Chapter 37: Cardiac Glycosides, Antianginals, and Antidysrhythmics

Key Points

• Digitalis preparations have come to be known for their effectiveness in treating heart
failure (HF). HF occurs when the heart muscle weakens and enlarges and loses its ability
to pump blood through the heart and into the systemic circulation.
• Heart failure can be left-sided or right-sided. The patient has left-sided HF when the left
ventricle does not contract sufficiently to pump the blood returned from the lungs and left
atrium out through the aorta into the peripheral circulation; this causes excessive amounts
of blood to back up into the lung tissue.
• Right-sided HF occurs when the heart does not sufficiently pump the blood returned into
the right atrium from the systemic circulation. As a result, the blood and its constituents
are backed up into peripheral tissues, causing peripheral edema.
• An increased preload results from an excess of blood volume in the ventricle at the end of
diastole.
• Increased afterload is an additional pressure or force in the ventricular wall caused by
excess resistance in the aorta.
• Cardiac glycosides are a group of drugs that inhibit the sodium-potassium pump,
resulting in an increase in intracellular sodium. This increase leads to an influx of
calcium, causing the cardiac muscle fibers to contract more efficiently.
• Digitalis preparations have three effects on heart muscle: (1) a positive inotropic action,
(2) a negative chronotropic action, and (3) a negative dromotropic action.
o The resultant increase in myocardial contractility strengthens cardiac, peripheral,
and kidney function by enhancing cardiac output, decreasing preload, improving
blood flow to the periphery and kidneys, decreasing edema, and promoting fluid
excretion.
• Cardiac glycosides are a secondary drug for heart failure. Cardiac glycosides are also
used to correct atrial fibrillation and atrial flutter owing to their negative chronotropic
effects and negative dromotropic effects.
• Nondrug therapy is an integral part of the regimen for controlling HF. The nondrug
component of the regimen should be tailored to meet the needs of each patient.
o Salt should be limited to 2 g/day; alcohol intake should be either decreased to 1
drink per day or completely avoided; fluid intake may be restricted; smoking
should be avoided, and mild exercise is recommended.
• Atrial natriuretic hormone, or peptide, is secreted from the atria of the heart and acts as an
antagonist to renin and aldosterone. It is released during expansion of the atrium,
produces vasodilation, and increases glomerular filtration rate.
• The brain natriuretic peptide (BNP) is primarily secreted from atrial cardiac cells and,
when tested, aids in the diagnosis of HF.
• Overdose or accumulation of digoxin causes digitalis toxicity. Signs and symptoms
include anorexia, diarrhea, nausea and vomiting, bradycardia, premature ventricular
contractions, cardiac dysrhythmias, headaches, malaise, blurred vision, visual illusions,
confusion, and delirium. Serum digoxin levels should be closely monitored.
• Digoxin-immune Fab may be given to treat severe digitalis toxicity. This agent binds with
digoxin to form complex molecules that can be excreted in the urine; thus, digoxin is
unable to bind at the cellular site of action.
• Hypokalemia increases the effect of digoxin at its myocardial cell site of action, resulting
in digitalis toxicity.
• The phosphodiesterase inhibitors are another positive inotropic group of drugs given to
treat acute HF. This drug group inhibits the enzyme phosphodiesterase, promoting a
positive inotropic response and vasodilation.
• Severe cardiac dysrhythmias might result from the use of phosphodiesterase inhibitors, so
the patient’s electrocardiogram (ECG) and cardiac status should be closely monitored.
• Vasodilators, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II–receptor
antagonists, diuretics, spironolactone, nesiritide, and some beta blockers are other drug
groups prescribed to treat HF.
• The vasodilators decrease venous blood return to the heart, resulting in a decrease in
cardiac filling, ventricular stretching (preload), and oxygen demand on the heart.
• The arteriolar dilators act in three ways: (1) to reduce cardiac afterload, (2) to dilate the
arterioles of the kidneys, and (3) to improve circulation to the skeletal muscles.
