Digoxin: Effects, Uses & Risks

Digoxin, like digitoxin, is extracted from foxglove (Digitalis lanata or Digitalis purpurea), which is why both are classified as digitalis glycosides. Cardiac glycosides increase the beating power of the heart muscle while lowering the heart rate.

What is digoxin?

Digoxin is a substrate of the P-glycoprotein from the group of so-called cardioactive glycosides (also cardiac glycosides). Digoxin is a substrate of the P-glycoprotein from the group of so-called cardiac glycosides (also cardiac glycosides). The active ingredient is extracted from Digitalis lanata (woolly foxglove) and is used in particular for heart failure (cardiac insufficiency) and atrial flutter and fibrillation. The cardiac glycoside increases the contractility and excitability of the heart muscle while slowing down the rate and conduction of excitation. Digoxin itself exists either as crystals or as a crystalline, whitish powder that is virtually impossible to dissolve in water.

Pharmacologic action

As a cardiac glycoside, digoxin has several effects on the myocardium (heart muscle). First, the drug increases the myocardium‘s beating force and rate of contraction (positive inotropic effect). On the other hand, it decreases the heartbeat rate (negative chronotropic effect) and slows down the conduction of excitation of the heart muscle from the area of the atrium (atrium) to that of the ventricles or heart chambers (negative dromotropic effect). In addition, digoxin increases excitability, especially that of the ventricular muscles (positive bathmotropic effect). The above mechanisms of action cause an increased stroke volume, which in turn has a positive effect on blood flow in the kidneys and increases urine excretion. Digoxin also has a direct renal effect via inhibition of Na+ reabsorption. The action of digoxin here is based on inhibition (inhibition) of the membrane-bound α-subunits of Na+/K+-ATPase in myocardial cells. Na+/K+-ATPase is a kind of pump that transports ions (sodium, potassium, calcium, chloride) into the cell interior or outward to maintain the specific ionic balance of the cell. Inhibition of Na+/K+-ATPase in turn leads to inhibited Na+ and Ca2+ exchange. The increased Ca2+ concentration in myocardial cells results in Ca2+ uptake into the sarcoplasmic reticulum and thus an increase in contraction velocity and beating force, because cardiac myocytes require calcium for their contractile activity, and with increasing calcium uptake, the contractile force increases. The inhibited Na+/K+-ATPase may also lead to an improvement in the sensitivity of the so-called baroreceptors (also called pressor receptors or pressure sensory corpuscles) and corresponding neurohormonal effects. Digoxin is primarily excreted renally, via the kidneys, and has a half-life of 2 to 3 days.

Medical use and application

Digoxin is used primarily in the context of therapy for acute and chronic heart failure (myocardial insufficiency) and certain cardiac arrhythmias (atrial fibrillation, atrial flutter) that can be attributed to delayed conduction of excitation. The active ingredient is usually administered orally in tablet form or, less frequently, intravenously as an injection solution. Due to the limited therapeutic range, carefully monitored and individualized dosage adjustment is recommended, especially in the case of renal function impairment. Digoxin therapy is contraindicated in the presence of hypersensitivity, ventricular tachycardia and/or fibrillation, thoracic aortic aneurysm (dilatation of the aortic vessel wall at chest level), second- and third-degree AV block (bradycardic arrhythmia), and hypertrophic cardiomyopathy (thickened heart muscle) with increasing obstruction. Hypercalcemia, hypokalemia, hypomagnesemia, and oxygen deficiency may also be contraindicators. Because the action of digoxin increases the oxygen demand of myocardial cells, therapy with this agent may be unfavorable in chronic or acute myocardial ischemia (e.g., in the context of coronary artery disease). Furthermore, in the context of therapy with digoxin, various interactions with other drugs must be considered. Calcium (especially intravenously) as well as diuretics or laxatives increase the glycoside toxicity of digoxin.Parallel therapy with calcium channel blockers, antiarrhythmic drugs (including amiodarone, quinidine), itraconazole, captopril, spironolactone, atropine, and certain antibiotics causes a strong increase in digoxin concentration. In addition, bradycardic effects are enhanced by beta-blockers and cardiac arrhythmias are favored by certain drugs (including suxamethonium chloride, sympathomimethics, phosphodiesterase inhibitors). Drugs that cause an increase in potassium levels reduce the positive inotropic effect of digoxin.

Risks and Side Effects

As a result of the severely limited therapeutic range of digoxin, it can be rapidly overdosed and lead to intoxications that can manifest symptomatically in the form of cardiac arrhythmias (AV block, ventricular fibrillation, extrasystoles), among other symptoms. Accordingly, individual therapy monitoring is important. In addition, side effects such as loss of appetite, vomiting, diarrhea, nausea, weakness, headache, facial pain and drowsiness can often be observed in the context of digoxin therapy. In rare cases, digoxin therapy causes perceptual disturbances, visual disturbances, disorientation, and/or psychosis. Very rarely, digoxin therapy is associated with convulsions, enlargement of the male mammary gland, blood count abnormalities, and/or hypersensitivity reactions.