Copyright 2014 by Mosby, an imprint of Elsevier Inc.

Lilley: Pharmacology and the Nursing Process, 7th Edition

Chapter 24: Heart Failure Drugs

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ANATOMY, PHYSIOLOGY, AND PATHOPHYSIOLOGY OVERVIEW

Heart failure is a clinical syndrome caused by numerous different cardiac disorders. It
is a pathologic state in which the heart is unable to pump blood in sufficient amounts from
the ventricles to meet the bodys 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.
Heart failure occurs due to a reduced ratio of ejection fraction to left ventricular end-diastolic
volume.
The physical defects causing heart failure are of two types: (1) a myocardial defect such as
myocardial infarction (MI) 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.
Heart failure is stratified into classes using the New York Heart Associations 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.
The best way to prevent heart failure is to control risk factors associated with heart failure
including hypertension, coronary artery disease, obesity, and diabetes.
Drug therapy is individualized based on the patients class of heart failure.

PHARMACOLOGY OVERVIEW
Inotropic drugs affect the force of myocardial contraction; positive inotropics (e.g.,
digoxin) increase the force of contractions, and negative inotropics (e.g., beta blockers,
calcium channel blockers) decrease myocardial contractility.
Chronotropics affect heart rate per minute, with positive chronotropics increasing
heart rate and negative chronotropics decreasing the heart rate.
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Dromotropic drugs affect the conduction of electrical impulses through the heart; positive
dromotropic drugs increase the speed of electrical impulses through the heart, whereas
negative dromotropic drugs have the opposite effect.
Be aware of the important physiologic concepts such as ejection fraction. A patients
ejection fraction reflects the contractility of the heart and is about 65% (0.65) in a normal
heart. This value decreases as heart failure progresses; therefore, patients with heart
failure have low ejection fractions because their hearts are failing to pump effectively.
The American Heart Association and American College of Cardiology (2005, updated in
2009) guidelines provide the protocol guidelines of treatment for heart failure, including the
following:
o Drugs of choice to initiate treatment are the angiotensin-converting enzyme
(ACE) inhibitors (lisinopril, enalapril, captopril, and others) or the angiotensin
II receptor blockers (ARBs) (valsartan, candesartan, losartan) and beta blockers
(metoprolol, a cardioselective beta blocker; carvedilol, a nonspecific beta
blocker).
o The loop diuretics (furosemide) are used to reduce the symptoms of heart failure
secondary to fluid overload.
o The aldosterone inhibitors (spironolactone, eplerenone) are added as the heart
failure progresses.
o Only after these drugs are used is digoxin added.
o Hydralazine/isosorbide dinitrate became the first drug approved specifically for use in
the African-American population.

Angiotensin-Converting Enzyme I nhibitors
The ACE inhibitors are a class of drugs that inhibit angiotensin-converting enzyme, which is
responsible for converting angiotensin I 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.
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Angiotensin I I Receptor Blockers
The therapeutic effects of 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.
The ARBs are not as likely to cause the cough associated with the ACE inhibitors.

Beta Blockers
Beta blockers work by reducing or blocking sympathetic nervous system stimulation to the
heart and the hearts 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
atrioventricular (AV) node conduction, reduced myocardial contractility, and
decreased myocardial automaticity.
Metoprolol is the beta blocker most commonly used to treat heart failure.
Carvedilol (Coreg) has many effects, including acting as a nonselective beta blocker, an
alpha
1
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.

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 that 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.
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Miscellaneous Heart Failure Drugs
Hydralazine/isosorbide dinitrate (BiDil) was the first drug approved for a specific ethnic
group, namely African Americans.
Dobutamine is a beta
1
-selective vasoactive adrenergic drug that is structurally similar to the
naturally occurring catecholamine dopamine. Dobutamine increases cardiac output by
increasing contractility (positive inotropy), which increases the stroke volume, especially in
patients with heart failure.

B-Type Natriuretic Peptide
The newest class of medications for heart failure, the B-type natriuretic peptides, currently
includes only one drug, nesiritide.
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, natriuresis, 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. Its use is
no longer recommended as a first-line drug for heart failure.

Phosphodiesterase I nhibitors
Phosphodiesterase inhibitors (PDIs) are a group of inotropic drugs that work by inhibiting the
action of an enzyme called phosphodiesterase.
Presently only one drug in this category is available in the United States: milrinone
(Primacor).
Milrinone causes an intracellular increase in cyclic adenosine monophosphate (cAMP),
which results in two beneficial effects in a patient with heart failure: a positive inotropic
response and vasodilation. For this reason, this class of drugs may also be referred to as
inodilators (inotropics and dilators).
PDIs are primarily used in the intensive care setting for the short-term management of acute
heart failure.
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The primary adverse effect seen with milrinone therapy is ventricular dysrhythmia.
Concurrent administration of diuretics may cause significant hypovolemia and reduced
cardiac filling pressure. Appropriately monitor the patient in an intensive care setting to
detect and respond to these problems.

