Preparations from the group of cardiac glycosides: classification and indications. Cardiac glycosides (application and toxicology). Non-steroidal cardiotonic drugs use and toxicology of cardiac glycosides Cardiac glycosides cause

Indications for the use of digoxin, digitoxin, strophanthin.

Apply cardiac glycosides mainly in acute and chronic heart failure. In acute heart failure, cardiac glycosides with a short latent period (strophanthin and digoxin IV) are administered. In addition, glycosides (digitalis preparations) are sometimes prescribed for the tachyarrhythmic form of atrial fibrillation. The effectiveness of glycosides in these arrhythmias is associated with an increase in the tone of the vagus nerve and inhibition of the conduction of excitation through the conduction system of the heart, the spread of atrial fibrillation to the ventricles is prevented.

Cardiac glycosides are administered most often orally (digitoxin, digoxin) and intravenously (strophanthin, digoxin), sometimes intramuscularly and rectally.

Contraindications to the use of cardiac glycosides are incomplete atrioventricular block, severe bradycardia, acute infectious myocarditis. When administered intravenously, strophanthin begins to act on the heart after 5-10 minutes. With the introduction of digoxin inside, the effect develops after 30 minutes, and when taking digitoxin - after about 2 hours.

Kidney function is normalized as a result of the favorable effect of cardiac glycosides on blood circulation. diuresis increases. In large doses, cardiac glycosides increase the automatism of the heart.

Amrinone, milrinone

1. The action is presumably associated with the inhibition of phosphodiesterase, as a result, the content of free calcium ions and cAMP in myocardial cells increases.

2. Increase the contractile activity of the myocardium.

3. Cause vasodilation.

1. The need of the heart for oxygen is not increased, the rhythm of diabetes and blood pressure in therapeutic doses is not affected.

2. Applied for heart failure, not amenable to conventional therapy with cardiac glycosides.

3. Side effects: thrombocytopenia, vomiting, jaundice, hypotension.

8. Enter intravenously and inside. (When administered enterally, milrinone lasts 4-7 hours)

8. Milrinone and dobutamine: mechanisms of cardiotonic action, application, side effects.

ANTI-ARITHMIC DRUGS

2. Quinidine: mechanism and localization of action, application, side effects.

3. Novocainamide: mechanism and localization of action, application, side effects.

4. Lidocaine and difenin: mechanism of antiarrhythmic action, application.

5. Comparative characteristics of antiarrhythmic drugs IA, IB and IC class.

6. Amiodarone: mechanism and localization of antiarrhythmic action, application, side effects.

7. Verapamil: mechanism and localization of antiarrhythmic action, application, side effects.

8. Verapamil and amiodarone: mechanisms of antiarrhythmic action, differences in use in arrhythmias.

9. What antiarrhythmic drugs are used: a) only for supraventricular arrhythmias; b) only with ventricular arrhythmias; c) with arrhythmias of any localization.

10. Means for the treatment of disorders of atrioventricular conduction (principles of action, preparations).

1. Classification of antiarrhythmic drugs (groups and names of drugs).

2. 3. Quinidine and novocainamide: mechanism and localization of action, application, side effects.

4. Lidocaine and difenin. Mechanism of antiarrhythmic action, application.

Lidocaine has a depressing effect on automatism (diastolic depolarization decreases - phase 4) in the Purkinje fibers and in the muscles of the ventricles, but not in the sinoatrial node. The noted influence is manifested by the suppression of ectopic foci of excitation. Lidocaine does not affect the rate of rapid depolarization, or slightly reduces it (Purkinje fibers). The effective refractory period decreases. It practically does not affect the conductivity and contractility of the myocardium. It also does not affect hemodynamics. That is why lidocaine is used mainly for ventricular arrhythmias (extrasystoles, tachycardia that occur during myocardial infarction, during open heart surgery, in the postoperative period). Use in / in the drip, acts briefly.

The mechanism of action of difenin is similar to that of lidocaine. It is used for ventricular arrhythmias, as well as for tachyarrhythmias caused by an overdose of cardiac glycosides.

Apply difenin inside and intravenously. Valid for several hours.

Diuretics

Influence of cardiac glycosides on force, contraction rate, atrioventricular conduction and automatism of the heart.

1. Cardiac glycosides have a cardiotonic effect, respectively, the strength of heart contractions increases.

2. They lower the heart rate, which is largely due to the cardio-cardiac reflex (vagus).

3. Cardiac glycosides lower atrioventricular conduction, because have a direct inhibitory effect on the conduction system of the heart, and tone the vagus nerve, reducing the rate of excitation.

4. Cardiac automatism is increased by cardiac glycosides, which can lead to arrhythmias (extrasystoles).

3. Effects of cardiac glycosides in congestive heart failure.

Cardiac glycosides contribute to the normalization of all hemodynamic parameters disturbed as a result of congestive heart failure!

1. Minute volume is increased by increasing the strength of heart contractions; it is important that the work of the heart increases without an increase in its oxygen consumption against the background of ®

2. decrease in heart rate (negative chronotropic effect) and lengthening of diastole.

3. Heart rate is reduced by increasing the inhibitory effect of the vagus on the sinus node

4. Venous pressure is reduced (normalized) by increasing contractility and normalizing hemodynamics

5. Diuresis - increase due to increased renal blood flow and a direct effect on the kidneys, remove excess fluid from the body, swelling disappears.

6. Blood supply and oxygenation of tissues improves, the functions of internal organs (liver, gastrointestinal tract, etc.) are restored.

4. Comparative characteristics of strophanthin, digoxin and digitoxin. The practical significance of differences in the pharmacokinetics of these drugs.

cardiac glycosides

drugs of a glycosidic structure with a selective cardiotonic effect. In nature, S. g. are found in 45 species of medicinal plants belonging to 9 families (kutrovye, lily, ranunculaceae, legumes, etc.), as well as in the skin poison of some amphibians. Separate preparations of this year (acetyldigitoxin, methylazide) are obtained semi-synthetically.

Digitalis preparations used in modern medical practice this year include digitalis preparations digitoxin, digoxin, acetyldigitoxin, celanide, lantoside, etc., strophanthus Kombe - strophanthin K., lily of the valley - corglicon, lily of the valley, as well as preparations of adonis - herb adonis, dry adonis and adonizide.

Chemical structure of cardiac glycosides. This year's molecules consist of genins (aglycones) and glycones. Chemically, genins are steroidal cyclopentane-perihydrophenanthrene structures that have an unsaturated lactone ring at the C17 position. Depending on the structure of the lactone ring, S.'s genins are divided into cardenolides (with a five-membered unsaturated ring) and bufadienolides (with a six-membered doubly unsaturated ring). The structure of aglycones, and in particular the structure of their lactone rings, determines the mechanisms of action and other features of the pharmacodynamics of cardiac glycosides. In addition, the structure of aglycones determines the degree of polarity and related features of the pharmacokinetics (in the gastrointestinal tract, binding to plasma proteins, etc.) of these drugs. The polarity of this year depends on the number of polar (ketone and alcohol) groups in their aglycones. Thus, S. g strophanthus and lily of the valley are distinguished by the highest polarity, the aglycones of which contain 4-5 polar groups each. Less polar are digoxin and celanide, containing 2-3 polar groups each. Digitoxin, in the aglycone of which there is only one polar group, is characterized by the smallest polarity among this year.

Glycones in the S. molecule mean the residues of cyclic sugars connected through an oxygen bridge with aglycones in the C 3 position. Used in medicine, S. g. contain from one to four residues, among which there can be both (for example, O-digitoxose, O-cymarose, etc.), found only in the composition of S. g., and sugars widely distributed in nature (D-glucose, D-fructose, L-rhamnose, etc.). The structure of glycone depends on the solubility of S. g., their stability in an acidic and alkaline environment, toxicity, as well as some features of pharmacokinetics (through cell membranes, absorption in the gastrointestinal tract, binding strength to blood plasma proteins, etc.).

