Digoxin: Mechanism of Action & Drug Interactions

Instructor: Adrianne Baron

Adrianne has a master's degree in cancer biology and has taught high school and college biology.

This lesson is going to discuss the drug, digoxin. We will gain an understanding of how the drug works and the drugs that interact with it in different ways.


We depend on all of the organs in our bodies to carry out their designated functions. When something goes wrong with one of our organs, this changes how our bodies feel and work. This may not be that big of a deal depending on which organ is affected. However, there are organs that are very important, and problems with these organs can have major consequences. The brain, heart, and lungs must do their jobs properly in order for us to stay alive and well.

Our hearts have the task of pumping blood throughout the body. Every other organ in the body depends on the action of the heart in order to get everything they need and get rid of everything they don't need. So problems with heart function must be addressed very quickly before it costs us our lives.

There are several drugs, procedures, and surgeries that can help to get the heart back up to par. One drug is digoxin. This medication is categorized as an antiarrhythmic drug that can help to maintain a proper heartbeat. An arrhythmia is an abnormal heartbeat. There are many different types of arrhythmias, but digoxin is used to treat only ones that affect the upper chambers of the heart, such as atrial fibrillation. It is also used to treat heart failure.

Mechanism of Action

You may be wondering how digoxin is able to correct an abnormal heartbeat. Well we first must remember a couple of things.

  1. We have to remember that the heart is a muscle.
  2. We have to remember what causes muscles to contract. After all, that heartbeat is really the heart muscles contracting.

The heart muscle contracts when a certain amount of electrolytes, sodium (Na+), potassium (K+) and calcium (Ca2+) , are on either side of the cell membranes in the heart muscle cells.

Muscle contractions depend on the sodium-potassium pump
Diagram of sodium-potassium pump

The electrolytes are moved from one side of the cell membrane to the other through the sodium-potassium pump. When enough sodium is on the outside of the cell, and calcium on the inside, fibers of the heart muscle will contract for a period of time. The muscles relax when the sodium and calcium move to the opposite sides of the cells again.

Some arrhythmias are due to malfunctions of this sodium-potassium pump, resulting in calcium levels being too low on the inside of the cell to cause a contraction. Digoxin helps by interfering with the action of the sodium-potassium pump. This leads to an increase of sodium inside the cell. When sodium within the cell increases, another electrolyte mover pushes the excess sodium out of the cell. This then pushes calcium into of the cell, leading to heart muscle contractions.

The goal when taking digoxin is to keep the amount of drug in the bloodstream consistent, so that it is able to continuously have this effect on the heart muscle. The heart will beat at regular, normal intervals as long as the amount of drug is maintained. If it is altered, then the heart will go back to beating abnormally.

Drug Interactions

Every drug that we take alters the way the body functions, and, as such, has the potential to interact with other drugs. Some interactions can have a positive effect, while other interactions are not good, and sometimes outright dangerous.

If you think that taking more than one drug that affects the heart could cause a drug interaction for digoxin, then you are on to something. Other drugs, like quinidine and propafenone, that are designed to also alter the heart rhythm, can interact with digoxin and lead to too much digoxin being in the body. This can cause the heart to not beat properly and make the side effects of digoxin more pronounced.

Another set of drugs that may increase the levels of digoxin are blood pressure drugs such as verapamil and dilitiazem. These alter the amount of fluids in the blood, and are harsh on the kidneys. The kidneys are responsible for removing digoxin from the body, so if they aren't functioning right, then they cannot remove digoxin and therefore the amount of digoxin in the blood continues to go up.

The drug tolvaptan works to decrease the amount of sodium in your body. You can probably already see the problem here. Both digoxin and tolyaptan are doing something to sodium, so they probably interact in some way. Taking both of these drugs at the same time increases the amount of digoxin in the body as well. Tolyaptan also decreases kidney function, which further increases digoxin levels as described above.

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