side effects of cardiac glycosides

Side Effects of Cardiac Glycosides

Cardiac glycosides are mainly prescribed for the treatment of cardiac arrhythmia and congestive heart failure. This Buzzle write-up provides information on the mechanism of action and side effects of cardiac glycosides.

Did You Know?
Though it is believed that Egyptians and Romans were aware of the therapeutic properties of cardiac glycosides found in the foxglove plant, it is a British botanist, chemist, and physician named William Withering who is credited with the discovery of the foxglove plant. He described the therapeutic uses, as well as the toxicity of the Digitalis purpurea plant in his work An Account of the Foxglove, and Some of Its Medical Uses (1785).
A class of drugs recommended for individuals affected by irregular heartbeats or congestive heart failure, cardiac glycosides are the active ingredients in drugs such as digoxin, digitoxin, and deslanoside. These drugs get their name from the Digitalis genus, which comprises about 20 species of herbaceous shrubs. Though the foxglove plant had long been used in folk medicines, it was Withering who believed that foxglove was the active ingredient of a traditional herbal remedy that helped in the treatment of dropsy (edema or swelling associated with heart failure). Though cardiac glycosides are still used for the treatment of atrial fibrillation and heart failure, it is also associated with toxicity. In fact, the consumption of the leaves of the Digitalis purpurea plant and Digitalis lanata in large amounts can lead to certain untoward effects. Similarly, an overdose of digoxin or other drugs that contain cardiac glycosides can have an adverse effect on the user's health.
Mechanism of Action
To understand the mechanism of action of cardiac glycosides, let's first understand the processes involved in the contraction of the heart. The contraction of the heart muscle is dependent on the creation of the electrical impulses, which in turn involves the passage of charged atoms of sodium, calcium, and potassium inside the molecular channels located inside and between the cells. In case of a resting potential, the inside of the plasma membrane is negatively charged, and the membrane of such a muscle cell is polarized due to the balance created by the potassium ions inside the cell and sodium ions outside the cell. Depolarization occurs with the opening of sodium ion channels and their passage into the cardiac muscle cell. These channels close rapidly. The elevated intracellular sodium triggers the opening of the calcium channels. Calcium ions enter from the sarcoplasmic reticulum within the cell, as well as from outside the cell through the slow-opening calcium channels in the plasma membrane. These calcium ions bind to the troponin/tropomysin complex. Thereafter, tropomysin moves out of the way of the active site on the actin filament. Actin and myosin filaments bind, thereby forming cross-bridges. The thin actin filament slides past the thick myosin filament. The sliding of the filaments gives rise to muscle contraction. While the calcium channels open, the leakage of potassium ions from the cells is restricted. The release of the calcium ions and restricted leakage of potassium ions leads to extended depolarization. However, potassium channels open, diffusing the potassium ions out of the cell, thereby leading to repolarization. The calcium channels close, which brings about the original polarization of the membrane. However, sodium ions are inside the cell, whereas potassium ions are outside the cell. After the muscle has contracted, calcium ATPase pump transports the calcium out of the cell into the sarcoplasmic reticulum. The cardiac muscle can contract only when the concentration of the potassium and sodium ions are restored to the resting potential states. This exchange of sodium and potassium ions requires energy, which in turn is provided by an enzyme called sodium-potassium adenosine triphosphatase. It is believed that cardiac glycosides inhibit this enzyme, which causes reduced sodium exchange with potassium. As a result, the intracellular sodium is elevated, which leads to increased intracellular calcium. It is an increase in the intracellular calcium concentration that is believed to bring about a positive inotropic effect. Cardiac glycosides have a positive inotropic action, which means that these drugs can improve the heart's strength of contraction. They most often are used to treat heart failure and atrial fibrillation. In individuals affected by heart failure, these drugs can cause a reduction of the size of the heart in diastole, which can increase cardiac output. The cardiac output increases with an increase in the force of contraction. As plateau phase of cardiac depolarization gets prolonged, ventricular contraction gets slowed. As a result, there's more time for the ventricles to fill. These drugs could be prescribed for the treatment of atrial fibrillation and atrial flutter, which are both characterized by an abnormal heart rhythm. Though the increased force of contraction can help improve the pumping function of the heart, cardiac glycosides are not the first choice for congestive heart failure. This is mainly due to the adverse effects that are associated with the use of these drugs.
Side Effects
The dangers or health risks associated with cardiac glycoside are mostly related to an overdose. Taking it in ways other than what has been recommended by the healthcare provider can lead to certain adverse effects. The accumulation of the drug in the body could cause the following symptoms: Confusion Disorientation Lethargy Fatigue Headaches Vision-related issues (double vision, blurred vision, or halos around things) Anorexia Nausea Vomiting Loss of appetite Abdominal pain Slow (bradycardia) or rapid (tachycardia) heartbeats Gynecomastia in men Cardiac glycosides such as digoxin can induce dysrhythmia due to the interference in the electrical conduction in the heart muscle. It can also lead to cardiotoxicity, which might lead to abnormally slow heartbeats. The drug should not be taken by those who are allergic to any of the ingredients present in the drug. Medical help must be immediately sought in case one develops anaphylaxis, which is a life-threatening allergic reaction that is characterized by the following symptoms: Hives Lightheadedness Swelling of the face, lips, tongue, or throat Breathing problems due to narrowing of the airways
Drug Interactions
It is advisable to inform the healthcare provider about the drugs that you are taking. To avoid adverse drug interactions, inform if you are taking any of the following drugs: Thiazide diuretics Loop diuretics The aforementioned drugs can put one at an increased risk of developing hypokalemia (low potassium levels), which can make one susceptible to dysrhythmia. Moreover, increased toxicity of these drugs has been associated with low potassium levels. Angiotensin-converting enzyme inhibitors (ACE inhibitors) Angiotensin II receptor blockers (ARBs) ACE inhibitors and ARBs can put the users at a risk of developing high potassium levels (hyperkalemia), which can lower the effects of cardiac glycosides. The risk of toxicity could also increase, if digoxin is taken with quinidine. Concurrent use with a calcium channel blocker called verampil can also lead to elevated plasma levels of digoxin. If one is also taking dopamine, it would be best to monitor cardiac function with the help of ECG. This is due to the fact that dopamine can also increase the rate and force of cardiac muscle contraction. This drug is placed in the Pregnancy category C, which is why it is contraindicated in case of pregnant women. It is also contraindicated in case of individuals affected by heart block (second/third degree), ventricular tachycardia, and ventricular fibrillation. Caution must be exercised in case of individuals affected by low potassium levels, advanced heart failure, kidney-related problems, partial AV block, etc.
Though the use of this drug has declined, cases of cardiac glycoside toxicity are still reported. Out of 2513 cases of exposure to cardiac glycoside that were reported to US poison control centers in 2011, 132 patients were diagnosed with major toxicity and 27 fatalities were reported. Thus, it is extremely essential to take this drug in prescribed doses for the duration recommended by the healthcare provider. Disclaimer: The information provided in this article is solely for educating the reader. It is not intended to be a substitute for the advice of a medical expert.

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