Copyright 2014 by Mosby, an imprint of Elsevier Inc.

Lilley: Pharmacology and the Nursing Process, 7th Edition

Chapter 23: Antianginal Drugs

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ANATOMY, PHYSIOLOGY, AND PATHOPHYSIOLOGY OVERVIEW

The hearts oxygen supply is delivered to the heart muscle by means of the coronary arteries.
Under ischemic conditions when the myocardium is deprived of oxygen, the heart shifts to anaerobic
metabolism to meet its energy needs. One of the by-products of anaerobic metabolism is lactic acid.
Accumulation of lactic acid and other metabolic by-products causes the pain receptors surrounding the heart
to be stimulated, which produces the heart pain know as angina.
Angina pectoris (chest pain) occurs because of a mismatch between the oxygen supply and oxygen demand,
with either too high a demand for oxygen or too little oxygen delivery.
Coronary artery disease is an abnormal condition of the arteries that delivers oxygen to the heart muscle.
These arteries may become narrowed, which results in reduced flow of oxygen and nutrients to the
myocardium. Poor blood supply to an organ is referred to as ischemia. The condition is called ischemic
heart disease. When the coronary arteries that deliver oxygen to the heart muscle become blocked, a heart
attack or myocardial infarction (MI) occurs.
Many substances and situations can increase heart rate and contractility and oxygen demand, including
caffeine, exercise, and stress, and result in stimulation of the sympathetic nervous system, leading to
increased heart rate and contractility.
Some of the drugs used to treat angina are aimed at correcting the imbalance between myocardial oxygen
supply and demand by decreasing heart rate and contractility.
There are three classic types of chest pain, or angina pectoris.
o Chronic stable angina has atherosclerosis as its primary cause. Chronic stable angina can be
triggered by exertion or other stress, as well as nicotine in tobacco, alcohol, coffee, and other drugs
that stimulate the sympathetic nervous system. The pain of chronic stable angina is commonly
intense but subsides within 15 minutes of either rest or appropriate antianginal drug therapy.
o Unstable (preinfarction) angina is usually the early stage of progressive coronary artery disease,
often ending in an MI in subsequent years. Another term for this type of angina is crescendo angina,
because the pain increases in severity, as does the frequency of attacks. Later, pain may even occur
while the patient is at rest.
o Vasospastic angina results from spasms in the layer of smooth muscle that surrounds atherosclerotic
coronary arteries, often occurring at rest and without any precipitating cause, but following a regular
pattern, such as the same time of day. This type of angina is also called Prinzmetal angina or variant
angina.
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o Dysrhythmias and electrocardiogram (ECG) changes often accompany these different types of
anginal attacks.

PHARMACOLOGY OVERVIEW

The three main classes of drugs used to treat angina pectoris are the nitrates and nitrites, the beta blockers,
and the calcium channel blockers (CCBs).
There are three main therapeutic objectives of antianginal drug therapy: (1) minimizing the frequency of
attacks and decrease the duration and intensity of the anginal pain; (2) improving the patients functional
capacity with as few adverse effects as possible; and (3) preventing or delaying the worst possible outcome,
MI.
The overall goal of antianginal drug therapy is to increase blood flow to ischemic myocardium, decrease
myocardial oxygen demand, or both.

Nitrates or Nitrites
Nitrates have long been the mainstay for both the prophylaxis and treatment for angina.
The rapid- and long-acting nitrates available for clinical use include amyl nitrite (rapid acting), nitroglycerin
(both rapid and long-acting), isosorbide dinitrate (both rapid and long-acting), and isosorbide mononitrate
(primarily long-acting).
Nitrates dilate constricted coronary arteries, helping to increase the supply of oxygen and nutrients to the
heart muscle, but they also dilate all blood vessels, predominantly affecting venous vascular beds. However,
they also have a dose-dependent arterial vasodilator effect.
Nitroglycerin is the prototypical nitrate. Isosorbide dinitrates were the first group of oral drugs used to treat
angina; isosorbide mononitrates are new and improved nitrates.
Exercise-induced spasms in atherosclerotic coronary arteries can also be reversed or prevented by
administration of nitrates, encouraging healthy physical activity in patients.
The nitrates are used to treat stable, unstable, and vasospastic (Prinzmetal) angina.
Dosage forms include conventional tablets, translingual spray, controlled-release and sustained-release
capsules, transdermal patch, topical ointment, and intravenous injection.
If the goal of treatment is to abort or treat a sudden attack of angina, then rapid onset of action is needed,
such as with intravenous infusion, sublingual tablet, and/or translingual spray, with pharmacokinetics that
allow quick entry of the drug into the bloodstream.
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Long-acting dosage forms are used more for prevention of anginal episodes.
Nitrates are well tolerated, and most adverse effects are usually transient and involve the cardiovascular
system. The most common undesirable effect is headache, which generally diminishes soon after the start of
therapy. Other cardiovascular effects include tachycardia and postural hypotension.
If nitrate-induced vasodilation occurs too rapidly, the cardiovascular system overcompensates and increases
the heart rate, a condition referred to as reflex tachycardia.
Topical nitrate dosage forms can produce various types of contact dermatitis (skin inflammation), but these
are actually reactions to the dosage delivery system.
Tolerance to the antianginal effects of nitrates can occur surprisingly quickly in some patients, especially
those taking long-acting formulations or taking nitrates around the clock. Cross-tolerance arises when
patients receive more than one nitrate dosage form. To prevent this, nitrate-free periods allow certain
enzymatic pathways to replenish themselves.

