Heart Failure Drugs



Heart Failure Drugs


Objectives


When you reach the end of this chapter, you will be able to do the following:



1 Differentiate between the terms inotropic, chronotropic, and dromotropic.


2 Briefly discuss the pathophysiology of heart failure.


3 Identify the approach to treatment of heart failure as outlined by the American Heart Association and American College of Cardiology Guidelines for the Diagnosis and Management of Heart Failure in Adults (last updated in 2009).


4 Compare the mechanisms of action, pharmacokinetics, indications, dosages, dosage forms, routes of administration, cautions, contraindications, adverse effects, and toxicity of the following drugs used in treatment of heart failure: lisinopril, valsartan, carvedilol, metoprolol, dobutamine, nesiritide, hydralazine/isosorbide dinitrate, milrinone, and digoxin.


5 Briefly discuss the process of rapid versus slow digitalization as well as the use of the antidote digoxin immune Fab.


6 Identify significant drug-drug, drug–laboratory test, and drug-food interactions associated with digoxin and other heart failure drugs.


7 Develop a nursing care plan that includes all phases of the nursing process for patients undergoing treatment for heart failure and that reflects the American Heart Association and American College of Cardiology Guidelines for the Diagnosis and Management of Heart Failure in Adults.


Drug Profiles



Key Terms


Atrial fibrillation A common cardiac dysrhythmia with atrial contractions that are so rapid that they prevent full repolarization of myocardial fibers between heartbeats. (p. 387)


Automaticity A property of specialized excitable tissue in the heart that allows self-activation through the spontaneous development of an action potential, such as in the pacemaker cells of the heart. (p. 385)


Chronotropic drugs Drugs that influence the rate of the heartbeat. (p. 384)


Dromotropic drugs Drugs that influence the conduction of electrical impulses within tissues. (p. 384)


Ejection fraction The proportion of blood that is ejected during each ventricular contraction compared with the total ventricular filling volume. (p. 383)


Heart failure An abnormal condition in which the heart cannot pump enough blood to keep up with the body’s demand. It is often the result of myocardial infarction, ischemic heart disease, or cardiomyopathy. (p. 383)


Inotropic drugs Drugs that influence the force of muscular contractions, particularly contraction of the heart muscle. (p. 384)


Left ventricular end-diastolic volume The total amount of blood in the ventricle immediately before it contracts, or the preload. (p. 383)


Refractory period The period during which a pulse generator (e.g., the sinoatrial node of the heart) is unresponsive to an electrical input signal, and during which it is impossible for the myocardium to respond. This is the period during which the cardiac cell is readjusting its sodium and potassium levels and cannot be depolarized again. (p. 388)


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Anatomy, Physiology, and Pathophysiology Overview


Heart failure is a not a specific disease per se but rather a clinical syndrome caused by numerous different cardiac disorders. More than 5.7 million people in the United States have heart failure. It is one of the most common causes for hospitalization in the United States, estimated to result in more than 3.5 million hospitalizations annually. This is especially true for elderly patients. Heart failure also causes more than 300,000 deaths annually. The findings of one of the largest and most frequently cited studies involving patients with heart failure, the Framingham study, show that the 5-year survival rate in patients with heart failure is approximately 50%. The best way to prevent heart failure is to control risk factors associated with heart failure including hypertension, coronary artery disease, obesity, and diabetes.


Heart failure is a pathologic state in which the heart is unable to pump blood in sufficient amounts from the ventricles (i.e., cardiac output is insufficient) to meet the body’s metabolic needs, or can do so only at elevated filling pressures. The signs and symptoms typically associated with this insufficiency make up the syndrome of heart failure. Initially, the patient is asymptomatic. As the disease progresses, so do the symptoms. Failure of the ventricle(s) to eject blood efficiently results in fluid volume overload, chamber dilation, and elevated intracardiac pressure. This syndrome can affect the left ventricle, the right ventricle, or both ventricles simultaneously. Left ventricular or “left-sided” heart failure often leads to pulmonary edema, coughing, shortness of breath, and dyspnea. Right ventricular heart failure typically involves systemic venous congestion, pedal edema, jugular venous distension, ascites, and hepatic congestion. Both syndromes occur due to increased hydrostatic pressure from the ventricles into the pulmonary and/or systemic circulation.


