Drugs affecting the cardiovascular and hematological system. Cardiac cycle. The time frame is from the beginning of one heartbeat to the beginning of another.
In systole, the ventricles contract. We have increased pressure that occurs from the ventricular contraction and this causes the mitral and the tricuspid valves to shut. The aortic and the tricuspid and the pulmonic valves open. and this allows ejection of the blood into the aorta and the pulmonary artery. During diastole, the ventricles relax.
This allows the mitral and the tricuspid valves to open and allows blood to flow into the atria. Atrial contraction occurs at the end of diastole and pushes the blood from the atria into the ventricles. Unoxygenated blood is returned via the superior and inferior vena cava to the right atrium, where it is moved then through the cycle to the right ventricle. Blood leaves the right ventricle via the pulmonary artery to be reoxygenated in the lungs.
The oxygenated blood returns to the left atrium via the pulmonary veins and then moves into the left ventricle. Blood is ejected from the left ventricle to the body via the aorta. The stroke volume is the amount of blood that leaves the left ventricle with each contraction. This is normally about 75 milliliters.
Now it is dependent upon several factors. First of all is the preload and this is the passive stretching force on the ventricular muscle that is created by the amount of blood that is filled the heart and so it's the amount of blood that is there at the end of diastole. The preload is affected also by several things and so we look at the venous return and this is the amount of blood that is returned from the periphery to the heart.
If there's not enough blood returning then you're going to have a lower preload. If the atrial contractility also will affect your preload. And so the ability of the atria to contract forcefully enough to move the blood from the atria into the ventricles will also affect this preload because otherwise you're going to have stasis. And then the amount of blood left in the ventricle also affects our preload. Think about somebody that has actual failure and they don't have the ability to move the blood out into the central circulation.
If that blood is actually staying in the ventricles, and the atria have good contractility and move that blood into the ventricles, you're going to have that buildup and increased stretching of the ventricular muscle. Some other things that actually will affect our stroke volume. This is the force of the ventricular squeezing so that the ventricle is able to achieve and eject the blood into the systemic circulation.
If you have a very weak muscle or a damaged muscle that, say, somebody had a myocardial infarction, and instead of replacing that with that elastic muscular strength, they replace it with scar tissue. they are going to have decreased ability and decreased contractility. Some of the other things that can also affect our stroke volume. This is the concentration of catecholamines in the heart.
The more catecholamines, the greater the contractility. And so somebody that has a lot of that force, you will see more force of contraction. The last thing we want to discuss is the afterload.
The afterload is the resistance against which the left ventricle must eject its blood and so it's the resistance that it has to overcome. When we look at this, I always have compared it to the straw and the garden hose. If you had a straw, a drinking straw, next to a garden hose, and you looked at the diameter, there's an obvious difference there.
Think if you were trying to force fluid into either of those structures, it would be a lot easier to do it in the holes because it's more open, more dilated. And so when we look at afterload, if we have somebody that has a constricted or smaller diameter of a vessel, it is going to require a lot more force and workload and therefore the heart may not be able to eject that blood. And so when we look at the peripheral resistance, this is a key factor. So the cardiac output is the volume of blood that leaves the left ventricle in one minute. The stroke volume, which remember we said is around 75 milliliters per stroke, times the heart rate.
And so when we're looking at the cardiac output, the body likes a set amount. Let's just say around two and a half to three. leaders. So if you have somebody that has a poor stroke volume due to damage to the heart or decreased volume, then the way that the body will compensate is by increasing the heart rate. So if you have a low stroke volume, then the heart rate is going to increase.
If they've got a lower heart rate, then usually we're going to see a heart that is able to have a larger stroke volume. And so what we look at is these factors are going to be going up and down so that the body ends up with a good cardiac output that is sufficient to meet its oxygen needs. of heart failure, several compensatory mechanisms attempt to maintain cardiac output and meet the body's systemic demands. This causes a chronic activation of the sympathetic nervous system.
So with all of the changes involved with the sympathetic nervous system and that we can start to see changes in myocardial hypertrophy and myocardial hypercontractility. The increased sympathetic drive also results in the activation of the renin-angiotensin-aldosterone system, the RAS system, everybody's favorite. This results in systemic vasoconstriction and sodium retention.
So let's break this down a little bit more. So when we have decreased cardiac output and systemic pressure, Renin is released as, again, the kidneys are not getting adequately perfused. Now, renin is the enzyme produced in the kidneys in response to impaired blood flow and tissue perfusion. The release of the renin acts on angiotensinogen, and this is from the liver, and it forms angiotensin 1. Now, this next part I really want you to listen to because when we talk about drugs, This is where we're interacting.
The vascular endothelium, particularly in the lungs, has the enzyme that is produced, the angiotensin converting enzyme. So this is where ACEs actually work. And this production of this enzyme stimulates the production of the angiotensin II. Now angiotensin II is a powerful vasoconstrictor. And it...
actually will trigger a cascade of effects that are aimed at restoring blood flow to the vital organs and enhancing tissue perfusion. So number one, it acts on the adrenal cortex to release aldosterone. Now this release of aldosterone acts on the kidneys to increase sodium retention, and with the sodium comes the fluid.