Pharmacological effects and mechanisms of action of cardiac glycosides. These have a direct selective effect on and cause a positive inotropic effect (increased heart rate, a negative chronotropic effect (decrease in heart rate) and a negative dromotropic effect (decrease in conductivity). In high doses, they also cause a positive bathmotropic effect, i.e. increase all elements of the conduction system of the heart, with the exception of the sinus node.Positive S.g. is clinically expressed only in conditions of heart failure, when the specific volume is limited due to a decrease in myocardial contractility.In healthy individuals, signs of a positive inotropic effect of S.g. can be detected only with the help of special hemodynamic studies.On the action of this year, there is an increase in the K wave, a narrowing of the QRS complex, an increase in the R-R and P-R intervals, a shortening of the Q-T interval, a decrease in the ST segment below the isoelectric line, a decrease, smoothing or T wave. insufficiency This year increase shock and minutes; they also reduce the volume of circulating blood, increase or normalize, improve myocardium. An increase in the strength of heart contractions under the influence of this year in heart failure is not accompanied by increased oxygen consumption by the myocardium, because by reducing the volume of the heart and the tension developed, this year they transfer it to an energetically more favorable level of work.

The mechanism of positive inotropic action of this year is associated with their ability to increase the content of calcium ions in cardiomyocytes and form calcium complexes with troponin, as a result of which the interaction of actin and myosin is facilitated and myofibrils increase. In addition, this year increase the activity of myosin ATPase, which is involved in the energy supply of this process.

An increase in the content of calcium ions in cardiomyocytes under the influence of this year occurs for the following reasons. Interacting with the sulfhydryl groups of Na, K + -dependent ATP-ase of cardiomyocyte membranes, S. g. inhibit the activity of this enzyme, which leads to an increase in the intracellular content of sodium ions. At the same time, the current of extracellular calcium to cardiomyocytes increases, possibly due to the stimulation of the mechanism of the transmembrane exchange of sodium ions for calcium ions, and the release of calcium from the sarcoplasmic reticulum also increases. It is also assumed that the permeability of calcium through the membranes of cardiomyocytes and the sarcoplasmic reticulum increases as a result of the formation of complexes of this year with the phospholipid, protein and carbohydrate components of these membranes. Besides, formation of chelapts of this year with calcium can facilitate the transport of calcium through the membranes of cardiomyocytes and the sarcoplasmic reticulum. It is possible that in the mechanisms of the inotropic effect of this year, the transmembrane transport of calcium ions dependent on the cyclic processes, as well as the increased release of endogenous analogs of cardiac glycosides (the so-called endodigins), are important.

The mechanism of the negative chronotropic effect of this year is due to the predominant activation of the influence of the vagus nerve on the myocardium. This effect is eliminated by atropotin. Activation of the vagus nerve under the influence of this year is carried out reflexively from the baroreceptors of the sinocarotid and aortic zones (sinocardial) and from myocardial stretch receptors (the so-called Bezold effect, or cardiocardial Bezold-Jarisch reflex). At the same time, the intensity of the Bainbridge reflex decreases due to a decrease in stretching of the receptors of the mouths of the vena cava.

This year's intoxication is observed, as a rule, as a result of an overdose of drugs. Various factors contribute to the development of intoxication, including. changes in the pharmacokinetics of this year with hypothyroidism, hypoalbuminemia, renal or hepatic insufficiency in old age, etc. to This year increases with cardiomyopathy, myocardial hypoxia, alkalosis, hypokalemia, hypomagnesemia and hypercalcemia. In addition, this year's toxicity may increase when they are used together with certain drugs (see Drug Incompatibility).

In case of development of intoxication, this year is canceled. For the relief of tachyarrhythmias resulting from intoxication, potassium preparations, difenin, lidocaine, disodium edetate unithiol, β-blockers (anaprilin) ​​are used. Potassium preparations are effective only in cases where this year's intoxication develops against the background of hypokalemia. Of the potassium preparations, for this purpose, mainly potassium chloride is used, which is administered intravenously in a 5% glucose solution for 1-3 h, or panangin. If this year's intoxication develops against the background of hyperkalemia or atrioventricular blockade, it is not advisable to use potassium preparations. In such cases, the drug of choice is difenin. Lidocaine effectively stops the ventricular tachyarrhythmias caused by this year, but it can be used only in the absence of atrioventricular blockade. For the same purpose, anaprilin can be used, which is administered intravenously in doses of 1-5 mg. With atrioventricular blockade caused by S.'s intoxication, not accompanied by ventricular arrhythmias, the most pronounced effect is caused by intravenous administration of disodium edetate (2-4 G at 500 ml 5% glucose solution) together with atropine (1 ml 0.1% solution) In the absence of effect, endocardial is indicated. At emergence of fibrillation of ventricles owing to intoxication This year resort to electric defibrillation of heart and enter difenin and potassium preparations intravenously. A promising method of therapy for this year's intoxication is the use of specific antibodies to these drugs.

The main S. g., their methods of application, doses, forms of release and storage conditions are given below.

Adonizide(Adonisidum) adults are used inside 20-40 drops 2-3 times a day. Higher oral doses for adults: single 40 drops, daily 120 drops. Release forms, bottles of 15 ml. Storage: list B; in a well-closed container, protected from light.

Digitoxin(Digitoxinum) is administered orally and rectally, on average, respectively, 0.0001 and 0.00015 G appointment. Higher oral doses for adults: single 0.0005 G, daily 0.001 G. Release form: tablets of 0.0001 G, rectal suppositories () by 0.00015 G

Digoxin(Digoxinum) is administered orally to adults at an average of 0.00025 G appointment. Higher daily intake for adults 1.0015 G. Intravenously (slowly!) Inject 1-2 ml of a 0.025% solution in 10 ml 5%, 20% or 40% glucose solution Release form: tablets 0.00025 ampoules 1 each ml 0.025% solution. Storage: list A; in a place protected from light.

Cardiovalen(Cardiovalenum) is used orally 15-20 drops 1-2 times a day. Release form: bottles of 15, 20 and 25 ml. Storage: list B; in a cool, dark place.

Korglikon(Corglyconum) is administered intravenously (slowly over 5-6 min) by 0.5-1 ml 0.06% solution in 10-20 ml 20% or 40% glucose solution. Highest intravenous doses for adults: single 1 ml, daily 2 ml 0.06% solutiona. Release form: ampoules 1 ml 0.06% solution Storage: list B, in a cool, dark place.

Strofantin K(Strophanthinim K) is administered intravenously (slowly over 5-6 min) by 0.5 ml 0.05% solution in 10-20 ml 5%, 20% or 40% glucose solution. Highest intravenous doses for adults: single 0.0005 G, daily 0.001 G respectively 1 ml and 2 ml 0.05% solution). Release form: ampoules 1 ml 0.05% and 025% solution. Storage: list A.

Celanide(Celanidum, synonym: isolanide, tantozide C, etc.) are administered orally to adults on average 0.00025 G in tablets or in drops of 10-25 drops per reception. Intravenously (slowly!) Enter 0.0002 G(1 ml 0.02% solution) in 10 ml 5%, 20% or 40% glucose solution. Higher doses for adults inside: single 0.0005 G, daily 0.001 G; intravenously: single 0.0004 G, daily 0.0008 G(respectively 2 and 4 ml 0.02% solution). Release form: tablets of 0.00025 G; vials of 10 ml 0.05% solution (for oral administration); ampoules 1 ml 0.02% solution. Storage: list A; in a place protected from light.

Bibliography: Budarin L.I., Sakharchuk I.I. and Chekman I.S. Physical chemistry and clinical cardiac glycosides, Kyiv, 1985; Gatsura V.V. and Kudrin A.N. Cardiac in the complex pharmacotherapy of heart failure, M., 1983, bibliogr; Handbook of clinical pharmacology and pharmacotherapy, ed. I.S. Chekman and others, p. 319, Kyiv, 1986.

1. Small medical encyclopedia. - M.: Medical Encyclopedia. 1991-96 2. First aid. - M.: Great Russian Encyclopedia. 1994 3. Encyclopedic dictionary of medical terms. - M.: Soviet Encyclopedia. - 1982-1984.

Cardiac glycosides are preparations of plant or chemical origin that have a positive effect on the functioning of the heart and increase myocardial contractility. Glycoside-containing plants include foxglove, lily of the valley, oleander, adonis and others. An increase in the rate and strength of heart contractions occurs without an increase in oxygen demand.

