Female 1: Drugs to treat hypertension. So we know that the pressure in the cardiovascular system is determined by three elements, the heart rate and the stroke volume. And these are actually going to be those components that make up our cardiac output and the peripheral resistance, which is affected by vasoconstriction and then our volume. And so I want to talk a little bit about some of the other things that affect this vasoconstriction and the volume. One thing we do know is that the small arterioles are very responsive to the sympathetic nervous system. And they play a big part in affecting our peripheral resistance. The baroreceptors affect a lot of this vasoconstriction and dilation. The baroreceptors are actually located in the arch of the aorta and in your carotid arteries, and they sense if there is sufficient pressure in the vessels. Now these pressure changes, either high or low, will trigger signals to be sent to the medulla. And these signals can cause the medulla to stimulate vasodilation and a decrease in cardiac rate and therefore an output if pressure is too high. If the pressure is too low, then the medulla sends a signal to stimulate vasoconstriction and an increase in the heart rate, which again will increase the cardiac output. Another regulatory system that affects our blood pressure is the renin-angiotensin-aldosterone system or the RAAS system. So this is going to affect our peripheral resistance. So when the blood pressure falls, the kidneys compensatory mechanism that basically helps ensure this blood flow is activated and this is the RAAS system. And so the blood pressure and low oxygenation stimulates the release of renin. The renin goes through the process of activating the angiotensinogen and its conversion from angiotensin I and then to angiotensin II. And all of these different changes result in vasoconstriction and stimulation to release aldosterone. Angiotensin II, remember, is a very potent vasoconstrictor. So with the release of aldosterone, this acts on the nephrons to cause retention of sodium and water, and this effect is going to increase the blood volume. And so we now have vasoconstriction and increased volume. And this is going to increase the peripheral resistance. So this is just a quick review of all the different components that actually affect your blood pressure. I really like this diagram that I have up here. And the reason is, is that when we go to make changes to blood pressure, we are actually going to be affecting some of these different components. We can decrease the cardiac output, decrease the heart rate, change the peripheral resistance, and hopefully again result in decreased blood pressure. Things that increase the chances that someone will develop hypertension are similar or the same to those for cardiovascular disease. We do note that when we are talking about ethnicity, Black, non-Latinos are at the highest risk for developing hypertension. And with men in this group more likely than women to develop the disease. In addition, Blacks have shown different responses to many of the proposed interventions. They, as a group, are more responsive to diuretics and calcium channel blockers and less responsive to ACE inhibitors and beta blockers, which as you're learning, are drugs that are commonly utilized for treatment. And so this does increase some of the difficulty. Diabetes increases the rate of atherosclerosis, which affects the ability of the vessels to dilate and can affect renal function. When we're talking about risk factors, again, men are at higher risk. They do start to show signs of increased blood pressure and cardiovascular disease around the early to late 40s. Women is usually around 55 and this is, again, premenopausal female. Around the age of 70, both male and female carry the same risk. And this is as women have lost the estrogen that is a protective hormone. Again, family history is a significant contributor. Some of the complications that can occur secondary to hypertension are as follows. First of all, heart disease. Because of the dilation and the increased peripheral resistance, the heart workload has to increase. This can cause left ventricular hypertrophy. We also can see increased incidence of angina and myocardial infarctions and heart failure. So all of these things can be a result of severe hypertension. People are at increased risk for strokes and transient ischemic attacks. Kidney damage. So our nephropathy. We can see increased incidence of peripheral arterial disease and hypertensive retinopathy. People a lot of times will come in having no knowledge that they either have hypertension and they will be complaining of changes in their vision. And this is one of the things that we will find. And so it is a significant problem. The changes actually take place in the retina and they will actually get little small bleeding. They can have exudates and they actually cause clouding of the vision. So as mentioned previously, the medications that we utilize to decrease hypertension are going to be acting on those components, the cardiac output and the peripheral resistance. So to decrease that cardiac output, we have drugs that will actually decrease the heart rate. So beta blockers, remember, have that negative dromotropic action. Our alpha beta blockers and our alpha-2 stimulators. We have drugs that will decrease the force of contraction. Again, beta blockers, negative inotropes and our alpha-beta blockers. And then we have medications that decrease that preload, the amount of blood that is available for circulation. And so this we see in our diuretics and also in our ARBs as they decrease that secretion of our aldosterone. Medications that act to decrease the peripheral resistance. Again, diuretics, they remove that volume, our calcium channel blockers as they cause that relaxation. Our ARBs and our