Cardiac Glycosides, Antianginals and Antidysrhythmics (Pharmacology) - PDF

UNIT XII Cardiovascular Drugs 40 Cardiac Glycosides, Antianginals, and Antidysrhythmics http://evolve.elsevier.com/McCuistion/pharmacology OBJECTIVES Differentiate the actions of cardiac glycosides, antianginal...

UNIT XII Cardiovascular Drugs 40 Cardiac Glycosides, Antianginals, and Antidysrhythmics http://evolve.elsevier.com/McCuistion/pharmacology OBJECTIVES Differentiate the actions of cardiac glycosides, antianginal drugs, Apply the Clinical Judgment [Nursing Process], including patient and antidysrhythmic drugs. teaching, related to cardiac glycosides, antianginal drugs, and Describe the signs and symptoms of digitalis toxicity. antidysrhythmic drugs. Compare the side effects and adverse reactions of nitrates, beta blockers, calcium channel blockers, quinidine, and procainamide. OUTLINE Introduction, 486 Phosphodiesterase Inhibitors, 491 Heart, 486 Other Agents Used to Treat Heart Failure, 491 Conduction of Electrical Impulses, 487 Antianginal Drugs, 492 Regulation of Heart Rate and Blood Flow, 487 Types of Angina Pectoris, 492 Circulation, 487 Nonpharmacologic Measures to Control Angina, 492 Blood, 488 Types of Antianginal Drugs, 492 Laboratory Tests to Diagnose Heart Failure, 488 Clinical Judgment [Nursing Process]—Antianginals, 497 Atrial Natriuretic Hormone or Peptide, 488 Antidysrhythmic Drugs, 497 Brain Natriuretic Peptide, 488 Cardiac Dysrhythmias, 497 Nonpharmacologic Measures to Treat Heart Failure, 488 Cardiac Action Potentials, 497 Agents Used to Treat Heart Failure, 488 Types of Antidysrhythmic Drugs, 498 Cardiac Glycosides, 488 Clinical Judgment [Nursing Process]—Antidysrhythmics, 502 Digoxin, 489 Critical Thinking Unfolding Case Study, 502 Clinical Judgment [Nursing Process]—Cardiac Glycosides: Review Questions, 506 Digoxin, 491 INTRODUCTION receives deoxygenated blood from the circulation, and the right ven- tricle pumps blood through the pulmonary artery to the lungs for gas The cardiovascular system includes the heart, blood vessels (arteries and exchange (carbon dioxide for oxygen). The left atrium receives oxygen- veins), and blood flow. Blood that is abundant in oxygen (O2), nutrients, ated blood, and the left ventricle pumps the blood into the aorta for and hormones moves through vessels called arteries, which narrow to systemic circulation. arterioles and then to capillaries. Capillaries transport nourished blood The heart muscle, called the myocardium, surrounds the ventricles to body cells and absorb waste products, such as carbon dioxide (CO2), and atria. The ventricles have thick walls, especially the left ventricle, to urea, creatinine, and ammonia. The deoxygenated blood returns to the produce the muscular force needed to pump blood to the pulmonary circulation by small venules and larger veins to be eliminated by the and systemic circulations. The atria have thin walls, have less pumping lungs and kidneys with other waste products (Fig. 40.1). action, and receive blood from the circulation and lungs. The heart’s pumping action serves as the energy source that circulates The heart has a fibrous covering called the pericardium, which blood to the cells of the body. Blockage of vessels can inhibit blood flow. protects it from injury and infection. The endocardium is a three- layered membrane that lines the inner part of the heart chambers. Four valves—two atrioventricular (tricuspid and mitral) and two semilunar HEART (pulmonic and aortic)—control blood flow between the atria and ven- The heart is composed of four chambers, including the right and left tricles, and between the ventricles and the pulmonary artery and the atria and the right and left ventricles (Fig. 40.2). The right atrium aorta. There are two main coronary arteries: the right coronary artery 486  CHAPTER 40 Cardiac Glycosides, Antianginals, and Antidysrhythmics 487 Cardiac output (4-8 L/min) = Artery Arteriole Capillary bed Venule Vein Heart rate Stroke volume (70 mL/beat) Preload Contractility Afterload Body cells and tissue Ventricular Ventricular Systemic filling contraction vascular Fig. 40.1 Basic structures of the vascular system. resistance Fig. 40.3 Cardiac Output and Stroke Volume. Three groups of drugs— cardiac glycosides, antianginals, and antidysrhythmics—are discussed in this chapter. Drugs in these groups regulate heart contraction, heart rate and rhythm, and blood flow to the myocardium (heart muscle). SA node influence heart contractions. The sympathetic nervous system and drugs that stimulate it increase heart rate; the parasympathetic nervous AV node Left atrium system and drugs that stimulate it decrease heart rate. Right atrium Mitral valve REGULATION OF HEART RATE AND BLOOD FLOW The heart beats approximately 60 to 80 times per minute in an adult, Tricuspid valve pumping blood into the systemic circulation. As blood travels, resistance to blood flow develops, and arterial pressure increases. The average sys- temic arterial pressure, known as blood pressure, is 120/80 mm Hg. Arte- rial blood pressure is determined by peripheral resistance and cardiac output, which is the volume of blood expelled from the heart in 1 minute, Right ventricle Left ventricle calculated by multiplying the heart rate by the stroke volume. The average Fig. 40.2 Anatomy of the heart. AV node, Atrioventricular node; SA cardiac output is 4 to 8 L/min. Stroke volume, the amount of blood ejected node, sinoatrial node. from the left ventricle with each heartbeat, is approximately 70 mL/beat. Three factors—preload, contractility, and afterload—determine divides into branches that supply blood to the right atrium and both the stroke volume (Fig. 40.3). Preload refers to the blood flow force ventricles of the heart, and the left coronary artery divides near its that stretches the ventricle at the end of diastole. However, an increase origin to form the left circumflex artery and the anterior descending in preload can increase stroke volume, and a decrease in preload can artery, which supply blood to the left atrium and both ventricles of decrease stroke volume. Contractility is the force of ventricular con- the heart. Blockage to one of these arteries can result in a myocardial traction, and afterload is the resistance to ventricular ejection of blood, infarction (MI), or heart attack. which is caused by opposing pressures in the aorta and systemic circu- lation. If afterload increases, stroke volume will decrease, and if after- load decreases, stroke volume will increase. CONDUCTION OF ELECTRICAL IMPULSES Specific drugs can increase or decrease preload and afterload, The myocardium can generate and conduct its own electrical impulses. affecting both stroke volume and cardiac output. Most vasodilators The cardiac impulse normally originates in the sinoatrial (SA) node decrease preload and afterload, thus decreasing arterial pressure and located in the posterior wall of the right atrium. The SA node is fre- cardiac output. quently called the pacemaker because it regulates the heartbeat (firing of cardiac impulses), which is approximately 60 to 80 beats/min in the normal adult. The atrioventricular (AV) node, located in the posterior CIRCULATION right side of the interatrial septum, has a continuous tract of fibers There are two types of circulation, pulmonary and systemic. With pul- called the bundle of His, or the AV bundle. The AV node has an adult monary circulation, the heart pumps deoxygenated blood from the rate of 40 to 60 beats/min. If the SA node fails, the AV node takes over right ventricle through the pulmonary artery to the lungs. The pulmo- as the pacemaker, thus causing a slower heart rate; the AV node sends nary artery carries blood that has a high concentration of carbon diox- impulses to the ventricles. These two conducting systems, the SA and ide. Oxygenated blood returns to the left atrium by the pulmonary vein. AV nodes, can act independently of each other. The ventricle can con- With systemic circulation, also called peripheral circulation, the heart tract independently 30 to 40 times per minute. pumps blood from the left ventricle to the aorta and into the general Drugs that affect cardiac contraction include calcium, digitalis circulation. Arteries and arterioles carry the blood to capillary beds. preparations, and quinidine and its related preparations. The auto- Nutrients in the capillary blood are transferred to cells in exchange for nomic nervous system (ANS) and drugs that stimulate or inhibit it waste products. Blood returns to the heart through venules and veins. 