Cardiotonic-inotropic drugs are particularly useful for patients with heart failure (HF), wherein the heart is not able to effectively pump the blood towards different body organs. As a result, cells of the body are deprived of oxygen and nutrients.

Cardiotonic agents are drugs used to increase the contractility of the heart. Included below is a pharmacology guide for nurses on the various effects of cardiotonic-inotropic agents.

Table of Common Drugs and Generic Names

Here is a table of commonly encountered cardiotonic-inotropic drugs, their generic names, and brand names:

Classification Generic Name Brand Name
Cardiac glycosides deslanoside Cedilanid-d
digitoxin Crystodigin
digoxin Lanoxin, Lanoxicaps
Phosphodiesterase inhibitors amrinone, inamrinone Inocor
cilostazol Pletal
milrinone Primacor
enoximone Perfan

Disease Spotlight: Heart Failure (HF)


Heart failure is a syndrome characterized by dysfunction of cardiac muscles.

  • It can occur in a number of heart conditions which can overwork the heart muscles. Some of these conditions include:
  • Coronary artery disease (CAD), which leads to insufficient blood supply for the myocardium and is also the most common cause of HF;
  • Cardiomyopathy, which leads to enlargement of the heart and myocardial fatigue; and
  • Valvular heart diseases, which can cause reflux and overloading of blood to the ventricles which consequently over stretches the myocardium.
  • Clinical manifestations depend on the side of the heart which failed:

Left-sided HF

  • Primarily reflects pulmonary manifestations because the left ventricle cannot push blood towards the peripheral systems.
  • As a result, there is engorgement of pulmonary veins, which leads to difficulty of breathing.
  • Other manifestations include: tachypnea (rapid breathing), dyspnea (discomfort associated with breathing), and orthopnea (increased difficulty of breathing when lying down). Patient also experiences coughing and hemoptysis (coughing up of blood). In severe cases, pulmonary edema (filling up of fluid in the lung spaces) occurs which is life-threatening because it interferes with gas exchange.

Right-sided heart failure

  • Occurs when the right side of the heart has the need to exert more force in order to push blood towards the pulmonary circulation.
  • This side is usually a low-pressure system so when this happens, the pressure in this side rises and venous return can’t enter.
  • Neck veins become distended and central venous pressure is increased. Organs like liver and spleen are enlarged because they are congested with blood.
  • Also, dependent areas like the limbs develop pitting edema because fluid pools in these areas.

Cardiac Glycosides


Description

  • Cardiac glycosides are cardiotonic agents from foxglove or digitalis plants. They exert their effects on the cardiac muscles by affecting levels of intracellular calcium. In turn, the contractility of the muscles is increased.

Therapeutic Action

  • Allows more calcium to enter during contraction, therefore increasing the force of contraction – positive inotropic effect.
  • Consequently, there is increased cardiac output and renal perfusion. A good blood supply to the kidney decreases renin release. This downplays the activity of renin-angiotensin-aldosterone system (RAAS) which causes more fluid to be excreted in the body through urine. A decrease in blood volume eases the workload of the heart.
  • Another mechanism of this drug is to decrease the workload of the heart and slow down relaxation of the cells. Therefore, this drug can increase the strength of contractility without increasing the rate of contraction (negative chronotropic effect).

Indications

  • Primarily indicated for decreasing workload of the heart and relieving HF.
  • Digoxin is especially indicated for atrial flutter, atrial fibrillation, and paroxysmal atrial tachycardia.

Children

  • Widely used in the treatment of heart defects in children but the margin of safety for drug dosage is small so the nurse should recalculate and re-validate the dose with another nurse before administration.
  • Serum level of digoxin and signs of digitalis toxicity should be monitored carefully.

Adults

  • This age group should be educated on manifestations that should be reported signifying drug toxicity.
  • Also, adults are cautioned against utilization of different brands of digoxin as differences in bioavailability can increase the chance of toxicity.
  • It is important for these patients to be taught how to take their own heart rate and assess its regularity.
  • Safety of this drug for pregnant women is not established. As for lactating women, although digoxin enters breast milk, it has not been associated with adverse effects in neonates but caution is still exercised.

Older adults

  • Older adults are more susceptible to drug toxicity because of underlying conditions that would interfere with metabolism and excretion of drug.
  • Renal and hepatic function should always be monitored.
  • Relatives should be instructed on how to take heart rate and assess its regularity.
  • Careful attention should be given to other drugs taken by older adult patients as well as their alternative therapies.

