Unit 9 Drugs Acting On The Cardiovascular System

Republic of the Philippines
Bulacan State University

City of Malolos
NCM 106 - Pharmacology
Drugs Acting on the Cardiovascular System
Prepared by:
Christopher E. Olipas, Ph.D.
Carmina O. Fabonan, RN
Marlyn Molina, MAN
A.Y. 2020-2021- 1st Semester
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Introduction
The cardiovascular or circulatory system consists of the heart , blood vessels and
blood. The general duties of the system are to distribute oxygen, calories, hormones,
antibodies and other compounds to all cells of the body and to extract waste products
from cell metabolism (carbon dioxide and others). The effectiveness of the machine
depends on the ability of the heart to pump blood, the disease and operation of the blood
vessels, and the consistency and quantity of blood.
Cardiovascular diseases, which are general causes of morbidity and death, are
often caused by defects in the blood vessels. In contrast, most vascular disorders are
caused by endothelial cell dysfunction or smooth muscle cells. Dysfunctional endothelial
dysfunction is known to be a significant cause in atherosclerosis, acute coronary
syndromes (symptomatic myocardial ischemia, asymptomatic myocardial infarction [MI],
and MI with or without ST-segment elevation), hypertension, and thromboembolic
diseases. The primary cause of endothelial dysfunction is damage to the wall of the blood
vessel due to infection or illness. Injury changes the usual regulatory processes which
results in vasospasm, thrombosis, expansion of the intimate layer of the blood flow,
rupture of the atherosclerotic plaque, ischemia which infarction of the heart, and
dysrhythmia. Pathological alterations in the composition of capillary and venous
endothelium often result in the deposition of extra fluid in interstitial space (edema), a
typical symptom of cardiovascular and other disorders.
Overall, cardiovascular diseases may include any form or feature of the
cardiovascular system. Since the circulatory system is a closed system, a disorder in one
part of the system inevitably disrupts the operation of all other parts of the system.
Cardiovascular conditions commonly treated with drug treatment include atherosclerosis,
heart disease, cardiac dysrhythmia, ischemia, myocardial infarction , stroke, hypotension,
and shock. Peripheral artery disease and valve disease are typically surgically treated.
Blood conditions that react to opioid treatment include some forms of anemia and
coagulation conditions.
The goal of drug therapy in cardiovascular disorders is to restore homeostasis or
physiologic balance between opposing factors like coagulant vs. anticoagulant,
vasoconstriction vs. vasodilation. Cardiovascular drugs may be given to increase or
decrease cardiac output, blood pressure, and heart rate; to alter heart rhythm; to increase
or decrease blood clotting; to alter the quality of blood; and to decrease chest pain of
cardiac origin. In addition, these drugs may be given for palliation of symptoms without
alteration of the underlying disease process.
This particular module is divided into 7 lessons:

● Lesson 1 Anti-Hypertensive Agents
● Lesson 2 Cardiotonic Agents
● Lesson 3 Antidysrhythmic Agents
● Lesson 4 Antianginal Agents
● Lesson 5 Lipid Lowering Agents
● Lesson 6 Drugs Affecting Blood Coagulations
● Lesson 7 Drugs Used to Treat Anemias
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As you navigate at the end of this module, you are expected to accomplish
competencies given below.
Objectives/Competencies
Upon completion of this module, you are expected to:
1. Explain the importance of the different drugs based on their
classification, it’s identified therapeutic actions, side effects and
adverse effects.
2. Apply the nursing process in drug therapy and patient safety.
3. Formulate a health teaching plan.
Pre-test. Multiple Choice. Circle the option that best answers the question or
completes the statement.
1. Renin induces the transfer of angiotensinogen to angiotensin I in the liver; angiotensin
I transforms ACE to angiotensin II in the lungs; angiotensin II then interacts with
particular receptor sites in the blood vessels to induce vasoconstriction to increase
blood pressure and to induce aldosterone release in the adrenal gland, which
contributes to fluid accumulation and increased blood flow.
a. True
b. False
c. Partly true
d. Partly false
2. Hypertension is a prolonged level of higher-than-nor-mal blood pressure that can lead
to injury to blood vessels, increased risk of atherosclerosis, and injury to small arteries
in the final organs. Since hypertension also has no signs or effects, it's considered a
silent killer.
a. True
b. False
c. First sentence is true, second sentence is false.
d. Second sentence is true, first sentence is false.
3. Important hypertension has no root cause, and treatment can differ significantly from
person to person. Treatment methods require behavioral improvements first, followed
by diligent use and application of multiple antihypertensive medications.
a. True
b. False
4. Atrial fibrillation is the most frequent form of dysrhythmia.
a. True
b. False
c. Partly true
d. Partly false
5. The activation of an electrical impulse relies mainly on the movement of sodium and
calcium ions into the myocardial cell and the movement of potassium ions out of the
cell.
a. True
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b. False
c. Partly true
d. Partly false
6. Tolerance to vascular and anti-anginal effects can grow with topical administration. To
mitigate this, begin with the smallest possible dosage and extract nitroglycerin (paste
or transdermal patches) from the patient for 10 to 12 hours a day (usually overnight).
a. True
b. False
7. Nitroglycerin loses its effectiveness when exposed to light, moisture, humidity and
disposable IV fluid bags.
a. True
b. False
c. Partly true
d. Partly false
8. Assess the blood pressure and pulse of the patient before and during nitroglycerin
treatment, as the medication can induce hypotension and reflex tachycardia.
a. True
b. False
c. Partly true
d. Partly false
9. The newest drug used to cure angina is ranolazine, a derivative of piperazine. It is not
clear precisely how angina reduces, but it is recognized that the drug causes more
sodium current to be stimulated and prolongs the potential for ventricular activity. It is
presumed that ranolazine can shift the metabolism of the cardiac muscle from fatty
acids to carbohydrates. The most frequent side effects of ranolazine are not severe
(dizziness, vomiting, constipation, and nausea). The most severe adverse effect is the
prolongation of the QT interval, which can lead to a type of ventricular tachycardia
referred to as torsades de pointes.
a. True
b. False
10. Adjunct drug treatment used in people with angina involves aspirin (including other
anti-platelet medications such as clopidogrel including glycoprotein IIb / IIIa receptor
antagonists), heparin, and lipid-lowering agents. These treatments do not minimize
the oxygen requirement for the heart, but hinder the development of coronary artery
disease or prevent / treat problems that may occur with angina. Morphine can be used
during acute angina attacks (acute coronary syndrome) to relieve pain and provide
some coronary vasodilation.
a. True
b. False
11. Some fats are transformed into HDLs that are capable of extracting fats and residues
from the periphery and provide a defensive impact against the growth of CAD.
a. True
b. False
c. Partly true
d. Partly false
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12. Cholesterol is an essential fat used to produce bile acids. It is the basis for steroid
hormones and provides the required support for cell membranes. Cholesterol can be
formed in all cells.
a. True
b. False
13. HMG-CoA reductase is an enzyme which controls the final step in the development of
cellular cholesterol.
a. True
b. False
c. Partly true
d. Partly false
14. Patients taking lipid-lowering medications need to make improvements in diet ,
exercise and lifestyle to reduce the risk of CAD.
a. True
b. False
c. Partly true
d. Partly false
15. Bile acid sequestrants bind to bile acids in the intestine which contribute to excretion
of the feces. This results in lower levels of bile acid as the liver uses cholesterol to
generate more bile acids. The end effect is a drop in serum cholesterol and LDL levels
when the liver adjusts the synthesis of these fats to satisfy the requirement for more
bilious acids.
a. True
b. False
c. Partly true
d. Partly false
16. Wetatic medications are used to avoid bleeding. They can replace missed clotting
factors or prevent the dissolving of shaped clots by the plasminogen system.
a. True
b. False
17. Hemophilia, a hereditary shortage of essential clotting agents, contributes to
prolonged bleeding. It is handled by substituting essential clotting factors.
a. True
b. False
18. Anemia is a condition of too few RBCs or inefficient RBCs. Anemia can be caused by
a lack of erythropoietin or by a lack of the components required for RBC ducts.
a. True
b. False
c. Partly true
d. Partly false
19. Iron deficiency anemia happens where there is a loss of iron consumption in the diet
or an inability to consume iron from the GI tract. Iron is required to make hemoglobin
that holds oxygen. Iron deficiency anemia is treated by the removal of iron.
a. True
b. False
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20. Iron is a particularly poisonous product at high doses. The body governs the
accumulation of iron and closely governs its concentration and movement inside the
body.
a. True
b. False
c. Partly true
d. Partly false
21. Folic acid and vitamin B12 are required to create a solid support network in the RBC
so that it can withstand 120 days of propulsion through the vascular system. They are
generally present in sufficient proportions in the diet. Deficiencies are treated by the
substitution of folic acid and vitamin B12.
a. True
b. False
22. Dietary deficiency or failure to absorb folic acid, vitamin B12, or both can cause
megaloblastic anemia in which RBCs are large and unstable and short-lived.
a. True
b. False
c. Partly true
d. Partly false
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Title of the Lesson: Anti-Hypertensive Agents
Duration: 2 hours
Antihypertensive medications are used to control hypertension, a widespread