ACE inhibitors both will result in relaxation of the vasculature as we do not have that effect of angiotensin II. And also, as they decrease the secretion of aldosterone so we do not have the sodium retention. Our alpha-beta blockers and our alpha-2 stimulators. So while I'm not going to cover these medications in this unit as we have previously covered them in another unit, I do want to mention that these are medications that can be used in the treatment of hypertension. So our ACE inhibitors, remember, are going to act in the lungs to inhibit the enzyme necessary to convert angiotensin I to angiotensin II. Without that, we do have that relaxation taking place and we block some of that release of aldosterone. Calcium channel blockers decrease the flow of calcium, which results in relaxation of the vasculature and some of the force of contraction of the heart. By blocking beta-1 in our beta blockers, this actually will decrease the rate negative chronotropic action and decrease the force of contraction, which is our negative inotropic action. Both of these decrease the cardiac output. Our diuretics, either loop diuretics or our thiazide diuretics, can result in decreased volume and this is going to decrease the peripheral resistance as well as the preload. And then vasodilators are going to dilate the vessels and decrease that peripheral resistance. Antagonist. These are our ARBs. [inaudible] blocks the angiotensin II from binding to the angiotensin receptors in the smooth muscle and in the adrenal cortex. And because of this action, it therefore blocks vasoconstriction and the release of aldosterone. Now this loss of or prevention of secretion of aldosterone leads to decreased aldosterone, which prevents the sodium and the bladder retention. And this also leads to decreased peripheral resistance. Pharmacokinetics. It's given orally, very well absorbed. It is metabolized in the liver and excreted in the urine and the feces. Again, just remember that when we talk about anybody that has possible dysfunction of the liver and kidneys because these organs are actively involved in processing this medication, this is sometimes a consideration or a contraindication for use. To treat hypertension, it can be used with instead of an ACE to treat heart failure. And we are seeing some really good result using this medication to slow renal disease. Now there are several contraindications if somebody is hypersensitive to the medication or individuals that are thinking of becoming pregnant, find themselves pregnant or are lactating. We do not know if it crosses into the breast milk, but it's contraindicated just because of the significant risk. Adverse effects. Now while we don't see the dry hacky cough, one of the things that we can see are upper respiratory infections and the cough associated with those. So it would be a loser cough. Patients can also experience dizziness. And I do want to mention that the hypotension, they do not have the reactive effect of the body. And so they may have significant periods of hypotension and syncope. We can see individuals experiencing diarrhea and nausea with GI effects, headache. And then, again, the weakness associated with a drop in blood pressure. We also see individuals experiencing a higher risk of some cancers. Now after having listed all those common adverse effects, it actually is very well tolerated. A lot of individuals that have been on ACE inhibitors and develop the dry hacky cough actually can be switched to the ARBs and have tolerated it very well because they do not have that same cough associated with it. There is caution in individuals who have both hepatic and renal dysfunction as it could result in decreased clearance of the drug and therefore, they might need altered doses. 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 oligohydramnios, which is that increased fluid surrounding the fetus. It also impairs lung developments. 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're 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. So it can cause dizziness and while chasing your tail may not stop it. We do need to make sure that we tell patients to change positions slowly and to sit at the side of the bed before getting up, especially during that first 24 to 48 hours that we know the medication is going to be effective. This is when they have some of their highest risks. So when we talk about nursing interventions to maximize those therapeutic effects, so very often when patients get prescribed a medication for hypertension, they think that oh, they don't have to continue with those lifestyle changes; losing weight and exercising and changing their diet. We need to continue to emphasize that they need to maintain and progress in their lifestyle changes because the medication is going to only be as effective as they're making those changes. Couple of other things. Hydrochlorothiazide has been shown to have an additive effect with this medication. And so it improves the function. And so you may see people that are also put on hydrochlorothiazide diuretic. If they have GI distress, it can be given with food so that they will, again, continue to take it as they should. To minimize those adverse effects, emphasize, again, assistance when they are getting out of bed and then to sit at the side of the bed to make sure that they are not dizzy. And then we will treat symptomatically for upper respiratory infections or complaints such as diarrhea. Educate patients, again, that if they are during those childbearing ages and they are considering becoming pregnant, they do need to consult with their physician because there are significant teratogenic effects or risks associated with it. Calcium channel blockers and amlodipine or Norvasc will be the prototype that we use, inhibit the movement of calcium ions across the membranes of myocardial and