chapter 53 Antianginal Drugs

Objectives
AFTER STUDYING THIS CHAPTER, THE STUDENT WILL BE ABLE TO:

1. Describe the types, causes, and effects of angina pectoris. 2. Describe general characteristics and types of antianginal drugs. 3. Discuss nitrate antianginals in terms of indications for use, routes of administration, adverse effects, nursing process implications, and drug tolerance.

4. Differentiate between short-acting and longacting dosage forms of nitrate antianginal drugs. 5. Discuss calcium channel blockers in terms of their effects on body tissues, clinical indications for use, common adverse effects, and nursing process implications. 6. Teach clients ways to prevent, minimize, or manage acute anginal attacks.

Critical Thinking Scenario Mrs. Sinatro, a 56-year-old housewife, experiences chest pressure after exercise. She is the mother of six and works 30 hours a week word-processing documents for a law rm. When she is told that her chest discomfort is probably secondary to coronary artery disease, she cannot believe it. She states, Im just too young to have heart problems! Mrs. Sinatro is referred to her primary care health care provider and given sublingual nitroglycerin tablets to use PRN for chest pain. Reect on: What assessment questions will you ask to determine Mrs. Sinatros risk factors for heart disease? Evaluate Mrs. Sinatros reaction to her new diagnosis and the client teaching implications. What lifestyle modications would help minimize the progression of coronary artery disease?

OVERVIEW
ngina pectoris is a clinical syndrome characterized by episodes of chest pain. It occurs when there is a deficit in myocardial oxygen supply (myocardial ischemia) in relation to myocardial oxygen demand. It is most often caused by atherosclerotic plaque in the coronary arteries but may also be caused by coronary vasospasm. The development and progression of atherosclerotic plaque is called coronary artery disease (CAD). Atherosclerotic plaque narrows the lumen, decreases elasticity, and impairs dilation of coronary arteries. The result is impaired blood ow to the myocardium, especially with exercise or other factors that increase the cardiac workload and need for oxygen. The continuum of CAD progresses from angina to myocardial infarction. There are three main types of angina: classic angina, variant angina, and unstable angina (Box 531). The Canadian Cardiovascular Society classies clients with angina
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according to the amount of physical activity they can tolerate before anginal pain occurs (Box 532). These categories can assist in clinical assessment and evaluation of therapy. Classic anginal pain is usually described as substernal chest pain of a constricting, squeezing, or suffocating nature. It may radiate to the jaw, neck, or shoulder, down the left or both arms, or to the back. The discomfort is sometimes mistaken for arthritis, or for indigestion, as the pain may be associated with nausea, vomiting, dizziness, diaphoresis, shortness of breath, or fear of impending doom. The discomfort is usually brief, typically lasting 5 minutes or less until the balance of oxygen supply and demand is restored. Current research indicates that gender differences exist in the type and quality of cardiac symptoms, with women reporting epigastric or back discomfort. Additionally, older adults may have atypical symptoms of CAD and may experience silent ischemia that may delay them from seeking professional help. Individuals with diabetes mellitus may present

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BOX 531

TYPES OF ANGINA PECTORIS

causes platelets to aggregate at the site of injury, form a thrombus, and release chemical mediators that cause vasoconstriction (eg, thromboxane, serotonin, platelet-derived growth factor). The disrupted plaque, thrombus, and vasoconstriction combine to obstruct blood ow further in the affected coronary artery. When the plaque injury is mild, blockage of the coronary artery may be intermittent and cause silent myocardial ischemia or episodes of anginal pain at rest. Thrombus formation and vasoconstriction may progress until the coronary artery is completely occluded, producing myocardial infarction. Endothelial injury, with subsequent thrombus formation and vasoconstriction, may also result from therapeutic procedures (eg, angioplasty, atherectomy). The Agency for Healthcare Research and Quality, in its clinical practice guidelines for the management of angina, denes unstable angina as meeting one or more of the following criteria: Anginal pain at rest that usually lasts longer than 20 minutes Recent onset (<2 months) of exertional angina of at least Canadian Cardiovascular Society Classication (CCSC) class III severity Recent (<2 months) increase in severity as indicated by progression to at least CCSC class III. However, myocardial ischemia may also be painless or silent in a substantial number of clients. Overall, the diagnosis is usually based on chest pain history, electrocardiographic evidence of ischemia, and other signs of impaired cardiac function (eg, heart failure). Because unstable angina often occurs hours or days before acute myocardial infarction, early recognition and effective management are extremely important in preventing progression to infarction, heart failure, or sudden cardiac death.

Classic Classic angina (also called stable, typical, or exertional angina) occurs when atherosclerotic plaque obstructs coronary arteries and the heart requires more oxygenated blood than the blocked arteries can deliver. Chest pain is usually precipitated by situations that increase the workload of the heart, such as physical exertion, exposure to cold, and emotional upset. Recurrent episodes of classic angina usually have the same pattern of onset, duration, and intensity of symptoms. Pain is usually relieved by rest, a fast-acting preparation of nitroglycerin, or both. Variant Variant angina (also called atypical, Prinzmetals, or vasospastic angina) is caused by spasms of the coronary artery that decrease blood ow to the myocardium. The spasms occur most often in coronary arteries that are already partly blocked by atherosclerotic plaque. Variant angina usually occurs during rest or with minimal exercise and often occurs at night. It often occurs at the same time each day. Pain is usually relieved by nitroglycerin. Long-term management includes avoidance of conditions that precipitate vasospasm, when possible (eg, exposure to cold, smoking, and emotional stress), as well as antianginal drugs. Unstable Unstable angina (also called rest, preinfarction, and crescendo angina) is a type of myocardial ischemia that falls between classic angina and myocardial infarction. It usually occurs in clients with advanced coronary atherosclerosis and produces increased frequency, intensity, and duration of symptoms. It often leads to myocardial infarction. Unstable angina usually develops when a minor injury ruptures atherosclerotic plaque. The resulting injury to the endothelium

without classic angina, although they may experience related symptoms. The American Heart Association has released guidelines for the management of angina. Numerous overlapping factors contribute to the development and progression of CAD. To aid understanding of drug therapy for angina, these factors are described in the following sections.

Coronary Atherosclerosis
Atherosclerosis (see Chap. 58) begins with accumulation of lipid-lled macrophages (ie, foam cells) on the inner lining of

coronary arteries. Foam cells, which promote growth of atherosclerotic plaque, develop in response to elevated blood cholesterol levels. Initially, white blood cells (monocytes) become attached to the endothelium and move through the endothelial layer into subendothelial spaces, where they ingest lipid and become foam cells. These early lesions progress to brous plaques containing foam cells covered by smooth muscle cells and connective tissue. Advanced lesions also contain hemorrhages, ulcerations, and scar tissue. Factors contributing to plaque development and growth include endothelial injury, lipid inltration (ie, cholesterol), recruitment of inflammatory cells (mainly monocytes and T lymphocytes), and smooth muscle cell proliferation. Endothelial injury may

BOX 532

CANADIAN CARDIOVASCULAR SOCIETY CLASSIFICATION OF PATIENTS WITH ANGINA PECTORIS

Class I: Ordinary physical activity (eg, walking, climbing stairs) does not cause angina. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation. Class II: Slight limitation of ordinary activity. Angina occurs on walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold, in wind, or under emotional stress. Walking more than two blocks on the level and climbing more than one flight of ordinary stairs at a normal pace and in normal conditions can elicit angina. Class III: Marked limitations of ordinary physical activity. Angina occurs on walking one or two blocks on the level and climbing one ight of stairs in normal conditions and at a normal pace. Class IV: Inability to carry on any physical activity without discomfortanginal symptoms may be present at rest.

