Module 2 Pre-quiz Review Lecture PDF

6/15/2024 NURS 306 Module 2 Pre-quiz Review Lecture Mary D. Bondmass, Ph.D., RN, CNE Professor in Residence, School of Nursing University of Nevada Las...

6/15/2024 NURS 306 Module 2 Pre-quiz Review Lecture Mary D. Bondmass, Ph.D., RN, CNE Professor in Residence, School of Nursing University of Nevada Las Vegas [email protected] 702-285-3460 Chapter 22: Antihypertension Drugs When you reach the end of this chapter, you will be able to do the following: 1. Discuss the normal anatomy and physiology of the autonomic nervous system, including the events that take place within the sympathetic and parasympathetic nervous system to maintain long-term and short-term control of blood pressure. 2. Define hypertension. 3. Compare primary and secondary hypertension. 4. Describe the protocol for treating hypertension as detailed in the Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8), including the rationale for its use. 5. List the criterion pressure values (in millimeters of mercury) for the hypertension categories of normal blood pressure, prehypertension, hypertension stage 1, and hypertension stage 2 as defined in JNC 8. 6. Using the most recent guidelines, compare the various drugs used in the pharmacologic management of hypertension with regard to mechanism of action, specific indications, adverse effects, toxic effects, cautions, drug interactions, contraindications, dosages, and routes of administration. 7. Discuss the rationale for the nonpharmacologic management of hypertension. 1  6/15/2024 Chapter 22: Key Terms Cardiac output: The amount of blood ejected from the left ventricle Hypertension (HTN): A common, often asymptomatic disorder in which systolic blood pressure persistently exceeds 150 mm Hg and/or diastolic pressure exceeds 90 mm Hg in patients over 60 years of age and 140/90 for patients younger than 60 and those who have chronic kidney disease or diabetes Essential hypertension: Elevated systemic arterial pressure for which no cause can be found; also called primary or idiopathic hypertension Secondary hypertension High blood pressure caused by another disease such as renal, pulmonary, endocrine, or vascular disease Orthostatic hypotension A common adverse effect of adrenergic-blocking drugs involving a sudden drop in blood pressure when a person changes position, especially when rising from a seated or horizontal position. Sympathetic vs Parasympathetic nervous system Review of Autonomic Neurotransmission Activation of the autonomic nervous system (ANS) consists of sympathetic stimulation of the adrenal medulla and nerve endings to rapidly secrete catecholamines (norepinephrine, epinephrine Two divisions of ANS Parasympathetic nervous system (PNS): stimulates smooth muscles, cardiac muscles, glands Sympathetic nervous system (SNS): stimulates heart, blood vessels, skeletal muscles Stimulation is controlled by neurotransmitters. Acetylcholine Norepinephrine Receptors located throughout the body 6 2  6/15/2024 Self-Review Autonomic Nervous System, 318 Anatomy of the Sympathetic Nervous System, p. 319 Anatomy of the Parasympathetic Nervous System, p. 321 Neurotransmitters and Neuroreceptors, p. 322 Functions of the Autonomic Nervous System, p. 322 Huether, Sue, McCance, K. L., Brashers, V. L. (2020). Understanding pathophysiology. (7th Ed.). Elsevier Health Sciences (US). 7 Pharmacology Overview Drug therapy for hypertension must be individualized. Seven main categories of drugs to treat hypertension Diuretics Adrenergic drugs Vasodilators Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Direct renin inhibitors 8 FIG. 22.1 Normal regulation of blood pressure and corresponding medications. ACE, Angiotensin-converting enzyme; CNS, central nervous system 3  6/15/2024 Beta Blockers (BB) Mechanism of Action block SNS stimulation of the beta-adrenergic receptors by competing with norepinephrine and epinephrine resulting in slowing the speed & force of the heart and thereby decreasing BP. Their antihypertensive effects are related to their reduction of the heart rate through beta1 receptor blockade. Furthermore, beta blockers also cause a reduction in the secretion of the hormone renin (see the section on ACE inhibitors later in the chapter), which in turn reduces both AII-mediated vasoconstriction and aldosterone- mediated volume expansion. Long-term use of beta blockers also reduces peripheral vascular resistance. Indications angina, MI, cardiac dysrhythmias, hypertension, and heart failure Contraindications known drug allergies and may include uncompensated heart failure, cardiogenic shock, heart block or bradycardia, pregnancy, severe pulmonary disease, and Raynaud’s disease. All beta blockers share a black box warning stating that therapy should not be withdrawn abruptly but should be tapered over 1 to 2 weeks. Adverse effects most common adverse effects of beta blockers include bradycardia, depression, impotence, constipation, and fatigue. Some of the most serious undesirable effects can be caused by acute withdrawal of the drug. For example, such sudden withdrawal may exacerbate underlying angina, precipitate an MI, or cause rebound hypertension. Beta blockers also delay the recovery from hypoglycemia in patients with type 1 diabetes (rarely in those with type 2). Adverse effects induced by beta blockers are listed by body system in Examples: Probably on Quiz (POQ): atenolol, carvedilol, metoprolol, propranolol Probably not on Quiz (PNOQ): esmolol, Labetalol,, sotalol, phentolamine, tamsulosin Calcium Channel Blockers (CCB) There are three chemical classes of CCBs (mechanisms of action differ slightly) Phenylalkylamines (e.g., verapamil) Benzothiazepines (e.g., diltiazem) dihydropyridines (e.g. amlodipine) (Table 23.4). More than nine CCBs are available today. Those that are used for the treatment of chronic stable angina are amlodipine, diltiazem, nicardipine, nifedipine, and verapamil. 