A characteristic feature of the drugs is the action aimed at narrowing the veins and arteries. Often this action can cause an increase in pressure, which is important to consider when prescribing them. This effect can be avoided by slow administration of drugs.

Operating principle

When a substance interacts with water, glycones and aglycones are released. The mechanism of action is based on the work of aglycones. Glycones do not have any effect on the work of the heart, but they contribute to the dissolution of glycosides and their connection with the plasma protein. Therefore, glycones ensure the penetration of glycosides into cells and have a direct effect on the mechanism of action of the drug.

After oral administration, the drug enters the gastrointestinal tract, and then into the circulatory system. Further, the elements of the drug are deposited in the tissues of the myocardium. The action of the drug is due to the strength of the bond between glycosides and plasma protein. Bond strength determines:

• accumulation of active substances in the blood;
• duration of action of the drug;
• crossing the blood-brain barrier.

The stronger the connection of the active substance with proteins, the longer the duration of the drug and the more pronounced the effect of cumulation.

The action of the drug has a significant impact on the functioning of the heart muscle. There is a decrease in the period of heart contractions and an increase in the duration of rest.

Thanks to glycosides, the work of the heart becomes clearer and more pronounced, the tone of the vagus nerve increases, the heart rate slows down.

Drugs have a similar effect on the conductive function of the cardiovascular system.

The effect of the drug on ion channels also depends on the concentration of the active substance in the blood and tissues of the heart muscle. The effect of the drug on the work of the cardiovascular system can be characterized by several categories:

• ionotropic effect. This is a positive effect, which is a consequence of an increase in the content of calcium ions in muscle tissues.
• Negative chronotropic effect. The negative impact is associated with the excitation of the vagus nerve.
• The dromotropic negative effect is the result of slowing down the transmission of nerve impulses.
• Bathmotropic positive effect is an undesirable effect, since it can lead to ventricular arrhythmias. An overdose of the drug leads to this factor.

Classification of cardiac glycosides

A unified classification of these drugs still does not exist. Today, the drug is classified according to two indicators: the concentration of the active substance in the drug and the duration of the drug.

Patients are treated with drugs consisting of one active ingredient or several. One-component preparations (Digoxin, Digitoxin, Strofantin) are produced synthetically. Multicomponent - herbal medicines, consisting of a mixture of active ingredients.

According to the classification, according to the duration of the action of the drug, cardiac glycosides can be divided into several categories:

1. Long acting drugs. After oral administration, they can affect the cardiovascular system for several days. Maximum efficiency is achieved after 9-12 hours. Medicines of this group often cause an overdose, because they can accumulate in the body. With intravenous administration, a positive effect is observed after 2 hours and earlier. Means of long-term action are obtained from digitalis by synthesis. They are able to quickly be absorbed into the stomach and penetrate into the tissues of the heart muscle, improving its contractile function.
2. Intermediate duration drugs. The process of removing them from the body occurs over several days. The maximum effect after administration can be expected after 6 hours. This group includes substances synthesized from rusty and woolly foxglove and adonis. Moderate absorption capacity of plants causes delayed action of drugs. When injected into a vein, the effect occurs after a quarter of an hour and lasts up to three days.
3. Means of short exposure. They are typically administered intravenously. Such medicines do not possess accumulative properties and are means of ambulance. Provide unstable, but fast effect. When injected into a vein, the effect occurs after 5 minutes and lasts up to two days.

In what cases are assigned

The use of medicines for heart failure is carried out in the following cases:

• Acute disorders of the cardiovascular system that have arisen against the background of atrial arrhythmia.
• Chronic insufficiency of the cardiovascular system.
• Constant atrial fibrillation in conjunction with a high heart rate. In this case, therapy begins with the introduction of maximum doses. This technique is prescribed until the severity of insufficiency decreases. This is followed by preventive treatment, which is characterized by taking the drug in smaller doses. If there are signs of toxic drug poisoning, the drugs are canceled, and then therapy with potassium and magnesium preparations is carried out.
• Circulatory failure.
• Supraventricular tachycardia.

The use of glycosides can reduce the heart rate and enhance the work of the heart muscle.

The effect of drugs in each individual case depends on the state of the body and the degree of expression of heart failure. After taking drugs in a healthy person, an increase in peripheral resistance is observed. The action of the drug is aimed at normalizing hemodynamic parameters, eliminating fluid stagnation and cardiac dysfunction (edema, shortness of breath, cyanosis, tachycardia). Appointment of cardiac glycosides is made in severe cases. Stagnation of blood circulation provokes the filling of veins, swelling. Due to insufficient cardiac output, it can develop. In this case, the main goal of therapy is to increase hypodynamic indicators.

Taking glycosides makes it possible to change atrial flutter to flicker and control the rhythm of ventricular contractions. Long-term therapy is indicated in cases where there is a risk of relapse. With the recurrence of heart failure, an increased cardiac output is diagnosed. The phenomenon can be caused by various anemias, infectious diseases, bypass of the circulatory system. These are signs of a weak reaction of the body to glycosides and their irrational purpose.

Contraindications for use

The use of drugs is strictly prohibited in the following cases:

• allergic reactions to the components of the drug;
• the appearance of intoxication as a result of prolonged use of glycosides;
• violation of the conduction of impulses from the atria to the ventricles;
• sinus bradycardia.

There is also a list of relative contraindications, in the presence of which the drug should be taken with caution:

• weakness of sinus rhythm;
• low frequency of atrial fibrillation;
• high sensitivity to drug components;
• serious diseases of the liver, lungs and urinary system;
• a state of infarction;
• anemia;
• aortic insufficiency.

Since there are a large number of contraindications to prescribing medications, only the attending physician should prescribe cardiac glycosides.

Almost all contraindications are relative, therapy is always prescribed individually. There is always an opportunity to choose the right treatment option. In diseases of the urinary system and liver, the intake of only certain types of medications is limited. Before prescribing a particular drug, in addition to excluding side effects, the following factors must be considered:

• patient's weight;
• the state of functioning of the kidneys;
• detection of atrial arrhythmias.

The presence of atrial arrhythmia indicates the need to increase the dosage of the drug compared with the treatment of heart failure. If the patient is overweight, it is necessary to accurately calculate the dosage (depending on age, height and weight). Since glycosides do not accumulate in fatty tissues, dose selection should be based on lean body mass.

Overdose of glycosides

This group of drugs belongs to the class of increased toxicity.

Drug poisoning can occur with a single use of an increased dose of the drug or as a result of long-term use.

Overdose symptoms:

• ventricular fibrillation or tachycardia;
• nausea and vomiting;
• characteristic changes in the ECG;
• disruption of the heart, up to its complete stop.

The presence of these signs is a signal for the complete cessation of medication. In fact, intoxication is rare. Poisoning can occur as a result of incorrect prescription or erroneous intake of a large dose. Self-treatment is especially dangerous. Medicines of this group must be kept away from children. The constant use of the drug for heart failure and its slow removal from the body can lead to the accumulation of active substances in the tissues and the appearance of complications.

In children, due to intoxication, arrhythmia most often occurs. In adults and the elderly - a violation of mental activity. With a large overdose, a fatal outcome is possible. Against the background of side effects of taking glycosides, it is necessary to call an ambulance. In parallel, it is necessary to take activated charcoal and gastric lavage, taking a laxative.

List of drugs used to eliminate signs of intoxication:

• Panangin, potassium orotate, potassium chloride - to ensure the supply of potassium to the myocardium, where, under the influence of glycosides, an element deficiency has formed.
• Citation salts and Trilon ensure the binding of calcium molecules.
• Lidocaine, anaprilin, propanalol - help get rid of arrhythmia.
• Difenin is used to remove glycosides from the body.

Side effects of drugs

While taking glycosides, the following side effects may occur:

• breast enlargement;
• headaches and dizziness, insomnia;
• violation of the heart rhythm;
• lack of appetite;
• hallucinations and clouding of consciousness;
• damage to the vessels of the mucous membranes, leading to bleeding;
• change in the perception of the color of objects.

Taking drugs can cause difficulty in blood flow and disruption of cardiac activity. As a result, urinary function is impaired. Disruptions in the digestive system can lead to anorexia, diarrhea, and stomach pain. Effects such as a skin rash may also occur.

