(GNUR 294) 2 Adams, Michael Patrick_ Urban, Carol Quam - Pharmacology_ connections to nursing practice (2018_2019, Pearson) - libgen.li-401-800

618  Unit 5  Pharmacology of the Cardiovascular System

CONNECTIONS:  NURSING PRACTICE APPLICATION (continued)

Implementation

Interventions and (Rationales) Patient-Centered Care

• Continue to monitor ECG, blood pressure, and pulse. (Nitrates cause • Teach the patient, family, or caregiver how to monitor pulse and blood
vasodilation and possible hypotension. Blood pressure assessment aids pressure. Ensure proper use and functioning of any home equipment
in determining drug frequency and dose. ECG monitoring helps detect obtained.
adverse effects such as reflex tachycardia, ischemia, or infarction.)

• Evaluate the need for adjunctive treatment with the healthcare provider • Encourage the patient to discuss any changes in character, severity, or
for angina prevention and treatment (e.g., beta blockers, aspirin frequency of angina episodes with the healthcare provider.
therapy) or further cardiac studies. (Patients with unstable angina may
require adjunctive drug therapy or definitive cardiac studies to deter- • Instruct the patient not to take routine (daily) aspirin without discuss-
mine the need for other treatment options.) ing with the provider first, because the drug may be contraindicated
depending on other conditions or medications.

• For patients on transdermal nitroglycerin patches, remove patch for • Instruct the patient on proper use of nitroglycerin and the rationale for
6–12 h at night, or as directed by the healthcare provider. (Removing removing transdermal patches. Also instruct patients using transdermal
the transdermal patch at night helps prevent or delay the development patches to always remove the old patch, to cleanse the skin under-
of tolerance to nitrates.) neath gently, and to rotate sites before applying a new patch.

• Encourage appropriate lifestyle changes: lowered fat intake, restricted so- • Encourage the patient, family, and caregivers to adopt a healthy
dium or fluid intake if ordered, gradually increased levels of exercise, limited lifestyle of low-fat food choices, increased exercise, decreased alcohol
alcohol intake, and smoking cessation. Provide for dietitian consultation as consumption, and smoking cessation. Provide educational materials
needed. (Healthy lifestyle changes will support the benefits of drug therapy.) on low-fat, low-sodium food choices.

Minimizing adverse effects: • Instruct the patient, family, or caregiver to report dizziness, faintness,
• Continue to monitor vital signs frequently. Lifespan: Be particularly palpitations, or headache unrelieved after taking nonnarcotic analge-
sics (e.g., acetaminophen).
cautious with older adults who are at increased risk for hypotension,
patients with a preexisting history of cardiac or cerebrovascular disease, • Instruct the patient on nitrates to rise from lying to sitting or standing
or patients with a recent head injury, which may be worsened by va- slowly to avoid dizziness or falls, especially if taking SL nitrates, or until
sodilation. Notify the healthcare provider immediately if angina remains drug effects are known. If dizziness occurs, the patient should sit or lie
unrelieved or if blood pressure or pulse decrease beyond established down and not attempt to stand or walk, until the sensation passes.
parameters, or if hypotension is accompanied by reflex tachycardia.
(Nitrates may cause significant vasodilation, resulting in the potential
for hypotension accompanied by reflex tachycardia. Reflex tachycardia
increases myocardial oxygen demand, worsening angina.)

• Continue cardiac monitoring (e.g., ECG) as ordered if IV nitrates are • To allay possible anxiety, teach the patient, family, or caregiver the
administered. (Monitoring devices assist in detecting early signs of rationale for all equipment used and the need for frequent monitoring.
adverse effects of drug therapy and myocardial ischemia or infarction,
as well as monitoring for therapeutic effects.)

• Continue frequent physical assessments, particularly neurologic, • When on PO therapy at home, the patient, family, or caregiver should
cardiac, and respiratory. Immediately report any changes in level of immediately report changes in mental status or level of consciousness,
consciousness, headache, or changes in heart or lung sounds. (Nitrate palpitations, dizziness, dyspnea, and increasing productive cough,
therapy may worsen preexisting neurologic, cardiac, or respiratory especially if frothy sputum is present, and seek medical attention.
conditions as blood pressure drops and perfusion to vital organs
diminishes. Lung congestion may signal impending HF.)

• Review the medications taken by the patient before sending the patient • Instruct the patient to not take sildenafil (Viagra), vardenafil (Levitra), or
home, and review all prescription as well as OTC medications with the tadalafil (Cialis) while taking nitrates and to discuss treatment options
patient. Current use of erectile dysfunction drugs, as noted on medica- for erectile dysfunction with the healthcare provider.
tion history, is contraindicated with nitrates. (Erectile dysfunction drugs
lower blood pressure and when combined with nitrates, can result in
severe and prolonged hypotension.)

Patient understanding of drug therapy: • The patient, family, or caregiver should be able to state the reason for
• Use opportunities during administration of medications and during as- the drug; appropriate dose and scheduling; what adverse effects to
observe for and when to report them; and the anticipated length of
sessments to discuss the rationale for the drug therapy, desired thera- medication therapy.
peutic outcomes, commonly observed adverse effects, parameters
for when to call the healthcare provider, and any necessary monitoring
or precautions. (Using time during nursing care helps to optimize and
reinforce key teaching areas.)

Patient self-administration of drug therapy: The patient should be able to state how to use SL nitroglycerin at home:
• When administering medications, instruct the patient, family, or care- • Take one nitroglycerin tablet, under the tongue, for chest pain. Remain

giver in the proper self-administration of drugs and when to contact seated or lie down to avoid dizziness or falls.
the provider. (Utilizing time during nurse administration of these drugs • If chest pain continues, repeat one nitroglycerin tablet, under the
helps to reinforce teaching.)
tongue, in 5 min. Remain seated or lying down.
• If chest pain continues, repeat nitroglycerin, under the tongue, in 5 min.
• If chest pain continues, even if reduced, do not take further nitroglycerin

unless specifically directed by the healthcare provider. Call EMS (e.g., 911)
for assistance. Do not drive self, or have family drive the patient, to the ED.
• If blood pressure monitoring equipment is available at home, have the
patient, family, or caregiver take blood pressure prior to the second
and third nitroglycerin doses. Hold the drug and contact EMS if blood
pressure is less than 90/60 mmHg.

Chapter 35  Pharmacotherapy of Angina Pectoris and Myocardial Infarction  619

Understanding Chapter 35

Key Concepts Summary 35.7 Beta-adrenergic antagonists are sometimes
preferred drugs for stable angina.
35.1 Myocardial ischemia develops when there is
inadequate blood supply to meet the metabolic 35.8 Calcium channel blockers are effective at reducing
demands of cardiac muscle. myocardial oxygen demand and treating stable
and variant angina.
35.2 Coronary artery disease is the major cause of
myocardial ischemia. 35.9 Early diagnosis and pharmacotherapy of
myocardial infarction increase chances of survival.
35.3 Angina pectoris is characterized by severe chest
pain brought on by physical exertion or emotional 35.10 Thrombolytic drugs can restore perfusion
stress. to ischemic regions of the myocardium if
administered soon after a myocardial infarction.
35.4 Therapeutic lifestyle changes can decrease the
frequency of anginal episodes and reduce the risk 35.11 Drugs are used to treat the symptoms and
of coronary artery disease. complications of acute myocardial infarction.

35.5 The pharmacologic management of angina 35.12 Vasopressors are used following cardiopulmonary
includes organic nitrates, beta-adrenergic arrest to reestablish coronary and cerebral blood
antagonists, and calcium channel blockers. flow.

35.6 Organic nitrates may be used to terminate or
prevent angina episodes.

CASE STUDY: Making the Patient Connection

Remember the patient 156/90 mmHg. He had no neck venous distention. His
“Michael Graff” at the white blood cell count was 7600/mm3; hematocrit, 43.8%;
beginning of the chapter? platelets, 256,000/mm3; CK, 87 international units/L; and
Now read the remainder troponin-I, less than 4.1 mcg/L. An ECG showed ST-
of the case study. Based segment elevation.
on the information
presented within this Once stabilized, Michael is transported to the coronary
chapter, respond to the critical thinking questions that care unit with the admission diagnosis of unstable angina
follow. and to rule out MI. In the coronary care unit, he receives IV
nitroglycerin 50 mg in D5W 25 mL. The nurse begins the
Early one morning, 60-year-old Michael Graff began to feel infusion at 10 mcg/min and titrates the rate based on his
severe anterior crushing chest pain that lasted for 35 min- report of chest pain every 5 to 10 min (5–10 mcg/min).
utes. He experienced dizziness, cold sweats, and nausea.
Although he considered driving to the local ED, his family Critical Thinking Questions
insisted on calling an ambulance for emergency transport
to the hospital. 1. Michael and his family ask you to explain what is
occurring with his heart. How would you describe the
Michael, a general contractor, is a 2-pack-per-day pathophysiology of Michael’s condition to them?
smoker and consumes alcohol (beer) 2 to 3 times per week.
He has a family history of CAD, diabetes mellitus, and 2. Discuss the reason Michael is receiving nitroglycerin.
hyperlipidemia. It has been at least 10 years since his last
physical examination. 3. What adverse effects should the nurse monitor with
patients receiving IV nitroglycerin?
On arrival at the ED, he presents with symptoms of
anxiety, moderate chest pain, and cold extremities. 4. How do nitroglycerin infusions differ from other
Auscultation of the thorax revealed tachycardia and clear IV infusions?
lung fields. Blood pressure was slightly above normal at
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.

620  Unit 5  Pharmacology of the Cardiovascular System

Additional Case Study 3. “I was told to report episodes of dizziness when I
stand up plus rapid heart rates. How does nitroglyc-
Bill Shackley, a 52-year-old man, is prescribed a daily nitro- erin cause these?”
glycerin transdermal patch. While discussing his medica-
tions, Bill shares several of his concerns. How would you Answers to Additional Case Study questions are available on
respond to the following questions? the faculty resources site. Please consult with your instructor.

1. “I heard that I can become ‘tolerant’ to this drug. What
does this mean? How can it be avoided?”

2. “Sometimes, after applying the nitroglycerin patch, I
get a throbbing headache. Is there anything I can do
about this?”

Chapter Review 4. The nurse is caring for a patient with chronic angina
pectoris. The patient is receiving isosorbide dinitrate
1. Nitroglycerin topical ointment is being initiated for a (Isordil) oral tablets. Which patient manifestations
patient with angina. Which health teaching would be would the nurse conclude are common adverse effects
most appropriate? of this medication?

1. Keep the medication in the refrigerator. 1. Flushing and headache
2. Take this medication only when chest pain is 2. Tremors and anxiety
3. Lightheadedness and dizziness
severe. 4. Sleepiness and lethargy
3. Remove the old paste before applying the next
5. The patient asks how atenolol (Tenormin) helps
dose. angina. The response provided by the nurse is based
4. Apply the ointment on the chest wall only. on which concept? This medication:

2. A patient with chest pain is receiving sublingual 1. Slows the heart rate and reduces contractility.
nitroglycerin. The nurse would include in the 2. Increases the heart rate and diminishes
care plan to monitor the patient for which
adverse effect? contractility.
3. Blocks sodium channels and elevates
1. Photosensitivity
2. Elevated blood pressure depolarization.
3. Vomiting and diarrhea 4. Decreases blood pressure and blocks the alpha2
4. Decreased blood pressure
receptors.
3. The patient states, “I always put my nitroglycerin
patch in the same place so I do not forget to 6. Which of the following assessment findings, if discov-
take it off.” The nurse’s response would be ered in a patient receiving verapamil (Calan) for
based on which of the following physiologic angina, would be cause for the nurse to withhold the
concepts? medication? (Select all that apply.)

1. Patients are more likely to remember to apply the 1. Bradycardia: heart rate of 40 beats/min
patch if the same site is used daily. 2. Tachycardia: heart rate of 126 beats/min
3. Hypotension: blood pressure 76/46 mmHg
2. Repeated use of the same application site will 4. Tinnitus with hearing loss
enhance medication absorption. 5. Hypertension: blood pressure 156/92 mmHg

3. Rebound phenomenon is likely to occur when the See Answers to Chapter Review in Appendix A.
same site is used more than once.

4. Skin irritation due to the nitroglycerin
ointment can occur if the same site is used
repeatedly.

Chapter 35  Pharmacotherapy of Angina Pectoris and Myocardial Infarction  621

References Sun, H., Qu, Q., Chen, Z. F., Tan, S. L., Zhou, H. J., Qu, J.,
& Chen, H. (2016). Impact of CYP2C19 variants on
Alaeddini, J. (2016). Angina pectoris. Retrieved from clinical efficacy of clopidogrel and 1-year clinical
http://emedicine.medscape.com/ outcomes in coronary heart patients undergoing
article/150215-overview percutaneous coronary intervention. Frontiers in
Pharmacology, 7, 453. doi:10.3389/fpharm.2016.00453
Arima, Y., Hokimoto, S., Akasaka, T., Mizobe, K., Kaikita, K.,
Oniki, K., . . . Ogawa, H. (2015). Comparison of the effect Tabata, N., Hokimoto, S., Akasaka, T., Arima, Y.,
of CYP2C19 polymorphism on clinical outcome between Yamamoto, E., Tsujita, K., . . . Ogawa, H. (2016).
acute coronary syndrome and stable angina. Journal of Patients with both CYP2C19 loss-of-function allele and
Cardiology, 65, 494–500. doi:10.1016/j.jjcc.2014.07.016 peripheral endothelial dysfunction are significantly
correlated with adverse cardiovascular events
Bhopalwala, A. M., Hong, R. A., Khan, Z. R., Valentin, M. following coronary stent implantation. Journal of
R., & Badawi, R. A. (2015). Routine screening for Cardiology, 67, 104–109. doi:10.1016/j.jjcc.2015.03.010
CYP2C19 polymorphisms for patients being treated
with clopidogrel is not recommended. Hawai’i Journal of University of Maryland Medical Center. (2015). Omega-3
Medicine and Public Health, 74(1), 16–20. fatty acids. Retrieved from http://umm.edu/health/
medical/altmed/supplement/omega3-fatty-acids
González, A., Moniche, F., Cayuela, A., Garcia-Lozano, J. R.,
Torrecillas, F., Escudero-Martinez, I., . . . Montaner, J. Wang, Y., Cai, H., Zhou, G., Zhang, Z., & Liu, X. (2016).
(2016). Effect of CYP2C19 polymorphisms on the platelet Effect of CYP2C19*2 and *3 on clinical outcome in
response to clopidogrel and influence on the effect of ischemic stroke patients treated with clopidogrel.
high versus standard dose clopidogrel in carotid artery Journal of the Neurological Sciences, 369, 216–219.
stenting. European Journal of Vascular and Endovascular doi:10.1016/j.jns.2016.08.025
Surgery, 51, 175–186. doi:10.1016/j.ejvs.2015.09.020
Zafari, A. M. (2017). Myocardial infarction. Retrieved from
National Center for Complementary and Integrative http://emedicine.medscape.com/
Health. (2015). Omega-3 supplements: In depth. Retrieved article/155919-overview
from https://nccih.nih.gov/health/omega3/
introduction.htm

Selected Bibliography Jones, D. A., Timmis, A., & Wragg, A. (2013). Novel drugs for
treating angina. BMJ, 347, 34–37. doi:10.1136/bmj.f4726
Clark, M. G., Beavers, C., & Osborne, J. (2015). Managing
the acute coronary syndrome patient: Evidence based Kee, J. L. (2014). Laboratory and diagnostic tests with nursing
recommendations for anti-platelet therapy. Heart & implications (9th ed.). Upper Saddle River, NJ: Pearson.
Lung: The Journal of Acute and Critical Care, 44, 141–149.
doi:10.1016/j.hrtlng.2014.11.005 Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K.,
Blaha, M. J., Cushman, M., . . . Turner, M. B. (2015).
Facchini, E., Degiovanni, A., Cavallino, C., Lupi, A., Executive summary: Heart disease and stroke
Rognoni, A., & Bongo, A. S. (2015). Beta-blockers and statistics—2015 update. Circulation, 131, 434–441.
nitrates: Pharmacotherapy and indications. Cardiovascular doi:10.1161/CIR.0000000000000157
& Hematological Agents in Medicinal Chemistry, 13, 25–30.
doi:10.2174/1871525713666141219114708 Ohman, E. M. (2016). Chronic stable angina. The New
England Journal of Medicine, 374, 1167–1176. doi:10.1056/
Giannopoulos, A. A., Giannoglou, G. D., & Chatzizisis, NEJMcp1502240
Y. S. (2016). Pharmacological approaches of refractory
angina. Pharmacology & Therapeutics, 163, 118–131. Smith, J. N., Negrelli, J. M., Manek, M. B., Hawes, E. M., &
doi:10.1016/j.pharmthera.2016.03.008 Viera, A. J. (2015). Diagnosis and management of acute
coronary syndrome: An evidence-based update. The
Gupta, A. K., Winchester, D., & Pepine, C. J. (2013). Journal of the American Board of Family Medicine, 28,
Antagonist molecules in the treatment of angina. Expert 283–293. doi:10.3122/jabfm.2015.02.140189
Opinion on Pharmacotherapy, 14, 2323–2342. doi:10.1517/
14656566.2013.834329 Winchester, D. E., & Pepine, C. J. (2015). Angina
treatments and prevention of cardiac events: An
Harris, J. R., Hale, G. M., Dasari, T. W., & Schwier, N. C. appraisal of the evidence. European Heart Journal
(2016). Pharmacotherapy of vasospastic angina. Journal Supplements, 17(Suppl. G), G10–G18. doi:10.1093/
of Cardiovascular Pharmacology and Therapeutics, 21, eurheartj/suv054
439–451. doi:10.1177/1074248416640161

“It seems that over the past
2 weeks, I have become more
short of breath just walking
around my apartment.
Walking around the market and
unloading my groceries
have become impossible.”

Patient “Thelma Walters”

Chapter 36

Pharmacotherapy of Heart Failure

Chapter Outline Learning Outcomes

cc Etiology of Heart Failure After reading this chapter, the student should be able to:
cc Pathophysiology of Heart Failure
1. Identify the major diseases associated with heart
Ventricular Hypertrophy failure.
cc Pharmacologic Management of Heart Failure
cc Drugs for Heart Failure 2. Relate how the symptoms associated with heart
failure may be caused by a weakened heart muscle
Angiotensin-Converting Enzyme Inhibitors and and diminished cardiac output.
Angiotensin Receptor Blockers
Diuretics 3. Identify compensatory mechanisms used by the
Beta-Adrenergic Antagonists body to maintain cardiac output in patients with
Vasodilators heart failure.
Cardiac Glycosides
PROTOTYPE  Digoxin (Lanoxin, Lanoxicaps), p. 632 4. Describe how heart failure is classified.
Beta-Adrenergic Agonists
Phosphodiesterase III Inhibitors 5. Describe the nurse’s role in the pharmacologic
PROTOTYPE  Milrinone (Primacor), p. 635 management of heart failure.

6. For each of the classes shown in the chapter outline,
identify the prototype and representative drugs and
explain the mechanism(s) of drug action, primary
indications, contraindications, significant drug
interactions, pregnancy category, and important
adverse effects.

7. Apply the nursing process to care for patients
receiving pharmacotherapy for heart failure.

622

Chapter 36  Pharmacotherapy of Heart Failure  623

Key Terms heart failure (HF), 623 reverse remodeling, 630
natriuretic peptides, 625
cardiac remodeling, 624 phosphodiesterase III, 634
digitalization, 632
diuretic resistance, 630

Heart failure is one of the most common and fatal of the condition; controlling associated diseases will greatly
cardiovascular diseases, and its incidence is increasing as reduce the risk of development and progression of HF.
the population ages. Although improved treatment of
myocardial infarction and hypertension has led to declines Because there is no cure for HF, the treatment goals are
in mortality due to heart failure, approximately one in five to prevent, treat, or remove the underlying causes when-
patients still dies within a year of diagnosis of heart failure, ever possible and treat its symptoms, so that the patient’s
and 50% die within 5 years. Historically, this condition was quality of life can be improved. Advances in understand-
called congestive heart failure; however, because not all inci- ing the pathophysiology of HF during the past two decades
dences of this disease are associated with congestion, the have led to a change in pharmacotherapeutic goals. No lon-
more appropriate name is heart failure. ger is therapy of HF focused on end stages of the disorder.
Pharmacotherapy is now targeted at prevention and slow-
PharmFACT ing the progression of HF. This change in emphasis has led
to significant improvements in survival and quality of life
Each year, about 670,000 new cases of heart failure are in patients with HF.
diagnosed and about 277,000 deaths are attributed to HF in
the United States. Although the incidence is equal in men Pathophysiology of Heart Failure
and women, women develop HF later in life and survive
longer with the disease (Dumitru, 2016). 36.2  The body attempts to compensate for heart
failure by increasing cardiac output.
Etiology of Heart Failure
Heart failure is a general term used to describe several dif-
36.1  Heart failure is closely associated with ferent types of cardiac dysfunction. The dysfunction may
disorders such as chronic hypertension, coronary occur on the left side, the right side, or on both sides of the
artery disease, and diabetes. heart.

Heart failure (HF) is the inability of the heart to pump Left-sided HF is sometimes called congestive heart fail-
enough blood to meet the metabolic demands of the body. ure (CHF) because it is characterized by an accumulation of
HF can be caused by any disorder that affects the heart’s fluid causing congestion in the pulmonary capillary beds.
ability to receive or eject blood. While weakening of car- Although left-sided HF is more common, the right side of
diac muscle is a natural consequence of aging, the process the heart can also become weak, either simultaneously with
can be caused or accelerated by the following: the left side or independently from the left side. In right-
sided HF, the blood pools in the veins, resulting in periph-
• Coronary artery disease (CAD) eral edema and engorgement of organs such as the liver.
• Mitral stenosis
• Myocardial infarction (MI) Left-sided HF is further subdivided into two types.
• Chronic hypertension (HTN) Systolic HF occurs when cardiac output (CO) is diminished
• Diabetes mellitus. due to decreased contractility of the myocardium. Approx-
imately 60% to 80% of left-sided HF is the systolic type.
The student should detect a common theme through- Diastolic HF occurs when the lungs become congested
out the chapters on cardiovascular pharmacology. That even though cardiac output is normal. Diastolic HF is
theme is the ability to prevent major causes of morbidity caused by a restriction in ventricular filling, resulting in
and mortality through control of healthy lifestyle choices. higher-than-normal pressure in the ventricle. Although
Controlling lipid levels, implementing a regular exercise cardiac output is normal, the increased pressure in the ven-
program, maintaining optimal body weight, and keeping tricle creates higher pressure in the pulmonary capillaries,
blood pressure within recommended limits reduce the inci- resulting in pulmonary edema. A patient may have both
dences of CAD and MI. Maintaining blood glucose within systolic and diastolic HF. Pharmacotherapy of the two
the normal range reduces the consequences of uncontrolled types differs somewhat. For example, inotropic drugs that
diabetes. Thus, for many patients, HF is a preventable increase contractility are more successful with systolic HF
than diastolic HF.

624  Unit 5  Pharmacology of the Cardiovascular System

(CKNKPI JGCTV &GETGCUGF
ECTFKCE QWVRWV

+PETGCUGF &KOKPKUJGF TGPCN
U[ORCVJGVKE DNQQF ƃQY

CEVKXKV[

+PETGCUGF JGCTV 8CUQEQPUVTKEVKQP #EVKXCVKQP QH
TCVG CPF HQTEG QH +PETGCUGF DNQQF TGPKP CPIKQVGPUKP

EQPVTCEVKQP RTGUUWTG CNFQUVGTQPG
+PETGCUGF U[UVGO
CHVGTNQCF
+PETGCUGF ECTFKCE 4GVGPVKQP QH 0C

YQTMNQCF CPF YCVGT
+PETGCUGF

RNCUOC XQNWOG
2WNOQPCT[ CPF
RGTKRJGTCN GFGOC

/[QECTFKCN F[UHWPEVKQP
YQTUGPKPI JGCTV HCKNWTG
Figure 36.1  Pathophysiology of heart failure.