Pharmacokinetics

Route Onset Peak Duration
Oral 30-120 min 2-6 h 6-8 d
IV 5-30 min 1-5 h 4-5 d
T1/2: 30-40 h
Metabolism: N/A
Excretion: urine (unchanged)

Contraindications and Cautions

  • Allergy to any component of digitalis preparation. Prevent severe hypersensitivity reactions.
  • Ventricular tachycardia or fibrillation. These are potentially fatal arrhythmias and should be treated with another drug.
  • Heart block (sick sinus syndrome). Can be worsened by drug’s effect on slowing conduction through AV node
  • Idiopathic hypertrophic subaortic stenosis (IHSS). Obstruction of outflow tract to the aorta can result from increasing the force of contraction and this can lead to other severe problems.
  • Acute myocardial infarction (MI). Increasing the force of contraction can damage the heart muscles more.
  • Renal insufficiency. Drug is excreted through urine and the existing renal insufficiency can contribute to development of drug toxicity.
  • Pregnancy and lactation. Can cause potential adverse effects to the fetus or neonate.

Adverse Effects

  • CNS: headache, weakness, drowsiness, vision changes (most commonly reported is seeing yellow halo around objects)
  • CV: arrhythmias
  • GI: GI upset, anorexia
  •  NURSING ALERT!  Signs and symptoms of digitalis toxicity: anorexia, nausea, vomiting, malaise, depression, irregular heart rhythms (e.g. heart block, heart arrhythmias, and ventricular tachycardia)

Interactions

  • Digoxin immune Fab or DigiFab: antidote; these antibodies bind molecules of digoxin, making them unavailable at site of action. Used when serum digoxin is >10 ng/mL and serum potassium is >5 mEq/L.
  • Verapamil, amiodarone, quinine, erythromycin, tetracycline, cyclosporine: increased therapeutic and toxic effects of digoxin. Combination of digoxin with any of these drugs would warrant decrease in dose of digoxin to prevent toxicity.
  • Potassium-losing diuretics: increased risk of cardiac arrhythmias
  • Thyroid hormones, metoclopramide, penicillamine: decreased therapeutic effects of digoxin. Increasing the dose of digoxin is important.
  • Cholestyramine, charcoal, colestipol, antacids, bleomycin, cyclophosphamide, methotrexate: decreased absorption of digoxin. In this case, digoxin must be taken 2-4 hours after taking any of these drugs.
  • St. John’s wort, psyllium: decreased therapeutic effect of digoxin
  • Ginseng, hawthorn, licorice: increased risk of digoxin toxicity

Nursing Considerations

Here are important nursing considerations when administering cardiac glycosides:

Nursing Assessment

These are the important things the nurse should include in conducting assessment, history taking, and examination:

  • Assess for the mentioned contraindications to this drug (e.g. renal insufficiency, acute MI, hypersensitivity, etc.) to prevent potential adverse effects.
  • Conduct thorough physical assessment before beginning drug therapy to establish baseline status, determine effectivity of therapy and evaluate potential adverse effects.
  • Obtain baseline status for weight while noting recent manifestations that increase or decreases to determine patient’s fluid status.
  • Assess closely patient’s heart rate and blood pressure to identify cardiovascular changes that may warrant a change in digoxin drug dose.
  • Auscultate heart sounds to note the presence of abnormal sounds and possible conduction problems.
  • Determine urinary pattern and output to assess gross indication of renal function.
  • Obtain baseline electrocardiogram (ECG) to identify heart rate and rhythm.
  • Monitor serum electrolyte and renal function test results to determine whether changes in drug dose is needed or not.

Nursing Diagnoses

Here are some of the nursing diagnoses that can be formulated in the use of this drug for therapy:

Implementation with Rationale

These are vital nursing interventions done in patients who are taking cardiac glycosides:

  • Check drug dose and preparation carefully to avoid medication errors because drug has narrow safety margin.
  • Do not administer drug with food and antacids to prevent decreased in drug absorption.
  •  IMPORTANT!  Count apical pulse for one full minute before administering drug to monitor for adverse effects.
    • Drug is withheld if pulse is less than 60 beats per minute in adults and 90 beats per minute in infants.
    • Apical pulse is taken after one hour and if it remains low, nurse must document it, withhold the dose, and inform doctor.
  • Assess pulse rhythm to detect arrhythmias which are early signs of drug toxicity.
  • Weigh the patient daily to monitor for fluid retention and HF. Assess dependent areas for presence of edema and note its degree of pitting to assess severity of fluid retention.
  • Monitor serum digoxin level as ordered (normal: 0.5-2 ng/mL) to evaluate therapeutic dosing and development of adverse effects.
  • Provide comfort measures (e.g. small frequent meals for GI upset, instituting safety measures for drowsiness and weaknesses, and providing adequate room lighting for patients with visual disturbances) to help patient tolerate drug effects.
  • Promote rest periods and relaxation techniques to balance supply and demand of oxygen.
  • Ensure maintenance of emergency drugs and equipment at bedside (e.g. potassium salts and lidocaine for arrhythmias, phenytoin for seizures, atropine in case of clinically significant low heart rate, and cardiac monitor) to promote prompt treatment in cases of severe toxicity.
  • Educate patient on drug therapy including drug name, its indication, and adverse effects to watch out for to enhance patient understanding on drug therapy and thereby promote adherence to drug regimen.

