circulation when it backs up into the pulmonary circulation it's just going to cause massive pulmonary edema and then you're going to be clogging up all of these alveoli right so you're going to end up with what's called pulmonary edema now pulmonary edema within the lungs can look a lot of different ways it could just cause maybe a little bit

of dyspnea so for some patients it may only just be that they're a little bit distinct and I think this is important to realize because whenever people just say oh it's for symptom control what kind of symptoms we should know that right so the patient has dyspnea if they have peroxismal nocturnal dizziness in other words whenever they're laying down at night flat that actually may be the worst time for them they're actually getting really short of breath or anytime they're laying flat like they're gonna watch the football game and they get on the recliner and

they pop that thing back and in that kind of situation so laying flat or just any kind of Disney in general is a concerning sign for patient the other thing is if they are completely hypoxic so hypoxic respiratory failure this is a terrible sign and usually asserted way that is associated with an acute heart failure and so this is a pretty you know fearful sign and then the ones that you just don't want to see in patients but it's something to consider so if a patient's left ventricular cardiac output is extremely low so they're left

ventricular cardiac output is really low it's going to cause this venous congestion and if the venous congestion occurs it can lead to subsequently this pulmonary edema especially if it's the pulmonary venous congestion now if patients have left heart failure that then progresses in other words if you start having a lot of pulmonary circulations just kind of getting a lot of fill with fluid it can then start causing this to transit to the actual right heart and then if the right heart stops actually being able to pump so now the right the right ventricular there's a

decrease in the right ventricular cardiac output for whatever reason in this situation then the blood is going to start backing up into the left to the right atrium which will then go up via the superior vena cava that'll maybe cause some jugular venous distension but that's not a concerning sign what would be a problem is if this kind of backs up down the inferior vena cava and starts kind of causing a lot of Edema within the abdomen or within the actual extremities so then you start into walking around with like these tree trunk legs because

they're so dang swollen so watch out for any kind of peripheral edema okay and sometimes this can even kind of accumulate with the abdomen cause a lot of like abdominal congestion so it can cause like ascites hepatomegaly things of that nature so watch out for that as well but this is a type of congestion as well and this is more of a systemic congestion so this is a systemic Venus congestion okay so systemic venous congestion and then pulmonary venous congestion so this is pulmonary congestion so you can see these two particular types of effects whenever

a patient has a reduction in cardiac output blood can back up into their venous circulations what I can do is give diuretics and what the diuretics are going to do is they're going to cause me to block sodium and water reabsorption at the kidney tubules caused me to pee out so what I'm going to do is I'm going to inhibit sodium and water reabsorption so whenever the blood's supposed to go through the kidneys and then it's going to you know undergo its actual filtration process and it leaves the kidneys I'm going to decrease the amount

of sodium and I'm going to decrease the amount of water that is reabsorbed okay so I'm going to decrease sodium and water reabsorption and what that's going to do is is then because of that if I don't reabsorb it I just pee out a lot of sodium and water so I increase the sodium and I increase the water that's present inside of the urine if I reabsorb lots of sodium and if I actually inhibit sodium and water reabsorption so I don't pull as much of that back into the circulation I'm going to drop my blood

volume all right and that's going to do two things here one is it's going to reduce the preload which will help to reduce further congestion so the heart is already filled with so much dang blood that it's already backing up if I drop the preload I'll drop any further congestion on top of that any fluid that's within the body I'm going to start removing it from the actual circulation so I'm going to get rid of fluid that's in our circulation and so that may reduce some of the edema that is the concept that we're seeing

with these drug categories now what are these drug categories good question there's two types loops and thiazide diuretics so Loop diuretics are going to be things like Furosemide and another one called bumetanide and another one called torsomide and really all these are doing is they're inhibiting sodium and water reabsorption at the Loop of henle that's it we'll go over these more in detail when we talk about diuretics but inhibiting the sodium potassium two chloricotransporter you don't reabsorb sodium you don't reabsorb water you excrete them out into the urine that's it they cause diuresis of sodium

and water thiazides are going to be things like hydrochlorothiazide chlorothalidone chlorothiazide and another really good one I've actually found to be pretty beneficial is metolazone I actually like metallism so I think one of the really interesting things with this drug is that really they do not reduce mortality what they do is they reduce edema symptoms edema symptoms so they can reduce some of the pulmonary venous congestion and the peripheral venous congestion such as the systemic congestion that you can see here now if a patient has this I think it's really important to realize that yes

it is important to not be having swollen up legs so yes diuretics should be used if a patient has peripheral pitting edema but I think the more Superior reason to do these is if the patient has pulmonary edema that should definitely be something that you incorporate into the patient's actual medical regimen but it's also important to make sure that you're having changes in their dietary recommendations so reducing their salt intake reducing their water intake those are important things swaying themselves to make sure that they're not gaining too much weight meaning they're retaining a lot of

sodium and water within their body those are important Concepts but the basic concept of this drug is that they are going to be utilized to reduce a lot of the edema symptoms so if the patient is kind of like having a super increase in their daily weight that's an indication to maybe up their diuretic regimen if a patient is having increasing um like actual like pitting edema this may be an indication to start upping a lot of their actual diuretic regimen and if they're having a lot of pulmonary edema this may be an indication to

up their actual diuretic regimen so think about these particular things okay that's really the indications of these drugs they're not supposed to provide any reduction in mortality they cannot actually drop your blood pressure if you actually use it in a patient who's truly volume overloaded you can give that but that's that's not their main indication they're really supposed to help with symptom control now because these drugs are helping to get rid of sodium and water some of the other things that you want to watch out for when you put a patient on these is that

if a patient is getting rid of a lot of sodium sometimes you may see hyponatremia they also can cause potassium expiration so watch out for any kind of hypokalemia they also can cause proton excretion so watch for any kind of like increased pH primarily what's called a metabolic alkalosis the other thing is that they can cause they actually can inhibit uric acid secretion and so they may cause a lot of high uric acid levels in the blood and worse in patients who have gout and then sometimes Loop Diuretics may actually cause some degree of ototoxicity

we'll go over all of these adverse drug reactions later in diuretic regimen but again just be aware of some of the potential things to watch out for especially electrolyte abnormalities some types of metabolic acid-base changes and then again hyperuricemia they can also increase your lipid levels your glucose levels and cause some ototoxicity especially Loop Diuretics but again think about these so so far we've covered drugs that reduce mortality beta blockers running Angiotensin aldosterone system Inhibitors drugs that increase BMP and hydralazine isosorbide nitrate then we talked about drugs that reduce the symptom problems so edema problems

this is the diuretic regimen okay and what I actually really like to do sometimes with these patients is if they're really kind of a demonis and I'm not shifting enough of that weight off I'm not getting their weight down I'm not getting enough of an actual diuretic effect I actually like to combine these so oftentimes I will put a patient on something like furosemide and metolazone to help to be able to pull off just a little bit extra sodium and water to really decrease the patient down and drop their weight drop their edema as symptoms

as well so a little kind of hacker trick that you may gain okay now that we covered that let's go into the next situation a patient at this point if you're on all of these medications so a patient is online let's say that they're on a beta blocker they're on an Ace inhibitor or an ARB or they can't tolerate that and they're on AR and I okay or they're African-American and they you know they haven't they have poor renal functions so instead they're on a hydralazine or isosorbide nitrate they're also not a doctor or an

antagonist and then they're also on diuretics for symptomatic control for edema symptoms and just a volume overload States but they're still refractory they're not getting any better that's when we're going to add in these next drugs so the next one we're going to talk about you probably won't see too often what we will mention is called Iva braiding so let's talk about that one and then we'll finish off with positive ionotropic agents all right next drug ivibrating really this drug is it's really not something that you'll see that often but it's primarily used in refractory