Beta Blockers
Most available beta blockers demonstrate antianginal efficacy, although not all have been approved for this
use. Those approved are atenolol, metoprolol, nadolol, and propranolol.
When beta receptors are blocked by beta blockers, the rate at which the pacemaker (sinoatrial [SA] node)
fires decreases, and the time it takes for the node to recover increases. The beta blockers also slow
conduction through the atrioventricular node and reduce myocardial contractility. Both effects serve to slow
the heart rate and reduce myocardial oxygen demand, which aids in the treatment of angina by reducing the
workload of the heart.
Following an MI, there is a high level of circulating catecholamines that will produce harmful consequences
if their actions go unopposed. They cause the heart rate to increase, which leads to a further imbalance in the
supply-and-demand ratio, and irritate the conduction system of the heart, which can result in potentially
fatal dysrhythmias. The beta blockers block all of these harmful effects, and their use has been shown to
improve the chances for survival in patients after MI.
The beta blockers are most effective in the treatment of exertional angina because the usual physiologic
effects of an increase in the heart rate and systolic blood pressure that occurs during exercise or stress is
blunted by the beta blockers, thereby decreasing the myocardial oxygen demand. For an elderly patient with
significant angina, exercise may simply be carrying out the activities of daily living, such as bathing,
dressing, or cooking.
Systolic heart failure and serious conduction disturbances are contraindications to beta blockers.
The adverse effects of the beta blockers result from their ability to block beta-adrenergic receptors in
various areas of the body, resulting in a decrease in heart rate, cardiac output, and cardiac contractility,
bronchoconstriction, and increased airway resistance.
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Calcium Channel Blockers
There are three chemical classes of CCBs: phenylalkylamines, benzothiazepines, and dihydropyridines,
commonly represented by verapamil, diltiazem, and amlodipine, respectively.
Relaxation of the smooth muscles that surround the coronary arteries causes them to dilate, increasing blood
flow to the ischemic heart, which in turn increases the oxygen supply and helps shift the supply/demand
ratio back to normal.
Because of the CCBs very acceptable adverse effect and safety profiles, they are considered first-line drugs
for the treatment of such conditions as angina, hypertension, and supraventricular tachycardia and are
often effective for the treatment of coronary artery spasms (vasospastic or Prinzmetal angina).
The adverse effects of the CCBs are limited and primarily relate to overexpression of their therapeutic
effects.
In review, antianginal drugs such as nitrates, nitrites, beta blockers, and CCBs are used to reduce
ischemia by increasing the delivery of oxygen-rich blood to cardiac tissues or by reducing oxygen
consumption by the coronary vessels. Either of these mechanisms can reduce ischemia and lead to a
decrease in anginal pain.

NURSING PROCESS

Before antianginal drugs are administered, obtain a thorough past and present medical health history and
medication history, and document the findings. Also measure weight, height, and vital signs, with attention
to supine, sitting, and standing blood pressures.
If the patient is experiencing pain, include description of onset, character, intensity, location, duration,
precipitating factors, alleviating factors, and presence of nausea or vomiting.
Significant interactions include alcohol, beta blockers, CCBs, phenothiazines, and erectile dysfunction
drugs, such as sildenafil, tadalafil, and vardenafil. Taking these drugs with nitrates will result in worsening
of hypotensive responses, paradoxical bradycardia, and a resultant increase in angina with subsequent
significant risk of cardiac or cerebrovascular complications due to the decreased perfusion.
Elderly patients often have difficulty with blood pressure control because of the occurrence of normal age-
related periods of hypotension, and the use of antianginals may lead to worsening of hypotensive responses.
Concerns arise with the use of nonselective beta blockers and beta
2
blockers in patients with bronchospastic
disease because of the drug-related effects of bronchoconstriction and increased airway resistance, which
results in wheezing and dyspnea as adverse effects.
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In patients taking CCBs, assess for possible drug-food interactions and toxicity, including grapefruit juice,
which reduces the metabolism of nifedipine.
Assess patients taking ranolazine (Ranexa), one of the newest antianginal drugs, for liver dysfunction
through specific liver function testing before taking the medication.
Always review and/or record the patients vital signs and description of chest pain for the duration of
therapy.
Carefully dispose of used, unneeded, or defective transdermal patches of any medication as indicated by
hospital policy or per discharge instructions.
Include in your evaluation a review for accomplishment of goals and outcomes, such as appropriate
decrease in blood pressure, increase in cardiac output and tissue perfusion with decrease in angina, and a
gradual increase in activity and performance of activities of daily living without exacerbation of anginal
episodes.
CCBs and beta blockers may be associated with the adverse effects of postural hypotension, dizziness,
headache, and edema. The nonselective beta blockers may exacerbate congestive heart failure, problems
related to respiratory bronchospasm, and hypoglycemia. Check the patients pulse rate before drug
administration, and if it is 60 beats/min or lower, contact the prescriber for further instructions.
Instruct patients to always keep a fresh supply of sublingual nitroglycerin on their person and in their home
because the drug is stable for only 3 to 6 months.