• ACE inhibitors dilate venules and arterioles, improving renal blood flow and decreasing
blood fluid volume. They also moderately decrease the release of aldosterone, which in
turn reduces sodium and fluid retention.
• ACE inhibitors can increase potassium levels, so serum potassium levels should be
monitored, especially if potassium-sparing diuretics are being taken concurrently.
• Angiotensin II–receptor blocker (ARB) agents have been approved for HF in patients
who cannot tolerate an ACE inhibitor.
• Diuretics are the first-line drug treatment for reducing fluid volume. They are frequently
prescribed with digoxin or other agents.
• Aldosterone secretions are increased in HF. This promotes body loss of potassium and
magnesium needed by the heart and increases sodium and water retention. Spironolactone
blocks the production of aldosterone, thereby improving heart rate variability and
decreasing myocardial fibrosis.
o Serum potassium level should be closely monitored in patients taking
spironolactone.
• Beta blockers have been shown to improve cardiac performance. Doses should be low
initially and gradually increased.
• Nesiritide is an atrial natriuretic peptide hormone that inhibits antidiuretic hormone
(ADH) by increasing urine sodium loss. Its effect in correcting HF is achieved by
promoting vasodilation, natriuresis, and diuresis. It is useful for treating patients who
have acute decompensated HF.
• A combination of hydralazine and isosorbide dinitrate, has received the U.S. Food and
Drug Association approval for treating HF, especially in African Americans.
• Antianginal drugs are used to treat angina pectoris. This is a condition of acute cardiac
pain caused by inadequate blood flow to the myocardium due to either plaque occlusions
within, or spasms of, the coronary arteries. With decreased blood flow, there is a decrease
in oxygen to the myocardium, which results in pain.
• There are three types of angina: (1) classic (stable), (2) unstable (preinfarction), and (3)
variant (vasospastic). The first two types are caused by a narrowing or partial occlusion
of the coronary arteries; variant angina is caused by vessel spasm.
• A combination of pharmacologic and nonpharmacologic measures is usually necessary to
control and prevent anginal attacks. Nonpharmacologic methods of decreasing anginal
attacks are to avoid heavy meals, smoking, extremes in weather changes, strenuous
exercise, and emotional upset.
• Antianginal drugs increase blood flow either by increasing oxygen supply or by
decreasing oxygen demand by the myocardium.
• Three types of antianginals are nitrates, beta blockers, and calcium channel blockers.
• Nitrates cause generalized vascular and coronary vasodilation, which increases blood
flow through the coronary arteries to the myocardial cells. This group of drugs reduces
myocardial ischemia but can cause hypotension.
• The sublingual (SL) nitroglycerin tablet, which is absorbed under the tongue, comes in
various dosages, but the average prescribed dose is 0.4 mg following cardiac pain. If pain
has not subsided, then 911 should be called.
• Nitroglycerin is not swallowed because it undergoes first-pass metabolism by the liver,
which decreases its effectiveness.
• Headaches are one of the most common side effects of nitroglycerin, but they may
become less frequent with continued use. Otherwise acetaminophen may provide some
relief.
• When nitroglycerin ointment or transdermal patches are discontinued, the dose should be
tapered over several weeks to prevent the rebound effect of severe pain caused by
myocardial ischemia.
• The nitroglycerin patch is applied once a day. It is important to note that the patch should
be removed nightly to allow for an 8- to 12-h nitrate-free interval. This is also true for
most other forms of nitroglycerin. This is necessary to avoid tolerance associated with
uninterrupted use or continued dosage increases of nitrate preparations.
• Beta blockers decrease the effects of the sympathetic nervous system by blocking the
action of the catecholamines (epinephrine and norepinephrine), thereby decreasing the
heart rate and blood pressure.
• Beta blockers should not be abruptly discontinued. The dose should be tapered over a
specified number of days to avoid reflex tachycardia and recurrence of anginal pain.