CHF okay um and really what we really should actually say is again it's just because this is what the evidence has shown us heart fail familiar with a reduced ejection fraction okay so if a patient has refractory heart failure where the reduced ejection fraction and this is just the way that they kind of they determine this based upon the studies it has to be an EF of less than or equal to 35 percent so this is a drug that will give to patients who have refractory heart failure with an EF of less than or equal

to 35 and we'll talk about some other inclusion criteria for it but this drug what in the living crap does it do how does it help patients it's really weird to be honest with you but it's a really kind of interesting mechanism so you know within our heart we have all of our conduction system right so if you guys remember we always always start off with something called the SA node and then the essay node will fire and then it'll go to the AV node and the AV node will go to the bundle of hiss

and then it'll go to the right bundle branch and also go to the left bundle branch left bundle branch and then from here these will go down to your purkinje so it'll go to your purkinje system and what we know is is that the SA node is really the the big dog right so this is the one that is what's called the pacemaker so in other words it kind of generates the the normal sinus type of Rhythm okay so what I want to do is I want to take an essay nodal cell and I want

to kind of zoom in on that essay notal cell because I have a braiding really works at the essay nodal cell so you know what's really funny about the essay neural cells they got these really interesting channels maybe it's corny but they're called funny sodium channels so we call them I F so these are inward sodium channels they're little funny channels and what they do is is when an essay node is it's the pacemaker so it's got to be willing to set the rate okay so it generates something called Pace maker potentials and the way

that you generate these pacemaking potentials is via these funny sodium channels so what happens is inside of this cell what we're going to do is we're going to look at an actual membrane potential so here's going to be what's called your resting membrane potential and then here's going to be your threshold potential all right in order for me to get to resting membrane potential to threshold potential I have to make the inside of the cell as I go up I'm more positive I'm going to make the cell more positive so what I do is these

funny sodium channels are going to open when the cell membrane is just a little more negative so when the cell membrane is negative in other words it's hyper polarized so it's in the relaxation State we're in the resting state it opens up these funny sodium channels and it allows for sodium to kind of trickle into the cell when the sodium trickles into the cell that makes the inside of the cell slightly positive so now what I'm going to do is I'm going to just kind of take my resting membrane potential and I'm going to bring

it up here about almost close to threshold potential I'm going to bring a pretty darn close and what I'll do is I'll cause the inside of the cell to become just positive enough that I activate other channels and these are called T-Type calcium channels so these are called T-Type calcium channels what they do is they allow for calcium to rush in to the cell and when they rush into the cell they make the cell more positive and when they make the cell more positive they get the actual resting membrane potential just to the patient's threshold

potential and then finally that activates the last Channel which is we'll just do this one in red here it activates that last Channel which is that l-type calcium channels if any of this sounds unfamiliar and go watch our video on the cardiac conduction system we talk about this in more detail but then what happens is this inner calcium activates this l-type calcium channels and then all that happens here is calcium will flood into this dang SA node cell and when it floods in it really makes the cell super positive and this will help to be

able to generate the action potential so then when you generate your action potential right and then from here you'll have that kind of phase where you come down and then you kind of start it all over again right so this will lead to the depolarization and then after the depolarization it'll kind of go into the repolarization and it'll start over again right so then it'll kind of do this you'll have again the funny channels open back up they'll get them close to the threshold but not completely there open up the T-Type that'll get the l-type

to open the l-type will open you'll depolarize and then you'll repolarize all right and then the same concept happens okay what I'm going to do is it's important to Remember That these channels are active during what phase well if the if it's during kind of when the when the patient is in the resting membrane potential that's when they actually open up at this point here so from this point here to this point here the patient is in diastole at this point here to this point here the patient is in diastole what I'm going to do

is I'm going to give a drug I have a braiding and it's going to block these funny sodium channels if I block the funny sodium channels I don't allow sodium to come in and trickle into this cell as easily so that means I have less sodium that enters into the cell that means I have less of these positive ions that means it takes a longer time for me to activate these T-Type calcium channels that means that whenever the T-Type calcium channels actually open up it's going to be way later and if it opens up way

later it's going to take a longer time for them to activate the l-type calcium channels to trigger a depolarization so now imagine this is normal now what I'm going to do is I'm going to take this situation here and I'm going to take a patient who's now on I have a braiding and what it's going to look like here is here's the resting membrane potential here's there's threshold potential and it's going to look like this now so let's say here in I'm going to do it here in red this was the normal patient so here

in red is the normal situation so we go here and we go here down here down okay that's going to be the normal patient now you have the patient who's on Iva braiding if they're on either braiding this phase as they work their way up towards threshold potential is going to take a longer time because I'm blocking the inward sodium channels so less of that inward sodium influx occurs less of the T-Type calcium influx occurs and it's going to take a longer time for me to activate the l-type calcium channels to trigger the depolarization so

because of that it's going to look like this oh so now what I'm doing is within this one point of time within this phase of time I'm just using this as kind of like a super generic example within this moment of time there was two action potentials now there's only one and this is actually very interesting because again it's really affecting the diastolic time frame so what you're going to see here is it's going to block the inward sodium channels and slow down the actual activation of the SA node which is going to decrease the

firing of the SA node all that do that'll drop the patient's heart rate so what I'm going to see out of this is I'm going to see a drop in the patient's heart rate okay that's one particular thing that I'll see the second thing is is that if this is determining diastole this kind of like space here if I look here for this patient here's their diastolic period right here so it's right before they begin to actually contract so that at this point here they're Contracting then they go into this depolar this repolarization phase and

then again they actually are going to still be relaxing relaxing and then they actually contract so what I'm going to do is is if I lower the patient's heart rate by actually delaying the depolarization effect I allow her for a longer diastolic filling process and so what I'm going to do is I'm going to increase the diastole time because I'm lowering the heart rate and prolonging or delaying the depolarization of the SA node so if I delay the depolarization of the SA node I drop the heart rate and I increase my diastolic time frame which

if I increase diastolic time that's going to increase the actual ventricular filling and it's going to increase coronary perfusion oh that's a good thing so I'm going to gain a couple benefits out of this I'm going to drop the patient's heart rate by blocking the SA node and reducing the actual amount of ions that are coming in via the funny sodium channels I'm going to prolong the actual or I'm going to delay the depolarization of the SA node if I delay the depolarization of the assay node I drop the patient's heart rate because it's not

firing as fast so then the conduction from the sceno to the AV node is reduced so there's going to be less signals that are moving via this pathway it's going to drop the patient's heart rate but also if I prolong or I delay the depolarization that means that a patient has a longer time period before it actually starts to contract so it's diastolic time frame is longer which allows for it to feel better and if you increase filling What do you do you improve the patient's stroke volume and you improve the patient's cardiac output so

this will increase stroke volume and cardiac output and it'll give them more time to perfuse their coronaries and give The myocardium oxygen it doesn't reduce mortality okay that's a big thing so the question is is when do I do this for a patient okay I know that it's going to drop heart rate it's going to suppress the SA node dropping heart rate delay or actually prolong the actual uh the phase before it actually causes depolarization it's going to it's going to delay depolarization of the SA node dropping the heart rate improving diastolic filling when do

I use it let's say they have once one particular situation they have an ejection fraction of less than or equal to 35 percent that's one particular scenario they have normal sinus rhythm and I can't stress this enough this is extremely important you're trying to suppress a sinus rhythm okay so when you're hitting the SA node you're trying to block or inhibit the AC note which is inhibiting the actual depolarization the conduction of action potentials from the SA node down you're not trying to block the AV node and so if a patient's in afib this is

not the particular indication for this drug you're trying to block the essay node you're drop blocking the funny sodium channels only in the SA node on top of that they have to be somewhat tachycardic so their heart rate has to be greater than 70 beats per minute and maxed on a beta blocker if they are maxed on a beta blocker they have a heart rate greater than 70 beats per minute and it's normal sinus and the EF is less than 35 then you'll consider giving this drug then you can start I have a braiding the

only other indication is if it's not Max on a beta blocker it would be or they have a contraindication to a beta blocker so somewhat of an alternative or add-on therapy it could be really an alternative if they have a contraindication to a beta blocker and maybe a um add-on if they have a Max on a beta blocker and you want to see if you can get a little bit more love with giving Ivory breeding to suppress that heart rate just a little bit more so again you need the patient to have an EF of

less than or equal to 35 percent you need them to have a normal sinus rhythm because you're suppressing the essay node you need them to be a little bit tachycardic even maximally acted on by a beta blocker or they have to have a contraindication to a beta blocker then you can consider I have a braiding now with this drug what should you watch out for if you put someone on Iva braiding be careful I mean one of the big things that you're suppressing the SEO note so you could potentially see bradycardia and here's the other

one it's a it's a weird one but it can cause um like Blurry kind of like luminous vision changes so it can actually cause like um like Bright Vision changes which is interesting exactly how there is the thought that the sodium channels that are present in like the retina can also be somewhat blocked by I have a braiding so it may kind of change some of that processes there so just be cognizant of that if a patient is coming in and they're saying man I'm having like this weird like bright like luminous vision changes it

could be due as a side effect of this drug so think about that all right so I have a braiding given to patients with refractory heart failure who generally have an EF less than 35 percent normal sinus heart rate greater than 70 maxed out or have a contraindication to a beta blocker you can consider I have a braiding things to watch out for bradycardia because you're suppressing the sinus uh silent atrial node and watch out for blurry kind of like luminous Bright Vision and then the other thing is how does it work it blocks the