chronic condition that affects an estimated 50 to 60 million adults and an undisclosed
number of children and teenagers in the United States. Hypertension raises the risk of
myocardial infarction, cardiac attack, brain infarction and hemorrhage, and kidney
disease. In order to consider hypertension and antihypertensive drug treatment, it is first
important to understand the biochemical processes that usually regulate blood pressure,
the symptoms of hypertension and the symptoms of antihypertensive medications.
Arterial blood pressure represents the blood flow exerted on the arterial walls.
Blood pressure usually maintains stable due to homeostatic processes that regulate blood
supply to satisfy tissue needs. The cardiac output (systolic pressure) and peripheral
vascular resistance (diastolic pressure) are the two main determinants of arterial blood
pressure.
Cardiac output is equal to the cardiac output and the volume of stroke (CO = HR
(SV). Stroke volume is the amount of blood produced by each heartbeat (approximately
60–90 mL). Thus, cardiac production depends on the intensity of myocardial contraction,
blood supply, and other influences. Peripheral vascular resistance is measured by local
blood flow and by the degree of constriction or dilation of arterioles and arteries (vascular
tone).
When hypotension (and reduced tissue perfusion) occurs, SNS is activated,
epinephrine and norepinephrine hormones are secreted by the adrenal medulla,
angiotensin II and aldosterone, and the kidneys maintain blood. These countervailing
processes increase blood pressure. Relevant results shall contain the following:
o Constriction of arterioles, which enhances peripheral artery resistance;
o Constriction of veins and increased vein tone
o Stimulation of beta-adrenergic cardiac receptors
o Increases heart rate and myocardial contraction intensity
o Activation of the process of renin – angiotensin – aldosterone
When blood pressure is raised, the following series of events occurs:
● Kidneys excrete more fluids (increase urinary output).
● Fluid deficiency decreases both the amount of extracellular fluid and blood
● Volume, guy.
● Decreased blood volume decreases venous blood supply to the heart and thus
lowers cardiac output.
● Decreased heart output decreases blood pressure.
● Vascular endothelium contains vasodilating agents (e.g. nitric oxide,
prostacycline) that minimize blood pressure.
Hypertension is a persistently elevated blood pressure due to defects in regulatory
processes. It is generally classified as systolic pressure above 140 mm Hg or diastolic
pressure above 90 mm Hg for multiple blood pressure measurements.
Main or necessary hypertension (that for which no cause can be found) accounts for
between 90% and 95% of identified cases. Secondary hypertension can result from renal,
endocrine, or central nervous system disorders and drugs that activate SNS or cause
sodium and water retention. Main hypertension can be managed by effective therapy;
secondary hypertension can also be treated by surgery.
The Seventh Report of the Joint National Committee on the Prevention , Diagnosis,
Assessment and Treatment of High Blood Pressure (JNC 7), issued in 2003, listed blood
pressures in adults (in mm Hg) as follows:
● Standard = systolic < 120 and diastolic < 80;
● Prehypertension = systolic 120–139 or 80–89 diastolic
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● Step 1 hypertension = systolic 140-159 or diastolic 90-99
● Phase 2 hypertension = systolic > 160 or diastolic 100 or more
This classification is markedly different from the four previously identified phases.
The inclusion of a prehypertension stage is aimed at people who are twice as likely to
move to hypertension as those with lower pressure values. Stages 3 and 4 were
withdrawn. These newer recommendations also suggest maximum blood pressure for
people with diabetes or kidney failure of less than 130/80 mm Hg. A systolic pressure of
140 or higher, with a diastolic pressure below 90, is termed late systolic hypertension and
is most frequent in the elderly. New JNC8 recommendations are scheduled to be issued
in 2009.
Hypertension significantly changes cardiovascular activity by increasing the
workload of the heart and inducing thickening and sclerosing of the arterial walls. As a
result of elevated cardiac workload, myocardial hypertrophy as a countervailing process
and heart failure will inevitably occur. As a result of endothelial dysfunction and arterial
changes (vascular remodeling), the arterial lumen is shortened, the blood flow to the
tissues is diminished and the chance of thrombosis is increased. In comparison, necrotic
areas may form in the arteries and may break with prolonged high blood pressure. The
regions most badly affected are the heart, the brain, the kidneys, and the eyes. This are
also referred to as goal organ
Drugs included in the treatment of primary hypertension belong to a variety of
various classes, including angiotensin converting enzyme ( ACE ) inhibitors; angiotensin
II receptor blockers (ARBs), sometimes referred to as angiotensin II receptor antagonists
(AIIRAs); antiadrenergics; calcium channel blockers; diuretics; and direct vasodilators. In
general, these medications minimize blood pressure by reducing heart output or
peripheral vascular resistance.
MEDICATIONS DESCRIPTION
Angiotensin-Converting Angiotensin-converting enzyme (also known as kininase)
Enzyme Inhibitors is specifically found in the endothelial lining of the blood
vessels, and is the site of development of most
angiotensin II. The same enzyme also metabolizes
bradykinin, an endogenous product with significant
vasodilating effects.
ACE inhibitors suppress the enzyme that usually
transforms angiotensin I into powerful vasoconstrictor
angiotensin II. By blocking the production of angiotensin
II, drugs reduce vasoconstriction (which has a vasodilating
effect) and reduce the production of aldosterone (reducing
sodium and water retention). In addition to inhibiting the
production of angiotensin II, the medications also prevent
the degradation of bradykinin by prolonging its
vasodilating effects. These and probably other effects help
inhibit or reverse cardiac muscle and blood vessel wall
remodeling that impairs cardiovascular function and
exacerbates cardiovascular disease processes.
ACE inhibitors can be used on their own or in conjunction
with other antihypertensive drugs, such as thiazide
diuretics.
Some ACE inhibitors (captopril, enalapril, fosinopril,
lisinopril, ramipril, and quinapril) are also used to regulate
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heart failure by decreasing peripheral vascular resistance,
cardiac workload, and ventricular remodeling.
ACE inhibitors are well absorbed by oral injection, develop
results within 1 hour that last nearly 24 hours, have
extended serum half-lives with reduced renal function, and
others are metabolized to active metabolites that are
excreted in urine and feces. These medications are well
tolerated and have a reduced frequency of severe adverse
reactions ( e.g., neutropenia, agranulocytosis, proteinuria,
glomerulonephritis, angioedema).
Angiotensin II Receptor Angiotensin II receptor blockers (ARBs) have been
Blockers developed to inhibit the powerful blood pressure-raising
activity of angiotensin II. Instead of reducing the
development of angiotensin II, as do ACE inhibitors, these
drugs compete with angiotensin II for tissue binding sites
and prohibit angiotensin II from being paired with its
receptors in body tissues. While several types of receptors
have been identified, most of the effects of angiotensin II
on cardiovascular and renal function are determined by
AT1 receptors found in brain, renal, myocardial, vascular
and adrenal tissue. ARBs block angiotensin II AT1
receptors and reduce blood pressure by decreasing
systemic vascular resistance. These medications are
close to ACE inhibitors in their impact on blood pressure
and hemodynamics and are as effective as ACE inhibitors
in the treatment of hypertension and probably heart failure.
They are less likely to cause hyperkalemia than ACE
inhibitors, and chronic cough is rare. Overall, the
medications are well tolerated and the frequency of most
adverse reactions is close to that of placeboHowever,
during breastfeeding, the FDA released a BLACK BOX
WARNING for medications that specifically affect the
renin-angiotensin system as their use may cause damage
and even death to a developing fetus.
Losartan, the first ARB, is easily absorbed and quickly
metabolized to the active metabolite by the cytochrome
P450 liver enzymes. Both losartan and its metabolite are
strongly bound to plasma albumin, and losartan has a
shorter time of action than its metabolite.However, during
breastfeeding, the FDA released a BLACK BOX
shorter time of action than its metabolite.However, during
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breastfeeding, the FDA released a BLACK BOX
shorter time of action than its metabolite. Maximum effects
on blood pressure typically develop within 3 to 6 weeks
after losartan treatment is begun. If losartan may not
regulate blood pressure on its own, a low dose of diuretic
can be inserted. A mixture of losartan and
hydrochlorothiazide is available.
Antiadrenergics Antiadrenergic (sympatholytic) medications block SNS
activity. As the SNS is activated (see Chapter 16), the
nerve impulse travels from the brain and the spinal cord to
the ganglia. From the ganglia, the impulse passes through
the postganglionic fiber to the effector organs ( e.g., the
heart, the blood vessels). Although SNS stimulation
causes widespread effects in the body, the effects of
increased heart rate, myocardial contraction, cardiac
activity , and blood pressure are important to this debate.
When the nerve impulse is hindered or diverted at some
place in its pathway, the result is a drop in blood pressure.
Alpha1-adrenergic receptor antagonists (e.g., prazosin)
dilate blood vessels and decrease peripheral vascular
resistance. This medications may be used on their own or
in multidrug regimens. One side reaction, named the first
dose syndrome, results in orthostatic hypotension with
palpitations, dizziness, and likely syncope 1 to 3 hours
after the first dose or elevated dosage. First doses and first
increased doses are taken at bedtime to avoid this effect.
Another effect associated with long-term or higher doses
contributes to sodium and fluid accumulation and the need
for ongoing diuretic treatment. Centrally acting
sympatholytics (e.g., clonidine) activate presynaptic
alpha2 receptors in the brain and are known as an alpha2
receptor agonist. As these medications are used, less nor-
epinephrine is released and the sympathetic outflow from
the vasomotor core is decreased.
Beta-adrenergic blocking agents (e.g., propranolol)
improve heart rate, myocardial contraction power, cardiac
production, and kidney release. BLACK BOX WARNING
has been given by the FDA to patients with CAD who
withdraw from oral formulations of atenolol, metoprolol,
nadolol, propranolol and timolol; sudden removal has
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resulted in exacerbation of angina, prevalence of
ventricular dysrhythmias and frequency of MIs.
Some antiadrenergic agents include alpha blockers
(phentolamine and phenoxybenzamine) that are
sometimes used in hypertension due to excess
catecholamine.
Calcium Channel Calcium channel blockers (e.g. verapamil) are used for a
Blocking Agents variety of cardiovascular diseases. The method of action
and usage for the treatment of tachydysrhythmias and
angina pectoris was discussed in chapters 49 and 50,
respectively. In hypertension, medications primarily dilate
peripheral arteries and reduce peripheral vascular
resistance by relaxing smooth artery muscles.
Many of the available medicines are licensed for use in
hypertension. Nifedipine, a short-acting calcium channel
blocker, has been used to treat hypertensive cases or
cases, either by puncturing the capsule and crushing the
contents under the tongue or by biting the patient and
swallowing the pill. Such use is no longer recommended,
since this procedure is associated with an elevated risk of
adverse cardio-vascular conditions precipitated by a
sudden and serious drop in blood pressure.
As a group, calcium channel blockers are well absorbed
from the gastrointestinal tract following oral administration
and are highly protein bound. The medicines are
metabolized in the liver and excreted in the urine.
Diuretics Antihypertensive symptoms of diuretics are commonly
due to sodium and water loss. In fact, diuretics typically
show the same effects as extreme sodium dietary
restrictions. In several cases of hypertension, diuretic
therapy alone can relieve blood pressure. Once diuretic
treatment is initiated, blood volume and heart activity
decline. With long-term diuretic administration, the cardiac
output returns to normal, but there is a persistent decline
in peripheral vascular resistance. This was due to a
consistent slight drop in extracellular water and plasma
content, reduced receptor sensitivity to vasopressant
compounds such as angiotensin, primary arteriolar
vasodilation, and arteriolar vasodilation secondary to
electrolyte depletion in the vessel surface. In mild to
extreme hypertension that may not lead to diuretics alone,
the diuretic may be continued and an alternative
antihypertensive treatment to monotherapy may be used
for a different sort of antihypertensive medication.
Thiazide diuretics (e.g. hydrochlorothiazide) are most
widely used for hypertension treatment. Loop diuretics
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(e.g. furosemide) or potassium-sparing diuretics (e.g.
spironolactone) can be effective in some conditions.
Vasodilators (Direct Vasodilator antihypertensive medications immediately
Acting) stimulate smooth muscles in the blood vessels , resulting
in dilation and reduced peripheral vascular resistance.
They often minimize postload and can be used in the
treatment of heart disease. Hydralazine and minoxidil
work primarily on arterioles; nitroprusside works on
arterioles and venoles. This medications have a minimal
effect on hypertension when administered on their own
since the vasodilating activity that decreases blood
pressure often activates the SNS and causes reflexive
countervailing responses (vasoconstriction, tachycardia,
and increased cardiac output) that increase blood
pressure. This influence can be avoided during long-term
treatment by the application of a drug that avoids
unnecessary sympathetic activation (e.g. propranolol, an
adrenergic blocker).These medications can induce
sodium and water accumulation, which can be reduced by
concomitant diuretic treatment. The FDA has issued
BLACK BOX Notice for minoxidil, as the medication can
intensify angina and precipitate pericardial effusion (which
can progress to cardiac tamponade). 1
Self-Check 1. Case Presentation
Mr. Kimchi is a 55-year-old man of African-American origin. He’s married, has four
daughters, and works as a car salesman. Mr. Kimchi has been developing hypertension
for the last 15 years. Its current drug prescription for maintaining blood pressure below
140/90 mm Hg consists of:
Valsartan 80 mg PO daily
Amlodipine 10 mg PO daily
Hydrochlorothiazide 12.5 mg PO daily
a. Mr. Kimchi is noncompliant with his drug regimen. How should you react?
1
Abrams, A. C., Lammon, C. B., & Pennington S. S., (2009). Clinical drug therapy rationales for
nursing practice. 9th ed. Lippincottt Williams & Wilkins, Chapter 52.
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b. The JNC 7 developed detailed recommendations for the treatment of patients
with hypertension. What do you teach a hypertensive patient about the
guidelines?
c. Mr. Kimchi asks you why amlodipine was chosen to control his hypertension.
What is the most appropriate response?
For further reading you may consult both the reference used in this unit by Abrams,
A. C., Lammon, C. B., & Pennington S. S., (2009). Clinical drug therapy rationales for
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Title of the Lesson: Cardiotonic Agents
Duration: 2 hours
Cardiotonic agents are medications used to improve the con-tractility of the heart
muscle in patients with heart failure (HF). Heart failure ( HF) is a disease in which the
heart fails to pump blood efficiently throughout the body. Since the cardiac cycle usually
requires a strong equilibrium between the pumping of the right and left sides of the heart,
every failure of the muscle to pump the nocturnal nerve: rising to the vacuum at night,
indicating increased renal perfusion with fluid changes in the supine position when a
person has a cardiac-dependent oedema due to heart failure. Other medical problems,
including urinary tract infection, increase the need to get up and empty orthopnea: trouble
breathing while lying down, also referred to as the amount of pillows required to enable a
person to breathe safely in a supportive inotropic: impact resulting in increased intensity
of pulmonary oedema contraction: extreme left-sided heart failure with backup of blood
to the lungs; If this continues, the blood vessels will become congested; finally, the body's
cells will be depleted of oxygen and nutrients , and waste products will build up in the
tissues. Main therapy for HF includes encouraging the heart muscle to contract more
effectively and maintain the rhythm of the mechanism.
Since the successful injection of blood into the tissues is necessary for survival,
the body has a variety of countervailing mechanisms that operate when the heart muscle
starts to malfunction. Decreased cardiac production activates the baroreceptors in the
aortic arc and the carotid arteries, triggering a positive stimulus. This sympathetic stimulus
induces an improvement in heart rate , blood pressure, and respiration rate and intensity,
as well as a positive inotropic effect, which is also known as an increase in the frequency
of the heart contraction and an improvement in blood volume via the release of
aldosterone. Decreased cardiac production also triggers the release of renin from the
kidneys and induces the renin – angiotensin – aldosterone pathway, which therefore
raises blood pressure and blood flow.
Compensation happens as these processes function successfully, and the patient
does not show signs or symptoms of HF. Over time, however, all these results improve
the workload of the heart and lead to the further production of HF. Eventually, the heart
muscle became overstretched by the elevated workload, and the chambers of the heart
are dilated due to the increased amount of blood they have to cope with. This hypertrophy
(enlargement) of the heart muscle, called cardiomegaly, leads to inadequate pumping
and ultimately increased HF.
Myocardial cells have been modified with extended HF. Unlike healthy heart cells,
the deficient heart cells tend to lack the capacity to generate the energy required for
successful contractions. Movement of calcium ions into and out of the cell is no longer
effective, leading to further weakening since the muscles contract ineffectively and are
unable to supply blood to the heart muscle.
Several different methods are used for the treatment of HF. This chapter focuses
on cardiotonic drugs often referred to as inotropic drugs that function specifically to
enhance the strength of cardiac muscle contraction. Some drug treatments used to treat
HF include:
Vasodilators Vasodilators, such as angiotensin-converting enzyme
(ACE ) inhibitors and nitrates, reduce cardiac workload,
relax vascular smooth muscle to reduce postload, and
allow vein pooling, thus reducing the preload of the heart
and helping to enhance function. In 2005, a combination
drug containing nitrate and vasodilator was expressly
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approved for the treatment of HF in African American
patients. Diuretics minimize blood flow, which lowers
venous return and blood pressure, resulting in reduced
postload, preload and cardiac workload.
Beta-adrenergic Beta-adrenergic agonists activate beta receptors in the
Agonists sympathetic nervous system, increase calcium distribution
to the myocardial cells and induce increased con-traction,
a beneficial inotropic reaction. Other sympathetic stimulus
effects can induce increased HF because the workload of
the heart is increased by the most sympathetic action.
Human B-type Human B-type natriuretic peptides are typically developed
Natriuretic Peptides by myocardial cells as a countervailing response to
increased cardiac workload and increased activation by
stress hormones. They bind to endothelial cells , leading
to dilation, resulting in reduced venous return, peripheral
resistance, and cardiac workload. They also disrupt the
body's response to stress hormones, leading to increased
fluid loss and a further reduction in cardiac workload.
Nesiritide (Natrecor) is the only drug commercially active
in a family of medicines called human B-type peptides.
Cardiotonic (inotropic) medications affect intracellular calcium levels in the heart
muscle, resulting in improved contractility. This increase in contraction strength
contributes to increased cardiac activity, which leads to increased renal blood flow and
increased production of urine. Increased renal blood supply inhibits the release of renin,
interferes with the action of the renin – angiotensin – aldosterone mechanism, and raises
the processing of urine, leading to a reduction in blood volume. The effect is a reduction
in cardiac workload and relief of HF Two types of cardiotonic drugs are used: classic
cardiac glycosides, which have been used for hundreds of years, and newer
phosphodiesterase inhibitors.
Cardiac Glycosides Cardiac glycosides were initially extracted from foxglove
or digitalis species. These plants were once grounded for
the development of the digitalis leaf. Still, digoxin
(Lanoxin) is the most effective drug used to treat HF.
Therapeutic actions Digoxin increases intracellular calcium and helps more
and indications calcium to reach myocardial cells during depolarization,
resulting in the following effects:
● Increased intensity of myocardial contraction
(positive inotropic effect)
● Increased cardiac production and renal perfusion
(which has a diuretic effect, increased urinary
production and decreased blood volume while
reducing renin release and stimulating the renin –
angiotensin – aldosterone system)
● Slow heart rate due to slowing of cellular
repolarization (negative chronotropic effect)
● Decreased conduction velocity of the
atrioventricular (AV) node
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The net result is a reduction in myocardial work-load and
relief of HF. Digoxin is recommended for the prevention of
HF, atrial flutter, atrial fibrillation and atrial paroxysmal
tachycardia. Digoxin has a very low safety margin
(meaning that the medicinal dosage is very close to the
harmful dosage), so great caution must be taken when
utilizing this drug.
Pharmacokinetics Digoxin is available for oral and parenteral use. The drug
has a fast onset of action and fast absorption (30–120
minutes when ingested orally, 5–30 minutes when
delivered intravenously). It is uniformly spread throughout
the body. Digoxin is excreted virtually unchanged in the
urine. Caution may also be practiced in the case of renal
dysfunction, as the drug should not be excreted and may
persist causing toxicity.
Contraindications and Cardiac glycosides are contraindicated to avoid
Cautions hypersensitivity reactions in the presence of allergy to any
part of the digitalis preparation. Digoxin is contraindicated
under the following conditions: ventricular tachycardia or
fibrillation, which are potentially dangerous arrhythmias
and should be treated with other drugs; heart block or sick
sinus syndrome, which may be worsened by reducing
conduction through the AV node; Idiopathic hypertrophic
subaortic stenosis (IHSS) because the increase in
contraction force can obstruct the outflow to the aorta and
cause serious problems; acute MI because the increase in
contraction force can trigger more muscle damage and
infarction; renal insufficiency because the drug is excreted
through the kidneys and toxic levels can develop; and
electrolyte irregularities.
Digoxin should be treated with caution in patients who are
pregnant or breastfeeding due to possible adverse effects
on the fetus or neonate. It is not understood if digoxin
induces fetal toxicity; it can only be administered during
pregnancy if the benefit to the mother obviously outweighs
the risk to the fetus. Digoxin reaches breast milk, but it has
not been shown to cause neonate disorders. Caution
should, however, be practiced during lactation. Pediatric
and geriatric patients are also at greater risk for allergic
reactions and should be carefully watched.
Adverse Effects Adverse effects most often associated in cardiac
glycosides include pain , fatigue, somnolence, and visual
changes (a yellow halo surrounding objects is frequently
reported). GI upset and anorexia are also popular.
Arrhythmias can evolve because glycosides impair the
capacity for action and the conduction of the heart. Digoxin
toxicity is a severe condition that can arise when digoxin
levels are too high. The patient may have pre-sent
Page | 16
anorexia, fatigue , anxiety, malaise, exhaustion, abnormal
heart rhythms, including heart block, atrial arrhythmias,
and ventricular tachycardia. This could be a life-
threatening condition. An antidote digoxin, digoxin
Immune Fab has been developed for the accelerated
treatment of digoxin toxicity.
Clinically Important There is a chance of improved clinical impact and harmful
Drug-Drug Interactions effects of digoxin when taken with verapamil, amiodarone,
quinidine, quinine, erythromycin, tetracycline or
cyclosporine. If digoxin is mixed with either of these
medications, the dosage of digoxin may need to be
reduced to avoid toxicity. If one of these medications has
become part of the digoxin protocol and is discontinued,
the dosage of digoxin may need to be raised. The risk of
cardiac arrhythmias can increase if these drugs are used
with potassium-losing diuretics. If this mixture is used, the
potassium level of the patient should be tested periodically
and the required replacement should be performed.
Digoxin can be less effective when paired with thyroid
hormones, metoclopramide, or penicillamine, and an
elevated dosage of digoxin may be needed. Absorption of
oral digoxin may be reduced if taken with cholestyramine,
charcoal, colestipol, antacids, bleomycin,
cyclophosphamide, or methotrexate. If used in conjunction
with both of these agents, the drugs should not be given
at the same time but should be administered 2 to 4 hours
apart.
Phosphodiesterase Phosphodiesterase inhibitors are part of a second class of
Inhibitors medicines that function as cardiotonic (inotropic) agents.
This involve milinone (Primacor).
Therapeutic actions Phosphodiesterase inhibitors are blocking the enzyme
and indications phosphodiesterase. This blocking effect contributes to an
increase in the cyclic adenosine monophosphate (cAMP)
myocardial cell, which raises the calcium level in the cell.
Elevated cellular calcium induces greater relaxation and
prolongs the symptoms of sympathetic stimulation, which
may contribute to vasodilation, increased oxygen
absorption, and arrhythmias. These medications are
recommended for short-term therapy of HF that did not
respond to digoxin or diuretics alone or had a weak
reaction to digoxin, diuretics and vasodilators. As these
medications have been linked with the production of
potentially lethal ventricular arrhythmias, their usage is
limited to certain cases.
Page | 17
Pharmacokinetics Inamrinone and milrinone are only available for
intravenous use. This medications are generally
administered after injection. They are metabolized in the
liver and excreted mostly in the urine.
Contraindications and Phosphodiesterase inhibitors are contraindicated in the
Cautions case of allergy to one of these medications or bisulphites
to prevent hypersensitivity reactions. They are also
contraindicated in the following conditions: extreme aortic
or pulmonary valvular disease, which could be worsened
by increased contraction; acute MI, which could be
worsened by increased oxygen intake and increased
contraction strength; a deficiency in the amount of fluid
that could be intensified by increased renal perfusion; and
ventricular arrhythmias, which could be exacerbated by
the rise in the concentration of oxygen.
Caution should be practiced in older people who are most
likely to have allergic reactions. There are no sufficient
reports on the efficacy of these medications during birth,
and their use should be reserved for cases where the
benefit to the mother obviously outweighs the possible
harm to the child. It is not clear if these medications reach
breast milk, so caution should be practiced while the
woman is breast-feeding.
Adverse Effects Adverse effects most often associated in these
medications include ventricular arrhythmias (which may
lead to severe ventricular fibrillation), hypotension, and
chest discomfort. The symptoms of GI include nausea,
fatigue, anorexia, and stomach pain. Thrombocytopenia
occurs often with inamrinone, and can also occur with
milrinone. Hypersensitivity reactions associated with
these medications include vasculitis, pericarditis, pleuritis,
and ascites. Burning at the intravenous injection site is
also a common adverse reaction.
Clinically Important Precipitates form as these medications are provided in a
Drug-Drug Interactions furosemide solution. Avoid this remedy mix. Using
substitute lines if any of these medications are delivered
intravenously.
MEDICATION USUAL DOSAGE USUAL INDICATIONS