So now we have increased fluid and being retained in the vascular system. And our sick heart wasn't doing well as it was. Number two, it stimulates the release of vasopressin, and this is the antidiuretic hormone. And this causes increased retention of fluid by the kidneys.
It also stimulates cardiac hypertrophy, and this is that adding of extra muscle. And then the last thing is it causes arterial vasoconstriction. The problem is that this increases the resistance, referred to as the afterload, that that left ventricle is having to pump again, making it even more ineffective.
So it increases the filling pressures inside the heart and it increases the stress on the heart. Because now we've got increased stretch of the muscle. When we have this increased stretch in the cardiac tissue, this stimulates the release of the natriuretic peptides. The response that the body follows is to increase sodium excretion. By the kidneys, increased diuresis, direct vasodilation, and it increases glomerular filtration rate.
It also reduces the renin production from the kidneys. So all of these things are aimed at correcting, or at least to assist in correcting, this fluid overload caused by this sympathetic innervation that took place. Previous slide. Heart failure is a condition that results in low cardiac output because the heart is unable to pump sufficient blood to meet the metabolic demands of the body.
The normal compensatory mechanisms of the body that cause fluid retention result in increased preload, while the vasoconstrictive actions of angiotensin do increase the afterload. The overall interaction can cause decreased cardiac output from the left ventricle. This results in an increased heart rate to ensure perfusion. Common risk factors are coronary artery disease and hypertension, and these are major causes.
We also see people developing heart failure following myocardial insults. Drug therapy for congestive heart failure aims to alter one or more of the factors affecting the heart to improve overall cardiac function. This is a common list of medications that can be utilized in the care of individuals with heart failure. Please do not think that the way they are listed is the order in which they would necessarily be utilized. It is just an easy way for you to remember.
So let's go through these ACE inhibitors, and I've also added the ARBs there. Again, we'll interrupt the RAS system and stop that production of the ACE enzyme and going from angiotensin I to angiotensin II. So it interrupts that.
It also decreases the secretion or the production of the aldosterone, which lessens the fluid and sodium retention. Beta blockers. Beta blockers can be utilized, though very cautiously, as they decrease the overall requirements for oxygen.
They also decrease the overall workload of the heart. Calcium channel blockers, again, can be utilized to slow and decrease the force of contraction. Didoxin is a cardiac glycoside.
Now, I am going to tell you up front that this is an older medication. We are all still learning it, as you will still frequently see it utilized and frequently see it on your NCLEX. This medication.
While it does have some very inherent risks associated with it, it does increase the overall force of the myocardial contraction. And so it can help people with a very poor ejection fraction have a better outflow of blood. And then diuretics.
These can be utilized by care providers to decrease the amount of blood. fluid retention. When we talk about treating somebody that has congestive heart failure or heart failure, our goal is going to be to decrease that workload of the heart while increasing circulation. So we want to unload some of that excess fluid.
We want to set the patient upright because that improves their ability to have that respiratory function. And then there's a lot of the medications which we are going to be discussing. Nitrates, you've previously discussed. But think about the effect they would have on the body and the heart.
As they vasodilate, they allow the heart to pump and circulate that blood with decreased effort. Diuretics, we're going to be talking about Lasix here shortly. ACE inhibitors and digoxin. Now if we're trying to unload fluid using medications such as furosemide or Lasix, we need to decrease their intake as well.
The whole goal is we're going to try and decrease the afterload or that peripheral resistance that the heart is having to pump against. And so some of the other things that can decrease that are are things like sodium restriction because it will decrease the amount of fluid that the body is holding on to. And then we want to go ahead and test things like digoxin levels and potassium levels.
So the way to remember it is the mnemonic unload fast. ACE inhibitors or angiotensin converting enzyme inhibitors are used in treatment of hypertension as well as in heart failure. Now, we are going to actually use Captopril or Capitan as our prototype.
Though I do want to make you aware that Enalapril or Vasotec may be more commonly seen if it is only being used for heart failure and not hypertension as well. The pharmacodynamics of Captopril is that it inhibits the angiotensin converting enzyme. This angiotensin converting enzyme changes the inactive angiotensin 1 to active angiotensin 2. So angiotensin 2 is a very potent vasoconstrictor.
With decreased angiotensin 2, we lose this vasoconstriction. And so we actually have relaxation of the peripheral vasculature. Decreases in angiotensin II also result in decreased aldosterone. Now, aldosterone actually is responsible for increasing retention of sodium in water, and this increases the circulating volume. If the aldosterone is decreased or blocked, it's going to prevent that sodium and water retention.
And so we will have decreased peripheral resistance and decreased circulating volume. Now when you think of somebody that has heart failure, all of these things are going to assist. The cardiac output is actually going to be increased without increasing the heart rate. and the peripheral resistance is going to be lowered without affecting this. It also will increase renal blood flow, but it doesn't have any effect on the glomerular filtration rate.
Now one thing to be aware of is that the potassium may be slightly increased, and this is actually a result of the decreased aldosterone. Remember I said that aldosterone will have you retaining sodium. Well, if there is no aldosterone, the sodium is actually excreted by the kidneys. But because the kidneys like to keep a balance of the electrolytes, they will hold on to another positive electrolyte with a similar charge. And this is usually potassium.
