Copyright © 2017, Elsevier Inc. All rights reserved. Chapter 24 Heart Failure Drugs Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Heart Failure Not a specific disease Complex clinical syndrome resulting from any functional or structural impairment to the heart, specifically ejection of blood or ventricular filling The heart is unable to pump blood in sufficient amounts from the ventricles to meet the body’s metabolic needs. Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Heart Failure (Cont.) Symptoms depend on the cardiac area affected “Left-sided” heart failure (HF): pulmonary edema, coughing, shortness of breath, and dyspnea “Right-sided” HF: systemic venous congestion, pedal edema, jugular venous distension, ascites, and hepatic congestion Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Heart Failure: Causes Myocardial infarction (MI) Coronary artery disease Cardiomyopathy Valvular insufficiency Atrial fibrillation Infection Tamponade Ischemia Copyright © 2017, Elsevier Inc. All rights reserved.

Heart Failure: Causes (Cont.) Pulmonary hypertension Systemic hypertension Outflow obstruction Hypervolemia Congenital abnormalities Anemia Thyroid disease Infection Diabetes Copyright © 2017, Elsevier Inc. All rights reserved.

Conduction System of the Heart Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. American College of Cardiology Foundation/ American Heart Association (ACCF/AHA) Stages of Heart Failure STAGE A: At high risk for Heart Failure but no symptoms or structural heart disease STAGE B: Structural heart disease but no symptoms STAGE C: Structural heart disease with symptoms STAGE D: Refractory HF requiring interventions Copyright © 2017, Elsevier Inc. All rights reserved.

Drug Therapy for Heart Failure Positive inotropic drugs: increase the force of myocardial contraction Positive chronotropic drugs: increase heart rate Positive dromotropic drugs: accelerate cardiac conduction Copyright © 2017, Elsevier Inc. All rights reserved.

Drug Therapy for Heart Failure (Cont.) Positive inotropic drugs Phosphodiesterase inhibitors Cardiac glycosides B-type natriuretic peptides Angiotensin-converting enzyme (ACE) inhibitors Angiotensin receptor blockers (ARBs) Beta blockers Diuretics Copyright © 2017, Elsevier Inc. All rights reserved.

Drugs of Choice for Early Treatment of Heart Failure ACE inhibitors (lisinopril, enalapril, captopril, and others) ARBs (valsartan, candesartan, losartan, and others) Certain beta blockers (metoprolol, a cardioselective beta blocker; carvedilol, a nonspecific beta blocker) Copyright © 2017, Elsevier Inc. All rights reserved.

Drugs of Choice for Early Treatment of Heart Failure (Cont.) Loop diuretics (furosemide) are used to reduce the symptoms of HF secondary to fluid overload. Aldosterone inhibitors (spironolactone, eplerenone) are added as the HF progresses. Only after these drugs are used is digoxin added. Copyright © 2017, Elsevier Inc. All rights reserved.

Drugs of Choice for Early Treatment of Heart Failure (Cont.) Dobutamine: positive inotropic drug Hydralazine and isosorbide dinitrate became the first drug approved for a specific ethnic group. Hydralazine/isosorbide dinitrate (BiDil) was approved specifically for use in the African-American population. Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. ACE Inhibitors Prevent sodium and water resorption by inhibiting aldosterone secretion. Diuresis results, which decreases preload, or the left ventricular end-volume, and the work of the heart. Examples: lisinopril, enalapril, fosinopril, quinapril, captopril, ramipril, trandolapril, and perindopril Copyright © 2017, Elsevier Inc. All rights reserved.

Lisinopril (Prinivil, Zestril) Uses: hypertension, HF, and acute MI Hyperkalemia Dry cough Decreased renal function Copyright © 2017, Elsevier Inc. All rights reserved.