SA node funny sodium channels prolonging or delaying I'm sorry delaying the depolarization of the essay node if you delay the depolarization of the SA node you cause the heart rate to drop and then prolong diastole which allows for better ventricular filling and also improves coronary perfusion okay beautiful now let's go on to the last drug category this is your positive inotropic agents all right so the last class of drugs is going to be positive inotropic ages they're going to be drugs that help to increase the contractility so if you increase contractility you should increase your

stroke volume increase your cardiac output and that might be beneficial in patients who have a heart failure with a reduced ejection fraction or even with a preserved ejection fraction right now really this drug category is only utilized in patients who have a reduced ejection fraction that's really really important okay and it's really those who have been refractory to all other categories or are an acute heart failure with maybe cardiogenic shock okay so let's talk about these drugs so really again remember that these are primarily utilized in refractory heart failure with a reduced ejection fraction that's

one of the big things is really when you look at heart failure with a preserved ejection fraction meaning that their EF is pretty good their ability to squeeze blood out of the hearts pretty good you don't need these drugs okay the only time where you really have a big difference is between heart failure or the preserved and reduced DF is that patients who have a reduced DF they need that increase in contractility so they depend upon that squeeze maybe a little bit more so positive minotropes really only in heart failure were the reduced not really

utilized or helpful at all and heart failure with a preserved ejection fraction because their contractility is okay okay so let's talk about these drugs digoxin is going to be the first one now digoxin is actually interesting okay now this drug is a drug that we give to patients might as well just knock out the indication for over here this isn't a drug that we would give to patients who are refractory to multiple meds so they have a refractory heart failure with a reduced ejection fraction and I'm talking that they've been refractory to the ACE inhibitors

or the arbs and if they can't tolerate this they've been you know refractory to the a r and I's or they've been on beta blockers they've been on aldosterone antagonists or maybe they couldn't tolerate an Ace inhibitor and ARB because they're African-American so if they're African-American maybe they've also been a hydralazine and isosor by dinitrate and on top of that they're also on diuretics for you know symptoms you know particularly like pulmonary edema peripheral edema congestive symptoms so they're on all of these medications and the patient's still not having Improvement in their symptoms they're still

not having an improvement of their injection injection fraction so despite all of these the patient is still symptomatic and still has a low ejection fraction in this particular situation we'll add on digoxin okay so let's say that a patient is on an Ace inhibitor they're on a beta blocker they're on a dash or an antagonist they're on diuretics all of these things they're still not actually able to have Improvement of their symptoms and they're still having refractory low EF you can get this drug now one of the things about this drug is it hasn't been

shown to increase mortality but it doesn't decrease mortality that's kind of interesting but the other thing is that it actually may reduce hospitalization rates and that kind of actually is kind of appealing in some way so this is a good drug to give outpatient okay and you can also give it inpatient these drugs down here dobutamine Mill were known they actually have been associated with higher mortality rates so we really want to avoid giving these drugs the only time we're really going to give these drugs is in patients who are in cardiogenic shock and we'll

talk about that a little bit later but and general digoxin we're going to utilize this drug as more of an outpatient medication that we could add on to this therapy so for example I said a patient's on an ace or an ARB or an arni they're on a beta blocker they're on an industrial antagonist they're on if they maybe they can't tolerate ACE inhibitor and ARB or an arni and they're African-American we put them on hydralazine or an isosorbidden nitrate and we're relieving their symptoms with diuretics if after that we add on the digoxin what

does the digoxin actually do to help these patients who have heart failure right okay we take here contractile cardiac muscles out zoom in on here we take the AV nodal cell zoom in on here let's see what it does on the contractile cardiac muscle cell it works via altering two particular pumps one pump is called the sodium potassium atpase this naturally pumps sodium out of the cell and pumps potassium into the cell when I give digoxin as a cardiac glycoside so it inhibits the sodium potassium pump I can't pump sodium out of the cell then

sodium then builds up inside of the cell that's an interesting concept because on this other channel here this channel actually is going to be a sodium calcium exchanger so calcium is present inside of the cell and I want to get rid of this whenever the patient's actually going into kind of a repolarization they're trying to relax and get their self ready to be stimulated again to depolarize I want to get calcium out of the cell right so generally what I want to do is I want to get calcium out of the cell and bring sodium

into the cell but the only way that I can bring sodium into the cell is if it's moving down its concentration gradient well generally sodium should be higher outside of the cell but now I have sodium also that's really high inside of the cell so what's the problem with this concentration gradient is sodium going to be able to move down its concentration gradient no so this process is inhibited I don't let sodium come in and therefore I don't let calcium go out so if that's the case what happens to the calcium level inside of the

actual contractile myocardial cell it increases if I have increased calcium inside of the contractile cell that's going to bind onto dripona like a son of a gun and stimulate it and that's going to increase contractility now if I increase contractility I will increase stroke volume and I will increase my cardiac output and hope to push more blood out of the heart that is one of the benefits to this drug so we call this drug a positive inotrope because it can help to squeeze blood out of the Heart by having it contract harder but it's also

a negative it's a negative type of chronotropic agent okay so it can also act as a negative chronotrope which is actually kind of cool man so watch this and the mechanism isn't completely layered out yet but here we have the vagus nerve and the vagus nerve acts on the AV node and what it does is it releases something called acetylcholine and then acetylcholine will bind onto this receptor here called a muscarinic 2 receptor and that'll help potassium to kind of leave this cell right so potassium will leave the cell and that makes the inside of

the cell super negative which triggers hyperpolarization hyper polarize if it hyperpolarizes meaning it becomes negative it doesn't actually generate action potentials as well and if it hyperpolarizes it drops the patient's heart rate if I drop the patient's heart rate what's the potential benefit to dropping a heart rate I may actually laugh for a longer diastolic filling process I may improve potential coronary perfusion but you know what else is a really good indication for this drug besides having them refractory to all of these above medications since it drops the heart rate at the AV node I

love to add this drug on and patients who have atrial fibrillation so it's also good to reduce the heart rate in patients who have atrial fibrillation and heart failure with a reduced ejection fraction that's another good indication for this drug so that's another really cool thing that I like about this drug the patient has afib and they have a very fast heart rate I can suppress their heart rate with digoxin and improve their contractility with digoxin that is a nice combo in combination to everything else that we talked about here now what are the downsides

so we know the indications patients who are fractured to the above therapy or have afib with a reduced DF that's another benefit we know how it works what's the downsides to this drugs some of the adverse reactions that you really want to watch out for is because it actually does again block the sodium and the potassium atpase so you're blocking this there's two negative connotations to this one is you make the inside of the cell super positive because you're going to have it having lots of calcium lots of sodium inside of the cell so this

increases the risk of you like having higher resting membrane potential causing the cell to be way more active and unfortunately that could put the patient at risk of arrhythmias so some of the things that you really want to watch out for with this is because it's suppressing the sodium potassium pumps it can increase the resting membrane potential and this can increase arrhythmias and that's not something that you want a patient to actually go through maybe even torsos to points here the other thing is you suppress the sodium potassium pump you don't push potassium in so

potassium builds up outside of the cell and so another thing that you can see is a potential complication of suppressing that pump is hyperkalemia one last thing and this is the one thing that's kind of complicated though it can cause hyperkalemia it can increase the resting membrane potential increasing the risk of the cell being super positive and causing it to become agitated and create irritable Foci causing atrial causing things like I'm sorry maybe tors odds to points okay so this could potentially increase the risk up towards the odds to points and it can prevent potassium

getting pushed into the cell which can bump the K up okay what's really dangerous though is that potassium competes with digoxin at the sodium potassium pump so if a patient has hypokalemia if they have low K it increases the digoxin toxicity because now you have less of the potassium to compete with the actual digoxin at the sodium potassium pump so if I have low k out here I'm not going to have as much of the actual blocking of the digoxin at this pump and so digoxin is going to hit that pump way harder than usual

and it's going to cause more toxic effects so yes digoxin will directly cause hyperkalemia and increase the risk of potential ventricular arrhythmias but on top of that just be aware if a patient has hypokalemia it has less competition with the digoxin at that pump and can increase the toxicity okay the other thing is that you could actually have higher digoxin levels if you're taking this drug with other medications and so you have less clearance of digoxin would you take this secondary to two particular drugs that I want you to remember one is Verapamil and the

other one is called amiodarone so just be cognizant of that that these drugs can decrease the clearance and this can increase the levels of digoxin which make it to be above super therapeutic levels okay and that has a very the therapeutic kind of index for this drug is kind of narrow so that's kind of the big thing to watch out for the other thing is that because the joxen helps to stimulate acetylcholine release from the vagal nerves you can get more of a cholinergic type of side effects profile so watch out for things like nausea

vomiting diarrhea because with the nausea and vomiting you can hit the emetic center in the medulla with diarrhea you can have increased motility of the git it also can cause vision changes so it can kind of cause like a bright yellow vision it's weird I want to write that down though because that's something that you may see on the exams because it's just super random is it may cause kind of a yellow vision like rings to form so just watch out for that so two vision changes problems one with I have a braiding and the

other one with digoxin so just be aware of that one of the things I think is important to kind of mention here is because digoxin is somewhat beneficial and actually does not reduce doesn't actually increase mortality it may reduce hospitalization rates what is bad is that higher digoxin levels higher digoxin levels will actually increase mortality and heart failure with reduced ejection fraction so that is important to remember and so what you should know is if a patient takes too much of their digoxin so if they have hydroxine levels you should know the antidote a drug

that you give to prevent the negative connotations of this drug and that drug is called digibond digibind okay so know these particular things especially with respect to this drug it can be toxic and have some negative connotations but if it's in a good appropriate level where it's providing positive inotropic action negative chronotropic agent without a lot of these negative side effects it can actually potentially reduce hospitalization and not increase mortality and that's a good thing okay that's the jocks of my friends okay let's talk about these other drugs down here dobutamine and milram because what