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be the initiating factor in plaque formation because it allows monocytes, platelets, cholesterol, and other blood components to come in contact with and stimulate abnormal growth of smooth muscle cells and connective tissue in the arterial wall. Atherosclerosis commonly develops in the coronary arteries. As the plaque lesions develop over time, they become larger and extend farther into the lumen of the artery. The lesions may develop for decades before they produce symptoms of reduced blood ow. Eventually, such events as plaque rupture, mural hemorrhage, formation of a thrombus that partly or completely occludes an artery, and vasoconstriction precipitate myocardial ischemia. Thus, serious impairment of blood ow may occur with a large atherosclerotic plaque or a relatively small plaque with superimposed vasospasm and thrombosis. If stenosis blocks approximately 80% of the artery, blood ow cannot increase in response to increased need; if stenosis blocks 90% or more of the artery, blood ow is impaired when the client is at rest. When coronary atherosclerosis develops slowly, collateral circulation develops to increase blood supply to the heart. Collateral circulation develops from anastomotic channels that connect the coronary arteries and allow perfusion of an area by more than one artery. When one artery becomes blocked, the anastomotic channels become larger and allow blood from an unblocked artery to perfuse the area typically supplied by the occluded artery. Endothelium-derived relaxing factors such as nitric oxide (NO) can dilate collateral vessels and facilitate regional myocardial blood ow. Although collateral circulation may prevent myocardial ischemia in the client at rest, it has limited ability to increase myocardial perfusion with increased cardiac workload. Myocardial ischemia impairs blood flow to the myocardium, especially with exercise, mental stress, exposure to cold, or other factors that increase the cardiac workload. Most individuals with myocardial ischemia have advanced coronary atherosclerosis. Hypertension is also a major risk factor for myocardial ischemia.

with exercise or other conditions that increase cardiac workload. When coronary arteries are partly blocked by atherosclerotic plaque, vasospasm, or thrombi, blood ow may not be able to increase sufciently. 2. The endothelium of normal coronary arteries synthesizes numerous substances (see Chap. 50) that protect against vasoconstriction and vasospasm, bleeding and clotting, inammation, and excessive cell growth. Impaired endothelium (eg, by rupture of atherosclerotic plaque or the shear force of hypertension) leads to vasoconstriction, vasospasm, clot formation, formation of atherosclerotic plaque, and growth of smooth muscle cells in blood vessel walls. One important substance produced by the endothelium of coronary arteries is NO (also called endotheliumderived relaxing factor). NO, which is synthesized from the amino acid arginine, is released by shear stress on the endothelium, sympathetic stimulation of exercise, and interactions with acetylcholine, histamine, prostacyclin, serotonin, thrombin, and other chemical mediators. NO relaxes vascular smooth muscle and inhibits adhesion and aggregation of platelets. When the endothelium is damaged, these vasodilating and antithrombotic effects are lost. At the same time, production of strong vasoconstrictors (eg, angiotensin II, endothelin-1, thromboxane A2) is increased. In addition, inammatory cells enter the injured area and growth factors stimulate growth of smooth muscle cells. All of these factors participate in blocking coronary arteries. 3. Sympathetic nervous system stimulation normally produces dilation of coronary arteries, tachycardia, and increased myocardial contractility to handle an increased need for oxygenated blood. Atherosclerosis of coronary arteries, especially if severe, may cause vasoconstriction as well as decrease blood ow by obstruction.

Nonpharmacologic Management of Angina

For clients at any stage of CAD development, irrespective of symptoms of myocardial ischemia, optimal management involves lifestyle changes and medications, if necessary, to control or reverse risk factors for disease progression. Risk factors are frequently additive in nature and are classied as nonmodiable and modiable. Nonmodiable risk factors include age, race, gender, and family history. The risk factors that can be altered include smoking, hypertension, hyperlipidemia, obesity, sedentary lifestyle, stress, and the use of drugs that increase cardiac workload (eg, adrenergics, corticosteroids). Thus, efforts are needed to assist clients in reducing blood pressure, weight, and serum cholesterol levels, when indicated, and developing an exercise program. For clients with diabetes mellitus, glucose and blood pressure control can reduce the microvascular changes associated with the condition. In addition, clients should avoid circumstances known to precipitate acute attacks, and those who smoke should stop. Smoking is harmful to clients because:

Myocardial Ischemia
Myocardial ischemia occurs when the coronary arteries are unable to provide sufcient blood and oxygen for normal cardiac functions. Also known as ischemic heart disease, CAD, and coronary heart disease, myocardial ischemia may present as an acute coronary syndrome with three main consequences. One consequence is unstable angina, with the occurrence of pain (symptomatic myocardial ischemia). A second is myocardial infarction (MI) that is silent or asymptomatic and diagnosed by biochemical markers only. A third is MI, with or without ST-segment elevation, which occurs when the ischemia is persistent or severe.

Resultant Cardiovascular Impairments

1. With normal cardiac function, coronary blood ow can increase to meet needs for an increased oxygen supply

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Nicotine increases catecholamines which, in turn, increase heart rate and blood pressure. Carboxyhemoglobin, formed from the inhalation of carbon monoxide in smoke, decreases delivery of blood and oxygen to the heart, decreases myocardial contractility, and increases the risks of life-threatening cardiac dysrhythmias (eg, ventricular brillation) during ischemic episodes. Both nicotine and carbon monoxide increase platelet adhesiveness and aggregation, thereby promoting thrombosis. Smoking increases the risks for myocardial infarction, sudden cardiac death, cerebrovascular disease (eg, stroke), peripheral vascular disease (eg, arterial insufciency), and hypertension. It also reduces high-density lipoprotein, the good cholesterol. Additional nonpharmacologic management strategies include surgical revascularization (eg, coronary artery bypass graft) and interventional procedures that reduce blockages (eg, percutaneous transluminal coronary angioplasty [PTCA], intracoronary stents, laser therapy, and rotoblators). However,

most clients still require antianginal and other cardiovascular medications to manage their disease.

ANTIANGINAL DRUGS
Drugs used for myocardial ischemia are the organic nitrates, the beta-adrenergic blocking agents, and the calcium channel blocking agents. These drugs relieve anginal pain by reducing myocardial oxygen demand or increasing blood supply to the myocardium. Nitrates and beta blockers are described in the following sections and dosage ranges are listed in Drugs at a Glance: Nitrates and Beta Blockers. Calcium channel blockers are described in a following section; indications for use and dosage ranges are listed in Drugs at a Glance: Calcium Channel Blockers.

