Cardiac Glycosides

What Are They, What Are They Used For, How Do They Work, Side Effects, and More

Author: Jennifer Cheung, RN, BS

Editors: Antonella Melani, MD, Nimmit Vyas, PharmD

Illustrator: Meg Gullotto


What are cardiac glycosides?

Cardiac glycosides are a class of medications commonly derived from foxglove plants, such as Digitalis lanata and Digitalis purpurea. The most commonly prescribed cardiac glycoside is digoxin.

What are cardiac glycosides used for?

Cardiac glycosides are used to treat patients with atrial fibrillation and atrial flutter. In addition, they can be prescribed for congestive heart failure when the use of other medications fails. 

How do cardiac glycosides work?

The mechanism of action of cardiac glycosides involves inhibiting the Na+ K+ ATPase enzyme, also known as the sodium-potassium pump. This causes sodium to build up inside the heart cells, decreasing the ability of the sodium-calcium exchanger to push calcium out of the cells, consequently causing calcium to build up in the sarcoplasmic reticulum. Increased intracellular calcium results in a positive inotropic effect, which in turn has the effect of increasing the force of the heart’s contractions.

Which receptor does the cardiac glycoside digoxin bind to?

Digoxin reversibly binds to a receptor site on the Na+ K+ ATPase enzyme, inhibiting its function of exchanging sodium and potassium across the cell membrane.

What are potential side effects of cardiac glycosides?

Cardiac glycosides can have some potential side effects, and can also be an important cause of poisoning and toxicity. The most frequent side effects of cardiac glycosides include unusual tiredness and fatigue, anxiety, and hallucinations. In addition, symptoms of toxicity can include visual disturbances, nausea or vomiting, and cardiac arrhythmias. 

Moreover, taking high doses of cardiac glycosides can cause electrolyte imbalances involving sodium, potassium, calcium, and magnesium. In addition, the concurrent use of certain medications can increase digoxin levels in the blood. These medications include diuretics, calcium channel blockers, amiodarone, cyclosporine, quinidine, and nonsteroidal anti-inflammatory drugs (NSAIDs). Finally, decreased renal function can also result in increased serum digoxin levels, as digoxin is primarily excreted through the kidneys.

Side effects can often be alleviated by reducing the dosage of digoxin. Additionally, individuals who have cardiac arrhythmias should be monitored with blood tests for serum levels of digoxin and electrolytes, as well as an electrocardiogram to assess the heart. In severe toxicity cases, administration of digoxin immune fab may be helpful to rapidly reduce serum digoxin levels.

Do cardiac glycosides decrease heart rate?

At low therapeutic doses, cardiac glycosides can have the effect of reducing heart rate and increasing gastrointestinal activity for individuals, as they act on the parasympathetic nervous system. The parasympathetic nervous system is the part of the central nervous system responsible for relaxing our bodies and conserving energy.

Are cardiac glycosides still used?

Cardiac glycosides are still in use. However, they can cause severe side effects and toxicity, so they’ve been replaced with other medications as first-line treatment; for instance, ACE inhibitors and beta-blockers. Cardiac glycosides are contraindicated in ventricular fibrillations. 

What are the most important facts to know about cardiac glycosides?

Cardiac glycosides are a class of medications that inhibit the  Na+ K+ ATPase enzyme, increasing the force of heart contractions. The most commonly prescribed cardiac glycoside is digoxin, which can be used to treat atrial fibrillation, atrial flutter, and congestive heart failure. However, cardiac glycosides can cause severe side effects and toxicity, so they’ve been replaced with other medications as first-line treatment, such as the ACE inhibitors and beta-blockers. Cardiac glycosides are contraindicated in ventricular fibrillations. 

Related links

Stroke Volume, Ejection Volume, Cardiac Output
Positive Inotropic
Congestive Heart Failure
Resting membrane potential
Atrial fibrillation
Atrial flutter

Resources for research and reference

Kapitanyan, R. (2017). Cardiac glycoside plant poisoning. In Medscape. Retrieved July 27, 2020, from https://emedicine.medscape.com/article/816781-overview

Fearnley, C. J., Roderick, H. L., & Bootman, M. D. (2011). Calcium Signaling in Cardiac Myocytes. Cold Spring Harbor Perspectives in Biology, 3(11). Retrieved July 27, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3220352/

Katzung, B. G. (2018). Basic and Clinical Pharmacology (14 edition). New York, NY: McGaw-Hill.

Whittlesea, C. & Hodson, K. (2019). Clinical Pharmacy and Therapeutics (6 edition). Oxford, UK: Elsevier.

Zipes, D. P., Libby, P., Bonow, R.O., Mann, D. L., Tomaselli, G. F., & Braunwald, E. (2019). Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine (11 edition). Philadelphia, PA: Elsevier.