Characteristics of drugs

Each type of medicine in this group has its own pharmacological characteristics. This is expressed in activity, speed and duration of exposure. The most common cardiac glycosides.

Digoxin

The drug is synthesized from the leaves of woolly foxglove.

It is characterized by prolonged exposure, does not provoke the appearance of serious side effects. The withdrawal period is usually 2-5 days, has a low cumulative capacity. It is used for chronic and acute heart failure, prevention of heart disease in patients with compensated heart defects. The drug is characterized by an average speed and an average duration of exposure.

Woolly foxglove leaves contain cardiotonic glycosides

Strofantin

The drug is fast-acting and lacks the effect of accumulation in the tissues. Complete excretion of the substance occurs a day after ingestion. The maximum effect is observed after a quarter of an hour after injection into a vein. Strofantin is prescribed only intravenously, since it is practically not absorbed from the gastrointestinal tract. Excreted through the urinary system. It is a fast-acting medicine with a short period of action. There is no cumulative effect. The drug does not change the frequency of contractions of the heart muscle. It is used in acute heart failure and in severe chronic heart failure.

Digitoxin

Used less frequently. The main features of the drug are a high cumulation effect and frequent intoxication with the active substance. Correctly calculating the dosage of the drug is quite difficult. After administration, the drug is absorbed almost completely and completely binds to plasma proteins. The maximum effect appears 5-12 hours after application. Release form - tablets and suppositories. A high cumulative effect determines the low rate of excretion of the active substance. Digitoxin is the longest acting and slowest drug. It is used for chronic diseases of the cardiovascular system, together with strophanthin.

Additionally, therapy with cardiac glycosides contained in plants is prescribed. These are pharmacy infusions or self-prepared medicines.

Cardiac glycosides- Group medicinal funds treatment sick with cardiovascular insufficiency.

Cardiac glycosides are composed of a sugar and an aglucone, a steroid ring bonded to a lactone. The sugar-free part (aglucone, genin) affects the heart. The nature of the sugary part determines the activity, solubility, absorption and distribution of the glycoside.

Mechanism actions different glycosides is generally the same, although some aspects actions they have their own characteristics. Pharmacodynamics of cardiac glycosides includes their effect on:

1) contractile proteins;
2) the exchange of electrolytes in the heart muscle;
3) phosphorus metabolism and the exchange of macroergic compounds;
4) oxygen exchange and, consequently, the processes of aerobic glycolysis;
5) autonomic nervous system;
6) the central nervous system.

The action of cardiac glycosides on the myocardium due to their valuable property to increase the strength and speed of heart contractions without significant oxygen consumption by the myocardium. Under the influence of drugs, the heart can perform the same work with less energy expenditure (with less oxygen consumption) or more work with almost unchanged energy expenditure. In other words, cardiac glycosides increase the coefficient of useful actions cardiac muscles.

The mechanism for improving the contractile function of the myocardium under the influence of cardiac glycosides (positive inotropic effect) may be:

1) in their primary favorable effect on the formation and use of energy by the myocardium;
2) in a change in the intracellular concentration of ions, in which the contractile function of the heart improves for the second time;
3) in direct action on myocardial contractile proteins.

Data from experimental studies testify both in favor and against each of these concepts of the mechanism of the positive inotropic effect of cardiac glycosides.

According to recent studies, cardiac glycosides exert their effect by blocking the sulfhydryl groups of potassium-sodium ATPase, changing the state of ion exchange in the cell. At the same time, the reduced cardiac Insufficiency of the intracellular content of potassium, the distribution of sodium between the cell and the extracellular space is normalized, which contributes to an increase in the contractile function of the muscle cell. There is evidence of the effect of these drugs on the system of calcium regulation of contraction: they increase the entry of calcium to contractile proteins and increase contraction. The introduction of cardiac glycosides causes an increase in the activity of a number of respiratory enzymes in the myocardium, which enhances energy production and improves oxygen utilization. In this case, the acceleration of actin polymerization leads to an acceleration of myosin contraction.

For example actions celanide (isolanide) and other cardiac glycosides under conditions of experimental subacute cardiac insufficiency of the hemodynamic type, it has been shown that cardiac glycosides contribute to an increase in the content in the muscle hearts DNA and RNA and improve the processes of oxidative phosphorylation, i.e., aerobic glycolysis. Of particular note is the fact that the positive effect of cardiac glycosides on the muscle hearts manifests itself only in conditions of myocardial dilatation and subject to the preservation of sufficient energy capacity of the heart, adequate to the applied doses of drugs in this group.

Nevertheless, the firmly established opinion that glycosides act only on the affected heart has now been shaken: a clearly pronounced positive inotropic (improving myocardial contractility) and negative chronotropic (slowing down the heart rate) effect of cardiac glycosides can also be observed in individuals with healthy heart.

Numerous studies have shown that the administration of cardiac glycosides sick With cardiac insufficiency leads to an increase in stroke and minute volumes of the heart. The size of the “insufficient” heart decreases, which is associated with a decrease in pressure in its cavities at the end of diastole and a decrease in venous flow to the heart. The speed and fullness of systole increase regardless of the initial diastolic length of myocardial fibers, which is undoubtedly the main consequence of positive inotropic actions cardiac glycosides.

And as a result of strengthening the negative dromotropic (inhibiting conductivity) influence of the vagus nerve under the action of proud glycosides, the absolute refractory period is shortened and the relative refractory period is lengthened. At therapeutic doses drugs suppress sinus automatism. bradycardic Effect Kick is associated with both direct and extracardiac vagal effects of cardiac glycosides on the automatism of the sinus node. In small doses, cardiac glycosides reduce, and in toxic doses they increase the automatism of the atria. In therapeutic doses cardiac glycosides cause a slowdown in atrioventricular conduction, which reaches the degree of atrioventricular blockade with an increase in the dose of the administered drug. Toxic doses increase the automatism of the atrioventricular node, which can lead to nodal extrasystoles, nodal forms of tachycardia, etc. Finally, the earliest direct manifestations actions cardiac glycosides on the ventricular myocardium - a decrease in excitability (automaticity), a decrease in the absolute and an increase in the relative refractory period. An increase in the doses of cardiac glycosides increases the automatism of the myocardium, which, combined with a decrease in conductivity in the Purkinje fibers, causes the appearance of "recurrent" extrasystoles, ventricular tachycardia and ventricular fibrillation.

Speaking about the effect of cardiac glycosides on the bioelectric function of the “insufficient” heart, it should be noted that the suppression of sinus automatism in most cases is positive, since with a slow rhythm, work hearts becomes more economical. However, the decrease in heart rate sick With cardiac insufficiency is more often secondary to the positive effect of cardiac glycosides and appears simultaneously with other clinical symptoms of improved blood circulation. An increase in minute volume is also beneficial. hearts and decline pressure in hollow veins. Atrioventricular conduction suppression may be beneficial sick atrial fibrillation. An increase in excitability and the appearance of foci of heterotropic automatism (positive bathmotropic effect) under the influence of cardiac glycosides in most cases affects the heart negatively, as it leads to the appearance of various ectopic arrhythmias. The foci of inflammation, ischemia, dystrophy, degeneration, which were not detected earlier, under the influence of drugs in this group, may manifest as extrasystoles.

Among the non-cardiac effects of cardiac glycosides, a diuretic effect should be noted, which is most associated with a general improvement in hemodynamics and blood circulation in the kidneys and only partly with the inhibition of tubular reabsorption. The idea that was formed in due time that cardiac glycosides impair coronary circulation is not confirmed by specially conducted studies in recent years.

cardiac glycosides in sick both left ventricular and right ventricular cardiac insufficiency Cause a decrease in peripheral pulmonary resistance, despite a direct vasoconstrictive effect on the pulmonary artery. At sick with decompensation and portal stagnation, they, with a simultaneous increase in minute volume, lead to a narrowing vessels abdominal organs and expansion of peripheral vessels. On the arterial pressure cardiac glycosides do not have a direct effect: it changes in accordance with the nature of central hemodynamics. The relationship between the value of peripheral venous pressure and cardiotonic effect of drugs, which, apparently, is due to their local action on peripheral foams, as a result of which venous pressure decreases.