More specifically, heart failure occurs due to a reduced ratio of ejection fraction to left ventricular end-diastolic volume. The ejection fraction is the amount of blood ejected with each contraction, whereas the left ventricular end-diastolic volume is the total amount of blood in the ventricle just before contraction. The ejection fraction is an index of left ventricular function, and the normal value is approximately 65% (0.65) of the total volume in the ventricle.


When a person has heart failure, the heart cannot then meet the increased demands, and the blood supply to certain organs is reduced. The organs that are most dependent on blood supply, the brain and heart, are the last to be deprived of blood. The kidney is relatively less dependent on blood supply and has its blood supply shunted away from it. Therefore, the filtration of fluids and removal of waste products is impaired. This can lead to acute or chronic renal failure. It also contributes to conditions such as pulmonary edema, shortness of breath, and peripheral edema.


The physical defects causing heart failure are of two types: (1) a myocardial defect such as myocardial infarction or valve insufficiency, which leads to inadequate cardiac contractility and ventricular filling; and (2) a defect outside the myocardium (e.g., coronary artery disease, pulmonary hypertension, or diabetes), which results in an overload on an otherwise normal heart. Either or both of these defects may be present in a given patient. These and other common causes of myocardial deficiency and systemic defects are listed in Box 24-1.



The emphasis of this chapter is on systolic dysfunction or inadequate ventricular contractions (systole) during the pumping of the heart. Less common, but still important, is diastolic dysfunction or inadequate ventricular filling during ventricular relaxation (diastole). This condition is most commonly associated with left ventricular hypertrophy secondary to chronic hypertension. However, it may also result from cardiomyopathy (e.g., virus induced), pericardial disease, and diabetes.


Heart failure is stratified into classes using The New York Heart Association’s functional classification. Class I describes a patient who is not limited with normal physical activity by symptoms. Class II occurs when ordinary physical activity results in fatigue, dyspnea, or other symptoms. Class III is characterized by a marked limitation in normal physical activity. Class IV is defined by symptoms at rest or with any physical activity. Drug therapy is individualized based on the patient’s class of heart failure.


Pharmacology Overview


Drugs that increase the force of myocardial contraction are called positive inotropic drugs, and they have a role in the treatment of failing heart muscle. Negative inotropic drugs reduce the force of contraction. Drugs that increase the rate at which the heart beats are called positive chronotropic drugs. Negative chronotropic drugs do the opposite. Drugs may also affect how quickly electrical impulses travel through the conduction system of the heart (the sinoatrial [SA] node, atrioventricular [AV] node, bundle of His, and Purkinje fibers) (Figure 24-1). Drugs that accelerate conduction are referred to as positive dromotropic drugs. Negative dromotropic drugs do the opposite. This chapter focuses on the positive inotropic drugs, phosphodiesterase inhibitors and cardiac glycosides, as well as the newest class of medications for heart failure, B-type natriuretic peptides. Although several other drugs are used in the treatment of heart failure, they are discussed in detail in other chapters; for example, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are covered in Chapter 22; beta blockers are discussed in Chapters 19, 22 and 23; and diuretics are discussed in Chapter 28. These drugs are mentioned in this chapter as well, but for specifics, refer to the indicated chapters.