arterial muscle cells. And this action alters the action potential and blocks the muscle cell contraction. So because of this, we see depressed myocardial contractility and so it slows that cardiac impulse formation. This is all going to result in relaxation. It dilates the arteries. And all of this will cause a falling blood pressure and decrease in venous return, which you're going to want to remember when we talk about adverse effects. Channel blockers inhibit calcium from moving across the cell membranes of the myocardial and arterial muscle cells. This action, or inaction, alters the action potential and blocks the muscle cell contraction. And so what our overall effect that you'll see in the patient is you'll see depressed myocardial contractility, so it will be less forceful. It slows the cardiac impulse formation. So you're going to have a slower rate and it relaxes and dilates the arteries and this causes a fall in blood pressure and a decrease in venous return. So I want to just kind of go back over this just a little bit. It's going to slow the heart rate, so it is going to be a negative chronotrope. It's going to be less forceful in the force of contraction, and it is also going to slow the velocity of conduction, going to block that constriction of the arteries. This is where it is used in Prinzmetal's angina. The other term is variant angina because by blocking that calcium, it makes it so the vessels cannot have the arterial spasm. And so the arteries remain open. We have the blood flow, the tissue is happy. So the calcium antagonist caused decreased contractility and decreased conductivity of the heart. All of these things result in decreased oxygen demands. So this is one of the reasons is it can be given for anginal episodes. The side effects are decreased blood pressure, which actually we use this for hypertension, bradycardia, they can have blockages of the AV and headache, some abdominal discomfort, nausea, constipation. One of the big things you do need to really monitor for is with that decreased blood return to the heart. We can see increased venous stasis and therefore some resulting peripheral edema. So calcium channel blockers are used for chronic stable angina. When the patient can't tolerate nitrates or beta blockers, or if their symptoms aren't controlled well enough. You may see it utilized as an additional medication for heart failure. And it is the drug of choice for Prinzmetal's or variant angina. This is angina that is secondary to vasospasms, not due to plaques. So it is well absorbed orally. It can be given IV short term. It is metabolized in the liver and excreted in the urine. Do be aware that it can cross the placenta and enter the breast milk. Therefore, we do have to do some education if we have an expectant mother. So this medication is contraindicated in patients with renal or hepatic dysfunction as it will not be excreted or metabolized properly. Also, a contraindication if they are allergic to the medication. Some of the adverse effects that patients and you need to monitor for while a patient is receiving this. So dizziness, lightheadedness. Patients will also complain sometimes of headaches, extreme fatigue, they can experience nausea, hypertension, bradycardia. So it is important that they are palpating their pulse. They also should be monitoring their weight and for peripheral edema. Again, this goes back to that decreased vasal return to the heart. One thing that is a little bit unique about this medication is this is a class of medication that is going to interact with grapefruit juice. And this goes to the metabolism, the CYP system. So patients that are using this medication need to be counseled that they should not be taking grapefruit juice or drinking it at this time. The reason being is that will actually decrease the metabolism and can cause toxic levels of the medication. Diuretics, we will be talking about thiazide, loop diuretics, potassium-sparing diuretics. All of these will decrease the circulating volume. Diuretics work in the nephron. The main organ of the renal system is the kidneys, which houses the tangled mass of nearly one million nephrons. The nephron is the structure known for its role in urine production. So the different diuretics work in different parts of the nephron, thiazide and thiazide like diuretics work in the distal convoluted tubule. Loop diuretics work in the ascending loop of Henle and potassium sparing diuretics and we're going to be using spironolactone work in the distal convoluted tubule. Now I do want to point out spironolactone acts as an aldosterone antagonist and so it blocks the actions of aldosterone in the distal tubule. The fluid and electrolyte alterations depend on where the specific diuretic works in the kidney. So the thiazide diuretic we will be looking at is hydrochlorothiazide or Hydrodiuril or HCTZ. The pharmacodynamics of HCTZ is that it inhibits the ion pumps that work in sodium and chloride reabsorption. It acts in the distal tubule and possibly in the diluting segment of the ascending loop of Henle. All of this cause is the kidneys to increase excretion of sodium and chloride and it inhibits the water reabsorption. Along with this, we have increased excretion of potassium bicarbonate and magnesium. It decreases the excretion of calcium. And so your calcium actually goes up with this medication. It may decrease the glomerular filtration rate and may increase the blood urea nitrogen level. So when you're looking at labs, those may be altered in that way. Because most of the sodium is reabsorbed before the distal tubule hydrochlorothiazide has a weak diuretic effect. It is absorbed rapidly when given orally. It distributes to all of the tissue. It is metabolized in the liver and excreted in the kidneys. It does cross the placenta and is considered a Category B. It is found