4  6/15/2024 Calcium Channel Blockers (CCB) Mechanism of Action Calcium plays an important role in the excitation-contraction coupling process that occurs in the heart and vascular smooth muscle cells, as well as in skeletal muscle. Preventing calcium from entering into this process prevents muscle contraction and promotes muscle relaxation. That is, the stop calcium from entering the cells of the heart and arteries. Since calcium causes the heart and arteries to contract more strongly, by blocking calcium, CCBs allow blood vessels to relax and open Indications angina, HTN, and supraventricular tachycardia, coronary artery spasms, short-term management of atrial fibrillation and flutter. The dihydropyridine CCB, nimodipine, is indicated solely for cerebral artery spasms associated with aneurysm rupture, Contraindications known drug allergy, acute MI, second- or third-degree AV block (unless the patient has a pacemaker), and hypotension Adverse effects Hypotension, palpitations, tachycardia or bradycardia, constipation, nausea, dyspnea, rash, flushing, peripheral edema Examples: Probably on Quiz (POQ): diltiazem, amlodipine, felodipine nifedipine, nimodipine, verapamil Probably not on Quiz (PNOQ):isradipine nicardipine Centrally Acting Adrenergics Adrenergic drugs are a large group of antihypertensive drugs, as shown in Box 22.1 (Lilley et al., 2023). Five specific drug subcategories are included in the adrenergic antihypertensive drugs as indicated in Box 22.1. Each of these subcategories of drugs can be described as having central action (in the brain) or peripheral action (at the heart and blood vessels). These drugs include the adrenergic neuron blockers (central and peripheral), the alpha2 receptor agonists (central), the alpha1 receptor blockers (peripheral), the beta receptor blockers (peripheral), and the combination alpha1 and beta receptor blockers (peripheral). Adrenergic Drugs: Five Subcategories Adrenergic neuron blockers (central and peripheral) Alpha2 receptor agonists (central) Alpha1 receptor blockers (peripheral) Beta receptor blockers (peripheral) Combination alpha1 and beta receptor blockers (peripheral) 15 5  6/15/2024 Centrally Acting Adrenergics: Mechanism of Action Stimulation of the SNS leads to an increase in heart rate and force of contraction, the constriction of blood vessels, and the release of renin from the kidney, resulting in hypertension. The centrally acting adrenergic drugs clonidine and methyldopa work by stimulating the alpha2-adrenergic receptors in the brain. The alpha2-adrenergic receptors are unique in that receptor stimulation actually reduces sympathetic outflow, in this case from the central nervous system (CNS). This results in a lack of norepinephrine production, which reduces blood pressure. In the periphery, the alpha1 blockers doxazosin, prazosin, and terazosin work by blocking the alpha1-adrenergic receptors. When alpha1-adrenergic receptors are stimulated by circulating norepinephrine, they produce increased blood pressure. Thus, when these receptors are blocked, blood pressure is decreased. Two dual-action alpha1 and beta receptor blockers, labetalol and carvedilol, also act in the periphery at the heart and blood vessels. They have the dual antihypertensive effects of reduction in heart rate (beta1 receptor blockade) and vasodilation (alpha1 receptor blockade). The beta blockers also act in the periphery and include propranolol, metoprolol, and atenolol, as well as several other drugs. Examples: Probably on Quiz (POQ): clonidine, methyldopa, doxazosin, prazosin, terazosin, propranolol, metoprolol, atenolol, labetalol and carvedilol Centrally Acting Adrenergics (cont) Indications HTN (either alone or in combination with other antihypertensive drugs). The alpha1 blockers doxazosin, prazosin, and terazosin have been used to relieve the symptoms associated with BPH (see Chapter 19). They have also proved effective in the management of severe heart failure when used with cardiac glycosides (see Chapter 24) and diuretics (see Chapter 28). Contraindications known drug allergy and may also include acute heart failure, concurrent use of monoamine oxidase inhibitors (see Chapter 16), peptic ulcer, and severe liver or kidney disease. Asthma also may be a contraindication to the use of any non-cardioselective beta blocker (e.g., carvedilol). Adverse effects The most common adverse effects of adrenergic drugs are bradycardia with reflex tachycardia, postural and postexercise hypotension, dry mouth, drowsiness, dizziness, depression, edema, constipation, and sexual dysfunction (e.g., impotence). Other effects include headache, sleep disturbances, nausea, rash, and palpitations. There is a high incidence of orthostatic hypotension (a sudden drop in blood pressure during changes in position) in patients taking alpha blockers. Examples of POQ on previous slide 6  6/15/2024 Angiotensin-converting Enzyme (ACE) Inhibitors Mechanism of Action Inhibit angiotensin-converting enzyme which is responsible for converting angiotensin I to angiotensin II; prevent sodium and water resorption by inhibiting aldosterone secretion, resulting in diuresis which decreases preload, or the left ventricular end-volume, and the work of the heart. Indications The therapeutic effects of the ACE inhibitors are related to their potent cardiovascular effects. They are excellent antihypertensives and adjunctive drugs for the treatment of heart failure. They may be used alone or in combination with other such as diuretics in the treatment of hypertension or heart failure Contraindications known drug allergy, especially a previous reaction of angioedema (e.g., laryngeal swelling) to an ACE inhibitor. Patients with a baseline potassium level of 5 mEq/L or higher may not be suitable candidates for ACE inhibitor therapy, because these drugs can promote hyperkalemia. All ACE inhibitors are contraindicated in lactating women, in children, and in patients with bilateral renal artery stenosis, and should be avoided in pregnancy (category D drugs for women in their second or third trimester) Adverse effects Major CNS effects include fatigue, dizziness, mood changes, and headaches. A characteristic dry, nonproductive cough may occur that is reversible with discontinuation of the therapy. A first-dose hypotensive effect can cause a significant decline in blood pressure. Other adverse effects include loss of taste, hyperkalemia, angioedema, and renal impairment. In patients with severe heart failure whose renal function may depend on the activity of the renin- angiotensin-aldosterone system, treatment with ACE inhibitors may cause acute renal failure. Examples: POQ: captopril (Capoten), (Lotensin), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil), PNOQ:perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik). Angiotensin II Receptor Blockers (ARB) Mechanism of Action ARBs block the binding of AII to type 1 AII receptors. In contrast to ACE inhibitors, the ARBs affect primarily vascular smooth muscle and the adrenal gland. By selectively blocking the binding of AII to the type 1 AII receptors in these tissues, ARBs block vasoconstriction and the secretion of aldosterone. AII receptors have been found in other tissues throughout the body, but the effects of ARB blocking of these receptors is unknown. Indications therapeutic effect are relatesd to their potent vasodilating properties. They are excellent antihypertensives and adjunctive drugs for the treatment of heart failure. They may be used alone or in combination with other drugs such as diuretics in the treatment of hypertension or heart failure. The beneficial hemodynamic effect of ARBs is their ability to decrease SVR (a measure of afterload). Contraindications