Indications for the appointment of cardiac glycosides: heart failure, supraventricular tachycardia and tachyarrhythmia, prevention cardiac insufficiency.

without touching treatment cardiac glycosides rhythm disturbances hearts(see "Antiarrhythmic drugs"), it should be borne in mind that for any cardiac insufficiency, regardless of its origin, the appointment of cardiac glycosides is indicated. In every case treatment this group of drugs should be carried out taking into account the etiology and pathogenesis of the disease itself, which led to the development cardiac insufficiency, and always against the background of etiological and pathogenetic complex treatment(treatment of myocarditis, rheumatism, collagenoses, heart attack myocardium, atherosclerosis, etc.).

The success of glycoside therapy depends primarily on the doctor's knowledge of the pharmacological properties of the drug, its rational dosage depending on the severity and severity. cardiac insufficiency, from the individual characteristics of the clinical picture of the disease, as well as taking into account factors that change the sensitivity and reactivity of the myocardium to cardiac glycosides.

With prolonged intoxication cardiac glycosides are contraindicated. With the so-called relative contraindications, in reality, we are talking either about hypersensitivity to the toxic effects of drugs in this group, or about the absence of indications for their appointment, or about the careful use of individual drugs for a certain type. cardiac pathology. So, for example, slowing atrioventricular conduction in sinus rhythm is not an unconditional contraindication to the appointment of cardiac glycosides. sick with circulatory failure, but requires certain caution and careful clinical and ECG control, especially in atrioventricular block II degree. According to B. E. Votchal and M. E. Slutsky (1973), with a complete transverse (atrioventricular) blockade, there is no need to fear a further deterioration in conductivity: it will not become “fuller”. In some cases, the number of ventricular contractions may increase due to an increase in the automatism of the atrioventricular connections or the bundle of His.

Below are drugs various groups of cardiac glycosides. For the success of treatment, as B.E. Votchal (1965, 1973) points out, it is enough for doctors to have a small amount of glycosides in their arsenal (one or two drugs of each group).

Digitalis purpurea preparations. This group includes foxglove, digitoxin and cordigite. (See List of drugs in the group Cardiac glycosides).

Woolly foxglove preparations. In woolly foxglove, glycosides are bound not only to the glucose molecule, but also to the anetyl radical, which gives them new properties. Acetylated glycosides act quickly and accumulate much less. In medical practice apply individual digitalis woolly glycosides (digoxin, celanide, acetyldigitoxin) and preparations containing the sum of glycosides (abicin, lantoside, dilanizide). (see List of drugs of the group Cardiac glycosides).

Adonis preparations. Use the herb from which preparations are made. The active principles of Adonis are glycosides, the main ones being cymarin and adonitoxin. The nature actions they are close to digitalis glycosides, however, they have a less pronounced systological and diastological effect, they have less effect on the tone of the vagus nerve. Significantly less stable in the body and have a shorter duration of action. Practically do not have cumulative properties. Adonis preparations give a sedative and diuretic effect. When taken orally, the action of drugs begins after a few hours and stops within a day. Recommended for long-term treatment on an outpatient basis.

Two drugs are used - an infusion of adonis herbs(adonis) and adonizide.

Oleander preparations. One drug of this group is of practical importance - neriolin.

Strophanthus preparations and glycosides strophanthin-like action. Depending on the plant, from the seeds of which strophanthin is obtained (Strophanthus Kome, or Strophanthus gratus), there are strophanthin K and strophanthin G. Other drugs in this group: Strophanthus tincture, Convallatoxin, Korglikon, Eryzimin, Erysimozide, Korezid, Cymarin, Olitorizide, Corhorizide, Gomphotin, Korelborin. From the plants growing in the USSR - kendyr prolomnikolisty, cannabis kendyr, golden adonis and spring adonis - K-strophanthin-ß was isolated. In terms of properties and therapeutic effect, domestic strophanthin does not differ from strophanthin-K obtained from imported raw materials.

Strofantin- one of the best remedies used in the most severe and acute cases cardiac insufficiency and often saving from death sick With cardiac asthma or pulmonary edema.

Comparison of different sides actions domestic drugs K-strophanthin-β and strophanthin-like medicines(cymarin, eryzimin, erysimoside, corhorizide and olithorizide) allows one to arrange them in descending order of effectiveness according to a number of features. By the speed of onset of action: K-strophanthin-β, cymarin, olitorizide, corhorizide, eryzimin and erysimoside; according to the diastolic effect, i.e., the decrease in tachycardia: corhorizide, eryzimin, olitorizide, K-strophanthin-β, cymarin and eryzimoside; in terms of overall therapeutic efficacy and cardiotonic action: corhorizide, olitorizide, K-strophanthin-β, cymarin, erizimin and eryzimoznd.

dosing strategy. As already noted, in the elimination mechanism heart failure there are no fundamental differences between individual cardiac glycosides. There are certain features that are associated with the speed of onset and duration actions the drug, its ability to bind to blood proteins, unequal absorption from the stomach and intestines, etc.

A very important property of cardiac glycosides is cumulation, which is unequally expressed in different drugs. Cumulation is associated with the peculiarities of the metabolism of glycosides in the conditions of the whole organism. It cannot be explained by their selective accumulation in the myocardium. Duration actions various glycosides is due to the duration of their circulation in the blood, which, in turn, depends on the rate of conversion and excretion of drugs from the body. This can be seen in the example of digitoxin. Digitoxin, firmly fixed in the liver, turns into digoxin and other cardioactive substances. Digntoxin is mainly excreted from the body through the kidneys. However, this process is very slow, since in the blood digitoxin enters into strong chemical bonds with serum albumins, which are not filtered by the kidneys. The digitoxin excreted in the bile is almost completely absorbed back into the blood in the intestines. This explains its long circulation in the blood.

Cardiac glycosides such as strophanthin are rapidly and in large quantities excreted unchanged in the feces and urine, since they are practically unable to bind to serum albumins. Free glycosides are well filtered through the kidneys.

In addition to cumulation, cardiac glycosides differ in the strength of their inotropic and bradycardic effects. Their positive inotropic Effect inversely proportional to bradycardic action, cumulative properties and absorption from the stomach and intestines. The main representatives of cardiac glycosides, in decreasing order of effectiveness, are arranged according to the bradycardic action in the following sequence: digitoxin, acetyldigitoxin, digoxin, celanide, strophanthin; by cumulative properties: digitoxin, acetyldigitoxin, digoxin, celanide, strophanthin; by absorbability: digitoxin, acetyldigitoxin, digoxin, celanide, strophanthin.

A necessary condition for the correct conduct of each type of drug therapy, including cardiac glycoside therapy, from the point of view of clinical pharmacology is to determine the value of the therapeutic concentration of the drug in the patient's blood in order to correct it. Currently, radionuclide methods for determining the concentration of cardiac glycosides in the blood are being increasingly introduced, which makes it possible to carry out treatment actively, adequately, to avoid drug overdose and possible intoxication. However, in clinic this is not always available, and therefore the determination of the therapeutic dose according to clinical data and its correction taking into account the absorbability of the drug and its elimination is of great importance.

In this regard, the concept of the average total dose has been introduced. actions(full therapeutic dose), which is understood as the amount of cardiac glycoside that gives the maximum therapeutic Effect most sick with circulatory failure without manifestation of toxic symptoms. In the first period treatment cardiac glycosides (saturation period) must be achieved for a more or less long time (depending on the patient's condition) full therapeutic dose. Later, in the second period treatment(period of maintenance therapy), prescribe such a dose of the drug (maintenance dose), which consolidates and stabilizes the therapeutic effect at the achieved level.

With intravenous administration, the average total dose for all cardiac glycosides is the same: for digitalis glycosides - about 0.002 g (2 mg), for strophanthin-like glycosides actions- 0.0006-0.0007 g (0.6-0.7 mg). When prescribing cardiac glycosides orally, given the unequal absorption of various drugs, the average complete dose actions will be different: it is the less, the better the glycoside is absorbed. For drugs that are completely absorbed (digitoxin), it will be the same as when administered intravenously (0.002 g, or 2 mg); for drugs, the absorbability of which is 50% - 2 times greater, 30% - 3 times greater, etc.

