Digoxin Immune Fab
Digitalis antidote, even digitalis antitoxin, is a medical " antidote " (Greek antidote ) or " antidote " (Greek anti- toxin) in a life-threatening digitalis ( Digitalis ), the result of excessive intake of digoxin, digitoxin or other digoxin derivatives can occur. These substances are referred to hereinafter as " digitalis " or simply " glycosides ".
Active substance
In Digitalis antitoxin is Fab antibody fragments ( Fab, short for. Fragment antigen binding) of IgG immunoglobulins from the blood serum of immunized sheep.
Areas of application
Digitalisintoxikationen occur when excessive amounts of the active ingredients are accidentally or with suicidal intent. Severe heart rhythm disturbances can lead to life-threatening complications. Particularly at risk are - in addition to people with suicidal poisoning - in older patients who have a serious cardiac underlying disease, such as congestive, ie imbalanced heart failure.
Clinical picture
The clinical picture can be represented varied and is always dramatic:
- Multifocal ventricular extrasystoles
- Ventricular
- Atrial tachycardia with AV block
- AV Knotentachykardien
- Combination of AV block with ectopic
- Ventricular flutter
- Ventricular fibrillation
Ventricular flutter and ventricular fibrillation affect the course of digitalis particularly unfavorable.
Operation
The clinical efficacy of digitalis antitoxin for digitalis glycosides has been demonstrated. It is based on a rapid and almost complete binding of the antitoxin to the present in the extracellular space free glycoside, which pharmacologically ineffective antitoxin - glycoside complexes are formed ( neutralization).
So there is a concentration gradient between the intra-and extracellular glycoside within the meaning of high to low. As a result, diffuses further intracellular glycoside into the extracellular space, where it is continuously neutralized by the antitoxin available here.
Speak of the high increase of the bound of antitoxin glycoside and the waste of free glycoside in the serum of infusion of digitalis antitoxin for this mechanism of action.
Metabolism and excretion
Immediately after the start of the infusion of digitalis antitoxin the concentration of the bound Fab glycosides rises steeply in the serum (previously measured maximum value of more than 300 ng / ml), while the free glycoside drops to values below the detection limit. After the peak is exceeded, the Gesamtglykosidspiegel decreases continuously according to the elimination rate of the Fab glycoside complexes, initially with a half-life of 15 hours, after one day of about 26 hours.
The serum containing the first 10 hours after administration of digitalis antitoxin Fab bound almost exclusively to the glycoside and thus neutralized. Between the eighth and twelfth hour after the administration of the free Fab Glykosidspiegel rises again.
From the behavior of the serum levels of free and bound to Fab glycosides in serum can be concluded that the volume of distribution of a compartment with the glycoside is, which is only adsorbed on the cell surface. This glycoside occurs after the infusion of digitalis antitoxin with a half -life of about 12 minutes, the serum over where it causes the initially very steep Glykosidanstieg. A deep located, far larger Gewebskompartiment ( cell membranes, intracellular ) leaves the Glykosidmoleküle with a half-life of about 8 hours pass into the serum, as long as free Fab are present in excess. In the urine correlates the concentration of free and total glycoside with the free and the total Glykosidspiegel in serum. Only when the binding capacity of the Fab is depleted in serum and continues to occur from the large volume of distribution for digitalis, namely the muscles, glycoside in the serum, is again free glycoside in both the serum and in the urine ( after an average of about 10 hours, s. above).
The glycoside - Fab complexes to about 56 % renal, ie via the kidneys excreted. Also not requiring kidney glycosides pass through the kidneys by binding to the Fab and achieve a comparable rate of elimination.
Side effects
( " Heterologous " ) As under each therapy originating from foreign organisms substances could cause allergic reactions also occur with the first application of digitalis - antitoxin; in the treatment cases described so far, however, no such side effects have been known.
Since it is a foreign serum obtained from ( sheep ) product, is in principle also the risk of sensitization. The application of digitalis - antitoxin must therefore be entered in the vaccinated animals, so that is thought necessary at a later application of Schafglobulinen to the possibility of serious or life-threatening anaphylactic reactions.
Immediately before the infusion of digitalis - antitoxin must be tested by intradermal and conjunctival on allergy. In addition, make the start of the infusion carefully for signs of shock, medical supervision is mandatory.
Precautions
Serum potassium control
In severe digitalis intoxication can occur through the glykosidbedingte inhibition of sodium-potassium ATPase of cell membranes, a massive increase in serum potassium, which can reach life-threatening proportions. However, due to a concomitant increased renal, ie via the kidneys taking place excretion of potassium may be associated hyperkalemia with a drop in the stock of body potassium. Although not the gift of the digitalis - antitoxin is the cause of these disorders, the serum potassium concentration should be monitored carefully.
In the course of the intracellular potassium concentration is raised by the neutralization of the glycosides with digitalis - antitoxin again with a simultaneous reduction in serum potassium concentration. From this hypokalaemia may develop very quickly. On the basis of regular serum potassium determinations, particularly during the first hour after administration of digitalis - antitoxin, possibly occurring potassium deficits should be corrected carefully.
Serum Glykosidspiegel control
A serum - glycoside - determination is part of the differential diagnosis of digitalis intoxication. But reliable quantitative information can only be obtained when the distribution phase is complete, ie no earlier than 8 hours after the last Glykosideinnahme, at very high Glykosidaufnahme often much later.
Therefore, the time of administration of digitalis - specific antitoxin serum Glykosidspiegel usually give no reliable indication of the actual required quantity of the antidote.
Contraindications
Besides allergy against Schafglobuline no contraindications are known. Because of the vital indication of the use of digitalis antitoxin is usually still necessary.
Dosage
Decisive for the amount of the required antitoxin dose that is administered as an intravenous infusion, is the present in the body Glykosidmenge. In order recalculation whenever possible the area occupied Glykosidmenge should be learned. The necessary antitoxin dose is given in the current prescribing information that comes with the pack of digitalis - antitoxin.
In calculating the dose the following aspects should be considered:
- If vomiting or gastric lavage, the standing resorption Glykosidmenge may be reduced.
- By laxative excretion of the glycoside can be accelerated.
- The biological availability of Glykosidpräparate limits the absorbable Glykosidmenge.
- A part of the absorbed Glykosidmenge may already be metabolized in the body.
If the area occupied Glykosidmenge can not be determined, a dose of 6 vials of digitalis- antitoxin should be administered according to the clinical experience. This is according to current knowledge, the dosage in the majority of cases.
Even in children, the dose depends on the recorded Glykosidmenge and not according to body weight. Therefore apply the same dosage and application recommendations.
Patients with renal impairment should be treated according to previous experience as kidneys healthy. It is recommended that a longer observation time, corresponding to the reduced contribution of renal elimination.
Therapeutic success
The cardiac arrhythmias are generally formed one to three hours after the start of therapy back and thus show an at least initially sufficient dose of digitalis antitoxin to. If in individual cases again arrhythmias occur even after ten or more hours, another dose of digitalis antitoxin may be indicated.