488 UNIT XII Cardiovascular Drugs BLOOD TABLE 40.1 The American College of Blood is composed of plasma, red blood cells (RBCs; erythrocytes), Cardiology Foundation/American Heart white blood cells (WBCs; leukocytes), and platelets. Plasma, made Association Stages of Heart Failure up of 90% water and 10% solutes, constitutes 55% of the total blood Stage Characteristics According to Stage volume. The solutes in plasma include glucose, protein, lipids, amino A At high risk for heart failure but without structural heart disease or acids, electrolytes, minerals, lactic and pyruvic acids, hormones, symptoms of heart failure enzymes, oxygen, and carbon dioxide. The major function of blood is to provide nutrients, including oxy- B Structural heart disease but without signs or symptoms of heart failure gen, to body cells. Most of the oxygen is carried on the hemoglobin of C Structural heart disease with prior or current symptoms of heart failure RBCs. WBCs are the major defense mechanism of the body and act by D Refractory heart failure requiring specialized interventions engulfing microorganisms. They also produce antibodies. The platelets are large cells that cause blood to coagulate. RBCs have a life span of Data from Maddox, T. M., Januzzi, J. L., Allen, L. A., et al.; (2021). Update approximately 120 days, whereas the life span of a WBC is only 2 to to the 2017 ACC Expert Consensus Decision Pathway for Optimization of 24 hours. Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure Three groups of drugs (cardiac glycosides, antianginals, and anti- With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee. Journal of the American dysrhythmics) are discussed in this chapter. Drugs in these groups reg- College of Cardiology, 77(6), 772-810. ulate heart contraction, heart rate, heart rhythm, and blood flow to the myocardium. AGENTS USED TO TREAT HEART FAILURE LABORATORY TESTS TO DIAGNOSE HEART Cardiac Glycosides FAILURE Digitalis use began as early as CE 1200, making it one of the oldest drugs. It is still used in a purified form. Digitalis is obtained from the Atrial Natriuretic Hormone or Peptide purple and white foxglove plant, and it can be poisonous. Digitalis Reference values: 20 to 77 pg/mL; 20 to 77 ng/L (SI units). An ele- preparations have come to be known for their effectiveness in treating vated atrial natriuretic hormone (ANH) or atrial natriuretic peptide HF, also known as cardiac failure (CF), and previously referred to as (ANP) may confirm heart failure (HF). ANH is secreted from the congestive heart failure (CHF). When the heart muscle (myocardium) atria of the heart and acts as an antagonist to renin and aldosterone. weakens and enlarges, it loses its ability to pump blood through the Released during expansion of the atrium, it produces vasodilation heart and into the systemic circulation. This is called heart failure, and increases glomerular filtration rate (GFR). Results of ANH secre- pump failure, or chronic heart failure. When compensatory mecha- tion include a large volume of urine that decreases blood volume and nisms fail and the peripheral and lung tissues are congested, the con- blood pressure. dition is called acute heart failure. The causes of HF include chronic hypertension, MI, coronary artery disease (CAD), valvular heart dis- Brain Natriuretic Peptide ease, congenital heart disease, and arteriosclerosis. Reference values: Desired value is less than 100 pg/mL; positive value is HF can be left-sided or right-sided. The patient has left-sided HF when greater than 100 pg/mL. The brain natriuretic peptide (BNP) is primarily the left ventricle does not contract sufficiently to pump the blood returned secreted from atrial cardiac cells and, when tested, aids in the diagnosis from the lungs and left atrium out through the aorta into the peripheral of HF. Diagnosing HF is difficult in persons with lung disease who are circulation; this causes excessive amounts of blood to back up into the experiencing dyspnea and in those who are obese or older. An elevated lung tissue. Usually the patient has shortness of breath (SOB) and dyspnea. BNP helps differentiate that dyspnea is due to HF rather than to lung Right-sided HF occurs when the heart does not sufficiently pump the blood dysfunction. Frequently the BNP is higher than 100 pg/mL in women returned into the right atrium from the systemic circulation. As a result, who are 65 years of age or older. An 80-year-old woman may have a BNP the blood and its constituents are backed up into peripheral tissues, caus- of 160 pg/mL; however, the BNP is markedly higher (i.e., 400 pg/mL) in ing peripheral edema. Left-sided HF may lead to right-sided HF and vice HF. BNP is considered a more sensitive test than ANP for diagnosing versa. Myocardial hypertrophy resulting in cardiomegaly, increased heart HF. Today, a bedside/emergency department machine can be used to size, can be a major problem associated with chronic HF. measure BNP. In the cardiac physiology of HF, an increase in preload and afterload occurs. The increased preload results from an excess of blood volume NONPHARMACOLOGIC MEASURES TO TREAT in the ventricle at the end of diastole. This occurs because of a patho- HEART FAILURE logic increase in the stretching and thickening of the ventricular walls, which allows a greater filling pressure associated with a weakened heart. Nondrug therapy is an integral part of the regimen for controlling HF. Increased afterload is an additional pressure or force in the ventricular The nondrug component of the regimen should be tailored to meet the wall caused by excess resistance in the aorta. This resistance must be needs of each patient, but the following are some general recommen- overcome to open the aortic valve so blood can be ejected into the circu- dations. The patient should limit salt intake to 2 g/day, approximately 1 lation. The American College of Cardiology Foundation (ACCF) and the teaspoon. Alcohol intake should be either decreased to 1 drink per day American Heart Association (AHA) have classified HF in stages accord- or completely avoided because excessive alcohol use can lead to cardio- ing to its severity. Table 40.1 lists the stages of HF according to the ACCF/ myopathy. Fluid intake may be restricted. Smoking should be avoided AHA. In the early stage of HF, there are no symptoms, and no structural because it deprives the heart of oxygen (O2). Obesity may increase car- heart damage occurs. Detailed information related to the staging process diovascular problems if it is associated with unhealthy behaviors; thus of HF can be found at http://www.heart.org/HEARTORG/Conditions/ obese patients should modify their behaviors as needed. Saturated fat HeartFailure/Heart-Failure_UCM_002019_SubHomePage.jsp. intake should be decreased. Mild exercise, such as walking or bicycling, Naturally occurring cardiac glycosides are found in several plants, is recommended. including Digitalis. Also called digitalis glycosides, this group of drugs  CHAPTER 40 Cardiac Glycosides, Antianginals, and Antidysrhythmics 489 inhibits the sodium-potassium pump, which results in an increase in effects (decreased heart rate) and negative dromotropic effects (decreased intracellular sodium. This increase leads to an influx of calcium, which conduction through the atrioventricular [AV] node). causes the cardiac muscle fibers to contract more efficiently. Digitalis When digoxin cannot convert atrial fibrillation to normal heart preparations have three effects on heart muscle: (1) a positive ino- rhythm, the goal is to slow the heart rate by decreasing electrical tropic action increases myocardial contraction stroke volume, (2) a impulses through the AV node. For management of atrial fibrillation, a negative chronotropic action decreases heart rate, and (3) a negative CCB such as verapamil may be prescribed. To prevent thromboemboli dromotropic action decreases conduction of heart cells. The increase resulting from atrial fibrillation, warfarin is prescribed concurrently in myocardial contractility strengthens cardiac, peripheral, and kidney with other drug therapy. Warfarin is discussed in Chapter 40. function by enhancing cardiac output, decreasing