known drug allergy, pregnancy, and lactation. They need to be used cautiously in older adults and in patients with renal dysfunction. As with other antihypertensives, blood pressure and apical pulse rate need to be assessed before and during drug therapy. Adverse effects most common are chest pain, fatigue, hypoglycemia, diarrhea, urinary tract infection, anemia, and weakness. Hyperkalemia and cough are less likely to occur than with the ACE inhibitors. All ARBs carry a black box warning regarding fetal toxicity and should not be used in pregnancy Examples: POQ losartan (Cozaar) ,valsartan (Diovan), irbesartan (Avapro), PNOQL candesartan (Atacand), eprosartan (Teveten), telmisartan (Micardis), olmesartan (Benicar) Miscellaneous Antihypertensive Drugs Eplerenone (Inspra) represents a new class of drugs called selective aldosterone blockers and is used for hypertension. Eplerenone is currently the only drug in a new class of antihypertensive drugs called selective aldosterone blockers. It reduces blood pressure by blocking the actions of aldosterone at its corresponding receptors in the kidney, heart, blood vessels, and brain. Eplerenone is indicated for both routine treatment of hypertension and for post-MI heart failure. Its use is contraindicated in patients with known drug allergy, elevated serum potassium levels (higher than 5.5 mEq/L), or severe renal impairment and in those using a medication that inhibits the action of cytochrome P-450 enzyme 3A4. Many commonly used medications inhibit the action of this enzyme, including several antibiotic, antifungal, and antiviral drugs. Bosentan (Tracleer) works by blocking the receptors of the hormone endothelin. Normally this hormone acts to stimulate the narrowing of blood vessels by binding to endothelin receptors (ETA and ETB) in the endothelial (innermost) lining of blood vessels and in vascular smooth muscle. Bosentan reduces blood pressure by blocking this action. However, currently it is specifically indicated only for the treatment of pulmonary artery hypertension in patients with moderate to severe heart failure. It is available only through a limited distribution program directly from the manufacturer. Bosentan has a black box warning regarding hepatotoxicity and teratogenicity. Its use is contraindicated in patients with known drug allergy, pregnancy, or significant liver impairment and in patients receiving concurrent drug therapy with cyclosporine or glyburide. POQ Eplerenone, Bosentan 7  6/15/2024 Chapter 28: Diuretic Drugs When you reach the end of this chapter, you will be able to do the following: 1. Describe the normal anatomy and physiology of the renal system. 2. Briefly discuss the impact of the renal system on blood pressure regulation. 3. Discuss how diuretics work in the kidneys and how they lower blood pressure. 4. Distinguish among the different classes of diuretics with regard to mechanisms of action, indications, dosages, routes of administration, adverse effects, toxicity, cautions, contraindications, and drug interactions. Chapter 28: Key Terms Afferent arterioles The small blood vessels approaching the glomerulus (proximal part of the nephron). Aldosterone A mineralocorticoid steroid hormone produced by the adrenal cortex that regulates sodium and water balance. Ascites An intraperitoneal accumulation of fluid (defined as a volume of 500 mL or more) containing large amounts of protein and electrolytes. Collecting duct The most distal part of the nephron between the distal convoluted tubule and the ureters, which lead to the urinary bladder. Distal convoluted tubule The part of the nephron immediately distal to the ascending loop of Henle and proximal to the collecting duct. Diuretics Drugs or other substances that promote the formation and excretion of urine. Efferent arterioles The small blood vessels exiting the glomerulus. At this point blood has completed its filtration in the glomerulus. Filtrate The material that passes through a filter. In the kidney, the filter is the glomerulus and the filtrate is the material extracted from the blood (normally liquid), which becomes urine. Chapter 28: Key Terms (cont) Glomerular capsule The open, rounded, and most proximal part of the proximal convoluted tubule that surrounds the glomerulus and receives the filtrate from the blood. Glomerular filtration rate (GFR) An estimate of the volume of blood that passes through the glomeruli of the kidney per minute. Glomerulus The cluster of kidney capillaries that marks the beginning of the nephron and is immediately proximal to the proximal convoluted tubule. Loop of Henle The part of the nephron between the proximal and distal convoluted tubules. Nephron The functional filtration unit of the kidney, consisting of (in anatomic order from proximal to distal) the glomerulus, proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct, which empties urine into the ureters. Open-angle glaucoma A condition in which pressure is elevated in the eye because of obstruction of the outflow of aqueous humor. Proximal convoluted (twisted) tubule The part of the nephron that is immediately distal to the glomerulus and proximal to the loop of Henle. 8  6/15/2024 Types of Diuretic Drugs Carbonic anhydrase inhibitors (CAIs) Potassium-sparing diuretics Loop diuretics Thiazide and thiazide-like diuretics Osmotic diuretics 26 Diuretics: Carbonic Anhydrase Inhibitors Mechanism of Action The carbonic anhydrase system in the kidney is located just distal to the glomerulus in the proximal tubules, where roughly two-thirds of all sodium and water is resorbed into the blood. In the proximal tubules, there is an active transport system that exchanges sodium for hydrogen ions. For sodium and water to be resorbed back into the blood, hydrogen must be exchanged for it. Without hydrogen, this cannot occur, and the sodium and water will be eliminated with the urine. Carbonic anhydrase makes hydrogen ions available for this exchange. When its actions are inhibited by a CAI, such as acetazolamide, little sodium and water can be resorbed into the blood and they are eliminated with the urine. The CAIs reduce the formation of hydrogen (H+) and bicarbonate (HCO3 –) ions from carbon dioxide and water through the noncompetitive, reversible inhibition of carbonic anhydrase activity. This results in a reduction in the availability of the ions, mainly hydrogen, for use by active transport systems. Indications Therapeutic uses of CAIs include the treatment of glaucoma, edema, and high-altitude sickness. Acetazolamide is also used to manage edema secondary to heart failure that has become resistant to other diuretics. However, as a class, CAIs are much less potent diuretics than loop diuretics or thiazides; because of the metabolic acidosis they induce, their effectiveness diminishes in 2 to 4 