I really want you to remember about these drugs in comparison is that these drugs actually have been shown to increase mortality so I really want to be careful putting patients on these medications because there is a higher risk of mortality so try to avoid these but the reason we would do this we're going to talk about a little bit is the patients in cardiogenic shock and we have to all right so when we talk about these particular drugs they are going to be positive inotropic agents one of the big things to be cognizant of is

that these are both really primarily only utilized and the patient who has acute heart failure acute heart failure that is progressing to cardiogenic shock so their cardiac output is so dang low that these are patients that aren't perfusing now so if that is the case where they are not even perfusing particular organs but unfortunately their risk of mortality is already high so therefore we need to put these medications on these patients because it may be the only thing that actually helps them to generate a perfusion to very vital organs you want your coronaries to perfuse

you want your brain arteries you want the actual circulatory vessels your anterior posterior circulation to perfuse your brain You Want Blood perfusion to your kidneys you want perfusion to your skin right so those are essential for you know survival so it's important to be able to understand why we would really utilize these drugs okay so with that being said do realize that we want to avoid them but if we have to we're doing it because the patient's at high risk of death anyway if we give these drugs like duped Amino alone they're primarily IV infusions

okay so we primarily give these as a kind of like an infusion okay so these need to be closely monitored and usually these patients are in a cardiac ICU for this when you give dobutamine how does it work versus how does MIL Renown work so I want you to be aware of these dobutamine is a beta Agonist that means that this puppy hits the beta 1 receptors on the heart on the contractile cells of the heart it'll actually have the beta1 receptors and it also hit the beta 2 receptors on the arterial smooth muscle cells

all right that's really interesting so now I give to be to mean it hits these beta 1 receptors what's it going to do to the contractile myocardial cells it's going to activate all of the the actual g-protein pathway which will help to increase calcium and that will stimulate the contractile myocardial cells and you'll have a increase in contractility so therefore if I increase contractility this is a positive I know Trope if I increase contractility my whole goal is that with this I'm increasing my cardiac output and hoping to perfuse a little bit better to generate

a better cardiac output increase the patient's blood pressure and perfuse organs that's the benefit of this drug the other concept is if I give a dobutamine okay so dobutamine is an Agonist so it's going to stimulate the beta 1 receptor so we call this a Agonist it's also going to bind onto the beta 2 receptors and when it binds onto the beta 2 receptors what we know about this one is that this works via the G stimulatory pathway but this actually leads to relaxation of the arterial smooth muscle because we know that it actually does

activate cyclic amp cyclic amp actually leads to the stimulation of what's called a protein kinase a protein kinase then the phosphorylates what's called myosin like chain kinase and that inhibits the myosin light chain kinase and therefore it won't be able to stimulate contraction that's the whole pathophysiology I don't want to go too crazy but the whole concept is it's going to trigger this smooth muscle to relax if the arterial smooth muscle relaxes what does it do then it's going to do what it's going to decrease your systemic vascular resistance which is going to do two

things it's going to drop the patients after load and that's one benefit because that's going to help to increase your stroke volume and your cardiac output if you have less work or pressure that you have to overcome to push blood out of the left ventricle into the artery it's going to improve forward flow the downside is that if you drop systemic vascular resistance and the patient is in cardiogenic shock meaning that if they are in cardiogenic shock they probably have a terrible cardiac output so now you're going to drop their systemic vascular resistance in combo

with them already having a drop in their cardiac output guess what you may do to their blood pressure you may drop their blood pressure and then you can actually have a problem where you're not maintaining an actual or a mean arterial pressure that you want that's one of the potential downsides and we'll talk about how we can counteract that a little bit later but that's something to think about so when we talk about these dobutamine is actually a beta one and beta 2 Agonist and so the way I like to think about this is that

dobutamine is an I know dilator it's an ionodilator so really what is this drug this drug dobutamine is an I know dilator because what it's going to do is it's going to cause increased inotropic activity but vasodilate so it increases the contractility reduces afterload to improve forward flow the only downside to that is it drops as a resistance a little bit and that may drop the patient's blood pressure a little bit because you're hoping to increase their cardiac output but if their cardiac output is so dang poor yes you may recruit enough of The myocardium

to get the cardiac output to go up but if their resistance drops enough it could potentially drop their blood pressure so just be cognizant of that with Mill Renown this is a different kind of drug so what happens is inside of this actual cell so there's this enzyme here it's called adenylate cyclase and what adenylate cyclase does it takes ATP and converts it into what's called cyclic amp and then cyclic amp will then go and activate something called protein kinase a and then protein kinase a will then stimulate um well actually it'll actually stimulate calcium

channels if you really wanted to know it'll actually stimulate calcium channels and if you stimulate calcium channels calcium will rush in and that'll stimulate the our the contractile myocardial cells to contract and so with that you'll see an increase in contractility and increase in cardiac output it'll act as a positive minotropic agent right so that's important to remember so milrinone will do the exact same thing but how will it do this generally the problem with this is that cyclic amp gets broken down by an enzyme here this enzyme is called phosphodiesterase three and what phosphodasterase

3 does is it actually will inhibit or break down the cyclic amp if I give millrenown what Melbourne will actually do is is millrenown Will inhibit the phosphodastrase 3. therefore it will not break down cyclic amp if it doesn't break down cyclic amp this increases cyclic amp increases protein kinase a increases calcium influx and increases contractility of the myocardial cells so that is the primary function of milrinone is it is an inhibitor of the phosphodastorase enzyme so then you don't break down cyclic amp and it builds up in the cell and the same concept here

in the arterial smooth muscle cell here's our adenylate cyclase ATP is converted into cyclic amp it can be broken down by this enzyme what is this enzyme called pde three what is this enzyme called again p d E3 phosphodastory three and that'll break down cyclic amp so there's less of it okay if I have cyclic amp it's supposed to activate protein kinase a that's supposed to stimulate the what it actually doesn't do control the calcium channels and the smooth muscle cells it actually works on a specific enzyme and this enzyme is called myosin light chain

kinase okay when you phosphorylate the myosin lichen kinase which is odd I know you inhibit it if you inhibit it it then does not have the ability to activate the myofilaments and this leads to them relaxing okay now if cyclic amp is broken down by phosphodasterates I'll have less cyclic amp less protein kinase a I won't inhibit myosin light chain I'll actually stimulate it and then I'll cause the myofilaments to contract if I give a drug that blocks the phosphodastarase three it inhibits phosphodus 3-3 okay actually I did this with red here it's the same

concept it's just in the smooth muscle it's a slightly different pathway it's going to inhibit the phosphodastrase I'm not going to break down the cyclic amp I'm going to build it up I'm going to increase protein kinase a I'm going to in increase the inhibition of myosin like chain kinase and I'm going to inhibit the smooth muscle from Contracting if I inhibit the smooth muscle from Contracting it'll then relax if it relaxes it'll drop the systemic vascular resistance it'll drop the patient's afterload and it'll improve forward flow out of the heart because if I drop

after load I reduce the amount of work that The ventricle has to do to push blood out of it the only downside is that if I reduce resistance I may drop the patient's blood pressure a little bit okay so again milrinone is an I know dilator to sum all of this up dobutamine acts as an iodilator by stimulating beta 1 receptors that's the ionotropic activity and then stimulating beta 2 receptors to cause vasodilation that's the dilator activity Mill Renown is a phosphodiesterase 3 inhibitor and the cardiac muscle that leads to increased cyclic amp increased protein

kinase activity increase calcium influx and increase cardiac contractility in the arterial smooth muscle cell and if you increase contractility that's the inotropic activity in the smooth muscle inhibits the phosphodastrases which leads to increased cyclic amp increased protein kinasea increase phosphorylation of myosin light chain kinase which is really weird but please don't forget this inhibits the enzyme and therefore it can't phosphorylate the myofilaments therefore they can't contract therefore the muscle relaxes if the muscle relaxes it then causes vasodilation if you dilate you reduce resistance that reduces afterload improves overflow but may drop the patient's blood pressure

a little bit so the category of these drugs is they are I know dilators what is the adverse effects to watch out for we know why we use them we know their mechanism of action the adverse effects here particularly for dobutamine is that it actually hits the beta receptors of the heart so dobutamine it directly stimulates the beta-1 receptors on the nodal cells so with that being said one of the things that you want to think about here with dobutamine is that it can really cause a lot of tachycardia so it may increase the patient's