And so you really do have to monitor for patients, especially renal patients or patients that are on other potassium substances as they are more at risk for hyperkalemia. So Captopril is actually fairly readily absorbed when taken orally, though it is a problem because food can decrease absorption. And so it's very important that we teach patients that this is taken an hour before meals or two hours after meals so that they can time it appropriately because we don't want them to have decreased effectiveness of the medication due to lack of education.
It does cross the placenta and it can enter breast milk. And as I mentioned previously, it is a category D. It does have some risk of teratogenicity.
And so it's very important that we make sure that patients that are of childbearing age females are on birth control and are aware of the risk factors. It is metabolized in the liver and excreted from the kidneys. And so it's very important also that we monitor how functional somebody's liver and kidneys are because it can affect our risk of toxicity and adverse effects with this medication.
These inhibitors may be utilized in the treatment for hypertension. They are very useful as part of the treatment in heart failure. They also are considered to be first-line therapy. in diabetics, in treatment with diabetic nephropathy, not neuropathy, nephropathy.
Some of the adverse effects that patients should be educated about, one of the more common ones can be a chronic cough. And this is due to the fact that the enzyme is actually in the endothelium of the lungs because we do not have that ACE. enzyme, we can have a decreased breakdown of the bradykine and the cytokines, which is thought to be the rationale for the cough. Therefore, they can have more reactive airways. They may develop a chronic cough.
While it isn't necessarily harmful, it is the reason most of the patients choose to voluntarily stop the medication, not always contacting their provider. And so it's very important that if the patient develops a cough, they are told to call their provider because we would much rather switch them to another medication. And so you don't want them to just stop the treatment.
Patients may also develop hyperkalemia, and this is due to the inhibition of the aldosterone, and therefore they do not hold on to sodium at the level of the renal tubules. and they will hold on therefore to potassium. Some of the signs and symptoms that you should teach patients to monitor for is an irregular pulse, if they start noticing that their pulse is irregular, if they have muscle cramping followed by extreme muscle weakness, nausea and vomiting.
Serious adverse effects is angioedema, And neutropenia, this is the decreased neutrophils. So angioedema, it's an acute, very rapid onset, painless. They get swelling of usually short duration involving the face, the neck, the lips, the hands and the feet.
They can have swelling in the throat, so it is important that they notify the provider. Patients also need to be aware of, again, neutropenia and agranulocytosis. And this agranulocytosis is a lack of all of the cells that are produced in the bone marrow. So you need to teach patients how to monitor for these things. If they start experiencing more infections, such strep throat, if they have bruising.
that is unexplained. Increased fatigue, which would be the lack of red blood cells. They may need to have occasional CBCs monitored. There is an FDA black box warning for both angiotensin converting enzyme drugs and your angiotensin receptor blocking drugs, your ACEs and your ARBs. There has been an increased risk of neonatal harm after in utero exposure to the ACEs or ARBs during the second and third trimester.
The mechanism is thought to probably be the inhibition of the fetal RAS system. And so this causes decreased kidney function, which results in something called. oligohydraminose, which is that increased fluid surrounding the fetus, it also impairs lung development. So they are considered to be a category D during the second and third trimester. Now, both drugs are also considered to be teratogenic in the first trimester.
In other words, if there is an individual contemplating pregnancy, they should not be prescribed either ACEs or ARBs. If they are currently taking them, the care provider should be approached about an alternative. If a person finds they are pregnant while taking these medications, they should be instructed to immediately notify the care provider so that they can be switched.
To maximize the therapeutic effects, patients should be taught to take the medication one hour before meals or two hours after meals. And this is because we do see decreased absorption with food. To minimize some of the adverse effects, clients need to be taught to continue to monitor their blood pressure.
Now, one of the things that we have noticed with ACE inhibitors is that the first couple of doses, we can see quite a severe drop in blood pressure and hypotension. For this reason, many care providers actually choose to administer their first couple of doses at night. But it's important for the patient to understand that we do need to monitor their blood pressure and to kind of make sure that it's staying within stable ranges.
They should be taught to continue lifestyle changes, so changing diet, exercising, all of the things that they had been previously taught to treat the hypertension. They should be taught signs and symptoms of hypotension, lightheadedness, dizziness. If they are...
seeing spots before their eyes. They should change positions slowly. They also need to be very aware of the signs and symptoms of hyperkalemia, irregular heart rate, muscle weakness, nausea, vomiting, and to notify the care provider if they are experiencing any of these things on a regular basis. We're progressing to the next medications. I want to cover some terminology, and you do want to be familiar with this terminology, as it will be included in test questions.
Inotropic. This is the term that refers to modifying the force or speed of the contraction of the muscles. So when we are talking about the heart, a positive inotropic drug increases the force of the cardiovascular muscle contraction, while a negative inotropic drug weakens the force of contraction.
Chronotropic describes the agent that can change the heart rate. So when we talk about the pacemaker of the heart, we're talking about the SA node. So when we talk about a chronotropic drug, chrono is time, A positive chronotropic drug will increase the rate that the SA node sends out the signal, so you will have an increased heart rate.