days. Acetazolamide is also effective in both the prevention and treatment of the symptoms of high-altitude sickness. These symptoms include headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue. Contraindications known drug allergy, hyponatremia, hypokalemia, severe renal or hepatic dysfunction, adrenal gland insufficiency, and cirrhosis. Although the product labeling lists sulfa allergy as a contraindication, the scientific basis for this has been questioned and they are often used in patients with sulfa allergy. Nonetheless, it is prudent to watch for hypersensitivity reactions. Adverse effects Common undesirable effects of CAIs are metabolic abnormalities such as acidosis and hypokalemia. Drowsiness, anorexia, paresthesias, hematuria, urticaria, photosensitivity, and melena (blood in the stool) can also occur. POQ = Probably on the quiz Acetazolamide 9  6/15/2024 Potassium-Sparing Diuretics Mechanism of Action Potassium-sparing diuretics work in the collecting ducts and distal convoluted tubules, where they interfere with sodium- potassium exchange. Spironolactone competitively binds to aldosterone receptors and therefore blocks the resorption of sodium and water that is induced by aldosterone secretion. Indications Spironolactone and triamterene are used to treat hyperaldosteronism and hypertension and to reverse the potassium loss caused by the potassium-wasting (e.g., loop, thiazide) diuretics. Spironolactone is also used in the management of heart failure. The uses for amiloride are similar to those for spironolactone and triamterene, but amiloride is less effective in the long term. It may be more effective than spironolactone or triamterene in the treatment of metabolic alkalosis, however. It is primarily used in the management of heart failure. As with certain other classes of diuretics, potassium-sparing diuretics may also be indicated in cases of heart failure resulting from diastolic dysfunction Contraindications known drug allergy, hyperkalemia (i.e., serum potassium level exceeding 5.5 mEq/L), and severe renal failure or anuria. Triamterene use may also be contraindicated in cases of severe hepatic failure... Adverse Effects Spironolactone can cause gynecomastia, amenorrhea, irregular menses, and postmenopausal bleeding. Triamterene may reduce folic acid levels and cause the formation of kidney stones and urinary casts. It may also precipitate megaloblastic anemia. Hyperkalemia may occur when potassium-sparing diuretics are used in combination with each other and/or with other potassium-sparing drugs such as angiotensin-converting enzyme (ACE) inhibitors (see Chapter 22 and the following “Interactions” section). Examples POQ Spironolactone , triamterene PNOQ amiloride Loop Diuretics Mechanism of Action act primarily along the thick ascending limb of the loop of Henle blocking chloride and, secondarily, sodium resorption. Loop diuretics are also thought to activate renal prostaglandins, which results in dilation of the blood vessels of the kidneys, the lungs, and the rest of the body (i.e., reduction in renal, pulmonary, and systemic vascular resistance). Indications used to manage the edema associated with heart failure and hepatic or renal disease, to control hypertension, and to increase the renal excretion of calcium in patients with hypercalcemia. Contraindications known drug allergy, hepatic coma, and severe electrolyte loss. Although allergy to sulfonamide antibiotics is listed as a contraindication, analysis of the literature indicates that cross-reaction with the loop diuretics is unlikely to occur. Loop diuretics are commonly given to such patients in clinical practice. Adverse effects hypokalemia is of serious clinical importance. Furosemide can produce erythema multiforme, exfoliative dermatitis, photosensitivity, and in rare cases aplastic anemia. Torsemide may rarely cause blood disorders, including thrombocytopenia, agranulocytosis, leukopenia, and neutropenia. It may also cause a severe skin disorder called Stevens-Johnson syndrome.. Examples POQ = Probably on the quiz bumetanide, ethacrynic acid, furosemide, and torsemide Thiazides and Thiazide-Like Diuretics Mechanism of Action The primary site of action of thiazides and thiazide-like diuretics is the distal convoluted tubule, where they inhibit the resorption of sodium, potassium, and chloride. This results in osmotic water loss. Thiazides also cause direct relaxation of the arterioles (small blood vessels), which reduces peripheral vascular resistance (afterload). Decreased preload (filling pressures) and decreased afterload (the force the ventricles must overcome to eject the volume of blood they contain) are beneficial hemodynamic effects. This makes them very effective for the treatment of both heart failure and hypertension. Indications used primarily in the treatment of HTN. They also can be used in the treatment of edema of various origins, idiopathic hypercalciuria, diabetes insipidus, and as adjunct drugs in the management of heart failure and hepatic cirrhosis. Any of these drugs can be used either as monotherapy or in combination with other drugs. Contraindications known drug allergy, hepatic coma (metolazone), anuria, and severe renal failure. Adverse Effects electrolyte and metabolic disturbances, mainly reduced potassium and sodium levels and elevated levels of calcium, lipids, glucose, and uric acid. other effects—such as gastrointestinal disturbances, skin rashes, photosensitivity, thrombocytopenia, pancreatitis, and cholecystitis—are less common. Dizziness and vertigo are common adverse effects of metolazone therapy and are attributed to sudden shifts in the plasma volume brought about by the drug. Headache, impotence, and decreased libido are other important adverse effects of these drugs. The more common adverse effects of the thiazide and thiazide-like diuretics are dizziness, headache, blurred vision, anorexia, nausea, vomiting, diarrhea, hypokalemia, hyperglycemia, hyperuricemia, hypochloremic alkalosis, Impotence. jaundice, leukopenia, agranulocytosis, urticaria, & photosensitivity Examples POQ hydrochlorothiazide (HCTZ).metolazone PNOQ amiloride, chlorthalidone &indapamide 10  6/15/2024 Mechanism of Action Osmotic Diuretics Mannitol works along the entire nephron. Its major site of action, however, is the proximal tubule and descending limb of the loop of Henle. Because it is not absorbed, it increases osmotic pressure in the glomerular filtrate, which in turn pulls fluid, primarily water, into the renal tubules from the surrounding tissues. This process also inhibits the tubular resorption of water and solutes, which produces a rapid diuresis. Ultimately this reduces cellular edema and increases urine production, causing diuresis. However, it produces only a slight loss of electrolytes, especially sodium. Therefore