Organic Nitrates
Organic nitrates relax smooth muscle in blood vessel walls. This action produces vasodilation, which relieves anginal pain

Drugs at a Glance: Nitrate and Beta-Blocker Antianginal Drugs

Generic/Trade Name Nitrates Nitroglycerin (Nitro-Bid, others) Indications for Use Routes and Dosage Ranges

Relieve acute angina Prevent exercise-induced angina Long-term prophylaxis to decrease the frequency and severity of acute anginal episodes

Isosorbide dinitrate (Isordil, Sorbitrate)

Treatment and prevention of angina

Isosorbide mononitrate (Ismo, Imdur)

Treatment and prevention of angina

PO Immediate-release tablets, 2.59 mg 2 or 3 times per day PO Sustained-release tablets or capsules, 2.5 mg 3 or 4 times per day SL 0.150.6 mg PRN for chest pain Translingual spray, one or two metered doses (0.4 mg/dose) sprayed onto oral mucosa at onset of anginal pain, to a maximum of 3 doses in 15 min Transmucosal tablet, 1 mg q35h while awake, placed between upper lip and gum or cheek and gum Topical ointment, 122 inches q48h; do not rub in Topical transdermal disc, applied once daily IV 510 mcg/min initially, increased in 10- to 20-mcg/min increments up to 100 mcg/min or more if necessary to relieve pain SL 2.510 mg PRN or q24h PO Regular tablets, 1060 mg q46h PO Chewable tablets, 510 mg q23h PO Sustained-release capsules, 40 mg q612h PO 20 mg twice daily, with rst dose on arising and the second dose 7 h later PO Extended-release tablets (Imdur), 3060 mg once daily in the morning, increased after several days to 120 mg once daily if necessary

Beta Blockers Propranolol (Inderal)

Atenolol (Tenormin) Metoprolol (Lopressor) Nadolol (Corgard)

Long-term management of angina, to reduce frequency and severity of anginal episodes Same as propranolol Same as propranolol Same as propranolol

PO 1080 mg 2 to 4 times per day IV 0.53 mg q4h until desired response is obtained PO 50 mg once daily, initially, increased to 100 mg/d after 1 wk if necessary PO 50 mg twice daily initially, increased up to 400 mg daily if necessary PO 40240 mg/d in a single dose

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Drugs at a Glance: Calcium Channel Blockers

Generic/Trade Name Amlodipine (Norvasc) Bepridil (Vascor) Diltiazem (Cardizem) Indications Angina Hypertension Angina Angina Hypertension Atrial brillation and utter PSVT Routes and Dosage Ranges PO 510 mg once daily PO 200 mg/d initially, increased to 300 mg daily after 10 d if necessary; maximum dose, 400 mg daily Angina or hypertension, immediate-release, PO 6090 mg 4 times daily before meals and at bedtime Hypertension, sustained-release only, PO 120180 mg twice daily Dysrhythmias (Cardizem IV only) IV injection 0.25 mg/kg (average dose 20 mg) over 2 min with a second dose of 0.35 mg/kg (average dose 25 mg) in 15 min if necessary, followed by IV infusion of 515 mg/h up to 24 h PO 510 mg once daily PO 2.55 mg twice daily Angina, immediate-release only, PO 2040 mg 3 times daily Hypertension, immediate-release, same as for angina, above; sustainedrelease, PO 3060 mg twice daily Angina, immediate-release, PO 1030 mg 3 times daily; sustainedrelease, PO 3060 mg once daily Hypertension, sustained-release only, 3060 mg once daily PO 60 mg q4h for 21 consecutive d. If patient unable to swallow, aspirate contents of capsule into a syringe with an 18-gauge needle, administer by nasogastric tube, and follow with 30 mL normal saline. PO, initially 20 mg once daily, increased by 10 mg/wk or longer intervals to a maximum of 60 mg daily. Average maintenance dose, 2040 mg daily. Adults with liver impairment or >65 y, PO, initially 10 mg once daily Angina, PO 80120 mg 3 times daily Dysrhythmias, PO 80120 mg 3 to 4 times daily; IV injection, 510 mg over 2 min or longer, with continuous monitoring of electrocardiogram and blood pressure Hypertension, PO 80 mg 3 times daily or 240 mg (sustained release) once daily

Felodipine (Plendil) Isradipine (DynaCirc) Nicardipine (Cardene)

Hypertension Hypertension Angina Hypertension Angina Hypertension Subarachnoid hemorrhage

Nifedipine (Adalat, Procardia) Nimodipine (Nimotop)

Nisoldipine (Sular)

Hypertension

Verapamil (Calan, Isoptin)

Angina Atrial brillation or utter PSVT Hypertension

PSVT, paroxysmal supraventricular tachycardia.

by several mechanisms. First, dilation of veins reduces venous pressure and venous return to the heart. This decreases blood volume and pressure within the heart (preload), which in turn decreases cardiac workload and oxygen demand. Second, nitrates dilate coronary arteries at higher doses and can increase blood ow to ischemic areas of the myocardium. Third, nitrates dilate arterioles, which lowers peripheral vascular resistance (afterload). This results in lower systolic blood pressure and, consequently, reduced cardiac workload. The prototype and most widely used nitrate is nitroglycerin. Nitrates are converted to NO in vascular smooth muscle. NO activates guanylate cyclase, an enzyme that catalyzes formation of cyclic guanine monophosphate, which decreases calcium levels in vascular smooth muscle cells. Because intracellular calcium is required for contraction of vascular smooth muscle, the result of decreased calcium is vasodilation. The NO derived from nitrate medications can be considered a replacement or substitute for the NO that a damaged endothelium can no longer produce. Clinical indications for nitroglycerin and other nitrates are management and prevention of acute chest pain caused by

myocardial ischemia. For acute angina and prophylaxis before a situation deemed likely to precipitate acute angina, fast-acting preparations (sublingual or chewable tablets, transmucosal spray or tablet) are used. For management of recurrent angina, long-acting preparations (oral and sustained-release tablets or transdermal ointment and discs) are used. However, they may not be effective long-term because tolerance develops to their hemodynamic effects. Intravenous (IV) nitroglycerin is used to manage angina that is unresponsive to organic nitrates via other routes or beta-adrenergic blocking agents. It also may be used to control blood pressure in perioperative or emergency situations and to reduce preload and afterload in severe heart failure. Contraindications include hypersensitivity reactions, severe anemia, hypotension, and hypovolemia. The drugs should be used cautiously in the presence of head injury or cerebral hemorrhage because they may increase intracranial pressure. Additionally, males taking nitroglycerin or any other nitrate should not take sildenal (Viagra) for erectile dysfunction. Both drugs decrease blood pressure and the combined effect can produce profound, life-threatening hypotension.

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Individual Nitrates Nitroglycerin (Nitro-Bid, others), the prototype drug, is used to relieve acute angina pectoris, prevent exercise-induced angina, and decrease the frequency and severity of acute anginal episodes. Oral dosage forms are rapidly metabolized in the liver, and relatively small proportions of doses reach the systemic circulation. In addition, oral doses act slowly and do not help relieve acute chest pain. For these reasons, several alternative dosage forms have been developed, including transmucosal tablets and sprays administered sublingually or buccally, transdermal ointments and adhesive discs applied to the skin, and an IV preparation. When given sublingually, nitroglycerin is absorbed directly into the systemic circulation. It acts within 1 to 3 minutes and lasts 30 to 60 minutes. When applied topically to the skin, nitroglycerin is also absorbed directly into the systemic circulation. However, absorption occurs at a slower rate, and topical nitroglycerin has a longer duration of action than other forms. It is available in an ointment, which is effective for 4 to 8 hours, and a transdermal disc, which is effective for about 12 hours. An IV form of nitroglycerin is used to relieve acute anginal pain that does not respond to other agents. Regardless of the route, nitroglycerin has a half-life of 1 to 5 minutes, supporting the benecial use of transdermal patches and sustained-release tablets. Isosorbide dinitrate (Isordil, Sorbitrate) is used to reduce the frequency and severity of acute anginal episodes. When given sublingually or in chewable tablets, it acts in about 2 minutes, and its effects last 2 to 3 hours. When higher doses are given orally, more drug escapes metabolism in the liver and produces systemic effects in approximately 30 minutes. Therapeutic effects last about 4 hours after oral administration. The effective oral dose is usually determined by increasing the dose until headache occurs, indicating the maximum tolerable dose. Sustained-release capsules also are available. Isosorbide mononitrate (Ismo, Imdur) is the metabolite and active component of isosorbide dinitrate. It is well absorbed after oral administration and almost 100% bioavailable. Unlike other oral nitrates, this drug is not subject to first-pass hepatic metabolism. Onset of action occurs within 1 hour, peak effects occur between 1 and 4 hours, and the elimination half-life is approximately 5 hours. It is used only for prophylaxis of angina; it does not act rapidly enough to relieve acute attacks.