Cardiac Glycoside Adult: loading dose 0.75– Acute heart failure (HF)
1.25 mg PO or 0.125– medication, atrial
digoxin (Lanoxin)
0.25 mg IV, then arrhythmias
maintenance dose of
0.125–0.25 mg/d PO;
decrease dose with renal
impairment
Page | 18
Pediatric (dose based on
age): 10–60 mcg/ kg PO
or 8–50 mcg/kg IV
loading dose;
maintenance is 25%–30%
of loading dose
Phosphodiesterase 50 mcg/kg IV bolus over Short-term control of HF
Inhibitors 10 min, then 0.375– 0.75 for adults acquiring
mcg/kg/min IV infusion; digoxin and diuretics2
milrinone (Primacor)
do not exceed 1.13
mg/kg/d; reduce dose in
renal impairment
For further reading you may consult both the reference used in this unit by Karch,
A.M. (2019), Focus on Nursing Pharmacology, 7th Edition. Wolters Kluwer, Chapter 44.
Self-Check 2. Multiple Choice

Circle the option that best answers the question or completes the statement.
1. The cardiovascular system is a closed system that relies on the difference in pressure
to ensure the supply of blood to the tissues and the return of blood to the heart.
a. True
b. False
c. Partly true
d. Partly false
2. Blood pressure is related to the heart rhythm, the amount of stroke, and the overall
peripheral resistance in which the heart needs to press the blood.
a. True
b. False
c. Partly true
d. Partly false
3. Peripheral resistance is mostly mediated by the constriction or relaxation of the

arterioles. Constricted arterioles increase the pressure; dilated arterioles lower the
pressure.
a. True
b. False
4. Regulation of blood pressure requires baroreceptor (pressure receptor) activation of

the medulla to stimulate the sympathetic nervous system, which triggers
vasoconstriction and increased fluid accumulation when the pressure in the aorta and
carotid arteries is minimal, and vasodilation and loss of fluid when the pressure is too
high.
a. True
b. False
c. Partly true
2
Karch, A.M. (2019), Focus on Nursing Pharmacology, 7th Edition. Wolters Kluwer, Chapter 44
Page | 19
d. Partly false
5. The kidneys activate the renin – angiotensin – aldosterone mechanism when blood
supply to the kidneys is diminished.
a. True
b. False
c. Partly true
d. Partly false
Page | 20
Title of the Lesson: Antiarrhythmics Agents
Duration: 2 hours
Antidysrhythmic agents are medicines used for the prevention and treatment of
heart dysrhythmias. Dysrhythmias, also referred to as arrhythmias, are disturbances of
heart rate or rhythm. They become important as they mess with heart activity and the
ability to scent body tissues. The structure of the heart conduction mechanism is reviewed
to better explain antidysrhythmic opioid treatment.
The heart is the electric pump. The "electrical" behavior occurs mainly in advanced
tissues that can produce and execute electrical impulses. Although the impulses are sent
through the muscle cells, the rate is much slower. Mechanical or "pump" operation is in
contractile tissue. Normally, these actions result in a successful contraction and
circulation of blood across the body. Each heartbeat occurs at regular intervals and
consists of four events: electrical impulse stimulation, transfer of electrical impulses to
adjacent conductive or contractile tissue, contraction of atria and ventricles, and
relaxation of atria and ventricles.
Automaticity is the ability of the heart to produce electrical impulses. Any part of
the conduction system will spontaneously initiate an impulse, but the sinoatrial ( SA) node
usually has the highest rate of automation and thus a higher rate of spontaneous impulse
creation. With this higher rate of electrical discharge or depolarization than other areas of
the conduction system, the SA node is used as a pacemaker site.
Conductivity is the ability of the heart tissue to transmit electrical impulses. For
effective myocardial contraction, orderly, rhythmic transmission of impulses to all cells is
needed. Normally, electrical impulses originate in the SA node and are transferred via
internaldal pathways to the atrioventricular (AV) node where the impulse is delayed for a
period of time. Then the impulse passes through the bundle of His bundle of limbs,
Purkinje fibers, and through the ventricular muscles.
Cardiac dysrhythmias can arise in any part of the conduction system or in the atrial
or ventricular muscles. They originate from disturbances in electrical impulse forming
(automaticity), conductivity (conductivity) or both. The ability of automaticity causes
myocardial cells other than the SA node to depolarize and trigger electrical impulses that
culminate in contraction. This may arise when the SA node fails to trigger an impulse or
does so too slowly. When an electrical impulse happens somewhere other than the SA
node, the emphasis is irregular or ectopic. If the ectopic focus depolarizes faster than the
SA node, the ectopic focus becomes the dominant pacemaker. Ectopic pacemakers can
be triggered by hypoxia, ischemia, or hypokalemia. Ectopic focal points suggest
myocardial irritability (increased sensitivity to stimuli) and potentially severe deterioration
of cardiac activity.
Dysrhythmias can be clinically relevant if they conflict with cardiac activity ( i.e., the
capacity of the heart to pump enough blood to the body tissues). Regular heart can
sustain sufficient cardiac production at ventricular frequencies ranging from 40 to 150
beats per minute. However, the diseased heart will not be able to sustain a sufficient
cardiac output of less than 60 beats per minute or more than 120 beats per minute.
Dysrhythmias are typically antidysrhythmic medications that change the electrical
conduction mechanism of the heart.
Medical use of antidysrhythmic medicines for tachydysrhythmias has improved.
One improvement is that the aim of drug treatment is to avoid or mitigate complications
or to extend survival, not only to eliminate dysrhythmias. This move stemmed from
research results in which patients infected for certain dysrhythmias had a higher death
risk than patients who did not undergo antidysrhythmic drug therapy. The higher mortality
Page | 21
rate was due to prodysrhythmic symptoms such as deterioration of current dysrhythmias
or triggering new dysrhythmias.
Another shift is the expanded usage of non-pharmacological dysrhythmia
treatment. These therapies include the disruption of dysrhythmogenic areas within the
heart with radio waves by radiofrequency catheter ablation or surgical procedures, thus
implanting detecting, cardioverting, defibrillating and/or patient-facing equipment such as
the implantable cardioverter defibrillator [ICD]).
Classified by the intensity, position, or pattern of conduction.
Antidysrhythmic drug treatment is usually indicated under the following conditions:
Conversion of atrial fibrillation (A-Fib) or atrial flutter to normal sine rhythm (NSR)
Maintaining NSR after A-Fib or atrial flutter conversion
Suppression of a high or erratic ventricular rate that alters the cardiac output. Altered
cardiac output induces signs of reduced heart, cerebral and/or systemic circulation.
Presence of harmful dysrhythmias, which could be lethal if not immediately
stopped. Drugs used to treat rapid dysrhythmia primarily decrease automation
(spontaneous depolarization of myocardial cells, like ectopic pacemakers), delay
conduction of electrical impulses through the muscle, and increase the refractory cycle of
myocardial cells (so that neighboring cells are less likely to be stimulated prematurely).
Several separate classes of medications carry out one or more of these acts. They are
categorized according to their mode of action and effects on the conduction system,
although they vary in some respects. In addition, certain medications have features of
more than one classification.
Drugs with tachydysrhythmia.
Class I Sodium Canal Blockers
Class 1A. Restoration of proper sinus rhythm (NSR) following transfer of atrial
fibrillation (A-Fib) or atrial flutter; treatment of symptomatic premature ventricular
contractions (PVCs), supraventricular tachycardia (SVT) and ventricular tachycardia
(VT); avoidance of ventricular fibrillation (V-fib).
MEDICATION ADULT CHILDREN
Quinidine PO 100–600 mg q4–6h; Safety and efficacy not
maximum dose, 3–4 g/d; established PO 30
maintenance dose, PO mg/kg/d in doses every
200– 600 mg q4-6h, or q4–6h
extended-action tablets,
324–972 mg q8–12h
Procainamide (Pronestyl, PO loading dose 1 g PO 15–50 mg/kg/d in
Procanbid) initially, then 250–500 mg divided doses q3–6h
q3–6h (500–1000 mg q6h
IV loading dose 3–6
for sustained-release
mg/kg over
tablets)
5 min (max 100 mg); may
IM loading dose, 500–
repeat q5–10 min to max
1000 mg followed by oral
total dose of
maintenance doses
15 mg/kg; then
IV loading dose 50–100
maintenance dose of 20–
mg; may repeat q5–10
80 mcg/kg/min; max 2 g/d
min or 15–18 mg/kg (max
1–1.5 g); then
maintenance infusion 3–4
mg/min
Page | 22
Disopyramide (Norpace) PO (weighing 50 kg and 12–18 y: 6–15 mg/kg/d in
more) 150 mg q6h (300 4 divided doses
mg q12h extended
5–11 y: 10–15 mg/kg/d in
release); (weighing less
4 divided doses
than 50 kg) 100 mg q6h
(200 mg q12h with 1–4 y: 10–20 mg/kg/d in 4
extended release) divided doses
<1 y: 10–30 mg/kg/d in 4
divided doses
Class 1B. Treatment of symptomatic premature ventricular contractions (PVCs)
and ventricular tachycardia (VT); prevention of ventricular fibrillation (V-fib).
Lidocaine (Xylocaine) IV 1 mg/kg bolus, not to IV injection 0.5–1 mg/kg
exceed 50–100 mg, as a bolus, may repeat but total
single bolus injection at dose not to exceed 3–5
25–50 mg/min, may be mg/kg; followed by IV
repeated in 5 min; give no infusion of 10–50
more than 200–300 mg in mcg/kg/min
1 h followed by a
continuous infusion of 1–4
mg/min; maximum dose
IM 4.3 mg/kg as a single
dose; may repeat in 60–90
min
Mexiletine (Mexitil) PO 200 mg q8h initially, 1.4–5 mg/kg per dose,
increased by 50–100 mg given every 8 h
every 2–3 d if necessary to
a maximum of 1200 mg/d
Tocainide (Tonocard) PO 400 mg q8h initial Safety and efficacy not
dose; 1.2–1.8 g/d in established
divided doses q8h
maintenance dose
Phenytoin (Dilantin) PO, loading dose 250 mg PO 5–10 mg/kg/d in 2–3
4 times a day for 1 day; divided doses
250 mg 2 times a day for
IV loading dose 1.25
2 days; maintenance dose
mg/kg q5 min; may repeat
300–400 mg/d 1–4 times
up to total dose of
per day
15 mg/kg; maintenance
IV loading dose 1.25
dose
mg/kg q5min; may repeat
5–10 mg/kg/d in 2–3
up to total dose of 15
divided doses
mg/kg
Class 1C. Treatment of life-threatening ventricular tachycardia (VT) or ventricular
fibrillation (V-fib) and supraventricular tachycardia (SVT) unresponsive to other drugs
Page | 23
Flecainide (Tambocor) PO 100 mg q12h initially, Initial 1–3 mg/kg/d in 3
increased by 50 mg q12h divided doses; usual 3–6
every 4 d until effective; mg/kg/d in 3 divided doses
maximum dose, 400 mg/d up to 8 mg/kg/d
Propafenone (Rythmol) PO 150 mg q8h initially, Safety and efficacy not
increase at established
3–4 day intervals to 225
mg q8h, then
to 300 mg q8h; maximum
dose of
900 mg/d
PO (extended release)
225 mg q12h initially, may
increase at 5 day
intervals; maximum 425
mg q12h
Moricizine (Ethmozine) PO 200–300 mg q8h; Safety and efficacy not
maximum dose 900 mg/d established
Class II Beta-Adrenergic Blockers. Treatment of supraventricular tachycardia
Acebutolol (Sectral) PO 200 mg q12h, Safety and efficacy not
increased gradually to established
Beta1
600–1200 mg/d in 2
divided doses
Atenolol (Tenormin) IV push 5 mg over 5 min; No dosing for this
may repeat in 10 min. indication
Beta1
Give IV infusion over 15
min PO 50–100 mg/d
Bisoprolol (Zebeta) PO 2.5–5 mg/d. May Safety and efficacy not
increase up to 20 mg/d. established
Beta1
Carteolol (Cartrol) PO 2.5–10 mg/d No dosing for this
indication
Beta1 Beta2
Esmolol (Brevibloc) IV 500 mcg/kg/min initially IV infusion 500
as a loading dose for 1 mcg/kg/min initially as a
Beta1
min, followed by a mainte- loading dose over 1 min,
nance dose of 50 with
mcg/kg/min over a maximum dose of 50–
4 min. If no response in 5 250 mcg/ kg/min
min, repeat the same
loading dose, and
increase maintenance
doses to 100 mcg/kg/min
for 4 min, continue to
increase by 50
Page | 24
mcg/kg/min up to 200
mcg/kg/min for 4 min.
Once desired response
is attained, stop leading
dose and increase
infusion by no more than
25 mcg/kg/min. Average
maintenance dose 100
mcg/kg/min. Infusion
administered over 24–48
h.
Metoprolol (Lopressor) IV injection 1–5 mg over 1 Safety and efficacy not
min every established
Beta1
2 min for 3 doses, followed
by 50 mg PO q6h for 48 h.
Begin oral dose 15 min
after last IV dose.
PO 50–450 mg/d
Nadolol (Corgard) PO 40 mg/d, may increase Safety and efficacy not
by 40–80 mg at 3–7 day established
Beta1
intervals.
Maximum 240–360 mg/d
Propranolol (Inderal) PO 10–20 mg q6-8h; may PO 0.5–1 mg/kg/d in
gradually increase dose to divided doses q6–8 h;
Beta1 Beta2
40–320 mg/d may increase every 3–5
days; usual dose 2–4
IV 0.5–3 mg repeat once
mg/kg/d; maximum 16
in 2 min, additional doses
mg/kg/d
at intervals of at least 4 h;
maximum 5 mg total IV
injection 0.01–0.1 mg/kg
slow IVP over 10 min, with
a maximum dose of 3 mg;
infant maximum dose of 1
mg
Sotalol (Betapace) Beta1 PO 80 mg q12h initially, Safety and efficacy not
Beta2 titrated to response; established
average dose, 160–320
mg daily. See
manufacturer’s
recommendations for
dosing in renal failure.
Timolol (Blocadren) Beta1 PO 10 mg twice a day Safety and efficacy not
Beta2 beginning 1–4 wk after established
infarction
Page | 25
Class III Potassium Channel Blockers. Treatment of ventricular tachycardia (VT)
and ventricular fibrillation (V-fib); conversion of atrial flutter or atrial fibrillation to sinus
rhythm; maintenance of sinus rhythm (amiodarone)
Amiodarone (Cordarone) Loading dose, IV 150 mg IV safety and efficacy not
over 10 min (15 mg/min), established Loading dose,
then 360 mg over the next PO 10–15 mg/kg/d in 1–2
6 h (1 mg/min), then 540 divided doses for up to 14
mg over the next 18 h (0.5 d or until dysrhythmia
mg/min); maintenance controlled. Dose should
dose, IV 720 mg/24 h (0.5 then be reduced to 5
mg/min) Loading dose, mg/kg/d once daily for
PO 800–1600 mg/d for 1– several weeks. Minimal
3 wk, with a gradual maintenance dose, PO
decrease to 600–800
2.5 mg/kg/d for 5–7 d/wk
mg/d for 1 month;
Safety and efficacy not
maintenance dose, PO
established
400 mg/d
Dofetilide (Tikosyn) IV 500 mcg twice daily Safety and efficacy not
with creatinine clearance established
� 60 mL/min, adjusted to
manage adverse effects
Ibutilide (Corvert) Weight >60 kg: IV infusion Safety and efficacy not
over 10 min, 1 mg established
Weight < 60 kg: IV infusion
over 10 min, 0.01 mg/kg
The dose can be repeated
once, after 10 min, if
necessary.
Sotalol (Betapace) PO 80 mg q12h initially, Safety and efficacy not
titrated to response; established
Class II and class III
average dose, 160–320
effects
mg daily. See
manufacturer’s
recommendations for
dosing in renal failure.
Class IV Calcium Channel Blockers. Treatment of supraventricular tachycardia
Diltiazem (Cardizem) IV injection 0.25 mg/kg Safety and efficacy not
(average dose 20 mg) established.
over 2 min. A second dose
of 0.35 mg/kg (average,
25 mg) may be given in 15
min, and an IV infusion
of 5–15 mg/h may be
Page | 26
given up to 24 h, if
necessary.
Verapamil (Calan, Isoptin PO 40–120 mg q6–8h 1–15 y: IV injection 0.1–
0.3 mg/kg (usual range 2–
IV 5–10 mg initially, then
5 mg for a single dose)
10 mg 30 min later, if
over 2 min with continuous
necessary
ECG monitoring; repeat
in 30 min if necessary �1
y: IV injection 0.1–0.2
mg/kg
(usual range, 0.75–2.0 mg
for a single dose) over 2
min with continuous ECG
monitoring
Unclassified. Adenosine is used to treat supraventricular tachycardia; magnesium
sulfate is used to treat torsades de pointes
Adenosine (Adenocard) IV 6 mg given rapidly over Neonates: Initial IV dose
1–2 sec. 0.05 mg/kg.
If first dose does not slow If first dose does not slow
the upraventricular the supraventricular
tachycardia within 1–2 tachycardia within 1–2
min, give 12 mg rapidly, min, increase dose by
and repeat one time, if 0.25 mg/kg.
necessary.
Infants and children: 0.1
mg/kg. If first dose does
not slow the
supraventricular
tachycardia, give 0.2
mg/kg.
Magnesium sulfate IV 1–2 g (2–4 mL of 50% Safety and efficacy not