HF may progress slowly over many years, or it may Ventricular Hypertrophy
have an acute onset. Once HF reaches the stage where car-
diac output is affected, tissues receive inadequate perfu- In left HF, the left ventricle is forced to work harder due
sion and organ failure is possible. The body has developed to the increased preload or afterload. Over time, the wall
a complex series of actions to compensate for HF. Knowl- of the left ventricle thickens and enlarges (ventricular
edge of these compensatory mechanisms is important to hypertrophy) in an attempt to compensate for the
understanding the pharmacotherapy of HF. Prior to con- increased workload. Changes in the size, shape, and
tinuing in this chapter, factors affecting cardiac output, structure of the myocardial cells (myocytes) occur. These
stroke volume, afterload, and preload, discussed in compensatory changes in structure benefit the heart by
Chapter 28, should be reviewed. The pathophysiology of allowing it to better maintain adequate stroke volume
HF is illustrated in Figure 36.1. and cardiac output. The term cardiac remodeling is

Chapter 36  Pharmacotherapy of Heart Failure  625

sometimes used to describe these changes to myocyte However, the heart has a limited ability to increase
structure and function. contractility. In a diseased heart, the increased preload
leads to volume overload and pulmonary congestion. In
The benefits of cardiac remodeling as a compensatory addition, the increased plasma volume increases blood
mechanism, however, are limited. Myocytes continually pressure, which further adds to afterload and to the burden
die, likely due to workload injury, and fibrotic tissue fills of an already weak heart.
the spaces between them. These tissue changes stiffen the
myocardium, causing diminished contractility and reduced Research has discovered additional detrimental effects
cardiac output. The heart responds with even more remod- related to activation of the RAAS. Angiotensin II has been
eling, continuing the destructive cycle. Without interven- found to promote ventricular hypertrophy, myocyte death,
tion, the abnormal structural changes can result in and fibrosis formation in the myocardium. Aldosterone
irreversible cardiac impairment. also has direct effects on the myocardium, promoting fibro-
sis and stiffening of the ventricular wall. Angiotensin-
Activation of the Sympathetic converting enzyme (ACE) inhibitors have become preferred
Nervous System drugs for HF, in part, because they are able to block these
detrimental effects of angiotensin II and aldosterone on
One of the fastest homeostatic responses to diminished cardiac remodeling.
cardiac output is activation of the sympathetic nervous
system (SNS). The increased heart rate resulting from sym- Natriuretic Peptides
pathetic activation is a normal compensatory mechanism and Neurohumoral Factors
that serves to increase cardiac output.
Natriuretic peptides are substances secreted in response
The SNS, however, also constricts arteries and acti- to increased pressure in the heart. Three types have been
vates the renin-angiotensin-aldosterone system (RAAS). identified:
Higher angiotensin II levels raise blood pressure and after-
load, causing the heart to work harder. The stressed myo- 1. Atrial natriuretic peptide (ANP) is secreted by the atria.
cardium, which already has reduced contractility and is 2. B-type natriuretic peptide (BNP) is secreted by the car-
having difficulty maintaining cardiac output, is faced with
even greater challenges by this additional workload. The diac ventricles.
diminished cardiac output caused by the high afterload 3. C-type natriuretic peptide (CNP) is secreted by the brain.
produces an ongoing activation of the SNS. Patients with
preexisting CAD may experience an anginal attack from ANP and BNP are secreted in response to left ventricu-
the increased SNS activity. Again, although there are cer- lar volume overload and dysfunction. The physiologic
tain compensatory benefits to activating the SNS to main- functions of ANP and BNP are to cause diuresis and reverse
tain cardiac output, a destructive cycle is created that can the negative effects of SNS and RAAS activation on the
lead to or worsen HF. heart. BNP is used as a biomarker to diagnose and establish
the severity of HF. Nesiritide (Natrecor), a drug structur-
CONNECTION Checkpoint  36.1 ally identical to BNP, has a limited role in the treatment of
HF, as discussed in Section 36.8.
Propranolol (Inderal) is an example of a negative inotropic drug. From
what you learned in Chapter 16, explain why this type of drug should Research has identified several other substances as
be administered with caution to a patient with heart failure who also potential mediators in the progression of HF. Two proin-
has asthma.  Answers to Connection Checkpoint questions are avail- flammatory substances, tumor necrosis factor (TNF) and
able on the faculty resources site. Please consult with your instructor. interleukin, are found in high levels in patients with HF
and are associated with a poor prognosis. The hormone
Increased Plasma Volume endothelin is a vasoconstrictor that also is associated with
and Preload a poor prognosis in HF patients. Vasopressin (antidiuretic
hormone), which is elevated in HF patients, causes fluid
When cardiac output in a patient with HF is diminished, retention and worsens this condition. It is likely that
blood flow to the kidneys is reduced. The kidneys respond research will identify additional mediators of HF, along
to the decreased perfusion by secreting renin and activating with potential novel therapies for the disease.
the RAAS. As a result of the action of angiotensin II, aldoste-
rone secretion is increased, and the body retains sodium and 36.3  Symptoms of heart failure occur when
water. This has the beneficial effects of increasing preload, compensatory mechanisms fail to maintain
stretching the myocardial fibers, and increasing contractility, adequate cardiac output.
thus returning cardiac output to normal levels. This is an
important compensatory mechanism in normal hearts. The classic symptoms of HF are dyspnea on exertion,
fatigue, pulmonary congestion, and peripheral edema.

626  Unit 5  Pharmacology of the Cardiovascular System

Table 36.1  Drugs That May Worsen Heart Failure Pharmacologic Management
of Heart Failure
Mechanism Example Drugs and Classes
36.4  The specific therapy for heart failure
Negative inotropic effect: Antidysrhythmics depends on the clinical stage of the disease.
slow heart rate or reduce Beta-adrenergic antagonists
contractility Calcium channel blockers Several models are available to guide the pharmacologic
Itraconazole (antifungal) management of HF. The New York Heart Association
Cardiotoxicity: damage (NYHA) classification has been widely used in clinical
to the myocardium Cyclophosphamide (antineoplastic) practice for the staging of HF. This model classifies symp-
Daunomycin (antineoplastic) tomatic HF into four functional classes:
Increase blood volume: Doxorubicin (antineoplastic)
cause sodium and water • I: Patients with cardiac disease but with no symptoms
retention and fluid Androgens during physical activity
overload Estrogens
Glucocorticoids • II: Patients with cardiac disease who have slight limi-
NSAIDs tations on physical activity, with symptoms such as
Rosiglitazone and pioglitazone (antidiabetics) fatigue, palpitations, dyspnea, or angina

Lung congestion causes a cough and orthopnea (difficulty • III: Patients with cardiac disease who have marked
breathing when recumbent). If pulmonary edema occurs, limitations during physical activity
the patient feels as if he or she is suffocating and extreme
anxiety may result. The condition often worsens at night. • IV: Patients with cardiac disease who are unable to per-
form physical activity and who have symptoms at rest.
Through pharmacotherapy and lifestyle modifications,
many patients with HF can be maintained in a symptom- A more recent model, proposed by the American
free, compensated state for years. The most common rea- College of Cardiology (ACC) and the American Heart
son patients experience decompensation is fluid overload Association (AHA), categorizes HF into four stages, as
due to nonadherence to sodium and water restrictions. The listed in Table 36.2. Although similar to the NYHA
second most common reason is nonadherence to the phar- model, the ACC/AHA model better illustrates the pro-
macotherapeutic regimen. The nurse must stress to patients gressive nature of the disease and the role of risk factor
the importance of sodium restriction and treatment adher- modification. In 2016, a focused review of the ACC/
ence to maintain a properly functioning heart. Cardiac AHA recommendations considered new research evi-
events such as myocardial ischemia, MI, or dysrhythmias dence and added two additions to drug therapy for HF:
can also precipitate acute HF. Certain medications can ivabradine (Corlanor) and Entresto, a combination drug
worsen HF, and the nurse should use these drugs with cau- containing valsartan and sacubitril (Yancy et al., 2016).
tion. A list of selected drugs that may worsen HF is shown Sacubitril is the first in a new class of drugs called the
in Table 36.1. neprilysin inhibitors.

Table 36.2  Stages for Treating Heart Failure

Stage Description Treatment Examples

A At high risk of developing HF but without Make lifestyle modifications.

structural heart disease or symptoms. Treat and control associated conditions: HTN, dyslipidemia, and diabetes.

If hypertensive, use ACE inhibitor or angiotensin receptor blocker (ARB).

B Structural evidence of heart disease, such as a Continue treatments for stage A.

previous MI or valvular disease, but no Treat with ACE inhibitor or ARB.
symptoms of HF. (Includes NYHA Class I Beta blockers are added for those with prior HF symptoms or history of MI.
patients.)

C Structural evidence of heart disease with Continue lifestyle modifications and treatment with ACE inhibitor, ARB, or beta blocker.

current symptoms of HF such as fatigue, fluid If needed to control symptoms, add digoxin or diuretic or combination of isosorbide dinitrate
retention, or dyspnea. (Includes NYHA Class II with hydralazine (in African Americans).
and III patients.)
In patients with a history of atrial fibrillation or thromboembolic event, implement

anticoagulation with drugs such as warfarin, dabigatran, apixaban, or rivaroxaban.

Consider supplementation with omega-3 fatty acids.

D Symptoms at rest or minimal exertion despite Continue lifestyle modifications.

optimal medical therapy. (Includes NYHA Class Treatment may include IV diuretics, dopamine, dobutamine, IV nitroglycerin, nitroprusside,
IV patients.)
nesiritide, or phosphodiesterase inhibitors.

From “2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice
Guidelines,” by C. W. Yancy et al., 2013, Circulation, 128, pp. e240–e327.

Chapter 36  Pharmacotherapy of Heart Failure  627

Pharmacotherapy Illustrated 36.1

Mechanisms of Action of Drugs Used for Heart Failure

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Drugs for Heart Failure reduction in morbidity and mortality from HF. These mecha-
nisms are illustrated in Pharmacotherapy Illustrated 36.1.
Pharmacotherapy of HF focuses on three primary goals:
36.5  Angiotensin-converting enzyme inhibitors
1. Reduction of preload are preferred drugs for heart failure.
2. Reduction of systemic vascular resistance (afterload
Due to their effectiveness and relative safety, the angiotensin-
reduction) converting enzyme (ACE) inhibitors have become first-line
3. Inhibition of both the RAAS and vasoconstrictor mecha- drugs for the treatment of chronic HF. Indeed, unless specifi-
cally contraindicated, all patients with HF and many patients
nisms of the sympathetic nervous system. at high risk of HF should receive an ACE inhibitor. The stu-
dent should refer to Chapter 31 for details on the
The first two goals provide symptomatic relief but do not pharmacology of the drugs in this class. The following
reverse the progression of the disease. In addition to reducing
symptoms, inhibition of the RAAS and vasoconstriction by
the sympathetic nervous system also result in a significant

628  Unit 5  Pharmacology of the Cardiovascular System

CONNECTIONS: Patient Safety pulse, the patient requests the nurse’s stethoscope and replies,
“I’ve been using my daughter’s stethoscope, she’s a nurse. I
Misunderstood Instructions count my heartbeats. It’s easier than trying to find my pulse,” and
proceeds to demonstrate. He obtains a pulse rate of 84.
A patient has been taking enalapril (Vasotec) and carvedilol (Coreg
CR) for stage B heart failure with history of prior MI. The patient is What is one possible underlying reason for the discrepancy
brought to the emergency department due to episodes of syn- in heart rate between the nurse’s and the patient’s values? What
cope at home whenever rising from lying or sitting to standing. should the nurse do to correct the patient’s technique?
When questioned, the patient reports taking “all medicines as
directed” and that he has been “counting my pulse rate before I Answers to Patient Safety questions are available on the faculty
take the Coreg. I am not to take it if my heart beat is less than 60 resources site. Please consult with your instructor.
in a minute.” On assessing the patient’s heart rate, the nurse notes
a pulse of 42. When asked to demonstrate how he is taking his

section focuses on the benefits of these drugs for patients adverse effects do not interfere with therapy. Symptomatic
with HF. relief from HF symptoms occurs within days of initiating
therapy, but maximum benefits may take several weeks.
Clinical research has clearly demonstrated that ACE
inhibitors slow the progression of HF and reduce mortality The ACE inhibitors are well tolerated by most patients
from this disease. Although this is probably true for all with HF. Hypotension is the most common adverse effect,
ACE inhibitors, the largest body of research has been con- and the risk is increased when the patient is receiving other
ducted using captopril (Capoten) and lisinopril (Prinivil, drugs that lower blood pressure such as diuretics and beta
Zestril). Doses for the ACE inhibitors indicated for HF are blockers. Hypotension is generally worse at the beginning
listed in Table 36.3. of therapy or when the dosage is increased. Multidrug
therapy is common in these patients, and the nurse serves
The two primary actions of the ACE inhibitors are to a key role in teaching patients how to space drug adminis-
lower peripheral resistance through the inhibition of angio- tration times to minimize hypotensive adverse effects.
tensin II formation and to reduce blood volume through
inhibition of aldosterone secretion. The resultant reduction An additional concern during ACE inhibitor therapy is
of arterial blood pressure diminishes afterload and functional renal insufficiency. Patients with severe HF have
increases cardiac output. An additional effect of the ACE high circulating levels of angiotensin II, which helps to main-
inhibitors is dilation of veins. This action, which is proba- tain renal blood flow by constricting efferent arterioles in the
bly not directly related to their inhibition of angiotensin, kidney. When ACE inhibitors are administered, the level of
lowers preload and reduces pulmonary congestion and angiotensin II declines rapidly, leading to reduced blood flow
peripheral edema. The combined reductions in preload, through the kidneys. During therapy with ACE inhibitors,
afterload, and blood volume from the ACE inhibitors sub- renal insufficiency may also result from sodium depletion,
stantially decrease the workload on the heart and allow it often secondary to the concurrent use of diuretics. To avoid
to work more efficiently for patients with cardiac impair- this potentially serious adverse effect, serum creatinine,
ment. Patients taking ACE inhibitors experience fewer HF- serum electrolytes, and blood urea nitrogen (BUN) should be
related symptoms, hospitalizations, and treatment failures. monitored during therapy. Should an assessment discover
Exercise tolerance is improved. signs of renal impairment, the dose should be immediately
decreased or the drug discontinued. Other adverse effects of
Research has also demonstrated that several ACE ACE inhibitors are angioedema, cough, and hyperkalemia.
inhibitors are effective in preventing HF following an acute The student should refer to Chapter 31 for additional infor-
MI. Furthermore, post-MI therapy with ACE inhibitors mation on the adverse effects of ACE inhibitors and for a
reduces mortality and decreases reinfarction rates. drug prototype feature for lisinopril (Prinivil, Zestril).
Although these effects are most prominent when therapy is
initiated within 36 hours after the onset of the MI, benefits Another class of drugs that blocks the effects of angio-
are also obtained when therapy is begun later and contin- tensin II are the angiotensin receptor blockers (ARBs). Phar-
ued for several years. macologically, the effects of the ARBs are very similar to
those of the ACE inhibitors, as would be expected, because
Therapy with ACE inhibitors is generally begun at low drugs from both classes inhibit the actions of angiotensin II.
doses, and the amount is gradually increased until the In patients with HF, ARBs show equivalent efficacy to the
desired therapeutic level is reached. Clinical research has not ACE inhibitors. Clinical research, however, has suggested
shown a significant difference in mortality between patients that combining ARBs with ACE inhibitors does not improve
receiving low versus high doses. Because higher doses patient survival but does increase the risk of adverse effects.
reduce HF symptoms more effectively, however, patients Because they show no clear advantage over other HF
often receive doses in the higher range, as long as significant

Chapter 36  Pharmacotherapy of Heart Failure  629

Table 36.3  Drugs for Early and Moderate Heart Failure

Drug Route and Adult Dose Adverse Effects
(Maximum Dose Where Indicated)
Headache, dizziness, orthostatic hypotension, cough
ACE Inhibitors and Angiotensin Receptor Blockers (ARBs) Severe hypotension (first-dose phenomenon), syncope, angioedema,
blood dyscrasias, fetal toxicity
candesartan (Atacand) PO: Start at 4 mg/day and increase gradually
(max: 32 mg/day) Loop and thiazides:
Electrolyte imbalances, fatigue, orthostatic hypotension
captopril (Capoten) PO: 6.25–12.5 mg tid (max: 450 mg/day) Severe hypotension, dehydration, serious hypokalemia,
hyponatremia, hyperglycemia (thiazides), ototoxicity (loop diuretics)
enalapril (Vasotec) PO: 2.5 mg qid–bid (max: 40 mg/day)
Potassium-sparing:
fosinopril (Monopril) PO: 5–40 mg/day (max: 40 mg/day) Hyperkalemia, gynecomastia in men, fatigue
Dysrhythmias due to hyperkalemia
lisinopril (Prinivil, Zestril) PO: 10 mg/day (max: 80 mg/day)
Fatigue, insomnia, drowsiness, weight gain, bradycardia, dizziness
quinapril (Accupril) PO: 10–20 mg/day (max: 40 mg/day) Agranulocytosis, laryngospasm, Stevens–Johnson syndrome,
anaphylaxis; if the drug is abruptly withdrawn, palpitations, rebound
ramipril (Altace) PO: 2.5–5 mg bid (max: 10 mg/day) HTN, life-threatening dysrhythmias, or myocardial ischemia may occur

valsartan (Diovan) PO: 80 mg/day (max: 320 mg/day) Nausea, vomiting, headache, and visual disturbances such as seeing
halos, a yellow or green tinge, or blurring
Diuretics Dysrhythmias, AV block
Headache, flushing of face, orthostatic hypotension, dizziness, reflex
Loop or High-Ceiling tachycardia
Fainting, severe headache, severe hypotension with overdose, lupus-like
bumetanide (Bumex) PO: 0.5–2 mg/day (max: 10 mg/day) reaction (hydralazine)
Bradycardia, HTN
furosemide (Lasix) PO: 20–80 mg in 1 or more divided doses Atrial fibrillation, fetal toxicity
(max: 600 mg/day) Hypotension, hyperkalemia, cough, dizziness
Renal failure, fetal toxicity, angioedema
torsemide (Demadex) PO/IV: 10–20 mg/day (max: 200 mg/day)

Thiazide and Thiazide-Like

hydrochlorothiazide (Microzide) PO: 25–200 mg in 1–3 divided doses
(max: 200 mg/day)

Potassium-Sparing (Aldosterone Antagonist)

eplerenone (Inspra) PO: 25–50 mg once daily (max: 100 mg/day)

spironolactone (Aldactone) PO: 5–200 mg in divided doses

Beta-Adrenergic Antagonists

carvedilol (Coreg CR) PO (extended release): 10–20 mg/day
(max: 80 mg/day)

metoprolol (Toprol XL) PO (extended release): 12.5–25 mg/day initial
dose (max: 200 mg/day)

Miscellaneous drugs PO: 0.125–0.5 mg/day
digoxin (Lanoxin, Lanoxicaps)

hydralazine with isosorbide PO: 1 tablet tid (max: 2 tablets tid); each tablet
dinitrate (BiDil) contains 37.5 mg of hydralazine and 20 mg of
isosorbide dinitrate

ivabradine (Corlanor) PO: 5 mg bid initial dose (max: 7.5 mg bid)

sacubitril with valsartan PO: 97 mg (sacubitril)/103 mg (valsartan)
(Entresto) bid maintenance dose

Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.

medications, the use of ARBs in the treatment of HF is usu- blocking neprilysin, the concentration of natriuretic pep-
ally reserved for patients who are unable to tolerate the tides in the blood increases and cardiac efficiency improves.
adverse effects of ACE inhibitors. The ARB losartan (Cozaar) The most significant finding of this new class of drugs is
is featured as a prototype drug in Chapter 31. that they are able to reduce mortality and the number of
hospitalizations in patients with HF. The neprilysin inhibi-
In 2015, Entresto, a combination of sacubitril (a nepri- tors are likely to lead to the discovery of other new
lysin inhibitor) and valsartan (an ARB), was approved. approaches to treating angina, HTN, and HF. Indeed, it is
This drug represents a new class called angiotensin recep- possible that the ARNIs may replace monotherapy with
tor neprilysin inhibitors (ARNIs). Neprilysin is an enzyme ACE inhibitors as the first-line therapy for many patients
normally present in the body that breaks down natriuretic with HF (Jhund & McMurray, 2016).
peptides and other substances that affect fluid balance. By

630  Unit 5  Pharmacology of the Cardiovascular System

36.6  Diuretics relieve symptoms of heart failure of aldosterone on the heart. High levels of aldosterone pro-
by reducing fluid overload and decreasing blood mote cardiac remodeling and the deposition of fibrotic tis-
pressure. sue in the myocardium of patients with HF. By blocking
these cardiac effects, spironolactone decreases mortality
Diuretics are common medications for the treatment of due to sudden death as well as progression to advanced HF.
patients with HF because they are effective at reducing
peripheral edema and pulmonary congestion and produce Diuretic use in HF patients should be carefully moni-
few adverse effects. By reducing blood volume and lower- tored to avoid dehydration or electrolyte imbalances. These
ing blood pressure, the workload on the heart is reduced, adverse effects are more likely to occur in HF patients who
and cardiac output increases. Diuretics are rarely used have CKD. During maintenance therapy, patients are urged
alone for HF but are frequently prescribed in combination to weigh themselves frequently and report significant
with other HF medications. Doses for selected diuretics are changes to their healthcare provider. Frequent laboratory
listed in Table 36.3. The student should refer to Chapter 32 tests for blood electrolyte levels are obtained to prevent the
for more detailed information on diuretics. development of hypokalemia during loop or thiazide
diuretic therapy. This is especially important in patients
Although diuretics are effective at relieving HF symp- who are also taking digoxin (Lanoxin), because hypokale-
toms, clinical research has not demonstrated their effective- mia may induce fatal dysrhythmias. Hydrochlorothiazide,
ness in slowing the progression of HF or in decreasing the furosemide, and spironolactone are featured as drug proto-
mortality rate associated with the disease. Indeed, some of types in Chapter 32.
the actions of the diuretics, particularly effects on potas-
sium balance, may increase the risk of adverse effects from CONNECTION Checkpoint  36.2
other HF drugs. Because of this, diuretics are only indi-
cated when there is evidence of fluid retention. In patients Conn’s syndrome is characterized by excess secretion of aldoste-
presenting with fluid retention, especially with symptoms rone. From what you learned in Chapter 31, what effect would you
of severe pulmonary congestion or peripheral edema, predict this syndrome would have on the heart, and what medica-
diuretics are essential medications. tion might be a preferred drug?  Answers to Connection Checkpoint
questions are available on the faculty resources site. Please consult
Of the diuretic classes, the loop diuretics are most com- with your instructor.
monly prescribed for HF, due to their effectiveness in
removing fluid from the body. Loop diuretics are also able 36.7  Beta-adrenergic antagonists can
to function in patients with chronic kidney disease (CKD), dramatically reduce hospitalizations and
an advantage for many patients with decompensated HF. increase the survival of patients with heart
Another major advantage in treating acute HF is that loop failure.
diuretics act quickly, within minutes for intravenous (IV)
formulations. For chronic HF, therapy is begun with low Cardiac glycosides, beta-adrenergic agonists, and other
doses and gradually increased until the desired volume medications that produce a positive inotropic effect serve
reduction is obtained. important roles in reversing the diminished contractility
that is the hallmark of HF. It may seem somewhat surpris-
As therapy continues with loop diuretics, some ing, then, to find beta-adrenergic antagonists—drugs that
patients become less responsive, a phenomenon known as exhibit a negative inotropic effect—prescribed for this dis-
diuretic resistance. The loop diuretics exhibit a ceiling ease. Even though this class of drugs has the potential to
effect; once the “ceiling dose” is reached, increases in dos- worsen HF, beta-adrenergic antagonists are standard ther-
age will not produce additional diuresis. To obtain addi- apy for many patients with this chronic disorder. Why is
tional diuresis and volume reduction, the loop diuretic this the case?
may be administered more frequently, or a diuretic from a
different class may be added to the regimen. In patients with HF, high levels of endogenous norepi-
nephrine and other catecholamines cause excessive activa-
Thiazide diuretics are also used in the pharmacother- tion of the sympathetic nervous system and are associated
apy of HF, sometimes combined with loop diuretics to with cardiac remodeling and progression of the disease.
achieve a more effective diuresis in patients with acute HF. Beta-adrenergic antagonists block the actions of these cate-
Because they are less effective than the loop diuretics, thia- cholamines, slowing the heart rate and reducing blood pres-
zides are generally reserved for patients with mild-to- sure, thus decreasing the cardiac workload. After several
moderate HF. months of therapy, heart size, shape, and function return to
normal in some patients, in essence producing a reverse
In addition to being a potassium-sparing diuretic, spi- remodeling of the heart. Careful use of beta-adrenergic
ronolactone is also classified as an aldosterone antagonist. antagonists can reduce the number of HF-associated hospi-
As a diuretic, spironolactone has a limited role in HF, due to talizations and deaths. They are effective in all stages of
its low efficacy. Clinical research, however, has demon-
strated that the drug is able to block the deleterious effects

Chapter 36  Pharmacotherapy of Heart Failure  631

symptomatic HF. Doses for selected beta-adrenergic antag- to be particularly effective in treating African Americans,
onists are listed in Table 36.3. who are sometimes resistant to therapy for HTN and HF.