How Can You Avoid This Medication Error?

Mr. Ely has Nitropaste (nitroglycerin ointment), 1 inch, ordered every 6 hours to decrease blood pressure and control angina. The nurse carefully measures out 1 inch of ointment on the measuring paper and spreads the ointment with her nger. Before she is able to administer the medication, she feels dizzy and unwell. She hands the medication to another nurse and asks her to give it. Identify the error and how it could be prevented.

Beta-Adrenergic Blocking Agents

Beta-adrenergic blocking agents are often prescribed in a variety of clinical conditions. Their actions, uses, and adverse effects are discussed in Chapter 19. In this chapter, the drugs are discussed only in relation to their use in angina pectoris. Sympathetic stimulation of beta1 receptors in the heart increases heart rate and force of myocardial contraction, both of which increase myocardial oxygen demand and may precipitate acute anginal attacks. Beta-blocking drugs prevent or inhibit sympathetic stimulation. Thus, the drugs reduce heart rate and myocardial contractility, particularly when sympathetic output is increased during exercise. A slower heart rate may improve coronary blood ow to the ischemic area. Beta blockers also reduce blood pressure, which in turn decreases myocardial workload and oxygen demand. In angina pectoris, beta-adrenergic blocking agents are used in long-term management to decrease the frequency and severity of anginal attacks, decrease the need for sublingual nitroglycerin, and increase exercise tolerance. When a beta blocker is being discontinued after prolonged use, it should be tapered in dosage and gradually discontinued or rebound angina can occur. These drugs should not be given to clients with known or suspected coronary artery spasms because they may intensify the frequency and severity of vasospasm. This probably results from unopposed stimulation of alpha-adrenergic receptors, which causes vasoconstriction, when beta-adrenergic receptors are blocked by the drugs. Clients who continue to smoke may have reduced efcacy with the use of beta blockers. Clients with asthma should be observed for bronchospasm from blockage of beta2 receptors in the lung. Beta blockers should be used with caution in clients with diabetes mellitus because they can conceal signs of hypoglycemia (except for sweating). Propranolol, the prototype beta blocker, is used to reduce the frequency and severity of acute attacks of angina. It is usually added to the antianginal drug regimen when nitrates do not prevent anginal episodes. It is especially useful in preventing exercise-induced tachycardia, which can precipitate anginal attacks. Studies indicate that beta blockers are more effective than nitrates or calcium channel blockers in decreasing the likelihood of silent ischemia and improving the mortality rate after transmural MI. Propranolol is well absorbed after oral administration. It is then metabolized extensively in the liver; a relatively small

Nursing Notes: Apply Your Knowledge

Mrs. Sinatro, a patient with newly diagnosed coronary artery disease (CAD), has been started on a nitroglycerin patch that she is to apply in the morning and remove before going to bed at night. Sublingual nitroglycerin, PRN, is ordered for episodes of chest pain. Discuss appropriate teaching for Mrs. Sinatro.

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proportion of an oral dose (approximately 30%) reaches the systemic circulation. For this reason, oral doses of propranolol are much higher than IV doses. Onset of action is 30 minutes after oral administration and 1 to 2 minutes after IV injection. Because of variations in the degree of hepatic metabolism, clients vary widely in the dosages required to maintain a therapeutic response. Atenolol, metoprolol, and nadolol have the same actions, uses, and adverse effects as propranolol, but they have long half-lives and can be given once daily. They are excreted by the kidneys, and dosage must be reduced in clients with renal impairment.

Muscle relaxation

******************************
A

Muscle cell

Muscle contraction

Calcium Channel Blocking Agents

Calcium channel blockers act on contractile and conductive tissues of the heart and on vascular smooth muscle. For these cells to function normally, the concentration of intracellular calcium must be increased. This is usually accomplished by movement of extracellular calcium ions into the cell (through calcium channels in the cell membrane) and release of bound calcium from the sarcoplasmic reticulum in the cell. Thus, calcium plays an important role in maintaining vasomotor tone, myocardial contractility, and conduction. Calcium channel blocking agents prevent the movement of extracellular calcium into the cell. As a result, coronary and peripheral arteries are dilated, myocardial contractility is decreased, and the conduction system is depressed in relation to impulse formation (automaticity) and conduction velocity (Fig. 531). In angina pectoris, the drugs improve the blood supply to the myocardium by dilating coronary arteries and decrease the workload of the heart by dilating peripheral arteries. In variant angina, calcium channel blockers reduce coronary artery vasospasm. In atrial brillation or utter and other supraventricular tachydysrhythmias, diltiazem and verapamil slow the rate of ventricular response. In hypertension, the drugs lower blood pressure primarily by dilating peripheral arteries. Calcium channel blockers are well absorbed after oral administration but undergo extensive rst-pass metabolism in the liver. Most of the drugs are more than 90% protein bound and reach peak plasma levels within 1 to 2 hours (6 hours or longer for sustained-release forms). Most also have short elimination half-lives (<5 hours), so doses must be given three or four times daily unless sustained-release formulations are used. Amlodipine (30 to 50 hours), bepridil (24 hours), and felodipine (11 to 16 hours) have long elimination half-lives and therefore can be given once daily. The drugs are metabolized in the liver, and dosage should be reduced in clients with severe liver disease. Dosage reductions are not required with renal disease. The calcium channel blockers approved for use in the United States vary in their chemical structures and effects on body tissues. Seven of these are chemically dihydropyridines, of which nifedipine is the prototype. Bepridil, diltiazem, and verapamil differ chemically from the dihydropyridines and each other. Nifedipine and related drugs act mainly on vascular smooth muscle to produce vasodilation, whereas verapamil

Muscle cell

Calcium-blocking drugs

Muscle cell

C Figure 531 Calcium channel blockers: mechanism of action. (A) During muscle relaxation, potassium ions are inside the muscle cell and calcium and sodium ions are outside the muscle cell. (B) For muscle contraction to occur, potassium ions leave the cell and sodium and calcium ions enter the cell through open channels in the cell membrane. (C) When calcium channels are blocked by drug molecules, muscle contraction is decreased because calcium ions cannot move through the cell membrane into the muscle cell. (Calcium ions = ; sodium ions = s; potassium ions = ; calcium channel blocking drugs = .)

and diltiazem have greater effects on the cardiac conduction system. The drugs also vary in clinical indications for use; most are used for angina or hypertension, and only diltiazem and verapamil are used to manage supraventricular tachydysrhythmias. In clients with CAD, the drugs are effective as monotherapy but are commonly prescribed in combination with beta blockers. In addition, nimodipine is approved for use only in subarachnoid hemorrhage, in which it decreases spasm in cerebral blood vessels and limits the extent of brain damage. In animal studies, nimodipine exerted greater effects on cerebral arteries than on other arteries, probably because it is highly lipid soluble and penetrates the bloodbrain barrier. Contraindications include second- or third-degree heart block, cardiogenic shock, and severe bradycardia, heart failure, or hypotension. The drugs should be used cautiously with milder bradycardia, heart failure, or hypotension and with renal or hepatic impairment.

