Digoxin

General characteristics. Structure:

Active ingredient: 0,25 mg of digoxin.

Excipients: magnesium stearate, cellulose microcrystallic, starch corn, sodium glikolit starch, lactose, sodium lauryl sulfate.

The drug used in cardiology, rendering inotropic and chronotropic effects uluchshayat cardiac performance, possesses antiarrhytmic action.

Pharmacological properties:

Pharmacodynamics. Cardiac glycoside, contains in a foxglove woolly. Has positive inotropic effect which is connected with the inhibiting influence on ^{Na+-K +} ATP-ase of a membrane of cardiomyocytes that leads to increase in intracellular maintenance of ions of sodium and decrease in potassium ions. Thereof there is an increase in intracellular content of the calcium responsible for contractility of cardiomyocytes that leads to increase in force of reductions of a myocardium. Improves cardiac performance, at the same time extends a diastole. Has negative chronotropic effect. Urezheny ChSS it is substantially connected with кардио - a cardial reflex. Reduces excessive sympathetic activity by increase in sensitivity of cardiopulmonary baroreceptors.

Causes antiarrhytmic effect which is caused by ability to reduce the speed of carrying out excitement through an AV node and to extend the effective refractory period thanks to increase in activity of a vagus nerve or by direct action on an AV node, or due to sympatholytic effect. In average doses does not influence the speed of carrying out and a refrakternost of the carrying-out Gisa-system of Purkinye. At the same time shortens the effective refractory period of auricles and reduces in them carrying out speed thanks to reflex increase in a tone of a vagus nerve and direct action at auricles.

Increases ventilation of the lungs in response to the stimulation of chemoceptors caused by a hypoxia. Contributes to normalization of function of kidneys and increase in a diuresis.

Pharmacokinetics. Bioavailability when using tablets of digoxin makes 60-85%. Therapeutic concentration - 1-2 ng/ml. Communication of digoxin with proteins of a blood plasma low. Excretion of not changed drug is carried out generally by kidneys. At patients with a chronic renal failure the renal clearance of digoxin decreases. Drug kumulirutsya in an organism.

Absorption. After intake it is quickly and completely absorbed from a GIT.

Distribution. It is quickly distributed in fabrics. Concentration of Digoxin in a myocardium is much higher, than in plasma. Digoxin is capable to get through a placenta; in insignificant quantities it is allocated with breast milk.

Removal. The elimination half-life makes 34 — 51 h. During 24 h after receipt in an organism about 27% of Digoxin are allocated with urine.

Indications to use:

Heart failure, takhiaritmichesky form of atrial fibrillation, ciliary arrhythmia, Bouveret's supraventricular disease.

Route of administration and doses:

The recommended doses are strictly individual.

Usually for adults doses are used: for a bystry digitalization (inside) - from 0,75 mg to 1,25 mg in two or more receptions; for a slow digitalization - from 0,125 mg to 0,5 mg once a day within 7 days. Maintenance doses at intake - from 125 mkg to 500 mkg once a day.

Sensitivity to cardiac glycosides (digoxin) increases at patients of advanced age.

Digoxin is accepted on an empty stomach, i.e. in 30-40 minutes prior to meal. Food, protein-rich, creates serious difficulty in achievement of the corresponding therapeutic concentration of digoxin in blood due to its chemical affinity to protein molecules. The food rich with fats accelerates elimination of digoxin from an organism due to increase in secretion of the cholecystokinins causing bile outflow, especially strong at reception of greasy food. Patients with an impaired renal function, elderly, exhausted, to patients with a pacemaker need careful selection of a dose of digoxin since at them the risk of toxic reactions increases.

To children up to 14 years Digoxin is appointed in a dose at the rate of 25 — 75 mkg/kg of body weight.

To patients with renal failures Digoxin is appointed in smaller doses: at glomerular filtering lower than 50 ml/min. it is necessary to apply 25 — 75% of an average dose, at glomerular filtering it is lower than 10 ml/min. — 10-25% of an average dose.