mannitol is not indicated for patients with peripheral edema because it does not promote sufficient sodium excretion. Mannitol may induce vasodilation; in doing so, it increases both glomerular filtration and renal plasma flow. This makes it an excellent drug for preventing kidney damage during acute renal failure. It is also often used to reduce intracranial pressure and cerebral edema resulting from head trauma. In addition, mannitol treatment may be tried when elevated intraocular pressure is unresponsive to other drug therapies. Indications treatment of patients in the early oliguric phase of acute renal failure. For it to be effective in this setting, however, enough renal blood flow and glomerular filtration must still remain to enable the drug to reach the renal tubules. Mannitol also can be used to promote the excretion of toxic substances, reduce intracranial pressure, and treat cerebral edema Contraindications known drug allergy, severe renal disease, pulmonary edema (loop diuretics are used instead), and active intracranial bleeding. Adverse Effects convulsions, thrombophlebitis, and pulmonary congestion Examples POQ mannitol PNOQ, urea, organic acids, and glucose Chapter 23: Antianginal Drugs When you reach the end of this chapter, you will be able to do the following: 1. Briefly discuss the pathophysiology of myocardial ischemia and the subsequent occurrence of angina. 2. Discuss the various factors that may precipitate angina and measures that decrease its occurrence. 3. Contrast the major classes of antianginal drugs (nitrates, calcium channel blockers, and beta blockers) with regard to their mechanisms of action, dosage forms, routes of administration, cautions, contraindications, drug interactions, adverse effects, patient tolerance, and toxicity. Chapter 23: Key Terms Angina pectoris Chest pain that occurs when the heart’s supply of blood carrying oxygen is insufficient to meet the demands of the heart. Atherosclerosis A common form of arteriosclerosis involving deposits of fatty, cholesterol-containing material (plaques) within arterial walls. Chronic stable angina Chest pain that is primarily caused by atherosclerosis, which results in a long-term but relatively stable level of obstruction in one or more coronary arteries. Coronary arteries Arteries that deliver oxygen to the heart muscle. Coronary artery disease (CAD) Any one of the abnormal conditions that can affect the arteries of the heart and produce various pathologic effects, especially a reduced supply of oxygen and nutrients to the myocardium. Ischemia Ischemia is damaged cells/tissue as the result of inadequate oxygen supply. Ischemic heart disease Poor blood supply to the heart via the coronary arteries. Myocardial infarction (MI) Necrosis of the myocardium after interruption of blood supply; it is almost always caused by atherosclerosis of the coronary arteries and is commonly called a heart attack. Reflex tachycardia A rapid heartbeat caused by a variety of autonomic nervous system effects, such as blood pressure changes, fever, or emotional stress. Unstable angina Early stage of progressive CAD. Vasospastic angina Ischemia-induced myocardial chest pain caused by spasms of the coronary arteries; also referred to as Prinzmetal or variant angina. 11  6/15/2024 Types of Antianginal Drugs/Objectives Three main classes of drugs to treat angina Nitrates, Beta Blockers, & Calcium Channel Blockers (CCB) There are three main therapeutic objectives of antianginal drug therapy: 1) minimize the frequency of attacks and decrease the duration and intensity of the anginal pain; 2) improve the patient’s functional capacity with as few adverse effects as possible; and 3) prevent or delay the worst possible outcome, MI. The overall goal of antianginal drug therapy is to increase blood flow to the ischemic myocardium, decrease myocardial oxygen demand, or both. Fig. 23.1 illustrates how drug therapy works to alleviate angina. 34 Nitrates and Nitrites The following are the rapid- and long-acting nitrates available for clinical use: nitroglycerin (both rapid and long acting) isosorbide dinitrate (both rapid and long acting) isosorbide mononitrate (primarily long acting) Nitrites are known to hold one nitrogen atom along with two oxygen atoms, whereas nitrates are known to hold one nitrogen atom, bonded to three different oxygen atoms. A nitrite can become a nitrate by the process of oxidation and similarly, a nitrate can become a nitrite by the process of reduction. Not on the quiz  12  6/15/2024 Mechanism of Action Nitrates and Nitrites Medicinal nitrates and nitrites, more commonly referred to as nitrates, dilate all blood vessels. They predominantly affect venous vascular beds; however, they also have a dose-dependent arterial vasodilator effect. These vasodilatory effects are the result of relaxation of the smooth muscle cells that are part of the wall structure of veins and arteries. The nitrates have a potent dilating effect on the large and small coronary arteries. This causes redistribution of blood and oxygen to previously ischemic myocardial tissue and reduction of anginal symptoms. By causing venous dilation, the nitrates reduce venous return and, in turn, reduce the left ventricular end-diastolic volume (or preload), which results in a lower left ventricular pressure. Left ventricular systolic wall tension is thus reduced, as is myocardial oxygen demand. These and other drug effects are summarized in Table 23.1. Indications treat stable, unstable, and vasospastic (Prinzmetal) angina. Long-acting dosage forms are used more for prevention of anginal episodes. Rapid-acting dosage forms, most often sublingual nitroglycerin tablets, or an intravenous drip in the hospital setting, are used to treat acute anginal attacks. Contraindications known drug allergy, as well as severe anemia, closed-angle glaucoma, hypotension, and severe head injury. Nitrates are also contraindicated with the use of the erectile dysfunction drugs sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) (see Chapter 35). Adverse effects Nitrates are well tolerated, and most adverse effects are usually transient and involve the cardiovascular system. The most common undesirable effect is headache, which generally diminishes soon after the start of therapy. Other cardiovascular effects include tachycardia and postural hypotension. If nitrate-induced vasodilation occurs too rapidly, the cardiovascular system overcompensates and increases the heart rate, a condition referred to as reflex tachycardia. Examples: POQ nitroglycerin, hydralazine/isosorbide dinitrate PNOQL sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) isosorbide dinitrate (Isordil) an organic nitrate. It exerts the same effects as the other nitrates. When isosorbide dinitrate is metabolized in the liver, it is broken down