While a negative chronotropic drug will decrease the rate from the SA node, and so you will have a slower heart rate. The last term is dromatropic, and a dromatropic agent is one which affects the conduction speed, primarily in the AV node. So what we're referring to is how fast the signals are passed through the AV node.
Think of it as a toll gate. So if it is negative, a negative dromatropic drug slows the conduction. And so you will have slower conduction through the AV node. Therefore, you will have slower response by the ventricles and response from the muscle. A positive dromatropic would increase the speed of conduction through the AV node, and you would have a faster response.
Beta adrenergic blockers. We will be studying two medications in this class. The first is the non-selective propranolol, and the second is the selective metoprolol. I will explain more about non-selective and selective drugs.
I refer to as being selective or non-selective. We are talking about their preference or their overall effect on different receptors. Now, when we are referring to betas, both beta-1 and beta-2 receptors can be acted upon. Beta-1 and beta-2 receptors are two types of adrenergic receptors.
The beta-1 receptors are located in the heart, the kidneys, and fat cells. Their action is to increase the heart rate and the strength of contraction. Beta-2 receptors are located in the bronchioles of the lungs and the arteries of the skeletal muscle. They relax the smooth muscles, they dilate the blood vessels, and they open the bronchioles. So when we refer to it in beta-adrenergic drugs being non-selective, it's referring that they will have a similar action or similar effect on both beta-1 and beta-2s.
So we will see both responses. On the other hand, if we are giving a selective drug like metoprolol, It is aimed more at beta 1s. So we are going to have more effect only on the cardiac and not on the lungs.
Now one of the ways to really remember that makes it easy is you have one heart, beta 1, and two lungs, beta 2s. And that kind of lets you know where the receptors are primarily affecting. So a couple of things to think about is when we're talking about the beta blockers, these are going to be blocking, if they are non-selective, both beta 1 and beta 2 receptors.
Because they are blocking, we are blocking the normal response. So for example, let's take a look at the chart. Normally, with beta-1 receptors, you have an increased heart rate and an increased force of contraction. With a beta blocker that is non-selective, such as propranolol, we will see a slowed heart rate. So think about the term that this applies to.
This is a negative chronotrope. And We will have a weaker, less forceful contraction, which term referred to the force of contraction, inotrope. So it is a negative chronotrope and a negative inotrope.
If it is non-selective, it will also affect the beta-2 receptors. So when we block the beta-2 receptors, we will see vasoconstriction in the skeletal muscle or peripheral vasoconstriction. We will also see bronchial constriction. Now think what patients this might cause a problem with. What if somebody has a pre-existing asthmatic condition or respiratory condition?
Giving a medication such as a non-selective beta blocker could lead to them having an asthma attack. So we have to be very, very careful with these. When we use cardio-selective drugs such as metoprolol, they offer the potential advantage of not interfering with the beta-2 receptors.
or at least having less likelihood of it. So let's say we gave a patient metoprolol. We would see decreased heart rate, decreased force of contraction, and we wouldn't see any beta-2 receptor activity. So we shouldn't see... Any change in peripheral vasoconstriction, nor should we see any difference in bronchial dilation.
Now, having said all this, there is always a risk as we increase doses in our selective beta-1 blockers, we can see some beta-2 effect. So it's important to monitor and to teach a patient to monitor after. any medication changes. So the pharmacodynamics of propranolol are that the blockage of Beta-1 will actually affect the heart, and this will result in a decreased rate and decreased contractility. Now this is a negative chronotropic and a negative inotropic action.
These will result in a decreased cardiac output and therefore decreased blood pressure. It will also slow the atrioventricular conduction and suppress the automaticity. This is a negative dermatropic. So just to be clear, you have a negative inotropic, a negative chronotropic, and a negative dermatropic when you are using a beta blocking M. All of this decreased workload of the heart will result in decreased oxygen demands.
This is one of the reasons that we do see better morbidity rates when somebody has suffered a myocardial infarction and they are then given a beta blocker is because it actually decreases the stress on the tissue and we're able to save a lot of that tissue. The effect on the kidneys is it will decrease the release of renin and this will ultimately result in decreased blood pressure. Now this is where the main difference between metoprolol which is a selective and propranolol which is non-selective is and it's the beta-2 blockage. Because propranolol is non-selective, it affects both beta-1 and beta-2. So it will have some beta-2 blocking effects.
Most of these are going to be seen as adverse effects because they are going to be affecting primarily the pulmonary system. So we see bronchospasms. we can actually see people having a much more difficult time breathing.
This is especially true, and this medication class can be problematic in our asthmatics. We have to watch for peripheral vasoconstriction. And so if you have somebody that has Raynaud's, this medication, again, is extremely harmful. hypoglycemia so again watching people that are diabetics or that suffer from hypoglycemia So uses for propranolol can be hypertension.
We also can use it for angina. Remember how we said it decreases the oxygen needs and the oxygen consumption in the heart. We can use it for cardiac arrhythmias, people with migraines.
It is very, very effective. One of the off-label uses is propranolol. Inaction can be for intention tremors.
We can see the beta blockers used. Heart failure. So there's a lot of different effects that can be used from this.