preload, improv- ing blood flow to the periphery and kidneys, decreasing edema, and Digoxin promoting fluid excretion. As a result, fluid retention in the lungs and Prototype Drug Chart: Digoxin gives the pharmacologic data for extremities is decreased. Digoxin does not prolong life; rather, it acts digoxin, a cardiac glycoside. by increasing the force and velocity of myocardial systolic contraction. Pharmacokinetics. The absorption rate of digoxin in oral tablet Digoxin is a secondary drug for HF. First-line drugs used to treat form is 70% to 80%. The rate is 75% to 85% in liquid form. The protein- acute HF include intravenous (IV) inotropic agents (dopamine and binding power for digoxin is 20% to 30%. The half-life is 30 to 40 hours. dobutamine) and phosphodiesterase (PDE) inhibitors, such as milri- Because of its long half-life, drug accumulation can occur. Side effects none. Other drugs prescribed for HF include oral diuretics, beta blockers, should be closely monitored to detect digitalis toxicity. Patients should angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor be made aware of side effects that need to be reported to the health blockers (ARBs), calcium channel blockers (CCBs), and vasodilators, care provider. Serum digoxin levels are most commonly drawn when all of which are more convenient to self-administer. Oral administra- actual digitoxicity is suspected. This allows the health care provider tion allows the patient to go home on these medications. to ascertain the extent of such toxicity and to confirm elimination Cardiac glycosides are also used to correct atrial fibrillation, cardiac of the drug after it is stopped or decreased in dosage (see the Digitalis dysrhythmia with rapid uncoordinated contractions of atrial myocar- [Digoxin] Toxicity section later in this chapter). dium, and atrial flutter, cardiac dysrhythmia with rapid contractions of Thirty percent of digoxin is metabolized by the liver, and 70% is 200 to 300 beats/min. This is accomplished by the negative chronotropic excreted by the kidneys mostly unchanged. Kidney dysfunction can PROTOTYPE DRUG CHART Digoxin Drug Class Dosage Cardiac glycoside Atrial fibrillation: A: PO: LD 10–15 mcg/kg in 3 divided doses (give 50% LD for dose 1, 25% for doses 2 and 3); maint: 3.4–5.1 mcg/kg/d A: IV/IM: LD 8–12 mcg/kg/d in 3 divided doses; maint: 2.4–3.6 mcg/kg/d TDM: 0.8–2 ng/mL Contraindications Drug-Lab-Food Interactions Ventricular fibrillation, hypersensitivity Drug: Increased digoxin serum level with quinidine, flecainide, verapamil, indomethacin; Caution: AMI, AV block, ventricular tachycardia, hypertension, thyroid decreased digoxin absorption with antacids, kaolin, pectin, psyllium, acarbose, colestipol; disorder, renal/hepatic dysfunction, bradycardia, electrolyte increased risk for digoxin toxicity with thiazide diuretics, loop diuretics, proton pump inhibitors imbalance, cardiomyopathy, breastfeeding, older adults Lab: Hypokalemia, hypomagnesemia, hypercalcemia can increase digitalis (digoxin) toxicity Pharmacokinetics Pharmacodynamics Absorption: PO tablet: 70%–80%; PO liquid: 75%–85% PO: Onset: 30 min-2 h Distribution: PB: 20%–30% Peak: 2–6 h Metabolism: t½: 36–48 h Duration: 3–4 d Excretion: 70% in urine; 30% by liver metabolism IV: Onset: 5–30 min Peak: 1–6 h Duration: UK Therapeutic Effects/Uses To treat heart failure, atrial fibrillation Mechanism of Action: Inhibits sodium-potassium ATPase, promoting increased force of cardiac contraction, cardiac output, and tissue perfusion; decreases ventricular rate Side Effects Adverse Reactions Anorexia, nausea, vomiting, diarrhea, abdominal pain, headache, Bradycardia, hallucinations, bowel necrosis, palpitations blurred or yellow vision, dizziness, weakness, confusion, visual Life-threatening: Dysrhythmias, thrombocytopenia impairment, anxiety A, Adult; AMI, acute myocardial infarction; ATPase, adenosine triphosphatase; AV, atrioventricular; d, day; h, hour; IM, intramuscular; IV, intravenous; LD, loading dose; maint, maintenance; min, minute; PB, protein binding; PO, by mouth; t½, half-life; TDM, therapeutic drug monitoring; UK, unknown; y, year; >, greater than. 490 UNIT XII Cardiovascular Drugs TABLE 40.2 Cardiac Glycosides and Inotropic Agents Drug Route and Dosage Uses and Considerations Rapid-Acting Digitalis Digoxin See Prototype Drug Chart: Digoxin Phosphodiesterase Inhibitors (Positive Inotropic Bipyridines) Milrinone lactate A: IV: LD: 50 mcg/kg infusion over 10 min; For acute decompensated heart failure. May cause headache, hypotension, tachycardia, maint: 0.125–0.75 mcg/kg/min infusion; dysrhythmias, injection site reaction, tremor, nausea, vomiting, hypokalemia, max: 0.75 mcg/kg/min infusion thrombocytopenia, and angina. PB: 70%; t½: 2.4 h Atrial Natriuretic Peptide Hormones Nesiritide A: IV bolus: 2 mcg/kg; maint: 0.01 mcg/ For acute decompensated heart failure. May cause orthostatic hypotension, headache, kg/min infusion; max: 0.03 mcg/kg/min drowsiness, anxiety, nausea, tachycardia, back pain, bradycardia, angina, insomnia, continuous infusion hypoglycemia, and dysrhythmias. PB: UK; t½: 18 min Antidote for Digitalis Toxicity Digoxin-immune Fab A: IV: 800 mg IV as a single dose or 400 mg, For digitalis overdose and toxicity and cardiac glycoside–induced dysrhythmias. May then 400 mg more if needed cause anaphylaxis, orthostatic hypotension, atrial fibrillation, heart failure exacerbation, angioedema, wheezing, infusion site reactions, phlebitis, and hypokalemia. PB: UK; t½: 15 h Guanylate Cyclase Stimulant Vericiguat A: PO: 2.5 mg/d with food; maint: 10 mg/d; For heart failure and ejection fraction less than 45%. May cause hypotension, anemia, max: 10 mg/d syncope, and birth defects. PB: 98%; t½: 30 h A, Adult; h, hours; IV, intravenous; maint, maintenance; max, maximum; min, minute; PB, protein binding; t½, half-life; UK, unknown. affect the excretion of digoxin. Thyroid dysfunction can alter the metab- to the health care provider. Digitalis toxicity may result in first-degree, olism of cardiac glycosides. For patients with hypothyroidism, the dose of second-degree, or complete heart block. digoxin should be decreased; in hyperthyroidism, the dose may need to be increased. Pharmacodynamics. In patients with a failing heart, cardiac COMPLEMENTARY AND ALTERNATIVE THERAPIES glycosides increase myocardial contraction, which increases cardiac Cardiac Glycosides, Antihypertensives, and output and improves circulation and tissue perfusion. Because these Antidysrhythmics drugs decrease conduction through the AV node, the heart rate Ginseng may falsely elevate digoxin levels. decreases. The onset and peak actions of oral and IV digoxin vary. The St. John’s wort decreases absorption of digoxin and thus decreases serum digoxin therapeutic serum level for dysrhythmias is 0.8 to 2.0 ng/mL. digoxin level. The target therapeutic serum level for HF is 0.5 to 1.0 ng/mL. Psyllium may decrease digoxin absorption. Digoxin can be administered orally or by the IV route. Table 40.2 lists Hawthorn may increase the effect of digoxin and hypotensive drugs. the digitalis preparations and their dosages, uses, and considerations. Licorice can potentiate the effect of digoxin; it promotes potassium loss (hypokalemia), which increases the effect of digoxin, and it may cause dig- Digitalis (Digoxin) Toxicity italis toxicity. Licorice also decreases the effectiveness of antihyperten- Overdose or accumulation of digoxin causes digitalis toxicity. Signs sives. and symptoms include anorexia, diarrhea, nausea and vomiting, bra- Aloe may increase the risk of digitalis toxicity. It increases potassium loss, dycardia (pulse rate below 60 beats/min), premature ventricular con- which increases the effect of digoxin. tractions, cardiac dysrhythmias, headaches, malaise, blurred vision, Ma-huang, or ephedra, increases the risk of digitalis toxicity. visual illusions (white, green, or yellow halos around objects), confu- Goldenseal may decrease the effects of cardiac glycosides and may sion, and delirium. Older adults are more prone to toxicity. increase the effects of antidysrhythmics. Cardiotoxicity is a serious adverse reaction to digoxin, and ven- Coleus may potentiate effects of antihypertensives. tricular dysrhythmias result. Three cardiac-altered functions can con- Ginger may cause a synergistic antiplatelet effect with nifedipine. tribute to digoxin-induced