into two active metabolites, both of which have the same therapeutic actions as isosorbide dinitrate itself. This drug is available in rapid-acting sublingual tablets, immediate-release tablets, and long-acting oral dosage forms. isosorbide mononitrate (Imdur) one of the two active metabolites of isosorbide dinitrate, but it has no active metabolites itself. Because of these qualities, it produces a more consistent, steady therapeutic response, with less variation in response within the same patient and between patients. It is available in both immediate- and sustained-release oral dosage forms but is most commonly used in the sustained-release form. Nitroglycerin (Nitro-Bid, Nitrostat) Nitroglycerin is the prototypical nitrate and is manufactured by many pharmaceutical companies; therefore it goes by many different trade names (e.g.,). It is often abbreviated as NTG or TNG. It has traditionally been the most important drug used in the symptomatic treatment of ischemic heart conditions such as angina. When given orally, nitroglycerin goes to the liver to be metabolized before it can become active in the body. During this process, a very large amount of the nitroglycerin is removed from the circulation. This is called a large first-pass effect (see Chapter 2). For this reason, nitroglycerin is administered by routes other than orally, to avoid the first-pass effect. Tablets administered by the sublingual route are used for the treatment of chest pain or angina of acute onset. They are also used for the prevention of angina when patients find themselves in situations likely to provoke an attack. Chapter 24: Heart Failure Drugs When you reach the end of this chapter, you will be able to do the following: 1. Differentiate among the terms inotropic, chronotropic, and dromotropic. 2. Compare the normal anatomy and physiology of the heart. 3. Discuss the pathophysiologic changes in the heart that has been affected by heart failure. 4. Briefly discuss the approach to treatment of heart failure as outlined by the American Heart Association and American College of Cardiology Guidelines for the Diagnosis and Management of Heart Failure in Adults (last updated in 2013). 5. Compare the mechanisms of action, pharmacokinetics, indications, dosages, dosage forms, routes of administration, cautions, contraindications, adverse effects, and toxicity of the following drugs used in treatment of heart failure: lisinopril, valsartan, carvedilol, metoprolol, dobutamine, hydralazine/isosorbide dinitrate, milrinone, and digoxin. 6. Briefly discuss the process of rapid versus slow digitalization and the use of the antidote digoxin immune Fab. 7. Identify significant drug-drug, drug–laboratory test, and drug-food interactions associated with digoxin and other heart failure drugs. 13  6/15/2024 Chapter 24: Key Terms Atrial fibrillation A common cardiac dysrhythmia with atrial contractions that are so rapid that they prevent full repolarization of myocardial fibers between heartbeats. Automaticity A property of specialized excitable tissue in the heart that allows self-activation through the spontaneous development of an action potential, such as in the pacemaker cells of the heart. Chronotropic drugs Drugs that influence the rate of the heartbeat. Dromotropic drugs Drugs that influence the conduction of electrical impulses within tissues. Ejection fraction The proportion of blood that is ejected during each ventricular contraction compared with the total ventricular filling volume. Heart failure An abnormal condition in which the heart cannot pump enough blood to keep up with the body’s demand. It is often the result of myocardial infarction, ischemic heart disease, or cardiomyopathy. Inotropic drugs Drugs that influence the force of muscular contractions, particularly contraction of the heart muscle. Left ventricular end-diastolic volume The total amount of blood in the ventricle immediately before it contracts, or the preload. Heart Failure Not a specific disease / Complex clinical syndrome resulting from any functional or structural impairment to the heart, specifically ejection of blood or ventricular filling The heart is unable to pump blood in sufficient amounts from the ventricles to meet the body’s metabolic needs. Symptoms depend on the cardiac area affected Common symptoms: dyspnea, fatigue, fluid retention and/or pulmonary edema “Left-sided” heart failure (HF): pulmonary edema, coughing, shortness of breath, and dyspnea “Right-sided” HF: systemic venous congestion, pedal edema, jugular venous distension, ascites, and hepatic congestion 41 Angiotensin Receptor–Neprilysin Inhibitors (ARNi) Mechanism of Action Valsartan/sacubitril (Entresto) is the first drug in a class called the ARNis. Sacubitril inhibits neprilysin which leads to increased levels of natriuretic peptides. Valsartan antagonizes the angiotensin I–induced vasoconstriction, aldosterone release, and catecholamine release. Valsartan/sacubitril is converted to an active metabolite, LBQ657, which plays a role in its half-life. Indications heart failure Contraindications known drug therapy, hypersensitivity to sacubitril or valsartan; history of angioedema related to previous ACE inhibitor or ARB therapy and use within 36 hours of an ACE inhibitor; and concomitant use of aliskiren in diabetic patients. it is a pregnancy category D drug and has a black box warning regarding its use in pregnancy. Adverse effects risk for angioedema, hyperkalemia, hypotension, and renal function deterioration; most common are hypotension, hyperkalemia, and increased serum creatinine. Example: POQ valsartan/sacubitril 14  6/15/2024 Cardiac Glycosides Mechanism of Action The beneficial effect of digoxin is thought to be an increase in myocardial contractility—known as a positive inotropic effect. This occurs secondarily to the inhibition of the sodium-potassium adenosine triphosphatase pump. When the action of this enzyme-complex is inhibited, the cellular sodium and calcium concentrations increase. The overall result is enhanced myocardial contractility. Digoxin also augments cholinergic (or parasympathetic) stimulation via the vagus nerve of the parasympathetic nervous system. This is more commonly referred to as vagal tone and results in increased diastolic filling between heartbeats secondary to reduced heart rate. Vagal tone is also believed to sensitize cardiac baroreceptors, which reduces sympathetic stimulation from the central nervous system. All of these processes further enhance cardiac efficiency and output. Indications primarily used in the treatment of systolic heart failure and atrial fibrillation. The latest heart failure treatment guidelines recommend that it be used as an adjunct to drugs of other classes, including beta blockers, diuretics, ACE inhibitors, and ARBs in selected