secreted in breast milk. And so we do need to be aware that it could have this effect on a newborn or a fetus. Thiazide can be used to treat hypertension. Now this can be used alone or it can be used with other agents. For example, anti-angiotensin receptor blockers such as losartan. Actually, it improves the effect when it is combined with a diuretic and they actually do have combined medications. If it is used alone, you may not see the therapeutic effects for two to four weeks for hypertension. It can be used for edema that like we see with heart failure. For individuals with hepatic or renal disease, it can help with that residual edema. And we also may utilize it for edema for secondary to drug use, long-term steroid use, estrogen therapy. Now there are significant contraindications for severe renal disease. And I know this seems like a contraindication because I just said that it could be used for the edema, but for persons with severe renal disease who may be anuric, no urine output or a severely decreased urine output. And the rationale is, is that it does decrease the glomerular filtration rate. So it will actually make the kidney function worse. If they have a hypersensitivity to sulfur, it is contraindicated as they will have a severe reaction. So some of the convert common adverse effects, it can increase your glucose levels. So diabetics need to be taught to increase monitoring. It can increase lipid levels. So this may not be the best choice of drug for somebody who's trying to lower or correct lipid levels. And it can increase uric acid levels, which can cause persons that are predisposed to gout to have flare ups. More common adverse effects. Dizziness. This is due to the loss of fluid, lightheadedness, vertigo. Some individuals may experience nausea, vomiting, and a lot of these can be due to fluid and electrolyte loss. Now they are at risk for most commonly hypokalemia, possibly hyponatremia, hypochloremia, hypercalcemia as it limits calcium excretion. It may increase the lipid levels and increase glucose levels as I previously mentioned. So the more serious adverse effect, and this is actually a very rare one, is drug-induced immune hemolytic anemia. And this is when a medicine triggers the body's defense, the immune system to attack its own red blood cells. And this causes the red blood cells to break down earlier than normal. So we will see a form of homolysis taking place. So to teach patients to maximize those therapeutic effects, they should take the medication in the morning. My grandmother used to always say, but I've got things I need to do. I can't be stopping at the bathroom. And she always wanted to take it later in the evening. The problem is, is that then they're getting up and if they're tired, it increases the risk of falls. And so we want patients to take this in the morning so it doesn't disturb their sleep. They need to continue lifestyle changes. This is especially important for our hypertensive and our heart failure patients, dietary, weight loss, exercise because then they're going to get the best effect from it. To minimize those adverse effects, they need to monitor their blood pressure. They should be weighing themselves every day, but at least three to four times a week. They need to monitor their intake and output. And no patients do not take home a graduate and measure their urine. But if you asked a patient how many times do you urinate in a day, they would usually be able to tell you, is it a small stream of urine or a large stream of urine? What we want to note and to emphasize to the patient is that they need to notify us if that changes because that could indicate that they are retaining that fluid and not getting the therapeutic diuretic effect that we would like them to have. Serum electrolyte levels, again, it is so important to teach patients how to monitor for them. So the most serious one is hypokalemia. Do they have an irregular pulse rate, muscle weakness, cramping? Are they having increased complaints of constipation? Now remember with loss of fluid, they're going to have some, do they have abdominal pain? One of the things if it's not contraindicated, if they do not have renal disease, is encouraging the patient to have increased oral potassium intake. Bananas, apricots, orange juice, things like avocados, potatoes are all really good sources of potassium. Teach them to monitor for hyperglycemia. If they are a diabetic, they may need to increase monitoring and to monitor for signs and symptoms of hypercalcemia, high calcium. Those signs are usually going to be slow bowels. They will have decreased -- -- skeletal muscle movements, decreased mentation. So sometimes getting them to monitor are not the best things. They should have periodic monitoring of electrolytes and a CBC to check for anemia or thrombocytopenia. For loop diuretic that we will be focusing on or that we'll be tested on is furosemide or Lasix. The pharmacodynamics of furosemide are that it inhibits the reabsorption of sodium chloride and water in the loop of Henle. It also has some effect in the proximal and distal tubules, though not as great. All of these actions increase the excretion of sodium chloride, potassium and water. Little magnesium and calcium are also added in there. It also can increase the blood glucose. It will also increase low density lipoproteins, cholesterol and triglycerides. It will decrease excretion of uric acid. This is something that you do need to be aware of. This is not a medication that always goes well with somebody that has gout. This is considered or this class is considered to be our most potent diuretics. So it is rapidly and well absorbed when given orally. And the onset when given IV is usually within 10 minutes. It is metabolized in the liver -- -- and it's excreted through the kidneys. This is a pregnancy Category C drug. It