Angiotensin II Receptor Blockers (ARBs) Potent vasodilators; decrease systemic vascular resistance (afterload) Used alone or in combination with other drugs such as diuretics in the treatment of hypertension or HF Examples: valsartan (Diovan), candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro), telmisartan (Micardis), olmesartan (Benicar), and losartan (Cozaar) Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Valsartan (Diovan) Valsartan shares many of the same adverse effects as lisinopril. ARBs are not as likely to cause the cough associated with the ACE inhibitors. ARBs are not as likely to cause hyperkalemia. Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Beta Blockers Cardioprotective quality of beta blockers: prevent catecholamine-mediated actions on the heart by reducing or blocking sympathetic nervous system stimulation to the heart and the heart’s conduction system Metoprolol Carvedilol (Coreg) Copyright © 2017, Elsevier Inc. All rights reserved.

Aldosterone Antagonists Spironolactone and eplerenone Useful in severe stages of HF Action: activation of the renin-angiotensin-aldosterone system causes increased levels of aldosterone, which causes retention of sodium and water, leading to edema that can worsen HF. Copyright © 2017, Elsevier Inc. All rights reserved.

Aldosterone Antagonists (Cont.) Spironolactone (Aldactone): potassium-sparing diuretic and aldosterone antagonist shown to reduce the symptoms of HF Eplerenone (Inspra): selective aldosterone blocker, blocking aldosterone at its receptors in the kidney, heart, blood vessels, and brain Copyright © 2017, Elsevier Inc. All rights reserved.

Miscellaneous Drugs to Treat Heart Failure hydralazine/isosorbide dinitrate (BiDil) First drug approved for a specific ethnic group, namely African Americans dobutamine Beta1-selective vasoactive adrenergic drug Structurally similar to dopamine Copyright © 2017, Elsevier Inc. All rights reserved.

B-Type Natriuretic Peptides nesiritide (Natrecor) Synthetic version of human B-type natriuretic peptide Vasodilating effects on both arteries and veins Effects of nesiritide Diuresis (urinary fluid loss) Natriuresis (urinary sodium loss) Vasodilation Indirect increase in cardiac output and suppression of neurohormonal systems such as the renin-angiotensin system Copyright © 2017, Elsevier Inc. All rights reserved.

B-Type Natriuretic Peptides: Adverse Effects Nesiritide is used in the intensive care setting as a final effort to treat severe, life-threatening HF, often in combination with several other cardiostimulatory medications. Hypotension Dysrhythmia Headache Abdominal pain Insomnia Copyright © 2017, Elsevier Inc. All rights reserved.

Audience Response System Question Which patient is the best candidate to receive nesiritide therapy? A patient with atrial fibrillation who has not responded to other drugs A patient needing initial treatment for HF A patient with reduced cardiac output A patient with acutely decompensated HF who has dyspnea at rest Correct answer: D Rationale: At this time, nesiritide is generally used in the intensive care setting as a final effort to treat severe, life-threatening HF, often in combination with several other cardiostimulatory medications. The manufacturer recommends that nesiritide not be used as a first-line drug for this purpose. In 2005, an expert panel reviewed nesiritide at the request of the U.S. Food and Drug Administration in response to reports of worsened renal function and mortality. The expert panel stated that the use of nesiritide should be strictly limited to treatment of patients with acutely decompensated HF who have dyspnea at rest. It should not be used to replace diuretics and should not be used repetitively or to improve renal function. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Phosphodiesterase Inhibitors Work by inhibiting the enzyme phosphodiesterase Result in Intracellular increase in cAMP Positive inotropic response Vasodilation Increase in calcium for myocardial muscle contraction. Inodilators (inotropics and dilators) Copyright © 2017, Elsevier Inc. All rights reserved.

Phosphodiesterase Inhibitors: Indications Short-term management of HF for patients in the intensive care unit (ICU) AHA and ACC advise against long-term infusions Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Milrinone Only available phosphodiesterase inhibitor Milrinone is available only in injectable form. Adverse effects: cardiac dysrhythmias, headache, hypokalemia, tremor, thrombocytopenia, and elevated liver enzyme levels Interactions: diuretics (additive hypotensive effects) and digoxin (additive inotropic effects) Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Cardiac Glycosides No longer used as first-line treatment Not been shown to reduce mortality Originally obtained from Digitalis plant, foxglove Digoxin is the prototype Used in HF and to control ventricular response to atrial fibrillation Copyright © 2017, Elsevier Inc. All rights reserved.