Significant contraindications. People that have bradycardic rhythms, complete heart block, because again, it is going to affect the conduction and the rate of the heart. And so...
This would actually further compromise their rhythm and their ability to meet the oxygen needs. Cardiogenic shock. I do want to clarify, this is an uncompensated cardiac failure. You can see this medication used in heart failure, but not in people that are unable to meet any of the body's needs.
So again, that would be a clarification that you would really have to monitor for. Raynaud's disease and reactive airway disease. So some of these we've already previously mentioned. Some of the adverse effects that you would need to monitor for is postural hypotension, bronchospasms, and then very seriously would be myocardial infarction or compromised ability to meet the needs. of the body with circulation.
This medication is well absorbed when given orally. It can also be given parenterally. It is well distributed.
One thing to be aware of is that the stability as far as the hypotensive sensitivity may actually not occur for two to three weeks. And so patients during this time Need to be very, very careful with movements and changing position. It is metabolized in the liver and excreted through the kidneys. So the nursing interventions that are going to help us maximize the therapeutic effects. So many of these interventions are going to be stressing and emphasizing to the patients and educating the patients.
So first of all, we want them to understand that this is not a medication that they should double the dose. If they have forgotten the dose, they need to leave it and go on to the next one when it comes around. This is not one you want to double up because of the effects that it does have on the blood pressure and on the heart. They should be taking it with food and this will actually increase the bioavailability. and decrease GI upset.
To minimize the adverse effects, first of all, minimize stressors. This makes it so the medication is actually going to be more effective. They should be checking a peripheral pulse prior to giving the medication and holding it if it is below 60 or if the rate is irregular.
they should notify their provider. They should be keeping appointments with their provider so that we can monitor EKGs and blood pressure. If you have this patient coming into the physician's office, into the hospital, this is somebody that we need to be assessing a respiratory assessment as well due to the risk of bronchoconstriction. So, listening to the airflow, asking if they're having any difficulty breathing. Make sure that if you ever have a patient that has a history of COPD, asthma, respiratory complaints, you should always question if this medication is ordered.
There are others that are selective that are not going to put this patient at the same risk. So it's very important that we want to prevent that beta 2 blockage. Know why your patient is receiving the medication. Are they receiving it to decrease angina pain? So we want to know what their pain level is.
Has it decreased? Watch for they should have increased tolerance with activity. So again, teach the patient and watch them.
Do they know how to take their own pulse, their heart rate? Can they detect if it's regular or irregular? Are they able to verbalize to you how to move safely?
Do they know to sit at the edge of the bed? Do they know to sit in a chair and make sure they're not having any dizziness when they first stand up? to stand for a second before they take off walking, any of those changing positions or safety related to postural hypotension.
It's very important they understand never abruptly stop taking the medication. They need to understand that, again, if we remove that blockage, not only is their blood pressure going to go high, but their heart rate. So I had students in the hospital and there was this wonderful little lady.
She was 83. She had an abdominal surgery and then had some complications and they were walking her. They were getting her up and walking her and she was getting ready to go to a rehab facility and she was funny, funny. She kept saying that she wanted to go to one facility over another because they had better looking young men aides. And I thought, if you're at 84, concerned about that, you go for it, girl. But I left the floor, the students were walking, and then I got a call, we need you to come really quickly.
The patient doesn't look well, and I said, okay, go back to your basics, take your vital signs. Well, her heart rate had doubled. I said, go back to her history.
Was this lady, I was walking at the time to the floor, was this lady, what was she on before surgery? Because they said, no, no, no, she's not on any beta blockers. And I said, go look at the prehistory.
Well, she had been on a beta blocker before surgery. Because of the complications, she was not restarted on it. Wasn't an issue until she got that stimulation.
Her heart rate was 135. Blood pressure was actually low because the heart didn't have time to fill. And of course, she felt very weak. Physician got called. They put her on a cardiac monitor, gave her an IV beta blocker, slowed her down, and then they were going to start her on a maintenance stels.
So it's very important that patients understand not to abruptly stop these medications because we can see the blood pressure go way high and the heart rate as well because we're going to lose that blockage effects. The toprolol is a selective beta adrenergic blocker. Selective beta blockers have an advantage over non-selective in some cases because they do not usually block the beta-2 receptors. Because of this, they do not block the sympathetic bronchodilation that is so important for patients with lung disease, who have asthma, allergic rhinitis.
These patients actually need that response. So the beta-1 effect of metoprolol is identical almost to that of propranolol. We see the beta-1 blockage, so the heart is going to decrease the rate and the contractility results in decreased cardiac output and decreased blood pressure.
It does also slow, again, the atrioventricular conduction, decreased automaticity, and all of this decreases the oxygen demands. So remember, again, these are negative inotropic, chronotropic, dromatropic. It's going to decrease the blood pressure and the oxygen demands, which will help with anginal pain.
It decreases the release of renin, so we do not have that vasoconstriction and decreases the blood pressure. I do want to point out. Though we do not routinely see beta-2 effects, if somebody is at very, very high doses, sometimes that selectivity is less dependable and they can have some minor to severe respiratory effects.