Cardiac Glycosides
Digoxin is primarily used in the treatment of systolic heart failure and atrial
fibrillation.
The latest heart failure treatment guidelines recommend that digoxin be used as an
adjunct to drugs of other classes, including beta blockers, diuretics, ACE inhibitors,
and ARBs.
Digoxin is the only cardiac glycoside currently available in the United States. Although a
powerful positive inotropic drug, it has not been shown to reduce mortality.
The beneficial effect of digoxin is thought to be an increase in myocardial contractility
known as a positive inotropic effect. Digoxin decreases the velocity (rate) of electrical
conduction and prolongs the refractory period in the conduction system.
The common undesirable effects associated with digoxin use are cardiovascular, central
nervous system, ocular, and gastrointestinal effects.
Digoxin has a low therapeutic index, so levels are monitored when the patient first starts
taking the drug. Low potassium or magnesium levels may increase the potential for digoxin
toxicity. Estimates are that as many as 20% of patients taking digoxin exhibit symptoms of
toxicity. A decrease in renal function is also a common cause of digoxin toxicity, because
digoxin is excreted almost exclusively via the kidneys. Signs and symptoms of digoxin
toxicity include bradycardia, headache, dizziness, confusion, nausea, and visual disturbances
(blurred vision or yellow vision). With toxicity, electrocardiographic (ECG) findings may
include heart block, atrial tachycardia with block, or ventricular dysrhythmias.
When significant toxicity develops as a result of digoxin therapy, digoxin immune Fab may
be indicated. Digoxin immune Fab is an antibody that recognizes digoxin as an antigen and
forms an antigen-antibody complex with the drug, thus inactivating the free digoxin.
Incorrect decimal placement can be lethal when calculating digoxin dosages. According to
the Institute for Safe Medication Practices (ISMP), trailing zeros are not to be used after
decimal points. The ISMP also recommends that leading zeros be used if a dose is less than a
whole number.
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NURSING PROCESS

Perform a thorough assessment, including assessment of the patients past and present
medical history, drug allergies, and family medical history with emphasis on any history of
cardiac, hypertensive, or renal diseases.
Hyperkalemia is an adverse effect; therefore, perform an assessment of serum potassium
before giving these drugs and administer potassium supplementation and/or potassium-
sparing diuretics with caution.
Assess respiratory history, specifically any previous problems of cough. ACE inhibitors may
cause a dry cough, which is not harmful but may be annoying.
Aldosterone antagonists, such as spironolactone and eplerenone, require close assessment of
heart and breath sounds as well as for the occurrence of edema, a known adverse effect.
It is always important to assess support systems at home, because safe and effective therapy
depends on close observation, monitoring of appropriate parameters (e.g., daily weight),
attention to patient complaints, and evaluation of how the patient is feeling and functioning.
Before giving digoxin, closely monitor the apical pulse rate and serum electrolytes,
especially potassium levels because low levels or hypokalemia may precipitate toxicity.
Nesiritide is strictly used in an intensive care setting in very ill patients who are experiencing
acute decompensated heart failure and receiving continuous cardiac monitoring. While the
drug is being administered intravenously, monitor the patient for all of its severe adverse
effects, such as hypotension, dysrhythmias, headache, and abdominal pain. Avoid co-
administration of drugs that decrease the patients blood pressure, such as ACE inhibitors and
diuretics, if at all possible.
Always check for compatibility of solutions when giving the PDI milrinone. Recognize that
hypotension, dysrhythmias, and thrombocytopenia are major adverse effects of milrinone.
Record intake and output, heart rate, blood pressure, daily weight, respiration rate, and heart
and breath sounds. Report any evidence of hypokalemia to the prescriber immediately, and
monitor the patient closely.
When heart failure drugs, such as digoxin, milrinone, and digoxin immune Fab, are
administered parenterally, use an infusion pump unless the order is to administer them as an
intravenous push.
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Monitoring patients after the administration of drugs to improve heart contractility, or
positive inotropic drugs, is critical for identifying therapeutic effects and adverse effects.
The therapeutic effects of these drugs include increased urinary output, decreased edema,
decreased dyspnea and crackles, decreased fatigue, resolution of paroxysmal nocturnal
dyspnea, and improved peripheral pulses, skin color, and temperature.