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Adjunctive Antianginal Drugs

In addition to antianginal drugs, several other drugs may be used to control risk factors and prevent progression of myocardial ischemia to myocardial infarction and sudden cardiac death. These may include: Aspirin. This drug has become the standard of care because of its antiplatelet (ie, antithrombotic) effects. Recommended doses vary from 81 mg daily to 325 mg daily or every other day; apparently all doses are benecial in reducing the possibility of myocardial reinfarction, stroke, and death. Clopidogrel (see Chap. 57), 75 mg/day, is an acceptable alternative for individuals with aspirin allergy. Antilipemics. These drugs (see Chap. 58) may be needed by clients who are unable to lower serum cholesterol levels sufciently with a low-fat diet. Lovastatin or a related statin is often used. The goal is usually to reduce the serum cholesterol level below 200 mg/dL and lowdensity lipoprotein cholesterol to below 130 mg/dL. Antihypertensives. These drugs (see Chap. 55) may be needed for clients with hypertension. Because beta blockers and calcium channel blockers are used to manage hypertension as well as angina, one of these drugs may be effective for both disorders.

Elevated cholesterol is a signicant risk factor for coronary atherosclerosis and angina and the risk is directly related to the degree of elevation. Cardiac enzyme levels, such as troponin, creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST), should all be normal in clients with angina. During an acute attack, assess the following: Location and quality of the pain. Chest pain is nonspecific. It may be a symptom of numerous disorders, such as pulmonary embolism, esophageal spasm or inflammation (heartburn), costochondritis, or anxiety. Chest pain of cardiac origin is caused by myocardial ischemia and may indicate angina pectoris or myocardial infarction. Precipitating factors. For example, what was the client doing, thinking, or feeling just before the onset of chest pain? Has the client had invasive procedures to diagnose or treat his or her coronary artery disease (CAD) (eg, cardiac catheterization, angioplasty, revascularization surgery)?

Nursing Diagnoses Decreased Cardiac Output related to altered stroke volume

or drug therapy Acute pain in chest related to inadequate perfusion of the myocardium Activity Intolerance related to chest pain Noncompliance related to drug therapy and lifestyle changes Decient Knowledge related to management of disease process and drug therapy Ineffective Individual Coping related to chronic disease process Sexual Dysfunction related to fear of precipitating chest pain

Nursing Process
Assessment
Assess the clients condition in relation to angina pectoris. Specic assessment data vary with each client but usually should include the following:

During the initial nursing history interview, try to answer

the following questions: How long has the client been taking antianginal drugs? For what purpose are they being taken (prophylaxis, treatment of acute attacks, or both)? What is the frequency and duration of acute anginal attacks? Has either increased recently? (An increase could indicate worsening coronary atherosclerosis and increased risk of myocardial infarction.) Do symptoms other than chest pain occur during acute attacks (eg, sweating, nausea)? Are there particular activities or circumstances that provoke acute attacks? Do attacks ever occur when the client is at rest? Where does the client t in the Canadian Cardiovascular Society classication system? What measures relieve symptoms of acute angina? If the client takes nitroglycerin, ask how often it is required, how many tablets are needed for relief of pain, how often the supply is replaced, and where the client stores or carries the drug. Assess blood pressure and pulse, electrocardiogram (ECG) reports, serum cholesterol, and cardiac enzyme reports.

Planning/Goals
The client will:

Receive or take antianginal drugs accurately Experience relief of acute chest pain Have fewer episodes of acute chest pain Have increased activity tolerance Identify and manage situations that precipitate anginal attacks Be closely monitored for therapeutic and adverse effects, especially when drug therapy is started Avoid preventable adverse effects Verbalize essential information about the disease process, needed dietary and lifestyle changes to improve health status, and drug therapy Recognize signs and symptoms that necessitate professional intervention Keep appointments for follow-up care and monitoring

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Interventions
Use the following measures to prevent acute anginal attacks: Assist in preventing, recognizing, and managing contributory disorders, such as atherosclerosis, hypertension, hyperthyroidism, hypoxia, and anemia. For example, hypertension is a common risk factor for CAD and morbidity and mortality increase progressively with the degree of either systolic or diastolic elevation. Management of hypertension reduces morbidity and mortality rates. However, most studies indicate that the reductions stem more from fewer strokes, less renal failure, and less heart failure, than from less CAD. Help the client recognize and avoid precipitating factors (eg, heavy meals, strenuous exercise) when possible. If anxiety is a factor, relaxation techniques or psychological counseling may be helpful. Help the client to develop a more healthful lifestyle in terms of diet and weight control, adequate rest and sleep, regular exercise, and not smoking. Ideally, these self-help interventions are practiced before illness occurs and they can help prevent or delay illness. However, most individuals are unmotivated until illness develops, and perhaps after it develops as well. These interventions are benecial at any stage of CAD. For example, for a client who already has angina, a supervised exercise program helps to develop collateral circulation. Smoking has numerous ill effects on the client with angina and decreases effectiveness of antianginal drugs. During an acute anginal attack in a client known to have angina or CAD: Assume that any chest pain may be of cardiac origin. Have the client lie down or sit down to reduce cardiac workload and provide rest. Check vital signs and compare them with baseline values. Record the characteristics of chest pain and the presence of other signs and symptoms. Have the client take a fast-acting nitroglycerin preparation (previously prescribed), up to three sublingual tablets or three oral sprays, each 5 minutes apart, as necessary. If chest pain is not relieved with rest and nitroglycerin, assume that a myocardial infarction has occurred until proven otherwise. In a health care setting, keep the client at rest and notify the clients physician immediately. Outside of a health care setting, call 911 for immediate assistance. Leave sublingual nitroglycerin at the bedside of hospitalized clients (per hospital policy). The tablets or spray should be within reach so they can be used immediately. Record the number of tablets used daily, and ensure an adequate supply is available.

Identify CAD lifestyle factors that are being successfully

modied or require modication (eg, diet, weight, activity, and smoking cessation). Interview regarding success and compliance with drug therapy.

PRINCIPLES OF THERAPY Goals of Therapy

The goals of drug therapy are to relieve acute anginal pain; reduce the number and severity of acute anginal attacks; improve exercise tolerance and quality of life; delay progression of CAD; prevent myocardial infarction; and prevent sudden cardiac death.

Choice of Drug and Dosage Form

For relief of acute angina and prophylaxis before events that cause acute angina, nitroglycerin (sublingual tablets or translingual spray) is usually the primary drug of choice. Sublingual or chewable tablets of isosorbide dinitrate also may be used. For long-term prevention or management of recurrent angina, oral or topical nitrates, beta-adrenergic blocking agents, or calcium channel blocking agents are used. Combination drug therapy with a nitrate and one of the other drugs is common and effective. Clients taking one or more long-acting antianginal drugs should carry a short-acting drug as well, to be used for acute attacks.