To benefit patients with HF, however, beta-adrenergic Hydralazine acts on arterioles to decrease peripheral
antagonists must be administered in a very specific man- resistance, reduce afterload, and increase cardiac output. It
ner. Initial doses must be 1/10 to 1/20 of the target dose. is an effective antihypertensive drug, although it is not a
Doses are doubled every 2 weeks until the target dose is preferred drug for this indication because hypotension and
reached. If therapy is begun with the target dose, or the reflex tachycardia are common and may limit therapy. The
dose is increased too rapidly, beta blockers can worsen HF. drug must be taken 3 to 4 times daily, which places an
Carvedilol and metoprolol are the two beta-adrenergic extensive pill burden on patients with HF, who often are
antagonists approved for HF, although bisoprolol has also taking multiple drugs. Hydralazine is presented as a proto-
been shown to be effective. When treating HF, beta block- type vasodilator for HTN in Chapter 34.
ers are almost always combined with other HF drugs.
Isosorbide dinitrate (Isordil) is a long-acting organic
Adherence to beta-blocker therapy can be a major clin- nitrate that reduces preload by directly dilating veins. The
ical challenge for some patients. The patient may not report drug is not very effective as monotherapy, and tolerance
symptomatic improvement with the drug and, in fact, may develops to its actions with continued use. Isosorbide dini-
feel worse at the initiation of therapy. To achieve maximum trate is usually combined with hydralazine (BiDil) because
patient adherence, the nurse must teach the patient the the two drugs act synergistically when used in patients with
important long-term benefits of beta blockers. HF. The high incidence of adverse effects, such as reflex
tachycardia and orthostatic hypotension, limits their use in
Beta-adrenergic antagonists are contraindicated in some patients. The use of isosorbide dinitrate in the phar-
patients with chronic obstructive pulmonary disease macotherapy of angina pectoris is presented in Chapter 35.
(COPD), severe bradycardia, or heart block. These medica-
tions should be used with caution in patients with diabetes, Nesiritide (Natrecor):  A third vasodilator used for HF is very
peripheral vascular disease, and hepatic impairment. Cau- different from hydralazine or isosorbide dinitrate. Approved
tion is needed with older adults because these patients in 2001, nesiritide (Natrecor) is a small-peptide hormone pro-
often require a reduced dose. Hepatic function tests should duced through recombinant DNA technology that is structur-
be performed periodically and the prescriber notified if ally identical to human beta-type natriuretic peptide (hBNP).
signs or symptoms of hepatotoxicity become apparent. When HF occurs, the ventricles begin to secrete hBNP in
response to the increased stretch on the ventricular walls.
A new drug was introduced in 2015 for patients in hBNP enhances diuresis and renal excretion of sodium.
whom beta blockers are contraindicated or when the maxi-
mum dose of the beta blocker fails to achieve therapeutic In therapeutic doses, nesiritide causes vasodilation,
goals. Ivabradine (Corlanor) acts by a unique mechanism which reduces preload. By lowering preload and afterload,
that slows ion (If ) currents across the sinoatrial (SA) node, the drug compensates for diminished cardiac function. The
which slows the heart rate and reduces myocardial oxygen use of nesiritide is limited because it can rapidly cause
demand. The subscript f stands for “funny,” so named severe hypotension, which can persist several hours after
because the original research determined this current had the infusion is discontinued. The drug is given by IV infu-
unusual properties, distinct from sodium, calcium, or sion, and patients require continuous monitoring. It is
potassium currents. Adverse effects include possible bra- approved only for patients with acutely decompensated
dycardia, hypotension and atrial fibrillation. heart failure. The dosage for nesiritide is shown in
Table 36.4. Nesiritide is pregnancy category C.
The basic pharmacology of the beta-adrenergic antago-
nists is presented in Chapter 16, where metoprolol is fea- CONNECTION Checkpoint  36.3
tured as a prototype for this class. Other applications of the
beta-adrenergic antagonists are discussed elsewhere in this Isosorbide dinitrate is also used for angina. From what you learned
text: HTN is discussed in Chapter 34, angina and MI in in Chapter 35, why is nitroglycerin a preferred drug for acute angina,
Chapter 35, and dysrhythmias in Chapter 37. rather than isosorbide dinitrate?  Answers to Connection Checkpoint
questions are available on the faculty resources site. Please consult
36.8  Vasodilators reduce symptoms of heart with your instructor.
failure by reducing preload or afterload.
36.9  Cardiac glycosides increase the force of
Vasodilators relax blood vessels and lower blood pressure, myocardial contraction and were once preferred
creating less workload on the heart. They serve a limited drugs for heart failure.
role in the pharmacotherapy of HF.
Once used as arrow poisons by African tribes and as
Hydralazine with isosorbide dinitrate (BiDil):  Hydralazine medicines by the ancient Egyptians and Romans, the
combined with isosorbide dinitrate (BiDil) is approved as an
adjunct to standard therapy for HF. The combination appears

632  Unit 5  Pharmacology of the Cardiovascular System

Table 36.4  Drugs for Advanced Heart Failure

Drug Route and Adult Dose Adverse Effects
Beta-Adrenergic Agonists (Maximum Dose Where Indicated) Headache, palpitations, nausea, vomiting, changes in
dobutamine (Dobutrex) blood pressure (hypo- or hypertension)
dopamine (Dopastat, Intropin) IV: Infused at a rate of 2.5–40 mcg/kg/min for a max of 72 h Dysrhythmias, gangrene, severe HTN
IV: 2–5 mcg/kg/min initial dose; may be increased to
epinephrine (Adrenalin) 20–50 mcg/kg/min (max: 50 mcg/kg/min) Headache, hypotension
Subcutaneous: 0.1–0.5 mL of 1:1000 every 10–15 min prn Dysrhythmias
isoproterenol (Isuprel) IV: 0.1–0.25 mL of 1:1000 every 10–15 min Hypotension, increased serum creatinine
norepinephrine (Levophed) IV infusion: 0.5–5 mcg/min Dysrhythmias
IV: Initially, 0.5–1 mcg/min until pressure stabilizes, then 2–4
Phosphodiesterase Inhibitor mcg/min for maintenance (max: 30 mcg/min)
milrinone (Primacor)
IV: 50 mcg/kg over 10 min; then 0.375–0.75 mcg/kg/min

Vasodilator IV: 2 mcg/kg bolus followed by continuous infusion
nesiritide (Natrecor) at 0.1 mcg/kg/min

Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.

value of the cardiac glycosides in treating heart disorders PROTOTYPE DRUG Digoxin (Lanoxin, Lanoxicaps)
has been known for over 2000 years. Originally extracted
from the beautiful flowering plants Digitalis purpura (pur- Classification Therapeutic: Drug for heart failure
ple foxglove) and Digitalis lanata (white foxglove), the Pharmacologic: Cardiac glycoside,
cardiac glycosides were the mainstay of HF treatment
until the discovery of the ACE inhibitors. During the past inotropic drug
20 years, the role of the cardiac glycosides in the pharma-
cotherapy of HF has become more limited. The dose for Therapeutic Effects and Uses:  The primary ben-
digoxin, the sole available drug in this class, is listed in efit of digoxin is its ability to increase the strength of
Table 36.3. myocardial contraction, a positive inotropic action. By
increasing myocardial contractility, digoxin directly
Because of its long historical use, the effectiveness of increases cardiac output, which alleviates symptoms of
digoxin in the pharmacotherapy of HF remained unques- HF and improves exercise tolerance. The higher cardiac
tioned until the late 1980s. Based on subsequent research output increases urine production and results in a desir-
and the development of safer and more effective drug able reduction in blood volume, relieving the distress-
classes, digoxin is now limited to late-stage HF, in combi- ing symptoms of pulmonary congestion and peripheral
nation with other drugs. Digoxin remains an important edema. In current clinical practice, digoxin use is usu-
therapy in HF patients with supraventricular tachyar- ally limited to patients who are not responding ade-
rhythmias because the drug has antidysrhythmic activity quately to ACE inhibitor therapy or to HF patients with
that can stabilize these types of cardiac conduction atrial fibrillation.
abnormalities.
In addition to its positive inotropic effect, digoxin
The margin of safety between a therapeutic dose and a also affects the speed of myocardial conduction. Through
toxic dose of cardiac glycosides is very narrow, and severe a mechanism not fully understood, digoxin decreases
adverse effects may result from poorly managed therapy. SNS activity and increases parasympathetic activity.
Digitalization refers to the procedure by which the dose of This helps attenuate the excessive sympathetic activa-
digoxin is gradually increased until tissues become satu- tion that causes tachycardia and worsens HF (see
rated with the medication, and the symptoms of HF dimin- Section 36.2). Digoxin has the ability to suppress the SA
ish. If the patient is critically ill, digitalization can be done node and slow electrical conduction through the atrio-
rapidly with IV doses in a controlled clinical environment, ventricular node. The heart rate decreases, allowing
where adverse effects may be carefully monitored. Using greater diastolic filling of the ventricles. Because the
oral (PO) dosing digitalization may be completed over a heart rate may decline too much, healthcare providers
period of 7 days. In either case, the goal is to determine the establish parameters for each patient. As a general rule,
proper dose of medication to be administered, without if the apical pulse falls below 60 beats/min, the medica-
undue adverse effects. tion is withheld and the healthcare provider notified.

Chapter 36  Pharmacotherapy of Heart Failure  633

Digoxin is sometimes used to treat dysrhythmias, as dis- that toxicity should be based on patient symptoms rather
cussed in Chapter 37. than serum level.

Digoxin is available by the PO or IV route. Because dif- Contraindications/Precautions:  Patients with AV
ferences in bioavailability of digoxin formulations can block or ventricular dysrhythmias unrelated to HF should
potentially affect drug action and the potential for adverse not receive digoxin, because the drug may worsen these
effects, patients are advised to continue with the same conditions. Digoxin should be administered with caution
trade name, unless otherwise changed by the prescriber. to older adults because these patients experience a higher
incidence of adverse effects. Patients with CKD should re-
Mechanism of Action:  Digoxin inhibits Na+-K+- ceive lower doses of digoxin, because the drug is excreted
ATPase, the critical enzyme responsible for pumping so- by this route. The drug should be used with caution in pa-
dium ions out of the myocardial cells in exchange for tients with MI, cor pulmonale, or hypothyroidism.
potassium ions. As sodium ions accumulate in myocytes,
calcium ions are released from their storage areas in the cell Drug Interactions:  Digoxin interacts with many
to activate contractile elements. The release of calcium ions drugs. Concurrent use of digoxin with diuretics must be
produces a more forceful contraction of myocardial fibers. carefully monitored, since diuretics can cause hypokale-
mia and increase the risk of dysrhythmias. Use with ACE
Pharmacokinetics:  inhibitors, spironolactone, or potassium supplements can
lead to hyperkalemia and reduce the therapeutic action
Route(s) PO, IV of digoxin. Administration of digoxin with other positive
inotropic drugs can cause additive effects on myocardial
Absorption 70–90% absorbed from the contractility. Concurrent use with beta blockers may re-
sult in additive bradycardia. Antacids and cholesterol-
gastrointestinal (GI) tract lowering drugs can decrease the absorption of digoxin. If
calcium is administered intravenously together with di-
Distribution Widely distributed; crosses the goxin, it can increase the risk of dysrhythmias. Quinidine,
verapamil, amiodarone, and alprazolam will decrease the
placenta; secreted in breast milk; distribution and excretion of digoxin, thus increasing the
risk of digoxin toxicity. Herbal/Food: The drug should be
20–25% bound to protein used with caution with ginseng, which may increase the
risk of digoxin toxicity.
Primary metabolism Hepatic, 14%
Pregnancy:  Category C.
Primary excretion Renal
Treatment of Overdose:  Digoxin overdose can be
Onset of action PO: 30–90 min; IV: 5–30 min fatal and the nurse should be prepared to administer
digoxin immune Fab (Digibind). Digoxin immune Fab
Duration of action Half-life: 3–4 days consists of digoxin-specific antibodies, which form a
complex with digoxin that prevents the drug from reach-
Adverse Effects:  Adverse effects of digoxin involve ing the tissues, and is removed through renal excretion.
multiple body systems and can be severe. The most dan- Reversal of adverse effects occurs quickly: 90% of patients
gerous adverse effect is ventricular dysrhythmias, which respond within an hour after IV administration. As digo­
may result in sudden cardiac death. The most common xin is removed from the body, the inotropic effects of the
cause of digoxin-induced dysrhythmias is hypokalemia drug will diminish, and the patient may be at risk of HF.
due to diuretic use. Other factors placing patients at risk The patient must be monitored continuously during the
for digoxin-induced dysrhythmias include hypomag- infusion.
nesemia, hypercalcemia, and impaired renal function.
Additional serious adverse cardiac effects include atrio- Nursing Responsibilities:  Key nursing implications
ventricular (AV) block, atrial dysrhythmias, and sinus bra- for patients receiving digoxin are included in the Nursing
dycardia. Frequent electrocardiograms (ECGs) should be Practice Application for Patients Receiving Pharmacother-
obtained to assess for cardiotoxicity. apy for Heart Failure.

Noncardiac adverse effects include general malaise, Drugs Similar to Digoxin
dizziness, headache, anorexia, nausea, and vomiting. The (Lanoxin, Lanoxicaps)
drug may produce unusual visual effects such as halos,
changes in color perception, and photophobia. Digoxin is the only cardiac glycoside available in the
United States.
Frequent serum digoxin levels should be obtained dur-
ing therapy, and the dosage adjusted based on the labora-
tory results and the patient’s clinical response. Digoxin
levels from 0.5 to 2 ng/mL give the most therapeutic ben-
efit, with an acceptable risk of adverse effects for most
patients. For each patient, the healthcare provider should
establish acceptable parameters for serum digoxin levels,
and the drug should be discontinued should the level rise
above the maximum. Digoxin levels greater than 2.0 ng/mL
are considered toxic. However, the nurse should remember

634  Unit 5  Pharmacology of the Cardiovascular System

CONNECTION Checkpoint  36.4 phosphodiesterase inhibitors. Doses for these drugs are
listed in Table 36.4.
Cholestyramine reduces the bioavailability of digoxin, thus potentially
decreasing the actions of the cardiac glycoside. From what you learned Beta-Adrenergic Agonists (Sympathomimetics): 
in Chapter 29, what is the primary indication for cholestyramine and Beta-adrenergic agonists used for HF include isoproterenol
what is the likely reason this drug causes a decrease in digoxin bio- (Isuprel), epinephrine, norepinephrine, dopamine, and
availability?  Answers to Connection Checkpoint questions are avail- dobutamine. Dobutamine has been a traditional preferred
able on the faculty resources site. Please consult with your instructor. drug in this class because it has the ability to rapidly
increase myocardial contractility, with minimal changes to
CONNECTIONS: Treating the heart rate or blood pressure. This is important because
Diverse Patient increases in heart rate or blood pressure will create greater
oxygen demands on the heart and possibly worsen HF.
The Impact of Health Literacy on Heart Failure Therapy with dobutamine is usually limited to 72 hours,
Outcomes as continuous infusion of the drug causes the heart to
become tolerant to beta-adrenergic activation, making the
The treatment of HF involves complex diet routines, fluid and salt drug less effective. The two most common adverse effects
restrictions, drug therapy including titration of medications, exer- with beta agonists are tachycardia and dysrhythmias.
cise prescriptions, and follow-up reassessment visits. The patient
must manage these routines and also monitor weight, vital signs, Patients who have both HF and hypotension benefit
and responses to medications. Low health literacy levels can from dopamine, which not only increases myocardial con-
have significant impact on the outcome of HF management. tractility but also activates alpha-adrenergic receptors to
increase blood pressure. However, tachycardia is more
Health literacy has been defined as an individual’s ability prominent with dopamine than with dobutamine. Patients
to obtain, communicate, process, and understand basic health who have been receiving a beta-adrenergic antagonist for
information and services and then make appropriate health their HF may require a higher initial dose of beta agonist.
decisions (Centers for Disease Control and Prevention, 2016). The basic pharmacology of the beta-adrenergic agonists
Low health literacy has been associated with increased risk of was presented in Chapter 15, where epinephrine and iso-
mortality, the inability to self-manage the disease adequately, proterenol were featured as prototypes for this drug class.
and a lower quality of life for HF patients (Cajita, Cajita, & Han,
2016; McNaughton et al., 2015). Particularly for patients in Phosphodiesterase III Inhibitors:  In the 1980s, two
acute HF, low health literacy has been associated with an medications became available that block the enzyme phos-
increased risk of death (McNaughton et al., 2015). phodiesterase III in cardiac and smooth muscle, which
leads to increases in the amount of calcium available for
Because of the significant impact health literacy has on myocardial contraction. The enzyme inhibition results in
the outcome of HF treatment, an assessment of a patient’s two main actions that benefit patients with HF: a positive
ability to understand the disorder and its treatment is essential inotropic action and vasodilation. Cardiac output is
to include during initial and subsequent nurse–patient interac- increased due to the increase in contractility and the
tions. In addition to assessing the patient’s ability to under- decrease in left ventricular afterload. There is little effect on
stand and use the information provided during patient heart rate. Arterial pressure is either decreased or, in some
education, assessing the patient’s skills as to when and how patients, it remains unchanged. Inamrinone was discontin-
to search for additional appropriate and credible information ued in 2011, leaving milrinone the only drug in this class.
and when to seek assistance with finding information is also
needed (Champlin, Mackert, Glowacki, & Donovan, 2016). Although the actions of milrinone are very similar to
those of dobutamine, it has a much longer half-life. This
Patient education has always been a major focus for makes it more difficult to make rapid changes in dose when
nurses, and it is especially crucial when caring for patients with controlling acute HF. In addition, if adverse effects do
HF. Assessing the level of health literacy, and helping patients occur, they are more prolonged than with dobutamine.
improve their knowledge of their disease, can have a signifi-
cant impact on the overall success of treatment. Milrinone has serious toxicity that limits its use in
patients with resistant HF who have not responded to ACE
36.10  Phosphodiesterase III inhibitors and inhibitors, digoxin, or other therapies. Therapy is limited to
other positive inotropic drugs are used for 2 to 3 days and the patient is continuously monitored for
acute advanced heart failure. ventricular dysrhythmias, including ectopic beats, supra-
ventricular dysrhythmias, premature ventricular contrac-
Advanced or decompensated HF can be a medical emer- tions, ventricular tachycardia, and ventricular fibrillation.
gency, and prompt, effective treatment is necessary to If the patient presents with hypokalemia, this should be
avoid organ failure or death. In addition to high doses of corrected before administering milrinone because this can
loop diuretics, positive inotropic drugs may be necessary. increase the likelihood of dysrhythmias.
The two primary classes of inotropic drugs used for
acute advanced HF are beta-adrenergic agonists and

Chapter 36  Pharmacotherapy of Heart Failure  635

PROTOTYPE DRUG Milrinone (Primacor) Adverse Effects:  The most serious adverse effect of
milrinone is ventricular dysrhythmia, which can occur
Classification Therapeutic: Drug for heart failure in more than 10% of patients taking the drug. The ECG
Pharmacologic: Phosphodiesterase III is monitored continuously during infusion of the drug to
prevent serious dysrhythmias. Blood pressure is also con-
inhibitor; inotropic drug tinuously monitored during the infusion to prevent hypo-
tension. Patients with NYHA Class IV HF are at high risk
Therapeutic Effects and Uses:  Approved in 1987, for life-threatening cardiovascular reactions. Less serious
milrinone is indicated for the short-term treatment of adverse effects include headache, nausea, and vomiting.
patients with acute advanced heart failure. It is only given
intravenously, and peak effects occur in 2 minutes. Imme- Contraindications/Precautions:  Milrinone is contra-
diate effects of milrinone include an increased force of con- indicated in patients with severe obstructive valvular heart
traction (positive inotropic effect) and a resulting increase disease. The drug should be used with caution in patients
in cardiac output. Research has not demonstrated any with preexisting dysrhythmias. Hypovolemia or electrolyte
decrease in mortality or morbidity with the use of milrinone imbalances should be corrected before starting the infusion,
infusions. Drug therapy with milrinone is generally limited and the dose should be reduced in patients with CKD.
to 48 hours.
Drug Interactions:  Caution should be used when ad-
Mechanism of Action:  Milrinone inhibits phospho- ministering milrinone with digoxin, dobutamine, or other
diesterase III, the enzyme responsible for the breakdown inotropic drugs, since their cardiac effects may be additive.
of cAMP to AMP, in cardiac and vascular smooth muscle. Use with antihypertensive drugs may cause additive
The rise in cAMP levels increases intracellular calcium, hypotension. Herbal/Food: Ginger may contribute to the
resulting in greater contractility. Cardiac output is increased cardiac actions of milrinone.
and pulmonary capillary wedge pressure is decreased.
Pregnancy:  Category C.
Pharmacokinetics: 
Treatment of Overdose:  Overdose of milrinone
Route(s) IV causes hypotension, which may be treated with the admin-
istration of normal saline or a vasopressor.
Absorption N/A
Nursing Responsibilities:  Key nursing implications
Distribution Unknown; 70% bound to plasma for patients receiving milrinone are included in the Nurs-
ing Practice Application for Patients Receiving Pharmaco-
protein therapy for Heart Failure.

Primary metabolism 83% is excreted unchanged; Drugs Similar to Milrinone (Primacor)

small amounts metabolized by Milrinone is the only drug in the phosphodiesterase inhib-
itor class.
liver

Primary excretion Renal

Onset of action 2–10 min

Duration of action Half-life: 3–6 h

CONNECTIONS:  NURSING PRACTICE APPLICATION

Patients Receiving Pharmacotherapy for Heart Failure

Assessment

Baseline assessment prior to administration:

• Obtain a complete health history: cardiovascular (including previous MI, HF, valvular disease, dysrhythmias [especially heart block]), renal dysfunction,
pregnancy, or lactation. Obtain a drug history including allergies, current prescription and over-the-counter (OTC) drugs, herbal preparations, and
alcohol use. Be alert to possible drug interactions.

• Obtain baseline weight, vital signs (especially pulse and blood pressure), breath sounds, and ECG. Assess for location and character of edema if present.
• Evaluate appropriate laboratory findings, electrolytes, especially potassium level, renal function studies, and lipid profiles.
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.

Assessment throughout administration:

• Assess for desired therapeutic effects (e.g., heart rate and blood pressure return to, or remain within, normal limits; urine output returns to, or is within,
normal limits; respiratory congestion [if present] is improved; peripheral edema [if present] is improved; level of consciousness, skin color, capillary refill,
and other signs of adequate perfusion are within normal limits; fatigue lessens).

• Continue periodic monitoring of electrolytes, especially potassium, renal function, and drug levels.
• Assess for adverse effects: hypotension, fatigue, dizziness, or drowsiness. Bradycardia, nausea, vomiting, anorexia, and visual changes (e.g., halos

around lights, yellow or yellowish-green tint to colors) may also occur with digoxin. A pulse rate below 60 or above 100 beats/min, palpitations, signifi-
cant dizziness or syncope, dyspnea, persistent anorexia or vomiting, or visual changes should be reported to the provider immediately.
• Lifespan: Exercise extra caution when giving the drug to older adults, pediatric patients, or patients with CKD. Immature renal function or declines in
renal function make these populations more susceptible to adverse effects.

(continued )

636  Unit 5  Pharmacology of the Cardiovascular System

CONNECTIONS:  NURSING PRACTICE APPLICATION (continued)

Implementation

Interventions and (Rationales) Patient-Centered Care

Ensuring therapeutic effects: • Teach the patient, family, or caregiver how to monitor the pulse and
• Continue frequent assessments as above for therapeutic effects. (As blood pressure. Ensure proper use and functioning of any home
equipment obtained.
the heart contracts more forcefully, blood pressure and pulse should
return to within normal limits or within the parameters set by the health-
care provider; urine output returns to within normal limits, peripheral
edema decreases, and lung sounds are clear.)

• Encourage appropriate lifestyle changes: lowered fat intake, restricted • Encourage the patient, family, or caregiver to adopt a healthy lifestyle
sodium or fluid intake if ordered, gradually increased levels of exercise, of low-fat food choices, increased exercise, decreased alcohol
limited alcohol intake, and smoking cessation. Provide for dietitian con- consumption, and smoking cessation. Provide educational materials
sultation as needed. (Healthy lifestyle changes will support the benefits on low-fat, low-sodium food choices.
of drug therapy.)