heart rate also if you increase contractility the reason why this is a problem is imagine you keep stimulating and stimulating and stimulating and stimulating the heart to contract eventually it's going to get weak that's one of the problems of CHF and so it can cause something called stress or taco cardiomyopathy which can actually worsen the patient's ejection fraction okay that's a problematic issue on top of that it also may cause vasodilation which may sound beneficial right it may sound beneficial because it's going to reduce afterload and that is a good thing so the positive thing

of that the positive is that reduces afterload the possible downside to that is that it can actually reduce your actual blood pressure potentially and that is where we actually have to consider that sometimes if it actually does drop your blood pressure you may need to add on a little bit of a presser like norepinephrine and so sometimes we need to just give them a little bit of norepinephrine to just squeeze the arteries just a little bit to maintain a blood pressure that's important and acute heart failure with cardiogenic shock it's not uncommon for patients to

be on duobutamine plus or minus norepinephrine to be able to maintain a proper blood pressure and still give good cardiac output okay because again remember blood pressure is dependent upon cardiac output and systemic vascular resistance if your resistance drops and you already have a poor cardiac output you're going to drop the blood pressure if you try to give you know the cardiac output a little bit of an increase that's good but sometimes you may need to just squeeze the arteries just a little bit to be able to help to improve the patient's blood pressure and

the same concept Mill were known has some of the similar side effects or adverse effects so when milrinone is added on what I would actually consider remembering for this one is that this one is really excreted so it is really excreted and so if a patient has acute renal failure this can increase the levels of milron which can cause it to actually have more adverse effects one of the things is that again it actually can be vasodilated it can cause vasodilation and again the positivity behind vasodilation for patients with CHF is that it will afterload

reduce and that sounds like a great thing and it is a great thing because it'll improve forward flow out of the heart but again it may reduce the systemic vascular resistance which may drop the blood pressure just a little bit because again you're dropping systemic vascular resistance that's going to drop blood pressure so you may need to add on a little bit of norepinephrine to be able to maintain a proper blood pressure for these patients who are in cardiogenic shock it's not uncommon all right my friends that's all the imotropic agents that's all the medications

but we're not done because I think one of the more important things is that we covered so many drugs we covered so many Pathways and mechanisms it can be so daunting and it can be very confusing to know okay well I just learned all these drugs if I have a patient that comes in and have heart failure I don't know if I'm gonna know how to treat them let me take you through if a patient has chronic heart failure how you'll medically manage them looking at potentially the New York Heart Association classification and then let's

say that you're in the ICU and you have a patient who comes in and they're in acute heart failure acute decompensated heart failure how do I know when to use some of these drugs and when to not use some other drugs we'll talk about that as well to finish off this look lecture all right my friend so now we have the patient who has chronic heart failure how are we going to manage these patients well we use something called the New York Heart Association classification and what this does is it looks like primarily like three

things it looks at the patient's symptoms it looks at the Patients if they're having symptoms present so in other words the pulmonary edema do they have fatigue do they have dyspnea do they have peripheral edema all of those symptoms that we discussed prior the thing I also want to know do they have structural heart disease so in other words do they have those remodeling changes do they have left ventricular dilation do they have left ventricular hypertrophy present and then do they have risk factors that put them at high risk for heart layer so like hypertension

and so that easily can kind of like help us to sparse out which one it is type A type B type c type D and that determines which types of medications we should put them on or what they belong on according to that so Heart Association Class A if we look at those three particular categories let's say first symptomatology does the patient have any symptoms usually in this particular classification they're usually having no particular symptoms and so if they're not really symptomatic that's one particular reason to think about these patients so not really symptomatic okay

the other thing is do they have any structural heart disease so they would have no structural heart disease so in other words they have no LVH they have no left ventricular dilation or cardiomyopathy present and then the last thing is do they have any risk factors that put them at high risk for heart failure and in this they would actually have that potentially presence so in this particular scenario they would have risk factors for heart failure so positive four risk factors and this could be things like hypertension that's pretty like very very prevalent in common

in patients with heart failure so with all of these this put you in class A what do they recommend well first they recommend like dietary changes things that are not meta like medication related so trying to risk factor modify reduce your dietary intake things of that nature working out all of these other things that you can do before you get put on medications but if you have to require medication the medication that is best suited here is an Ace inhibitor or an ARB so that's the first way that we start off not too bad then

we go to the next particular situation here now the patient has negative for symptoms but they have some type of left ventricular hypertrophia or left ventricular dilation and they have some type of risk factor so they're POS they're negative for symptoms they have some type of presence of left ventricular hypertrophy left ventricularation and they do have presence of risk factors such as hypertension or CKD Etc so in this particular scenario you have a patient who is not symptomatic they do have structural heart disease and they do have risk factors so now you're in a patient

population that fits in class B in that situation if the patient is on an Ace inhibitor okay or they're on an ARB then you add on another drug and so this is when you add on a beta blocker and again the beta blocker is best situated the patient has a low EF because it's going to initially drop it but it'll increase it eventually if they are post MI because it's been shown to reduce mortality or if they have coronary artery disease add this drug on it can reduce mortality okay then we move into class C

for Class C they do have symptomatology so they develop dyspnea exertional Edition they develop fatigue they have cool poor perfusion they have lots of like venous congestion within the pulmonary and peripheral circulation they do have structural heart disease left ventricular hypertrophy dilated cardiomyopathy present they do have positive risk factors such as hypertension CKD Etc so they have all three all three of these particular problems this puts them in class C so at this point the patients should be on a ace inhibitor or they should be on a ARB they should also be on a beta

blocker if they have a low EF their post MI or they have coronary heart disease the next thing to add on is you should add on a aldosterone antagonist so we should add on a aldosterone antagonist and then the other thing that we should consider here is alternative therapies so in other words if the patient is on Max so they're on max Ace inhibitor or an ARB and they're still symptomatic on Max Ace inhibitor or an ARB then you can do what then you can consider another drug what's that other drug that we actually talked

about then we can put them on and a r n i so that was succubital and valzartan if the patient is African-American or has some type of acute renal failure then they should be not on so then you can actually stop their ACE inhibitor so this would actually be not best so it shouldn't do an Ace inhibitor or an ARB instead you should do hydralazine and isosorbide dinitrate so you see how we're kind of going through this process here then if they have lots of symptoms like venous congestion within the pulmonary peripheral circulation then you

can add on diuretics all right so up to this point if a patient is Class C the way that we should look at these patients is if they have symptoms structural heart disease and risk factors they should be on a ace or an ARB okay they should be on a beta blocker add on an aldosterone antagonist if they're Max on an ace or an ARB and they're still not having benefit switch over to an arni if they have are African-American so if they're African-American with heart failure or they have acute renal failure you should not

be on Aces and arms so discontinue the Acer ARB and switch over to hydralazine and if the patient is symptomatic add-on diuretics all right so the last classification is a patient is refractory to everything so in other words despite everything that we have done for this patient okay they are still despite everything that we've done they're still symptomatic they're still having presence of structural heart disease such as left ventricular approach if you are cardiomyopathy like dilation effect and then they're still having presence of risk factors such as hypertension all right so all these things are

present so every single one of these are still present despite everything that we've done up above so at this point the patient should have been on let's say all of these things above they're on an ace inhibitor or an ARB if they're maxed and still having low EF and symptoms then you can do an a r and I if they are African-American and have acute renal failure switch so you'll switch to an arni for this one so switch to a r n i here you'll switch to hydralazine and isos or by dinitrate on top of

that they should also be on a beta blocker especially if they have a low EF their post MI you guys are gonna never forget this up and then CAD they should also be present on a aldosterone antagonist and then lastly they should also be present on a diuretic for symptom control of their venous congestion okay despite all that then what do we do then we add on I have a braiding and the reason we would add on I have a braiding is if they have an EF that's less than 35 percent normal sinus rhythm greater

than 70 beats per minute and they're maxed on a beta blocker as above okay or they have a contraindication to a beta blocker and then lastly we can add on a positive ionotrope like digoxin it's the only one that we should add on we can talk about acute heart failure the other ionotropes but this one we would add on as well and especially potential benefit afib if a patient has atrial fibrillation this may confer an actual additional benefit to this drug my friends this is how you would actually manage a patient who has chronic heart

failure step by step by step by step in a stepwise manner according to this classification system the difference is patient comes in with an acute heart failure so they have a history of chronic heart failure you're managing these patients and all of a sudden they come into the actual hospital and they're in Frank cardiogenic shock or they're in a hypertensive crisis and they're having an acute CHF exacerbation then how do you manage them let's quickly talk about that all right patient comes in with acute heart failure exacerbation they start to decompensate so generally a patient

who has heart failure right so if a patient has heart failure we already know that their problem is that they are going to have difficulty being able to generate the proper you know cardiac output so we know that their problem is going to be that they're going to have a reduced cardiac output but now they have an exacerbation the reasons why this could happen there's so many and I think it kind of goes beyond the scope of this lecture to talk about that because that's more of like the actual pathophysiology the clinical medicine aspect this

