Cardiac glycosides are drugs that have a positive effect on the beating power of the heart while lowering the heart rate. They are used to treat heart disease.
What are cardiac glycosides?
Cardiac glycosides are often referred to as digitalis. This name is in reference to the foxglove (digitalis), which contains cardiac glycosides in fairly high doses. Cardiac glycosides are active substances whose action is related to the heart. Chemically, the active ingredients are characterized by three deoxy sugars that occur very rarely in nature. These deoxy sugars are attached in a glycosidic bond to a steroid derivative. In some cases, the glycosidic bond is also present in derivatives of the gonan. Cardiac glycosides are also often referred to as digitaloids or, more simply, digitalis. This designation is in reference to the foxglove (digitalis), which contains cardiac glycosides in quite high dosages. Today, only digitoxin and digoxin are used clinically. Digitoxin is a steroidal glycoside from the cardiac glycoside class of active ingredients. It is obtained from the red foxglove (Digitalis purpurea). Digoxin is also a digitalis glycoside from the foxglove. Digoxin and digitoxin belong to the endogenous glycosides. This means that they function as hormones. In humans, digoxin is formed in small quantities in the adrenal gland. Cardiac glycosides are used primarily in the treatment of acute and chronic heart failure. They are also used in the treatment of atrial fibrillation and atrial flutter. Cardiac glycosides are usually administered in tablet form. Only strophanthin is given intravenously because of its poor absorption rate. Excretion of the substances occurs mainly through the liver and bile.
Pharmacologic action
Cardiac glycosides exhibit a positive inotropic effect. The term inotropy is used in describing the influence on the contractility of cardiac muscle tissue. In positive inotropy, the contractile force of the heart is increased. This increase is based on an increased provision of calcium ions in the cardiac muscle cells. To achieve this, cardiac glycosides bind to the α-subunits of sodium–potassium ATPase, inhibiting the active transport of potassium ions into the cell. At the same time, the efflux of sodium ions from the cell is impeded. The sodium concentration within the cell increases. As a result, the sarcoplasmic reticulum, a special form of the endoplasmic reticulum within muscle cells, takes up more calcium ions. These calcium ions are available to the heart muscle for contraction, so that the force of contraction increases. At the same time, cardiac glycosides also have a negative dromotropic effect. They lower the nerve conduction velocity. This effect is achieved by increasing the initial outflow of potassium from the muscle cell. As a result of the slowed conduction of the stimulus, the heart contracts less frequently. This allows for a more vigorous contraction with more ejection volume. Cardiac glycosides also have a positive bathmotropic effect. Bathmotropy refers to the influence of stimulus thresholds and the excitability of the heart. Positively bathmotropic substances lower the excitability threshold so that the heart can contract more easily.
Medical application and use
The main uses of cardiac glycosides are acute and chronic heart failure. In heart failure, the heart is no longer able to supply the body with sufficient blood. Acute heart failure develops within a few hours to days. Causes include cardiac arrhythmias, cardiac tamponade, pulmonary embolism, valvular insufficiency or myocardial infarction. Chronic heart failure develops within months to years. Causes include chronic lung disease. Cardiac glycosides are also administered for atrial fibrillation or atrial flutter. Atrial fibrillation and atrial flutter can be completely asymptomatic. Often, those affected only notice a drop in performance. However, symptoms such as dizziness, shortness of breath, anxiety, or chest pain are also possible.
Risks and side effects
The use of cardiac glycosides and, in particular, the use of digoxin are controversial. For example, recent studies show that patients with heart failure treated with digoxin had a 72 percent higher mortality than patients treated with other drugs.Cardiac glycosides also have a fairly narrow therapeutic window. Even small deviations from the optimal dose can lead to undesirable effects and symptoms of poisoning. The therapeutic and toxic ranges overlap in many cases. Patients often complain of loss of appetite and nausea. Digitalisin intoxication due to overdose manifests as vomiting, diarrhea, and cardiac arrhythmias. Headaches, inner restlessness and even psychotic states of confusion can also occur. Typical of digitalis intoxication is green-yellow vision. In addition, those affected see bluish asterisks or dots. These phenomena are called cornflower phenomenon. Causally, intoxications are treated with inhibition of further drug absorption. Gastric lavage is performed for this purpose. Alternatively, activated charcoal can be administered. In addition, the circulation between the intestine and the liver is interrupted by the administration of colestyramine. Symptomatically, mainly the electrolyte disturbances are compensated and the cardiac arrhythmias are treated. It is also possible to administer a digitalis antidote. Here, however, there is a risk of an allergic reaction, which can extend to allergic shock. It should be noted that the potency of cardiac glycosides can be influenced by various drugs and also by fluctuating concentrations of electrolytes in the blood. Therefore, the use must always be in an individual dosage. In addition, close-meshed blood controls are required when taking cardiac glycosides. The cardiac glycoside digoxin must not be administered in renal insufficiency. Digitoxin is contraindicated in combined renal and hepatic insufficiency.
