Digoxin

Digoxin belongs to the therapeutic group of cardiac glycosides.

[ 1 ]

Indications Digoxin

It is used to eliminate heart rhythm disorders ( arrhythmias ) that have a supraventricular form (paroxysmal atrial tachyarrhythmia, atrial fibrillation and regular atrial tachyarrhythmia).

The drug is included in the structure of therapeutic regimens for CHF of the 3rd and 4th subclasses, and in addition, it is used in the case of CHF of the 2nd subclass, when diagnosing pronounced clinical symptoms.

[ 2 ]

Release form

The drug is released in the form of an injection liquid or tablets.

[ 3 ], [ 4 ]

Pharmacodynamics

The medicine is of plant origin, the component digoxin is extracted from Digitalis lanata.

The drug has a powerful cardiotonic effect (positive inotropic effect and increase in contractile activity of the heart muscle by increasing calcium ion levels inside cardiomyocytes), which allows increasing minute values and stroke rates of blood. Reduces the need for oxygen saturation of myocardial cells.

Along with this, Digoxin has a negative chronotropic and dromotropic effect - it reduces the frequency of electrical impulse generation processes in the sinus node area, and in addition, the speed of impulse movement through the AV-conducting cardiac system. In addition, it indirectly affects the endings of the aortic arch and stimulates the activity of the vagus nerve, as a result of which the activity of the sinoatrial node is inhibited.

These mechanisms allow to reduce the heart rate level in case of supraventricular tachyarrhythmias.

In the development of severe heart failure, as well as symptoms of congestion in the area of the small and large circles of blood flow, the drug has an indirect vasodilatory effect, developing by reducing systemic vascular resistance (within the peripheral bed) and reducing the severity of dyspnea and peripheral edema.

[ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ], [ 10 ], [ 11 ]

Pharmacokinetics

The substance taken orally is absorbed in the gastrointestinal tract by 70%, reaching Cmax values after 2-6 hours. When taken with food, a slight increase in the absorption period is noted. The exception is products containing a large amount of plant fiber - in this case, part of the active element is adsorbed by its dietary fiber, after which it ceases to be available.

It is capable of cumulating within tissues with fluids (also within the myocardium), which is used when selecting the mode of use: the effect of the drug is calculated not by the values of plasma Cmax, but by equilibrium pharmacokinetic parameters.

50-70% of the drug is excreted through the kidneys; in severe stages of kidney disease, digoxin may accumulate inside the body. The half-life is 2 days.

[ 12 ], [ 13 ], [ 14 ], [ 15 ], [ 16 ]

Dosing and administration

Digoxin should be included in therapeutic regimens only in hospital. The medicinal interval of the drug (between the therapeutic dose and the toxic dose) is very short, which is why it is necessary to strictly follow all indications for the use of the drug.

In the first phase of therapy (the stage of digitalization of the patient's body with the drug), the medication is used in a portion called saturating: the patient takes 2-4 tablets (corresponding to 0.5-1 mg), and then switches to taking 1 tablet with a 6-hour interval. The intake according to this scheme continues until the medicinal result is obtained, and a stable blood level of digoxin is maintained for 7 days.

In the 2nd phase of treatment, it is necessary to regularly take a maintenance dose of the medication, often 0.5-1 tablet per day. It is forbidden to skip doses of the drug, as well as to take a double dose if the dose was missed. In this case, poisoning may develop, which can lead to death.

In cardiology and cardiac resuscitation, Digoxin is also used for intravenous administration to stop supraventricular tachyarrhythmias of a paroxysmal nature.

[ 24 ], [ 25 ], [ 26 ]

Use Digoxin during pregnancy

The effect of the drug on the fetus has not been studied during clinical trials, although it is known that its active element can pass through the hematoplacental barrier. Digoxin can be used during pregnancy only under strict indications.

When administering drugs during lactation, the infant's heart rate should be regularly monitored.

Contraindications

Main contraindications:

• symptoms of glycoside poisoning;
• presence of severe sensitivity to digoxin;
• WPW syndrome;
• AV block of 2nd degree or complete AV block;
• bradycardia;
• individual signs of coronary heart disease (unstable form of angina);
• exacerbation of myocardial infarction;
• isolated mitral valve stenosis;
• HF that has a diastolic form (cardiac tamponade, constrictive pericarditis, amyloid cardiopathy or cardiomyopathy);
• obesity;
• severe dilation of the heart chambers;
• renal or liver parenchyma failure;
• inflammation affecting the myocardium;
• hypertrophy in the area of the septum between the ventricles;
• subaortic stenosis;
• ventricular tachyarrhythmia.

[ 17 ], [ 18 ], [ 19 ], [ 20 ], [ 21 ]

Side effects Digoxin

The first step is to respond to the appearance of negative symptoms associated with the work of the cardiovascular system, because they may be the first manifestations of emerging glycoside poisoning.