Evaluation

Here are aspects of care that should be evaluated to determine effectiveness of drug therapy:

  • Monitor patient response to therapy through assessing manifestations of HF, arrhythmia, and serum level of digoxin.
  • Monitor for adverse effects (e.g. visual changes, HF, and arrhythmias).
  • Evaluate patient understanding on drug therapy by asking patient to name the drug, its indication, and adverse effects to watch for.
  • Monitor patient compliance to drug therapy.

Phosphodiesterase Inhibitors


Description

  • Phosphodiesterase inhibitors aid in increasing force of myocardial contractility through their enzyme-blocking effect. This in turn, increases the flow of calcium into the myocardial cells.

Therapeutic Action

  • By blocking the enzyme phosphodiesterase, cyclic adenosine monophosphate (cAMP) increases. cAMP stimulates flow of calcium towards the myocardium and thereby, increases force of cardiac contractility.
  • Increases intracellular calcium and prolongs effect of sympathetic stimulation. This leads to three major effects: vasodilation, increased oxygen consumption, and arrhythmias.

Indications

  • Only indicated for short-term treatment of patients not responding to cardiac glycosides, vasodilators, and diuretics.
  •  Drug use is only limited to severe situations because it is associated with fatal ventricular arrhythmias.

Children

  • Drug is not recommended for this age group

Adults

  • This age group should be educated on manifestations that should be reported signifying drug adverse effects.
  • It is important for these patients to be taught how to take their own heart rate and assess its regularity.

Pregnant women

  • Safety of this drug for pregnant and lactating women is not established.

Older adults

  • Are more susceptible to drug toxicity because of underlying conditions that would interfere with metabolism and excretion of drug.
  • Renal and hepatic function should always be monitored. Relatives should be instructed on how to take heart rate and assess its regularity.
  • Careful attention should be given to other drugs taken by older adult patients as well as their alternative therapies.

Pharmacokinetics

Route Onset Peak Duration
Oral Immediate 10 min 8 h
T1/2: 2.3-3.5 h
Metabolism: liver
Excretion: urine and feces

Contraindications and Cautions

  • Allergy to phosphodiesterase inhibitors and bisulfites. Prevent severe hypersensitivity reactions.
  • Severe aortic or pulmonary valvular disease. Exacerbated by increased contraction.
  • Acute MI. Exacerbated by increased contraction and oxygen demand.
  • Conditions with fluid volume deficit. Exacerbated by increased renal perfusion which ultimately leads to increased urine output.

Adverse Effects

  • CV: ventricular arrhythmias, ventricular fibrillation, hypotension, chest pain
  • GI: nausea, vomiting, GI upset, abdominal pain
  • Hema: thrombocytopenia
  • Associated hypersensitivity reactions: vasculitis, pericarditis, pleuritis, and ascites
  • Burning at intravenous injection site

Interactions

  • In solution together with furosemide: precipitate formation

Nursing Considerations

Here are important nursing considerations when administering phosphodiesterase inhibitors:

Nursing Assessment

These are the important things the nurse should include in conducting assessment, history taking, and examination:

  • Assess for the mentioned contraindications to this drug (e.g. fluid volume deficit, acute MI, hypersensitivity, etc.) to prevent potential adverse effects.
  • Conduct thorough physical assessment before beginning drug therapy to establish baseline status, determine effectivity of therapy, and evaluate potential adverse effects.
  • Obtain baseline status for weight while noting recent manifestations that increases or decreases to determine patient’s fluid status.
  • Assess closely patient’s heart rate and blood pressure to identify cardiovascular changes that may warrant change in drug dose.
  • Determine urinary pattern and output to assess gross indication of renal function.
  • Obtain baseline electrocardiogram (ECG) to identify heart rate and rhythm.
  • Monitor serum electrolyte, complete blood count, and renal and hepatic function test results to determine whether changes in drug dose is needed or not.