Titration of Dosage
Dosage of all antianginal drugs should be individualized to achieve optimal benet and minimal adverse effects. This is usually accomplished by starting with relatively small doses and increasing them at appropriate intervals as necessary. Doses may vary widely among individuals.

Tolerance to Long-Acting Nitrates

Clients who take long-acting dosage forms of nitrates on a regular schedule develop tolerance to the vasodilating (antianginal) effects of the drug. The clients more likely to develop tolerance are those on high-dose, uninterrupted therapy. Although tolerance decreases the adverse effects of hypotension, dizziness, and headache, therapeutic effects also may be decreased. As a result, episodes of chest pain may occur more often or be more severe than expected. In addition, shortacting nitrates may be less effective in relieving acute pain. Opinions seem divided about the best way to prevent or manage nitrate tolerance. Some authorities recommend using short-acting nitrates when needed and avoiding the

Evaluation Observe and interview for relief of acute chest pain. Observe and interview regarding the number of episodes
of acute chest pain.

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CLIENT TEACHING GUIDELINES

Antianginal Drugs
General Considerations Angina is chest pain that occurs because your heart is not getting enough blood and oxygen. The most common causes are hypertension and atherosclerosis of the coronary arteries. The chest pain usually lasts less than 5 minutes and episodes can be managed for years without causing permanent heart damage. However, if the pain is severe or prolonged, a heart attack and heart damage may develop. You need to seek information about your heart condition to prevent or decrease episodes of angina and prevent a heart attack. Several types of drugs are used in angina, and you may need a combination of drugs for the best effects. Most clients take one or more long-acting drugs to prevent anginal attacks and a fast, short-acting drug (usually nitroglycerin tablets that you dissolve under your tongue, or a nitroglycerin solution that you spray into your mouth) to relieve acute attacks. You should seek emergency care immediately if rest and three sublingual tablets or oral sprays 5 minutes apart do not relieve your chest pain. The long-acting medications are not effective in relieving sudden anginal pain. As with any medications for serious or potentially serious conditions, it is extremely important to take antianginal medications as prescribed. Do not increase dosage or discontinue the drugs without specic instructions from your health care provider. With sublingual nitroglycerin tablets, keep them in the original container, carry them so that they are always within reach but not where they are exposed to body heat, and replace them approximately every 6 months because they become ineffective. It may be helpful to record the number and severity of anginal episodes, the number of nitroglycerin tablets required to relieve the attack, and the total number of tablets taken daily. Such a record can help your health care provider know when to change your medications or your dosages. Headache and dizziness may occur with nitrate antianginal drugs, especially sublingual nitroglycerin. These effects are usually temporary and dissipate with continued therapy. If dizziness occurs, avoid strenuous activity and stand up slowly for approximately an hour after taking the drugs. If headache is severe, you may take aspirin or acetaminophen with the nitrate drug. Do not reduce drug dosage or take the drug less often to avoid headache. Loss of effectiveness may occur. Keep family members or support individuals informed about the location and use of antianginal medications in case help is needed. Avoid over-the-counter decongestants, cold remedies, and diet pills, which stimulate the heart and constrict blood vessels and thus may cause angina. With nitrate antianginal drugs, avoid alcohol. Both the drugs and alcohol dilate blood vessels and an excessive reduction in blood pressure (with dizziness and fainting) may occur with the combination. Several calcium channel blockers are available in both immediate-acting and long-acting (sustained-release) forms. The brand names often differ very little (eg, Procardia is a brand name of immediate-release nifedipine; Procardia XL is a long-acting formulation). It is extremely important that the correct formulation is used consistently. Self- or Caregiver Administration Take or give as instructed; specic instructions differ with the type of antianginal drug being taken. Take or give antianginal drugs on a regular schedule, at evenly spaced intervals. This increases drug effectiveness in preventing acute attacks of angina. With nitroglycerin and other nitrate preparations: Use according to instructions for the particular dosage form. The dosage forms were developed for specific routes of administration and are not interchangeable. For sublingual nitroglycerin tablets, place them under the tongue until they dissolve. Take at the rst sign of an anginal attack, before severe pain develops. If chest pain is not relieved in 5 minutes, dissolve a second tablet under the tongue. If pain is not relieved within another 5 minutes, dissolve a third tablet. If pain continues or becomes more severe, notify your health care provider immediately or report to the nearest hospital emergency room. Sit down when you take the medications. This may help to relieve your pain and prevent dizziness from the drug. For the translingual solution of nitroglycerin, spray onto or under the tongue; do not inhale the spray. For transmucosal tablets of nitroglycerin, place them under the upper lip or between the cheek and gum and allow them to dissolve slowly over 3 to 5 hours. Do not chew or swallow the tablets. Take oral nitrates on an empty stomach with a glass of water. Oral isosorbide dinitrate is available in regular and chewable tablets; be sure each type is taken appropriately. Do not crush or chew sustainedrelease nitroglycerin tablets. For sublingual isosorbide dinitrate tablets, place them under the tongue until they dissolve. If an oral nitrate and topical nitroglycerin are being used concurrently, stagger the times of administration. This minimizes dizziness from low blood pressure and headache, which are common adverse effects of nitrate drugs. For nitroglycerin ointment, use the special paper to measure the dose. Place the ointment on a nonhairy part of the upper body and apply with the applicator paper. Cover the area with plastic wrap or tape. Rotate application sites (because the ointment can irritate the skin) and wipe off the previous dose before applying a new dose. Wash hands after applying the ointment. The measured paper must be used for accurate dosage. The paper is used to apply the ointment (continued)

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CLIENT TEACHING GUIDELINES

Antianginal Drugs (Continued )

because the drug is readily absorbed through the skin. Skin contact should be avoided except on the designated area of the body. Plastic wrap or tape aids absorption and prevents removal of the drug. It also prevents soiling of clothes and linens. For nitroglycerin patches, apply at the same time each day to clean, dry, hairless areas on the upper body or arms. Rotate sites. Avoid applying below the knee or elbow or in areas of skin irritation or scar tissue. Correct application is necessary to promote effective and consistent drug absorption. The drug is not as well absorbed from distal portions of the extremities because of decreased blood flow. Rotation of sites decreases skin irritation. Also, used patches must be disposed of properly because there is enough residual nitroglycerin to be harmful, especially to children and pets. With sustained-release forms of calcium channel blockers, which are usually taken once daily, do not take more often than prescribed and do not crush or chew.

long-acting forms. Others recommend using the long-acting forms for 12 to 16 hours daily during active periods and omitting them during inactive periods or sleep. Thus, a dose of an oral nitrate or topical ointment would be given every 6 hours for three doses daily, allowing a rest period of 6 hours without a dose. Transdermal discs should be removed at bedtime. If anginal symptoms occur during sleeping hours, short-acting nitrates may be beneficial in relieving the symptoms. All nitrates should be administered at the lowest effective dosage.