solution), diluted in 10 mL established for treatment
of 5% dextrose solution of torsades de pointes 3
Self-Check 3. Short Answer Exercise
1. A patient is taking antidysrhythmic agent, what assessment health teaching

should be given to the patient considering the effects of the medication to the
body?
3
Abrams, A. C., Lammon, C. B., & Pennington S. S., (2009). Clinical drug therapy rationales for
Page | 27
For further reading you may consult the reference used in this unit by Abrams, A.
C., Lammon, C. B., & Pennington S. S., (2009). Clinical drug therapy rationales for nursing
practice. 9th ed. Lippincottt Williams & Wilkins, Chapter 49.
Page | 28
Title of the Lesson: Antianginal Agents
Duration: 2 hours
Angina pectoris is a chronic condition that is characterized by symptoms of chest

pain. It happens when there is a deficiency in the supply of myocardial oxygen (myocardial
ischemia) in contrast to the need for myocardial oxygen. It is more commonly induced by
atherosclerotic plaque in the coronary arteries, but may also be induced by coronary
vasospasm. The formation and progression of atherosclerotic plaque is known as
coronary artery disease (CAD). The atherosclerotic plaque narrows the lumen, lowers the
elasticity and impairs the dilation of the coronary arteries. As a result, the blood flow to
the myocardium is reduced, particularly with exercise or other conditions that increase
the cardiac workload and the need for oxygen.
The CAD spectrum develops from angina to myocardial infarction ( MI). There are
three primary forms of angina: classical angina, variant angina, and dysfunctional angina.
The Canadian Cardiovascular Society classifies angina cases by the level of physical
exercise they can handle before angina discomfort occurs. These categories can assist
in the clinical assessment and evaluation of therapy.
Classic anginal pain is generally defined as constricting, crushing, or suffocating
chest pain. It can radiate to the head, spine, or shoulder; to the left or to both arms; or to
the back. Discomfort is often mistaken for arthritis or indigestion, since discomfort can be
correlated with nausea , vomiting, dizziness, diaphoresis, shortness of breath, or fear of
imminent death. The pain is generally short, usually lasting 5 minutes or less until the
equilibrium between oxygen supply and demand is restored.
Current literature suggests that there are gender differences in the form and
intensity of cardiac signs, with women experiencing epigastric or back pain. In addition,
older people may have atypical signs of CAD and may have "silent" ischemia that may
delay them from obtaining health assistance. Individuals with diabetes mellitus may
evolve without classical angina, but they may experience similar symptoms. The
American Heart Association has published recommendations for the treatment of angina.
Numerous conflicting factors contribute to the growth and success of CAD. These
factors are described in the following sections to help understand angina drug therapy.
Nitrates:
MEDICATION INDICATIONS FOR USE ROUTES AND DOSAGE
RANGES
Nitroglycerin (Nitro-Bid, Relieve acute angina PO immediate-release
others) Prevent exercise-induced tablets, 2.5–9 mg 2 or 3
angina Long-term times per day
prophylaxis to decrease
PO sustained-release
the frequency and severity
tablets or capsules, 2.5
of acute anginal episodes
mg 3 or 4 times per day
SL 0.15–0.6 mg PRN for
chest pain
Translingual spray, one or
two metered doses (0.4
mg/dose) sprayed onto
oral mucosa at onset of
anginal pain, to a
maximum of 3 doses in 15
min Transmucosal tablet,
Page | 29
1 mg q3–5h while awake,
placed between upper lip
and gum or cheek and
gum
Topical ointment, 1/2–2
inches q4–8h; do not rub
in
Topical transdermal disc,
applied once daily
IV 5–10 mcg/min initially,
increased in 10- to 20-
mcg/min increments up to
100 mcg/min or more if
necessary to relieve pain
Isosorbide dinitrate Treatment and prevention SL 2.5–10 mg PRN or q2–
(Isordil) of angina 4h
PO regular tablets, 5–40
mg 4 times/d PO
chewable tablets, 5–10
mg q2–3h
PO sustained-release
capsules, 40 mg q6–12h
Isosorbide mononitrate Treatment and prevention PO 5–20 mg twice daily,
of angina with first dose on arising
(Ismo, Imdur)
and the second dose 7 h
later PO extended-release
tablets (Imdur), 30–60 mg
once daily in the morning,
increased after several
days; maximum dose 240
mg once daily
Beta Blockers:
RANGES
Propranolol (Inderal) Long-term management PO 10–80 mg 2 to 4 times
of angina, to reduce per day
frequency and severity of
IV 0.5–3 mg q4h until
anginal episodes
desired response is
obtained
Atenolol (Tenormin) Long-term management PO 50 mg once daily,
of angina, to reduce initially, increased to 100
frequency and severity of mg/d after 1 wk if
anginal episodes necessary
Page | 30
Metoprolol (Lopressor) Long-term management PO 100–450 mg/d in 2–3
of angina, to reduce divided doses
anginal episodes
Nadolol (Corgard) Long-term management PO 40–240 mg/d in a
of angina, to reduce single dose
anginal episodes
Metabolic Modulator:
RANGES
Ranolazine (Ranexa) Long-term management PO 500 mg twice daily, if
of angina, not responsive needed; maximum
to other antianginal recommended dose is
medications 1000 mg twice daily
Calcium Channel Blockers:
RANGES
Amlodipine (Norvasc) Angina Hypertension PO 5–10 mg once daily
Diltiazem (Cardizem) Angina Angina or hypertension,
Hypertension immediate-release, PO
Atrial fibrillation and flutter 60–90 mg 4 times daily
PSVT before meals and at
bedtime
Hypertension, sustained-
release only, PO 120–180
mg twice daily
Dysrhythmias (Cardizem
IV only), IV injection 0.25
mg/kg (average dose 20
mg) over 2 min with a
second dose of 0.35
mg/kg (average dose 25
mg) in 15 min if
necessary, followed by IV
infusion of 5–15 mg/h up
to 24 h
Felodipine (Plendil) Hypertension PO 5–10 mg once daily
Isradipine (DynaCirc) Hypertension PO 2.5–5 mg twice daily
Page | 31
Nicardipine (Cardene) Angina Hypertension Angina, immediate-
release only, PO 20–40
mg 3 times daily
Hypertension, immediate-
release, same as for
angina, above; sustained-
release, PO 30–60 mg
twice daily
Nifedipine (Adalat, Angina Hypertension Angina, immediate-
Procardia) release, PO 10–30 mg
3 times daily; sustained-
release, PO 30–60 mg
once daily
Hypertension, sustained-
release only, 30–60 mg
once daily
Nimodipine (Nimotop) Subarachnoid PO 60 mg q4h for 21
hemorrhage consecutive days. If
patient unable to swallow,
aspirate contents of
capsule into a syringe with
an 18-gauge needle,
administer by nasogastric
tube, and follow with 30
mL normal saline.
Nisoldipine (Sular) Hypertension PO, initially 20 mg once
daily, increased by 10
mg/wk or longer intervals
to a maximum of 60 mg
daily. Average
maintenance dose, 20–40
mg daily. Adults with liver
impairment or �65 y, PO,
initially 10 mg once daily
Verapamil (Calan, Isoptin) Angina Angina, PO 80–120 mg 3
Atrial fibrillation or flutter times daily
PSVT
Dysrhythmias, PO 80–120
Hypertension
mg 3 to 4 times daily; IV
injection, 5–10 mg over 2
min or longer, with
continuous monitoring of
electrocardiogram and
blood pressure
Hypertension, PO 80 mg 3
times daily or 240 mg
Page | 32
(sustained-release) once
daily 4
A.M. (2019), Focus on Nursing Pharmacology, 7th Edition. Wolters Kluwer, Chapter 50.
Self-Check 4. Case Presentation
Mr. Helsinki is a 72 year-old man with a diagnosis of hypertension , coronary artery

disease (CAD) and myocardial infarction ( MI). After his MI, he quit smoking and started
a routine fitness regimen.
1. Mr. Helsinki is given nitroglycerin in both sublingual and transdermal ways.
When checking his prescription orders for Mr. Gerald, the nurse discovers that
he has had a history of erectile dysfunction and that he has sildenafil treatment
in the drug cabinet prescribed for him prior to his MI. The nurse leaves the
nitroglycerin patient information orders with Mr. Helsinki and leaves the room.
How do you stop this mistake?
2. In comparison to nitroglycerin, metoprolol is recommended by the practitioner.

Mr. Helsinki knows that nitroglycerine is helpful to his disease. He 's asking for
metoprolol and whether he has to take this drug. How are you expected to
respond?
4
Karch, A.M. (2019), Focus on Nursing Pharmacology, 7th Edition. Wolters Kluwer, Chapter 50.
Page | 33
3. Mr. Helsinki had anginal pain at rest, and his doctor recommended diltiazem.
He wonders what this new drug is going to do for him. How are you responding?
Page | 34
Title of the Lesson: Lipid Lowering Agents
Duration: 2 hours
Drugs mentioned in this chapter are lower blood levels of cholesterol and other
lipids. These medications are often referred to as antihyperlipidemic agents used to treat
hyperlipidemia — a rise in the level of lipids in the blood. There is growing evidence that
the prevalence of coronary artery disease ( CAD), the leading adult killer in the western
world, is higher amongst people with elevated serum lipid levels. The cause of CAD is not
well known, although some research suggests that cholesterol and fat may play a major
role in the development of the disease. Lipid and triglyceride levels play a role in metabolic
syndrome, a set of causes, including insulin tolerance, abdominal obesity, low-density
lipoprotein and elevated triglyceride levels, hypertension, and pro-inflammatory and
prothrombotic symptoms, which have been shown to improve the prevalence of CAD.
Lipid reducing agents reduce the blood levels of cholesterol and other lipids. That
include bile acid sequestrants, HMG-CoA reductase inhibitors, and cholesterol absorption
inhibitors. Some medications used to influence lipid levels do not fall into any of the
sections but are licensed for use in conjunction with improvements in diet and exercise.
Bile Acid Sequestrants Bile acid sequestrants are used to increase plasma
cholesterol levels. Three of the bile acid sequestrants
currently in use are cholestyramine (Questran), colestipol
(Colestid) and colesevelam (WelChol).
Therapeutic actions Bile acid sequestrants bind to bile acids in the intestine to
and indications create an insoluble complex, which is then excreted in the
feces. biliary acids contain elevated levels of cholesterol.
As a result, the liver must use cholesterol to produce more
bilious acids. Hepatic intracellular cholesterol decreases,
due to increased incorporation of cholesterol-containing
segments of LDL from circulation to the recovery of cell
cholesterol. Serum amounts of cholesterol and LDL
decline as circulating cholesterol is used to supply the
cholesterol required by the liver to produce bile acids. Both
medications are used to lower serum cholesterol in
patients with primary hypercholesterolemia (poor
cholesterol and high LDL) as an alternative to diet and
exercise. Cholestyramine is also used for the treatment of
pruritus along with partial biliary obstruction.
Pharmacokinetics Bile acid sequestrants are not routinely consumed. They
function when in the stomach and are excreted in the
feces. Their behavior is limited to their impact when they
are still in the intestines. Cholestyramine is a powder that
has to be blended with liquids and used up to six times a
day. Colestipol is used in both powder and tablet form and
is only taken four times a day. Colesevelam is available as
a tablet and is taken once or twice a day.
Contraindications and Bile acid sequestrants are contraindicated in the case of
Cautions resistance to any biliary acid sequestrant to avoid hyper-
sensitivity reactions. These medications are also
Page | 35
contraindicated under the following conditions: total biliary
obstruction, which would preclude bile from being
secreted into the intestine; irregular intestinal activity,
which could be exacerbated by the use of these
medications; and breastfeeding or lactation, as a possible
reduction in the absorption of fat and fat-soluble vitamins
could have a negative effect on the fetus. However, if a
lipid-lowering drug is required, a bile acid sequestrant is
the drug of choice.
Adverse Effects Adverse effects associated with the use of these
medications include headaches , nausea, fatigue, and
somnolence, which may be associated with changes in
serum cholesterol levels. Direct gastrointestinal ( GI) pain,
including nausea, constipation that may lead to fecal
impaction, and aggravation of hemorrhoids, may occur.
Other symptoms include prolonged bleeding times
associated with decreased absorption of vitamin K and
thus decreased production of clotting factors; vita-min A
and D deficits associated with decreased absorption of fat-
soluble vitamins; rash; and muscle aches and pains.
Clinically Important Malabsorption of fat-soluble vitamins happens when
Drug-Drug Interactions combined with these medications. These medications
minimize or postpone the absorption of thiazide diuretics,
digoxin, warfarin, thyroid hormones and corticosteroids.
As a consequence, both of these medications should be
given 1 hour before or 4 to 6 hours after the bile acid
sequestrant.
HMG-CoA Reductase (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pita-
Inhibitors vastatin (LIvalo), the newest statin approved in 2010,
pravastatin (Pravachol), rosuvastatin (Crestor), and
simvastatin (Zocor).
Therapeutic actions The early rate-limiting step in cellular cholesterol synthesis
and indications includes the enzyme HMG-CoA reductase. If this enzyme
is inhibited, serum cholesterol and LDL levels will decline
as more LDLs are processed by the cells for cholesterol
production. In comparison, with this shift in fat metabolism,
HDL levels rise significantly. HMG-CoA reductase
inhibitors block HMG-CoA reductase from completing
cholesterol synthesis. Most of these drugs are chemical
modification of com-pounds formed by fungi. As a
category, they are sometimes referred to as "statins."
Since these medications have a pronounced first-pass
action in the liver, most of their symptoms are found in the
liver (see Adverse Symptoms). These medications can
also have some effects on the mechanism that induces
Page | 36
atheromas in the walls of the vessel. The precise
mechanism of operation is not established. These
medications are recommended as adjuncts to diet and
exercise for the treatment of elevated levels of cholesterol
and LDL, which alone do not respond to dietary
restrictions.
Pravastatin, lovastatin (one of the oldest HMG-CoA
medications available), and simvastatin are
recommended for patients with known CAD to reduce
disease progression. These three agents and atorvastatin
are used to avoid early myocardial infarction ( MI) in
patients who have several risk factors for developing CAD.
Table 47.4 addresses the normal indications for each
HMG-CoA reductase inhibitor. Several statin medications
have been developed as combination therapy.
Pharmacokinetics Statins are both processed from the GI tract and undergo
first-time synthesis in the liver. They are excreted by feces
and urine. The peak effect of these medications is typically
seen in 2 to 4 weeks. These medications are more
effective when used at night when most lipids are
produced by the liver. These medications cross the
placenta, and most of them have been detected in breast
milk.
Contraindications and These medications are contraindicated in the case of
Cautions allergy to either of the statins or fungal by-products or
compounds to deter hypersensitivity reactions. Statins are
also contraindicated in patients with acute liver disease or
history of chronic liver disease, and can be exacerbated,
leading to serious liver dysfunction and breastfeeding or
lactation due to the risk for adverse effects on the fetus or
neonate. These drugs are known as type X pregnancy.
Atorvastatin levels are not affected by renal failure,
although close monitoring is needed in patients with
compromised renal function who are taking other statins.
Caution may be used in individuals with compromised
endocrine activity due to possible alteration in the
development of steroid hormones.
Adverse Effects The most frequent adverse reactions associated with
these medications indicate their effects on the GI system:
flatulence, stomach pain, cramping, nausea , vomiting,
and constipation. CNS symptoms can include headache,
dizziness , blurred vision, nausea, nausea, and cataract
formation, which may indicate improvements in cell
membrane which cholesterol synthesis. Increased
amounts of liver enzymes are widely reported and acute
liver failure with the use of atorvastatin and fluvastatin has
been reported. Lovastatin, pravastatin and simvastatin are
Page | 37
not associated with any of the extreme liver damage seen
with other compounds. Rhabdomyolysis, a degradation of
muscles whose waste products can cause glomerulus
damage and acute renal failure, has also occurred with the
use of all these medications. Rosuvastatin is associated
with an elevated rate of rhabdomyolysis in Asian American
patients and should be taken into account when taking
statins for these patients. In 2011, research found that
patients taking the maximum dosage of simvastatin, 80
mg, had an elevated rate of cardiovascular incidents, and
the Food and Drug Administration (FDA) cautioned that an
80 mg dosage of simvastatin could not be begun in new
patients and only proceeded if patients taking simvastatin
did so without adverse effects.
Clinically Important The risk of rhabdomyolysis rises if either of these
Drug-Drug Interactions medications were paired with erythromycin, cyclosporine,
gemfibrozil, niacin or antifungal medications; these
combinations should be avoided.
Increased serum levels and subsequent toxicity can occur
when these medications are paired with digoxin or
warfarin; if this mixture is used, serum digoxin levels
and/or clotting periods should be closely checked and the
prescriber reviewed for appropriate dosage adjustments.
Increased amounts of estrogen can occur if these
medications are used with oral contraceptives; the patient
should be watched closely if this mixture is used.
Serum levels and the risk of contamination rise as these
medications are mixed with grapefruit juice.
Cholesterol Absorption The first in a new generation in medications with lower
Inhibitors cholesterol levels was approved in 2003—ezetimibe
(Zetia). There is actually a debate over cholesterol-
lowering medications , especially ezetimibe, attributable to
the ENHANCE research (full title of the report: Impact of
Combination Ezetimibe and High-Dose Simvastatin vs.
Simvastatin Alone on the Atherosclerotic Mechanism in
Heterozygous Family Hypercholesterolemia).
Therapeutic actions Ezetimibe acts at the brush boundary of the small intestine
and indications to reduce the removal of dietary cholesterol from the small
intestine. As a consequence, fewer dietary cholesterol is
provided to the liver, and the liver raises the serum
clearance of cholesterol to cover up for a decrease in
dietary cholesterol, resulting in a decline in overall serum
cholesterol.
Page | 38
Pharmacokinetics Ezetimibe is well absorbed after oral administration, hitting
peak levels in 4 to 6 hours. It is metabolized in the liver
and small intestines, with a half-life of 22 hours. Excretion
is caused by feces and urine. It is not clear whether the
medication passes the placenta or if it reaches breast milk.
Contraindications and Ezetimibe is contraindicated in patients with allergy to any
Cautions part of the medication to prevent hypersensitivity
reactions. If used in conjunction with statin, it cannot be
used during breastfeeding or lactation or with serious liver
disease due to documented statin effects, including
potential complications with the liver and renal failure.
The drug should be used with caution as monotherapy
during breastfeeding or lactation since the effects on the
fetus or neonate are not known and due to the risk for
adverse reactions in elderly patients or patients with liver
disease.
Adverse Effects Mild stomach pain and diarrhea are the most frequent side
effects associated with ezetimibe. It is not associated with
the bloating and flatulence of bile acid sequestrants and
another class of lipid-lowering medications called fibrates.
Some adverse symptoms reported include headaches,
dizziness , nausea, upper respiratory tract infection (URI),
back pain, and body aches and pain.
Clinically Important The chance of elevated serum levels of ezetimibe
Drug-Drug Interactions increases when provided with cholestyramine, fenofibrate,
gemfibro-zil or antacids. If these medications are used in
conjunction, ezetimibe can be taken at least 2 hours
before or 4 hours after the other medications.
The risk of toxicity also increases when ezetimibe is mixed
with cyclosporine. If this mixture cannot be prevented, the
patient should be watched closely.
If ezetimibe is mixed with some fibre, the chance of
cholethiasis increases. The patient should be carefully
watched.
Warfarin levels rise in a patient who is not taking
ezetimibe; if this mixture is used, the patient should be
watched closely.
Other Lipid-Lowering Fibrate promotes the degradation of lipoproteins from the
Agents: Fibrates tissues and their elimination from the plasma. They
contribute to a decline of lipoprotein and triglyceride
synthesis and secretion. The fibers are absorbed from the
GI tract and are metabolized in the liver and excreted in
Page | 39
the urine. The following agents are used in today's use of
fibers:
Fenofibrate (TriCor and others) inhibits triglyceride
synthesis in the liver, resulting in lower LDL levels;
enhances uric acid secretion; and can promote triglyceride
breakdown. It is used in adults with extremely high
triglyceride levels that are not immune to stringent dietary
steps and are at risk for pancreatitis. Peak symptoms are
typically observed within 4 weeks, and the patient's serum
lipid levels can be re-evaluated at that point.
Gemfibrozil (Lopid) prevents peripheral lipid degradation,
decreases the development of triglycerides and LDLs, and
increases HDL concentrations. It's correlated with GI and
muscle pain. The medicine should not be mixed with
statins. There is an elevated chance of rhabdomyolysis
from 3 weeks to several months following treatment if this
formulation is used. If this mixture can not be prevented,
the patient should be watched closely.
In 2009, the FDA approved a new form of alpha-activator
alpha-receptor proliferator fibrate. Fenofibric acid (Trilipix)
is the first drug of this kind. This drug acts to stimulate a
particular hepatic receptor that results in enhanced lipid
breakdown, removal of triglyceride-rich particles from the
plasma, and a decline in the output of an enzyme that
normally prevents lipid breakdown. The effect is seen as
a decline in triglyceride levels, improvements in LDL
production that make them more readily broken down in
the body, and a rise in HDL levels. Fenofibric statin to
decrease triglyceride levels and raise HDL levels in
patients with mixed lipid disorders; monotherapy to
minimize triglyceride levels in patients with serious
hypertriglyceridemia; and monotherapy to decrease LDL,
total cholesterol and triglycerides and to improve HDL
levels in patients with primary hyperlipidemia or mixed lipid
disorders. Fenofibric acid is steadily absorbed from the GI
tract, with peak levels occurring in 4 to 5 hours;
metabolized in the liver, has a half-life of 20 hours and
excreted in the urine. Caution should be used in patients
with reduced renal function and should be minimized in
patients with serious renal dysfunction. The most frequent
adverse symptoms reported include fatigue, back pain,
nausea , diarrhea, muscle pain, runny nose, and
respiratory infections. Gallstones has also been
documented with this drug. Patients talking of gall-stone-
like discomfort should be closely screened. There is an
elevated risk of muscle breakdown and rhabdomyolysis
when administered with statin and careful monitoring of
patients using this combination is needed. Caution must
be used with warfarin anticoagulants; increased bleeding
Page | 40
can occur. The patient should be closely watched and the
anticoagulant dosage controlled to obtain therapeutic
anticoagulation should be tracked.
Other Lipid-Lowering Vitamin B3, known as niacin (Niaspan) or nicotinic acid,
Agents: Vitamin B stimulates the release of free fatty acids from adipose
tissue, raises the rate of triglyceride elimination from
plasma, and typically lowers LDL and triglyceride levels
and raises HDL levels. It can also reduce the levels of
apoproteins required to produce chylomicrons. The initial
effect on lipid levels is typically observed within 5 to 7
days, with a median effect seen within 3 to 5 weeks. Niacin
is associated with intense skin flushing, nausea and
abdominal pain, making its use somewhat limited. It also
raises uric acid serum levels and can predispose patients
to the development of gout. Niacin is also paired with bile
acid sequestrants for improved effects. It is given at
bedtime to allow full use of nighttime cholesterol synthesis
and must be given 4 to 6 hours after the bile sequestrant
to ensure absorption. 5
A.M. (2019), Focus on Nursing Pharmacology, 7th Edition. Wolters Kluwer Chapter 47.