is supposed to be more of the pharmacology but if a patient develops an acute exacerbation I can mention a few of them some of the ones that you probably should consider that would actually cause this acute exacerbation it could be due to it could be secondary to things like an MI so if a patient actually knocks out like a piece of their myocardium their cardiac outputs you know considerably going to drop the other one is like medication non-compliance so if they stop taking their medications that's also going to be a problematic issue um another one

could be if they have acute renal failure because then it causes them to become volume overloaded and now they're dealing with more volume than they usually can another one is actually a hypertensive crisis so for whatever reason the patient's blood pressure shoots up to like 270 over you know 140 for whatever reason I'm just kind of giving you guys the point here but they have like a hypertensive crisis so their blood pressure is like crazy crazy high so this could be some of the reasons why the patient would go into an acute heart failure type

of reason they could blow a mitral valve they could blow an aortic valve there's a lot of different things of why this could happen but the whole concept is the patient had a reduction in the cardiac output they had some type of trigger and that trigger led to a further reduction in the cardiac output if I'm dropping my cardiac output that means that that's very little blood that is getting out of my left ventricle that's the primary one so that means that all the blood that I'm supposed to be squeezing out of my left ventricle

very little of it is getting pushed out of the actual left ventricle if that happens there's two problematic issues with that one is if I drop my cardiac output I know that I'm going to drop my perfusion of particular tissues and so what's going to result as a as a problematic issue of this further dropping cardiac output is I'm going to see a drop in my perfusion to the tissues now the question that you probably should be asking is what does a decrease in perfusion to the tissues look like we talked about this already right

guys so we said that it could be cool or pale type of skin we said that you could have decreased urine output because you're not perfusing the kidneys or this could look like what just Frank cardiogenic shock so the patient could be extremely extremely hypotensive and in multi-system organ failure right so there's a lot of different things that this could look like this is usually the concern and patients who are an acute heart failure this is the scary scary process of it is that they could stop actually perfusing multiple different organs and go into multi-system

organ failure what is this called again this is cardiogenic shock so this is the concern with this particular disease now that's the perfusion aspect the other thing that you've got to think about is yes I'm not pushing out as much of this blood so here's all this like volume of like blood inside of the left ventricle I'm not squeezing blood out as well so there's a reduction of cardiac out but if I'm not squeezing Blood Out it means a lot of it's sitting in here and that means a lot of it is going to back

up into the venous circulation one of those problems yes it could be it backs up into the systemic circulation that's definitely a possibility here so it could back up into like your superior vena cava could back up into the inferior vena cava cause peripheral edema jvd but that's not the real big issue here it's when it backs up into the lungs and so what it does is it increases Venus congestion like profoundly increases venous congestion so now because you're getting less blood out of the heart more of it's actually going to back up into your

pulmonary and systemic veins and cause venous congestion the real problem with this is that yes it can cause peripheral edema that but that's not what's dangerous that's not going to be like kill a person let's just make them feel they're very uncomfortable what's really bad is if it accumulates in the lungs because now all your alveoli and interstitial spaces are going to be filled with all of this fluid and so now your lungs are going to be super super congested and just ballooned up with all of this fluid and so you're going to end up

with all like this pulmonary edema that's going to accumulate here what's the problem with pulmonary edema my friends you start filling the alveoli and the interstitial spaces with fluid you're going to decrease uh V like the gas exchange process and that can reduce the O2 causing hypoxia and this is a terrible situation as well so the two like worst case scenarios with a patient Who develops acute heart failure is they don't get blood out of their heart which makes them have very poor perfusion to multiple organs with risk of cardiogenic shock and fluid back up

into the lungs causing VQ mismatch leading to significant hypoxic respiratory failure dangerous situation so you can see how this is the imbalance but not every single patient looks like this this is the worst case scenario all right so let's look at this this like really cool thing called the Forester classification because not every single patient like we said looks venous congested and low perfusion not every single one of them look like that so the Forester classification puts like perfusion on the y-axis and then congestion on the x-axis and what's cool about this is that as

you go further this way congestion increases right so we can say that congestion will increase as you go this direction and we'll say that perfusion sucks if you go down this way but perfusion is okay let's actually kind of say instead of saying increased the perfusion is normal or appropriate as you go upwards okay but congestion increases as you go this way so congestion is going to be increases you go this way perfusion is going to be somewhat normal and then it's going to be the lowest perfusion down here so let's actually look at it

like that like the worst case scenario perfusion is lowest at the bottom of the y-axis and then congestion is the worst at the tip of the x-axis okay so that puts us into four classifications and this one here I'd like to actually start here so this top one here they have normal perfusion they have normal perfusion right and they have decreased or like little congestion so they don't really have much congestion so if they have normal perfusion and very little congestion in this particular situation according to this kind of like Forester classification then they're well

perfused so their extremity should be warm they should be making urine their blood pressure should be appropriate they shouldn't mean Frank's shock so because that we call these patients warm congested they shouldn't have a lot of venous congestion their lungs shouldn't be super wet instead they should be relatively dry so in this patient population we use the term of this CHF patient is going to be warm and dry and this patient population they're stable you could actually send these outpatient and treat them the same way that you would The Chronic heart failure patient okay they're

stable this is a good patient if we go to the other particular extreme here we're now you have a patient who has normal perfusion their perfusion is appropriate so if their perfusion is appropriate they're perfusing their skin they're perfusing their kidneys they're actually generating a proper blood pressure they're not in front cardiogenic shocks so they're warm but they're congested they have a lot of fluid within their lungs so it's very wet lungs so if they have a lot of congestion in this particular situation they're warm because they're well perfused but they're wet because their lungs

are filled with a lot of flu because there's lots of venous congestion this is the patient population that you call warm and wet and this is the one that's actually not too bad all you got to do is just kind of increase their diuresis they're just a little bit kind of like volume overloaded maybe they're diuretic isn't it an optimal dose and all you got to do is just erase them a little bit to get off some of that extra flu because they're perfusing well so that's not the problem with perfusion it's just you got

to get some of that excess fluid out of their circulation they're a little hypervolemic the next classification here is they're poorly perfused but their congestion isn't so bad so in this particular situation this patient has a decreased perfusion so they're not going to be perfusing their skin they're not going to be freezing their kidneys they're not going to be having as good of a blood pressure so their blood pressure may be potentially a little bit on the lower end and they may look a little bad and so in this patient they're going to be cold

because they're not well perfusing their extremities but their congestion is actually not too bad so their congestion should be a little bit lower so their lungs aren't actually going to be filled with a lot of fluid so they're not going to be wet they're going to be dry dry lungs okay not a lot of venous congestion so we call these patients cold and dry for these patients they're actually pretty sick when they have a reduced perfusion that means that their cardiac output is very impaired you're likely going to need to put this patient to the

cardiac ICU so I would actually send this patient to the cardiac ICU and start them on inotropes okay because they're probably going to need a little bit of benefit to push blood out of their heart these patients actually do have somewhat of an increased mortality rate okay the last classification is the worst case scenario this is this patient this is the scary patient you need to be able to recognize this patient as we go this way congestions increase in perfusion is at the worst so this patient has very poor perfusion so they're going to be

cold cold extremities and they're going to have lots and lots of congestion so their lungs are going to be filled with fluid lots of venous congestion so they're going to be wet so this is the worst case scenario where you have a patient who is cold and wet they need to be in the cardiac ICU and they need to be on a lot of medications that we're going to talk about above so it's likely that they're going to need multiple interventions and that's what we're going to focus on right now is talking about those interventions

that we're going to utilize for these patients because these are the sickest patients these are the ones that have the highest mortality rate highest mortality rate so we need to be able to know how to treat these patient populations because this is the key thing okay so let's talk about that now because the problem is with these patients is they have poor perfusion and they have lots of venous congestion what I got to do is is decrease the congestion how do I do that I'll talk about that and then reduce the perfusion I'm sorry uh

increase their perfusion so how do I do that let's talk about that next all right my friends so a patient who is cold and wet is the scariest one okay so they're congested that means that their lungs are wet they probably have a lot of like peripheral pitol edema maybe even some actual like fluid in their abdomen sometimes they can even have an abdominal compartment syndrome so that's a pretty bad situation right how do we get that kind of excessive amount of like volume or fluid out of their body because right now the fluid is

where I don't want it to be it's some of it's in their vasculature but a lot of it is in third space into the pulmonary interstitium alveoli inter social spaces in my abdomen interstitial places in the lungs and I mean in the lower extremities so how do I get rid of that reduce the blood volume reduce the amount of sodium and water inside of our circulation so if I reduce the blood volume I'll reduce the amount of actual like preload and reduce a lot of that kind of like third spacing of fluid reduce the edema