Features of use:

The probability of developing of glikozidny intoxication increases at a hypopotassemia, a hypomagnesiemia, a hypercalcemia, the hypernatremia, a hypothyroidism expressed to dilatation of cardial cavities, a pulmonary heart, myocarditis at elderly patients. In these cases the Digoxin combination with potassium drugs, in particular, with Pananginum is reasonable.

During use of digoxin it is regularly necessary to carry out control of an ECG, definition of concentration of electrolytes (potassium, calcium, magnesium) in blood serum.

Side effects:

From cardiovascular sistemy:bradikardiya, AV blockade, disturbances of a cordial rhythm; in isolated cases - thrombosis of mezenterialny vessels.

From the alimentary system: anorexia, nausea, vomiting, diarrhea.

From TsNS and peripheral nervous system: headache, feeling of fatigue, dizziness; seldom - a xanthopsia, flashing of "front sights" before eyes, decrease in visual acuity, scotoma, macro - and a micropsia; in isolated cases - confusion of consciousness, a depression, sleep disorders, euphoria, a delirious state, a syncopal state.

From endocrine system: at prolonged use development of a gynecomastia is possible.

Interaction with other medicines:

At a concomitant use of digoxin and Amiodaronum increase in concentration of digoxin in blood to toxic level is possible (it is necessary to reduce a digoxin dose by 50%).

The concomitant use of digoxin with antiarrhytmic means or drugs of Rauwolfia, or sympathomimetics increases risk of developing of arrhythmias.

Propafenon at reception with digoxin increases concentration of the last in blood serum ranging from 35 to 85%.

The diuretics strengthening removal of potassium ions (буметанид, Acidum etacrynicum, furosemide, индапамид. Mannitolum, tiazidovy diuretics), or the drugs causing a hypopotassemia at a concomitant use with digoxin increase toxicity of the last.

Spironolactonum can increase T 1/2 digoxin.

Antacids reduce absorption of digoxin from a GIT in blood therefore its plasma concentration decreases.

Sukralfat reduces digoxin absorption therefore it is recommended to accept сукралфат 2 hours later after digoxin reception.

Anti-diarrheal adsorbents, холестирамин, колестипол, chop off (large number), Neomycinum (orally) and Sulfasalazinum slow down absorption of digoxin and reduce its therapeutic effect. BKK (verapamil) can increase concentration of digoxin in blood serum at their concomitant use.

At reception of digoxin and indometacin the renal clearance of digoxin can be reduced that leads to increase in plasma concentration of digoxin and, respectively, risk of development of toxic reaction (it is recommended to reduce a digoxin dose by 50%).

Contraindications:

Cardiomyopathy (hypertrophic, obstructive), heart blocks;

hypersensitivity to cardiac glycosides;

predisposition to digitalis intoxication.

For the prevention of toxic reactions of digoxin at patients of advanced and senile age it is necessary to reduce drug doses as at this category of patients the clearance of digoxin is reduced and there are age changes of function of a liver and kidneys.

Overdose:

Symptoms: various arrhythmias, cross blockade of different degree of manifestation, vision disorder and color perception, fatigue, muscular weakness, dispeptic phenomena, mental disturbances.

Treatment: for absorption reduction — absorbent carbon, холестирамин; at a hypopotassemia — potassium drugs; at arrhythmias — lidocaine, Phenytoinum; at a bradyarrhythmia — atropine or temporary electrocardiostimulation; Unithiolum.

Storage conditions:

List A. To store in the place protected from moisture and light at a temperature not over +25 ºС. To store in the place, unavailable to children. Period of validity 3 years.

Issue conditions:

According to the recipe

Packaging:

On 30 or 50 tablets in bank of polymeric. On 10 tablets in a blister strip packaging. 1 bank or 3, 5 blister strip packagings together with a leaf insert in secondary packaging.