Use in Renal Impairment

Little information is available about the use of antianginal drugs in clients with impaired renal function. A few studies indicate that advanced renal failure may alter the pharmacokinetics of calcium channel blockers. Although the pharmacokinetics of diltiazem and verapamil are quite similar in clients with normal and impaired renal function, caution is still advised. With verapamil, about 70% of a dose is excreted as metabolites in urine. Dosage reductions are considered unnecessary with verapamil and diltiazem but may be needed with nifedipine and several other dihydropyridine derivatives. With nifedipine, protein binding is decreased and the elimination half-life is prolonged with renal impairment. In a few clients, reversible elevations in blood urea nitrogen and serum creatinine have occurred. With nicardipine, plasma concentrations are higher in clients with renal impairment, and dosage should be reduced. Bepridil should be used with caution because its metabolites are excreted mainly in urine.

Use in Children
The safety and effectiveness of antianginal drugs have not been established for children. Nitroglycerin has been given IV for heart failure and intraoperative control of blood pressure, with the initial dose adjusted for weight and later doses titrated to response.

Use in Older Adults Use in Hepatic Impairment

Antianginal drugs are often used because cardiovascular disease and myocardial ischemia are common problems in older adults. Adverse drug effects, such as hypotension and syncope, are likely to occur, and they may be more severe than in younger adults. Blood pressure and ability to ambulate safely should be closely monitored, especially when drug therapy is started or dosages are increased. Ambulatory clients also should be monitored for their ability to take the drugs correctly. With calcium channel blockers, older adults may have higher plasma concentrations of verapamil, diltiazem, nifedipine, and amlodipine. This is attributed to decreased hepatic metabolism of the drugs, probably because of decreased hepatic blood flow. In addition, older adults may experience more hypotension with verapamil, nifedipine, and felodipine than younger clients. Blood pressure should be monitored with these drugs. Nitrates, beta blockers (see Chap. 19), and calcium channel blockers are metabolized in the liver, and all should be used with caution in clients with signicant impairment of hepatic function from reduced blood ow or disease processes. With oral nitrates, it is difcult to predict effects. On the one hand, rst-pass metabolism is reduced, which increases bioavailability (amount of active drug) of a given dose. On the other hand, the nitrate reductase enzymes that normally deactivate the drug may increase if large doses are given. In this case, more enzymes are available and the drug is metabolized more rapidly, possibly reducing therapeutic effects of a given dose. Relatively large doses of oral nitrates are sometimes given to counteract the drug tolerance (reduced hemodynamic effects) associated with chronic use. In addition, metabolism of nitroglycerin and isosorbide dinitrate normally produces active metabolites. Thus, if metabolism is re-

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duced by liver impairment, drug effects may be decreased and shorter in duration. With calcium channel blockers, impairment of liver function has profound effects on the pharmacokinetics and pharmacodynamics of most of these drugs. Thus, the drugs should be used with caution, dosages should be substantially reduced, and clients should be closely monitored for drug effects (including periodic measurements of liver enzymes). These recommendations stem from the following effects: An impaired liver produces fewer drug-binding plasma proteins such as albumin. This means that a greater proportion of a given dose is unbound and therefore active. In clients with cirrhosis, bioavailability of oral drugs is greatly increased and metabolism (of both oral and parenteral drugs) is greatly decreased. Both of these effects increase plasma levels of drug from a given dose (essentially an overdose). The effects result from shunting of blood around the liver so that drug molecules circulating in the bloodstream do not come in contact with drug-metabolizing enzymes and therefore are not metabolized. For example, the bioavailability of verapamil, nifedipine, felodipine, and nisoldipine is approximately double and their clearance is approximately one third that of clients without cirrhosis. Although hepatotoxicity is uncommon, clinical symptoms of hepatitis, cholestasis, or jaundice and elevated liver enzymes (eg, alkaline phosphatase, creatine kinase [CK], lactate dehydrogenase [LDH], aspartate aminotransferase [AST], alanine aminotransferase [ALT]) have occurred, mainly with diltiazem, nifedipine, and verapamil. These changes resolve if the causative drug is stopped.
NURSING ACTIONS NURSING ACTIONS 1. Administer accurately a. Check blood pressure and heart rate before each dose of an antianginal drug. Withhold the drug if systolic blood pressure is below 90 mm Hg. If the dose is omitted, record and report to the health care provider. b. Give antianginal drugs on a regular schedule, at evenly spaced intervals. c. If oral nitrates and topical nitroglycerin are being used concurrently, stagger times of administration. d. For sublingual nitroglycerin and isosorbide dinitrate, instruct the client to place the tablets under the tongue until they dissolve. e. For oral isosorbide dinitrate, regular and chewable tablets are available. Be sure each type of tablet is taken appropriately. f. For sublingual nitroglycerin, check the expiration date on the container.

Use in Critical Illness

Antianginal drugs have multiple cardiovascular effects and may be used alone or in combination with other cardiovascular drugs in clients with critical illness. They are probably used most often to manage severe angina, severe hypertension, or serious cardiac dysrhythmias. For example, IV nitroglycerin may be used for angina and hypertension; an IV beta blocker or calcium channel blocker may be used to improve cardiovascular function with angina, hypertension, or supraventricular tachydysrhythmias. With any of these drugs, dosage must be carefully titrated and clients must be closely monitored for hypotension and other drug effects. In addition, absorption of oral drugs or topical forms of nitroglycerin may be impaired in clients with extensive edema, heart failure, hypotension, or other conditions that impair blood ow to the gastrointestinal tract or skin.

Home Care
The role of the home care nurse may vary, depending largely on the severity of the clients illness. Initially, the nurse should assess the frequency and severity of anginal attacks and how the attacks are managed. In addition, the nurse can assess the home setting for lifestyle and environmental factors that may precipitate myocardial ischemia. When causative factors are identied, plans can be developed to avoid or minimize them. Other aspects of home care may include monitoring the clients response to antianginal medications; teaching clients and caregivers how to use, store, and replace medications to ensure a constant supply; and discussing circumstances for which the client should seek emergency care.

Antianginal Drugs
RATIONALE/EXPLANATION

Hypotension is an adverse effect of antianginal drugs. Bradycardia is an adverse effect of propranolol and nadolol. Dosage adjustments may be necessary if these effects occur. To increase effectiveness in preventing acute attacks of angina To minimize risks of additive hypotension and headache

Sublingual tablets of nitroglycerin are volatile. Once the bottle has been opened, they become ineffective after approximately 6 mo and should be replaced. (continued )

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NURSING ACTIONS g. To apply nitroglycerin ointment, use the special paper to measure the dose. Place the ointment on a nonhairy part of the body, and apply with the applicator paper. Cover the area with plastic wrap or tape. Rotate application sites and wipe off previous ointment before applying a new dose.