The treatment of heart failure has changed dramatically over the past decade. Digoxin used to be the mainstay in heart failure treatment, but because of adverse effects and drug interactions, it has been replaced by other drugs. According to the latest American Heart Association and American College of Cardiology Guidelines for the Diagnosis and Management of Heart Failure in Adults (2005, updated in 2009), the approach to the treatment of chronic heart failure revolves around reducing the effects of the renin-angiotensin-aldosterone system and the sympathetic nervous system. Therefore, the drugs of choice at the start of therapy are the ACE inhibitors (lisinopril, enalapril, captopril, and others) or the angiotensin II receptor blockers (valsartan, candesartan, losartan, and others) and certain beta blockers (metoprolol, a cardioselective beta blocker; carvedilol, a nonspecific beta blocker). Loop diuretics (furosemide) are used to reduce the symptoms of heart failure secondary to fluid overload, and the aldosterone inhibitors (spironolactone, eplerenone) are added as the heart failure progresses. Only after these drugs are used is digoxin added. Dobutamine, a positive inotropic drug, has also been used to treat heart failure. In 2005, a combination drug containing 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.


Angiotensin-Converting Enzyme Inhibitors


The angiotensin-converting enzyme (ACE) inhibitors are a class of drugs that, as their name implies, inhibit angiotensin-converting enzyme, which is responsible for converting angiotensin I (formed through the action of renin) to angiotensin II. Angiotensin II is a potent vasoconstrictor and induces aldosterone secretion by the adrenal glands. Aldosterone stimulates sodium and water resorption, which can raise blood pressure. Together, these processes are referred to as the renin-angiotensin-aldosterone system. The ACE inhibitors are beneficial in the treatment of heart failure 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.


Numerous ACE inhibitors are available, including lisinopril, enalapril, fosinopril, quinapril, captopril, ramipril, trandolapril, and perindopril. These drugs are all very similar, and lisinopril will be used as the class representative.


Drug Profile


♦ lisinopril


Lisinopril (Prinivil, Zestril) is a commonly used ACE inhibitor and is available in a generic form. It is used for hypertension, heart failure, and acute myocardial infarction. Like all ACE inhibitors, it is classified as a category C drug for women in the first trimester of pregnancy and a category D drug for women in the second and third trimesters; it can cause fetal death when used in the last two trimesters. Hyperkalemia may occur with any ACE inhibitor, and potassium supplementation or potassium-sparing diuretics need to be used with caution. Like all ACE inhibitors, lisinopril can cause a dry cough, which will not harm the patient but is annoying. Lisinopril (and all ACE inhibitors) may be associated with a decrease in renal function and hyperkalemia. For drug interactions, see Chapter 22.



Angiotensin II Receptor Blockers


The therapeutic effects of angiotensin II receptor blockers (ARBs) in heart failure are related to their potent vasodilating properties. They may be used alone or in combination with other drugs such as diuretics in the treatment of hypertension or heart failure. The beneficial hemodynamic effect of ARBs is their ability to decrease systemic vascular resistance (a measure of afterload). Seven ARBs are currently available: valsartan (Diovan), candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro), telmisartan (Micardis), olmesartan (Benicar), and losartan (Cozaar). All of the ARBs are similar in action. Valsartan will be used as the class representative.


Drug Profile


♦ valsartan


Valsartan (Diovan) is a commonly used ARB. Like all ARBs, it is a pregnancy category D drug. Valsartan shares many of the same adverse effects as lisinopril, profiled earlier. The ARBs are not as likely to cause the cough associated with the ACE inhibitors, nor are they as likely to cause hyperkalemia. For drug interactions, see Chapter 22.



Beta Blockers


Beta blockers (also discussed in Chapters 19, 22, and 23) work by reducing or blocking sympathetic nervous system stimulation to the heart and the heart’s conduction system. By doing this, beta blockers prevent catecholamine-mediated actions on the heart. This is known as a cardioprotective quality of beta blockers. The resulting cardiovascular effects include reduced heart rate, delayed AV node conduction, reduced myocardial contractility, and decreased myocardial automaticity. Metoprolol is the beta blocker most commonly used to treat heart failure. Metoprolol is available as an immediate-release and a sustained-release product, as well as an intravenous formulation.