So they use this for metoprolol, again very similar, hypertension, angina, cardiac arrhythmias, heart failure. We do also see it used for people with open angle glaucoma who have increased pressure. They can use it for this to make it so that the fluid can flow out.
Chondroindications, bradycardia, complete heart block, shock. People whose heart failure is not compensated, this is not a time to give this medication. Now, while we do see metoprolol being less restrictive and causing that vasoconstriction in the periphery that somebody with Raynaud's cannot tolerate, they still say that it should be used in extreme caution.
Adverse effects, again, people still have to watch for postural hypotension and serious. If they go off it abruptly, they could risk a myocardial infarction. It is absorbed or relieved very well.
Bioavailability is increased when taken with food. And if somebody needs immediate results, we can give it intravenously. It is excreted through the kidneys and metabolized in the liver. For the nursing interventions, I'm just going to have you review those of propranolol. Because other than the risk of respiratory involvement, they are identical.
Again, I do want to emphasize, if a patient is taking extremely high doses, you do still want to do a very thorough... respiratory assessment and ask them if they are having any complications because patients on higher doses do run the risk of allergic rhinitis up to bronchospasms. Cardiac glycosides exert positive inotropic effects on the contractility of the heart muscle.
Inotropic means related to or influencing the force of myocardial contractility. And so what we're going to end up with when we talk about a positive inotropic effect is an increased force of contraction. Digoxin or linoxin, which is derived from the foxglove plant, is the prototype of this class.
And this is just a picture of the foxglove. And so when we talk about heart failure and that needing for increased force of contractility, this is one of the medications that you will see. Now, this is an older medication and you will generally not see it utilized except for somebody that has left-sided heart failure.
The pharmacodynamics of digoxin. are several different ones and we're going to talk about the direct and the indirect effects that it has on the cardiac muscle. The overall effect that we see is that it does increase the cardiac output. The first effect is the direct one and it acts on the cardiac muscle itself.
It strengthens the force of contraction and this is the positive inotropic effect which was previously mentioned. It does this through increasing the movement of calcium across the myocardial cell membrane during the depolarization. And as calcium is needed for contractions, then we actually get a stronger contraction because we have more calcium that is actually available.
It also will affect the electrical conduction system. And so it increases the refractory. period at the AV node.
This allows the pausing or that period of time that the heart muscles cannot actually be stimulated into contracting again and so this actually allows for a little bit of delay. This refractory time is actually very helpful when you have somebody that has rapidly conducted atrial fibrillation. Some of the indirect effects that we can see resulting from digoxin is actually the stimulation of the ANS or the sympathetic nervous system.
So it has a vagomimetic effect. It mimics the action of the vagus nerve and slow it slows conduction. And this is actually a negative dromatropic effect. and it depresses the sinoatrial node and prolongs conduction to the AV node.
So it slows the heart rate, and this is a negative chronotropic effect. And you want to be familiar with these. So it has a negative chronotropic, and the way to remember that is chrono is time.
So it slows the timekeeper of the heart. It slows conduction, and this is a negative dromatropic. and it increases the force of contraction and so it's a positive inotropic. Because of the prolonged conduction time, the cardiac output is increased as a result of all of these factors we've just talked about.
Absorption can vary some with the type of preparation. How much is absorbed and the time it takes to be absorbed can be affected. One of the things to be aware of is that food, while it can slow down the rate of absorption, it doesn't usually affect the overall preparation.
As digoxin can be irritating to the lining of the stomach, we do usually encourage people to take it with food because again, as they do that on a regular basis, the overall percentage and level of absorption will be balanced out. It can also be administered IV. So a couple of things to be aware of is that it is highly concentrated in the myocardium.
We also see increased levels in skeletal muscle, the liver, the brain, and the kidneys. It does cross the blood-brain barrier and the placenta. Therefore, if you have an expectant mother, it will get to the fetus.
It has a very long half-life. Now, because of that, it takes longer sometimes to get up to that therapeutic level. where we've got that therapeutic index.
And so because of that, we may sometimes do what we refer to as digitalization. And this is a loading dose. We usually will give three divided loading doses, two to three, depending on the patient, over a 24-hour period. They are usually given IV, and then they are started on a therapeutic. Maintenance stoles.
What this does is it gets the blood level up high enough that we can get and achieve that steady state quicker. This is usually done more in somebody that has a rapid atrial fibrillation. It is not as common of a practice in heart failure. So it is metabolized in the liver and excreted in the kidneys. One of the things to be aware of is that because it is excreted in the kidneys, people that have poor renal function, a lot of times in our elderly we see this, then we do need to use lower doses because it is not excreted fully and it does make them more at risk for having dig toxicity.
This medication again is used in heart failure, atrial fibrillation, and atrial flutter. Do understand that this medication is an older medication. It is not used as a first-line drug in most patients. You will see it used in left-sided heart failure and for fibrillation and flutter.
But we have found that the mortality rate is decreased in patients that we use first our ACE inhibitors, beta blockers, and some of the other classes of medications. One of the things that we do notice is that it can cause some of the same arrhythmias that is actually used to treat. And so, it is a difficult medication to use. It does have a higher incidence of problems with it.