Minimizing adverse effects: • Teach the patient, family, or caregiver how to take a peripheral pulse
• Continue to monitor vital signs. Take an apical pulse for 1 full minute for 1 full minute before taking the drug. Assist the patient to find the
most convenient and easily felt pulse area. Record daily pulse rates
before giving the drug. Hold the drug and notify the healthcare and bring the record to each healthcare visit. Instruct the patient to
provider if heart rate is below 60 or above 100 beats/min. Monitor not take the drug if pulse is below 60 or above 100 beats/min, and
ECG during infusion of milrinone (Primacor) and during the to contact the provider for further direction. If the patient, family,
digitalization period for dysrhythmias or bradycardia. (Drugs that or caregiver chooses to buy a stethoscope to take pulse, ensure
are positive inotropes increase myocardial contractility but may proper understanding of heart sounds (i.e., the “lub-dub” sound of a
affect cardiac conduction. Milrinone is associated with serious and heartbeat is one heartbeat) and appropriate stethoscope placement.
potentially life-threatening dysrhythmias. Digoxin slows the heart rate Have the patient, family, or caregiver return demonstrate. (With easier
and may cause bradycardia.) accessibility to OTC medical equipment such as stethoscopes,
patients, family, or caregivers may try to emulate the healthcare
provider. Ensure proper use before the patient goes home.)

• Instruct patients receiving milrinone by infusion to immediately report
any chest pain.

• Continue to monitor electrolyte levels periodically, especially • Instruct the patient on the need to return periodically for laboratory work.
potassium, renal function laboratory values, drug levels, and • Advise the patient to carry a wallet identification card or wear medical
ECG. (Hypokalemia increases the risk of dysrhythmias from drugs
used to treat HF.) identification jewelry indicating drug therapy for HF.

• Weigh the patient daily and report a weight gain or loss of 1 kg (2 lb) • Have the patient weigh self daily, ideally at the same time of day, and
or more in a 24-h period. (Daily weight is an accurate measure of fluid record weight along with pulse measurements. Instruct the patient to
status and takes into account intake, output, and insensible losses. report a weight loss or gain of more than 1 kg (2 lb) in a 24-h period.
Weight gain or edema may signal impending HF with reduced organ
perfusion, stimulating renin release.)

• Monitor for signs of worsening HF (e.g., increasing dyspnea or • Instruct the patient to immediately report any severe shortness of
postural nocturnal dyspnea, rales or crackles in lungs, frothy pink- breath, frothy sputum, profound fatigue, or swelling of extremities as
tinged sputum) and report immediately. (Positive inotropic drugs such possible signs of HF.
as digoxin or phosphodiesterase inhibitors are usually reserved for
patients with more advanced stages of HF. If signs and symptoms
worsen, other treatment options may need to be considered.)

• For patients taking digoxin, report signs of possible toxicity immediately • Instruct the patient, family, or caregiver on signs to report to the health-
to the provider and obtain a drug level. Digoxin levels should remain care provider. Encourage the patient to report any significant change in
less than 1.8 mg/mL. Signs and symptoms such as bradycardia, overall health or mental activity promptly.
nausea and vomiting, anorexia, visual changes, depression, changes
in level of consciousness, fatigue, dizziness, or syncope should
be reported. Lifespan: Digoxin is on the Beers list of potentially
inappropriate drugs for the older adult and warrants careful monitoring.
(Decreased excretion of digoxin and phosphodiesterase inhibitors due
to age-related changes may increase the risk of adverse effects.)

• Lifespan: Use extra caution when measuring the precise dose of • Caution the patient, family, or caregiver on taking the precise dose of
medication ordered, and use extreme caution when measuring liquid medication ordered, not doubling the dose if a dose is missed, and
doses, especially for pediatric patients. (For drugs such as digoxin to use extreme caution when measuring liquid doses, especially for
with a long half-life and duration, toxic levels may result with only small pediatric patients.
amounts of additional drug.)

• Lifespan: Assess for the possibility of pregnancy before beginning the • Instruct female patients who may be considering pregnancy, or are
drug. (Many drugs for HF are pregnancy category C drugs and should pregnant or breastfeeding, to notify their provider before starting the
be used with caution during pregnancy or breastfeeding.) drug.

Patient understanding of drug therapy: • The patient, family, or caregiver should be able to state the reason for
• Use opportunities during administration of medications and during the drug, appropriate dose and scheduling, what adverse effects to
observe for and when to report them, and the anticipated length of
assessments to discuss the rationale for the drug therapy, desired medication therapy.
therapeutic outcomes, commonly observed adverse effects, parameters
for when to call the healthcare provider, and any necessary monitoring
or precautions. (Using time during nursing care helps to optimize and
reinforce key teaching areas.)

Chapter 36  Pharmacotherapy of Heart Failure  637

CONNECTIONS:  NURSING PRACTICE APPLICATION (continued)

Implementation

Interventions and (Rationales) Patient-Centered Care

Patient self-administration of drug therapy: • The patient, family, or caregiver is able to discuss appropriate dosing
• When administering medications, instruct the patient, family, or care- and administration needs.

giver in the proper self-administration techniques. (Utilizing time during • The drug should be taken at the same time each day, and doses
nurse administration of these drugs helps to reinforce teaching.) should not be skipped or doubled.

• The brand of the drug prescribed should not be switched without
consultation with the provider to ensure consistent effects.

Understanding Chapter 36

Key Concepts Summary 36.7 Beta-adrenergic antagonists can dramatically
reduce hospitalizations and increase the survival
36.1 Heart failure is closely associated with disorders of patients with heart failure.
such as chronic hypertension, coronary artery
disease, and diabetes. 36.8 Vasodilators reduce symptoms of heart failure by
reducing preload or afterload.
36.2 The body attempts to compensate for heart failure
by increasing cardiac output. 36.9 Cardiac glycosides increase the force of
myocardial contraction and were once preferred
36.3 Symptoms of heart failure occur when drugs for heart failure.
compensatory mechanisms fail to maintain
adequate cardiac output. 36.10 Phosphodiesterase III inhibitors and other
positive inotropic drugs are used for acute
36.4 The specific therapy for heart failure depends on advanced heart failure.
the clinical stage of the disease.

36.5 Angiotensin-converting enzyme inhibitors are
preferred drugs for heart failure.

36.6 Diuretics relieve symptoms of heart failure by
reducing fluid overload and decreasing blood
pressure.

CASE STUDY: Making the Patient Connection

Remember the patient in a recliner and is unable to lie flat in bed at night. Her past
“Thelma Walters” at the medical history includes a mild stroke occurring 8 years ago
beginning of the chapter? with mild residual weakness on her right side, MI 3 years
Now read the remainder of ago, and an episode of HF 1 year ago. The HF was treated
the case study. Based on with captopril (Capoten) and furosemide (Lasix), which she
the information presented has been taking since that time. Her surgical history includes
within this chapter, a hysterectomy 20 years ago. She has never used tobacco or
respond to the critical alcohol.
thinking questions that
follow. As the nurse performs the initial physical assess-
ment, the following relevant findings are discovered. The
Thelma Walters is a 77-year- patient is 1.7 m (5′6″) tall and weighs 82 kg (180 lb). She
old woman who arrives via EMS at the emergency depart- uses a walker or a cane to feel more secure and avoid
ment (ED) after experiencing increasing dyspnea for the past falls, due to the mild residual weakness on her right side.
2 days. She has also noticed swelling in her feet and ankles. The patient’s blood pressure is 162/92 mmHg, her heart
Due to her onset of shortness of breath, she has had to sleep rate is 148 beats/min and irregular, and her respiratory
rate is 38 breaths/min and labored. The neck veins of the

638  Unit 5  Pharmacology of the Cardiovascular System

patient are distended when she is placed at a 45-degree will receive milrinone (Primacor) by IV infusion after
incline. She is orthopneic and cannot tolerate the head of admission to the ICU.
the bed being lowered below 45 degrees. The nurse notes
scattered crackles bilaterally throughout the lung fields. Critical Thinking Questions
The patient has a productive cough with frothy, pink-
tinged sputum; 4+ pitting edema of both hands and legs 1. Describe how milrinone (Primacor) aids in treating HF.
is noted with the nail beds moderately cyanotic. Circum-
oral cyanosis is also noted. 2. During the infusion of milrinone (Primacor), Thelma’s
ECG and blood pressure will be monitored closely.
Immediately upon arrival at the ED, the patient What adverse effects does milrinone have on the heart
received oxygen therapy and an IV line was started. rhythm and blood pressure?
Blood was collected for initial laboratory data with the
following results: serum sodium 136 mEq/L (normal: 3. Because Thelma has been taking furosemide (Lasix)
135–147 mEq/L), serum potassium 3.1 mEq/L (normal at home and has received another dose in the ED,
3.5–5.2 mEq/L), and arterial blood gases on room air: what will the nurse assess prior to starting the
pH 7.32, PaO2 54, PaCO2 48, SpO2 68%, indicating overall milrinone (Primacor)? What electrolyte imbalance
hypoxemia. Thelma is in acute distress and admitted to must be corrected before Thelma receives the
the intensive care unit (ICU) with a diagnosis of HF. milrinone (Primacor)?
She is given a dose of furosemide (Lasix) 20 mg IV and she
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.

Additional Case Study 2. Jim will have a digoxin serum level collected during
the healthcare provider office visit. What does he need
Jim Mabry, a 77-year-old man, currently takes the follow- to know about this procedure?
ing medications daily: digoxin (Lanoxin) 0.125 mg;
furosemide (Lasix) 20 mg daily; and potassium supple- 3. Prepare a list of foods that are rich in potassium as
mentation (K-Dur) 20 mEq. As his nurse, you will be dis- requested by Jim.
cussing Jim’s medication regimen and his next healthcare
provider office visit after discharge from the hospital. Answers to Additional Case Study questions are available on the
faculty resources site. Please consult with your instructor.
1. Discuss the relationship among the three
medications.

Chapter Review (Lanoxin) therapy. Which point would the nurse
include in the patient’s teaching?
1. A patient newly diagnosed with heart failure follow-
ing an acute myocardial infarction has a prescription 1. Take the drug in the morning before rising.
for enalapril (Vasotec). This drug class is frequently 2. Monitor the pulse daily prior to taking the drug.
used in early heart failure because of what clinical 3. Discontinue the drug if the pulse rate is 70 beats
improvement?
per minute.
1. It strengthens the force of myocardial contraction 4. Eat a diet high in bran fiber and calcium.
to improve cardiac output.
3. The nurse is evaluating the therapeutic effects of mil-
2. It decreases peripheral resistance, increasing rinone (Primacor). The nurse knows that this drug is
cardiac output. given to:

3. It slows the heart rate, improving filling time and 1. Increase the force of cardiac contractions and
increasing cardiac output. improve cardiac output.

4. It has diuretic effects, decreasing peripheral edema 2. Decrease the volume of the cardiac output to
and pulmonary congestion. reduce hypertension.

2. In providing the patient with heart failure informa-
tion prior to discharge, the nurse will discuss digoxin

Chapter 36  Pharmacotherapy of Heart Failure  639

3. Relax the myocardial muscle, decreasing 3. The beta-adrenergic antagonist dosage must be
myocardial oxygen requirements. lowered if the patient is also on ACE inhibitors.

4. Inhibit cardiac irregularities, decreasing the 4. Beta-adrenergic antagonists are almost never used
sensation of palpitations. in HF and the order must be confirmed.

4. The patient is receiving hydralazine with isosorbide 6. When planning patient education, the nurse knows
(BiDil) for heart failure. The nurse should monitor this that patient adherence to beta-adrenergic antagonist
patient for: therapy in heart failure may be difficult to achieve
despite the usefulness of these drugs. What will the
1. Confusion and agitation. nurse need to address in the teaching plan? (Select all
2. Bleeding. that apply.)
3. Tingling or cramping in the legs.
4. Dizziness and rapid heart rate. 1. The dosage must be gradually adjusted over time
to a beneficial dose.
5. A patient will begin taking carvedilol (Coreg) for heart
failure. Before teaching the patient about this drug, the 2. The patient may not notice significant
nurse will discuss the strategy for drug dosage with the improvement during early therapy.
healthcare provider because of which recommended
routine for beta-adrenergic antagonists in heart failure? 3. The drug may require changes to many other
medications the patient is taking.
1. Significantly lower dosages are used first and
gradually increased to a target dose. 4. The drug has significant benefit in reducing
mortality from heart failure.
2. A loading dose that is higher than the subsequent
daily dose must be given. 5. The drug will require extensive lifestyle changes.

See Answers to Chapter Review in Appendix A.

References and mortality: A cohort study of patients hospitalized
for acute heart failure. Journal of the American Heart
Cajita, M. I., Cajita, T. R., & Han, H. R. (2016). Health Association, 4, e001799. doi:10.1161/JAHA.115.001799
literacy and heart failure: A systematic review. The Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D.
Journal of Cardiovascular Nursing, 31, 121–130. E., Colvin, M. M., . . . Westlake, C. (2016). 2016 ACC/
doi:10.1097/JCN.0000000000000229 AHA/HFSA focused update on new pharmacological
therapy for heart failure: An update of the 2013 ACCF/
Centers for Disease Control and Prevention. (2016). What AHA guideline for the management of heart failure: A
is health literacy? Retrieved from https://www.cdc. report of the American College of Cardiology/
gov/healthliteracy/learn American Heart Association Task Force on Clinical
Practice Guidelines and the Heart Failure Society of
Champlin, S., Mackert, M., Glowacki, E. M., & Donovan, America. Journal of the American College of Cardiology, 68,
E. E. (2016, May 12). Towards a better understanding of 1476–1488. doi:10.1016/j.jacc.2016.05.011
patient health literacy: A focus on the skills patients Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D.
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Stewart, S. (2013). What is the optimal place for heart
failure treatment and care: Home or hospital? Current

“I will never forget the fear that
overwhelmed me as I woke up
in the emergency department.

I had no idea what had
happened. I only remember a
strange sensation in my chest. It
was like my heart was fluttering.
Then I must have passed out.”

Patient “Jada Chinn Nguyen”

Chapter 37

Pharmacotherapy of Dysrhythmias

Chapter Outline Learning Outcomes

cc Etiology of Dysrhythmias After reading this chapter, the student should be able to:
cc Phases and Measurement of the Cardiac
1. Identify disorders associated with an increased risk
Action Potential of dysrhythmias.
cc Classification of Dysrhythmias
cc General Principles of Dysrhythmia Management 2. Explain how rhythm abnormalities can affect cardiac
cc Drugs for Dysrhythmias function.

Sodium Channel Blockers: Class I 3. Sketch a typical cardiac action potential and label
PROTOTYPE  Procainamide, p. 649 the flow of potassium, sodium, and calcium ions
Beta-Adrenergic Antagonists: Class II during each phase.
Potassium Channel Blockers: Class III
PROTOTYPE  Amiodarone (Pacerone), p. 653 4. Design a table that indicates the classification of
Calcium Channel Blockers: Class IV dysrhythmias and the types of drugs used to treat
Miscellaneous Antidysrhythmics them.

5. Describe general principles guiding the management
of dysrhythmias.

6. Identify the primary mechanisms of action of
antidysrhythmic drugs.

7. For each of the classes shown in the chapter outline,
identify the prototype and representative drugs and
explain the mechanism(s) of drug action, primary
indications, contraindications, significant drug
interactions, pregnancy category, and important
adverse effects.

8. Apply the nursing process to care for patients
receiving pharmacotherapy for dysrhythmias.

641

642  Unit 5  Pharmacology of the Cardiovascular System

Key Terms electrocardiogram (ECG), 644 repolarization, 643
paroxysmal supraventricular tachydysrhythmias, 645
bradydysrhythmias, 645 threshold potential, 643
cardioversion, 646 tachycardia (PSVT), 645 torsades de pointes, 645
cinchonism, 651 polarized, 643
defibrillation, 646 prodysrhythmics, 642
depolarization, 643 refractory period, 643
dysrhythmias, 642

Dysrhythmias are disorders of cardiac rhythm character- Table 37.1  Selected Prodysrhythmic Drugs
ized by abnormal heart rate or irregular contractions. Also
called arrhythmias, they encompass a number of different Class of Medication Example Drugs
disorders that range from harmless to life threatening. Dys-
rhythmias are diagnosed based on medical and family his- Antidysrhythmic drugs amiodarone, disopyramide, dofetilide,
tories, a physical exam, and the results from tests and flecainide, ibutilide, procainamide,
procedures. To diagnose the exact type of rhythm disorder, Autonomic drugs propafenone, quinidine, sotalol
patients must be connected to an electrocardiogram (ECG)
when they are experiencing symptoms. Proper diagnosis Calcium channel blockers atenolol, clonidine, methyldopa, nadolol,
and optimal pharmacotherapy can significantly affect the Cardiac glycosides propranolol
frequency of dysrhythmias and their consequences. Miscellaneous drugs
diltiazem, nifedipine, verapamil
Etiology of Dysrhythmias
digoxin
37.1  Some dysrhythmias produce no patient
symptoms, whereas others may be life amitriptyline, chloroquine, cimetidine,
threatening. haloperidol, lithium carbonate,
phenothiazines
Some dysrhythmias are asymptomatic and have no effect
on cardiac function, whereas others require immediate • Low or high potassium levels in the blood
treatment. Typical symptoms of dysrhythmias include diz- • Myocardial infarction (MI)
ziness, weakness, fatigue, decreased exercise tolerance, pal- • Stroke
pitations, dyspnea, and syncope. It is difficult to estimate • Diabetes mellitus
the frequency of the disease, although it is likely that dys- • Heart failure.
rhythmias are quite common in the population. Patients
often wait until these symptoms occur more frequently or In addition to the preceding list, a number of medica-
become acute before seeking medical intervention. tions have been found to cause new dysrhythmias or worsen
existing ones. Caution must be used when administering
Dysrhythmias occur in all age groups and in both prodysrhythmic drugs to patients with preexisting cardiac
healthy and diseased hearts. While the actual cause of impairment or who may have any of the above conditions.
most dysrhythmias is elusive, the majority are closely Table 37.1 lists selected drugs known to have prodysrhyth-
associated with certain conditions, primarily heart disease mic properties.
and myocardial infarction (MI): 90% of patients experienc-
ing an MI will develop a dysrhythmia. Persistent dys- Phases and Measurement
rhythmias are associated with increased risk of stroke and of the Cardiac Action Potential
heart failure (HF), and severe dysrhythmias may result in
sudden death. Conditions that promote the formation of 37.2  The phases of cardiac action potential
cardiac rhythm abnormalities are called prodysrhythmics. include rapid depolarization, a long plateau,
Some of the diseases and conditions associated with dys- and repolarization.
rhythmias are as follows:
Dysrhythmias are alterations in the normal generation or
• Hypertension (HTN) conduction of electrical impulses, or action potentials,
• Cardiac valve disease such as mitral stenosis across the myocardium. Because antidysrhythmic drugs
• Coronary artery disease (CAD) act by correcting or modifying impulse conduction, a firm
grasp of cardiac electrical properties is essential to under-
standing drug mechanisms. Before proceeding, the student
should review the normal pathway of impulse conduction
in the heart presented in Chapter 28.

Chapter 37  Pharmacotherapy of Dysrhythmias  643

Phase 1 and close rapidly, these sodium channels are
sometimes referred to as “fast” channels. Dur-
+20 Ca2+ Ca2+ Phase 2 ing this period, Ca2+ also enters the cell
Ca2+ through calcium ion channels, although the
0 Na+ influx is slower than that of sodium. In myo-
Membrane Potential (mV) Na+ K+ K+ cytes located in the SA and atrioventricular
(AV) nodes, it is the influx of Ca2+, rather than
Na+ K+ Phase 3 Na+, that generates the rapid depolarization of
Na+ K+ the membrane.
–70 Na+ Phase 0
K+ Phase 1:  During depolarization, the inside
Threshold of the plasma membrane temporarily reverses
potential its charge, becoming positive. This is a brief,
transient phase.

–90 Phase 4 Phase 2:  During phase 2, a plateau is reached

in which depolarization is maintained. The

entry of Ca2+ into the cells signals the release of

Time additional calcium ions that had been held in

Figure 37.1  Phases of the myocardial action potential. Ion movements during storage inside the sarcoplasmic reticula. This
each phase are shown. large and sudden increase in intracellular Ca2+
is responsible for the contraction of cardiac

muscle. Gated potassium ion channels open,
Action potentials occur in neurons and cardiac muscle causing an efflux of K+ from the cells. The plateau is main-
cells (myocytes) due to the changes in the concentration of tained as long as the positive calcium ions entering the
specific ions found inside and outside the cell. Under rest- myocytes are balanced by the positive potassium ions leav-
ing conditions, sodium ions (Na+) and calcium ions (Ca2+) ing the cell. Action potentials in skeletal muscle lack this

are in higher concentrations outside of myocytes, whereas plateau phase.
potassium ions (K+) are found in higher concentration
inside these cells. These imbalances are, in part, responsible Phase 3:  During phase 3, the calcium channels close and
for the inside of a myocyte plasma membrane having a additional potassium channels open, thus causing a net
slightly negative charge (80–90 mV), relative to the outside loss of positive ions from the cell. This repolarization
of the membrane. A cell having this negative membrane returns the negative resting membrane potential to the cell.
potential is polarized.
The synchronized pumping action of the heart requires
An action potential illustrating the steps in electrical alternating periods of contraction and relaxation. There is a
conduction is shown in Figure 37.1. The changes in ions, or brief period of time following depolarization and most of
fluxes, occurring during an action potential may be repolarization during which the cell cannot initiate a subse-
grouped into five phases. quent action potential. This refractory period ensures that
the myocardial cell finishes contracting before a second
Phase 4:  It is easiest to begin with phase 4 because this is action potential begins.

the period during which the myocyte is “resting” and the Although learning about the different ions involved

action potential has not yet occurred. Note in Figure 37.1, in an action potential may seem complicated, they are

however, that during phase 4 the membrane potential is very important to cardiac pharmacology. Blocking potas-

slowly increasing toward a potential that will trigger an sium, sodium, or calcium ion channels is a pharmaco-

action potential: the threshold potential. Sodium is slowly logic strategy used to terminate or prevent dysrhythmias.

“leaking” into the cell during this period, causing the In addition, the therapeutic effect of some antidysrhyth-

change in potential, which gives certain regions such as mic drugs is due to their prolongation of the refractory

the sinoatrial (SA) node the property of automaticity, the period. It is not possible to understand drug mechanisms

ability to depolarize spontaneously, without input from without adequate knowledge of the normal electrical

the nervous system. conduction properties of the heart. In general, most car-

Phase 0:  An action potential begins when the threshold diac drugs:

potential is reached and gated sodium ion channels located • Increase impulse formation (or automaticity).

in the plasma membrane become activated and open. • Increase conduction velocity.

Sodium ions rush into the cell, producing a rapid depolar- • Increase both impulse formation and conduction

ization, or loss of membrane potential. Because they open velocity.

644  Unit 5  Pharmacology of the Cardiovascular System

OR QRS Complex
• Decrease impulse formation or automaticity. Ventricles depolarize
• Decrease conduction velocity. and contract.
• Decrease both impulse formation or automa-
R
ticity and conduction.

CONNECTION Checkpoint  37.1 P Wave T Wave
Atria depolarize Ventricles repolarize
From what you learned in Chapter 30, what are the three and contract. and relax.
types of calcium channels? Which type is blocked by
calcium channel blocker medications?  Answers to Con- P T
nection Checkpoint questions are available on the faculty
resources site. Please consult with your instructor.

37.3  The electrocardiogram is used to P–R Interval Q
measure electrical conduction across the S
myocardium.
QT Interval
The electrocardiogram (ECG) is a graphic record-
ing of the wave of electrical conduction across the Figure 37.2  Relationship of the electrocardiogram to electrical conduction in
myocardium. The ECG is a primary tool in the diag- the heart.
nosis of dysrhythmias and other heart diseases. A
normal ECG and its relationship to impulse con-
duction in the heart are shown in Figure 37.2.

Three distinct waves are produced by a normal
ECG: the P wave, the QRS complex, and the T wave.
Changes to the wave patterns or in their timing are
associated with certain pathologies. The different
classes of antidysrhythmic drugs also affect the ECG
in characteristic manners. A summary of the differ-
ent waves, segments, and intervals, and their impor-
tance to cardiac physiology is given in Table 37.2.

Table 37.2  ECG Waves and Intervals

Wave or Interval Physiologic Significance Importance

P wave Represents atrial depolarization. A large P wave (voltage greater than 2.5 mm) suggests the atria may be
enlarged.
PQ segment Represents the delay at the AV node; sometimes
referred to as the PR segment. This delay is vital so the ventricles can fill with blood. Prolonged PQ
segments suggest slow or nonconducting fibrotic areas in the
PQ interval Represents all electrical activity prior to the impulse myocardium.
QRS complex reaching the ventricles and contains the P wave and
the PQ segment; sometimes referred to as the PR Normal measurements range between 0.12 and 0.20 sec. Slightly
interval. prolonged PQ intervals are common and considered harmless. More
prolonged PQ intervals suggest a first-degree heart block.
Represents ventricular depolarization and atrial
repolarization. An exaggerated R wave suggests enlargement of the ventricles. The QRS
should not be longer than 0.10 sec. Patients experiencing an MI may
T wave Represents ventricular repolarization. show QRS complexes that are abnormally high or that have extended
ST segment durations.
QT interval Represents the plateau phase of the action potential
when the ventricles are depolarized. A flat T wave suggests ischemia to the myocardium; an elevated T wave
Represents the time from the start of ventricular indicates hyperkalemia.
depolarization to the completion of ventricular
repolarization. Elevated ST segments are used to guide the pharmacotherapy of MI.