Patients who have decreased heart rate and blood pressure usually cannot take beta
blockers.
• The cardioselective beta blockers act more strongly on the beta1 receptor, which
decreases heart rate but avoids bronchoconstriction because of their lack of activity at the
beta2 receptor.
• Calcium channel blockers (CCBs) relax coronary artery spasm and relax peripheral
arterioles, decreasing cardiac oxygen demand. They also decrease cardiac contractility,
decrease afterload, decrease peripheral resistance, and reduce the workload of the heart.
• The side effects of calcium blockers include headache, hypotension, dizziness, and
flushing of the skin. Reflex tachycardia can occur as a result of hypotension. Peripheral
 edema may occur with several CCBs.
• Nifedipine, in its immediate-release form, has been associated with an increased
incidence of sudden cardiac death, especially when prescribed in high doses for
outpatients.
• A cardiac dysrhythmia is defined as any deviation from the normal rate or pattern of the
heartbeat. This includes heart rates that are too slow, too fast, or irregular. The
electrocardiogram identifies the type of dysrhythmia.
• Atrial dysrhythmias prevent proper filling of the ventricles and decrease cardiac output.
• Ventricular dysrhythmias are life threatening because ineffective filling of the ventricle
and ineffective pumping result in decreased or absent cardiac output. With ventricular
tachycardia, ventricular fibrillation is likely to occur, followed by death.
• Cardiac dysrhythmias frequently follow a myocardial infarction or can result from
hypoxia, hypercapnia, thyroid disease, coronary artery disease, cardiac surgery, excess
catecholamines, or electrolyte imbalance.
• Electrolyte transfer occurs through the cardiac muscle cell membrane. When sodium and
calcium enter the cardiac cell, depolarization occurs. Sodium enters rapidly to start the
depolarization, and calcium enters later to maintain it. Calcium influx leads to an
increased release of intracellular calcium from the sarcoplasmic reticulum, resulting in
cardiac contraction. In the presence of myocardial ischemia, the contraction can be
irregular.
• The desired action of antidysrhythmic drugs is to restore the cardiac rhythm to normal.
The antidysrhythmics are grouped into four classes: (1) fast (sodium) channel blockers
IA, IB, and IC; (2) beta blockers; (3) drugs that prolong repolarization; and (4) slow
(calcium) channel blockers.
• A sodium channel blocker decreases sodium influx into cardiac cells. Responses to the
drug are decreased conduction velocity in cardiac tissues, suppression of automaticity,
and increased recovery time.
• Lidocaine, an IB sodium channel blocker, is still used by some cardiologists to treat acute
ventricular dysrhythmias. It slows conduction velocity and decreases action potential
amplitude.
• The drugs in the second class, beta blockers, decrease conduction velocity, automaticity,
and recovery time.
• Drugs in the third class prolong repolarization and are used in emergency treatment of
ventricular dysrhythmias when other antidysrhythmics are ineffective.
• The fourth class consists of the calcium channel blockers, which block calcium influx,
thereby decreasing the excitability and contractility of the myocardium. They increase the
refractory period of the atrioventricular node, which decreases ventricular response.
• Quinidine, the first drug used to treat cardiac dysrhythmias, has many side effects,
including nausea, vomiting, diarrhea, confusion, and hypotension. It can also cause heart
block and neurologic and psychiatric symptoms.
• High doses of lidocaine can cause cardiovascular depression, bradycardia, hypotension,
seizures, blurred vision, and double vision. Less-serious side effects may include
dizziness, lightheadedness, and confusion.
• The side effects of beta blockers are bradycardia and hypotension. They may also cause
 nausea, vomiting, and neurologic problems.
• The side effects of calcium blockers include nausea, vomiting, hypotension, and
bradycardia.
• It should be noted that all antidysrhythmic drugs are potentially prodysrhythmic. This is
because of both the pharmacologic activity of the drug on the heart and the inherently
unpredictable activity of a diseased heart, with or without the use of drugs.