1. CAD is the leading cause of death in the West. It is associated with the formation of
atheromas or plaques in arterial liners that contribute to narrowing of the artery lumen
and hardening of the artery wall, lack of distensibility and resistance to contraction or
dilation stimuli.
a. True
b. False
c. Partly true
d. Partly false
2. The cause of CAD is not known, but several related risk factors have been reported,
including growing age , ethnicity, genetic predisposition, high fat diet, sedentary
lifestyle, smoking, obesity, high stress levels, bacterial infections, diabetes,
hypertension, gout, and menopause. The existence of many of these causes is a
metabolic syndrome.
a. True
b. False
3. The care and prevention of CAD is directed at manipulating established risk factors to
minimize the occurrence and advancement of CAD.
a. True
b. False
c. Partly true
5
Karch, A.M. (2019), Focus on Nursing Pharmacology, 7th Edition. Wolters Kluwer Chapter 47.
Page | 41
d. Partly false
4. Fats are metabolized with the aid of bile acids, which serve as a detergent to break
down fats into small molecules called micelles. Micles are incorporated into the
intestinal wall and mixed with proteins to form chylomicrons, which can be transferred
in the circulatory system.
a. True
b. False
5. Such fats are directly used for energy or preserved in adipose tissue; some are
converted into LDLs in the liver, and are correlated with the growth of CAD. LDLs are
broken down in the periphery and leave several traces (e.g. fats) that need to be
eliminated from the blood vessels. This process requires an inflammatory reaction and
can trigger or lead to the development of the atheroma.
a. True
b. False
Page | 42
Title of the Lesson: Drugs Affecting Blood Coagulations
Duration: 2 hours
The coronary system is a closed system, while the blood remains in a fluid state.
Since the blood is contained in a closed room, it retains the disparity in forces needed to
keep the machine going. Anything in the cardiovascular system is going from elevated
pressure to lower pressure. If the vascular system is damaged — from a wound, puncture,
or capillary destruction — the fluid blood may spill out, allowing the system to lose control
in that region and to alter the flow of the circulation, eventually shutting it down completely.
In order to deal with the issue of blood leakage and actually closing down the system, the
blood that is exposed to harm in the body is almost automatically formed into a stable
state or a clot that blocks the void in the system and holds the necessary pressure
variations intact.
People damage blood vessels all the time (e.g. by breathing too hard, by banging
at the corner of the desk while sitting down). As a result, the vascular system must achieve
a complex equilibrium between the propensity to clot or to form a stable state, called
coagulation, and the need to "unclog" or reverse coagulation to keep the arteries open
and the blood circulating. If there is a significant amount of vascular injury, such as
significant cuts or incisions, the equilibrium in the area changes to the procoagulation
mode and a significant clot is formed. Around the same time, the enzymes in the plasma
work to remove this clot until the blood supply to the tissues is lost, which may eventually
lead to hypoxia and possible cell death.
Drugs that affect blood clotting function at different stages of blood clotting and
clot-dissolving processes to restore the equilibrium required to sustain the cardiovascular
system.
Blood coagulation is a complex mechanism involving vasoconstriction, platelet
clumping or accumulation, and a cascade of clotting factors generated in the liver that
gradually react to break down fibrinogen (a protein also formed in the liver) into insoluble
fibrin strings. When a clot is formed, plasmin (another protein in the blood) works to break
it down. Blood coagulation may be impaired at any stage of this complex mechanism by
changing the manner in which blood clotting occurs.
Disorders that specifically influence the coagulation mechanism fall under two
major categories : ( 1) diseases requiring overproduction of clots or thromboembolic
disorders; and (2) situations in which the coagulation process does not function properly
, resulting in the possibility of excessive bleeding or hemorrhagic disorders.
CONDITION DESCRIPTION
Thromboembolic Medical disorders including the development of thrombi
Disorders result in reduced blood flow into or complete occlusion of
a blood vessel. Both diseases are characterized by signs
and symptoms of hypoxia, anoxia, or even necrosis of
areas affected by insufficient blood supply. In any of these
conditions, portions of the thrombus, or emboli, will split off
and pass through the coronary system until they are stuck
in a tiny vessel, plugging it up.
Conditions that predispose a person to the development
of clots and emboli are known as thromboembolic
disorders. Coronary artery disease ( CAD) entails the
narrowing of coronary arteries due to damage to the
endothelial lining of these vessels. Thrombi appears to
develop along the weakened endothelial liner. If the
Page | 43
damage piles up, the lumens of the vessels get smaller
and smaller. Over time, coronary arteries are unable to
supply enough blood to satisfy the needs of the heart
muscle, and hypoxia is developing. If the artery becomes
so small that the tiny clot entirely occludes it, the blood
flow to that region will be cut off and anoxia will result,
followed by infarction and necrosis. With age, many of the
arteries in the body will be weakened and have related
issues with narrowing and blood flow. These conditions
are treated with medications that interfere with the natural
coagulation mechanism in order to avoid the development
of clots in the blood.
Hemorrhagic Disorders Hemorrhagic diseases with excess bleeding are less
frequent than thromboembolic diseases. These disorders
include hemophilia in which there is a hereditary
deficiency of clotting factors; liver disease in which clotting
factors and proteins required for clotting are not produced;
and bone marrow disorders in which platelets are not
developed in adequate amounts to be efficient. These
diseases are treated with clotting factors and medications
that facilitate the mechanism of coagulation.
Drugs that influence the development of clots include antiplatelet drugs that modify
the accumulation of platelets and the production of platelet plugs; anticoagulants that
interact with cascade and thrombin development of clots; and thrombolytic agents that
break down the thrombus or clot that has been formed by stimulating the plasma system.
Antiplatelet Agents Antiplatelet agents limit the development of the plate by
limiting the resistance of the platelets to the stimuli that
would allow them to attach and attach to the surface of the
vessel. Antiplatelet agents available for use include
abciximab (ReoPro), anagrelide (Agrylin), aspi-rin,
cilostazole (Pletal), clopidogrel (Plavix), dipyridamole
(Persantine), eptifibatide (Integrilin), ticlopidine (Ticlid),
ticagrelor (Brilinta), and tirofiban (Aggrastat).
Therapeutic actions Antiplatelet agents hinder platelet adhesion and
and indications aggregation by blocking receptor sites on the platelet
membrane, avoiding platelet-platelet interactions or
platelet interactions with other clotting chemicals. One
medication, anagrelide, is blocking the development of
platelets in the bone marrow. These agents are used
successfully to treat coronary conditions that are pro-duce
occluded vessels; to protect venous and arterial grafts; to
prevent cerebrovascular occlusion; and as adjuncts to
thrombolytic therapy in the treatment of myocardial
infarction ( MI) and to prevent re-infarction after MI. The
choice of treatment by the prescriber depends on the
expected use and the patient's tolerance to the related
adverse effects.
Page | 44
Pharmacokinetics Abciximab, eptifibatide and tirofiban are provided
intravenously (IV). Antiplatelet agents prescribed orally
include anagrelide, aspirin, cilostazole, clopidogrel,
ticagrelor, and ticlopidine. Dipiridamole is used orally or as
an IV agent.
Generally, these medications are widely consumed and
strongly bound to plasma proteins. They are metabolized
in the liver and excreted in urine, and appear to enter
breast milk.
Contraindications and Antiplatelet agents are contraindicated in the case of a
Cautions serious drug allergy to prevent hypersensitivity reactions.
Caution can be used under the following conditions: the
involvement of some documented bleeding disease due to
the risk of significant blood loss; new surgery due to the
risk of additional bleeding under unhealed arteries; and
closed head trauma due to the risk of bleeding from
wounded veins in the brain.
While there are no sufficient trials with these medications
during pregnancy, they are contraindicated with
pregnancy due to the possibility for excessive bleeding
(see Adverse Effects); they can only be used during
pregnancy if the advantages to the mother significantly
outweigh the potential hazards to the child. These
medications are often contraindicated during lactation due
to possible adverse effects on the infant or neonate; if they
are desired by a breast-fed mother, another way of fed the
baby should be used.
Anagrelide should be treated with caution in any history of
thrombocytopenia since it lowers the development of
platelets in the bone marrow. Platelet levels should be
monitored frequently to monitor thrombo-cytopenia while
a patient is on this drug.
Adverse Effects The most frequent adverse reaction observed with these
medications is bleeding, which mostly appears as
enhanced swelling and bleeding when cleaning the teeth.
Other frequent issues include headaches , dizziness, and
weakness; the cause of such reactions is not known.
Nausea and gastrointestinal ( GI) discomfort may occur
due to direct irritating effects of the oral drug on the GI
tract. Skin rash, another typical result, can be linked to the
direct effects of drugs on the dermis.
Clinically Important The risk of severe bleeding rises if one of these
Drug-Drug Interactions medications is paired with another medicine that
influences blood clotting.
Page | 45
Anticoagulants Anticoagulants are medications that interact with the or-
mal coagulation mechanism by preventing the cascade of
clotting and thrombin production. Drugs in this class
include antithrombin III (Thrombate III), argatroban
(Acova), bivalirudin (Angiomax), desirudin (Iprivask),
fondaparinux (Arixtra), heparin (generic), and warfarin
(Coumadin) as well as two newest oral anticoagulants,
dabigatran (Pradaxa) and rivaroxaban (Xarelto).
Therapeutic actions As noted above, anticoagulants interact with the usual
and indications series of events occurring in the clotting process. Warfarin,
an oral drug in this class, induces a reduction of the
development of vitamin K-dependent clotting factors in the
liver. The final result is the reduction of these clotting
variables and the prolongation of the duration of clotting.
It is used to preserve anticoagulation in cases where the
patient is vulnerable to potentially harmful clot formation
(the high cost of the medication and the lack of a fast
overdose cure have been seen by many health care
professionals to be very wary regarding transitioning to
this treatment. Rivaroxaban (Xarelto) is a factor Xa
receptor that prevents the cascade of coagulation at this
early stage. It is licensed to avoid deep vein thrombosis,
which can lead to pulmonary embolism, in patients
undergoing knee or hip replacement surgery.
Heparin, argatroban, and bivalirudin block the
development of prothrombin thrombin. Popular indications
for heparin include emergency treatment and prevention
of venous thrombosis and pulmonary embolism; treatment
of AF with embolization; prevention of blood clotting and
dialysis and venous tubing; and diagnosis and
management of disseminated intravascular coagulation
(DIC). Since heparin needs to be injected, it is also not the
medication of choice for outpatients that will be
responsible for delivering the medication multiple times
during the day. Patients can begin with heparin in acute
circumstances and then turn to oral warfarin.
Antithrombin interferes with the development of
prothrombin thrombin; it is a naturally occurring
anticoagulant, as stated earlier, and a natural protection
mechanism of the clotting mechanism. Fondaparinux is a
more recent anticoagulant. It prevents factor Xa and
blocks the cascade of clotting to avoid the development of
clots. It is distributed in pre-filled syringes, making it handy
for patients who are self-administering medications at
home.
Pharmacokinetics Heparin is injected as IV or subcutaneously and has an
nearly instantaneous initiation of action. It's excreted in the
body. Warfarin, dabigatran, and rivaroxaban are used by
Page | 46
mouth. Many other drugs in this class (heparin,
antithrombin, argatroban, desirudin, fondaparinux, and
bivalirudin) are prescribed parenterally. Warfarin is easily
absorbed by the GI system, metabolized in the liver, and
excreted in urine and feces. Warfarin 's period of action is
about 3 days; its effects continue for 4 to 5 days. Owing to
the time delay, warfarin is not the medication of choice in
an acute situation, but is comfortable and effective for
extended effects. Dabigatran has a fast onset of activity,
peaking in 1-2 hours. It has a half-life of 12 to 17 hours
and is excreted in the urine after it is metabolized in the
liver. Rivaroxaban is also quickly consumed with peak
effects in 2 to 4 hours. It has a much reduced half-life of 5
to 9 hours and is excreted in the urine and feces following
metabolization in the liver. Patients must take care of
keeping this dabigatran (in a dim, non-humid environment)
and in the original bottle, and it is only safe for 60 days
from the time the bottle is opened.
Since antithrombin is an exogenous type of a naturally
occurring anticoagulant, it is processed by the body in the
same manner as it treats naturally occurring antithrombin.
Argatroban is delivered as a continuous IV infusion.
Desirudin and fondaparinux are readily absorbed from
subcutaneous sites and metabolized and excreted by the
kidneys. Bivalirudin is given IV and excreted through the
kidneys.
Contraindications and Anticoagulants are contraindicated in the context of known
Cautions drug allergies to discourage hypersensitivity reactions.
They should also not be used for any diseases that may
be impaired by abnormal bleeding rates, including
hemorrhagic disorders, recent trauma, spinal puncture, GI
ulcers, recent surgery, intrauterine implant positioning,
tuberculosis, indwelling catheters, and threatened
abortion. Warfarin is contraindicated in pregnancy due to
fetal injury and death; in lactation due to a possible danger
to the baby; and in renal or hepatic disease which may
interact with the absorption and efficacy of these
medications. While some adverse fetal effects have been
reported during breastfeeding, heparin does not penetrate
breast milk and is thus the anticoagulant of choice if one
is required during lactation. Caution may be used in
patients with cardiac disease, thyrotoxicosis, senility or
insanity owing to the risk for unpredictable results and in
patients with diarrhoea or fever, which may change the
usual clotting mechanism by removing vitamin K from the
intestine or stimulating plasminogen. Caution should be
used in breastfeeding and lactation with anticoagulants
other than warfarin due to the potential for toxic effects;
the benefits are supposed to outweigh the potential risks.
Page | 47
Adverse Effects Bleeding, ranging from bleeding gums with teeth brushing
to serious internal hemorrhage, is the most frequent side
effect of anticoagulants. Patients need to think about the
management, handling of syringes, and symptoms of
bleeding to be controlled. Periodic blood testing may be
expected to determine the effects of the drug on the body.
Clotting periods should be carefully tracked in order to
prevent these issues. Severe adverse reactions can occur
when a medication is added or withdrawn from the
medication of a patient receiving warfarin without proper
patient supervision and dosage correction of warfarin (see
Clinically Significant Medication – Drug Interactions).
Warfarin has been linked with alopecia and dermatitis,
bone marrow depression and, less commonly, persistent
and painful erections. The following function with
Concentrate on Safe Drug Administration addresses the
management of toxicity of heparin. Nausea, GI upset,
diarrhoea, and hepatic instability can also be secondary to
overt opioid toxicity.
Clinically Important Increased bleeding can occur if heparin is mixed with oral
Drug-Drug Interactions anticoagulants, salicylates, penicillins, or cephalosporins.
Decreased anticoagulation can occur when heparin is
mixed with nitroglycerin.
Warfarin has recorded drug-drug reactions with a
significant variety of other drugs. It is a good idea never to
add or withdraw a drug from the warfarin regimen of a
patient without thorough medical observation and
modifying the warfarin dosage to avoid severe adverse
reactions. Owing to the many factors that can influence the
clinical dose of warfarin, it is also very difficult to obtain a
stable level and sustain that level. Dabigatran and
rivaroxaban should be used with caution with antifungals,
erythromycin, ritonavir, phenytoin, rifampin due to
metabolism alterations. All these drugs should be used
with caution if they are combined with any other drugs
known to increase bleeding effects.
Thrombolytic Agents Thrombolytic agents break down the thrombus produced
by the activation of the plasma system. This method is
called the Clot Resolution method. Thrombolytic agents
include alterplase (Activase), reteplase (Retavase),
tenecteplase (TNKase) and urokinase (Abbokinase).
Therapeutic actions If a thrombus has already formed in an artery (e.g. during
and indications acute MI), it may be important to remove the clot to clear
the channel and return the flow of blood to the dependent
tissue. Both medications available for this reason are used
Page | 48
to enable the natural anticlotting system — the conversion
of plasminogen to plasmin. The triggering of this
mechanism breaks down fibrin threads and dissolves
every sort of clot. Thrombolytics are successful only if the
patient has plasma plasminogen.
Pharmacokinetics These medications are given IV and are eliminated from
the body during the metabolism of the liver. They pass the
placenta, but it is not clear whether or not they reach
breast milk.
Contraindications and The use of thrombolytic agents is contraindicated in the
Cautions case of allergy to any of these medications to avoid
reactions of hypersensitivity. They should also not be used
for any situation that could exacerbate the dis-solution of
the clots, like recent surgery, active internal bleeding,
cerebrovascular accident (CVA) within the last 2 months,
aneurysm, obstetrical delivery, organ biopsy, recent
extreme GI leakage, breakdown of non-compressible
blood vessels, recent major trauma (including cardio-
pulmonary resuscitation), documented blood clotting
diseases, cerebrovascular disease, unregulated
hypertension, and liver failure (which may impact the
body's condition).
Ses medications are also contraindicated during
breastfeeding.
Due to potential adverse effects on the fetus or neonate.
This medications should not be used during breastfeeding
until the benefits for the mother greatly outweigh the
possible risks to the child. Caution should be used during
lactation due to the possible possibility of bleeding in the
nursing infant.
Adverse Effects Blood is the most frequent side effect associated with the
use of thrombolytic agents. Patients should be carefully
watched for heart arrhythmias (coronary reperfusion) and
hypotension. Hypersensitivity reactions are not unusual;
they range from rash and flushing to bronchospasm to
anaphylactic reactions.
Clinically Important The risk of hemorrhage increases when thrombolytic
Drug-Drug Interactions agents are used with either anticoagulant or antiplatelet
treatment.
Other drugs that affect clot formation are also effective in preventing
thromboembolic episodes. These drugs include the low-molecular-weight heparins,
adjunctive agents used to help alleviate adverse reactions to these drugs, and a
hemorheological agent.
Page | 49
Low-Molecular-Weight A variety of low-molecular - weight heparins have been
Heparins developed in the late 1990s. These medications inhibit
thrombus and clot forming by blocking the Xa and IIa
influences. Owing to the size and function of the
compounds, these medications do not substantially affect
thrombin, clotting, or PT; thus, they cause less systemic
adverse reactions. These medications are recommended
for very particular use in the prevention of clots and emboli
formation following such operations or extended bed rest.
The condition of a patient taking one of these medications
is close to that of a patient receiving heparin. The
medication is supplied just before (or just after) surgery
and then lasts for 7 to 14 days throughout the
postoperative healing period. Caution should be used to
prevent pairing these medications with regular heparin
therapy; severe bleeding episodes and deaths have been
reported where this mixture has been mistakenly used.
Low molecular weight heparins include dalteparin,
enoxaparin and tinzaparin.
Anticoagulant The agents used in anticoagulant adjunctive therapy
Adjunctive Therapy include lepirudin, protamin sulfate and vitamin K. See
Focus on Safe Drug Administration under Adverse Effects
for anticoagulants for further information on vitamin K and
protamine sulfate.
Lepirudin (Refludan) is an IV drug that has been
developed to treat a rare allergic response to heparin. In
certain patients, heparin allergy precipitates heparin-
induced thrombocythemia with concurrent
thromboembolic disease. Lepirudin specifically removes
thrombin and prevents the thromboembolic effects of this
reaction. The normal therapy is 0.4 mg / kg of initial IV
bolus followed by a regular infusion of 0.15 mg / kg for 2
to 10 days. Patients should be checked for bleeding from
every position and for the creation of possible hepatic
injury.
Hemorrheologic Agent Pentoxifylline (Trental) is classified as a hemorrhage
agent or a drug that can cause hemorrhage. It is a
xanthine that, like caffeine and theophylline, reduces
platelet aggregation and decreases the concentration of
fibrinogens in the blood. These effects can minimize the
formation of blood clots and improve the flow of blood into
narrowed or weakened vessels. The mechanism of action
by which pentoxifylline does these things is unclear. It is
one of the very few medications reported to be effective in
the treatment of intermittent claudication, a debilitating
vascular condition in the legs.
Since pentoxifylline is a xanthine, it is associated with
multiple cardiovascular stimulating effects; people with
Page | 50
ongoing cardiovascular conditions need to be closely
controlled when taking this drug. Pentoxifylline can also
induce headaches, dizziness , nausea and stomach
distress. It is taken orally three times a day for at least 8
weeks to determine its efficacy.
There are various bleeding conditions at the other end of the continuum with
coagulation issues. These shall contain the following:
● Hemophilia, in which there is a hereditary loss of clot-ting variables, which makes
the patient vulnerable to prolonged bleeding due to injury.
● Liver disease, where the clotting factors and proteins required for clotting are not
made.
● Bone marrow disorders in which platelets are not produced in adequate amounts
to be successful.
● Bleeding conditions are treated with clotting agents and medications that facilitate
the mechanism of coagulation.
Antihemophilic Agents Drugs used to cure hemophilia are replacements for
essential clotting mechanisms that are genetically absent
in this unique form of hemophilia. These medications
include antihemophilic factor (Bioclate, ReFacto, and
others), coagulation factor VIIa (NovoSeven) and factor IX
(BeneFix, Profilnine SD, and others), fac-to-IX complex
(Bebulin VH, Profilnine SD), anti-inhibitor coagulant
complex (Felba NA), factor XIII (Corifact).
Therapeutic actions Antihemophilic medications replace clotting factors that
and indications are either either absent or poor in a common form of
hemophilia. The medication of choice depends on the
individual hemophilia being treated. Antihemophilic factor
is factor VIII, a clotting factor that is absent in classical
hemophilia (hemophilia A). This agent is used to fix or
avoid bleeding episodes or to facilitate surgery.
Coagulation factor VIIa and factor IX and factor IX
complexes are seen in patients with hemophilia A or B.
Coagulation factor VIIa is a formulation made from mouse,
hamster and bovine proteins containing varying
concentrations of preformed clotting factors (see
Contraindications and Cautions). Factor IX complex
comprises plasma fractions of several clotting factors and
raises the blood volumes of factors II, VII, IX and X. Factor
XIII replaces factor XIII in patients with congenital
deficiency. Antiinhibitor coagulant complex is used to
control accidental bleeding or to treat surgery in patients
with hemophilia A and B with inhibitors. The drug of choice
for any given condition is determined by its unique
coagulation disorders.
Pharmacokinetics These compounds substitute natural clotting factors and
are treated by the body as such. They must be
Page | 51
administered intravenously and are treated by the body in
the same manner as naturally occurring clotting factors
are processed in the plasma, typically with a half-life of 24
to 36 hours.
Contraindications and Antihemophilic factor is contraindicated in the case of
Cautions known mouse protein allergy to prevent hypersensitivity
reactions. Factor IX is contraindicated in the case of liver
disease or symptoms of intravascular coagulation or
fibrinolysis to prevent severe deterioration of these
disorders. Coagulation factor VIIa is contraindicated for
documented allergies of rat, hamster or bovine products
to avoid hypersensitivity reactions. These medications are
not approved for use during lactation, and due to the risk
for adverse effects on the infant or the baby, caution
should be used during breastfeeding. They can only be
used during pregnancy if the benefit to the mother
significantly outweighs the possible harm to the child. It is
advised that a separate way of feeding the baby be used
when certain medications are required during lactation.
Since these medications are used to avoid severe
bleeding complications or to treat bleeding episodes, there
are few contraindications for their use.
hemophilic agents include hazards involved with the use
of blood products ( e.g. hepatitis, AIDS). Headache,
flushing, chills , fever, and lethargy can occur as a reaction
to foreign protein injections. Nausea and vomiting can also
occur, such as stinging, pain, and burning at the injection
site.
Antihemophilic Agents Drugs used to cure hemophilia are substitutive agents for
the same clotting factors that are naturally absent in the
particular form of hemophilia. These medications include
antihemophilic factor (Bioclate, ReFacto, and others),
coagulation factor VIIa (NovoSeven) and factor IX
(BeneFix, Profilnine SD, and others), fac-to-IX complex
(Bebulin VH, Profilnine SD), anti-inhibitor coagulant
complex (Felba NA), factor XIII (Corifact).
Therapeutic actions Antihemophilic medications replace clotting factors that
and indications are either either absent or poor in a common form of
hemophilia. The medication of choice depends on the
individual hemophilia being treated. Antihemophilic factor
is factor VIII, a clotting factor that is absent in classical
hemophilia (hemophilia A). This agent is used to fix or
avoid bleeding episodes or to facilitate surgery.
Page | 52
Coagulation factor VIIa and factor IX and factor IX
complexes are seen in patients with hemophilia A or B.
Coagulation factor VIIa is a formulation made from mouse,
hamster and bovine proteins containing varying
concentrations of preformed clotting factors (see
Contraindications and Cautions). Factor IX complex
comprises plasma fractions of several clotting factors and
raises the blood volumes of factors II, VII, IX and X. Factor
XIII replaces factor XIII in patients with congenital
deficiency. Antiinhibitor coagulant complex is used to
control accidental bleeding or to treat surgery in patients
with hemophilia A and B with inhibitors. The drug of choice
for any given condition is determined by its unique
coagulation disorders.
Pharmacokinetics These compounds substitute natural clotting factors and
are treated by the body as such. They must be
administered intravenously and are treated by the body in
the same manner as naturally occurring clotting factors
are processed in the plasma, typically with a half-life of 24
to 36 hours.
Contraindications and Antihemophilic factor is contraindicated in the case of
Cautions known mouse protein allergy to prevent hypersensitivity
reactions. Factor IX is contraindicated in the case of liver
disease or symptoms of intravascular coagulation or
fibrinolysis to prevent severe deterioration of these
disorders. Coagulation factor VIIa is contraindicated for
documented allergies of rat, hamster or bovine products
to avoid hypersensitivity reactions. These medications are
not approved for use during lactation, and due to the risk
for adverse effects on the infant or the baby, caution
should be used during breastfeeding. They can only be
used during pregnancy if the benefit to the mother
significantly outweighs the possible harm to the child. It is
advised that a separate way of feeding the baby be used
when certain medications are required during lactation.
Since these medications are used to avoid severe
bleeding complications or to treat bleeding episodes, there
are few contraindications for their use.
hemophilic agents include hazards involved with the use
of blood products ( e.g. hepatitis, AIDS). Headache,
flushing, chills , fever, and lethargy can occur as a reaction
to foreign protein injections. Nausea and vomiting can also
occur, such as stinging, pain, and burning at the injection
site.
Page | 53
Hemostatic Agents Any conditions result in a fibrinolytic state with severe
plasminogen production and a risk of clot-dissolving
bleeding. For example , patients undergoing repeat
coronary artery bypass surgery (CABG) are extremely
vulnerable to excessive bleeding and may require a blood
transfusion. Wetatic agents are used to avoid bleeding.
Wetatic medications can be either systemic or topical.
The haemostatic medicine that is used routinely is
aminocaproic acid (Amicar). Topical haemostatic agents
include absorbable gelatin (Gelfoam), human fibrin seal
(Artiss, Evicel), microfibrillar collagen (Avitene), thrombin
(Thrombinar, Thrombostat) and recombinant thrombin
(Recothrom).
Therapeutic actions Widespread haemostatic agents are used to avoid a
and indications significant or widespread breakdown of the body's clot,
(Systemic Hemostatic thus avoiding blood loss in conditions where severe
Agents) systemic bleeding or hyperfibrinolysis can occur. There is
only one systematic haemostatic agent available for use
in the United States.
Aminocaproic acid inhibits plasminogen-active
compounds and has some antiplasmin activity. When
taking an oral form of aminocaproic acid, the patient may
need to take 10 pills in the first hour and then continue to
take the medication around the clock. Aprotinin, another
systemic haemostatic agent used to minimize blood
pressure and the need for CABG-related transfusions,
was withdrawn from the market in 2008 after evidence of
an elevated risk of cardiovascular incidents in patients
treated with this drug.
Therapeutic actions Any surface cuts cause so much damage to small arteries
and indications (Topical in the region that there is no clotting and blood is steadily
Hemostatic Agents) and constantly lost. Topical or territorial haemostatic
agents are also used in these cases. The application of
these medications is also utilized as an adjunctive
procedure in the treatment of wounds or decubitus ulcers.
The medication of choice depends on the extent of the
accident and the desire of the prescriber. Human fibrin
sealant is the newest topical haemostatic agent. Thrombin
recombinant is the first licensed topical hemostatic agent
to be developed using recombinant DNA technology (this
would eliminate many of the possible allergic reactions
associated with bovine thrombin
Pharmacokinetics Any surface cuts cause so much damage to small arteries
in the region that there is no clotting and blood is steadily
Page | 54
(Systemic Hemostatic and constantly lost. Topical or territorial haemostatic
Agents) agents are also used in these cases. The application of
these medications is also utilized as an adjunctive
procedure in the treatment of wounds or decubitus ulcers.
The medication of choice depends on the extent of the
accident and the desire of the prescriber. Human fibrin
sealant is the newest topical haemostatic agent. Thrombin
recombinant is the first licensed topical hemostatic agent
to be developed using recombinant DNA technology.
Pharmacokinetics Aminocaproic acid is used in oral and IV form. It is quickly
consumed and broadly spread throughout the body. It is
(Topical Hemostatic
excreted relatively unchanged in urine, with a 2-hour half-
Agents)
life.
Contraindications and Aminocaproic acid is contraindicated in the case of allergy