The therapeutic features of individual glycosides are also associated with differences in the speed of the therapeutic effect, which, in turn, depends on their greater or lesser ability to bind to blood proteins. In a bound state, cardiac glycosides are inactive, although the glycoside-protein complex constitutes a depot, from which, upon destruction, the glycoside enters the blood again and exerts an effect. Thus, it is necessary to know the initial and maximum Effect drug, the duration of its possible actions in the body. Duration actions and the degree of cumulation of various drugs are given in table. 7.

Table 7. Duration and degree of accumulation of various cardiac glycosides

It has been established that the daily loss of the drug is proportional to its destruction and excretion (elimination) from the body. A strictly constant percentage of the drug is eliminated per day, which is designated as the elimination coefficient. The lower the elimination coefficient, the greater the residual effect coefficient. This also depends on the support dose drug.

In table. 8 shows the quantitative parameters of the main cardiac glycosides according to B. E. Votchal et al. (1973, 1974).

The coefficient of daily elimination, or the coefficient of residual actions(their sum is always equal to 100%), one can replace the vague concept of cumulation. Moreover, each of these coefficients is a quantitative measure of cumulation. For example, if, after reaching the optimal therapeutic effect, maintenance dose strophanthin will exceed 40% of the total dose actions drug, celanide and digoxin - 20%, acetyldigitoxin - 10%. digitoxin - 7%, symptoms of intoxication may appear.

TABLE 8 - Quantitative parameters of the main cardiac glycosides

In the initial period of the use of cardiac glycosides, it is necessary to determine the rate of digitalization individually for the patient: fast (during the day), medium (3-4 days) or slow (more than 5 days). In table. 9 shows an indicative scheme for the use of the main cardiac glycosides at various rates of digitalization.

The faster the onset and the more severe heart failure, the greater the need for rapid saturation of the patient's body with cardiac glycosides. At the same time, the faster the pace of digitalization, the greater the likelihood of toxic complications, i.e., the most dangerous is the rapid pace of digitalization. Before deciding on it, it is necessary to weigh all the circumstances in each case. The higher the rate of digitalization, the more frequent and thorough clinical and ECG monitoring should be. In this regard, with a fast, as well as with an average rate of digitalization, the patient should be placed in the intensive care unit under constant round-the-clock monitoring with a monitor connected.

In the second period treatment cardiac glycosides, it is necessary to maintain an effective concentration of the drug. Medium support dose calculated by the elimination coefficient and the average total dose of glycoside. For example, for digoxin, complete dose actions when given orally, the average is 3 mg, and the elimination coefficient is 20%. Medium support dose will be equal to:

(3mg * 20%) / 100% = 0.6mg

Having received the optimal therapeutic effect, it is not difficult for each patient to calculate an individual dose of full action, and then a maintenance dose. To simplify the mathematical calculation of individual doses and more frequent monitoring of the administered drug, there are electronic computing computer installations that perform operations very quickly and simultaneously for many patients.

In the case of switching from one digitalis preparation to another, there are usually no special difficulties, although one should keep in mind the possible difference in the absorption of the drug and its elimination. Knowing the average total and maintenance doses of each drug, as well as individual doses, it is easy to calculate. If this rule is not observed, substitution of one drug for another may

Table 9. Indicative scheme for the use of the main cardiac glycosides at various rates of digitalization

be ineffective due to insufficient dosage. B. E. Votchal and M. E. Slutsky (1973), when replacing strophanthin with foxglove leaf powder, recommend in the first 2 days after the abolition of strophanthin to prescribe digitalis at 0.45 g per day, on the 3rd-4th day, 0, 3 g, and on the 5th day - 0.2 g each, and from the 6th day switch to a maintenance dose of the drug - 0.15 g.

If it is necessary to prescribe strophanthin instead of drugs of the digitalis group, for example, when signs of acute cardiac insufficiency, increasing circulatory disorders, it is recommended to take a break from 3 to 7 days, depending on the drug used. Knowing the elimination coefficient of each drug of the digitalis group, it is possible to accurately calculate the timing of the administration of strophanthin and the dose. So, with a decrease in digitalization to 80% of the total dose actions the patient can enter 0.125 mg (1 / 4 ampoules) strophanthin, since this dose is about 20% of its average total dose of action. Such dose strophanthin can be administered after the abolition of digitoxin on the 4th day, after the abolition of digitalis - on the 2nd day and after the abolition of lantoside - the next day. A dose of strophanthin 0.25 mg, i.e. 40% of its full dose of action, can be administered with a decrease in the level of digitalization to 60%, i.e. for the above drugs, respectively, after cancellation on the 7th, 4th and 2nd th day.

In acute circulatory disorders due to insufficient digitalization (less than 75% of the total dose of action), the risk of overdose is small, therefore practically strophanthin or better corglicon (intravenously drip or intramuscularly in fractional doses) in these cases can be administered without any interruption in treatment. At the same time, careful monitoring is necessary, which is most reliably carried out in the wards of intensive observation and treatment, especially if one takes into account the often arising need to increase the doses of potent drugs of cardiac glycosides.

If it is necessary to replace one drug with another, it is of great practical importance to identify the relationship between the values ​​of optimal maintenance therapeutic doses of various cardiac glycosides. Comparative studies conducted in the same patients made it possible to establish, for example, that the ratio of optimal therapeutic doses of corglicon and strophanthin is adequate in terms of therapeutic effect is 3: 1, olithoriznda and strophanthin is 2: 1, beta-methyldigoxin and digoxin (when prescribing them inside) - 1: 1.6, and equivalent maintenance doses - 2: 1, respectively; 1.75:1 and 1:1.48.

Clinical indicators of the level of digitalization. Clarification of the degree of saturation with cardiac glycosides without data on their concentration in the blood is a very important clinical problem. Clinical indicators of the therapeutic level of digitalization can be reduced to the following main features: 1) change from tachycardia to a normal number of heartbeats; 2) reduction of clinical signs of circulatory failure (shortness of breath, cyanosis, edema); 3) the transition of the tachysystolic form of atrial fibrillation to the bradysystolic form (at a 100% level of digitalization, physical activity or an injection of atropine does not cause a significant increase in ventricular contractions).

Intoxication with cardiac glycosides. Symptoms of intoxication with cardiac glycosides are not associated with the use of a specific glycoside for therapeutic purposes. Different glycosides can cause the same signs of poisoning, and, conversely, repeated intoxication with the same glycoside can manifest itself differently in the same patient. Therefore, the terms "intoxication with cardiac glycosides" and "digitalis intoxication" are equivalent.

It has been established that 1 out of 5 patients receiving cardiac glycosides has some degree of intoxication with digitalis. The development of intoxication is facilitated by a small interval between therapeutic and toxic doses: therapeutic dose is approximately 60% toxic. Symptoms of overdose are observed in 8-22% of adults treated with cardiac glycosides, and in acute heart attack myocardium - in 32%. In recent years, cases of digitalis intoxication have become more frequent, which is associated with the appearance of highly active purified cardiac glycosides, diuretics, the wider use of digitalis preparations, especially in the elderly, and improved ECG diagnostics. The main value is still a decrease in the threshold of sensitivity to digitalis preparations. The reason for this is a pronounced damage to the myocardium by a pathological process (inflammation, necrosis, sclerosis), as well as potassium deficiency as a manifestation of postdiuretic syndrome (abundant diuresis and kaliuresis after the use of powerful diuretics), the widespread use of glucocorticoid hormones and insulin with glucose. In this case, it is important to reduce the level of potassium not in the blood, but in cardiac muscle, which is observed in myocarditis, heart attack myocardium, repeated pulmonary thromboembolism and other diseases. Hypokalemia is associated with postdefibrillation arrhythmias in patients who received cardiac glycosides before electropulse treatment (“leakage” of intracellular potassium into the extracellular environment through cell membranes damaged by electric current). The reason for the decrease in tolerance to cardiac glycosides can also be hypercalcemia and hypomagnesemia, damage to the kidneys and liver, leading to delayed elimination of the drug and its accumulation in the body, hypoxemia and a violation of the acid-base state.