so the way that I can do that is I can actually reduce preload and the way that I reduce preload is I can do it in two ways one is if I reduce preload I can I can actually again reduce a lot of the venous congestion so the whole concept is if I help to be able to reduce preload I reduce the congestion of the actual I reduce the blood volume I reduce the amount of blood going back to the heart I reduce the excessive congestion of the venous circulation and that's the benefit to this

so preload I can utilize doing this to help to be able to cause less sodium and water reabsorption and instead cause me to pee out a lot of the sodium in water and this is where diuretics are actually very very crucial so I'll give them diuretics and I'll give them very high generally for these patients they may need IV and I'll give them a combo usually I'll give them something like a loop and a thiazide like I told you that combo sometimes I'll do a combo where I'll do like metolazone and furosemide to help them

to really augment their diuresis and put a lot of excess fluid because if I decrease the preload I'm going to decrease the venous congestion so that'll decrease the venous congestion and then drop some of the blood volume because right now this patient is hypervolemic the other way that I can reduce preload to reduce the venous congestion as I can Vino dilate so if I drop the preload again I can drop venous congestion which is the problem in this particular disease one of the ways that can do this may be causing Vino dilation so if IV

no dilate I reduce venous return and that reduces preload the drugs that I can utilize for that is going to be things like nitroglycerin and morphine and then that is going to be the big things now morphine is actually not going to be something that we commonly utilize but you can consider it'll actually Vino dilate and again if I reduce the venous return I reduce the amount of blood coming back to the heart and I prevent any further congestion so if you imagine this poor left ventricle here it's already got this amount of fluid sitting

in it okay and then if I have a lot of venous return I'm going to add more fluid on top of that and then on top of that on top of that and it's just going to keep backing up at the lungs if I inhibit that process and inhibit any further filling of the lungs I'm going to prevent any further venous congestion reduce the blood volume and help to prevent any of that more fluid from accumulating so that's going to be a potential benefit and I actually may remove some of that fluid that's going to

be the potential benefit from the medical therapy some other things that you could do that are non-medical is BiPAP I love BiPAP for these patients and on top of that maybe even like positional changes having them kind of like seated upwards having their legs kind of dangling down that actually can be a somewhat potentially beneficial as well okay so reducing congestion is going to be helping to give them diuretics this is going to be front line so first line nice IV diuretics and then second would be helping to Vino dilate to reduce the preload things

like nitroglycerin or morphine okay for the other situation I want to improve perfusion so right now my extremities are cold I'm not making urine my blood pressure's low and I'm not perfusing a lot of organs I'm at risk of multi-system organ failure what do I do for these patients and these patients there's two patient populations and it seems confusing but it is possible in one patient population you can have an extremely hypertensive hypertensive CHF patient so you can have a hypertensive acute heart failure patient believe it or not and these patients they have a significantly

reduced cardiac output but for some reason their systemic vascular resistance is through the roof so if they're systemic vascular resistance is through the roof that could be the problem because remember blood pressure is dependent upon two things it's dependent upon cardiac output and it's also dependent upon systemic vascular resistance so though this may be kind of like low and that will drop the blood pressure if I increase the systemic vascular resistance that may increase the blood pressure okay so in these patients they are super super vasoconstricted now if I have this patient who is in

a hypertensive acute heart failure this is an interesting patient population so sometimes we call this uh we call this like flash pulmonary edema or we call this like sympathetic crashing acute pulmonary edema but this is a patient who has a lot of venous congestion because their afterload is so high so they're so clamped down on the arteries that their afterload is just insanely insanely high so it's almost impossible to get blood from the left ventricle out into the aorta and into the systemic circulation this is pretty much like inhibited so you don't get any blood

out of the heart so cardiac output drops but your arteries are so dang clamped down that the blood pressure is so high and on top of that if you can't get blood out of the heart it backs up into the lungs so this is actually called sympathetic crashing acute pulmonary edema or Flash pulmonary edema and you can see this was super super hypertensive patients now the strategy for these patients is a little bit different you can still put the you can still do like things like nitrates like nitroglycerin or morphine BiPAP for these patients I

wouldn't direese them because they're not a volume they're not a hypervolemic type of patient this is the patient who you just need to kind of like dilate their arteries you dilate their arteries you reduce their afterload and you improve forward flow and prevent any of that backflow back into the lungs that's really it and so for this patient population it's all about afterload reduction in other words I need to decrease my systemic vascular resistance that's all I got to do and so the drugs that I actually find to be very beneficial in this particular situation

is high dose nitroglycerin so high dose nitroglycerin another one could be hydralazine and isosorbide dinitrate I like this combo just because patients usually take in this situation they have a lot of acute kidney injuries because if they're not perfusing organs so I can I like to do hydralazine and isosorbide nitrate another option is you could consider potentially a ace inhibitor or an ARB because all of these are going to afterload reduce they're going to reduce your systemic vascular resistance if they reduce your systemic vascular resistance what do they do to this equation then so in

this patient right now their blood pressure is like through the dang roof and that's impairing their cardiac output because their resistance is so high I can't get blood out of the heart so what I'm going to do with this patient is I'm now going to reduce their systemic vascular resistance and I'm going to allow for Less afterload if I have less afterload then I'm going to help to be able to push more blood out of the heart so the cardiac output will start to improve and go up a little bit and so less fluid will

back up into the lungs and the blood pressure will start kind of normalizing to coming down okay and that's what my goal is is to try to get this to actually come down a little bit or to normalize so that's kind of the goal with this particular therapy now you have the other patient this is the one that's really scary so again when we talk about acute heart failure patients just remember this is one of those variants this is a kind of a relative variant where a patient has acute heart failure due to their systemic

vascular resistance being so high they're super hypertensive that they actually require afterload reduction nitroglycerin and BiPAP for all the other patient populations they infarcted their M they have an MI they stopped taking their medications they blew a mitral valve they blew an aortic valve they went into acute renal failure one of those particular reasons and their cardiac output dropped so much that they didn't get blood out of their heart they caused fluid to back up with their lungs and the perfusion dropped so much that they went into potentially cardiogenic shock then you start thinking about

diuretics again nitrates potentially morphine BiPAP and then you go into this next particular situation and this patient who may be is hypotensive hypotensive so this patient has a very low blood pressure high potential acute heart failure so this is that cardiogenic shock and these patients their systemic vascular resistance may be somewhat normal but their cardiac output is so dang reduced that their blood pressure is crazy low okay so their blood pressure is so dang low because their cardiac output is so reduced in the systemic vascular resistance is normal so their blood pressure tanks in this

particular situation it's all about getting this myocardium to squeeze harder and push more blood out and so what I'll do is I'll do positive inotropes and in this situation you'll do things like dobutamine or you'll do things like Miller known but what did I tell you can happen with these drugs what's a potential adverse effect because yes you are increasing their contractility to increase their cardiac output but you'll vasodilate them a little bit they can reduce your systemic vascular resistance if your cardiac output's already reduced and then you drop the systemic vascular resistance a little

bit you may drop their pressure so a potential adverse effect of this is that you may drop the patient's blood pressure and they're already hypotensive so sometimes it is not uncommon to be on dobutamine or mil Renown plus or minus norepinephrine which is a presser an oppressor will help to be able to squeeze their arteries so this will help too increase their systemic vascular resistance enough to be able to increase their blood pressure Okay so to summate here a patient who comes in who has what type of problem they're cold and then they're wet and

that patient there the worst case scenario they have very poor profusion they have lots of congestion you reduce the venous congestion by direesing them giving them things that reduce their preload by actually causing Vino dilation nitrates morphine you can also consider BiPAP and then positioning of the patient where their legs are dangling and they're kind of seated upwards you can improve perfusion but there's two different scenarios this is one completely different animal hypertensive a heart acute heart failure is like scape or Flash pulmonary edema their resistance is so high because their blood pressure is high

and their vasoconstricting like a son of a gun so because they're vasoconstricting all you need to do is relax those arteries because the problem is if they're vasoconstricted imagine how hard it is for the left ventricle to pump blood into that vasoconstricted artery if I relax them I'll help to get blood flow out of the heart and improve cardiac output and reduce the venous congestion how do I do that after load reduction okay if I have a hypotensive patient on the other hand that's a completely different animal and this situation maybe their systemic vascular resistance

is normal but their cardiac output is in the tuchus if that's the case I need to squeeze The myocardium to generate a better cardiac output and improve the forward flow and if I squeeze blood out of the heart that's a great thing and if I afterload reduce that seems like a great thing because that again helps get forward flow out of the heart but it may dilate them a little bit and drop their pressure a little bit more so sometimes you got to give them a little bit of resistance of their vessels to increase their

blood pressure and that's the thing to remember one thing I please this this annoys me so much is if I put a patient who's hypotensive on dobutamine or I put them on some type of like pressure of kind of that nature hold their beta blockers it makes no dang sense to be on a beta blocker and also be on dobutamine pick what you want okay so hold their actual beta blocker if they're on a binotrope like dovetamine I would also be careful with ACE inhibitors ARB I would consider holding these medications if the patient has