ventricular dysrhythmias: (1) suppression Ginkgo may increase drug levels or side effects of nifedipine. of AV conduction, (2) increased automaticity, and (3) a decreased Korean ginseng may decrease effectiveness of antihypertensives. refractory period in ventricular muscle. The antidysrhythmics phe- Laxative (anthraquinone-containing) herbs may potentiate cardiac glyco- nytoin and lidocaine are effective in treating digoxin-induced ven- sides and antidysrhythmics. tricular dysrhythmias. Lidocaine should be limited to short-term Milk thistle may delay absorption rate of nifedipine. treatment. Antidote for Cardiac/Digitalis Glycosides Drug Interactions Digoxin-immune Fab may be given to treat severe digitalis toxicity. Drug interaction with digitalis preparations can cause digitalis toxicity. This agent binds with digoxin to form complex molecules that can Many of the potent diuretics, such as furosemide and hydrochlorothia- be excreted in the urine; thus digoxin is unable to bind at the cellular zide, promote the loss of potassium from the body. The resultant hypo- site of action. Serum digoxin levels should be closely monitored, and kalemia, low serum potassium level, increases the effect of digoxin at signs and symptoms of digoxin toxicity should be reported promptly its myocardial cell site of action, resulting in digitalis toxicity. Cortisone  CHAPTER 40 Cardiac Glycosides, Antianginals, and Antidysrhythmics 491 CLINICAL JUDGMENT [NURSING PROCESS] Cardiac Glycosides: Digoxin Concept: Perfusion Monitor serum digoxin level (normal therapeutic drug range is 0.8 to 2 The passage of blood flow through the arteries and capillaries that deliver ng/mL). A serum digoxin level greater than 2 ng/mL is indicative of digitalis oxygen and nutrients to body cells toxicity. Recognize Cues [Assessment] Monitor serum potassium level (normal range is 3.5 to 5.0 mEq/L), and Obtain a drug and herbal history. Report if a drug-drug or drug-herb inter- report if hypokalemia (, greater than. SUGGESTED STEPS FOR TREATMENT OF CLASSIC AND VARIANT ANGINA Classic angina pectoris Variant angina pectoris Steps Steps 1 1 Nitrates or Nitrates calcium blockers 2 2 Nitrates plus Nitrates plus beta blockers calcium blockers 3 Nitrates plus 3 Coronary artery beta blockers plus bypass graft calcium blockers 4 Coronary artery bypass graft Fig. 40.4 Suggested steps for treating classic and variant angina pectoris. of the calcium blockers, promotes vasodilation of the coronary and Reflex tachycardia can occur as a result of hypotension. Peripheral edema peripheral vessels, and hypotension can result. The onset of action is may occur with several CCBs, including nicardipine, nifedipine, and 10 minutes for verapamil and 30 minutes for nifedipine and diltiazem. verapamil. CCBs can cause changes in liver and kidney function, and Verapamil’s duration of action is 6 to 8 hours when given orally and serum liver enzymes should be checked periodically. CCBs are frequently 10 to 20 minutes when given intravenously. The duration of action for given with other antianginal drugs such as nitrates to prevent angina. nifedipine and diltiazem is 6 to 8 hours. In its immediate-release form (10- and 20-mg capsules), nifedip- Side Effects and Adverse Reactions. The side effects of calcium ine has been associated with an increased incidence of sudden car- blockers include headache, hypotension (more common with nifedipine diac death, especially when prescribed in high doses for outpatients. and less common with diltiazem), dizziness, and flushing of the skin. This is not true of the sustained-release preparations. For this reason,  CHAPTER 40 Cardiac Glycosides, Antianginals, and Antidysrhythmics 497 CLINICAL JUDGMENT [NURSING PROCESS] Antianginals Concept: Perfusion Patient Teaching The passage of blood flow through the arteries and capillaries that deliver General oxygen and nutrients to body cells. Administer SL nitroglycerin tablet if chest pain occurs. If pain has not subsided or has worsened in 5 minutes, call 911. Recognize Cues [Assessment] Advise patients not to ingest alcohol while taking nitroglycerin to avoid hypo- Obtain baseline vital signs for future comparisons. tension, weakness, and faintness. Obtain health and drug histories. Nitroglycerin is contraindicated for marked Advise patients to notify a health care provider if chest pain is not completely hypotension or acute myocardial infarction (AMI). alleviated. Tolerance to nitroglycerin can occur. Inform patients not to discontinue beta blockers and calcium blockers Analyze Cues and Prioritize Hypothesis [Patient Problems] without a health care provider’s approval. Withdrawal symptoms (reflex Dyspnea tachycardia and pain) may be severe. Myocardial tissue injury Pain Self-Administration Decreased tissue perfusion Demonstrate how SL nitroglycerin tablets are taken. The tablet is placed Hypoxemia under the tongue for quick absorption. A stinging or biting sensation indicates Anxiety that the tablet is fresh; however, with newer SL nitroglycerin tablets, the Reduced functional ability biting sensation may not be present. Teach patients to store medication bottles away from light in a dry place and Generate Solutions [Planning] to keep the drug in its original screw-cap, amber glass bottle. The amber color The patient will report that angina pain is controlled by nitroglycerin or other provides light protection, and the screw-cap closure protects from moisture in antianginals. the air, which can easily reduce tablet potency. Teach patients about nitroglycerin patches, applied once a day, usually in the Take Action [Nursing Interventions] morning. Rotate skin sites. The patch is usually applied to the chest wall, but Monitor vital signs. Hypotension is associated with most antianginal drugs. the thighs and arms may also be used. Avoid hairy areas. Position the patient sitting or lying down when administering a nitrate for Advise patients to seek medical attention if nitroglycerin does not relieve pain. the first time. After administration, check vital signs while the patient is lying down and then sitting up. Have the patient rise slowly to a standing position. Side Effects Offer sips of water before giving sublingual (SL) nitrates; dryness may inhibit Suggest acetaminophen to patients for relief of headache, which commonly drug absorption. occurs when first taking nitroglycerin products and lasts about 30 minutes. Monitor effects of intravenous (IV) nitroglycerin. Report angina that per- Place patients in a supine position with legs elevated if hypotension sists. results from SL nitroglycerin. Apply nitroglycerin ointment to a designated mark on paper. Do not use fin- Instruct patients how to check their pulse rate. gers because drug can be absorbed; use tongue blade or gloves. When using Advise patients taking beta blockers and calcium blockers to notify a health care a nitroglycerin patch, do not touch the medication portion. provider if dizziness or faintness occurs because it may indicate hypotension. Do not apply nitroglycerin ointment or a nitroglycerin patch in any area on the chest in the vicinity of defibrillator-cardioverter paddle placement. Explosion Evaluate Outcomes [Evaluation] and skin burns may result. Evaluate the patient’s response to nitrate products for relieving anginal pain. Note headache, dizziness, or faintness. immediate-release nifedipine is usually prescribed only as needed in dysrhythmias are life-threatening because ineffective filling of the ven- the hospital setting for acute increases in blood pressure. tricle and ineffective pumping result in decreased or absent cardiac output. With ventricular tachycardia, ventricular fibrillation is likely to occur, followed by death. Cardiopulmonary resuscitation (CPR) is ANTIDYSRHYTHMIC DRUGS necessary to treat these patients. Cardiac Dysrhythmias Cardiac dysrhythmias frequently follow an MI (heart attack) or A cardiac dysrhythmia (arrhythmia) is defined as any deviation from can result from hypoxia (lack of oxygen to body tissues), hypercapnia the normal rate or pattern of the heartbeat. This includes heart rates that (increased carbon dioxide in the blood), thyroid disease, CAD, cardiac are too slow (bradycardia), too fast (tachycardia), or irregular. The terms surgery, excess catecholamines, or electrolyte imbalance. dysrhythmia (disturbed heart rhythm) and arrhythmia (absence of heart rhythm) are used interchangeably despite the slight difference in meaning. Cardiac Action Potentials The ECG identifies the type of dysrhythmia. The P wave of the ECG Electrolyte transfer occurs through the cardiac muscle cell membrane. reflects atrial activation, the QRS complex indicates ventricular depo- When sodium and calcium enter the cardiac cell, depolarization larization, and the T wave reflects ventricular repolarization (return (myocardial contraction) occurs. Sodium enters rapidly to start the of cell membrane potential to resting after depolarization). The PR depolarization, and calcium enters later to maintain it. Calcium influx interval indicates AV conduction time, and the QT interval reflects ven- leads to an increased release of intracellular calcium from the sarco- tricular action potential duration. Atrial dysrhythmias prevent proper plasmic reticulum, resulting in cardiac contraction. In the presence of filling of the ventricles and decrease cardiac output by 33%. Ventricular myocardial ischemia, the contraction can be irregular. 