The toxic effect of cardiac glycosides is potentiated by catecholamines (appearance of extrasystolic arrhythmia), purines, especially eufillin (appearance of ectopic rhythms), reserpine, quinidine, and a number of quinidine-like antiarrhythmic drugs.

Higher sensitivity to cardiac glycosides is observed in men, as well as in the elderly and senile age.

Symptoms of digitalis intoxication can be divided into the following main groups: cardiac, gastrointestinal, ocular, neuropsychiatric, endocrine-like and allergic.

Main manifestations on the part hearts with digitalis intoxication, they consist either in an increase in circulatory failure, or in the appearance of arrhythmias.

Increased circulatory failure in digitalis intoxication is a consequence of damaging actions drug on myocardial contractile proteins and deterioration of its contractile function. The degree of circulatory insufficiency does not decrease, and may progress even more, despite the use of cardiac glycosides. Cancellation of the drug leads to a decrease in decompensation. This type of digitalis intoxication accounts for approximately 7.5% of all cases of intoxication.

Toxic doses cardiac glycosides give a coronary effect, as a result of which angina attacks may appear or become more frequent. This complication is observed in 4.8% of cases of intoxication and, as a rule, is combined with cardiac arrhythmias or other symptoms of digitalis intoxication.

Arrhythmias are the most common symptom of digitalis intoxication. In this case, any violations of the rhythm and conduction are possible. Most often, extrasystole and slowing of atrioventricular conduction are observed. Of the extrasystoles, there are more often ventricular by the type of bigeminy, much less often - atrial. Atrioventricular blockade is observed, mostly incomplete, I, less often II degree, although it may be complete. Less common are sinus bradycardia, atrial and ventricular tachycardia, atrial fibrillation, atrioventricular rhythm and tachycardia, atrioventricular dissociation, sinus arrhythmia, sinoauricular block, or pacemaker migration. Very rarely, ventricular fibrillation occurs.

With digitalis intoxication, two or more types of cardiac arrhythmias usually occur simultaneously, ectopic rhythms are combined with conduction disturbances.

Arrhythmias caused by cardiac glycosides do not have specific signs and can be equally caused by heart disease, extracardiac influences, or concomitant therapy. However, the recognition of digitalis arrhythmias is of great practical importance, since it is necessary to decide whether to cancel cardiac glycosides or increase their dose if these arrhythmias are associated with cardiac insufficiency. In such cases, careful questioning helps. sick regarding symptoms of overdose in the past and the appearance along with arrhythmia of extracardiac signs of intoxication.

Despite the lack of a clear correlation between the toxic reaction to digitalis and the type of arrhythmia, some of them are still very suspicious: atrial tachycardia with atrioventricular block and non-paroxysmal atrioventricular tachycardia, atrioventricular block with accelerated nodal excitation, ectopic arrhythmias simultaneously from different foci, ventricular extrasystole with atrial tachycardia and blockade, bidirectional ventricular tachycardia, the coexistence of ectopic rhythms with inhibition of conduction. In these cases, it is necessary to cancel digitalis preparations until the final decision on the causes of the rhythm disturbance.

Diagnosis of an overdose of cardiac glycosides Thus, in some cases it is very difficult. In this regard, a number of tests have been proposed to determine the saturation of the body with digitalis preparations. One group of such tests is unsafe (administration of acetylstrophantidine, corglycone, calcium salts), as it is based on a transient increase in the toxic effect of digitalis, i.e., it is accompanied by an increase in heart rhythm disturbance. The second group includes methods based on the introduction of digitalis antidotes into the body (potassium salts, magnesium sulfate, anaprilin, etc.) or on the creation of artificial hypocalcemia by introducing salts of EDTA (ethylenediaminetetraacetate) or, at the suggestion of B.E. Votchal and M.E. Slutsky (1973), sodium citrate (1-5 g in 50-250 ml of liquid). If, after the introduction of these drugs, the arrhythmia disappears or decreases, the sample is considered positive. At treatment Difenin and unithiol are also effective for dngitalys arrhythmias, which can also be used to detect glycoside intoxication in a patient. This group of samples is safe, although all of these methods in general are not strictly specific for the removal of digitalis arrhythmias, which reduces their diagnostic value.

For diagnostics of all the above arrhythmias due to an overdose of cardiac glycosides, the ECG is of great importance, since their diagnostics only clinical methods are often difficult, and topical diagnostics often not possible at all. In addition, the use of digitalis preparations leads to certain ECG changes.

Under the influence of digitalis on the ECG, the phase of myocardial repolarization is accelerated, which is reflected in the shortening of the Q-T interval and the gradual decrease in the S-T interval. The S-T interval has either a rectilinear shape with a gradual decrease towards the T wave, or the shape of an arc, convex downward, which, merging with the ascending T wave knee, acquires a characteristic trough-shaped or saddle shape. The T wave may flatten, then become biphasic (-+), and later negative. Changes in the S-T interval and the T wave under the influence of atropine do not disappear, which is explained by a direct effect on the myocardium.

Shortening not only electrical systole hearts- Q-T segment, but also mechanical systole and systolic index. Unsharp widening and serration of the QRS complex is sometimes noted. It should be emphasized that shortening of the QT interval is often the first ECG sign of digitalis exposure. In some cases, a slight lengthening of the P-Q interval joins the listed changes.

The changes in the S-T interval and the T wave due to the influence of digitalis are most clearly manifested in hypertrophy of one of the ventricles of the heart. In the case of left ventricular hypertrophy, a decrease in the S-T interval and a negative or two-phase (-+) T wave are recorded in I, II, avL (less often avF and III) and left chest leads, and a positive T wave with a slight upward displacement of the S-T interval - in the right chest leads and avR. In the case of right ventricular hypertrophy, a negative or biphasic (---+) T wave and a decrease in the S-T interval are recorded in II, III, avF and right chest leads, and a positive T wave is recorded in I, avL and left chest leads. With hypertrophy of both ventricles under the influence of digitalis, the S-T interval and the T wave change both in the left chest leads (discordant to qR) and in the right (concordant to rS). In these cases, a positive T wave is recorded only in the avR lead, and in the remaining 11 leads, the above-mentioned shifts in the S-T interval and the T wave are noted.

However, the above ECG changes, as well as various types of arrhythmia, cannot serve as a quantitative indicator of either therapeutic or toxic effects. actions cardiac glycosides.

The earliest symptom of digitalis intoxication is often loss of appetite, very rarely diarrhea. Anorexia is followed by nausea and vomiting 2-3 days later. However, vomiting can develop suddenly, without warning. Dyspeptic disorders are often accompanied by discomfort and pain in the abdomen. Purified glycosides cause nausea and vomiting less frequently than digitalis leaf. The development of these symptoms is currently associated by most authors with direct or reflex excitation of the vomiting center by cardiac glycosides, and not with irritation by ballast substances (mainly saponins), which are contained in foxglove powder and its herbal preparations. This is evidenced by the appearance of vomiting during intravenous infusion of cardiac glycosides. The frequency of dyspeptic symptoms of digitalis intoxication, according to various authors, varies, ranging from 11 to 40% of all cases of intoxication. It must be remembered that dyspeptic disorders can also be the result of circulatory failure itself (congestion along the digestive apparatus).

Eye symptoms digitalis intoxication: color hallucinations (staining of all objects in yellow or green), flickering of “flies” before the eyes, dark and colored spots, rings, balls, stripes, trembling of objects, decreased visual acuity, cattle, macro- and micropsia (perception of objects enlarged and reduced). These disorders are associated with the development of retrobulbar neuritis. Even blindness, intermittent or permanent, may occur. Many of these disorders are found only with a special survey of the patient and in general rarely, usually only with intoxication with very large doses of cardiac glycosides.

To neuropsychiatric symptoms digitalis intoxication include weakness, fatigue, insomnia, headache, dizziness, depression, confusion, adynamia, aphasia, delirium, etc. Psychoses, known in the literature as "digitalis delirium", are especially common in the elderly and during decompensation sick with aortic heart disease. A special study of this issue in France in healthy people who tried to poison themselves with digitalis showed the specificity of these mental abnormalities for intoxication with cardiac glycosides. Less commonly, symptoms of digitalis intoxication develop in the form of damage to the peripheral nervous system: neuritis of the trigeminal and lumbar nerves, intercostal neuralgia, sciatica of the thoracic and lumbar spine.