RATIONALE/EXPLANATION The measured paper must be used for accurate dosage. The paper is used to apply the ointment because the drug is readily absorbed through the skin. Skin contact should be avoided except on the designated area of the body. Plastic wrap or tape aids absorption and prevents removal of the drug. It also prevents soiling of clothes and linens. Application sites should be rotated because the ointment can irritate the skin. To promote effective and consistent drug absorption. The drug is not as well absorbed from distal portions of the extremities because of decreased blood ow. Rotation of sites decreases skin irritation. The drug should not be given by direct IV injection. The drug is potent and may cause hypotension. Dosage (ow rate) is adjusted according to response (pain relief or drop in systolic blood pressure of 20 mm Hg). To decrease hypotension and other adverse effects Sublingual nitroglycerin usually relieves pain within 5 min. If pain is not relieved, two additional tablets may be given, 5 min apart. If pain is not relieved after three tablets, report to the health care provider or seek emergency care.

h. For nitroglycerin patches, apply at the same time each day to clean, dry, hairless areas on the upper body or arms. Rotate sites. Avoid applying below the knee or elbow or in areas of skin irritation or scar tissue. i. For intravenous (IV) nitroglycerin, dilute the drug and give by continuous infusion, with frequent monitoring of blood pressure and heart rate. Use only with the special administration set supplied by the manufacturer to avoid drug adsorption onto tubing. j. With IV verapamil, inject slowly, over 23 min. 2. Observe for therapeutic effects a. Relief of chest pain with acute attacks

b. Reduced incidence and severity of acute attacks with prophylactic antianginal drugs c. Increased exercise tolerance 3. Observe for adverse effects a. With nitrates, observe for hypotension, dizziness, lightheadedness, tachycardia, palpitations, and headache. Adverse effects are extensions of pharmacologic action. Vasodilation causes hypotension, which in turn causes dizziness from cerebral hypoxia and tachycardia from compensatory sympathetic nervous system stimulation. Hypotension can decrease blood ow to coronary arteries and precipitate angina pectoris or myocardial infarction. Hypotension is most likely to occur within an hour after drug administration. Vasodilation also causes headache, the most common adverse effect of nitrates. Beta blockers lower blood pressure by decreasing myocardial contractility and cardiac output. Excessive bradycardia may contribute to hypotension and cardiac dysrhythmias. Bronchospasm is more likely to occur in clients with asthma or other chronic respiratory problems. Adverse effects result primarily from reduced smooth muscle contractility. These effects, except constipation, are much more likely to occur with nifedipine and other dihydropyridines. Nifedipine may cause profound hypotension, which activates the compensatory mechanisms of the sympathetic nervous system and the reninangiotensinaldosterone system. Peripheral edema may require the administration of a diuretic. Constipation is more likely to occur with verapamil. Diltiazem reportedly causes few adverse effects.

b. With beta-adrenergic blocking agents, observe for hypotension, bradycardia, bronchospasm, and heart failure.

c. With calcium channel blockers, observe for hypotension, dizziness, lightheadedness, weakness, peripheral edema, headache, heart failure, pulmonary edema, nausea, and constipation. Bradycardia may occur with verapamil and diltiazem; tachycardia may occur with nifedipine and nicardipine.

4. Observe for drug interactions a. Drugs that increase effects of antianginal drugs: (1) Antidysrhythmics, antihypertensive drugs, diuretics, phenothiazine antipsychotic agents Additive hypotension

(continued )

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NURSING ACTIONS (2) Cimetidine

RATIONALE/EXPLANATION May increase beta-blocking effects of propranolol by slowing its hepatic clearance and elimination. Increases effects of all calcium channel blockers by inhibiting hepatic metabolism and increasing serum drug levels. Additive bradycardia when given with beta-blocking agents Adrenergic drugs, which stimulate beta receptors, can reverse bradycardia induced by beta blockers. Drugs with anticholinergic effects can increase heart rate, offsetting slower heart rates produced by beta blockers. May decrease therapeutic effectiveness of calcium channel blockers May decrease effects of calcium channel blockers by inducing hepatic enzymes and thereby increasing their rate of metabolism

(3) Digoxin b. Drugs that decrease effects of antianginal drugs: (1) Adrenergic drugs (eg, epinephrine, isoproterenol) (2) Anticholinergic drugs (3) Calcium salts (4) Carbamazepine, phenytoin, rifampin

Nursing Notes: Apply Your Knowledge

Answer: Assess Mrs. Sinatros knowledge about CAD and her readiness to learn about her new medications and other methods to manage this problem. Give Mrs. Sinatro written handouts about CAD and written information about her antianginal medications. Demonstrate how to apply the patch, stressing to rotate sites and not use hairy or scarred areas because they may decrease drug absorption. The patch is removed at night because the oxygen demand of the heart is usually less at rest, and continuous application can increase the development of drug tolerance. Discuss side effects, including headache and hypotension, that can cause dizziness and falls. Teaching must include how to manage an episode of chest pain. First stress the importance of never ignoring chest pain. Some clients may deny they are experiencing chest pain and delay treatment. Tell her to rest if chest pain occurs. If pain does not subside, instruct her to place a nitroglycerin tablet under the tongue to dissolve and avoid swallowing the tablet. This can be repeated every 5 minutes up to three nitroglycerin tablets. If the pain has not subsided with rest and nitroglycerin, the client or family should call 911. The client should not drive or be driven by family to the hospital or clinic because she may be having a heart attack (myocardial infarction). The nurse should also stress the importance of keeping nitroglycerin with her at all times and making sure the prescription is relled before it reaches the expiration date. The tablets should be kept in the original amber bottle to protect them from sunlight and stored away from moisture and excessive heat.

Review and Application Exercises

1. What is angina pectoris? 2. What is the role of endothelial dysfunction in the development of coronary artery atherosclerosis and myocardial ischemia? 3. How do nitrates relieve angina? 4. Develop a teaching plan for a client who is beginning nitrate therapy. 5. How do beta blockers relieve angina? 6. Why should beta blockers be tapered and discontinued slowly in clients with angina? 7. How do calcium channel blockers relieve angina? 8. Develop a teaching plan for a client taking a calcium channel blocker. SELECTED REFERENCES
Brater, D. C. (2000). Clinical pharmacology of cardiovascular drugs. In H. D. Humes (Ed.), Kelleys Textbook of internal medicine, 4th ed., pp. 651672. Philadelphia: Lippincott Williams & Wilkins. Braunwald, E., Antman, E. M., Beasley, J. W., et al. (2000). ACC/AHA guidelines for the management of patients with unstable angina and nonST-segment elevation myocardial infarction: Executive summary and recommendations. A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). Circulation, 102, 11931209. Drug facts and comparisons. (Updated monthly). St. Louis: Facts and Comparisons. Jones, S. (2001). Oral or intravenous beta blockers in acute myocardial infarction. Emergency Medicine Journal, 18(4), 270271. Porth, C. M. (2002). Pathophysiology: Concepts of altered health states, 6th ed., pp. 487530. Philadelphia: Lippincott Williams & Wilkins. Rockett, J. L. (1999). Endothelial dysfunction and the promise of ACE inhibitors. American Journal of Nursing, 99(10), 4449. Smith, S. C. & Goldberg, A. C. (2001). Ischemic heart disease. In S. N. Ahya, K. Flood, & S. Paranjothi (Eds.), The Washington manual of medical therapeutics, 30th ed., pp. 96130. Philadelphia: Lippincott Williams & Wilkins. Talbert, R. L. (2002). Ischemic heart disease. In J. T. DiPiro, R. L. Talbert, G. C. Yee, G. R. Matzke, B. G. Wells, & L. M. Posey (Eds.), Pharmacotherapy: A pathophysiologic approach, 5th ed., pp. 219250. New York: McGraw-Hill.

How Can You Avoid This Medication Error?

Answer: Actually, there are two errors in this situation. A nurse can only safely administer medication that she has prepared. In this situation, after the medication has been spread on the paper, the dosage will be unclear. Also, a nurse or a family member should never touch Nitropaste without wearing gloves. Hands should be washed after administration. This potent vasodilator is absorbed through the skin, causing systemic effects such as dizziness and headache.