Cautions to the medication to avoid hypersensitivity reactions and
acute DIC due to the possibility of tissue necrosis. Caution
(Systemic Hemostatic
can be used in heart disease due to the possibility of
Agents)
arrhythmias and renal and hepatic dysfunction that may
impair the excretion of these medications and normal
clotting processes. While efficacy for the use of this drug
during pregnancy has not been defined, it can only be
used if the benefits to the mother significantly outweigh the
possible hazards to the neonate due to the potential for
harmful effects on the fetus. It is advised that
breastfeeding mothers use a new way of feeding the baby
if this medication is used because of the risk for adverse
effects on the infant.
Contraindications and Using thrombin with caution in people who have an
Cautions aversion to bovine products. Since thrombin comes from
animal origins, it can precipitate an allergic reaction; the
(Topical Hemostatic
patient needs to be closely watched for such reactions.
Agents)
Many of the possible allergic reactions associated with
bovine thrombin would be reduced as a result of the
approval of the recombinant thrombin to be generated
using recombinant DNA technology. Protection for the use
of recombinant thrombin in children has not been
identified.
Adverse Effects Excessive clotting is the most frequent side effect
associated with systemic hemostatic agents. In 2007,
there were several records of rising coronary events,
Agents)
including deaths in patients taking hemostatic medication
aprotinin. Any of the incidents happened months following
the use of the medication. In 2008, the drug was pulled
from the marketCNS symptoms of aminocaproic acid can
include nausea, somnolence, dizziness, headache, and
psychiatric disorders, many of which may be due to
changes in cerebral blood flow associated with
Page | 55
improvements in clot breakdown. GI symptoms, including
fatigue, cramps, and diarrhea, can be associated with
prolonged clotting of the GI tract, inducing GI reflexive
enhancement. Weakness, weakness, malaise, and
muscle pain can arise as small clots build up in muscles.
Intrarenal obstruction and renal dysfunction has also been
recorded
Adverse Effects The use of absorbable gelatin and microfibrillar collagen
can pose a risk of infection as bacteria may become stuck
(Topical Hemostatic
in the vascular region when the sponge is applied.
Agents)
Immediate removal of the sponge and cleaning of the area
can help to minimize this harm.
Clinically Important Aminocaproic acid is associated with the risk of
Drug-Drug Interactions hypercoagulation when it is paired with oral contraceptives
or estrogens. The risk of bleeding increases when
provided with heparin.
Agents)
Clinically Important No drug-drug reactions with topically applied hemostatic
Drug-Drug Interactions agents have been documented.
(Topical Hemostatic
Agents)
Note, diseases that are closely linked to the clotting mechanism include
thromboembolic diseases, in which too much clotting can lead to embolism and occlusion
of blood vessels, and hemorrhagic disorders, including hemophilia, in which lack of
successful clotting can contribute to extra blood. 6
loss.