498 UNIT XII Cardiovascular Drugs Cardiac action potentials are transient depolarizations followed drugs prolong conduction with little to no effect on repolarization by repolarizations of myocardial cells. Fig. 40.5 illustrates the action (flecainide). potential of a ventricular cardiac cell (myocyte) during a heartbeat. Lidocaine, a class IB sodium channel blocker, was used in the 1940s There are five phases: phase 0 is the rapid depolarization caused by an as a local anesthetic and is still used for this purpose. It was later dis- influx of sodium ions; phase 1 is initial repolarization, which coincides covered to have antidysrhythmic properties as well. Lidocaine is still with termination of sodium ion influx; phase 2 is the plateau and is used by some cardiologists to treat acute ventricular dysrhythmias. It characterized by the influx of calcium ions, which prolong the action slows conduction velocity and decreases action potential amplitude. potential and promote atrial and ventricular muscle contraction; phase Onset of action (IV) is rapid. About one-third of lidocaine reaches the 3 is rapid repolarization caused by influx of potassium ions; and phase general circulation, and a bolus of lidocaine is short-lived. Another 4 is the resting membrane potential between heartbeats and is nor- class IB sodium channel blocker is mexiletine. mally flat in ventricular muscle, but it begins to rise in the cells of the SA node as they slowly depolarize toward the threshold potential just Phase before depolarization occurs, initiating the next heartbeat. 1 Phase 2 calcium influx Types of Antidysrhythmic Drugs The desired action of antidysrhythmic (antiarrhythmic) drugs is to restore the cardiac rhythm to normal. Box 40.1 describes the various mechanisms by which this is accomplished. Antidysrhythmics are Phase 0 Phase 3 high-alert drugs that may cause significant harm to the patient when given inappropriately. sodium influx The antidysrhythmics are grouped into four classes: (1) sodium Phase (fast) channel blockers IA, IB, and IC; (2) beta blockers; (3) drugs that 4 prolong repolarization; and (4) calcium (slow) channel blockers. Table 40.5 lists the classes, actions, and indications for cardiac antidysrhyth- Fig. 40.5 Action potential of a ventricular myocyte during the course of a heartbeat. mic drugs. Table 40.6 lists the commonly administered antidysrhyth- mics and their dosages, uses, and considerations. Class I: Sodium Channel Blockers BOX 40.1 Pharmacodynamics of A sodium channel blocker decreases sodium influx into cardiac cells. Antidysrhythmics Responses to the drug are decreased conduction velocity in cardiac Mechanisms of Action tissues; suppression of automaticity, which decreases the likelihood Blocks adrenergic stimulation of the heart of ectopic foci; and increased recovery time (repolarization or refrac- Depresses myocardial excitability and contractility tory period). There are three subgroups of sodium channel blockers: Decreases conduction velocity in cardiac tissue those in class IA slow conduction and prolong repolarization (quini- Increases recovery time (repolarization) of the myocardium dine, procainamide, disopyramide); those in class IB slow conduction Suppresses automaticity (spontaneous depolarization to initiate beats) and shorten repolarization (lidocaine, mexiletine HCl); and class IC TABLE 40.5 Classes, Actions, and Indications of Antidysrhythmic Drugs Classes Actions Indications Class I Sodium Channel Blockers IA Slow conduction and prolong repolarization Atrial and ventricular dysrhythmias, paroxysmal atrial tachycardia (PAT), supraventricular dysrhythmias IB Slow conduction and shorten repolarization Acute ventricular dysrhythmias IC Prolong conduction with little to no effect on repolarization Life-threatening ventricular dysrhythmias Class II Beta blockers Reduce calcium entry Atrial flutter and fibrillation, tachydysrhythmias, ventricular and supraventricular Decrease conduction velocity, automaticity, and recovery dysrhythmias time (refractory period) Class III Drugs that prolong Prolong repolarization during ventricular dysrhythmias Life-threatening atrial and ventricular dysrhythmias resistant to other drugs repolarization Prolong action potential duration Class IV Calcium channel Block calcium influx Supraventricular tachydysrhythmias; prevention of paroxysmal supraventricular blockers Slow conduction velocity tachycardia (PSVT) Decrease myocardial contractility (negative inotropic) Increase refraction in atrioventricular node  CHAPTER 40 Cardiac Glycosides, Antianginals, and Antidysrhythmics 499 TABLE 40.6 Antidysrhythmics Drug Route and Dosage Uses and Considerations Class I Sodium Channel Blockers IA Disopyramide phosphate Immediate release: For life-threatening dysrhythmias, such as ventricular tachycardia. A >18 y >50 kg: PO: 150–300 mg q6h; max: 800 mg/d May cause dizziness, headache, fatigue, blurred vision, dry A >18 y 50 kg: PO: 300 mg q12h; max: 800 mg/d A 60 kg: IV: 1 mg over 10 min; may repeat with 1 mg in 10 For atrial flutter and fibrillation. May cause headache, palpitations, min; max: 2 mg over 20 min nausea, tachycardia, bradycardia, orthostatic hypotension, and A , greater than; , greater than. Side Effects Adverse Reactions Headache, alopecia, fever, Purple-toe syndrome, bone fracture, hypoten- weakness, priapism, petechiae, sion, chest pain, hematuria, ocular hemor- ecchymosis rhage, intracranial/vaginal/GI bleeding Life-threatening: Hemorrhage Anticoagulant Antagonists A, Adult; ALT, alanine transaminase; aPTT, activated partial Bleeding occurs in about 10% of patients taking oral anticoagulants. thromboplastin time; AST, aspartate transaminase; d, day; DIC, disseminated intravascular coagulation; DVT, deep venous Phytonadione, an antagonist of warfarin, is vitamin K1 and is used for thrombosis; GI, gastrointestinal; h, hour; HIT, heparin-induced warfarin overdose or uncontrollable bleeding. Usually 5 to 10 mg of thrombocytopenia; INR, international normalized ratio; IV, intravenous; vitamin K1 is given by slow intravenous infusion at once, and if it fails maint, maintenance; MI, myocardial infarction; min, minute; NSAIDs, to control bleeding, fresh whole blood or fresh frozen plasma or plate- nonsteroidal antiinflammatory drugs; PB, protein binding; PCI, lets are generally given. percutaneous coronary intervention; PE, pulmonary embolism; PO, by mouth; q, every; SSRI, selective serotonin reuptake inhibitor; subcut, subcutaneous; t½, half-life; UK, unknown; y, years; >, greater than.  