Some of the contraindications are things like heart block, ventricular fibrillation, a sick sinus syndrome. The reason is, think about the effect that we talked about that digoxin has. It delays the conduction.
It delays the heart rate. And so if you have somebody that already has problematic or spotty conduction of the electrical system or it has a poor pacemaker you don't want to use digoxin because it's going to thoroughly compromise your heart muscle we have to really watch because it can cause severe bradycardia and block and this is again seen primarily with dig toxicity Some of the adverse effects to be aware of. Common ones that we watch for are cardiac toxicity. And again, this is primarily seen with somebody that's going to have that lower heart rate. Some of the causes can be electrolyte imbalances, primarily hypokalemia.
So you have somebody with a lower potassium or a low magnesium. they are going to get a larger effect in the cardiac tissue with the digoxin. Hypercalcemia, it potentiates the effect of the digoxin. Now, there are in your textbook a table that talks about some of the antidotes that we will use. One of the ones that is expensive and not used really frequently, but I do want to mention it, is digoxin immune fab, DigiBind.
And this actually, when we have high levels of digoxin that we do need to remove. We can give this IV. It does bind with certain percentages of the digoxin and makes it unable to bind with the receptors of the tissue. And therefore, the medication is ineffective and we lose some of that overall effect. This is just a reminder.
Educate your patients. So there are several things that we can do to actually maximize the therapeutic effects. First of all, digitalization.
As I mentioned previously, this will be given usually for atrial fibrillation and so they will receive two or three evenly spaced larger than normal doses. These are loading doses. What we are doing is raising the level of the medication and so that the patient is at a steady state much quicker. And so then we can go ahead and put them on a maintenance dose.
It is very, very important that when we do this, that we make sure that the patient is on cardiac monitoring, that we are making sure that they have adequate fluid intake. and that they have good excretion because remember this is excreted through the kidneys and we do have to monitor that so it does help us to achieve that rapid onset of therapeutic effects and we do then just need to monitor for the adverse effects digoxin has a very narrow therapeutic window and so The therapeutic range is 0.5 to 2.0 nanograms per milliliter. We do actually see some patients that can start exhibiting signs of toxicity even when they are within that normal range.
The patients we usually see this occurring with are our renal patients because they seem to build up and to start showing signs of. toxicity much quicker than other patients. And so we do want to monitor patients to make sure that they are within that normal range, as well as assessing them for any signs of toxicity. It's important that when patients are on digoxin and they come into a facility, that we look when their last therapeutic range was, when it was drawn.
that we check what the physician do that you want it checked, that we make sure that patients know how frequently they should be getting blood work done. We also want to assess patients for bradycardia. Now this is something that we assess prior to administration. In an adult we want their heart rate to be greater than 60 and so we're going to listen to the apical pulse for a full minute.
This has to be for a full minute because especially if somebody has atrial fibrillation, you do not want to get it during a period of rapid heart rate or slow heart rate and get a number that is actually inaccurate. And so it's very important that we take it for a full minute. In an adult, we want the rate to be greater than 60. In a teen or younger child, we want it to be greater than 70. And in a young infant, we want it to be greater than 110. So what we're looking at is that we want it to be greater than a bradycardic rate for that age group.
So it's important that we assess for any bradycardia. We want to monitor for any electrolyte imbalances. We've already mentioned that low potassium and magnesium can actually place the patient at risk for digitoxicity.
Now, guys, I don't know about you, but I do not sit at home and suddenly have a little light come over my head and I say, oh, I think I'm experiencing hyperkalemia. It would be really nice if that happened, but it doesn't. Oh, I've got hypokalemia, hypomagnesemia.
You need to teach patients what that feels like. And so one of the easiest ways to be able to have a patient identify both the low potassium and the magnesium because they have very similar signs and symptoms. They actually, you will get a lot of...
Cramping in the legs, they have increased electrical conduction with the magnesium and so they get a lot of irritability. So if you say you've got a lot of cramping, maybe the paresthesias, that's probably the easiest one for them to identify. High calcium actually will also place a patient at risk for digitoxicity.
So. With high calcium or hypercalcemia, everything gets very slow. Unfortunately, mentation, muscle movements, bowels, everything slows down.
And so it's important that if the patient says, you know, I just feel so tired and sluggish and I'm falling, that we look for other things that could indicate that they may have high calcium and then know who's at risk for it. So it's very important that you as the nurse be aware if they are taking other medications that do put them at risk for this. For example, if you have a patient that is taking hydrochlorothiazide, hydrochlorothiazide is a diuretic.
It can cause them to lower their potassium magnesium, but it also causes them to hold on to the calcium. So it puts them at increased risk of having some of these electrolyte imbalances. So this is why it is so important that as a nurse that you are putting that picture together and educating your patients. So you have to monitor, make sure that the imbalances are corrected before we are doing administration. You also want to assess for non-cardiac signs of digoxin toxicity.
These, if you will remember GI, a lot of anorexia, nausea, vomiting, diarrhea. Patients will complain of headache and blurred vision. You will also hear them complaining or saying they've got yellow vision.
A lot of patients will complain of yellow halos around objects and lights. I have heard some that are a little bit blue. but yellow, and so you'll hear it referred to as yellow vision.