1. Coagulation is a transfer of fluid blood into a stable state to plug gaps in the artery
system.
a. True
b. False
c. Partly true
d. Partly false
2. Coagulation includes many mechanisms, including vasoconstriction, plug-forming
platelet aggregation, and the development of intestinal and extrinsic clots triggered by
the Hageman factor to cover any splits in the flow.
a. True
b. False
c. Partly true
d. Partly false
6
Karch, A.M. (2019), Focus on Nursing Pharmacology, 7th Edition. Wolters Kluwer Chapter 48.
Page | 56
3. The final step in the development of a clot is the conversion of prothrombin to
thrombin, which breaks down fibrinogen to form insoluble fibrin strings.
a. True
b. False
c. Partly true
d. Partly false
4. When a clot is formed, it must be extracted to avoid the occlusion of blood vessels
and the lack of blood flow to tissues.
a. True
b. False
c. Partly true
d. Partly false
5. Plasminogen is the foundation for a clot-dissolving mechanism. A variety of variables,
including Hageman factor, transform to plasmin (fibrinolysin). Plasmin dissolves fibrin
fibers and dissolves the clot.
a. True
b. False
Page | 57
Title of the Lesson: Drugs Used to Treat Anemias
Duration: 2 hours
Blood is important for cell life because it provides oxygen and nutrients and
eliminates waste materials that can be toxic to tissues. It also includes fac-towers that
help to support the vascular system and keep it sealed. In addition, blood contains
important components of the immune and inflammatory systems to protect the body from
infection.
Blood is made up of liquid and formed elements. The liquid portion of your blood
is called the plasma. Plasma is mainly water, but it also includes proteins that are
important for immune response and blood clotting. The blood constituents include
leukocytes (white blood cells) which are an integral part of the immune system
erythrocytes (red blood cells [RBCs]) which bring oxygen to the tissues and extract carbon
dioxide for delivery to the lungs; and platelets which play an important role in coagulation.
Anemia is the result of any modification in erythropoiesis, the RBC development
mechanism that occurs in the myeloid tissue of the bone marrow. The rate of RBC
development is regulated by glycoprotein erythropoietin, which is released from the
kidneys in response to reduced blood flow or reduced blood pressure in the kidneys.
Under the control of erythropoietin, the undifferentiated cell in the bone marrow has
become a hemocytoblast. This cell uses many amino acids, lipids, sugars, vitamin B12,
folic acid and iron to make RBC immature. In the last step of RBC development, the cell
loses its nucleus and goes into circulation. This cell, called a reticulocyte, finishes the
ripening process in circulation.
While mature RBC does not have a nucleus, it has a large surface area to enhance
its ability to transport oxygen and carbon dioxide. Since it lacks a nucleus, RBC is unable
to replicate or sustain itself, and will ultimately wear out. The estimated period of the RBC
is roughly 120 days. At that point, the elderly RBC was lysed in the stomach, spleen, or
bone marrow. RBC building blocks like iron, vitamin B12, are then recycled and returned
to the bone marrow for the development of new RBCs. The only component of RBC that
cannot be recovered is harmful pigment bilirubin, which is conjugated in the liver,
transferred into bile and excreted in the stool or urine from the body. Bilirubine is what
brings meaning to all of these excretions.
Erythropoiesis is a continuous mechanism that kills and restores approximately
1% of the RBCs of the body every day. Anemia can occur if erythropoietin levels are low.
This is found in renal failure as the kidneys are no longer capable of processing
erythropoietin. It can also occur if the body does not have enough building blocks to shape
RBCs, or if an individual has a genetic predisposition to shape severe RBCs, such as
sickle cell anemia. In order to develop healthy RBCs, the bone marrow must have the
following:
Adequate levels of iron required in the creation of hemoglobin rings to bear oxygen.
Minimal quantities of vitamin B12 and folic acid, providing a solid support system
that can withstand a 120-day trickle into blood vessels.
Necessary amino acids and carbohydrates for the completion of hemoglobin rings,
cell membrane and basic structure.
Normally, an human diet provides sufficient amounts of all these ingredients, which
are absorbed from the gastrointestinal ( GI ) tract and transported to the bone marrow.
However, if a diet cannot provide enough nutrients or if enough nutrient cannot be
absorbed, a person can develop a deficiency anemia. Fewer RBCs are produced and
those produced are young and inefficient iron carriers. This form of anemia is referred to
as deficiency anemia. Another type of anemia is megaloblastic anemia, which includes a
decline in RBC development and the inefficiency of those RBCs that are produced
(usually do not last for 120 days, which is normal for RBC life). Patients of megaloblastic
anemia typically lack vitamin B12 or folic acid.
Page | 58
The third form of anemia is hemolytic anemia, which includes the lysing of RBCs
due to genetic causes or exposure to toxins. Sickle cell anemia is a type of hemolytic
anemia.
Erythropoiesis- Patients who are no longer able to produce sufficiently
Stimulating Agents erythropoietin in their kidneys can benefit from treatment
with exogenous erythropoietin, which is available as
epoetin alfa (Epogen, Procrit) and darbepoetin alfa
(Aranesp) medications. When agents are used to activate
the bone marrow to produce more RBCs, it is necessary
to ensure that the patient has sufficient quantities of the
components needed to make RBCs, including sufficient
iron.
Therapeutic actions Epoetin alfa functions as a normal glycoprotein
and indications erythropoietin to promote the development of RBCs in the
bone marrow. This drug is recommended for the
prevention of anemia associated with renal failure and for
patients on dialysis; for anemia associated with AIDS
therapy; and for anemia associated with cancer
chemotherapy where the bone marrow is depressed and
the kidneys may be impaired by toxic drugs (Procrit only).
It is not approved for the treatment of any anemia and is
not a supplement for whole blood in the emergency
treatment of anemia.
Pharmacokinetics Both of these medications can be delivered by IV or
subcutaneous injection. Epoetin alfa, which is like
endogenous erythropoietin, is metabolized in the
bloodstream by a natural mechanism used by the body to
extract erythropoietin. It has a gradual onset and peaks in
5 to 24 hours, and the duration of the affect is typically 24
hours. It has a half-life of between 4 and 13 hours and is
excreted in the urine. Darbepoetin alfa has a half-life of 21
hours after intravenous ( IV) administration or 49 hours
after subcutaneous administration. It has peak results in
14 hours (if given IV) or 34 hours (subcutaneously). Impact
duration is 24 to 72 hours, and excretion happens by the
urine. Peginesatide has a half-life of between 25 and 32
hours. It has a sluggish start and hits peak results in 48
hours. It is therefore removed in the blood and excreted in
the urine. It is not clear whether epoetin alfa or
peginesatide is in breast milk.
Contraindications and All three of these medications are contraindicated in the
Cautions presence of unregulated hypertension due to the
possibility of more hypertension as RBC numbers rise and
strain inside the vascular system increases; with
documented hypersensitivity to every part of the
medication to prevent hypersensitivity reactions; and with
Page | 59
lactation due to the potential for allergic-type neonatal
reactions. There are no sufficient trials of breastfeeding,
but use can be limited to cases where the benefit to the
mother obviously outweighs the possible harm to the child.
Use care when prescribing any of these medications to
patients with normal renal function and sufficient levels of
erythropoietin due to rebound reductions in erythropoietin
and when administered to patients with anemia and proper
renal function, as this may cause more serious anemia.
Adverse Effects The side symptoms most often associated with these
medications include the symptoms of headache,
weakness, asthenia and dizziness on the CNS and the risk
for severe seizures. These symptoms may be the product
of a cellular reaction to glycoproteins. Nausea, vomiting ,
and diarrhea are also typical symptoms. Cardiovascular
signs may include hypertension, edema, and even chest
pain, both of which may be linked to a rise in RBC numbers
that may alter the equilibrium within the cardiovascular
system. Significant cardiovascular symptoms and
elevated risk of DVT have been shown when hemoglobin
is greater than 12 g / dL. Patients undergoing IV
administration should also be checked for potential clotting
of the access line due to the immediate cellular effects of
the medication. Rapid cancer development happens when
hemoglobin is greater than 12 g / dL. Post-marketing trials
have shown that pure red cell aplasia associated with
erythropoietin neutralizing antibodies may occur with both
of these products. In 2008, following review of many post-
marketing trials, these medications were forced to add
black-box alerts to their prescription information as stated
in the Section on Safe Medication Administration below.
Agents Used for Iron While most people get all the iron they need from diet, diet
Deficiency Anemia alone might not be sufficient in certain cases. The iron
preparations available include ferrous fumarate (Feostat),
ferrous gluconate (Fergon), ferrous sulfate (Feosol),
ferrous sulfate exsicated (Feratab, Weak FE),
ferrumoxytol (Feraheme), iron dextrane (InFeD), iron
sucrose (Venofer) and sodium ferric gluconate complex
(Ferrlecit).
Therapeutic actions Iron formulations improve the concentration of blood iron.
and indications They are either converted to hemoglobin or stuck in
reticuloendothelial cells for storage and eventual release
and conversion into a functional source of iron for RBC
development. Oral iron formulations are often used to help
these patients restore a positive iron balance; these
Page | 60
formulations need to be complemented by a sufficient
dietary consumption of iron. They are recommended for
the treatment of iron deficient anemia and can also be
used as an adjunctive therapy in patients taking an
erythropoietic-stimulating drug. The medication of choice
relies on the personal interest and expertise of the
prescriber, and also on the variety of samples available to
the patient.
Pharmacokinetics Ferrous fumarate, ferrous gluconate, ferrous sulfate and
ferrous sulfate exsicated are available for oral
administration. Iron dextran is a parenteral source of iron
delivered by the Z-track system, and can be used if the
oral source fails or cannot be handled. Patients with
serious problems with GI absorption can need this kind of
iron. Patients should be switched to oral form if necessary
due to discomfort connected with intramuscular (IM)
administration of iron. Iron sucrose, ferumoxytol and
sodium ferric gluconate complex are delivered
intravenously directly to those undergoing chronic
hemodialysis or who are in renal failure and not on dialysis
but are getting concurrent erythropoietin therapy.
Iron is mostly absorbed by the active delivery mechanism
from the small intestine. It is borne in the blood, bound to
transferrin. Limited quantities are lost every day in saliva ,
urine, sloughing of skin and mucosal cells, and sloughing
of digestive cells, as well as in the menstrual discharge of
women. Any of the oral medicine taken is lost in the urine,
but eventually some of the metal is absorbed into the
intestine and transported to the bone marrow. It can take
2 to 3 weeks to see progress and up to 6 to 10 months to
recover to a healthy iron level after a deficiency has arisen.
It is used during breastfeeding and lactation to help the
mother satisfy the elevated need for iron that exists at that
time.
Contraindications and These medications are contraindicated in patients with
Cautions known allergy to any of these formulations because
extreme hyper-sensitivity reactions have been correlated
with the parenteral type of iron. They are also
contraindicated under the following conditions:
hemochromatosis (excessive iron); hemolytic anemia,
which can increase serum iron levels and trigger toxicity;
natural iron absorption because the medicine may not be
consumed and would merely travel through the body; and
peptic ulcer, colitis, or regional enteritis because the
medicine may be potentially harmful to certain tissues and
can trigger exacerbation.
Adverse Effects The most frequent side effects associated with oral iron
are due to overt GI pain, including GI discomfort, anorexia,
Page | 61
fatigue, vomiting , diarrhea, dark stools, and constipation.
As serum levels increase, iron can be specifically toxic to
the CNS, causing coma and even death. Parenteral iron is
associated with extreme anaphylactic responses, skin
inflammation, tissue staining, and phlebitis. Ferumoxytol is
a supermagnetic iron oxide capable of modifying MRI
images and perception for up to 3 months after
administration; patients should be informed that they have
been given this drug and should be encouraged to
disclose it before any laboratory examinations have been
carried out.
Clinically Important Iron absorption reduces if iron preparations are taken with
Drug-Drug Interactions antacids, tetracyclines or cimetidine; if these medications
are to be used, they should be kept at least 2 hours apart.
Anti-infective reaction to ciprofloxacin, norfloxacin, or
ofloxacin can decrease if these medications are taken with
iron due to reduced absorption; they should also be
administered at least 2 hours apart.
Increased levels of iron occur as iron preparations are
taken with chloramphenicol; any symptoms of iron toxicity
should be carefully watched in patients undergoing this
com-bination. Effects of levodopa can decrease if taken
with iron preparations; patients taking all of these drugs
should take at least 2 hours apart.
Clinically Important Iron is not consumed as treated with antacids, eggs , milk,
Drug-Food Interactions coffee or tea. Both drugs should not be treated at the same
time. Acid liquids should increase the absorption of iron
and should not be given at the same time.
Vitamin B12 Folic acid and vitamin B12 are important for cell growth
and division and for the formation of high stroma in RBCs
Folic Acid (Folate)
Vitamin B12 is also essential for the preservation of the
myelin sheath in the nerve tissue. Both are prescribed as
a replacement medication for food disorders, as a
supplement in high-demand conditions such as maternity
and lactation, and for the treatment of megaloblastic
anemia. Folic acid is used as a recovery medicine for cells
exposed to such poisonous chemical agents. Leucovorin
is used as a rescue medication after methotrexate therapy
to mitigate the risk of methotrexate due to diminished
removal or abuse of folic acid antagonists such as
trimethoprim and to treat multiple megaloblastic anemias.
Levoleucovorin is the newest medication in this class and
is only approved to minimize the toxicity of methotrexate
Page | 62
due to reduced absorption or overdose of folic acid
antagonists of the treatment of osteosarcomas.
Therapeutic actions Folic acid can be delivered in oral, IM, IV and
and indications subcutaneous forms. Parenteral medications are
recommended for patients with potential absorption
problems; if possible, all other patients should be offered
oral form. Leucovorin is a reduced source of folic acid that
is required for oral, IM and IV use. Levoleucovorin is only
available in the form of IV.
Hydroxocobalamin must be administered intramuscularly
every day for 5 to 10 days to build up quantities, then once
a month for life. It can not be taken orally because the
problem with pernicious anemia is the failure to digest
vitamin B12 secondary to low levels of intestinal factor. It
can be used in states of elevated need (e.g. breastfeeding,
growth spurts) or nutritional deficit, but oral vitamins are
favored in most situations. Cyanocobalamin is not as
closely bound to proteins and does not survive as long as
hydroxocobalamin in the body. This drug is mainly
processed in the liver and released slowly when required
for metabolic function. It is available as an intranasal gel
that enables the absorption of vitamin B12 directly through
the nasal mucosa. Nascobal is used once a week as an
intranasal spray in a single nostril.
Since infusion, folic acid and vitamin B12 are well
absorbed, metabolized primarily in the liver and excreted
in the urine. These vitamins are considered necessary
during pregnancy and lactation due to the increased
demands of the mother's metabolism.
Pharmacokinetics These medications are contraindicated in the case of
known allergies to these medications or their ingredients
in order to prevent hypersensitivity reactions. They should
be treated with caution in patients that are pregnant or
lactating or who have any anemias to ensure that the right
dosage of the drug is used to have the maximum clinical
benefit and to minimize the possibility of harmful effects.
Nasal cyanocobalamin should be used with caution in the
case of nasal degradation or ulcers that may change the
absorption of the medication.
Contraindications and These medications have comparatively little side effects
Cautions when they are used as a supplement for the chemicals
needed. Hydroxocobalamin has been linked with
scratching, rash, and symptoms of elevated vitamin B
levels, which can also include peripheral edema and heart
failure. Mild diarrhoea has been documented with these
medications. Pain and irritation can occur at injection sites.
Page | 63
Nasal discomfort can occur with the use of intranasal
spray.
Therapeutic actions Hydroxyurea, taken for several months, increases the
and indications amount of fetal hemoglobin formed in the bone marrow
and dilutes the development of defective hemoglobin S in
Hydroxyurea
adults with sickle cell anemia. This results in less clogging
of small vessels and painful, anoxic symptoms of RBC
sickling or piling.
Pharmacokinetics Hydroxyurea is well absorbed by the oral route from the GI
tract, reaching peak levels in 1 to 4 hours. It is metabolized
in the liver and excreted in the urine for a half-life of 3 to 4
hours. It is believed to cross the placenta and enter breast
milk.
Contraindications and Hydroxyurea is contraindicated with documented allergy
Cautions to any part of the medication to avoid hypersensitivity
reactions and extreme anemia or leukopenia because it
may induce further repression of the bone marrow. It may
be used with caution in the case of compromised liver or
kidney activity, which could conflict with the absorption
and excretion of the medication, and can only be used
during pregnancy and lactation if the benefit to the mother
significantly outweighs the possible harm to the fetus or
baby because the medication crosses the placenta and
enters the breast milk and may cause serious effects in
the fetus or the baby.
Adverse Effects Hydroxyurea is cytotoxic and is associated with adverse
effects associated with the death of cells, especially in
cells that are rapidly turning over. GI effects include
anorexia, nausea, vomiting, stomatitis, diarrhea, or
constipation; dermatological effects include rash or
erythema; and bone marrow suppression usually occurs.
Headache, dizziness, disorientation, fever, chills, and
malaise have been reported, possibly related to the effects
of cell death in the body. As with other cytotoxic drugs,
there is an increased risk of cancer development.
Clinically Important There is an elevated risk of uric acid levels when this drug
Drug-Drug Interactions is paired with other uricosuric agents; if this mixture is to
be used, dose changes would be required for the
uricosuric agent.

