Synonyms
cardiac glycosides
- Drugs Cardiac arrhythmia
- Digitoxin
Digoxin is an active ingredient that belongs to the group of cardiac glycosides. Among other things, it improves the efficiency of the heart and is therefore prescribed, for example, in cases of heart failure (cardiac insufficiency).
Origin
Digoxin and digitoxin can be extracted from the same plant: The foxglove (Latin: digitalis), therefore they are sometimes described synonymously with the term digitalis or digitalis glycosides.
Effect and mechanism of action
Digoxin works on the heart as follows:
- Increase there the contact force of the heart muscles (positive inotropic)
- Delayed transmission of excitation from the atrial region (antrum) to the ventricles (ventricles) (negative dromotropic)
- Reduction of the beat frequency (negative chronotropic effect).
In order to contract, the heart muscle – like all other muscles of the body, both the striated skeletal muscles, which are tensed at random, and the smooth muscles of vessels and organs, which contract involuntarily – needs calcium. In the heart, the principle applies: the more calcium, the stronger the contraction force. And the higher this force, the more blood can be pumped with a heartbeat.
The heart consists of many heart muscle cells, which contain contractile elements, thus making a contraction of the heart possible at all. These filaments are called sarcomeres. The calcium must therefore be present within the cell (intracellularly) in order to be able to influence the force, since this is where the sarcomeres are located.
In order to understand the mechanism of cardiac glycosides, it is necessary to delve a little further into the biochemistry of the cell: Every cell needs a certain ionic balance to survive. This means that certain concentrations of potassium, sodium, chloride and calcium, among others, must be present inside and outside the cell. If these concentrations are exceeded, the cell would burst (water influx at high intracellular ion concentration to achieve charge balance between inside and outside) or shrink (water outflow at high extracellular charge concentration to achieve dilution of the higher concentration of particles outside).
This principle of distributing water in the direction of higher concentration is called osmosis. In order to prevent an osmotic equilibrium from being established, as this would be fatal for the cell, there are pumps that are located in the cell wall and actively transport ions from the inside to the outside or from the outside to the inside. The most important of these pumps is the sodium–potassium ATPase.
It pumps three sodium ions from the inside out, in exchange for two potassium ions, which it pumps from the outside in. It ensures that there is a lot of potassium inside the cell and a lot of sodium outside the cell. For all this it needs the typical energy currency of the body: ATP (Adenosine Triphosphate), which it has to split in order to be able to produce the necessary energy.
Hence the name ATPase, which means ATP cleaving. In addition to this primarily active pump, there are also transporters that do not directly cleave ATP to have enough energy to transport ions, but that use the energy of natural ion gradients across the cell membrane to be able to work. Due to the sodium-potassium pump there is a lot of potassium inside the cell, but little outside.
Therefore, potassium flows by diffusion (i.e. without the help of transporters) from inside the cell to the outside to balance this charge imbalance. In addition, the pump means that there is a lot of sodium outside and little inside. Therefore, sodium ions flow from the outside to the inside to balance this imbalance.
These so-called ion gradients have a certain “force” and thus the potential to transport other ions that would not be able to overcome the membrane on their own because their gradient is not strong enough or even opposite. This is the case for example for the transport of calcium from intracellular to extracellular. The sodium-calcium-exchanger is used for this purpose.
Sodium is transported with its gradient from the outside to the inside and builds up enough “strength” to transport calcium against its gradient from the inside to the outside. What do the cardiac glycosides do now? (Digoxin) It was described above that the higher the concentration of calcium within the cell, the greater the contractive force of the heart.
However, the sodium-calcium exchange now ensures that calcium leaves the cell. That can be – with patients, whose heart does not beat strongly enough, thus is insufficient – very problematic.This transport must therefore be counteracted in order to have more calcium available within the cell. The cardiac glycosides (digoxin) do not directly inhibit this exchanger, but act by inhibiting the sodium-potassium ATPase.
As described above, they normally pump sodium outwards and potassium inwards. If it is inhibited, less sodium is outside. This means that the sodium gradient from outside to inside, which drives the sodium-calcium exchanger, is lower.
Therefore, less sodium can be exchanged for calcium and thus more calcium remains inside the cell. Now more calcium is available for contraction. More blood can be pumped per heartbeat.
Digoxin and digitoxin differ in their pharmacological properties. Digoxin: when taken orally (i.e. as a tablet), it has a bioavailability of about 75%. It is mainly excreted via the kidneys (renal) and has a half-life of 2-3 days.