CHAPTER 43 Anticoagulants, Antiplatelets, and Thrombolytics 539 325 mg/day for stroke prophylaxis and 75 to 162 mg/day for MI pro- ANTIPLATELET DRUGS phylaxis. Because aspirin has prolonged antiplatelet activity, it should Antiplatelets are used to prevent thrombosis in the arteries by sup- be discontinued at least 7 days before surgery. pressing platelet aggregation. Heparin and warfarin prevent thrombo- Other antiplatelet drugs include anagrelide, clopidogrel, dipyr- sis in the veins. idamole, prasugrel, ticagrelor, vorapaxar, cangrelor, abciximab, Antiplatelet drug therapy is mainly for prophylactic use in (1) pre- eptifibatide, and tirofiban. Clopidogrel and dipyridamole have vention of MI or stroke for patients with a family history of these, (2) effects similar to those of aspirin, but they are known as adenosine prevention of repeat MI or stroke, and (3) prevention of stroke for diphosphate (ADP) antagonists, and they affect platelet aggregation. patients having transient ischemic attacks (TIAs). Cilostazol inhibits platelet aggregation and is a vasodilator that may Long-term, low-dose aspirin therapy has been found to be both an be used for intermittent claudication. Ticagrelor 90 mg twice a day effective and inexpensive treatment for suppressing platelet aggrega- is taken in conjunction with aspirin 75 to 100 mg in a maintenance tion. Aspirin inhibits cyclooxygenase (COX), an enzyme needed by regimen. Doses greater than 100 mg of aspirin should be avoided. platelets to synthesize thromboxane A2 (TxA2). For patients with a Table 43.3 lists the antiplatelet drugs and their dosages, uses, and family history of stroke or MI, the recommended aspirin dose is 50 to considerations. TABLE 43.3 Antiplatelets Drug Route and Dosage Uses and Considerations Anagrelide A: PO: Initially 0.5 mg qid or 1 mg bid for 1 wk; maint: 1.5–3 mg/d; For treatment of thrombocytosis, chronic myelogenous leukemia, and hydrochloride max: 10 mg/d polycythemia vera. May cause headache, dizziness, palpitations, peripheral edema, weakness, flatulence, abdominal pain, nausea, diarrhea, anorexia, and dyspnea. PB: UK; t½: 1.5 h Aspirin (ASA) Thromboembolus prophylaxis: For prevention and treatment of stroke; MI, TIA, prosthetic heart A: PO: 75–100 mg/d valves, and thromboembolism prophylaxis. May cause abdominal TDM: Salicylate toxicity is >300 mcg/mL pain, nausea, dyspepsia, gastritis, GI bleeding, intracranial bleeding, and epistaxis. PB: 20%–90%; t½: 3–10 h Cilostazol A: PO: 50–100 mg bid 30 min ac or 2 h pc; max: 200 mg/d For claudication and PVD. Smoking may decrease serum levels. May cause headache, nausea, abdominal pain, diarrhea, nasopharyngitis, rhinitis, dizziness, infection, palpitations, and peripheral edema. PB: 95%–98%, t½: 11–13 h Clopidogrel See Prototype Drug Chart: Clopidogrel Bisulfate Dipyridamole Thromboembolism prophylaxis: For prevention of thromboembolism associated with prosthetic heart A: PO: 75–100 mg qid in combination with warfarin valves. May cause dizziness, headache, nausea, abdominal pain, dyspnea, flushing and chest pain. PB: 91%–99%; t½: 13.6 h Prasugrel A 60 kg: PO: Loading dose: 60 mg; maint: 10 mg/d in For thromboembolism prophylaxis. May cause headache, back combination with 75–325 mg ASA pain, dizziness, bleeding, nausea, hypo/hypertension, dyspnea, A , greater than. PROTOTYPE DRUG CHART Clopidogrel Bisulfate Drug Class Dosage Antiplatelet Thromboembolism prophylaxis in AMI: A: PO: LD: 300 mg and then 75 mg/d in combination with aspirin 75–325 mg/d Contraindications Drug-Lab-Food Interactions Intracranial hemorrhage, GI bleeding Drug: May increase bleeding when taken with NSAIDs, anticoagulants, omeprazole, Caution: Hepatic/renal disease, surgery, peptic ulcer, thrombotic antineoplastics, azole antifungals, SSRIs, and barbiturates; interferes with metabolism of thrombocytopenia purpura, trauma, older adults, pregnancy, phenytoin, warfarin, fluvastatin, tamoxifen, tolbutamide, NSAIDs, torsemide, calcium channel breastfeeding blockers, morphine, and amiodarone; increases effects of valsartan, rosuvastatin, glipizide, glyburide; effects are decreased with grapefruit juice. Lab: Prolongs bleeding time Herb: May increase bleeding when taken with ginger, garlic, ginkgo, feverfew, green tea Pharmacokinetics Pharmacodynamics Absorption: Rapid PO: Onset: Initially 2 h for dose of 300–600 mg/d, 2 d for dose of 50–100 mg/d Distribution: PB: 94%–98% Peak: Initially 5–7 d, once established 30–60 min Metabolism: t½: 6 h Duration: UK Excretion: 50% in urine and 50% in feces Therapeutic Effects/Uses To prevent thromboembolism associated with unstable angina, AMI, stroke, TIA Mechanism of Action: Inhibits platelet aggregation and prevents ADP from binding with the ADP platelet receptor Side Effects Adverse Reactions Abdominal pain, dizziness, confusion, epistaxis, headaches, Hypotension, hypertension, bronchospasm, bleeding, peptic ulcer, intracranial/GI bleeding hematoma, dyspepsia, diarrhea, constipation, purpura, Life-threatening: Agranulocytosis, aplastic anemia, thrombocytopenia, pancytopenia, hepatic peripheral edema, rash, pruritus failure, Stevens-Johnson syndrome A, Adult; ADP, adenosine diphosphate; AMI, acute myocardial infarction; d, day; GI, gastrointestinal; h, hour; LD, loading dose; MI, myocardial infarction; PB, protein binding; PO, by mouth; NSAID, nonsteroidal antiinflammatory drug; SSRI, serotonin reuptake inhibitor; t½, half-life; TIA, transient ischemic attack; UK, unknown. Clopidogrel is an antiplatelet drug frequently used after MI or Pharmacokinetics. Clopidogrel is rapidly absorbed and has a stroke to prevent a second event. It may be prescribed singly or with high protein-binding power. Studies have not established a relation- aspirin. It has been stated that clopidogrel and aspirin are more effec- ship between the concentration of the main metabolite and platelet tive in inhibiting platelet aggregation if used together than if used as aggregation. The half-life is 6 hours; it is usually prescribed once a separate antiplatelet therapies. Prototype Drug Chart: Clopidogrel day. Excretion of the drug metabolite occurs equally in the urine and Bisulfate lists the pharmacologic data for clopidogrel. in feces.  CHAPTER 43 Anticoagulants, Antiplatelets, and Thrombolytics 541 Pharmacodynamics. Clopidogrel prevents platelet aggregation has passed. The health care provider needs to determine whether the by blocking the binding of ADP to the platelet ADP receptor. ADP- patient has taken any of these drugs before seeking treatment. mediated activation of the GP IIb/IIIa complex inhibits platelet aggre- Pharmacokinetics. The commercial preparation of alteplase is gation. Clopidogrel prolongs bleeding time; therefore it should be identical to natural human tissue plasminogen activator (tPA), the discontinued for 7 days preceding surgery. The onset of action and enzyme that converts plasminogen to plasmin. Alteplase is initially peak of clopidogrel is dependent on dosage. The drug should not be administered with 10% of dose as an IV bolus over 1 minute and 90% taken if the patient has a bleeding peptic ulcer, any active bleeding, or of dose is then infused over 60 minutes. A total dose of 90 mg is the intracranial hemorrhage. Abciximab, eptifibatide, and tirofiban are used primarily for acute PROTOTYPE DRUG CHART coronary syndromes (unstable angina or non-Q-wave MI) and for pre- venting reocclusion of coronary arteries after percutaneous translumi- Alteplase nal coronary angioplasty (PTCA). These drugs are usually given before and after PTCA. The drug of choice for angioplasty is abciximab. Drug Class Dosage Abciximab, eptifibatide, and tirofiban block the binding of fibrinogen Thrombolytic agent PE treatment: to the GP IIb/IIIa receptor on the platelet surface. They are called plate- A: IV: 100 mg infusion over 2 h let glycoprotein IIb/IIIa receptor antagonists. After IV infusion, the anti- Ischemic CVA treatment: platelet effects at low levels for abciximab persist for up to 10 days; for A: IV: 0.9 mg/kg (give 10% of dose as bolus eptifibatide and tirofiban, the antiplatelet effects last for 4 hours. over 1 min then 90% as an infusion over Complementary and alternative therapy products can interact with 1 h) within 3 h of symptom onset antiplatelet drugs. Contraindications Drug-Lab-Food Interactions COMPLEMENTARY AND ALTERNATIVE THERAPIES Intracranial bleeding, aneurysm, Drug: Increased bleeding when taken with Antiplatelets CVA, brain tumor, head anticoagulants, NSAIDs, cefotetan, trauma, thrombocytopenia, plicamycin, SNRIs, SSRIs, and Dong quai, feverfew, garlic, ginger, Korean ginseng, saw palmetto, and ginkgo coagulopathy cephalosporins; decreased effect when biloba interfere with platelet aggregation. When these herbs are taken with Caution: Atrial fibrillation, taken with aminocaproic acid, aprotinin an antiplatelet drug such as aspirin, increased bleeding may occur. Licorice hepatic/renal disease, Lab: Decrease in plasminogen, fibrinogen, may cause hypokalemia, which can potentiate drug toxicity. St. John’s wort CABG, bleeding, peptic ulcer hematocrit, and hemoglobin with clopidogrel may potentiate drug effects. disease, diabetic