Drugs that lengthen the QT interval have been linked to cardiac
dysrhythmias, cardiac arrest, and sudden death. At the same time,
prolongation of the action potential duration is a primary antidysrhythmic
mechanism.

Chapter 37  Pharmacotherapy of Dysrhythmias  645

PharmFACT AV node. None of the impulses originating in the atria
can make their way through the block into the ventri-
Inherited long QT syndrome (LQTS) is a dysrhythmia that cles. Second- and third-degree blocks require pharma-
causes about 4000 sudden deaths in children and young cotherapy or the insertion of a temporary or
adults each year. It is usually diagnosed during childhood permanent pacemaker. Some AV blocks are temporary
and is more common in females than males. LQTS is usually in origin and can be due to cardiac drug toxicity. Any
treated with beta-adrenergic blockers (Sovari, 2015). drug that slows AV conduction can cause a temporary
form of AV block.
Classification of Dysrhythmias
Tachydysrhythmias are disorders exhibiting a heart
37.4  Dysrhythmias are classified by the rate greater than 100 beats/min. The incidence of tachydys-
impulse origin and type of rhythm abnormality rhythmias increases in older adults and in patients with
produced. preexisting cardiovascular disease. The simplest method
for categorizing tachydysrhythmias is according to the
There are many types of dysrhythmias and they are classi- type of rhythm abnormality produced and its location.
fied by a number of different methods. The two broad cat- Dysrhythmias that originate in the atria are sometimes
egories of rhythm abnormalities are those that affect referred to as supraventricular. Those that originate in the
impulse formation and those that affect impulse conduc- ventricles are generally more serious because they are more
tion. Although a correct diagnosis of the type of dysrhyth- likely to interfere with the normal function of the heart.
mia is sometimes difficult, it is essential for effective
treatment. • Atrial tachycardia. This may be caused by a rapidly
firing SA node or by an ectopic focus in the atria that
Bradydysrhythmias are disorders characterized by a suppresses the SA node and establishes a rapid heart
heart rate of less than 60 beats/min. Bradydysrhythmias rate, often between 160 and 200 beats/min. When
are very common in older adults because the number of these episodes alternate with periods of normal
cells in the SA node declines progressively such that by age rhythm, it is called paroxysmal atrial tachycardia
75 about 90% of the cells are nonfunctional. Similar age- (PAT), or paroxysmal supraventricular tachycardia
related changes occur in the AV node, where normal cells (PSVT).
progressively die and are replaced by fibrotic tissue. Brady-
dysrhythmias are the major indication for pacemaker • Atrial flutter. This is a rapid, regular heartbeat in
implantation. Common bradydysrhythmias include the which the atria may beat 250 to 350 times per minute.
following: During atrial flutter, the job of the AV node is to selec-
tively block some of the impulses coming from the
• Sinus bradycardia. This is the most common slow atria, so the ventricular rate (pulse) is 125 to 175 beats/
heart rhythm. Sinus bradycardia generally does not min (usually two, three, or four atrial beats for each
require treatment unless the patient is experiencing ventricular beat).
syncope or dizziness due to lack of sufficient blood
flow to the brain, or if the heart rate fails to increase • Atrial fibrillation. A complete disorganization of
during periods of exertion. rhythm, this is the most common type of dysrhythmia.
It is caused by multiple sites of impulse formation in
• Sinoatrial node dysfunction (sick sinus syndrome). the atria, all firing in a chaotic fashion. The atrial rate
The SA node fails to generate or transmit sufficient can range from 300 to 600 beats/min, causing an irreg-
electrical impulses. Patients with this condition may ular ventricular rate ranging from 50 to 200 beats/
experience severe bradycardia (less than 40 beats/min min. The rapid atrial rate causes a loss of organized
resting), failure of the heart rate to increase with exer- atrial contraction and results in quivering (fibrilla-
cise, or significant sinus “pauses.” Severe episodes of tion). This lack of contraction causes blood to lie dor-
bradycardia may alternate with periods of abnormally mant in parts of the atria and may give rise to clots.
rapid heart rates. Because of the potential for clot formation, atrial fibril-
lation is a leading risk factor for stroke.
• Atrioventricular conduction block. The AV node fails
to conduct impulses to the rest of the myocardium. AV • Ventricular tachycardia. This is usually recognized by
blocks are classified by degree. In first-degree AV regular, rapid, wide beats with a ventricular rate of
block, the AV node conducts the impulse slowly, and 100 to 200 beats/min. Patients with sustained or
conduction is delayed. In second-degree AV block, symptomatic ventricular tachycardia must be treated
some, but not all, impulses are prevented (blocked) immediately because this condition is associated with
from leaving the AV node. Second-degree AV block a high risk of sudden death. Torsades de pointes is a
results in nonconducted P waves. A third-degree AV specific type of ventricular tachycardia that is charac-
block results in total stoppage of impulses through the terized by rates between 200 and 250 beats/min and

646  Unit 5  Pharmacology of the Cardiovascular System

“twisting of the points” of the QRS complex on the CONNECTIONS: Lifespan
ECG. Considerations
• Ventricular fibrillation. This is a complete disorgani-
zation of rhythm in which the ventricles pump little or Dental Health and Dysrhythmias
no blood, quickly starving the tissues of oxygen. Ven- in the Older Adult
tricular fibrillation is now considered cardiac arrest.
Atrial fibrillation is the most common sustained cardiac dys-
General Principles rhythmia in the older adult and is a known risk factor for
of Dysrhythmia Management strokes and MIs. Evidence suggests that inflammation may
play an important role in the development of atrial fibrillation,
37.5  Antidysrhythmic drugs are only used when and dental caries (tooth decay) have been shown to increase
there is a clear benefit to the patient. inflammatory chemicals in the body (Vedin, 2014).

Most antidysrhythmic drugs have the potential to produce Aging is often associated with increasing dental concerns
serious adverse effects. The very drugs used to treat dys- and tooth loss, and nurses should continue to encourage the
rhythmias may actually worsen or create new dysrhyth- older adult to maintain adequate dental hygiene. Hygiene is
mias. Furthermore, research suggests that mortality may not only a method for preserving teeth and dental function, it
actually increase when some of these drugs are used is also a possible preventive measure against other more
to treat or prevent dysrhythmias. The following guide­ serious conditions such as coronary heart disease and
lines are used in the management of the patient with dysrhythmias.
dysrhythmias.
activity will allow the SA node to automatically return
Asymptomatic dysrhythmias:  Research has shown lit- conduction to a normal sinus rhythm.
tle or no benefit to the patient in treating asymptomatic
dysrhythmias with medications. Antidysrhythmic drugs Other types of nonpharmacologic treatment include
are normally reserved for patients experiencing overt identification and destruction of the myocardial cells
symptoms or for those whose condition cannot be con- responsible for the abnormal conduction through a surgical
trolled by other means. procedure called catheter ablation. Cardiac pacemakers are
sometimes inserted to correct the types of dysrhythmias
Acute dysrhythmias:  Some types of dysrhythmias are that cause the heart to beat too slowly. Implantable cardio-
serious and may be life threatening. In these cases, phar- verter defibrillators (ICDs) are placed in a patient to restore
macotherapy or cardioversion is warranted. For example, normal rhythm by either pacing the heart or giving it an
ventricular dysrhythmias often interfere with cardiac out- electric shock when dysrhythmias occur. In addition, the
put and have greater potential for harm than atrial dys- ICD is capable of storing information regarding the heart
rhythmias. Dysrhythmias that are sustained may worsen rhythm for the healthcare provider to evaluate.
and affect cardiac function. Several antidysrhythmics
available by the intravenous (IV) route have an immediate Drugs for Dysrhythmias
onset of action to terminate life-threatening dysrhythmias.
37.6  Antidysrhythmic drugs are classified
Prophylaxis of dysrhythmias:  Patients who are afflicted by their mechanism of action.
with recurring dysrhythmias or who have a comorbid con-
dition, such as preexisting heart disease, may benefit from The therapeutic goals of antidysrhythmic pharmacother-
prophylactic therapy with antidysrhythmics. These apy are to terminate existing dysrhythmias or to prevent
patients should be monitored regularly to assess for pro- abnormal rhythms for the purpose of reducing the risks of
dysrhythmic effects from the drugs. Drug combinations sudden death, stroke, or other complications resulting
that have the potential to prolong the QT interval are from the disease. Antidysrhythmic drugs act by altering
avoided and doses are kept as low as possible to minimize specific electrophysiologic properties of the heart. They do
risk. Prophylactic therapy should be initiated only for this through two basic mechanisms: blocking flow through
high-risk patients. ion channels (conduction) or altering autonomic activity
(automaticity).
Nonpharmacologic treatment:  Serious types of dys-
rhythmias are corrected through electrical stimulation of In use since 1985, the most common method of classi-
the heart, a treatment called cardioversion or defibrilla- fying antidysrhythmic drugs is the Vaughan Williams clas-
tion. The electrical shock momentarily stops all electrical sification. This classification scheme groups drugs as
impulses in the heart, both normal and abnormal. Under Classes I, II, III, and IV based on the stage at which they
ideal conditions, the temporary cessation of electrical affect the action potential. A fifth group includes miscella-
neous drugs not acting by one of the first four mechanisms.
Although widely used, the Vaughan Williams classification

Chapter 37  Pharmacotherapy of Dysrhythmias  647

Table 37.3  Classification of Antidysrhythmics

Class Actions Primary Indications

I: Sodium Channel Blockers Delays repolarization; slows conduction velocity; increases Atrial fibrillation, premature atrial contractions,
IA duration of the action potential. premature ventricular contractions, tachycardia
IB Severe ventricular dysrhythmias
IC Accelerates repolarization; slows conduction velocity;
II: Beta-Adrenergic Antagonists decreases duration of action potential. Severe ventricular dysrhythmias
III: Potassium Channel Blockers
IV: Calcium Channel Blockers No significant effect on repolarization; slows conduction Atrial flutter and fibrillation, tachydysrhythmias,
velocity. ventricular dysrhythmias
Severe atrial and ventricular dysrhythmias
Slows conduction velocity; decreases automaticity; prolongs
refractory period. Paroxysmal supraventricular tachycardia,
supraventricular tachydysrhythmias
Slows repolarization; increases duration of action potential;
prolongs refractory period.

Slows conduction velocity; decreases contractility; prolongs
refractory period.

method is simplistic because some of these drugs act by The sodium channel blockers are similar in structure
more than one mechanism, and the drugs within each class and action to local anesthetics. In fact, the Class I antidys-
have unique properties that distinguish them from each rhythmic lidocaine is a prototype local anesthetic in
other. For example, the Class I drugs have three subclasses. Chapter 26. This anesthetic-like action slows impulse con-
The categories of antidysrhythmics and their mechanisms duction across the heart. Some, such as quinidine and pro-
are shown in Table 37.3. cainamide, are effective against many types of
dysrhythmias. The remaining Class I drugs are more spe-
The use of antidysrhythmic drugs has significantly cific and indicated only for life-threatening ventricular
declined in recent years. The reason for this decline is that dysrhythmias.
research studies determined that the use of antidysrhyth-
mic medications for prophylaxis can actually increase The adverse effects of the sodium blockers vary with
patient mortality. Drugs affecting cardiac electrophysiol- each individual drug. All these medications can cause new
ogy have a narrow margin of safety between a therapeutic dysrhythmias or worsen existing ones. The slowing of the
effect and a toxic effect. While they have the ability to cor- heart rate can cause hypotension, dizziness, and fainting.
rect dysrhythmias, they can also worsen or even create new During pharmacotherapy, the ECG should be monitored
dysrhythmias. These prodysrhythmic effects have resulted for signs of cardiotoxicity, such as increases in the PR and
in less use of these drugs, especially those medications in QT intervals and widening of the QRS complex. Some
Class I. Class I drugs have significant anticholinergic adverse
effects such as dry mouth, constipation, and urinary reten-
Another reason for the decline in antidysrhythmic tion. Special precautions should be taken with older adults,
drug use is the success of nonpharmacologic techniques. because anticholinergic adverse effects may worsen uri-
Catheter ablation and implantable defibrillators are more nary hesitancy in men with prostate enlargement.
successful in managing many types of dysrhythmias than
is the prophylactic use of medications. Class IA:  The Class IA antidysrhythmics include
quinidine, disopyramide (Norpace), and procainamide.
Sodium Channel Blockers: Class I Although quinidine is the oldest and best known Class
IA drug, procainamide is the prototype because it has
37.7  Class I antidysrhythmics act by blocking been more widely used than quinidine in recent decades.
ion channels in myocardial cells. All are available by the oral (PO) route and act by block-
ing sodium ion channels during phase 0 of the action
Sodium channel blockers, the Class I drugs, are the largest potential.
group of antidysrhythmics. They are further divided into
three subgroups (IA, IB, and IC) based on subtle differ- The primary action responsible for the antidysrhyth-
ences in their mechanisms of action. Because initiation of mic effects of the Class IA drugs is a slowing of conduction
the action potential is dependent on the opening of gated velocity. These drugs also inhibit potassium channels,
sodium ion channels, a blockade of these channels will which delays repolarization and increases the refractory
prevent depolarization of the myocardium. The spread of period. Subsequent action potentials must wait slightly
the action potential will slow, and areas of ectopic pace- longer before triggering the next electrical impulse. These
maker activity will be suppressed. The sodium channel actions allow the Class IA drugs to inhibit the formation of
blockers are shown in Table 37.4 and Figure 37.3. ectopic foci in both the atria and ventricles.

648  Unit 5  Pharmacology of the Cardiovascular System

Table 37.4  Antidysrhythmic Drugs

Drug Route and Adult Dose Adverse Effects
(Maximum Dose Where Indicated)

Class IA: Sodium Channel Blockers

disopyramide (Norpace) PO (immediate release): 400–800 mg in divided doses Nausea, vomiting, diarrhea, dry mouth, urinary retention,
procainamide PO (extended release): 300 mg bid cinchonism (quinidine), anorexia, rash, photosensitivity
quinidine gluconate
IV: 100 mg q5min at a rate of 25–50 mg/min May produce new dysrhythmias or worsen existing ones;
(max: 1 g) hypotension, torsades de pointes, blood dyscrasias,
hepatotoxicity (quinidine), lupus (procainamide)
PO: 324–648 mg tid–qid (max: 3–4 g/day)
IV: 0.25 mg/kg/min (max: 5–10 mg/kg)

quinidine sulfate PO: 200–400 mg tid–qid (max: 3–4 g/day); therapeutic
serum drug level is 2–5 mcg/mL

Class IB: Sodium Channel Blockers

lidocaine (Xylocaine) IV: 1–4 mg/min infusion (max: 3 mg/kg per 5–10 min) Nausea, vomiting, drowsiness, dizziness, lethargy,
mexiletine (Mexitil) confusion (phenytoin)
phenytoin (Dilantin) PO: 200–300 mg tid (max: 1200 mg/day)
May produce new dysrhythmias or worsen existing ones;
IV: 50–100 mg q10–15min until dysrhythmia is terminated hypotension, bradycardia, central nervous system (CNS)
(max: 1 g/day) toxicity (lidocaine), malignant hyperthermia (lidocaine),
cardiac arrest (lidocaine), blood dyscrasias (phenytoin)

Class IC: Sodium Channel Blockers

flecainide (Tambocor) PO: 50 mg bid (max: 400 mg/day) Nausea, vomiting, fatigue, dizziness, headache, visual
propafenone (Rythmol) PO (extended release): 225 mg bid (max: 425 mg q12h) disturbances (flecainide)

May produce new dysrhythmias or worsen existing ones;
hypotension, bradycardia, cardiac arrest (flecainide), blood
dyscrasias, lupus (propafenone), HF (propafenone), acute
liver injury (propafenone)

Class II: Beta-Adrenergic Antagonists

acebutolol (Sectral) PO: 200–600 mg bid–tid (max: 1200 mg/day) Fatigue, insomnia, drowsiness, impotence, decreased
esmolol (Brevibloc) libido, dizziness, bradycardia, confusion
propranolol (Inderal, InnoPran XL) IV: 50–300 mcg/kg/min (maintenance dose)
Agranulocytosis, HF, bronchospasm, hypotension,
PO: 10–30 mg tid–qid (max: 480 mg/day) Stevens–Johnson syndrome, anaphylaxis; if the drug is
IV: 0.5–3.1 mg q4h or prn abruptly withdrawn, palpitations, rebound HTN, life-
threatening dysrhythmias, or myocardial ischemia may
occur.

Class III: Potassium Channel Blockers

amiodarone (Pacerone) PO: 400–600 mg/day in 1–2 divided doses Blurred vision (amiodarone), photosensitivity, nausea,
(max: 1600 mg/day as loading dose) vomiting, anorexia

dofetilide (Tikosyn) PO: 125–500 mcg bid based on creatinine clearance May produce new dysrhythmias or worsen existing ones;
dronedarone (Multaq) hypotension, HF, heart block, bradycardia, pneumonia-like
ibutilide (Corvert) PO: 400 mg bid syndrome (amiodarone, dronedarone), angioedema
(dofetilide), CNS toxicity (ibutilide)
IV: 1 mg infused over 10 min (for patients over 60 kg);
(max: 2 mg infused over at least 20 min)

sotalol* (Betapace, Betapace AF, PO: 80 mg bid (max: 320 mg/day)
Sorine)

Class IV: Calcium Channel Blockers

diltiazem (Cardizem, Dilacor, IV: 5–10 mg/h continuous infusion for a maximum of 24 h Flushed skin, headache, dizziness, peripheral edema,
Taztia XR, Tiazac)
(max: 15 mg/h) lightheadedness, nausea, diarrhea, syncope

verapamil (Calan, Isoptin SR, PO: 240–480 mg/day in divided doses Hepatotoxicity, MI, HF, confusion, mood changes,
Verelan) IV: 5–10 mg direct; may repeat in 15–30 min hypotension

Miscellaneous Antidysrhythmics

adenosine (Adenocard, IV: 6–12 mg given as a bolus injection every 1–2 min as Facial flushing, dyspnea, headache
Adenoscan) needed (max: 12 mg/dose)
May produce new dysrhythmias or worsen existing ones,
AV block

digoxin (Lanoxin, Lanoxicaps) PO: 0.125–0.5 mg qid Nausea, vomiting, headache, diarrhea, visual disturbances
Therapeutic serum drug level: 0.8–2 ng/mL May produce new dysrhythmias or worsen existing ones

Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
*Sotalol is a beta blocker, but because its cardiac effects are more similar to amiodarone, it is in Class III. Adverse effects are those of Class II and Class III.

Chapter 37  Pharmacotherapy of Dysrhythmias  649

Class II
Beta-adrenergic antagonists
• Propranolol

Class IV
Calcium channel blockers
• Verapamil

+20 mV Ca2+
0 mV
Class I Class III
Na+
Sodium channel Potassium
blockers channel blockers
• Procainamide K+ • Amiodarone

–90 mV

Na+ K+ Ca2+
channel channel channel

Na+ Ca2+ Na+ Na+ Na+ Ca2+ Na+ K+ Ca2+ Na+ Ca2+ Na+
– K+ K+ Ca2+ – – – –– –– –– K+ K+ Ca2+ –

– –– ––

+ + + ++ + + ++ + + ++ + + +

K+ K+ K+ Na+ K+ K+ Ca2+ Na+ K+ K+ K+ K+ Na+ K+ Ca2+
Na+ Ca2+ Ca2+

(a) Resting state before (b) Depolarization (c) Repolarization (d) Return to resting state
action potential • Sodium and calcium • Potassium channel • All channel gates closed
• All channel gates closed
channel gates open gates open

Figure 37.3  Ion channels in myocardial cells: (a) resting state before action potential (all channel gates closed); (b) depolarization (sodium
and calcium channel gates open); (c) repolarization (potassium channel gates open); (d) return to resting state (all channel gates closed).

The effects of the Class IA drugs can be recognized on paroxysmal atrial tachycardia, atrial flutter, or atrial fibril-
the ECG. The QRS complex widens, owing to the slowed lation; and treatment or prophylaxis of PSVT. Procainamide
depolarization of the ventricles. The QT interval is increased is now considered a drug of last choice for advanced cardiac
due to the delay in repolarization of the ventricles. life support due to its toxicity; it is used when other drugs
have failed to reverse a severe dysrhythmia. The major
PROTOTYPE DRUG Procainamide hepatic metabolite of the drug, N-acetyl procainamide, also
has antidysrhythmic activity. Because the rate of acetylation
Classification Therapeutic: Antidysrhythmic, Class IA to the active metabolite is genetically determined, “slow
Pharmacologic: Sodium channel blocker acetylators” and “fast acetylators” will require adjustments
in dosages to obtain optimal therapeutic results.
Therapeutic Effects and Uses:  Approved in 1950,
procainamide is a broad-spectrum antidysrhythmic chemi- Procainamide is available in IV and intramuscular
cally related to the local anesthetic procaine that has the (IM) formulations: PO forms of procainamide have been
ability to correct many different types of atrial and ventricu- discontinued. Dosage is guided by periodic serum drug
lar dysrhythmias. Indications include ventricular tachycar- levels, which are maintained between 4 and 8 mcg/mL.
dia during cardiopulmonary resuscitation (CPR); refractory The supine position should be used during IV administra-
ventricular fibrillation or pulseless ventricular tachycardia tion because severe hypotension may occur during the
during CPR; conversion to sinus rhythm in patients with infusion. Use of procainamide must be terminated if the
QRS widens more than 50% of its original width.

650  Unit 5  Pharmacology of the Cardiovascular System

Mechanism of Action:  Procainamide blocks sodium Drug Interactions:  Additive cardiac depressant
ion channels in myocardial cells, thus reducing auto- effects may occur if procainamide is administered with other
maticity and slowing the velocity of the action potential antidysrhythmics. Additive anticholinergic adverse effects
across the myocardium. This slight delay in conduction will occur if procainamide is used concurrently with
velocity prolongs the refractory period and can suppress anticholinergic drugs. Procainamide may increase plasma
dysrhythmias. levels of amiodarone or quinidine. Use with antihyperten-
sives may result in hypotension. Herbal/Food: Although
Pharmacokinetics:  IV, IM no interactions have been well documented, the use of all
Route(s) herbal products or supplements should be avoided unless
Absorption Readily absorbed approved by the healthcare provider due to the toxicity of
Distribution the drug.
Widely distributed; crosses the
Primary metabolism placenta; secreted in breast milk; Pregnancy:  Category C.
15% bound to plasma protein
Primary excretion Treatment of Overdose:  No specific therapy is avail-
Onset of action Hepatic; metabolized to active able for overdose. Supportive treatment is targeted to re-
Duration of action metabolite versing hypotension with vasopressors and preventing or
treating procainamide-induced dysrhythmias.
Renal, 50–70% unchanged
Nursing Responsibilities:  Key nursing implications
IV: immediate; IM: 10–30 min for patients receiving procainamide are included in the
Nursing Practice Application for Patients Receiving Phar-
IM/IV: 3–4 h macotherapy for Dysrhythmias.