Cardiac Glycosides: Mechanism of Action Increase myocardial contractility Change electrical conduction properties of the heart Decrease rate of electrical conduction Prolong the refractory period Area between sinoatrial (SA) node and atrioventricular (AV) node Copyright © 2017, Elsevier Inc. All rights reserved.

Cardiac Glycosides: Drug Effects Positive inotropic effect Increased force and velocity of myocardial contraction (without an increase in oxygen consumption) Negative chronotropic effect Reduced heart rate Negative dromotropic effect Decreased automaticity at SA node, decreased AV nodal conduction, and other effects Copyright © 2017, Elsevier Inc. All rights reserved.

Cardiac Glycosides: Drug Effects (Cont.) Increased stroke volume Reduction in heart size during diastole Decrease in venous BP and vein engorgement Increase in coronary circulation Decrease in exertional and paroxysmal nocturnal dyspnea, cough, and cyanosis Improved symptom control, quality of life, and exercise tolerance No apparent reduction in mortality Copyright © 2017, Elsevier Inc. All rights reserved.

Audience Response System Question A patient is in the emergency department with new-onset atrial fibrillation. Which order for digoxin would most likely have the fastest therapeutic effect? Digoxin 0.25 mg PO daily Digoxin 1 mg PO now; then 0.25 mg PO daily Digoxin 0.5 mg IV push daily Digoxin 1 mg IV push now; then 0.25 mg IV daily Correct answer: D Rationale: A digitalizing dose is often used to quickly bring serum levels of the drug up to a therapeutic level. IV doses would accomplish this more quickly. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Cardiac Glycosides: Adverse Effects digoxin (Lanoxin) Very narrow therapeutic window Drug levels must be monitored. 0.5 to 2 ng/mL Low potassium levels increase its toxicity. Electrolyte levels must be monitored. Copyright © 2017, Elsevier Inc. All rights reserved.

Cardiac Glycosides: Adverse Effects (Cont.) digoxin (Lanoxin) (Cont.) Cardiovascular: dysrhythmias, including bradycardia or tachycardia Central nervous system: headaches, fatigue, malaise, confusion, convulsions Copyright © 2017, Elsevier Inc. All rights reserved.

Cardiac Glycosides: Adverse Effects (Cont.) digoxin (Lanoxin) (Cont.) Eyes: colored vision (seeing green, yellow, purple), halo vision, flickering lights Gastrointestinal: anorexia, nausea, vomiting, diarrhea Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Digoxin Toxicity digoxin immune Fab (Digibind) therapy Hyperkalemia (serum potassium greater than 5 mEq/L) in a digitalis-toxic patient Life-threatening cardiac dysrhythmias Life-threatening digoxin overdose Copyright © 2017, Elsevier Inc. All rights reserved.

Audience Response System Question A patient is receiving digoxin 0.25 mg/day as part of treatment for HF. The nurse assesses the patient before medication administration. Which assessment finding would be of most concern? Apical heart rate of 58 beats/min Ankle edema +1 bilaterally Serum potassium level of 2.9 mEq/L Serum digoxin level of 0.8 ng/mL Correct answer: C Rationale: The hypokalemia may precipitate digoxin toxicity; therefore, it is the biggest concern. The apical pulse is slightly under 60 beats/min, but bradycardia may occur with digoxin therapy, and the heart rate should be monitored. The ankle edema may be a manifestation of his HF and not a new concern. The digoxin level is within the normal range. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Conditions That Predispose to Digoxin Toxicity Hypokalemia Use of cardiac pacemaker Hepatic dysfunction Hypercalcemia Dysrhythmias Hypothyroid, respiratory, or renal disease Advanced age Copyright © 2017, Elsevier Inc. All rights reserved.