Nursing Diagnoses

Here are some of the nursing diagnoses that can be formulated in the use of this drug for therapy:

Implementation with Rationale

These are vital nursing interventions done in patients who are taking phosphodiesterase inhibitors:

  • Protect drug from light to prevent drug from degradation.
  • Ensure patency of intravenous access to promote safe administration of drug.
  • Weigh patient daily and fluid intake and output to evaluate resolution of HF.
  • Assess skin condition, noting presence of petechiae and other manifestations of easy bruising and bleeding to assess presence of thrombocytopenia.
  • Monitor intravenous injection site to promote prompt interventions in cases of burning sensation and/or irritation.
  • Provide comfort measures (e.g. small frequent meals for GI upset, instituting safety measures for drowsiness and weaknesses, and providing adequate room lighting for patients with visual disturbances) to help patient tolerate drug effects.
  • Educate patient on drug therapy including drug name, its indication, and adverse effects to watch out for to enhance patient understanding on drug therapy and thereby promote adherence to drug regimen.

Evaluation

Here are aspects of care that should be evaluated to determine effectiveness of drug therapy:

  • Monitor patient response to therapy through assessing for manifestations of resolution of HF.
  • Monitor for adverse effects (e.g. thrombocytopenia, HF, and arrhythmias).
  • Evaluate patient understanding on drug therapy by asking patient to name the drug, its indication, and adverse effects to watch for.
  • Monitor patient compliance to drug therapy.

Practice Quiz: Cardiotonic-Inotropic Agents


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Questions


1. The primary treatment for heart failure (HF) is ___________.

A. Increasing the heart rate so the heart can pump more blood
B. Decreasing the heart rate so the heart can rest
C. Increasing contractility so the heart will be able to pump more blood
D. Decreasing contractility to prevent muscle fatigue

2. The most common cause of HF is ______________.

A. Hypertension
B. Valvular heart diseases
C. Cardiomyopathy
D. Coronary artery disease (CAD)

3. Digoxin was prescribed to a patient with ventricular tachycardia. What should the nurse do?

A. Administer the drug as ordered.
B. Discuss the order with the doctor.
C. Discontinue other intravenous medications before administering digoxin.
D. Count apical pulse for one full minute before administering.

4. What is the antidote for digoxin intoxication?

A. Diphenhydramine
B. Atropine sulfate
C. Digoxin immune fab (Digibind, DigiFab).
D. Phosphodiesterase inhibitors

5. An infant who is receiving cardiac glycosides has an apical pulse of 80 beats per minute. Which is the best nursing intervention for this assessment finding?

A. Administer drug as ordered.
B. Withdraw the drug and notify doctor.
C. Assess apical pulse every hour for the next five hours.
D. Decrease drug dose and administer.

6. What signals the novice nurse that intravenous milrinone was combined to furosemide in management of patients with heart failure?

A. Presence of bubbles
B. Pink discoloration of the solution
C. Formation of precipitates
D. No obvious sign. Solution is clear.

7. What is the therapeutic level for digoxin?

A. 0.5-2 ng/mL
B. 1.5-2 ng/mL
C. 0.5-1.5 mg/mL
D. 0.5-2 mg/mL

8. In severe cardiac glycoside toxicity, all of the following should be in the bedside, except _________.

A. Lidocaine
B. Phenytoin
C. Calcium channel blocker
D. A and B only

Answers and Rationale


1. Answer: C. Increasing contractility so the heart will be able to pump more blood.

The complete answer would be to make the heart beat efficiently, that is to increase its force of contraction without increasing the heart rate. Through this, more blood is pumped every beat without overwhelming the heart because rate of contraction is not increased.

2. Answer: D. Coronary artery disease (CAD).

It accounts for 95% of HF cases. CAD results to insufficient supply of blood in the heart. This leads to hypoxia and loss of function of heart muscles.

3. Answer: B. Discuss the order with the doctor.

Digoxin is contraindicated in patients with ventricular tachycardia and fibrillation because these are potentially fatal arrhythmias and need to be treated with other medications.

4. Answer: C. Digoxin immune fab (Digibind, DigiFab).

Digoxin Immune Fab or DigiFab, DigiBind should be administered for serum digoxin levels of >10 ng/mL and serum potassium level of >5 mEq/mL.

5. Answer: B. Withdraw the drug and notify doctor.

A low apical pulse (less than 90 for infants and less than 60 for adults) can signal drug toxicity.

6. Answer: C. Formation of precipitates.

Phosphodiesterase inhibitor-furosemide combination should be avoided. Alternate lines should be used if both of these drugs are given intravenously.

7. Answer: A. 0.5-2 ng/mL.

8. Answer:  C. Calcium channel blockers.

Lidocaine and potassium salts are used to treat arrhythmias. Phenytoin is for treatment of seizures. Other medications and equipment at the bedside include atropine for treatment of increased heart rate, and a cardiac monitor.

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