Adverse Effects:  Procainamide has a narrow thera- Drugs Similar to Procainamide
peutic index and dosage must be monitored carefully
to avoid serious adverse effects. Nausea, vomiting, There are similar Class IA, IB, and IC antidysrhythmics.
abdominal pain, and headache are common during Other Class IA antidysrhythmics include disopyramide
therapy. The drug can cause fever, accompanied by and quinidine. Moricizine, a unique oral antidysrhythmic
anorexia, weakness, nausea, and vomiting. High doses that possessed some properties attributed to all three Class I
may produce central nervous system (CNS) effects such subclasses, was discontinued in 2007 due to lack of market
as confusion or psychosis. Rapid IV administration of demand.
procainamide can cause severe hypotension. Black Box
Warnings: Chronic administration may result in an in- Disopyramide (Norpace):  Approved in 1977, disopyra-
creased titer of antinuclear antibodies (ANAs). A lupus- mide has actions and indications similar to those of other
like syndrome may occur in 30% to 50% of patients Class IA drugs. Available only by the PO route, the drug is
taking the drug for more than a year. Procainamide used infrequently due to a high incidence of anticholiner-
should be reserved for life-threatening dysrhythmias gic effects such as xerostomia (dry mouth) and urinary
because it has the ability to produce new dysrhythmias retention in patients with benign prostatic hyperplasia.
or worsen existing ones. Agranulocytosis, bone mar- The anticholinergic effects cause an increase in heart rate,
row depression, neutropenia, hypoplastic anemia, and which may directly cancel out the therapeutic cardiac
thrombocytopenia have been reported, usually within depressant effects of the drug. Off-label uses include main-
the first 3 months of therapy. Complete blood counts tenance of, or conversion to, sinus rhythm in patients with
should be monitored carefully and the drug discontin- atrial flutter or atrial fibrillation. Disopyramide has a black
ued at the first sign of potential blood dyscrasia. box warning that the drug should be restricted to patients
with life-threatening ventricular dysrhythmias. This drug
Contraindications/Precautions:  Procainamide is is pregnancy category C.
contraindicated in patients with second- or third-degree
AV block (unless controlled by a pacemaker), severe HF, Quinidine:  Approved in 1938, quinidine is the oldest
peripheral neuropathy, and myasthenia gravis. Because antidysrhythmic drug, originally obtained as a natural
procainamide may activate or worsen lupus, the drug is substance from the bark of the South American cinchona
only used in these patients when there is no safer alterna- tree. Like procainamide, quinidine is a broad-spectrum
tive. Doses must be lowered in patients with chronic kid- drug having the ability to correct many different types of
ney disease (CKD) due to possible accumulation of the atrial and ventricular dysrhythmias. The two salts of
drug. Patients in shock or with severe hypotension should quinidine are sulfate, which is given PO, and gluconate,
not receive this drug due to additive hypotension. Procain- which is given PO and IV. Like other drugs in this class,
amide may worsen blood dyscrasias; thus, it should be quinidine blocks sodium ion channels in myocardial
used with caution in patients with preexisting bone mar-
row suppression.

Chapter 37  Pharmacotherapy of Dysrhythmias  651

cells, thus reducing automaticity and slowing the velocity Less common, though potentially serious, adverse effects
of the action potential across the myocardium. In addition include blood dyscrasias, pulmonary fibrosis, and wors-
to dysrhythmias, quinidine gluconate may be used to treat ening of HF. A black box warning has been issued regard-
malaria and persistent hiccups. The most common ing the possibility of acute liver damage in patients
adverse effect of quinidine is diarrhea, which occurs in taking mexiletine. The target range for serum mexiletine
about one third of patients and may be intense. The drug concentration is 0.5 to 2 mcg/mL. This drug is pregnancy
can induce various types of dysrhythmias when serum category C.
levels rise above normal. High doses result in a syndrome
called cinchonism with symptoms such as tinnitus, head- Phenytoin (Dilantin):  The primary use for phenytoin is to
ache, blurred vision, hearing loss, and dysrhythmias. treat seizures, and it was presented in Chapter 22 as a pro-
These symptoms are reversible once the drug is discontin- totype antiseizure medication. Phenytoin is rarely used for
ued. Quinidine is contraindicated in patients with incom- its antidysrhythmic properties and is not approved by the
plete AV block because it can induce total blockage of U.S. Food and Drug Administration (FDA) for this pur-
conduction. Quinidine carries a black box warning that pose. Historically, it has been used off-label to treat dys-
the drug has resulted in increased mortality when used rhythmias secondary to digoxin (Lanoxin) toxicity. This
for non–life-threatening dysrhythmias. This drug is preg- drug is pregnancy category D.
nancy category C.
Class IC:  The Class IC antidysrhythmics include two
Class IB:  The Class IB antidysrhythmics include lido- drugs: flecainide and propafenone. Like other Class I
caine, mexiletine, and phenytoin. Like other Class I drugs, drugs, these medications block gated sodium ion channels
these agents act by blocking gated sodium ion channels in in cardiac muscle cells. The Class IC antidysrhythmics pro-
cardiac muscle cells. Unlike the Class IA drugs, the Class foundly decrease conduction velocity. Thus the PR, QRS,
IB agents shorten the refractory period and have little and QT intervals are often prolonged. The refractory
effect on conduction velocity. The Class IB drugs have period may be shortened slightly but is mostly unchanged
minimal effects on the ECG and their primary indication is by the Class IC drugs. Their primary indication is for life-
ventricular dysrhythmias. threatening atrial dysrhythmias, although they can also
prevent ventricular dysrhythmias. Research has shown
Lidocaine (Xylocaine):  Lidocaine, the most frequently these drugs to have a pronounced prodysrhythmic effect
prescribed Class IB antidysrhythmic, was featured as a that has the potential to increase mortality in patients who
prototype local anesthetic in Chapter 26. It is an important have experienced a recent MI.
treatment for life-threatening ventricular dysrhythmia,
although amiodarone is considered a preferred drug for Flecainide (Tambocor):  Flecainide is an oral drug used
this indication. It is not effective in preventing or treating primarily to treat or prevent paroxysmal atrial fibrillation
atrial dysrhythmias. Lidocaine decreases the refractory or atrial flutter due to its ability to markedly decrease con-
period of the action potential, especially in ischemic myo- duction velocity. It is indicated for the prophylaxis of life-
cardial tissue. For acute conditions, lidocaine is adminis- threatening ventricular dysrhythmias, although it is rarely
tered by IV bolus or infusion; it is rarely given by the IM or used for this purpose. The FDA has issued several black
subcutaneous routes. Serum lidocaine levels may be moni- box warnings regarding flecainide. The prodysrhythmic
tored and should be between 2 and 6 mcg/mL. The first effects of the drug may generate new ventricular dysrhyth-
signs of lidocaine toxicity usually involve the CNS and mias in about 10% of the patients. Due to an excessive
include confusion, anxiety, tremors, and paresthesias. As mortality rate, the drug is contraindicated in patients with
doses increase, the patient may become comatose and left ventricular dysfunction who have experienced a recent
experience seizures or respiratory arrest. The correct lido- MI. Serum flecainide levels should be monitored, espe-
caine formulation must be used for IV infusions: Local cially in patients with CKD or hepatic impairment, and
anesthetic lidocaine preparations may contain preserva- maintained between 0.2 and 1 mcg/mL. Pulmonary fibro-
tives and epinephrine and should not be given IV. This sis and bone marrow suppression are potentially serious
drug is pregnancy category B. adverse effects. Other adverse effects include dizziness,
headache, asthenia, tremor, and malaise. This drug is preg-
Mexiletine (Mexitil):  Approved in 1985, mexiletine is nancy category C.
chemically similar to lidocaine, has local anesthetic prop-
erties, and is used only for serious ventricular dysrhyth- Propafenone (Rythmol):  Approved in 1989, propafenone
mias. Mexiletine is well absorbed orally and may be used is an oral drug similar to flecainide that is used primarily
off-label for the treatment of neuropathic pain. The most for atrial fibrillation and the prophylaxis of PSVT. Its pro-
common adverse effects are nausea and vomiting. CNS dysrhythmic activity limits its use in treating ventricular
effects such as dizziness, tremor, and ataxia are common. dysrhythmias. Unlike flecainide, propafenone exhibits clin-
ically significant beta-adrenergic antagonist activity. This

652  Unit 5  Pharmacology of the Cardiovascular System

beta-blocker action may cause a negative inotropic effect especially in older adults. Abrupt discontinuation of beta
that can worsen symptoms of HF. Furthermore, the beta- blockers can lead to dysrhythmias and HTN.
blocking actions may cause bronchospasm in patients with
asthma or chronic obstructive pulmonary disease (COPD). Acebutolol (Sectral):  Approved in 1984, acebutolol is a
An extended release formulation (Rythmol SR) allows for cardioselective beta1-adrenergic antagonist available only
twice-daily dosing. Propafenone is metabolized to active by the oral route. Like other beta blockers, acebutolol
metabolites, which account for much of the drug’s effects. reduces sympathetic activity to the heart, thus lowering
In addition to exacerbating or creating new dysrhythmias, heart rate. It also has a negative inotropic effect. As an anti-
propafenone may cause dizziness and dysgeusia (altered dysrhythmic, it is used to treat premature ventricular con-
sense of taste). Like some of the other antidysrhythmics, tractions and reduce exercise-induced tachycardia. Other
propafenone has a black box warning that it should be indications include chronic, stable angina and HTN.
restricted to patients with life-threatening ventricular dys- Adverse effects such as hypotension and bradycardia are
rhythmias. This drug is pregnancy category C. extensions of its beta-blocking action. At high doses, the
selectivity for beta1 receptors diminishes and the drug may
Beta-Adrenergic Antagonists: Class II cause bronchoconstriction (beta2 receptors). Because the
negative inotropic effects of the drug may worsen symp-
37.8  Beta-adrenergic antagonists reduce toms of HF, it is usually contraindicated in patients with
automaticity and slow conduction velocity HF. This drug is pregnancy category B.
in the heart.
Esmolol (Brevibloc):  Approved in 1986, esmolol differs
Beta-adrenergic antagonists, or blockers, are used to treat from the other antidysrhythmic beta blockers in that it has
HTN, MI, HF, and dysrhythmias. The basic pharmacology a very short half-life of 9 minutes and is only given by IV
of beta-adrenergic antagonists was explained in Chapter infusion. As an antidysrhythmic, esmolol is used for the
16; the student should refer to that chapter for nursing immediate termination of atrial tachyarrhythmias and
responsibilities and patient and family education related noncompensatory sinus tachycardia and to control ven-
to this drug class. Only the actions of these drugs that tricular rate in patients with atrial flutter or fibrillation.
relate to dysrhythmias are discussed in this section. When a loading dose is administered, peak plasma levels
can be reached in 5 minutes. Off-label indications include
As expected from their effects on the autonomic ner- treatment of hypertensive emergencies, acute MI, and
vous system, beta-adrenergic antagonists slow the heart unstable angina. Hypotension and bradycardia are com-
rate (negative chronotropic effect) and decrease conduction mon adverse effects but they quickly resolve once the
velocity. These effects are primarily caused by the blockade infusion is discontinued. At therapeutic doses, the drug is
of calcium ion channels in the SA and AV nodes, although selective for beta1-adrenergic receptors. This drug is preg-
these drugs also block gated sodium ion channels in the nancy category C.
atria and ventricles. The reduction in myocardial automa-
ticity stabilizes many types of dysrhythmias. The main Propranolol (Inderal, InnoPran XL):  Propranolol is a non-
value of beta blockers as antidysrhythmic drugs is to treat selective beta-adrenergic antagonist. Because it slows auto-
atrial dysrhythmias associated with HF. When adminis- maticity, propranolol is indicated for many types of
tered to post-MI patients, beta blockers decrease the likeli-
hood of sudden death due to fatal dysrhythmias. CONNECTIONS: Treating the
Tachydysrhythmias respond well to beta blockers, includ- Diverse Patient
ing those that are induced by exercise.
Sensitivity of Asian Patients to Propranolol
Only a few beta blockers are approved for dysrhyth-
mias, due to potential adverse effects, and these are listed in Growing evidence from research studies has shown a differen-
Table 37.4. Unless a functioning pacemaker is present, these tial drug response to propranolol among Asians and Asian
drugs are contraindicated in patients with severe bradycar- Americans. These individuals typically lack a specific enzyme
dia, sick sinus syndrome, or advanced AV block because (mephenytoin hydroxylase) that is needed to metabolize pro-
they depress conduction through the AV node. Blockade of pranolol. Because of this sensitivity, propranolol has a signifi-
beta-adrenergic receptors in the heart causes bradycardia, cantly greater effect on heart rate. In other words, individuals of
which may not be well tolerated in patients with preexisting Asian descent will develop signs of toxicity more quickly than
cardiac disease, and hypotension may cause dizziness and non-Asians. The nurse should assess this population for signs
possible fainting. Nonselective beta blockers may affect and symptoms of early drug toxicity, possible overdosage, and
beta2 receptors in the lung, causing bronchospasm in adverse reactions due to high drug levels. Assessing for unique
patients with asthma or COPD. Higher doses may produce cultural sensitivity to drug therapies is necessary for safe drug
depression, as well as hallucinations and psychosis, administration.

Chapter 37  Pharmacotherapy of Dysrhythmias  653

dysrhythmias including suppression of exercise-induced Therapeutic Effects and Uses:  Approved in 1985,
tachycardia, atrial dysrhythmias, ventricular dysrhyth- amiodarone is the most frequently prescribed Class III
mias, premature ventricular contractions, and digoxin- antidysrhythmic. It is considered a broad-spectrum
induced tachydysrhythmias. Propranolol exhibits few antidysrhythmic because it is effective in terminating both
serious adverse effects at therapeutic doses. At high doses, atrial and ventricular dysrhythmias. It is approved for the
patients may experience bradycardia, hypotension, HF, treatment of resistant ventricular tachycardia and recur-
and bronchospasm. Propranolol is featured as a prototype rent fibrillation that may prove life threatening, and it has
beta-adrenergic antagonist in Chapter 16. This drug is become a preferred medication for the treatment of atrial
pregnancy category C. dysrhythmias in patients with HF.

CONNECTION Checkpoint  37.2 Amiodarone is available as PO tablets and as an IV
infusion. IV infusions are limited to short-term therapy
Both alpha1 blockers and beta1 blockers are used to treat HTN (2–4 days). Although its onset of action may take several
but only the beta1 blockers are antidysrhythmics. From what you weeks when the medication is given PO, its effects can last
learned in Chapter 16, explain why the selective alpha1 blockers are 4 to 8 weeks after the drug is discontinued because it has an
not used to treat dysrhythmias.  Answers to Connection Checkpoint extended half-life that may exceed 100 days. Amiodarone is
questions are available on the faculty resources site. Please consult a structural analog of thyroid hormone. The therapeutic
with your instructor. serum level for amiodarone is 1 to 2.5 mcg/mL.

Potassium Channel Blockers: Class III Mechanism of Action:  Amiodarone exerts multiple,
complex actions on the heart and its exact mechanism of
37.9  Potassium channel blockers prolong the action is not completely known. In addition to blocking
refractory period of the heart. potassium ion channels, some of this drug’s actions relate
to its blockade of sodium ion channels and inhibiting sym-
The potassium channel blockers are a small but diverse pathetic activity to the heart. Repolarization is delayed, the
class of drugs that have very important applications to the refractory period prolonged, and automaticity reduced.
treatment of dysrhythmias. After the action potential has In addition to prolonging the QT interval, amiodarone
passed and the myocardial cell is in a depolarized state, increases the PR interval and widens the QRS complex on
repolarization depends on removal of potassium from the the ECG.
cell. The drugs in Class III exert their actions by blocking
potassium ion channels in myocardial cells. Although there Pharmacokinetics: 
are significant differences among the drugs, all have in
common the ability to delay repolarization and prolong the Route(s) PO, IV
refractory period. This action is reflected by an increase in
the QT interval on the ECG. Automaticity is also reduced. Absorption Completely absorbed by the

Most drugs in this class have multiple actions on the gastrointestinal (GI) tract
heart and also affect adrenergic receptors or sodium channels.
For example, in addition to blocking potassium channels, Distribution Widely distributed; crosses the
sotalol (Betapace) is considered a beta-adrenergic antagonist.
The potassium channel blockers are listed in Table 37.4. placenta; secreted in breast milk;

Drugs in this class have limited uses due to potentially concentrated in the lung, kidneys,
serious toxicity. Like other antidysrhythmics, potassium
channel blockers slow the heart rate, resulting in bradycar- spleen, and adipose tissue
dia and possible hypotension in a significant percentage of
patients. These drugs can create or worsen dysrhythmias, Primary metabolism Hepatic to active metabolites;
especially during the first few doses. Older adults with pre-
existing HF must be carefully monitored because these some enterohepatic recirculation;
patients are at higher risk for the cardiac adverse effects of
potassium channel blockers. inhibits some CYP450 enzymes

PROTOTYPE DRUG Amiodarone (Pacerone) Primary excretion Primarily biliary; some feces

Classification Therapeutic: Antidysrhythmic, Class III Onset of action PO: 2–3 days; IV: 2 h
Pharmacologic: Potassium channel
Duration of action PO/IV; 10–150 days
blocker
Adverse Effects:  Potentially serious adverse effects
limit the use of amiodarone. Amiodarone may cause nau-
sea, vomiting, anorexia, fatigue, dizziness, and hypoten-
sion. Visual disturbances are common in patients taking
this drug for extended periods and include blurred
vision due to cornea deposits, photophobia, xerostomia,
cataracts, and macular degeneration. Rashes, photosen-
sitivity, and other skin reactions occur in 10% to 15% of
patients taking the drug. Certain tissues concentrate this
medication; thus, adverse effects may be slow to resolve,

654  Unit 5  Pharmacology of the Cardiovascular System

persisting long after the drug has been discontinued. Nursing Responsibilities:  Key nursing implica-
Black Box Warning (oral form only): Amiodarone causes tions for patients receiving amiodarone are included in the
a pneumonia-like syndrome in the lungs. Because the pul- Nursing Practice Application for Patients Receiving Phar-
monary toxicity may be fatal, baseline and periodic as- macotherapy for Dysrhythmias.
sessments of lung function are essential. Amiodarone has
prodysrhythmic action and may cause bradycardia, car- Drugs Similar to Amiodarone (Pacerone)
diogenic shock, or AV block. Mild liver injury is frequent
with amiodarone. Other Class III antidysrhythmics include dofetilide, drone-
darone, ibutilide, and sotalol.
Contraindications/Precautions:  Amiodarone is
contraindicated in patients with severe bradycardia, car- Dofetilide (Tikosyn):  Approved in 1999, dofetilide is an
diogenic shock, sick sinus syndrome, severe sinus node oral drug indicated for conversion of symptomatic atrial
dysfunction, or third-degree AV block. Because amio- flutter or fibrillation to normal sinus rhythm. Like other
darone contains iodine in its chemical structure, patients potassium channel blockers, dofetilide prolongs the
who have hypersensitivity to this element should not re- refractory period and action potential duration, thus
ceive the drug. It should be used with caution in patients increasing the QT interval. Dofetilide does not exhibit a
with HF because it has a negative inotropic effect that negative inotropic effect, as do amiodarone and sotalol.
can worsen symptoms. Electrolyte imbalances, especially The drug has no effect on the PR interval and it does not
hypokalemia and hypomagnesemia, should be corrected widen the QRS complex. Dofetilide has many potentially
before administering amiodarone because these conditions serious adverse effects, and a black box warning states
predispose the patient to the development of dysrhyth- that therapy should begin in a clinical setting under con-
mias. Due to the drug’s pulmonary toxicity, it is contrain- tinuous monitoring for a minimum of 3 days. The drug
dicated in patients with COPD or respiratory insufficiency. exhibits significant dose-related prodysrhythmic effects,
Breastfeeding during amiodarone therapy may cause in- including heart block, ventricular tachycardia, and tors-
fant hypothyroidism; thus, the drug is contraindicated ades de pointes. The risk for drug-induced dysrhythmias
during lactation. is increased when dofetilide is administered concurrently
with other medications that prolong the QT interval,
Drug Interactions:  Amiodarone is metabolized by the including Class I and Class III antidysrhythmics. Dofeti-
cytochrome CYP450 enzymes and markedly inhibits the lide may accumulate to toxic levels in patients with CKD.
metabolism of many other drugs. This can raise the serum Therefore, serum creatinine levels are monitored fre-
levels of these drugs and cause toxicity. For example, quently during therapy. Electrolyte imbalances, especially
amiodarone can increase serum digoxin levels by as much hypokalemia or hypomagnesemia, should be corrected
as 70%. Amiodarone greatly enhances the actions of before administering dofetilide because these conditions
anticoagulants; thus the dose of warfarin must be cut by as predispose the patient to developing dysrhythmias. This
much as half. Use with beta-adrenergic antagonists or cal- drug is pregnancy category C.
cium channel blockers (CCBs) may potentiate sinus brady-
cardia, sinus arrest, or AV block. Amiodarone may increase Dronedarone (Multaq):  Approved in 2009, dronedarone
phenytoin levels two- to threefold. Caution must be used is given PO to reduce the risk of hospitalization in patients
during therapy with loop diuretics because hypokalemia with atrial dysrhythmias and associated cardiovascular
can enhance the prodysrhythmic properties of amioda- risk factors such as HTN, diabetes, or previous stroke. The
rone. Because of the large number of potential drug inter- drug has a black box warning that it is contraindicated in
actions, the nurse should regularly check current reference patients with advanced HF with recent decompensation. It
sources when patients are taking amiodarone concurrently is also contraindicated in patients with bradycardia (less
with other medications. Herbal/Food: Use with echinacea than 50 beats/min), prolonged QT interval, and severe
may increase the risk of hepatotoxicity. Aloe may increase hepatic impairment. The most common adverse effects are
the effect of amiodarone. When the drug is administered diarrhea, nausea, abdominal pain, vomiting, and asthenia.
PO, grapefruit juice can increase serum amiodarone levels Dronedarone inhibits CYP450 enzymes and can partici-
by over 80%. pate in multiple drug–drug interactions with other cardio-
vascular medications. Dronedarone is a category X drug
Pregnancy:  Category D. and should not be taken during pregnancy or lactation.

