Digitalis antidote

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Digitalis antidote , also digitalis antitoxin , is a medical "antidote" ( Greek antidote ) or "antidote" (Greek antitoxin ) in the case of life-threatening digitalis intoxication (digitalis poisoning) caused by excessive intake of digoxin , digitoxin or other digoxin derivatives can occur. These substances are also referred to below as " digitalis glycosides " or "glycosides" for short.

Active ingredient

In Digitalis antitoxin is Fab antibody fragments (Fab, short for English. Antigen fragment binding ) of IgG immunoglobulins from the blood serum of immunized sheep.

application areas

Digitalis intoxication occurs when excessive amounts of the active ingredients are ingested accidentally or with suicidal intent. Serious cardiac arrhythmias can then lead to life-threatening complications. In addition to people with suicidal poisoning, patients of older age who have a serious underlying cardiac disease, such as decompensated heart failure , that is out of balance, are considered to be particularly at risk .

Clinical picture

The clinical picture can be manifold and is always dramatic:

Ventricular flutter and ventricular fibrillation have a particularly adverse effect on the course of digitalis intoxication.

Mode of action

The clinical effectiveness of digitalis antitoxin for digitalis glycosides has been demonstrated. It is based on the rapid and almost complete binding of the antitoxin to the free glycoside present in the extracellular space , which creates pharmacologically inactive antitoxin-glycoside complexes ( neutralization ).

This leads to a concentration gradient between the intra- and extracellular glycosides in the sense of high to low. As a result , further intracellular glycoside diffuses into the extracellular space, where it is continuously neutralized by the antitoxin present here.

This mechanism of action is supported by the high increase in the glycoside bound to antitoxin and the decrease in free glycoside in the serum upon infusion of digitalis antitoxin.

Metabolism and Excretion

Immediately after the start of the digitalis antitoxin infusion, the concentration of Fab-bound glycosides in the serum rises steeply (maximum value measured so far above 300 ng / ml), while the free glycoside drops to values ​​below the detection limit. After the maximum is exceeded, the total glycoside level decreases continuously according to the rate of elimination of the Fab-glycoside complexes, initially with a half-life of 15 hours, after a day of about 26 hours.

During the first 10 hours after the application of digitalis antitoxin, the serum almost exclusively contains glycoside bound to Fab and thus neutralized. The free glycoside level rises again between the eighth and twelfth hour after the start of the Fab administration.

From the behavior of the serum levels of free and Fab-bound glycosides in the serum, it can be concluded that there is a compartment in the distribution volume with the glycoside fraction that is only adsorbed on the cell surfaces . After the infusion of digitalis antitoxin, this glycoside component passes into the serum with a half-life of about 12 minutes, where it causes the initially very steep increase in glycosides. A deeper, far larger tissue compartment ( cell membrane , intracellular space ) allows the glycoside molecules to pass into the serum with a half-life of about 8 hours, as long as there is excess free Fab. The concentration of free and total glycosides in the urine correlates with the free and total glycoside levels in the serum. Only when the binding capacity of the Fab in the serum is exhausted and glycoside continues to transfer from the large volume of distribution for digitalis, namely the muscles , into the serum, free glycoside can again be detected both in the serum and in the urine (on average after about 10 hours, see above ).

About 56% of the glycoside-Fab complexes become renal; H. via the kidneys , excreted. Even glycosides that do not require kidney disease become kidney-permeable due to the binding to the fabulous and achieve a comparable rate of elimination.

Side effects

As with any therapy with ("heterologous") substances originating from foreign organisms, allergic reactions could also occur with the first use of digitalis antitoxin ; In the therapeutic cases described so far, however, no such side effects have become known.

Since it is a product obtained from foreign serum (from sheep), there is in principle a risk of sensitization . The application of digitalis antitoxin must therefore be entered in the vaccination certificate, so that if sheep globulins need to be applied again later, the possibility of severe or life-threatening anaphylactic reactions is considered.

Immediately before the infusion of digitalis antitoxin, an intracutaneous and conjunctival test must be tested for allergies. Furthermore, at the beginning of the infusion, careful attention must be paid to symptoms of shock ; medical supervision is imperative.

Precautions

Serum potassium control

In severe digitalis intoxication, by the glykosidbedingte inhibiting sodium-potassium ATPase of the cell membranes, a solid serum potassium can achieve the life-threatening carried -increase. Due to the simultaneous increased renal, ie via the kidneys taking place excretion of potassium, however, can hyperkalemia associated in potassium with a decrease of the body stock. Although the administration of the digitalis antitoxin is not the cause of these disorders, the serum potassium concentration should be carefully monitored.

In the further course of the neutralization of the glycoside effect with digitalis antitoxin, the intracellular potassium concentration is increased again with a simultaneous decrease in the serum potassium concentration. Hypokalaemia can develop from this very quickly . Potassium deficits should be carefully corrected on the basis of regular serum potassium determinations, especially during the first hour after administration of digitalis antitoxin .

Serum glycoside level control

A serum glycoside determination is part of the differential diagnosis of digitalis intoxication. Reliable quantitative information can only be obtained when the distribution phase has ended, i.e. 8 hours after the last glycoside intake at the earliest, and often much later if the glycoside intake is very high.

Therefore, the serum glycoside levels determined at the time of administration of digitalis antitoxin usually do not provide any reliable information about the amount of antidote actually required.

Contraindications

Apart from allergies to sheep globulins, there are no known contraindications. Because of the vital indication , the use of digitalis antitoxin is generally advisable.

dosage

The amount of glycoside present in the body is decisive for the level of the required antitoxin dose , which is given as an intravenous infusion . For the purpose of back-calculation, the amount of glycoside consumed should always be found out. The required antitoxin dose can be found in the current product information enclosed with the digitalis antitoxin pack.

When calculating the dose, the following points should be taken into account:

  • In the event of vomiting or gastric lavage, the amount of glycoside available for absorption may be reduced.
  • Laxatives can accelerate the excretion of the glycoside.
  • The biological availability of the individual glycoside preparations limits the amount of glycoside that can be absorbed.
  • A part of the resorbed amount of glycoside can already be metabolized in the body.

If the amount of glycoside consumed cannot be determined, a dose of 6 vials of digitalis antitoxin should be administered based on clinical experience. According to the knowledge available to date, this is the dosage in the majority of cases.

In children too, the dose is based on the amount of glycoside ingested and not on body weight. The same dosage and application recommendations therefore apply.

Experience to date has shown that patients with impaired kidney function should be treated like people with healthy kidneys. A longer observation period is recommended, corresponding to the reduced proportion of renal elimination.

Therapy success

The cardiac arrhythmias generally regress one to three hours after the start of therapy and thus indicate an at least initially sufficient dose of digitalis antitoxin. If, in individual cases, arrhythmias occur again after ten or more hours, further administration of digitalis antitoxin may be indicated.

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