It's a very common thing. Unfortunately, confusion, and so we do need to monitor for this. We need to teach patients how to monitor for these things as well.
And so when we're teaching them to look for bradycardia, they're not going to listen to an apical pulse. Teach them how to do a radial pulse, and that if it's below 60, Rest for a little bit and take it again if it's still below 60 to call their physician and not take their medication until they talk with the physician. It's important that they know the signs and symptoms of DIG toxicity.
If they start having a lot of GI upset, if they notice that they've got a lot of diarrhea, are they having trouble? remembering things or our family members picking up on that. Along with a slower heart rate, they may need to go in and get their DIG level checked. This is a medication that comes in little white and little yellow tablets. It does not really have a nasty taste.
A lot of elderly people, so they don't forget to take their medication, will put them out on tables. This is not a medication you want. a grandchild getting into or anybody getting into. So make sure they understand to keep this out of the reach of children and that if they um to decrease their GI upset it can be taken with food to decrease that.
This is just a fun little mnemonic to kind of help you remember some of the signs and symptoms of digitoxicity. So bradycardia or heart block, remember we're going to usually go with the number 60. Anything below 60, the patient shouldn't be taking it and we shouldn't be giving it. Blurred vision or yellow vision, remember those yellow halos. Occasionally we can see a rash, abdominal pain, nausea, vomiting, diarrhea. a lot of GI symptoms, and then delirium and confusion.
Nesiratide is the prototype drug in the human BNP class of drugs. This is a newer class of drugs, and I just want to mention it because I think we're going to see more of them as time progresses. So Nesiratide is actually a vasodilator, and it acts just like the B-naturitic peptide.
Now the B-nat... B-naturidic peptide is secreted primarily by the ventricles in response to fluid and pressure overload. So when we get that increased stretch happening on the tissues, then we see an increase in the B-naturidic peptide being actually excreted.
So it is administered primarily by a bolus and then an IV administration. So you will most likely not see this medication unless you are working in a monitored critical care bed. It is usually fairly immediate and they actually start seeing effects within 15 minutes. So if somebody comes in in extreme fluid overload, this is a good way to help them relax those vessels and get that fluid down a little bit more in the periphery so that we can get some other interventions in place.
And then the serotide acts to compensate for the decreased cardiac function because it decreases or reduces the cardiac preload and the afterload. And because it does all this, it actually will produce something similar to a diuretic effect because it increases the sodium secretion. and it suppresses the RAS system.
And so all of these things help a heart that is actually not functioning well. So another class of drugs I would like you to at least be familiar with, because I do think we are going to see more use from this, are the angiotensin receptor naprilicin inhibitors. And I am going to use the trade name because I really could not find a good pronunciation for the other. So this is Entresto.
Entresto actually is going to assist in modulation of the natriuretic system and it inhibits the enzyme naprilicin. Now naprilicin actually degrades the vasoactive peptides and so because of this what it does is when it's added to an ARB it helps decrease and block the activity in the RAS. And so we don't have the aldosterone and the sodium and the fluid retention.
It also is going to decrease the conversion of angiotensin 1 to angiotensin 2. And then we get some of that vasorelaxation going on in the periphery. And so we have that decreased preload and decreased afterload. So because of this, it's got a really good effect in people with chronic heart failure that does not react well to other medications.
Now, I do want you to be aware that the drug is a prodrug, which means that it's given in its less active form and it is more active following metabolism. It takes about 30 minutes after it's administered to start seeing it in the system. It takes about three days to reach steady state and this is when it's given twice daily.
So nursing interventions, this medication can actually be given without regard for food. Again, you do want to give it usually twice daily and so we want that to be evenly spaced. We do need to make sure that if people are switching from an Arbor and ACE that they usually have about 36 hours, what they call a washout period, to get the other drug out of the system before we start this one.
So we do not have that duplication of efforts. Assessing for therapeutic effects. Why were we giving that? Monitor for if we have increased stabilization of the signs and symptoms in their chronic heart failure. Do they have increased activity tolerance, decreased shortness of breath, decreased nocturia?
What are their labs showing us? What are the BUN and the creatinine and the potassium? It's important.
important that we make sure that these remain within acceptable limits. When we're looking for adverse effects, it's very important that we monitor for vital signs, monitor for hypotension, and that they monitor themselves at home. We want to look for any abnormal lab values, especially for the creatinine and the potassium, kidneys, and then our electrolytes.
And then for anything that indicates a worsening of their heart failure, a cough, persistent coughing, or dizziness. Teach the patient that frequent blood pressure monitoring is necessary. And again, go over the options and where they can get it checked. They need to be reminded to change positions slowly. And then to tell their provider if they are...
put on a potassium supplement or are currently taking a potassium supplement or a potassium sparing diuretic. Now remember this is important because with an ARB they do not have that aldosterone secretion, they don't have the sodium retention and therefore they do have a little bit more potassium retention. So this does put them more at risk for hyperkalemia.
They need to notify the provider of any swelling. Again, we are still at some risk for angioedema and to let the provider know immediately. And then they are encouraged to drink adequate fluids so that they do not have hypotensive episodes.