patients. Contraindications known drug allergy and may include second- or third-degree heart block, ventricular fibrillation, and heart failure resulting from diastolic dysfunction. However, if recommended by a seasoned cardiologist, digoxin may be used to treat some of these conditions, depending on the given clinical situation. Adverse effects common undesirable effects are cardiovascular, central nervous system, ocular, and gastrointestinal effects including bradycardia or tachycardia; hypotension, headache, fatigue, confusion, convulsions, unusual colored vision (i.e., green, yellow), halo vision, anorexia, nausea, vomiting, diarrhea Example: POQ digoxin MB1 Toxicity and Management of Digoxin Overdose Digoxin has a low therapeutic index (see Chapter 2). Digoxin levels are monitored when the patient first starts taking the drug. However, once the drug reaches steady state, monitoring is usually necessary only if there is suspicion of toxicity, noncompliance, or deteriorating renal function. Normal therapeutic levels for digoxin are 0.5 to 2 ng/mL. Low potassium or magnesium levels may increase the potential for digoxin toxicity. Therefore frequent monitoring of serum electrolytes is also important. A decrease in renal function is a common cause of digoxin toxicity, because digoxin is excreted almost exclusively by the kidneys. Signs and symptoms of digoxin toxicity include bradycardia, headache, dizziness, confusion, nausea, and visual disturbances (blurred vision or yellow vision). With toxicity, ECG findings may include heart block, atrial tachycardia with block, or ventricular dysrhythmias. Predisposing factors to digoxin toxicity are listed in Table 24.2. The treatment strategies for digoxin toxicity depend on the severity of the symptoms. These strategies can range from simply withholding the next dose to instituting more aggressive therapies. When significant toxicity develops as a result of digoxin therapy, the administration of digoxin immune Fab may be indicated. Digoxin immune Fab is an antibody that recognizes digoxin as an antigen and forms an antigen-antibody complex with the drug, thus inactivating the free digoxin. Digoxin immune Fab therapy is indicated only for the following: Hyperkalemia (serum potassium level higher than 5 mEq/L) in a patient with digoxin toxicity; Life-threatening cardiac dysrhythmias, sustained ventricular tachycardia or fibrillation, and severe sinus bradycardia or heart block unresponsive to atropine treatment or cardiac pacing; and Life-threatening digoxin overdose: more than 10 mg digoxin in adults and more than 4 mg digoxin in children. Miscellaneous Heart Failure Drugs digoxin immune fab (Digifab) is the antidote for severe digoxin overdose and is indicated for the reversal of life- threatening cardiotoxic effects. Use of digoxin immune Fab is contraindicated in patients who have shown a hypersensitivity to it. It is available only in parenteral form. It is dosed based on the patient’s serum digoxin level in conjunction with his or her weight. It is important to bear in mind that after digoxin immune Fab is given, all subsequent measurements of serum digoxin level will be elevated for days to weeks. Therefore, after its administration, the clinical signs and symptoms of digoxin toxicity, rather than the digoxin serum levels, are the primary focus in monitoring for the effectiveness of reversal therapy. POQ dignoxin immune fab 15 Slide 43 MB1 Mary Bondmass, 2/19/2024  6/15/2024 Miscellaneous Heart Failure Drugs (cont) hydralazine/isosorbide dinitrate (BiDil) was the first drug approved for a specific ethnic group, namely Blacks. This combination of two older drugs contains 37.5 mg of hydralazine and 20 mg of isosorbide dinitrate. The individual drugs are discussed in detail in Chapter 22 (hydralazine) and Chapter 23 (isosorbide). Dobutamine Dobutamine (generic, formerly Dobutrex) is a beta1-selective vasoactive adrenergic drug that is structurally similar to the naturally occurring catecholamine dopamine. Through stimulation of the beta1 receptors on heart muscle (myocardium), it increases cardiac output by increasing contractility (positive inotropy), which increases the stroke volume, especially in patients with heart failure. Dobutamine is available only as an intravenous drug and is given by continuous infusion. See Chapter 18 for further discussion on this drug. Ivabradine (Corlanor) Ivabradine) is the first drug in a new class of drugs called SA node modulators. It inhibits f-channels within the SA node, which ultimately results in reduced heart rate. Ivabradine is indicated to reduce the risk for hospitalization in patients with stable, symptomatic heart failure with an ejection fraction of 35% or less. It can increase the risk for atrial fibrillation, bradycardia, and conduction disturbances. Common side effects include bradycardia, hypertension, atrial fibrillation, heart block, and visual disturbances. Ivabradine is a major substrate of CYP3A4 and should not be given with strong CYP3A4 inhibitors or inducers. It should not be given with grapefruit juice. Fetal harm may occur when given to pregnant women. POQ hydralazine/isosorbide dinitrate (BiDil) Chapter 26: Coagulation Modifier Drugs When you reach the end of this chapter, you will be able to do the following: 1. Briefly discuss the coagulation process and the impact coagulation modifiers, including anticoagulants, antiplatelets, thrombolytics, and antifibrinolytics, have on this process. 2. Compare the mechanisms of action, indications, cautions, contraindications, drug interactions, adverse effects, routes of administration, and dosages of the various anticoagulants, antiplatelets, thrombolytics, and antifibrinolytics. 3. Discuss the administration procedures and techniques as well as related standards of care associated with the various coagulation modifiers. 4. Identify the antidotes for the coagulation modifiers. 