Cardiac glycosides

In 1775, Dr. William Withering (1741 - 1799) was the first to describe both the effect of cardiac glycosides on "dropsy" (heart failure) and digitalis overdose. This marked the beginning of the digitalis era (Bühring 2016).

Cardiac glycosides include natural substances from various plants. They can be found, for example, in woolly foxglove, red foxglove, lily of the valley and sea onion. In pharmacotherapy, methylated or acetylated glycoside derivatives are generally used; in Germany mainly digoxin, digitoxin and semi-synthetic glycosides (Erdmann 2009).

Pharmacodynamics

Cardiac glycosides cause an inhibition of the

- cardiac Na+

- K+

- ATPase membrane pump (Kasper 2015)

- Increase in the intracellular Na+ concentration (Herold 2021)

The basic effects of cardiac glycosides are therefore:

- Positive bathmotropic (increase in the excitability of the heart)

- Positive inotropic (increasing the contractility of the heart)

- Negative dromotropic (slowing of the conduction velocity)

- Negative chronotropic (slowing of the heart rate at rest)

(Herold 2021)

The indirect effect via the excitation of the vagus nerve causes

• in the AV node:
  • Prolongation of the refractory period
  • Slowing of the conduction of excitation (Lüllmann 2006)
• in the sinus node:
  • Reduction in the frequency of the pacemaker
  • Reduction of the heart rate (Lüllmann 2006)

The direct effect of the glycosides causes:

• in the ventricular musculature
  • a shortening of the refractory period
  • an increase in the conduction velocity
• in the Purkinje fibers to a
  • shortening of the refractory period with possible occurrence of extrasystoles
• in the atrial musculature
  • shortening of the refractory period with an increase in automatism
• in the AV node
  • increase in the refractory period and slowing of the conduction of excitation
• in the myocardial cell to an
  • Inhibition of the Na+ / K+- ATPase
  • Intracellularly to an increase in Ca2+ with an increase in contractile force (Boeckh 2002)

The systemic effects on the entire body are:

• Disappearance of dyspnea
• Reduction of venous congestion symptoms
• Onset of flushing out and significant reduction in edema
• Decrease in heart rate due to
  • Decrease in sympathetic tone
  • Excitation of the vagus nuclei
  • Reduction in central venous pressure and thus relief of the stretch receptors (Lüllmann 2006)

Indication

- Tachyarrhythmia in atrial fibrillation (Herold 2021) and atrial flutter (Hitchings 2020), if beta blockers do not allow sufficient control of the frequency (Herold 2021)

- Heart failure with severe symptoms. From stage NYHA III, add-on therapy with digitalis can be attempted if basic therapy has been exhausted (Herold 2021).

Dosage and method of administration

Digoxin:

The therapeutic range is between 0.5 - 0.9 ng / ml, the half-life is 40 h (Herold 2021). When administered intravenously, the effect sets in after 10 - 40 min, when administered orally only after several hours. Digoxin is 50 - 90 % bioavailable. Elimination is exclusively renal (Erdmann 2009).

The first dose of digoxin should be administered as a slow saturation over 2 - 5 days at 1.0 - 1.5 mg / d. The maintenance dose is 0.25 - 0.2 mg / d (Erdmann 2009).

Digitoxin:

The therapeutic range is between 8 - 18 ng / ml, the half-life is 6 - 8 h (Herold 2021). When administered intravenously, the effect sets in after 10 - 40 min, with oral administration only after several hours. Digitoxin is up to 100 % bioavailable. Elimination takes place both renally and hepatically (Erdmann 2009).

The first dose of digitoxin should be administered as a slow saturation over 2 - 5 days at 1.0 - 1.5 mg / d. The maintenance dose is 0.07 mg / d (Erdmann 2009).

Undesirable effects

In general, it can be said that cardiac glycosides are well tolerated (Erdmann 2009). Undesirable side effects can only occur with a plasma level in the therapeutic range if there is a reduced glycoside tolerance due to certain diseases or conditions (Herold 2021).

Otherwise, side effects of digitalis intoxication only occur in the form of various types of cardiac arrhythmia, gastrointestinal complaints and neurological symptoms (Herold 2021).

Contraindication

Contraindications for cardiac glycosides are:

- Bradycardic arrhythmias such as carotid sinus syndrome, sick sinus syndrome, SA block

- WPW syndrome

- Ventricular tachycardia

- Hypokalemia

- Hypercalcemia (Herold 2021)

- In the presence of a muscular ejection obstruction, e.g. in the context of subvalvular aortic valve stenosis

- Aortic valve insufficiency (can lead to a worsening of the haemodynamic situation)

- Acute hypoxic muscle damage (Lüllmann 2006)

- Ventricular arrhythmias

- AV block II°

- Hypomagnesemia (Hitchings 2020)

Interactions

A digitized patient should never be administered calcium i.v., as there is a risk of tachyarrhythmias and even ventricular fibrillation (Herold 2021).

There are also interactions with loop and thiazide diuretics, as these can cause hypokalemia. Other medications such as amiodarone, calcium channel blockers, quinine, spironolactone and some antibiotics can increase the toxic effect of cardiac glycosides (Hitchings 2020).

Preparations

- Lanicor: The maintenance dose is 0.25 mg / d

- Novodigal: The maintenance dose is 0.2 mg / d

- Digacin: The maintenance dose is 0.25 mg / d (Erdmann 2009)

An effective drug level is reached after 5 - 10 days with this dosage (Erdmann 2009).

- Cardiac glycosides have a very low therapeutic range of 1.5 - 2.0, so the risk of digitalis intoxication is high (Herold 2021).

- The excretion of digoxin must be adjusted in the event of renal insufficiency, but not that of digitoxin. From a GFR of < 60 ml / min. digitoxin should therefore be preferred (Herold 2021).

- As cardiac glycosides prolong the QT time, caution should be exercised with other substances with the same mode of action (Lüllmann 2006).

- To date, cardiac glycosides have not been shown to have any effect on mortality (Herold 2021).

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