retinopathy, Complementary and Alternative Therapies: older adults, pregnancy Increased bleeding with ginkgo biloba, THROMBOLYTICS garlic, feverfew, ginger, green tea, omega-3 fatty acids Thromboembolism, occlusion of an artery or vein caused by a throm- bus or embolus, results in ischemia (deficient blood flow) that causes Pharmacokinetics Pharmacodynamics necrosis (death) of the tissue distal to the obstructed area. It takes Absorption: Direct IV A: IV: Onset: Immediate approximately 1 to 2 weeks for the blood clot to disintegrate by natural Distribution: PB: UK Peak: 5–10 min fibrinolytic mechanisms. If a new thrombus or embolus can be dissolved Metabolism: t½: 30 min Duration: 1 h more quickly, tissue necrosis is minimized, and blood flow to the area is Excretion: Urine reestablished faster. This is the basis for thrombolytic therapy. Thrombolytics have been used since the early 1980s to promote the Therapeutic Effects/Uses fibrinolytic mechanism (converting plasminogen to plasmin, which To promote fibrinolysis associated with thrombosis in patients with AMI, PE, destroys the fibrin in the blood clot). The thrombus, or blood clot, dis- ischemic stroke, occluded IV catheter integrates when a thrombolytic drug is administered as soon as possi- Mechanism of Action: Alteplase promotes conversion of plasminogen to ble after symptoms of an acute myocardial infarction (AMI), acute plasmin, an enzyme that digests the fibrin matrix of clots. Alteplase also heart attack. Ideally, the thrombolytic should be administered within initiates fibrinolysis. 3 to 4 hours or within 30 minutes after arriving at the hospital for treatment. However, benefits may be seen when administered within Side Effects Adverse Reactions 12 hours after initial symptoms. Necrosis resulting from the blocked Epistaxis, infection, ecchymosis, Anaphylactoid reactions, laryngeal artery is prevented or minimized, and hospitalization time may be nausea, vomiting, rash edema, angioedema; cholesterol decreased. The need for cardiac bypass or coronary angioplasty can microembolization, bleeding, hypo/ be evaluated soon after thrombolytic treatment. A thrombolytic drug hypertension, GI bleeding, MI, cerebral should be administered within 3 hours of a thrombotic stroke. These edema, rhabdomyolysis, bradycardia, drugs are also used for PE, DVT, noncoronary arterial occlusion from tachycardia, heart failure, intracranial an acute thromboembolism, and thrombotic stroke. hemorrhage, seizures Commonly used thrombolytics include alteplase, also known as tissue Life-threatening: Stroke; dysrhythmias; plasminogen activator (tPA), and tenecteplase (TNK tPA). Alteplase is clot pulmonary edema, renal failure specific and binds to the fibrin surface of a clot, promoting the conversion of plasminogen to plasmin. Plasmin, an enzyme, digests the fibrin in the A, Adult; AMI, acute myocardial infarction; CABG, coronary artery clot. Plasmin also degrades fibrinogen, prothrombin, and other clotting bypass graft; CVA, cerebrovascular accident; GI, gastrointestinal; h, factors. These drugs all induce fibrinolysis (fibrin breakdown). Prototype hours; IV, intravenous; MI, myocardial infarction; min, minute; NSAIDs, Drug Chart: Alteplase lists the pharmacologic data for alteplase. nonsteroidal antiinflammatory drugs; PB, protein binding; PE, pulmonary Anticoagulants and antiplatelet drugs increase the risk of hemor- embolism; SNRI, selective norepinephrine reuptake inhibitor; SSRI, rhage; therefore they should be avoided until the thrombolytic effect selective serotonin reuptake inhibitor; t½, half-life; UK, unknown. 542 UNIT XII Cardiovascular Drugs recommended maximum; a larger dose could result in risk for intra- receiving tenecteplase. Anaphylactoid reactions following alteplase cranial bleeding. Allergic reactions to alteplase occur less frequently and tenecteplase are severe and involve rash, laryngeal edema, than with other thrombolytics. angioedema, and anaphylactic shock. If the drugs are adminis- Pharmacodynamics. Alteplase is similar to natural human tissue tered through an intracoronary catheter after MI, reperfusion plasminogen activator. It promotes thrombolysis by converting plas- dysrhythmia or hemorrhagic infarction at the myocardial necrotic minogen to plasmin, which degrades fibrin, fibrinogen, and factors V, area can result. The major complication of thrombolytic drugs is VIII, and XII. Peak action of alteplase occurs in 5 to 10 minutes. The hemorrhage. The antithrombotic drug aminocaproic acid is used to duration of action is 1 hour. stop bleeding by inhibiting plasminogen activation, which inhibits thrombolysis. Side Effects and Adverse Reactions Table 43.4 lists the thrombolytic drugs and their dosages, uses, and Allergic reactions can complicate thrombolytic therapy. Ana- considerations. phylaxis (vascular collapse) occurs in less than 1% of patients CLINICAL JUDGMENT [NURSING PROCESS] Thrombolytics Concept: Clotting Observe for signs and symptoms of active bleeding from the mouth or rec- A process in which blood is changed into a semisolid gel tum. Hemorrhage is a serious complication of thrombolytic treatment. Amino- caproic acid can be given as an intervention to stop bleeding. Recognize Cues [Assessment] Examine the patient for active bleeding for 24 hours after thrombolytic Assess baseline vital signs for comparison with future values. therapy has been discontinued: this should be done every 15 minutes for the Check baseline complete blood count (CBC), prothrombin time (PT), or interna- first hour, then every 30 minutes until the eighth hour, and then hourly. tional normalized ratio (INR) values before administration of thrombolytics. Observe for signs of allergic reaction to thrombolytics, such as itching, Obtain a medical and drug history. Contraindications for use of thrombolytics hives, flushing, fever, dyspnea, bronchospasm, hypotension, and/or cardio- include recent cerebrovascular accident (CVA), active bleeding, severe hyper- vascular collapse. tension, and anticoagulant therapy. Report if a patient takes aspirin or non- Avoid administering aspirin or NSAIDs for pain or discomfort when the patient steroidal antiinflammatory drugs (NSAIDs). Thrombolytics are contraindicated is receiving a thrombolytic. Acetaminophen can be substituted. for patients with a recent history of traumatic injury, especially head injury. Monitor the electrocardiogram (ECG) for presence of reperfusion dysrhythmias as the blood clot is dissolving; antidysrhythmic therapy may be indicated. Analyze Cues and Prioritize Hypothesis [Patient Problems] Avoid venipuncture/arterial sticks. Bleeding Tissue injury Patient Teaching Dehydration General Explain thrombolytic treatment to patients and family. Be supportive. Generate Solutions [Planning] The patient’s vital signs will be within normal limits. Side Effects The patient will be free of excessive bleeding. Advise patients to report any side effects such as lightheadedness, dizziness, palpitations, nausea, pruritus, or urticaria. Take Action [Nursing Interventions] Monitor vital signs. Increased pulse rate followed by decreased blood pres- Evaluate Outcomes [Evaluation] sure usually indicates blood loss and impending shock. Record vital signs, and Determine the effectiveness of drug therapy: the clot should have dissolved, report changes. vital signs should be stable with no signs or symptoms of active bleeding, and the patient should be pain free. TABLE 43.4 Thrombolytics Drug Route and Dosage Uses and Considerations Thrombolytics Tenecteplase A: IV: 30–50 mg bolus over 5 s; administer within To promote fibrinolysis associated with coronary artery thrombosis and AMI. May cause 30 min of arrival to hospital; max: 50 mg/dose bleeding, stroke, hematoma, epistaxis, and GI bleeding. PB: UK; t½: 90–130 min Reteplase, r-PA A: IV: 10 units over 2 min, follow in 30 min with For fibrinolytic therapy in AMI. Reteplae penetrates clots and activates plasminogen inside second dose of 10 units; max: 20 units the clot, which may lead to a higher clot lysis rate. May cause bleeding, GI/intracranial bleeding, and purple-toe syndrome. PB: UK; t1⁄2: 13–16 min Alteplase See Prototype Drug Chart: Alteplase Hemostatics Aminocaproic A: PO: LD: 5 g over first h; follow with 1–1.25 g/h For bleeding due to hyperfibrinolysis. May cause hypotension, headache, dyspnea, edema, acid for 8 h or until bleeding is controlled; max: 30 g/d dizziness, bradycardia, vision impairment, and nausea, diarrhea. PB: UK; t½: 2 h A: IV: 4–5 g over first h, follow with 1 g/h for 8 h; or until bleeding controlled; max: 30 g/d A, Adult; AMI, acute myocardial infarction; d, day; GI, gastrointestinal; h, hour; IV, intravenous; LD, loading dose; max, maximum; min, minutes; PB, protein binding; PO, by mouth; s, seconds; t½, half-life; UK, unknown.  