does cross the placenta and may enter the breast milk. So again, you do have to watch the effect that it has on a newborn. So this is our potent diuretic and we will use it to remove edema from congestive heart failure. People who have pulmonary edema, hepatic and renal disease, the resulting fluid excess that may be there. It may be used for hypertension usually after other medications have been tried that are a little less potent. It is the first choice of a diuretic for somebody with hypertension that does have pre existing renal disease because unlike the thiazides, it does not decrease the glomerular filtration rate. Some significant contraindications, if a person is anuric in chronic renal failure, that means they have absolutely no urine. Giving them a diuretic is not going to suddenly make the kidneys functional. It will actually cause more damage. Some of the adverse effects. So common ones are going to be related to flu and electrolyte loss and we will go over those a little bit more as we go along. But some of the common ones, CNS, going to be dizziness, vertigo, you can get some weakness, GI, they may have nausea, vomiting, anorexia, constipation due to the fluid loss. Cardiovascular, orthostatic hypertension is such a big issue. We do have to worry about hematologic problems. Leukopenia, anemia, thrombocytopenia, very similar to what we mentioned with the thiazide diuretics. Dermatologic, people can become photos sensitive, so they do need to take precautions. If they are on higher doses and out in the sun, they may have a rash hives which is our urticaria. Muscle cramps and muscle spasms. Again, these are usually related to electrolyte loss or shifts. We can see increases in glucose, uric acids and lipids. Now one of the things that you do need to remember, this medication can cause permanent deafness if it is given too rapidly intravenously. Ototoxicity can occur when the medication is given faster than over one to two minutes. So you really need to make sure that when you're giving this medication, it will tell you how many milligrams over how many minutes you need to make sure that it's followed. This is especially a risk factor in people that have poor renal function. Older adults are more sensitive to fluid loss and more likely to have the orthostatic hypertension. The nursing interventions are similar to those that we talked about with is thiazide diuretics. Teach your patients to change positions. Teach them to take the medication as ordered and to take it in the morning. They should be weighing themselves. Teach them to change positions slowly and then assess what is their blood pressure. Is the edema going down? Are their breath sounds better? They should be weighing themselves daily and monitoring their intake and output. Teach them how to evaluate if they're having complications from electrolyte changes. Spironolactone acts as an aldosterone antagonist and so it blocks the action of aldosterone in the distal tubule. This results in the sodium not being retained, fluid not being retained, but potassium is retained at higher levels. Pharmacokinetics is orally, it's very well absorbed. It is protein bound. So you do have to know that people have adequate protein and nutrition. It does cross the placenta and can enter breast milk. It is metabolized in the liver and excreted in the kidneys. So again, people that have any compromise in those areas, you do have to look at dosing levels. Can it be used in hypertension and people that have edema for CHF, maybe cirrhosis? It is usually used when they are on another diuretic. And the hope is that it balances out some of that electrolyte loss. It actually has one of the weakest diuretic effects because again if it's given alone, because it is working in the distal tubule, but it does work very well and has a good synergistic effect when given with other diuretics. So significant contraindication. If the patient is already receiving a potassium sparing diuretic, you should always question this because we don't want them to have too much potassium retained if they were in renal disease or anuric because again, we could have hyperkalemia. And then the literature says it should be used very sparing during pregnancy. The effect and the outcome and the benefit to the fetus and the mother has to be weighed against the risks that are there. Common adverse effects are actually probably going to be due to electrolyte shifts, but we do look for nausea, vomiting, dizziness, headaches, some drowsiness or rash. Serious we're going to again be looking for hyperkalemia. And this is the lethargy ataxia, which is that inability, deformed learned movements, muscle cramping, and most serious are cardiac arrhythmias. Older adults due to the decreased kidney function are usually who we are most at risk for with hyperkalemia. So nursing interventions to maximize the therapeutic effects, teach your patients again to administer or to take the diuretic in the morning so that we have all day to have that effect. They should be counseled to monitor the potassium levels. So they need to keep doctor's appointments for lab values and then teach them signs and symptoms so they know when they have low potassium or high potassium. You really want to teach the patient so they're able to notify us when they have any problems. They need to be taught to avoid potassium rich foods. And, sorry, I realize that the scribbling is so attractive on the slide, but things like potassium, avocados, potatoes, salt substitutes that actually use a potassium iodide salt, they do have to look and read the labels. So you need to make sure that they're not taking any additional potassium supplements. And if the physician orders that question him, are they aware that they are already on a potassium sparing diuretic. We just don't want to get that potassium level too high.