Heart Failure Drugs: Nursing Implications Assess history, drug allergies, and contraindications. Assess clinical parameters, including: BP Apical pulse for 1 full minute Heart sounds, breath sounds Copyright © 2017, Elsevier Inc. All rights reserved.

Heart Failure Drugs: Nursing Implications (Cont.) Assess clinical parameters (Cont.) Weight, input and output measures Electrocardiogram Serum labs: potassium, sodium, magnesium, calcium, renal, and liver function studies Copyright © 2017, Elsevier Inc. All rights reserved.

Heart Failure Drugs: Nursing Implications (Cont.) Before giving any dose, count apical pulse for 1 full minute. For an apical pulse less than 60 or greater than 100 beats/min: Hold dose. Notify prescriber. Copyright © 2017, Elsevier Inc. All rights reserved.

Heart Failure Drugs: Nursing Implications (Cont.) Hold dose and notify prescriber if the patient experiences signs or symptoms of toxicity. Anorexia, nausea, vomiting, diarrhea Visual disturbances (blurred vision, seeing green or yellow halos around objects) Copyright © 2017, Elsevier Inc. All rights reserved.

Heart Failure Drugs: Nursing Implications (Cont.) Check dosage forms carefully and follow instructions for administering. Avoid giving digoxin with high-fiber foods (fiber binds with digitalis). Patients should immediately report a weight gain of 2 lb or more in 1 day or 5 lb or more in 1 week. Copyright © 2017, Elsevier Inc. All rights reserved.

Heart Failure Drugs: Nursing Implications (Cont.) Nesiritide or milrinone Use an infusion pump Monitor input and output, heart rate and rhythm, BP, daily weights, respirations, and so on Copyright © 2017, Elsevier Inc. All rights reserved.

Heart Failure Drugs: Nursing Implications (Cont.) Monitor for therapeutic effects: Increased urinary output Decreased edema, shortness of breath, dyspnea, crackles, fatigue Resolution of paroxysmal nocturnal dyspnea Improved peripheral pulses, skin color, temperature Monitor for adverse effects. Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Case Study A patient with a history of HF presents to the emergency department with difficulty breathing, cough, and edema of the lower extremities. The nurse anticipates administration of which type of medication? Positive chronotrope Negative chronotrope Positive inotrope Negative inotrope Correct answer: C Rationale: Positive inotropes are used to increase the force of myocardial contraction in the treatment of patients with HF. Negative inotropes would cause the heart to have a decreased force of myocardial contraction and would not be effective. Positive chronotropes increase the rate at which the heart beats, and negative chronotropes decrease the rate at which the heart beats. Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Case Study (Cont.) The patient is prescribed an ACE inhibitor. The nurse understands the primary mechanism by which the ACE inhibitors exert their therapeutic effect in a patient in HF is to inhibit catecholamine release. to inhibit acetylcholine release. to inhibit aldosterone secretion. to prevent vagal stimulation. Correct answer: C Rationale: The ACE inhibitors are beneficial in the treatment of HF because they prevent sodium and water resorption by inhibiting aldosterone secretion. This causes diuresis, which decreases blood volume and blood return to the heart. This in turn decreases preload, or the left ventricular end-diastolic volume, and the work required of the heart. Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved. Case Study (Cont.) The patient is discharged home and returns to the emergency department 4 days later. The patient is admitted to the ICU with acute decompensated HF with dyspnea at rest. The nurse anticipates administration of which medication? atropine carvedilol (Coreg) lisinopril (Prinivil) nesiritide (Natrecor) Correct answer: D Rationale: Nesiritide is used in the ICU setting as a final effort to treat severe, life-threatening HF, often in combination with several other cardiostimulatory medications. Lisinopril (Prinivil) is an ACE inhibitor that is used in the management of HF. Carvedilol (Coreg) has been shown to slow the progression of HF and to decrease the frequency of hospitalization in patients with mild to moderate (class II or III) HF. Atropine is used to increase heart rate. Copyright © 2017, Elsevier Inc. All rights reserved.