5. Compare the laboratory tests used in conjunction with treatment for the various coagulation modifiers and their implications for the therapeutic use. Chapter 26: Key Terms 16  6/15/2024 Chapter 26: Key Terms (cont) Chapter 26: Key Terms (cont) Anticoagulants Mechanism of Action Anticoagulants are also called antithrombotic drugs because they work to prevent the formation of a clot or thrombus, a condition known as thrombosis All anticoagulants work in the clotting cascade, but they do so at different points. Heparin works by binding to a substance called antithrombin III, which turns off three main activating factors: activated factor II (also called thrombin), activated factor X, and activated factor IX. (Factors XI and XII are also inactivated but do not play as important a role as the other three factors.) Of these, thrombin is the most sensitive to the actions of heparin. Antithrombin III is the major natural inhibitor of thrombin in the blood. The overall effect of heparin is that it turns off the coagulation pathway and prevents clots from forming. However, it cannot lyse a clot. The drug name heparin usually refers to unfractionated heparin, which is a relatively large molecule and is derived from animal sources. In contrast, low molecular weight heparins (LMWHs) are synthetic and have a smaller molecular structure. These include enoxaparin (Lovenox) and dalteparin (Fragmin). Heparin primarily binds to activated factors II, X, and IX, whereas the LMWHs differ from heparin in that they are much more specific for activated factor X (Xa) than for activated factor II (IIa, or thrombin). This property gives LMWHs a much more predictable anticoagulant response. As a result, frequent laboratory monitoring of bleeding times using tests such as activated partial thromboplastin time (aPTT), which is imperative with unfractionated heparin, is not required with LMWHs. When heparin is used for flushing catheters (10 to 100 units/mL), no monitoring is needed.. 17  6/15/2024 Indications Anticoagulants The ability of anticoagulants to prevent clot formation is of benefit in certain settings in which there is a high likelihood of clot formation. These include MI, unstable angina, atrial fibrillation, use of indwelling devices such as mechanical heart valves, and conditions in which blood flow may be slowed and blood may pool, such as major orthopedic surgery or prolonged periods of immobilization such as hospitalization or even long plane rides. The ultimate consequence of a clot can be a stroke or a heart attack, DVT, or PE; therefore the prevention of these serious events is the ultimate benefit of these drugs. Anticoagulants are used for both prevention and treatment of clots. Patients at risk for clots are given DVT prophylaxis while in the hospital and after major surgery. LMWHs, especially enoxaparin, are routinely used as anticoagulant bridge therapy in situations in which a patient must stop warfarin for surgery or other invasive medical procedures. The term bridge therapy refers to the fact that enoxaparin acts as a bridge to provide anticoagulation while the patient must be off of warfarin therapy. Contraindications Contraindications to the use of anticoagulants are similar for all of the different drugs. They include known drug allergy, any acute bleeding process, or high risk for such an occurrence. Warfarin is strongly contraindicated in pregnancy, whereas the other anticoagulants are rated in lower pregnancy categories (B or C). LMWHs are contraindicated in patients with an indwelling epidural catheter; they can be given 2 hours after the epidural is removed. This is very important to remember, because giving an LMWH with an epidural has been associated with epidural hematoma. Adverse Effects Anticoagulants Adverse Effects Bleeding is the main complication of any anticoagulation therapy, and the risk increases with increasing dosages. Bleeding may be localized (e.g., hematoma at the site of injection) or systemic. It also depends on the nature of the patient’s underlying clinical disorder and is increased in patients taking high doses of aspirin or other drugs that impair platelet function. One particularly notable adverse effect of heparin is heparin-induced thrombocytopenia (HIT). There are two types of HIT. Type I is characterized by a more gradual reduction in platelets. In this type, heparin therapy can generally be continued. In contrast, in type II HIT there is an acute fall in the number of platelets (more than 50% reduction from baseline). Heparin therapy must be discontinued in patients with type II HIT. The greatest risk to the patient with HIT is the paradoxical occurrence of thrombosis, something that heparin normally prevents or alleviates. Thrombosis that occurs in the presence of HIT can be fatal. The incidence of this disorder ranges from 5% to 15%. The direct thrombin inhibitors lepirudin and argatroban are both specifically indicated for the treatment of HIT. Warfarin can cause skin necrosis and “purple toes” syndrome. Other adverse effects are listed in Table 26.2. All of the novel oral anticoagulants, rivaroxaban, apixaban, edoxaban, betrixaban, and dabigatran have black box warnings related to premature discontinuation, which can lead to increased clots and a risk for spinal hematoma with neuraxial anesthesia. Warfarin has a black box warning regarding bleeding risk, although all anticoagulants share the risk for bleeding. Heparin 18  6/15/2024 Enoxaparin Warfarin Antiplatelet Drugs Another class of coagulation modifiers that prevent clot formation comprises the antiplatelet drugs. Remember, the anticoagulants work in the clotting cascade. In contrast, antiplatelet drugs work to prevent platelet adhesion at the site of blood vessel injury, which actually occurs before the clotting cascade. 19  6/15/2024 Antiplatelet Drugs Chapter 27: Antilipemic Drugs When you reach the end of this chapter, you will be able to do the following: 1. Explain the pathologic processes of primary and secondary hyperlipidemia, including causes and risk factors. 2. Discuss the different types of lipoproteins and their role in cardiovascular diseases and in hyperlipidemia. 3. List the specific drugs within the various classifications of antilipemics. 4. Compare the various antilipemic drugs with regard to the rationale for treatment, indications, mechanisms of action, dosages, routes of administration, adverse effects, toxicity, cautions, contraindications, and associated food-drug and drug-drug interactions. 20  6/15/2024 Chapter 29: Fluid and Electrolytes When you reach the end of this chapter, you will be able to do the following: 1. Discuss the function of fluid volume and compartments within the body and the role of each of the major electrolytes in maintaining homeostasis. 2. Identify the various electrolytes and their normal serum values. 3. Briefly discuss the various fluid and electrolyte abnormalities that commonly occur in the body with attention to fluid volume and electrolyte excesses and deficits. 3. Identify the fluid and electrolyte solutions commonly used to correct states of excesses and deficiencies. 4. Discuss the mechanisms of action, indications, dosages, routes of administration, contraindications, cautions, adverse effects, toxicity, and drug interactions of the various fluid and electrolyte solutions. 5. Discuss the mechanisms of action, indications, dosages, routes of administration, contraindications, cautions, adverse effects and drug interactions associated with the various drugs used to expand a patient’s volume. 21  6/15/2024 Thank you for your attention! Questions???? Mary D. Bondmass, Ph.D., RN, CNE Professor in Residence, School of Nursing University of Nevada Las Vegas [email protected] 702-285-3460 22