Treatment of Overdose:  Overdose will cause brady- Ibutilide (Corvert):  Approved in 1995, ibutilide is only
cardia, hypotension, and life-threatening dysrhythmias. administered as an IV infusion. Continuous ECG monitor-
Supportive treatment is targeted to reversing hypoten- ing should be conducted for at least 4 hours following the
sion with vasopressors and bradycardia with atropine or infusion to identify the potential development of new or
isoproterenol. worsening dysrhythmias. Administered over 10 minutes,

Chapter 37  Pharmacotherapy of Dysrhythmias  655

ibutilide is a preferred drug for rapidly converting atrial tissues are more dependent on calcium channels than other
flutter or fibrillation to normal sinus rhythm. The drug areas of the myocardium. This slows the heart rate and pro-
prolongs the duration of the cardiac action potential with- longs the refractory period. On an ECG, the most promi-
out affecting the PR interval or QRS complex. The infusion nent effect of CCBs is prolongation of the PR interval.
is stopped as soon as the dysrhythmia is terminated. Ibuti- Indications include the control of ventricular rate in cases
lide is generally well tolerated, although it does have pro- of atrial flutter or fibrillation, and prophylaxis of PSVT.
dysrhythmic effects, including induction of ventricular CCBs are effective only against atrial dysrhythmias.
tachycardia and torsades de pointes. Like other Class III
drugs, precautions must be taken when administering this CCBs are well tolerated by most patients. As with many
drug concurrently with other medications that prolong the other antidysrhythmics, patients should be carefully moni-
QT interval or if given to patients with hypokalemia or tored for bradycardia and hypotension. Because their car-
hypomagnesemia, as these conditions increase the risk of diac effects are almost identical to those of beta-adrenergic
dysrhythmias. This drug is pregnancy category C. antagonists, patients concurrently taking drugs from both
classes are especially at risk for bradycardia and possible HF.
Sotalol (Betapace, Betapace AF, Sorine):  Approved in Because older adults often have multiple cardiovascular dis-
1992, sotalol is unique in that the medication has both orders, such as HTN, HF, and dysrhythmias, it is not unusual
Class II and Class III antidysrhythmic properties. As a to find older patients taking drugs from multiple classes.
Class II drug, it is a nonselective beta blocker that slows
conduction through the AV node. Its Class III actions delay Diltiazem (Cardizem, Dilacor, Taztia XR, Tiazac):  Like
repolarization and prolong the refractory period, thus other CCBs, diltiazem inhibits the transport of calcium
widening the QT interval. Its mixed mechanisms are into myocardial cells. The actions and indications for dilti-
reflected in the diversity of indications for the drug. azem are the same as those of verapamil. The IV form of
the drug is indicated for the management of acute atrial
Betapace and its generic equivalents are indicated for dysrhythmias, including paroxysmal supraventricular
sustained ventricular fibrillation that is deemed to be life tachycardia. In addition to its use in treating and prevent-
threatening. Betapace AF converts atrial fibrillation to nor- ing atrial dysrhythmias, the oral forms are indicated for
mal sinus rhythm and is indicated for highly symptomatic HTN as well as stable and vasospastic angina. Adverse
atrial dysrhythmias. The drugs contain a black box warn- effects of diltiazem are generally not serious and are
ing stating that they are not interchangeable. related to vasodilation: headache, dizziness, and edema of
the ankles and feet. Because of its profound depressant
Because of its prodysrhythmic activity, the first 3 days of effects on nodal tissue, diltiazem is contraindicated in
therapy with sotalol are usually conducted in a controlled patients with severe bradycardia, AV block, or sick sinus
clinical setting with continuous monitoring. The drug syndrome. Concurrent use of diltiazem with digoxin or
should be used with caution when taken concurrently with beta-adrenergic antagonists may cause partial or complete
other medications that prolong the QT interval or if given to heart block, HF, or dysrhythmias.
patients with hypokalemia or hypomagnesemia, as these
conditions increase the risk of dysrhythmias. Other adverse Verapamil (Calan, Isoptin SR, Verelan):  Verapamil was
effects and contraindications for beta-adrenergic antagonists the first CCB approved by the FDA. In the heart, verapamil
are given in Chapter 16. This drug is pregnancy category B. slows conduction velocity and stabilizes dysrhythmias.
The IV form of the drug is indicated for the rapid control
Calcium Channel Blockers: Class IV of acute atrial dysrhythmias. Because verapamil can cause
bradycardia and AV block, patients with HF should be
37.10  Calcium channel blockers are used to treat carefully monitored. Because the drug may produce pro-
atrial dysrhythmias. found bradycardia, patients should notify their healthcare
provider if their heart rate falls below 60 beats/min or if
Although about 10 CCBs are available to treat cardiovas- systolic blood pressure falls below 90 mmHg. The thera-
cular disease, only a limited number are approved for peutic serum level is 0.08 to 0.3 mcg/mL. A prototype drug
dysrhythmias. Review Chapter 30 for details regarding feature that describes other indications for verapamil is
the mechanism of actions, indications, and nursing presented in Chapter 30.
responsibilities for this drug class. Only actions relevant
to dysrhythmias are discussed in this section. The antidys- CONNECTION Checkpoint  37.3
rhythmic CCBs are listed in Table 37.4.
Nifedipine (Procardia) is a prototype CCB discussed in Chapter 30.
Blockade of calcium ion channels has a number of From what you learned in Chapter 30, why is this drug (and other
effects on the heart that are very similar to those of beta- dihydropyridines) not effective in treating dysrhythmias?  Answers to
adrenergic antagonists. Effects include reduced automatic- Connection Checkpoint questions are available on the faculty re-
ity in the SA node and slowed impulse conduction through sources site. Please consult with your instructor.
the AV node. These effects are predictable, because nodal

656  Unit 5  Pharmacology of the Cardiovascular System

PharmFACT immediately after instillation of the medication is neces-
sary due to its short half-life. Immediate medical assistance
Sudden cardiac arrest (SCA) occasionally occurs in young must be nearby during the procedure. If the tachycardia
athletes. About half of the athlete SCAs occurred in high has not been eliminated in 1 to 2 minutes, a second rapid
school students and 82% occurred during competition or bolus may be given. The primary indication for adenosine
training. Only 11% occurred in females (Mozaffarian et al., is PSVT, for which adenosine is a preferred drug. It is also
2015). used to assist in the diagnosis of coronary artery disease of
dysrhythmias in patients who are unable to undergo a car-
Miscellaneous Antidysrhythmics diac exercise stress test. It is not effective in treating
ventricular dysrhythmias. Although the drug has prodys-
37.11  Adenosine and digoxin are used for rhythmic effects and dyspnea is common, adverse effects
specific dysrhythmias. are generally self-limiting because of its 10-second half-life.
In 2013, the FDA issued a safety alert that the use of ade-
Two other medications, adenosine and digoxin, are occa- nosine may be associated with an increased risk of heart
sionally used to treat specific dysrhythmias, but they do attack and death. This drug is pregnancy category C.
not act by the mechanisms described above. Doses for
these miscellaneous drugs are listed in Table 37.4. Digoxin (Lanoxin, Lanoxicaps):  Although digoxin is pri-
marily used to treat HF, it is also prescribed for atrial flutter
Adenosine (Adenocard, Adenoscan):  Adenosine is a natu- or fibrillation and PSVT because of its ability to decrease
rally occurring nucleoside that activates potassium chan- automaticity of the SA node and slow conduction through
nels in the SA and AV nodes, causing the potassium to the AV node. The drug is not effective against ventricular
leave cardiac muscle cells. When given as a rapid 1- to dysrhythmias. Because excessive levels of digoxin can pro-
2-second IV bolus, adenosine blocks reentry pathways in duce serious dysrhythmias, and interactions with other
the AV node and terminates the tachycardia. It is usually medications are common, patients must be carefully moni-
followed by a 1- to 5-second period of asystole. Patients tored during therapy. Additional information on the mech-
should be laid supine prior to adenosine use and warned anism of action, adverse effects, and nursing responsibilities
that they may feel faint. The IV site used to give adenosine for digoxin may be found in Chapter 36, where the drug is
should be antecubital or above, and an 18-gauge angio- featured as a prototype.
catheter or larger should be used. A rapid saline flush

CONNECTIONS:  NURSING PRACTICE APPLICATION

Patients Receiving Pharmacotherapy for Dysrhythmias
Assessment

Baseline assessment prior to administration:

• Obtain a complete health history including cardiovascular (including previous dysrhythmias, HTN, MI, HF) and the possibility of pregnancy. Obtain a drug
history including allergies, current prescription and over-the-counter (OTC) drugs, herbal preparations, and alcohol use. Be alert to possible drug interactions.

• Obtain baseline weight, vital signs (especially blood pressure and pulse), ECG (rate and rhythm), cardiac monitoring (such as cardiac output if
appropriate), and breath sounds. Assess for location, character, and amount of edema, if present.

• Evaluate appropriate laboratory findings: electrolytes, especially potassium, calcium, and magnesium levels; renal and liver function studies; and lipid profiles.
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.

Assessment throughout administration:

• Assess for desired therapeutic effects (e.g., control or elimination of dysrhythmia, blood pressure and pulse within established limits).
• Continue frequent monitoring of ECG (continuous if hospitalized). Check pulse quality, volume, and regularity, along with ECG. Assess for complaints

of palpitations and correlate symptoms with ECG findings. Assess for changes in level of consciousness (LOC).
• Continue periodic monitoring of electrolytes, especially potassium and magnesium.
• Assess for adverse effects: lightheadedness or dizziness, hypotension, nausea, vomiting, headache, fatigue or weakness, flushing, sexual dysfunction,

or impotence. Immediately report bradycardia, tachycardia, or new or different dysrhythmias to the healthcare provider.

Implementation

Interventions and (Rationales) Patient-Centered Care

Ensuring therapeutic effects: • To alleviate possible anxiety, teach the patient, family, or caregiver the
• Continue frequent assessments as above for therapeutic effects. rationale for all equipment used and the need for frequent monitoring.

(Dysrhythmias have diminished or are eliminated. Blood pressure and
pulse should be within normal limits or within parameters set by the
healthcare provider.)

• Encourage appropriate lifestyle changes: lowered fat intake, increased • Encourage the patient, family, or caregiver to adopt a healthy lifestyle
exercise, limited alcohol intake, limited caffeine intake, and smoking of low-fat food choices, increased exercise, reduced caffeine intake,
cessation. Provide for dietitian consultation as needed. (Healthy lifestyle decreased alcohol consumption, and smoking cessation.
changes will support and minimize the need for drug therapy.)

Chapter 37  Pharmacotherapy of Dysrhythmias  657

CONNECTIONS:  NURSING PRACTICE APPLICATION (continued)

Implementation

Interventions and (Rationales) Patient-Centered Care

Minimizing adverse effects: • Teach the patient, family, or caregiver how to take a peripheral pulse
• Continue to monitor ECG and pulse for quality and volume. Take the for 1 full minute before taking the drug. Assist the patient to find the
pulse area most convenient and easily felt. Record daily pulse rates
pulse for 1 full minute to assess for regularity. Continue to assess and regularity, and bring the record to each healthcare visit. Instruct
for complaints of palpitations and correlate palpitations or pulse the patient to notify the provider if the pulse is below 60 or above
irregularities with the ECG. (Not all dysrhythmias are symptomatic. 100 beats/min, there is a noticeable change in regularity from previously
Correlating symptoms with an ECG may help determine the need for felt pulse rate, or if palpitations develop or worsen.
further symptom management. Diverse Patients: Because of differ-
ences in acetylation and because some antidysrhythmics metabolize
through the CYP450 pathways, monitor ethnically diverse patients
more frequently to ensure optimal therapeutic effects and to minimize
adverse effects.)

• Take the blood pressure lying, sitting, and standing to detect ortho- • Teach the patient to rise from lying or sitting to standing slowly to
static hypotension. Lifespan: Be particularly cautious with the first few avoid dizziness or falls. If dizziness occurs, the patient should sit
doses of the drug and with the older adult who is at increased risk for or lie down and not attempt to stand or walk until the sensation
hypotension. (Antidysrhythmic drugs may cause hypotension. A first- passes.
dose effect may occur with a significant drop in blood pressure with
the first few doses. Orthostatic hypotension may increase the risk of • Instruct the patient to take the first dose of the new prescription in the
falls and injury.) evening before bed if possible, and to be cautious during the next few
doses until the drug effects are known.

• Teach the patient, family, or caregiver how to monitor blood pressure
if required. Ensure proper use and functioning of any home equipment
obtained.

• Instruct the patient to notify the healthcare provider if blood pressure is
90/60 mmHg or below, or below the parameters set by the healthcare
provider.

• Continue to monitor periodic electrolyte levels, especially potassium, • Instruct the patient on the need to return periodically for laboratory
calcium, and magnesium; renal function laboratory values; and drug work.
levels as needed. (Hypokalemia, hypocalcemia, and hypomagne-
semia increase the risk of dysrhythmias. Inadequate or high levels • Advise the patient to carry a wallet identification card or wear medical
of antidysrhythmic drugs may lead to increased or more lethal identification jewelry indicating antidysrhythmic therapy.
dysrhythmias.)

• Weigh the patient daily and report weight gain or loss of 1 kg (2 lb) or • Have the patient weigh self daily, ideally at the same time of day, and
more in a 24-h period. Continue to assess for edema, noting location record weight along with pulse measurements. Have the patient report
and character. (Daily weight is an accurate measure of fluid status and weight loss or gain of more than 1 kg (2 lb) in a 24-h period.
takes into account intake, output, and insensible losses. Weight gain or
edema may indicate adverse drug effects or worsening cardiovascular
disease processes.)

• Monitor for breath sounds and heart sounds (e.g., increasing dyspnea • Instruct the patient to immediately report any severe shortness of
or postural nocturnal dyspnea, rales or crackles in lungs, frothy pink- breath, frothy sputum, profound fatigue, or swelling of extremities as
tinged sputum, murmurs, or extra heart sounds) and report immedi- possible signs of HF or pulmonary toxicity.
ately. (Increasing lung congestion or new or worsening heart murmurs
may indicate impending HF. Potassium channel blockers are associ-
ated with pulmonary toxicity.)

• Report any visual changes, skin rashes, or unusual sunburn to • Teach the patient to report any visual changes promptly and to
the healthcare provider. (Potassium channel blockers may cause maintain regular eye examinations.
photosensitivity, skin rashes, and blurred vision.)
• Teach the patient about the importance of wearing protective
clothing and applying sunscreen regularly during periods of sun
exposure.

• Lifespan: Assess for the possibility of pregnancy before • Instruct female patients who may be considering pregnancy, or are
beginning the drug. (Some antidysrhythmics such as amiodarone pregnant or breastfeeding, to notify their provider before starting the
are pregnancy category D drugs and should not be used during drug.
pregnancy.)

Patient understanding of drug therapy: • The patient, family, or caregiver should be able to state the reason for
• Use opportunities during administration of medications and the drug, appropriate dose and scheduling, what adverse effects to
observe for and when to report them, equipment needed as appropri-
during assessments to discuss the rationale for the drug ate and how to use that equipment, and the required length of medica-
therapy, desired therapeutic outcomes, commonly observed tion therapy needed, with any special instructions regarding renewing
adverse effects, parameters for when to call the healthcare or continuing the prescription as appropriate.
provider, and any necessary monitoring or precautions. (Using
time during nursing care helps to optimize and reinforce key
teaching areas.)

Patient self-administration of drug therapy: • Teach the patient to take drugs as evenly spaced apart as possible
• When administering medications, instruct the patient, family, or and not to double dose if a dose is missed.

caregiver in proper self-administration techniques. (Utilizing time during • Teach the patient, family, or caregiver not to stop the medication
nurse administration of these drugs helps to reinforce teaching.) abruptly, and to call the healthcare provider if the patient is unable to
take the medication for more than 1 day due to illness.

658  Unit 5  Pharmacology of the Cardiovascular System

Understanding Chapter 37

Key Concepts Summary 37.6 Antidysrhythmic drugs are classified by their
mechanism of action.
37.1 Some dysrhythmias produce no patient
symptoms, whereas others may be life 37.7 Class I antidysrhythmics act by blocking ion
threatening. channels in myocardial cells.

37.2 The phases of cardiac action potential include 37.8 Beta-adrenergic antagonists reduce automaticity
rapid depolarization, a long plateau, and and slow conduction velocity in the heart.
repolarization.
37.9 Potassium channel blockers prolong the refractory
37.3 The electrocardiogram is used to measure period of the heart.
electrical conduction across the myocardium.
37.10 Calcium channel blockers are used to treat atrial
37.4 Dysrhythmias are classified by the impulse origin dysrhythmias.
and type of rhythm abnormality produced.
37.11 Adenosine and digoxin are used for specific
37.5 Antidysrhythmic drugs are only used when there dysrhythmias.
is a clear benefit to the patient.

CASE STUDY: Making the Patient Connection

Remember the patient Asian woman; vital signs: blood pressure, 102/68 mmHg;
“Jada Chinn Nguyen” at heart rate, 116 beats/min; respiratory rate, 18 breaths/min;
the beginning of the afebrile; weight 53 kg (116 lb). She has clear bilateral breath
chapter? Now read the sounds and active bowel sounds heard in all four quad-
remainder of the case rants. Her ECG reveals atrial fibrillation with a ventricular
study. Based on the infor- rate of 116 beats/min. She is admitted to the coronary care
mation presented within unit for further testing and observation.
this chapter, respond to the critical thinking questions
that follow. Critical Thinking Questions

The day had been busy as Jada prepared for her daughter’s 1. Jada’s ECG shows atrial fibrillation. Trace the electrical
upcoming wedding. There were so many arrangements to conduction system through the heart. What part of the
be made, and Jada felt overwhelmed. During the day she ECG complex would be most affected by this patient’s
experienced heaviness in her chest, but she attributed it to medical diagnosis?
the stress of the wedding and perhaps a touch of bronchitis.
Nonetheless, she knew there was no time to stop and rest; 2. While in the coronary care unit, Jada will receive amio-
there was too much to do. darone IV infusion. She wants to know how long she
will need to receive the IV medication and how it
Later that afternoon, she realized that she had to take it works. How would you respond to this patient’s
easy. Then she experienced that strange sensation once questions?
again. As she sat in a chair, Jada suddenly felt dizzy with
extreme weakness and difficulty breathing. Her family 3. The patient is being discharged on amiodarone 400 mg
members report that she became pale and unexpectedly twice daily. What instructions should this patient
collapsed. Emergency personnel were called to the scene, receive?
and Jada was taken to the nearest hospital.
4. List any drug–food interaction concerns you should
In the emergency department, Jada’s physical exami- discuss with Jada.
nation revealed the following findings: weak, middle-aged
Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.

Chapter 37  Pharmacotherapy of Dysrhythmias  659

Additional Case Study 2. “If I’m on a calcium channel blocker, does that mean
my bones might get weak?”
Malcolm Hibbert is a 56-year-old man who was diagnosed
with a rapid atrial dysrhythmia and placed on diltiazem 3. “Might any of my medications cause an increase in
(Cardizem) to control the condition. He has been surfing dysrhythmias?”
the internet to find out more about his condition and drug
therapy. When he returns to the clinic, he has multiple Answers to Additional Case Study questions are available on
questions to ask you. How would you respond to each of the faculty resources site. Please consult with your instructor.
the following?

1. “My neighbor had a fast heartbeat and now he’s on some-
thing called digoxin. Why didn’t they use that for me?”

Chapter Review 3. Over 20 to 30 minutes IV.
4. By a rapid IV bolus injection over 1 to 2 seconds.
1. A healthcare provider has ordered procainamide for
each of four patients. A nurse should question the 5. The patient is prescribed propranolol (Inderal) for the
order for a patient with which condition? treatment of atrial dysrhythmias associated with heart
failure. The nurse knows this drug is used cautiously
1. Ventricular tachycardia in patients with heart failure because of which effect?
2. Paroxysmal atrial tachycardia
3. Atrial fibrillation 1. It causes sodium retention, worsening congestion.
4. Severe heart failure 2. Its adverse effects include hypertension, worsening

2. A patient is receiving intravenous lidocaine for ven- heart failure.
tricular dysrhythmias. Which nursing intervention is 3. It is a negative inotropic drug and will decrease
appropriate for this therapy?
myocardial contractility and cardiac output.
1. Monitor the patient for decreased platelet levels. 4. It may cause bronchoconstriction.
2. Place the patient in a supine position during
6. A patient is being discharged with a diagnosis of dys-
administration. rhythmias. The nurse is teaching the patient about
3. Monitor for paresthesias, drowsiness, or confusion. amiodarone. What patient teaching is needed related
4. Encourage coughing and deep breathing to remove to this medication?

secretions. 1. Avoid crowds while taking this medication.
2. Avoid birth control pills and use an alternate form
3. The patient with a rapid atrial dysrhythmia is being
treated with verapamil (Calan). The nurse would of birth control.
monitor for therapeutic effectiveness by noting which 3. Wear protective clothing and adequate sunscreen.
of the following? 4. Use an electric razor to shave.

1. Change in the blood pressure See Answers to Chapter Review in Appendix A.
2. Increase in the serum potassium level
3. Changes in the cardiac rhythm
4. Reduction in the urine output

4. A patient is to receive adenosine (Adenocard) for
rapid supraventricular tachycardia. This drug must be
administered:

1. Over a 24-hour period by IV drip.
2. Along with potassium chloride to prevent

electrolyte imbalance.

660  Unit 5  Pharmacology of the Cardiovascular System Sovari, A. A. (2015). Long QT syndrome. Retrieved from
http://emedicine.medscape.com/article/
References 157826-overview#a3

Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Vedin, O. (2014). Should dental health now be considered
Blaha, M. J., Cushman, M., . . . Turner, M. B. (2015). a marker of coronary heart disease? European Heart
AHA statistical update heart disease and stroke Journal, 35, 2200–2201.
statistics—2015 update. Circulation, 131, e29-e322.
doi:10.1161/CIR.0000000000000152

Selected Bibliography Opinion in Cardiology, 29(1), 36–44. doi:10.1097/
HCO.0000000000000020
American Heart Association. (2016). About arrhythmia. National Heart, Lung, and Blood Institute. (2016). What is
Retrieved from http://www.heart.org/HEARTORG/ sudden cardiac arrest? Retrieved from http://www.
Conditions/Arrhythmia/AboutArrhythmia/About- nhlbi.nih.gov/health/health-topics/topics/scda
Arrhythmia_UCM_002010_Article.jsp#.V_RSkijt4RY Nattel, S., Andrade, J., Macle, L., Rivard, L., Dyrda, K.,
Mondesert, B., & Khairy, P. (2014). New directions in
Atwood, S., Stanton, C., & Storey-Davenport, J. (2013). cardiac arrhythmia management: Present challenges
Introduction to basic cardiac dysrhythmias (4th ed.). and future solutions. Canadian Journal of Cardiology,
Burlington, MA: Jones & Bartlett. 30(12 Suppl.), S420–S430. doi:10.1016/j.cjca.2014.09.027
Tse, G. (2016). Mechanisms of cardiac arrhythmias. Journal
Brenyo, A., & Aktas, M. K. (2013). Review of of Arrhythmia, 32, 75–81. doi:10.1016/j.joa.2015.11.003
complementary and alternative medical treatment of Turagam, M. K., Flaker, G. C., Velagapudi, P., Vadali, S., &
arrhythmias. The American Journal of Cardiology, 113, Alpert, M. A. (2015). Atrial fibrillation in athletes:
897–903. doi:10.1016/j.amjcard.2013.11.044 Pathophysiology, clinical presentation, evaluation and
management. JAFIB: Journal of Atrial Fibrillation, 8(4),
Ferdinand, K. C., & Puckrein, G. A. (2015). Race/ethnicity 1309. doi:10.4022/jafib.1309
in atrial fibrillation stroke: Epidemiology and Vamos, M., Erath, J. W., & Hohnloser, S. H. (2015).
pharmacotherapy. Journal of the National Medical Digoxin-associated mortality: A systematic review and
Association, 107(1), 59–67. doi:10.1016/ meta-analysis of the literature. European Heart Journal, 36,
S0027-9684(15)30010-9 1831–1838. doi:10.1093/eurheartj/ehv143

Ferreira, J. P., & Santos, M. (2015). Heart failure and atrial
fibrillation: From basic science to clinical practice.
International Journal of Molecular Sciences, 16, 3133–3147.
doi:10.3390/ijms16023133

Joglar, J. A., & Page, R. L. (2014). Management of
arrhythmia syndromes during pregnancy. Current

“Ever since I returned from my
trip to Bangkok, my right calf
has really hurt. I first thought
my arthritis was flaring up

again, especially after sitting on
the plane for so long.”

Patient “Jihyo Yun”

Chapter 38

Pharmacotherapy
of Coagulation Disorders

Chapter Outline Learning Outcomes

cc Disorders of Hemostasis After reading this chapter, the student should be able to:
cc Overview of Coagulation Modifiers
cc Anticoagulants 1. Describe primary risk factors for thromboembolic
disorders.
PROTOTYPE  Heparin, p. 666
PROTOTYPE  Warfarin (Coumadin), p. 669 2. Explain the etiology and symptoms of coagulation
Direct Thrombin Inhibitors disorders.
PROTOTYPE  Dabigatran (Pradaxa), p. 671
cc Antiplatelet Drugs 3. Identify the primary mechanisms by which
Aspirin coagulation-modifying drugs act.
Adenosine Diphosphate Receptor Blockers
PROTOTYPE  Clopidogrel (Plavix), p. 675 4. Explain how laboratory testing of coagulation
Glycoprotein IIb/IIIa Receptor Inhibitors parameters is used to monitor anticoagulant
PROTOTYPE  Abciximab (ReoPro), p. 677 pharmacotherapy.
cc Drugs for Intermittent Claudication
cc Thrombolytics 5. Describe the nurse’s role in the pharmacologic
PROTOTYPE  Alteplase (Activase), p. 681 management of patients with coagulation disorders.
cc Hemostatics
PROTOTYPE  Aminocaproic Acid (Amicar), p. 684 6. For each of the classes shown in the chapter outline,
cc Drugs for Hemophilia identify the prototype and representative drugs and
explain the mechanism(s) of drug action, primary
indications, contraindications, significant drug
interactions, pregnancy category, and important
adverse effects.

7. Apply the nursing process to care for patients
receiving pharmacotherapy for coagulation
disorders.

661

662  Unit 5  Pharmacology of the Cardiovascular System

Key Terms hemophilia, 663 thrombocytopenia, 663
intermittent claudication (IC), 679
activated partial thromboplastin plasminogen, 680 thromboembolic disorder, 662
time (aPTT), 664 procoagulants, 662
prothrombin time (PT), 664 venous thromboembolism
anticoagulants, 662 pulmonary embolism, 663 (VTE), 662
antithrombin III (AT-III), 666
deep vein thrombosis (DVT), 662 von Willebrand’s
fibrinolysis, 680 disease (vWD), 687

Everyone is familiar with the bleeding associated with sim- describe conditions in which the body forms undesirable
ple cuts and scrapes, and we take for granted that bleeding clots. Thromboembolic disorders may be classified as either
will stop in a few minutes. The stoppage of blood flow, or venous or arterial.
hemostasis, is complex and essential to our well-being. The
underlying mechanisms of hemostasis promote blood clot- Venous thromboembolism (VTE) is a common condi-
ting that protects us from injuries that could lead to shock tion that occurs when blood flow through a vein is very
and perhaps death. Too much clotting, however, can be just slow (stasis). Venous stasis allows procoagulation factors to
as dangerous. The physiologic processes of hemostasis accumulate and overcome the natural anticoagulant sub-
must maintain a delicate balance between blood fluidity stances in the blood. There are two manifestations of VTE:
and coagulation. deep vein thrombosis and pulmonary embolism.