CHAPTER 43 Anticoagulants, Antiplatelets, and Thrombolytics 543 CRITICAL THINKING CASE STUDY A 57-year-old man has thrombophlebitis in the right lower leg. IV hep- 4. What is the pharmacologic action of warfarin? Is the warfarin dose arin, 5000 units by bolus, was given. After the IV bolus, heparin 5000 within the safe daily dosage range? Explain your answer. units given subcutaneously every 6 hours was prescribed. Other thera- 5. What are the half-life and protein binding for warfarin? If a patient peutic means to decrease pain and alleviate swelling and redness were takes a drug that is highly protein bound, would there be a drug also prescribed, and an aPTT test was ordered. interaction? Explain your answer. 1. Was the patient’s heparin order within the safe daily dosage range? 6. Why was an INR ordered for the patient? What is the desired range? 2. What are the various methods for administering heparin? 7. What serious adverse reactions could result with prolonged use or 3. Why was an aPTT test ordered? How would you determine whether large doses of warfarin? the patient is within the desired range? Explain your answer. 8. What patient teaching interventions should the nurse include? List After 5 days of heparin therapy, the patient was prescribed oral war- three interventions. farin 5 mg daily. An INR test was ordered. 9. Months later, the patient has hematemesis. What nursing action should be taken? REVIEW QUESTIONS 1. A patient is placed on heparin, and the nurse acknowledges that 5. A patient is being changed from an injectable anticoagulant to an heparin is effective for preventing clot formation in patients who oral anticoagulant. Which anticoagulant does the nurse realize is have which disorder(s)? (Select all that apply.) administered orally? a. Coronary thrombosis a. Enoxaparin b. Acute myocardial infarction b. Warfarin c. Deep vein thrombosis c. Bivalirudin d. Hemorrhagic stroke d. Dalteparin e. Disseminated intravascular coagulation e. Tenecteplase 2. A patient who received heparin begins to bleed. The nurse antici- f. Fondaparinux pates that the health care provider will order which antidote? 6. A patient is taking warfarin 5 mg/day for atrial fibrillation. The a. Protamine sulfate patient’s international normalized ratio is 3.8. The nurse would con- b. Phytonadione sider the international normalized ratio to be what? c. Aminocaproic acid a. Within normal range d. Potassium chloride b. Elevated range 3. A patient is prescribed enoxaparin. The nurse knows that low- c. Low range molecular-weight heparin has what kind of half-life? d. Low-average range a. A longer half-life than heparin 7. Cilostazol is being prescribed for a patient with coronary artery dis- b. A shorter half-life than heparin ease. The nurse understands that which of the following is the major c. The same half-life as heparin purpose for antiplatelet drug therapy? d. A four-times shorter half-life than heparin a. Dissolve the blood clot 4. A patient had an orthopedic surgery and is prescribed enoxaparin. b. Decrease tissue necrosis What would the nurse teach the patient and/or family members c. Inhibit hepatic synthesis of vitamin K about this low-molecular-weight heparin before discharge? d. Suppress platelet aggregation a. Visual demonstration of intramuscular heparin administration is recommended. b. Prothrombin time and international normalized ratio monitor- ing will be done weekly. c. Avoidance of green leafy vegetables is recommended. d. Watch for bleeding or excessive bruising.  44 Antihyperlipidemics and Drugs to Improve Peripheral Blood Flow http://evolve.elsevier.com/McCuistion/pharmacology OBJECTIVES Describe the action of the two main drug groups: Differentiate the side effects and adverse reactions of peripheral antihyperlipidemics and drugs that improve peripheral blood flow. vasodilators and blood viscosity reducer agents. Compare the side effects and adverse reactions of Apply the Clinical Judgment [Nursing Process], including patient antihyperlipidemics. teaching, for antihyperlipidemics and blood viscosity reducer agents. OUTLINE Lipoproteins, 544 Cilostazol, 548 Apolipoproteins, 544 Pentoxifylline, 548 Nonpharmacologic Methods of Cholesterol Reduction, 544 Clinical Judgment [Nursing Process]—Antihyperlipidemics, 549 Antihyperlipidemics, 545 Clinical Judgment [Nursing Process]—Peripheral Vasodilator: Statins, 545 Cilostazol, 551 Drugs to Improve Peripheral Blood Flow, 546 Critical Thinking Case Study, 551 Review Questions, 552 Various drugs are used to maintain or decrease blood lipid concentra- Serum cholesterol and triglyceride measurements are frequently tions and promote dilation of vessels. Drugs that lower blood lipids are part of a regular physical examination or readmission evaluation and called antihyperlipidemics, antilipidemics, antilipemics, and hypolipid- are used as baseline test results. If the levels are high, a 12- to 14-hour emics. In this chapter, drugs used to lower lipoproteins are called anti- fasting lipid profile may be ordered. When cholesterol, triglycerides, hyperlipidemics. Drugs that improve blood flow are called peripheral and LDL are elevated, the patient is at increased risk for coronary vasodilators, as they dilate vessels that have been narrowed by vaso- artery disease (CAD). Table 44.1 lists the various serum lipids and their spasm, and blood viscosity reducer agents, which decrease viscosity of reference values (normal serum levels) according to risk classification. blood and increase erythrocyte flexibility. APOLIPOPROTEINS LIPOPROTEINS Apolipoproteins are within the lipoprotein shell and contain apo- Lipids—cholesterol, triglycerides, and phospholipids—are bound lipoprotein (apo) A-1, B, and E. The major component of apoA-1 is in the inner shell of protein, a carrier that transports lipids in the HDL. The major component of apoB is LDL, which exists in two forms, bloodstream. When there is an excess of one or more lipids in the apoB-100 and apoB-48. ApoB-100 has VLDL as well as LDL and is a blood, the condition is known as hyperlipidemia or hyperlipopro- better indicator of risk for CAD than LDL alone. teinemia. The four major categories of lipoprotein are high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low- NONPHARMACOLOGIC METHODS OF density lipoprotein (VLDL), and chylomicrons. HDL, also known as “friendly” or “good” lipoprotein, is the smallest and densest lipo- CHOLESTEROL REDUCTION protein, meaning that it contains more protein and less fat than Before drugs to lower LDL and raise HDL are prescribed, nondrug the others. The function of HDL is to remove cholesterol from the therapy should be initiated to decrease cholesterol. Saturated fats and bloodstream and deliver it to the liver for excretion in bile. LDL, cholesterol in the diet should be reduced. Total fat intake should be the “bad” lipoprotein, contains 50% to 60% of cholesterol in the 30% or less of caloric intake, and cholesterol intake should be 300 mg/ bloodstream. With an elevated LDL, the risk is greater for develop- day or less. The patient should be advised to read labels on containers ing atherosclerotic plaques and heart disease. VLDL carries mostly and buy appropriate foods. Patients should choose lean meats, espe- triglycerides and less cholesterol. The chylomicrons are large par- cially chicken and fish. ticles that transport fatty acids and cholesterol to the liver. They are In many cases, diet alone will not lower blood lipid levels. Because composed mostly of triglycerides. 75% to 85% of serum cholesterol is endogenously (internally) derived, 544  CHAPTER 44 Antihyperlipidemics and Drugs to Improve Peripheral Blood Flow 545 TABLE 44.1 Serum Lipid Values LEVEL OF RISK FOR CAD Lipids Desirable (mg/dL) Low Risk (mg/dL) Moderate Risk (mg/dL) High Risk (mg/dL) Cholesterol 150–200 200 200–240 >240 Triglycerides 40–150 Values vary with age. Values vary with age >190 Lipoproteins LDL 160 HDL >60 50–60 35–50 , greater than;