Carvedilol (Coreg) has many effects, including acting as a nonselective beta blocker, an alpha1 blocker, and possibly a calcium channel blocker and antioxidant. It is used primarily in the treatment of heart failure but is also beneficial for hypertension and angina. It has been shown to slow the progression of heart failure and to decrease the frequency of hospitalization in patients with mild to moderate (class II or III) heart failure. Carvedilol is most commonly added to digoxin, furosemide, and ACE inhibitors when used to treat heart failure. Carvedilol is available only for oral use. A controlled-release formulation, called Coreg CR, was recently approved. The dosages are different from those for immediate-release Coreg, and the two dosage forms cannot be interchanged.


Aldosterone Antagonists


Aldosterone antagonists spironolactone and eplerenone are useful in severe stages of heart failure. 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 heart failure. Spironolactone (Aldactone) is a potassium-sparing diuretic and is discussed in detail in Chapter 28. It also acts as an aldosterone antagonist, which has been shown to reduce the symptoms of heart failure. Eplerenone (Inspra) is a selective aldosterone blocker, blocking aldosterone at its receptors in the kidney, heart, blood vessels, and brain. It is discussed in detail in Chapter 22.


Miscellaneous Heart Failure Drugs


Drug Profiles


hydralazine/isosorbide dinitrate


Hydralazine/isosorbide dinitrate (BiDil) was the first drug approved for a specific ethnic group, namely African Americans. This combination of two older drugs contains 37.5 mg of hydralazine and 20 mg of isosorbide dinitrate. The individual drugs are discussed in detail in Chapter 22 (hydralazine) and Chapter 23 (isosorbide). Peak plasma levels of hydralazine/isosorbide dinitrate are achieved in 1 hour. The dose is 1 tablet three times a day, titrated up to a maximum of 2 tablets three times a day.


♦ dobutamine


Dobutamine (generic, formerly Dobutrex) is a beta1-selective vasoactive adrenergic drug that is structurally similar to the naturally occurring catecholamine dopamine. Through stimulation of the beta1 receptors on heart muscle (myocardium), it increases cardiac output by increasing contractility (positive inotropy), which increases the stroke volume, especially in patients with heart failure. Dobutamine is available only as an intravenous drug and is given by continuous infusion. See Chapter 18 for further discussion on this drug.


B-Type Natriuretic Peptide


The newest class of medications for heart failure, the B-type natriuretic peptides, currently includes only one drug, nesiritide.


Drug Profile


♦ nesiritide


Nesiritide (Natrecor) is classified as a synthetic version of human B-type natriuretic peptide. B-type natriuretic peptide (BNP) is a substance secreted from the ventricles of the heart in response to changes in pressure that occur when heart failure develops. The level of BNP in the blood increases when heart failure symptoms worsen. A related hormone that occurs naturally in the body is atrial natriuretic peptide, which affects vascular permeability. Vascular permeability refers to the ability of plasma to flow between blood vessels and their surrounding tissues, and it serves as one way for the body to regulate blood pressure.


Nesiritide is a synthetic b-type natriuretic hormone that has vasodilating effects on both arteries and veins. This vasodilation takes place in the heart itself and throughout the body. The effects of nesiritide have been shown to include diuresis (urinary fluid loss), natriuresis (urinary sodium loss), and vasodilation. These properties lead to an indirect increase in cardiac output and suppression of neurohormonal systems such as the renin-angiotensin system.


Nesiritide is used in the intensive care setting as a final effort to treat severe, life-threatening heart failure, often in combination with several other cardiostimulatory medications. It is no longer recommended to be used as a first-line drug for heart failure. 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 be strictly limited to treatment of patients with acutely decompensated heart failure who have dyspnea at rest. It is not to be used to replace diuretics and is not to be used repetitively or to improve renal function. Its only current contraindication is drug allergy, although it is not recommended for use in patients with low cardiac filling pressures, as typically measured in the intensive care unit. Adverse effects include hypotension, cardiac dysrhythmias, insomnia, headache, and abdominal pain. Currently identified drug interactions include additive hypotensive effects with coadministration of ACE inhibitors and diuretics. This drug is available only in injectable form. Recommended dosages are given in the table below.



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May 9, 2017 | Posted by in NURSING | Comments Off on Heart Failure Drugs

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