Circle the option that best answer the question or complete the statement.
Page | 64
1. Blood is composed of liquid plasma and formed components (white blood cells, RBCs,
and platelets) and includes oxygen and nutrients that are necessary for cell survival;
it provides them to the cells and extracts waste products from the tissues.
a. True
b. False
c. Partly true
d. Partly false
2. RBCs are produced in the bone marrow in a phase called erythropoiesis, which is
regulated by glycoprotein erythropoietin produced in the kidneys..
a. True
b. False
c. Partly true
d. Partly false
3. RBCs do not have a nucleus, and their lifetime is about 120 days, after which time
they are lysed and their building blocks are recycled to produce new RBCs.
a. True
b. False
c. Partly true
d. Partly false
4. The bone marrow uses magnesium, amino acids , sugars, folic acid and vitamin B12
to generate safe and effective RBCs.
a. True
b. False
c. Partly true
d. Partly false
5. Insufficient quantity or immaturity of RBCs results in low levels of oxygen in the

tissues, fatigue , and lack of reserve.
a. True
b. False
c. Partly true
d. Partly false
Page | 65
Post-test. Multiple Choice. Circle the option that best answers the question or
completes the statement.
1. Drug treatment for hypertension is directed at modifying one or more of the natural
reflexes that regulate blood pressure: diuretics reduce sodium and volume,
sympathetic nervous system medications modify the sympathetic reaction and
contribute to vascular dilation and reduced pumping capacity of the heart, ACE
inhibitors prevent the transfer of angiotensin I to angiotensin II, ARBs prevent the body
from repeating.
a. True
b. False
c. Partly true
d. Partly false
2. Hypotension is a condition of lower than average blood pressure that can lead to
reduced tissue oxygenation, cell death, tissue injury, and even death.
a. True
b. False
c. Partly true
d. Partly false
3. Hypotension is more frequently treated by sympathomimetic medications that activate
sympathetic receptor sites that induce vasoconstriction, fluid retention, and a
restoration of regular pressure.
a. True
b. False
c. Partly true
d. Partly false
4. Quinidine, a class IA antidysrhythmic template, decreases automaticity, delays
conduction and prolongs the refractory period. Phenytoin can be used to treat
dysrhythmias caused by digoxin intoxication.
a. True
b. False
5. Lidocaine is a prototype of class IB antidysrhythmics used to treat extreme ventricular
dysrhythmias associated with acute myocardial infarction , heart catheterization,
cardiac surgery, and digital ventricular dysrhythmias.
a. True
b. False
c. Partly true
d. Partly false
6. Flecainide, propafenone and moricizine are class 1C drugs that have little effect on
the repolarization system but substantially suppress conduction in the ventricles.
a. True
b. False
c. Partly true
d. Partly false
7. As a class II drug, beta-adrenergic antagonists are used more widely because of their
success in reducing post-myocardial infarction mortality and in patients with heart
disease.
a. True
b. False
c. Partly true
d. Partly false
8. As class IV medications, diltiazem and verapamil are the only calcium channel
blockers approved for the treatment of dysrhythmias.
Page | 66
a. True
b. False
c. Partly true
d. Partly false
9. The FDA has issued BLACK BOX Notice for disopyramide due to its established
prodysrhythmic properties; this medication should be reserved for patients with life-
threatening ventricular dysrhythmias.
a. True
b. False
c. Partly true
d. Partly false
10. Amiodarone is a potassium channel blocker that prolongs the conduction of all cardiac
tissues and reduces the heart rate and reduces the contractility of the left ventricle.
a. True
b. False
c. Partly true
d. Partly false
11. The FDA has issued a BLACK BOX WARNING for amiodarone that is approved for
use only in patients with life-threatening dysrhythmias due to the possibility of
experiencing potentially lethal pulmonary toxicity as used.
a. True
b. False
c. Partly true
d. Partly false
12. Three classes of medications form the mainstay of angina therapy — beta blockers,
calcium channel blockers, and nitrates. A younger classification that is a derivative of
piperazine can now be applied to the treatment.
a. True
b. False
13. Beta blockers suppress the activation of beta-receptors in the heart; this affects the
function of the heart. Beta blockers slow heart rate, suicidal atrioventricular (AV)
conduction, decrease cardiac activity, and lower blood pressure. These findings
reduce the oxygen pressure of the heart, which reduces the angina.
a. True
b. False
14. Calcium channel blockers prevent calcium from passing across cell membranes. This
also affects the structure of the heart. Calcium channel blockers slow heart rate,
suicidal impulse forming (automaticity) and slow conduction velocity. These results
lower the oxygen demands of the heart. Calcium channel blockers can induce
arteriolar dilation, which decreases the afterload so that the heart does not have to
function as much as it does. Calcium channel blockers are used in chronic stable
angina where the patient cannot withstand beta blockers or nitrates or where the
effects are not sufficiently managed throughout the usage of both treatments.
a. True
b. False
Page | 67
15. Nitroglycerin relaxes the smooth muscle of the vascular and dilates all arterial and
venous arteries, but it has greater effect on venous veins. Venous dilation lowers
preload, reducing blood pressure. Arteriolar dilation decreases systemic artery
resistance and arterial pressure, reducing afterload. Myocardial oxygen intake is
diminished due to these effects. Nitroglycerin also redistributes blood supply to the
heart and increases drainage to ischemic regions.
a. True
b. False
16. Nitroglycerin is used to relieve acute angina (sublingual, transmucosal or translingual
spray), to reduce chronic persistent angina (topical, transdermal, translingual spray,
transmucosal or oral sustained-release) and serious hypertension (intravenous [IV]).
a. True
b. False
c. Partly true
d. Partly false
17. HMG-CoA reductase inhibitors, or statins, suppress the enzyme HMG-CoA reductase,
resulting in lower serum cholesterol levels, a resulting LDL degradation, and a small
rise in HDLs.
a. True
b. False
c. Partly true
d. Partly false
18. Ezetimibe, a cholesterol absorption regulator, acts at the brush boundary of the small
intestine to avoid the ingestion of dietary cholesterol, which contributes to improved
removal of cholesterol in the liver and to a decrease in serum cholesterol.
a. True
b. False
c. Partly true
d. Partly false
19. Other compounds used for reducing cholesterol include fibrates and niacin. Lipid-
lowering agents are often used in tandem to lower cholesterol at various locations.
a. True
b. False
c. Partly true
d. Partly false
20. Research is being performed on the effects of suppressing the endocannabinoid

pathway, resulting in weight loss, strengthened lipid profiles and reduced pro-
inflammatory and prothrombotic symptoms. Questions on the safety or efficacy of
drugs that obstruct this mechanism have not been addressed.
a. True
b. False
c. Partly true
d. Partly false
21. Anticoagulants prevent blood coagulation by disrupting one or more of the steps
involved, such as preventing platelet aggregation or inhibiting the intestinal or extrinsic
routes to clot formation.
a. True
Page | 68
b. False
c. Partly true
d. Partly false
22. Thrombolytic drugs eliminate clots or thrombies that have been developed. They
trigger the plasminogen system to cause a breakdown of the normal clot.
a. True
b. False
23. Pernicious anemia is a deficiency of vitamin B12 that is often used by the body to
preserve the myelin sheath on the nerve axons. If vitamin B12 is absent, these
neurons can degenerate and induce several symptoms of the CNS.
a. True
b. False
24. Pernicious anemia is caused by a deficit in the development of the intestinal factor by
gastric cells.
a. True
b. False
c. Partly true
d. Partly false
25. Intrinsic factor is required to allow the body to absorb vitamin B12. If there is a lack of
an inherent element, vitamin B12 must be supplied parenterally or intranasally for life
to ensure absorption.
a. True
b. False
26. Sickle cell anemia is a genetic disease that is characterized by the development of S
hemoglobin. RBCs are sickle-shaped and can build up in blood vessels and cause
anoxia, discomfort, and even cell death.
a. True
b. False
27. Sickle cell anemia is treated with antibiotics, pain-relieving steps, and cytotoxic
hydroxyurea, which induces enhanced development of fetal hemoglobin in the bone
marrow and dilution of S hemoglobin, resulting in a decrease of RBC stacking and
clogging of blood vessels.
a. True
b. False
c. Partly true
d. Partly false
Page | 69
Final Requirement
Tyrone Brown is a 74-year old man with cardiovascular disease. He has just
undergone cardiac bypass surgery for three coronary artery bypasses. During the
postoperative period, Mr. Brown develops premature ventricular complexes (PVCs) and
atrial fibrillation (AF).
a. Application of Understanding.
1. You are assigned to care for Mr. Brown. He is prescribed lidocaine and started
on IV lidocaine to control his PVCs. What therapeutic level should you monitor
for?
2. Mr. Brown’s AF is converted to NSR pharmacologically. The physician

prescribes amiodarone at 200 mg PO daily. Why is Mr. Brown given this drug
and what adverse effects should you monitor?
3. While Mr. Brown is receiving his IV lidocaine, his heart rate decreases to 52
beats per minute with continued PVCs. You continue to monitor the IV and the
ECG. How can you avoid this medical error?
Page | 70
b. Formulate your own Drug study for the patient following the BSU format. (You can
use a separate paper for this one).
Suggested Readings and Website

Abrams, A. C., Lammon, C. B., & Pennington S. S., (2009). Clinical drug therapy
rationales for nursing practice. 9th ed. Lippincottt Williams & Wilkins
Karch, A.M. (2019), Focus on Nursing Pharmacology, 7th Edition. Wolters Kluwer
References
Abrams, A. C., Lammon, C. B., & Pennington S. S., (2009). Clinical drug therapy
rationales for nursing practice. 9th ed. Lippincottt Williams & Wilkins
Karch, A.M. (2019), Focus on Nursing Pharmacology, 7th Edition. Wolters Kluwe
Page | 71
Page | 72

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Republic of the Philippines

Bulacan State University

NCM 106 - Pharmacology

Drugs Acting on the Cardiovascular System

Christopher E. Olipas, Ph.D.

Marlyn Molina, MAN

A.Y. 2020-2021- 1st Semester

This particular module is divided into 7 lessons:

● Lesson 2 Cardiotonic Agents

● Lesson 3 Antidysrhythmic Agents

● Lesson 4 Antianginal Agents

● Lesson 5 Lipid Lowering Agents

● Lesson 6 Drugs Affecting Blood Coagulations

● Lesson 7 Drugs Used to Treat Anemias

Antihypertensive medications are used to control hypertension, a widespread

Self-Check 1. Case Presentation

MEDICATION USUAL DOSAGE USUAL INDICATIONS

Self-Check 2. Multiple Choice

3. Peripheral resistance is mostly mediated by the constriction or relaxation of the

4. Regulation of blood pressure requires baroreceptor (pressure receptor) activation of

Magnesium sulfate IV 1–2 g (2–4 mL of 50% Safety and efficacy not

Self-Check 3. Short Answer Exercise

1. A patient is taking antidysrhythmic agent, what assessment health teaching

Angina pectoris is a chronic condition that is characterized by symptoms of chest

Self-Check 4. Case Presentation

Mr. Helsinki is a 72 year-old man with a diagnosis of hypertension , coronary artery

2. In comparison to nitroglycerin, metoprolol is recommended by the practitioner.

Self-Check 5. Multiple Choice

Contraindications and Aminocaproic acid is contraindicated in the case of allergy

Self-Check 6. Multiple Choice

Self-Check 7. Multiple Choice

5. Insufficient quantity or immaturity of RBCs results in low levels of oxygen in the

20. Research is being performed on the effects of suppressing the endocannabinoid

2. Mr. Brown’s AF is converted to NSR pharmacologically. The physician

Suggested Readings and Website

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