renal failure acute renal failure I wouldn't do these they're going to potentially increase the creatinine even more so with that being said this covers everything that we need to know about heart failure management or drugs that are used in heart failure I hope it made sense let's do a couple cases and put this into practice and really understand it all right the engineers let's do some questions here all right so we have a patient who's newly diagnosed with heart failure with reduced DF is asymptomatic which of the following is the most appropriate drug to initiate

for symptomatic and survival benefits it's always going to be an Ace inhibitor and ARB and then a beta blocker okay that's generally going to be the first kind of starting process here so which one of those is an Ace inhibitor ARB that'll be the first line and the next one will be a beta blocker so in this case lisinopril will be the first option because against your Cuba drill valzartan that's an Anri we don't do that unless the patient's been a maximal or optimal ACE inhibitor or ARB and they're still not having the exact point

that we want them to be at they still have a low EF and again they have a contraindication to them so it should be C Lisinopril which of the following best describes the action of Base Inhibitors on the failing heart well again ACE inhibitors are going to reduce vascular resistance so it's not a it's going to increase cardiac output so it's not B it's going to reduce preload that's actually true because again it's going to inhibit the ADH and aldosterone which will inhibit the sodium water reabsorption and and decrease your preload your your actual venous

return to the heart and Angiotensin II you're going to block that so you're actually going to inhibit the venal constriction mechanism so it should reduce preload C Hispanic man with half ref currently takes maximally tolerated doses of metoprolol succinate and allopril along with moderate dose furosemide he is euvolemic but continues to have heart failure symptoms the systolic blood pressure is low but the patient doesn't have any signs or symptoms of hypotension which is good which is the best recommendation to improve heart failure symptoms and survival in this patient okay so they're already on a beta

blocker so again if we go off the New York Heart Association a you add on ACE inhibitor or an ARB they're on that then beta blocker for type B they're on a beta blocker then for symptom control that you can add on things like furosemite but the other thing that you should do in heart failure Class C is consider if the patient's on an Ace inhibitor or an ARB you can also add on an aldosterone antagonist because that's going to reduce the mortality associated with reduced ejection fraction so if they have a low EF and

they're again on an Ace inhibitor and ARB and they could tolerate nadashtrian antagonists give them that so it should be spironolactone or Epler known so it should be D in this case all right four beta blockers improve cardiac function and heart failure by well they they do decrease cardiac remodeling so that's definitely going to be one that's likely the answer but increase heart rate No it decreases it it decreases rent and release and it decreases the activation of norepinephrine or per box norepinephrine if you want to think about it so it should be a 70

year old woman has half ref and hypertension she takes lisinopril so that's the first imase inhibitor in group a she's on metoprolol tartari so that's for type for the class B she feels well has no cough shortness of breath or edema which of the following changes is most appropriate for her drug therapy well she's asymptomatic at this point she's controlled on metoprolol and lisinopril which is great but here's the problem as we talked about in the lecture metoprolol tartarate is better for hypertension metoprolol succinate which is the extend to release the long-acting one usually that's

going to be way more Superior in patients who have heart failure so I would switch her from metoprol tartarate to metoprolol succinate because her heart sucks okay that's literally how we remember right so the heart socks Doom metoprolol sucks in a because it's better in patients who have heart failure so it should be D all right and again just to kind of go through this initiate digoxin again we would do we would add on other therapies if the patient was still symptomatic or was having worsening structural heart disease or the refractory so I have a

braiding would be refractory to Medical therapies changing lisinopril to losartan she has no adverse effects from it so that's not necessarily necessary and again digoxin will be for refractory heart failure that's not responding to Optimal medical therapy she's not having that problem so change it to the metoprolol succinate because the heart sucks 75 year old white man has hefref reports stable heart failure symptoms current drug therapy includes optimal dose of nalapril Carvedilol which is a beta blocker so they're on ACE inhibitor on a beta blocker and they're also on spironolactone okay so they tolerate it

up to this point these three particular drugs which is the best recommendation to improve heart failure symptoms and survival that's a great question so in these patients who are on let's say an Ace inhibitor they're on a Max dose of an Ace inhibitor or a Max dose of an ARB they're on a beta blocker they're on a aldosterone antagonist and they still have a reduced DF but they have stable heart failure symptoms but we want to improve them that's when we add on or we switch and get rid of the enalapril and do a neprolysin

inhibitor with an ARB okay so it's a cubitril and valzartan that would actually be this particular situation so it would be replace the enalapril with circuitry on Valsartan because if a patient has a low EF they're on maximal dose of enalapril okay or an ARB or they have a contraindication to those you should try and switch them over to a an AR and I in this case this is the perfect situation just to cross out the other answers hydralazine isosorbate and nitrate it's usually better in African-American I have a braiding that's usually if the patient

we would have to have specifically in there the abnormal sinus rhythm greater than 70 beats per minute they're already on Max dose beta blocker or they can't tolerate a beta blocker then you would talk about either braiding this is not a scenario where that mentions any of that starting digoxin that's not a bad idea but the patient has stable heart failure symptoms it would be if they were having refractory heart failure symptoms despite being on a nalopril Carvedilol spirinolactone or an a uh arni then you could say okay then we could consider digoxin as long

as we've also provided symptomatic control with diuretics and again then if you're at the last point where you're a fractory you can add on digoxin if they have a half ref so in this case it should be C how is spironolactone beneficial in heart failure promotes a potassium excretion no it actually blocks that acts as an aldosterone Agonist no it actually acts as an adoctrine antagonist prevents cardiac hypertrophy yes in general it prevents like cardiac remodeling which could be a hypertrophy or could be dilation but in general it prevents cardiac remodeling so yes and that's

why it reduces mortality it should be seed decreases blood glucose has no effect on it okay which of the long is important to monitoring patients taking Digoxin it should always be potassium hypokalemia can worsen and increase digoxin toxicity but digoxin itself can cause hyperkalemia so watch that potassium my friends which of the following best describes the mechanism of action of Melbourne and heart failure what's a phosphodiesterase inhibitor of the type 3 in a flavor and it works and the cardiac muscle to increase contractility in the arterial smooth muscle it causes vasodilation so if we look

at this decreases intracellular calcium no it'll actually not do that it should actually not affect that calcium pathway increases cardiac contractility it actually will increase cardiac contractility how because it inhibits the phosphodastrase you don't break down the actual sick so in this situation let me start this one over all right next question here we have which of the following describes the mechanism of action of milron and heart failure decreased intracellular calcium no not necessarily increases cardiac contractility decreased cyclic ampere activates phosphorus rates okay mechanism of action it inhibits phosphodiesterosis if you inhibit phosphodiesterase and generally

what that's going to do is that's going to increase cyclic amp that'll activate the protein kinase a protein kinase a will then do two things one in the cardiac muscle cells it'll increase calcium influx so that already gets rid of a it increases cyclic amp that gets rid of c and it inhibits phosphodastarases so that gets rid of D and then it's B Y because if we increase calcium influx into the cardiac muscle cell we have more activation of the myofilaments and then increase in the cardiac contractility so it should be B uh BH is

a 52 year old African-American woman who has hephraf she has seen in clinic today reporting stable heart failure symptoms but is having occasional peripheral brightness interesting otherwise vision is unchanged current medication regimen includes circuitry valzartan Carvedilol fix dose hydralazine and isosorbidden nitrate I have a brainine and bimetanide so this patient is on an AR and I okay so she either did not tolerate an ace inhibit or an ARB or she would not be the best candidate for an Ace inhibitor or ARB or again she would experience more benefit because she has a low EF and

she would have benefit more from an AR and I okay she's on a beta blocker car beta law she's on high hydralazine and isosore by nitrate which is really interesting because that's been shown to be better than ACE inhibitors or arbs and patients who have uh heart failure and they are African-American so that's a good component there I have a braiding so she must be normal sinus rhythm with a heart rate greater than 70 and already Max on Carvedilol and then lastly bumetonide which is a diuretic to help the symptomatic edema that she may have

which is the best recommendation to minimize the adverse effects of peripheral brightness well peripheral brightness the only one that could potentially even do this would be two drugs generally digoxin could cause like some visual changes and I have a braiding digoxin is not mentioned here so because of that the only other option here is going to be the Iva braiding so I would not stop all the heart family medications you're probably put into a heart failure don't discontinue the succubital zartane and has no effect on that and do nothing this adverse effect will slowly improve

over time that's not necessarily true and then reduce the dose of vibrating that is actually I think that's the valid reason because again there's only two drugs the Jackson or I have a braiding I would reduce the dose of the average and see if she's okay so that is the answer all right my friends that covers the actual questions and the cases here on heart failure medications I hope it made sense I hope that you guys enjoyed it as always thank you love you and until next time [Music]