Among the manifestations are inhibition of AV conduction, resulting in a slowing of the heart rhythm (development of bradycardia), and in addition to this, the emergence of heterotropic areas of myocardial excitation, resulting in ventricular extrasystole and ventricular fibrillation.

Extracardiac negative symptoms do not threaten the patient's life, which distinguishes them from intracardiac signs. Among them are disorders in the digestive system (vomiting, pain in the abdominal area, nausea and diarrhea) or NS (psychosis or depression, headaches and visual analyzer dysfunction, manifested by "flies" in the eyes, etc.).

A disorder of the morphological picture of hematopoietic activity in the form of thrombocytopenia may be observed, due to which petechiae appear on the epidermis.

In addition, allergy symptoms may occur - itching, rashes and erythema on the epidermis.

[ 22 ], [ 23 ]

Overdose

Signs of overdose (glycoside poisoning): slowing of heart rate and development of sinus bradycardia. ECG shows signs of slowing of AV conduction, which can even reach complete AV block. Ventricular extrasystoles develop under the influence of heterotropic rhythm sources; ventricular fibrillation may be observed.

Extracardiac manifestations of glycoside poisoning include dyspepsia (diarrhea, nausea or anorexia), memory impairment and weakening of cognitive activity, headaches, a feeling of drowsiness, muscle weakness, as well as gynecomastia, xanthopsia, impotence, a feeling of euphoria or anxiety, psychosis, deterioration of visual acuity and other disorders of the visual analyzer function.

When symptoms of glycoside overdose develop, the treatment regimen is determined by the severity of the disorders: if the symptoms are mild, it is enough to reduce the dose of the drug. When negative symptoms progress, the drug should be discontinued for a period of time determined by the dynamics of the symptoms of poisoning. In case of acute intoxication, gastric lavage should be performed and a large number of sorbents should be consumed. In addition, the patient should take a laxative.

Ventricular arrhythmias are treated with intravenous KCl in combination with insulin. Potassium-containing agents are prohibited in cases of slowing of AV conduction. If arrhythmia persists, intravenous phenytoin should be administered.

In case of bradycardia, atropine is prescribed. Along with this, oxygen therapy and drugs that increase the amount of circulating blood are used. Unithiol is an antidote to the drug.

It is important to take into account that intoxication can cause death.

[ 27 ], [ 28 ]

Interactions with other drugs

It is prohibited to combine Digoxin with acids, alkalis, tannins, and heavy metal salts.

Administration together with insulin, diuretic drugs, calcium salts, GCS and sympathomimetics increases the likelihood of developing signs of glycoside poisoning.

Combination with amiodarone, quinidine, and erythromycin leads to an increase in blood digoxin levels. Quinidine slows down the excretion of the active component of the drug.

Verapamil, which blocks the activity of Ca channels, reduces the rate of renal elimination of digoxin, which causes the level of SG to increase. This effect of verapamil is then gradually leveled out (after prolonged simultaneous use of drugs - more than 1.5 months).

Concomitant use of amphotericin B increases the risk of glycoside intoxication due to hypokalemia that may develop under the influence of amphotericin B.

In hypercalcemia, the susceptibility of cardiomyocytes to SG increases, which is why people using SG are prohibited from administering calcium agents intravenously.

The combination of the drug with propranolol, reserpine, and phenytoin increases the risk of ventricular arrhythmia.

The level and therapeutic effectiveness of the drug are weakened when combined with barbiturates or phenylbutazone. At the same time, the activity of Digoxin is reduced by potassium agents, metoclopramide and drugs that reduce gastric pH.

Concomitant use with gentamicin, antibiotics and erythromycin increases plasma levels of the glycoside.

The combination of the drug with cholestyramine, cholestipol, and magnesium-type laxatives weakens its intestinal absorption, which also reduces the digoxin level in the body.

The rate of glycoside metabolism processes increases when administered together with sulfosalazine and rifampicin.

[ 29 ], [ 30 ], [ 31 ], [ 32 ], [ 33 ]

Storage conditions

Digoxin should be stored in a place closed to children. Temperature values are within the range of 15-30°C.

[ 34 ], [ 35 ]

Shelf life

Digoxin can be used within a 36-month period from the date of manufacture of the pharmaceutical product.

[ 36 ], [ 37 ], [ 38 ]

Use in children

It is prohibited to prescribe tablets in pediatrics.

Analogues

Analogues of the drug are the drugs Celanide and Novodigal.

[ 39 ], [ 40 ], [ 41 ], [ 42 ], [ 43 ], [ 44 ], [ 45 ]

Reviews

Digoxin receives a small number of positive reviews, stating that the drug has an extremely powerful effect and can only be used under medical supervision.

However, there are quite a lot of negative comments regarding Digoxin – they note that the medication does not have the desired effect, while leading to the development of many side effects.