Many common diseases and conditions affect hemo- When thrombosis occurs in the legs it is called deep
stasis, including myocardial infarction (MI), stroke, venous vein thrombosis (DVT). Because blood flow is slowest in
or arterial thrombosis, sepsis, and cancer. Because these the deep veins of the lower limbs, these vessels are the
conditions are prevalent in clinical practice, nurses will most common sites for VTE. Conditions associated with
have frequent occasions to administer and monitor the venous stasis and DVT include the following:
effects of coagulation-modifying medications. Drugs may
be used to enhance coagulation, inhibit coagulation, or dis- • Extended immobility. During major illness or follow-
solve existing clots to restore blood flow. ing surgery, patients may be supine or otherwise
immobile for extended periods. Because the move-
Disorders of Hemostasis ment of blood through the deep veins is entirely
dependent on the squeezing action from skeletal mus-
38.1  Thromboembolic disorders are cular contraction, blood in the deep veins of these
abnormalities of hemostasis that include deep patients has difficulty returning to the heart.
vein thrombosis and pulmonary embolism.
• Major trauma. Trauma often causes serious bleeding
Coagulation is regulated by a large number of natural sub- that activates procoagulation factors. In addition,
stances circulating in the blood. Some of these are proco- stasis will likely occur surrounding the injured area,
agulants, which favor the formation of clots, while others promoting the development of DVT. Trauma involv-
are anticoagulants, which inhibit clot formation. Coagula- ing the lower extremities places the patient at high risk
tion, then, can be thought of as a delicate balance between for DVT.
procoagulants and anticoagulants. For example, injuries to
blood vessels release procoagulants that tip the balance in • Major surgery. Surgery of the lower extremities, espe-
favor of initiating coagulation. The student should review cially knee and hip replacements, are common causes
the coagulation cascade presented in Chapter 28 before of DVT for the same reasons as trauma; bleeding acti-
proceeding. vates procoagulation factors and stasis occurs around
the surgical site.
Once a stationary clot, or thrombus, forms in a vessel,
it often grows larger as more fibrin is added. Pieces of the • Hypercoagulability states. Malignancy, lupus, and
thrombus may break off and travel in the bloodstream to pregnancy are examples of conditions associated with
block other vessels. A traveling clot is called an embolus. an increased risk of coagulation and DVT. Certain
Because these two conditions often occur concurrently in genetic disorders also produce hypercoagulability, the
patients, the term thromboembolic disorder is used to most common being a genetic deficiency of protein C,
a natural anticoagulant.

• Drug therapy. High amounts of estrogen, prescribed
as replacement therapy or as a component of oral

Chapter 38  Pharmacotherapy of Coagulation Disorders   663

contraceptives, have been associated with DVT in 38.2  Coagulation disorders are caused
numerous studies. Selective estrogen receptor modu- by decreased numbers of platelets or by
lators (SERMs), such as raloxifene (Evista), are also deficiencies in specific clotting factors.
associated with a higher risk of DVT.
Whereas thromboembolic disorders are caused by too
The second primary thromboembolic disorder is much clotting, coagulation disorders result from too little
pulmonary embolism, which occurs when a venous clot clotting. Serious consequences result if the body does not
dislodges, migrates to the pulmonary vessels, and blocks form clots in a timely manner. The two most common eti-
arterial circulation to the lungs. Pulmonary emboli are the ologies of coagulation disorders are decreased numbers of
most serious consequence of VTE because death may occur platelets and deficiencies in one or more clotting factors.
within minutes after the onset of symptoms. The factors
associated with an increased risk of pulmonary embolism Platelets are central to the process of coagulation. Rec-
are the same as those for patients with DVT: prolonged ognizing a site of vessel injury, activated platelets release
immobility, major trauma, lower extremity surgery, hyper- von Willebrand’s factor, which causes platelets to become
coagulability states, and estrogen therapy. Prevention of “sticky” and adhere to the site. Following adhesion, platelets
pulmonary embolism is a primary goal for all patients with secrete substances such as adenosine diphosphate (ADP)
VTE and a major indication for pharmacotherapy. and thromboxane A2 that promote platelet aggregation and
the formation of a platelet plug at the site. Procoagulation
Patients with DVT are sometimes asymptomatic, or factors become activated on the platelets and a fibrin mesh
report nonspecific symptoms such as pain, swelling, or clot results. Nearly every step of this pathway requires suf-
warmth of the legs. The disorder may be present for years, ficient numbers of properly functioning platelets.
causing progressive damage to venous valves, thus wors-
ening blood flow in the region and increasing the risk of an The most common coagulation disorder is a deficiency
acute episode. A pulmonary embolism, however, produces of platelets, or thrombocytopenia, which occurs when
a sudden onset of cough, chest pain, tachypnea, dyspnea, platelet counts fall below 150,000 mm3. Thrombocytopenia
tachycardia, and hemoptysis. Symptoms of pulmonary is the result of either decreased platelet production or
embolism resemble an MI, and rapid diagnosis and treat- increased platelet destruction. Any condition or disease
ment are essential. that suppresses bone marrow function has the potential to
cause decreased platelet production. Other common
PharmFACT causes of decreased platelet production are folic acid or
vitamin B12 deficiencies and decreased production of
Up to 30% of patients presenting with DVT have a malignancy. thrombopoietin by the liver during hepatic failure.
This is because about 90% of patients with cancer have some Increased destruction of platelets may occur in patients
abnormal clotting factors (Patel, 2016). with thrombocytopenic purpura, disseminated intravas-
cular coagulation (DIC), or lupus.
Arterial thromboembolism may deprive an area of
blood flow and is a medical emergency because tissue Of special concern is thrombocytopenia caused by
hypoxia and cellular death will result soon after blood drug therapy. A significant number of drugs have the
stoppage. The most serious arterial thromboembolism dis- potential to increase platelet destruction, either by direct
orders are MI and stroke. toxic effects on bone marrow or by inducing the immune
system to destroy them. When caring for patients receiving
Arterial thrombi and emboli commonly result from these drugs, the nurse must be vigilant in assessing the
procedures involving arterial punctures such as angiogra- results of blood laboratory tests and observing for signs of
phy and stent placement. They may also originate from the thrombocytopenia such as bleeding gums, nosebleeds, and
heart. Emboli are common complications of mitral valve extensive bruising. Selected drugs that cause thrombocyto-
disease, prosthetic heart valves, and atrial dysrhythmias. penia are listed in Table 38.1. Heparin-induced thrombocy-
Emboli originating from the left side of the heart may lodge topenia, a particularly serious form of this disorder, is
in any organ in the body. discussed in Section 38.4.

CONNECTION Checkpoint  38.1 Deficiencies in specific clotting factors may prolong
coagulation and lead to excess bleeding. Deficiencies in
Coagulation occurs by intrinsic and extrinsic pathways. From what multiple coagulation factors occur frequently in patients
you learned in Chapter 28, which pathway is activated when blood with serious hepatic impairment, because the liver synthe-
leaks from a vessel? Which is more complex and takes several min- sizes most clotting factors. Deficiency in a single coagula-
utes? Which results in the formation of fibrin?  Answers to Connection tion factor suggests hemophilia, a series of coagulation
Checkpoint questions are available on the faculty resources site. Please disorders caused by genetic deficiencies in specific clotting
consult with your instructor. factors. Hemophilia disorders are typified by prolonged
coagulation times, resulting in persistent bleeding that can

664  Unit 5  Pharmacology of the Cardiovascular System

Table 38.1  Selected Drugs That Cause Thrombocytopenia

Class Examples

Analgesics acetaminophen, aspirin, diclofenac, ibuprofen, indomethacin, morphine, naproxen
Anticoagulants and antiplatelets
Anti-infectives clopidogrel, glycoprotein IIb/IIIa inhibitors, heparin

Antineoplastic and immunotherapy drugs acyclovir, amphotericin B, ampicillin, clarithromycin, ethambutol, fluconazole, indinavir, isoniazid,
Cardiovascular drugs itraconazole, linezolid, oxacillin, piperacillin, rifampin, sulfonamides, trimethoprim, vancomycin

Central nervous system drugs carboplatin, interferon-alfa, methotrexate
Other drug classes
atorvastatin, captopril, digoxin, hydrochlorothiazide, inamrinone, nitroglycerin, procainamide, quinidine,
simvastatin

carbamazepine, chlorpromazine, diazepam, haloperidol, lithium, phenobarbital, phenytoin, valproic acid

cimetidine, isotretinoin, MMR vaccine, octreotide, ranitidine, sirolimus

be acute or chronic. Patients may experience various forms Table 38.2  Overview of Coagulation Modifiers
of the disease, with symptoms ranging from mild to severe.
Approximately two thirds of patients with hemophilia will Type of Mechanism Drug
report a family history of the disease. The pharmacother- Modification Classification
apy of hemophilia is described in Section 38.14.
Prevention of clot Inhibition of specific Anticoagulants
To diagnose coagulation and thromboembolic disor- formation clotting factors
ders, a thorough medical history and physical examination Antiplatelet drugs
are necessary. Laboratory tests measuring coagulation Removal of an Inhibition of platelet
must be obtained. These usually include a whole-blood existing clot actions Thrombolytics
clotting time, prothrombin time (PT), thrombin time, acti- Promotion of clot
vated partial thromboplastin time (aPTT), liver function formation Clot dissolved by the Hemostatics
tests, platelet count, and, in some instances, a bleeding drug
time. Another test frequently ordered to assess hemostatic Clotting factor
function is the D-dimer. D-dimer tests are used to help rule Inhibition of fibrin concentrates
out the presence of a thrombus, DVT, and pulmonary destruction
embolisms. Additional tests, such as serum levels of spe-
cific clotting factors, may be indicated. Administration of
missing clotting factors
Overview of Coagulation
Modifiers Inhibition of Aspirin
platelet Abciximab
38.3  The normal coagulation process can be
modified by a number of different mechanisms. aggregation

Medications can be used to modify hemostasis in a num- Inhibition of Inhibition of
ber of ways. An overview of the basic mechanisms of platelet adhesion clotting factors
coagulation-modifying drugs is presented in Table 38.2.
These mechanisms are illustrated in Figure 38.1. to injury site and cascade

The most commonly prescribed coagulation modifiers Clopidrogel Dabigatran
are the anticoagulants and antiplatelet drugs. Although Ticlopidine Heparin
they work by different mechanisms, both of these drug
classes have the ability to prevent clot formation or enlarge- Low-molecular-
ment. Some basic differences between the two are as weight heparins
follows:
Warfarin
• Anticoagulants inhibit specific clotting factors in the
coagulation cascade. Patients usually call these drugs Decreased blood
“blood thinners,” but that is an inaccurate description viscosity
because they do not change the viscosity or thickness
of the blood. Examples include heparin and warfarin Pentoxifylline
(Coumadin).
Figure 38.1  Mechanisms of action of coagulation modifiers.

• Antiplatelet drugs inhibit the clotting action of
platelets. Examples include aspirin and clopidogrel
(Plavix).

Compared to antiplatelets, anticoagulants are consid-
ered more aggressive therapy for those at high risk for
strokes. Anticoagulants carry a higher risk of serious

Chapter 38  Pharmacotherapy of Coagulation Disorders   665

adverse effects, participate in more drug interactions, and each patient. Serious adverse effects may occur if the drugs
require more extensive follow-up (American Stroke Asso- are not used properly; therefore, these patients will require
ciation, 2014). Anticoagulants and antiplatelets are widely frequent assessment and monitoring to ensure that the goal
used for thromboembolic disease and are discussed in of normal coagulation is being achieved, without serious
Sections 38.4 through 38.6. adverse events.

Once an abnormal clot has formed, it may block blood Anticoagulants
vessels that serve critical tissues and it must be quickly
removed to restore normal function. This is particularly 38.4  Heparin is the traditional drug for rapid
important for vessels serving the heart, lungs, and brain. A anticoagulation.
specific class of drugs, the thrombolytics, has been devel-
oped to dissolve life-threatening clots. These drugs are pre- Extensively used in the treatment of thromboembolic dis-
sented in Section 38.12. ease, anticoagulants lengthen clotting time and prevent
thrombi from forming or growing larger. Since thrombo-
Coagulation modifiers are also used to promote the embolic disease can be life threatening, therapy is often
formation of clots. Drugs called hemostatics inhibit the begun by administering anticoagulants parenterally to
normal removal of fibrin, thus keeping the clot in place for achieve the most rapid onset of action. As the disease sta-
a longer period of time. These drugs are primarily used to bilizes and the desired degree of anticoagulation has been
speed clot formation to limit bleeding from a surgical site; achieved, the patient is gradually switched to oral antico-
they are discussed in Section 38.13. For patients with hemo- agulants, with careful monitoring of appropriate coagula-
philia, clotting factors may be administered to promote tion laboratory values. Traditionally, the most frequently
clotting by providing a missing or deficient component in prescribed parenteral anticoagulant has been heparin;
the coagulation cascade, as presented in Section 38.14. warfarin is the most common oral anticoagulant (see
Section 38.5). The anticoagulants are listed in Table 38.3.
Because hemostasis involves a fine balance of factors
favoring clotting versus those inhibiting clotting, pharma-
cotherapy with coagulation modifiers is individualized to

Table 38.3  Anticoagulants

Drug Route and Adult Dose (Maximum Dose Where Indicated) Adverse Effects
Minor bleeding, nausea, vomiting, transient
antithrombin, recombinant (ATryn) IV infusion: Dose is individualized based on pretreatment thrombocytopenia (heparin), anemia
antithrombin level and body weight (fondaparinux)
Hemorrhage, anaphylaxis, heparin-induced
fondaparinux (Arixtra) Subcutaneous: 2.5 mg/day starting at least 6 h postop thrombocytopenia
for 5–9 days (max: 10 mg/day)
Minor bleeding, nausea, vomiting, hematoma,
heparin IV: 5000-unit bolus dose, then 20,000–40,000 units infused over local pain, fever
24 h (use agency-specific heparin nomogram) Hemorrhage, thrombocytopenia, pancytopenia,
anaphylaxis, local site reactions
Subcutaneous: 10,000–20,000 units followed by
8000–20,000 units q8–12h Fever, nausea, allergic skin reactions, hepatic
impairment, pneumonia, fever, minor bleeding,
warfarin (Coumadin) PO: Dose varies based on target international normalized ratio back pain (bivalirudin)
(INR), which is usually within the range of 2–3 Serious internal hemorrhage, hemoptysis,
hematuria, sepsis, heart failure
Low-Molecular-Weight Heparins (LMWHs)
Minor bleeding, rash
dalteparin (Fragmin) Subcutaneous (DVT prophylaxis): 2500–5000 units/day Major bleeding, including stroke; anemia;
for 5–10 days (max: 18,000 international units/day) hypersensitivity reactions

Subcutaneous (DVT treatment): 120 international units/kg bid

enoxaparin (Lovenox) Subcutaneous (DVT prophylaxis): 30 mg bid

Subcutaneous (DVT treatment): 1 mg/kg q12h or 1.5 mg/kg/day
IV (acute STEMI): 30-mg bolus followed by subcutaneous doses

Direct Thrombin Inhibitors

argatroban (Acova, Novastan) IV: 2 mcg/kg/min (max: 10 mcg/kg/min)

bivalirudin (Angiomax) IV: 0.75 mg/kg initial bolus followed by 1.75 mg/kg/h for 4 h

dabigatran (Pradaxa) PO: 75–150 mg bid

desirudin (Iprivask) Subcutaneous: 15 mg bid for 9–12 days (max: 80 mg/day)

Factor Xa Inhibitors

apixaban (Eliquis) PO: 5 mg bid

betrixaban (Bevyxxa) PO: Single dose of 160 mg followed by 80 mg once daily

edoxaban (Savaysa) PO: 30–60 mg once daily

rivaroxaban (Xarelto) PO: 10–20 mg once daily

Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.

666  Unit 5  Pharmacology of the Cardiovascular System

Heparin is a natural chemical found in the liver and members or the patient can be trained to give the necessary
the lining of blood vessels. As a drug, heparin has been subcutaneous injections at home. Like heparin, the LMWHs
used for many decades and is one of the few drugs still do not cross the placenta. LMWHs have become preferred
obtained from animal tissue, usually beef lung or pig intes- drugs for a number of clotting disorders, including the pre-
tine. Chemically, heparin is a special type of carbohydrate vention of DVT following surgery. One disadvantage is
called a glycosaminoglycan that consists of repeated disac- that LMWHs are more expensive than heparin.
charide units of differing lengths. Thus, heparin is actually
a mixture of different molecules, varying in size. This drug When using LMWHs, the aPTT laboratory value
is also called unfractionated heparin because it contains a does not reflect the anticoagulant effects of the drugs
mixture of different molecular pieces or “fractions.” This because aPTT is insensitive to changes in Factor Xa.
mixture affects protein binding and drug bioavailability Instead, dosage calculations with LMWHs are fixed and
and is partially responsible for the wide variation in patient based on the patient’s weight. A given amount of subcu-
responses to heparin. taneous LMWH results in a predictable plasma drug
level. This is a major advantage over heparin, for which
Heparin produces its anticoagulant effects by binding levels continually fluctuate and doses must be adjusted
to antithrombin III (AT-III). As its name implies, anti- based on aPTT levels. In highly unstable patients or those
thrombin inactivates thrombin (as well as several other with chronic kidney disease (CKD), measurement of anti-
clotting factors). The binding to heparin produces a struc- factor Xa activity may be used to gauge therapeutic
tural change in AT-III that makes it 1000 times more active response. Acceptable target values for antifactor Xa range
in inhibiting thrombin, Factor Xa, Factor IXa, and other from 0.5 to 1 unit/mL.
substances involved in coagulation. Within minutes after
intravenous (IV) administration, the loss of these activated PROTOTYPE DRUG Heparin
clotting factors prevents the formation of fibrin clots.
Classification Therapeutic: Anticoagulant
Because responses to heparin anticoagulation vary Pharmacologic: Indirect thrombin
considerably among patients, regular monitoring of labo-
ratory values during heparin therapy is essential to patient inhibitor
safety. The aPTT value is the conventional measurement
that guides heparin therapy, with normal values ranging Therapeutic Effects and Uses:  Heparin is the tradi-
from 25 to 40 seconds. For therapeutic anticoagulation, the tional standard to which other parenteral anticoagulants
aPTT should be between 1.5 and 2 times the patient’s base- are compared. Because it has an immediate onset of action
line, or 60 to 80 seconds. Elevated aPTT values indicate the when administered IV, heparin is a first-line drug for acute
patient is at high risk for bleeding and that a reduction in thromboembolic disorders where rapid anticoagulation is
heparin dose is necessary. aPTT values of less than 60 sec- necessary. Subcutaneous heparin is injected into the deep
onds indicate the need for higher heparin doses. During fatty layers of the abdomen and may take up to 1 hour
continuous IV heparin therapy, the aPTT is measured daily to achieve a therapeutic effect. A continuous IV infusion
and 6 to 8 hours after any changes in dosage. allows for better titration and finer management of aPTT
values. Indications include DVT, pulmonary embolism,
Low-molecular-weight heparins:  The heparin mole- unstable angina, evolving MI, and prevention of throm-
cule has been shortened and modified to create a new class bosis in high-risk patients. Heparin and LMWHs are pre-
of drugs called low-molecular-weight heparins (LMWHs). ferred anticoagulants during pregnancy because heparin
Given subcutaneously, the mechanism of action of these molecules are too large to cross the placenta. Heparin is
drugs is very similar to that of heparin, except the shorter also used to maintain the patency of peripheral catheters
heparin molecules are unable to bind thrombin, making (heparin locks) and arterial lines.
them more selective for Factor Xa inhibition. For some
applications, the LMWHs have begun to replace tradi- Heparin prolongs coagulation time, thereby inhibiting
tional heparin anticoagulation. excessive clotting within blood vessels. As a result, it pre-
vents the enlargement of existing clots and the formation of
LMWHs possess the same anticoagulant activity as new ones. It has no ability to dissolve existing clots. Clot-
heparin but have several advantages. They produce a more ting time is prolonged, although bleeding time is only
predictable anticoagulant response than heparin because affected at high doses.
there is less binding of the drug to proteins and macro-
phages; therefore, less frequent laboratory monitoring is Mechanism of Action:  Heparin activates the enzyme
required. They are about 10 times less likely to cause throm- antithrombin III, which in turn inhibits thrombin. To a
bocytopenia, a potentially serious adverse effect of hepa- lesser extent, and by a separate mechanism, heparin also
rin. They also exhibit a half-life that is 2 to 4 times longer inactivates Factor Xa. Other clotting factors are affected
than heparin that permits once-daily dosing, and family by heparin, but these have less clinical significance. High
doses interfere with platelet aggregation.

Chapter 38  Pharmacotherapy of Coagulation Disorders   667

Pharmacokinetics:  bleeding, serious bleeding pathologies, severe hyperten-
sion (HTN), recent trauma, intracranial hemorrhage, or
Route(s) Subcutaneous, IV bolus injection, bacterial endocarditis. Some heparin products may contain
sulfites and should not be administered to patients with
or continuous infusion sulfite sensitivity. Patients with severe thrombocytopenia
or HIT should not be given heparin. Whenever possible,
Absorption Heparin is poorly absorbed by intramuscular (IM) injections of other medications should
be avoided because they may cause serious bruising,
the gastrointestinal (GI) mucosa bleeding, or hematomas. Although relatively safe during
pregnancy, the drug should be used with caution during
because of rapid metabolism by the peripartum period due to the risk of maternal hemor-
rhage. Caution must be used when administering hepa-
the hepatic enzyme, heparinase rin to patients with serious CKD or hepatic impairment
because the drug may rise to toxic levels.
Distribution Unknown; does not cross the
Drug Interactions:  Oral anticoagulants, including
placenta and is not secreted in warfarin, potentiate heparin activity. Drugs that inhibit
platelet aggregation (such as aspirin, indomethacin, and
breast milk ibuprofen) may induce bleeding. Nicotine, digoxin, tetra-
cyclines, or antihistamines may inhibit anticoagulation.
Primary metabolism Hepatic and by reticuloendothe- Herbal/Food: Herbal supplements that may affect coagu-
lation such as ginger, garlic, green tea, feverfew, or ginkgo
lial system should be avoided because they may increase the risk of
bleeding.
Primary excretion Reticuloendothelial system
Pregnancy:  Category C.
Onset of action Subcutaneous: 30–60 min; IV:
Treatment of Overdose:  If serious hemorrhage
immediate occurs, a specific antagonist, protamine sulfate, may be
administered IV (1 mg for every 100 units of heparin) to
Duration of action 8–12 h; half-life: 90 min neutralize the anticoagulant activity of heparin. Protamine
sulfate has an onset of action of 5 minutes and a duration
Adverse Effects:  Abnormal bleeding occurs in about of 2 hours. Multiple doses may be necessary to control
10% of patients, and is the most serious adverse effect. extensive hemorrhaging. Protamine is also an antagonist
Bleeding may be major or minor and may involve any sys- to the LMWHs.
tem in the body. The risk of bleeding is dose dependent;
the higher the dose, the greater the risk. Should the aPTT Nursing Responsibilities:  Key nursing implications
become excessively prolonged or bleeding be observed, for patients receiving heparin are included in the Nursing
discontinuation of the drug will result in loss of anticoagu- Practice Application for Patients Receiving Pharmacother-
lant activity within hours. Black Box Warning: Epidural apy with Anticoagulants.
or spinal hematomas may occur when heparin or LMWHs
are used in patients receiving spinal anesthesia or lumbar Drugs Similar to Heparin
puncture. Because these can result in long-term or perma-
nent paralysis, frequent monitoring for neurologic impair- The LMWHs include dalteparin and enoxaparin. A third
ment is essential. LMWH, tinzaparin, is no longer marketed in the United
States. Antithrombin (recombinant) and fondaparinux are
Heparin-induced thrombocytopenia (HIT) is a serious parenteral anticoagulants that act by unique mechanisms.
complication that occurs in up to 30% of patients taking the
drug. Symptoms range from mild to severe. More severe Antithrombin, recombinant (ATryn):  ATryn is a unique
symptoms usually appear after 5 to 10 days of therapy; coagulation modifier approved in 2009 to treat patients
thus, frequent blood laboratory testing should be con- who have a congenital deficiency of antithrombin III. These
ducted during this period. Although thrombocytopenia patients have a high incidence of blood clots, especially
usually leads to excessive bleeding, HIT causes the oppo- DVT. The drug is indicated for the prevention of periopera-
site effect: an increase in adverse thrombotic events. HIT tive and peripartum thromboembolic events in hereditary
markedly increases platelet aggregation and the patient antithrombin-deficient patients. Antithrombin (ATryn) is
may experience serious and even life-threatening thrombo- unusual because it is obtained from genetically engineered
sis. Although the half-life of heparin is brief, it may take a goats. The goats are engineered through recombinant
week after the drug is discontinued for platelets to recover.
In addition, HIT may not even become evident until sev-
eral weeks after the drug is discontinued.

Because heparin is derived from animal sources,
hypersensitivity reactions are possible. Mild allergic symp-
toms include fever, chills, and urticaria. Anaphylaxis is
rare. Osteoporosis has been reported in patients taking the
drug longer than 30 days and may be severe enough to
cause bone fractures. Skin lesions may develop, especially
at the site of parenteral injections.

Contraindications/Precautions:  Heparin should
not be administered to patients with active internal