Digoxin

Synonyms

Cardiac glycosides

also read:

• Medication irregular heartbeat
• Digitoxin

definition

Digoxin is an active ingredient that belongs to the group of cardiac glycosides. Among other things, it improves the beating power of the heart and is therefore prescribed for heart failure, for example.

origin

Digoxin and Digitoxin can be extracted from the same plant: Dem thimble (Latin: digitalis), which is why they are sometimes synonymous with the term digitalis or Digitalis glycosides described.

Effect and mechanism of action

Digoxin affects the heart as follows:

• There increase the contact force of the Heart muscles (positive inotropic)
• Delay in the transmission of excitation from the area of ​​the atrium (antrum) to the chambers of the heart (ventricle) (negative dromotropic)
• Reduction in beat frequency (negative chronotropic effect).

physiology

In order to be able to contract, the Heart muscle - as well as all other muscles of the body, both the striated Skeletal musclesthat one tenses voluntarily, as well as the smooth muscles of vessels and organs that involuntarily contract - Calcium.
The principle applies to the heart: The more calcium, the stronger the force of contraction. And the higher this power, the more blood can be pumped with a heartbeat.
The heart consists of many cardiac muscle cells that contain contractile elements, which is what makes the heart possible in the first place. These filaments are called sarcomeres. The calcium must therefore be inside the cell (intracellular) to be able to influence the strength, as this is where the sarcomeres are located.
In order to understand the mechanism of cardiac glycosides, one has to dig a little further into the biochemistry of the cell: Every cell needs a certain ionic equilibrium in order to survive. So there have to be very specific concentrations of among other things potassium, sodium, chloride and Calcium prevail inside and outside the cell, since if these concentrations are exceeded or not reached, the cell will burst (Water influx with high intracellular ion concentration in order to achieve a charge balance between inside and outside) or shrink (Water outflow at high extracellular charge concentration in order to dilute the higher concentration of particles on the outside) would. This principle of distributing water in the direction of higher concentration is known as osmosis. To prevent an osmotic equilibrium from being established, as this would be fatal for the cell, there are pumps that sit 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. So it ensures that there is a lot of potassium inside the cell and a lot of sodium outside the cell. For all of this, she needs the body's typical energy currency: ATP (Adenosine triphosphate) that it has to split in order to gain the necessary energy. Hence the name ATPase, which means something like ATP-splitting.

More transporters

Besides this primary active pump There are also transporters that do not split ATP directly in order to have enough energy for ion transport, but that use the energy of natural ion gradients across the cell membrane in order to be able to work. Through the Sodium-Potassium Pump there is a lot of potassium inside the cell, but little outside. That's why the diffusion (so without the help of vans) Potassium from inside the cell to the outside to compensate for this charge imbalance. In addition, the pump means there is a lot of sodium outside and little inside.This is why sodium ions flow from the outside in to compensate for this. These so-called Ion gradients have a certain “power” and thus the potential to transport other ions with them that would not be able to cross 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. Sodium is transported with its gradient from the outside to the inside and in the process 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 force of contraction of the heart. However, the sodium-calcium exchange now ensures that calcium leaves the cell. That can - for patients whose heart is not beating strong enough, that is insufficient is - be very problematic. This transport must therefore be counteracted in order to have more calcium available within the cell. The Cardiac glycosides (Digoxin) do not inhibit this exchanger directly, but act by inhibiting sodium-potassium-ATPase. As described above, it normally pumps sodium outwards and potassium inwards. If it is inhibited, there is less sodium on the outside. This means that the sodium gradient from the outside in, which drives the sodium-calcium exchanger, is lower. So less sodium can be exchanged for calcium and so more calcium stays inside the cell. Now there is more calcium available for contraction. So more blood can be pumped per heartbeat.

Pharmacokinetics

Digoxin and Digitoxin differ in terms of their pharmacological properties.
Digoxin: When taken orally it has (as a tablet) a Bioavailability of about 75%. It is mostly about that Kidneys (renally) excreted and has a half-life of 2-3 days.

Indications

Digoxin is used for the following indications:

• Heart failure (Pumping weakness of the heart)
• Atrial flutter and fibrillation (by delaying the conduction of excitation)

Side effects

Digoxin has a narrow therapeutic index. That means it's very easy to overdose on them, resulting in a poisoning (Intoxication) leads. The sodium-potassium pump should only be inhibited in moderation, as otherwise the entire cell stability will be shaken. Symptoms of overdose can include:

• at the Hearts: Cardiac arrhythmias how Ventricular fibrillation, Extrasystoles in the ventricular muscles, AV block
• in the central nervous system: Color vision problems, tiredness, confused states
• in the Gastrointestinal tract: Nausea, Vomit

The therapy one Digoxin intoxication consists in the gift of Potassium-containing infusion solution (because an increased potassium concentration displaces the cardiac glycosides from the sodium-potassium-ATPase and thus inhibits their effect), Antiarrhythmics (Drugs that limit the cardiac arrhythmias that may be triggered), Digitalis antibodies (which specifically capture free cardiac glycoside molecules and thus render them ineffective).

Interactions

Many factors and the parallel administration of other drugs can reduce the risk Digoxin effect influence, therefore a precise anamnesis (systematic questioning of the patient about previous illnesses, medication intake, etc.) must be carried out before prescribing and taking. Factors that can cause interactions include:
Potassium concentration – Hyperkalemia (increased potassium concentration) leads to reduced effectiveness, Hypokalemia (reduced potassium concentration), on the other hand, intensifies the effect and can thus - if a normal dose is given - lead to symptoms of intoxication
Renal failure - Patients with dysfunction of the kidneys should not be treated with digoxin; digitoxin should be used here, as it is less excreted via the kidneys
Medication, the drug-degrading enzymes of the liver activate or inhibit (Induction or repression of CYP enzymes). These include some Antibiotics, Anti-epileptic drugs, Johannis herbs and antiarrhythmics.