Endocrine-like disorders due to intoxication with cardiac glycosides include gynecomastia, the occurrence of which is associated with the estrogen-like action of drugs in this group. This type of complication is rare.

Even rarer complications of digitalis therapy are urticaria and eosinophilia. Isolated cases of thrombocytopenia with bleeding have been described.

Treatment of digitalis intoxications is reduced to the abolition of cardiac glycoside, to measures aimed at increasing tolerance to the drug, to the elimination of arrhythmias that pose a threat to the life of the patient.

With a mild degree of intoxication, it is enough to cancel the cardiac glycoside for several days so that all its manifestations pass. However, not always with mild intoxication (the presence of dyspeptic phenomena), the drug should be canceled. You can change the method of administration (replacement of oral administration with rectal or parenteral administration), connect means that increase the patient's tolerance to the glycoside. With the appearance of digitalis arrhythmias, cardiac glycosides are canceled.

In each case of digitalis intoxication that did not result from an obvious overdose, after discontinuation of the drug, an attempt should be made to find out the cause of the decrease in tolerance to cardiac glycosides and eliminate it. First of all, a correct and effective complex etiological and pathogenetic treatment underlying disease (rheumatism, myocarditis, heart attack myocardium, ischemic disease heart, pulmonary thromboembolism, pulmonary hearts etc.), elimination or reduction of hypoxemia, hypokalemia, hypercalcemia, hypomagnesemia, if these changes are confirmed by laboratory tests. Normalization of the acid-base state (elimination of acidosis, alkalosis), alignment of other biochemical constants of the crop are also important.

Therapeutic efficacy of cardiac glycosides in sick with severe decompensation and functional liver failure increases significantly when combined with corticosteroids and alternately prescribed saluretics and spironolactone.

To prevent post-defibrillation arrhythmias, short-acting glycosides actions(celanide, digoxin) should be canceled 3-5 days in advance, and long-term glycosides actions(digitoxin, acetyldigitoxin, cordigit, digitalis powder) - 7-10 days before electropulse therapy.

After these events, sick digitalis arrhythmias may disappear. If they are not enough, a number of drugs are prescribed, which at the same time can increase tolerance. sick to cardiac glycosides. Arrhythmias that worsen hemodynamics in the systemic and pulmonary circulation (supraventricular tachysystoles and tachyarrhythmias, partial atrioventricular blockade, etc.) are subject to special treatment. In addition, the so-called prefibrillatory extrasystoles (close to normal systole, polytopic and group ventricular extrasystoles, paroxysmal ventricular tachycardia, ventricular flutter) are subject to immediate elimination.

One of the most effective means treatment various digitalis atrial and ventricular tachyarrhythmias are potassium salts and similar drugs(see "Antiarrhythmic drugs"). However, when blockade from the introduction of these drugs should refrain. As antiarrhythmic agents that reduce intoxication with cardiac glycosides, disodium salt of ethylenediaminetetraacetic acid, sodium citrate, unithiol, heparin can be prescribed, and rheopolyglucin and gemodez as detoxification agents.

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For heart problems, very serious drugs are prescribed, which, if used incorrectly, can be extremely dangerous. After all, some of them are made from poisonous plants - for example, cardiac glycosides. Let's find out the names of these drugs, get acquainted with their action and rules for taking. This will help avoid unwanted consequences.

Poison or medicine for the heart?

If the heart has ceased to cope with its functions, then to improve the performance of the myocardium, the activity of the organ as a whole, cardiac glycosides (CG) are prescribed. What it is? These are herbal medicines that contain aglycone or genin (components that do not contain sugar) and glycone (a sugary substance). Here is how you can briefly describe their action: they increase the contractions of the heart, making them more rare. After their application, edema, shortness of breath, cyanosis disappear, blood stasis in the veins decreases, diuresis increases. They are prescribed only after the diagnosis of "heart failure" is confirmed and the patient passes tests for compatibility.

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When is this group of drugs used?

Cardiac glycosides are prescribed for severe cardiac pathologies that can threaten a person's life. Here are the main indications for the use of such drugs:

• acute violations of the cardiovascular system, provoked by atrial arrhythmia or infarction;
• chronic heart failure, in particular, associated with high loads on the heart (with a defect, arterial hypertension, atherosclerotic vascular damage);
• angina;
• constant atrial fibrillation, which is accompanied by a rapid heartbeat;
• atrial flutter;
• supraventricular tachycardia;
• prevention of intoxication in severe pneumonia.

The most famous drugs from the list of cardiac glycosides

Most cores are well aware of the names of cardiac glycosides, a list of which is given below. After all, they have to regularly take such drugs:

• Digoxin (and its analogues - Tsedigalan, Novodigal, Dilacor, Lanatozid). According to many doctors and patients, this is the most effective treatment for CHF. For its production, leaves of a poisonous plant - woolly foxglove are used. The drug has a long action, but it does not produce serious side effects.

Digoxin is prescribed at 1 mg per day in two doses (maintenance dose is from 250 to 500 mcg daily). However, the cardiologist may recommend taking the medication in other doses. This drug is prescribed even to small patients. The main indications for taking it are CHF and edema. It also lowers blood pressure and slightly increases diuresis;

• Strofantin. Refers to chemically pure preparations: it is obtained from Kombe strophanthus - perennial vines. This is a fast-acting remedy: after 15 minutes. after intravenous administration, the patient feels its influence. Another property of Strofantin is that it almost does not accumulate in the body. A day later, its components are practically not detected in human blood. The drug is administered by intravenous injection at a dose of 0.5 to 1.0 ml once a day (or twice, but not earlier than 8 hours after the first injection);
• Digitoxin. It is prescribed somewhat less frequently, as doctors have difficulty choosing the optimal dose. It does not differ in instant action, but the therapeutic effect of its use lasts quite a long time. When using this drug, intoxication often develops.

The drug is usually taken in 1-2 tablets. (0.1-0.2 mg) 2 to 3 r. in a day. After achieving a therapeutic effect, the dosage is changed - 1 table. per day (or every other day). This tool should be used only under the supervision of a physician, because it can lead to the development of arrhythmias and an increase in intraocular pressure;

• Korglikon. The basic raw material for its manufacture is lily of the valley. This remedy does not stimulate the heart muscle very well, but it produces a good sedative effect. It is used as a drug for emergency care and for the treatment of acute heart failure;
• Izolanid. Produced from foxglove. Assigned to 5-10 cap. (or 1 tab.) three times a day with circulatory failure, paroxysmal tachycardia;
• Cymarin. The main raw material for its production is lily of the valley. The action of the drug is close to Strofanthin. Effectively relieves swelling, has a pronounced diuretic effect. It is administered intravenously 1-2 times a day. The course of treatment is 10-30 injections;
• Acedoxin. Standard dosage - 2-4 tablets. per day (0.4-0.8 mg). When it is possible to achieve a therapeutic effect, the dose is reduced to 0.5-1 table.

In addition, semi-synthetic cardiac glycosides are widely used in cardiology. Here are the pharmacy names of such drugs: Betamethyldigoxin, Strophanthin acetate.

Affairs of the heart: how to take such drugs?

Treatment is usually carried out according to this scheme. First appoint the maximum dose. When the severity of symptoms of insufficiency decreases significantly (indicating the onset of the saturation phase), the dosage is reduced. At the first signs of intoxication with these drugs (and this is nausea, loss of appetite, visual disturbances, a sharp slowdown in the heart rate), they resort to replacement therapy with medicines containing potassium and magnesium. The most commonly used is Verapamil.

Inside it is allowed to take only the so-called non-polar SG. They are well absorbed from the gastrointestinal tract. These include Acedoxin, Digoxin, Beta-methyldigoxin, Digitoxin. Drugs of the same spectrum, which are poorly absorbed from the digestive tract, are usually used parenterally. So, Strofantin and Convallatoxin are injected into a vein (previously diluted with sodium chloride or glucose).

SG is not prescribed for patients who have unstable angina pectoris, idiopathic subaortic stenosis, Wolff-Parkinson-White syndrome, acute infectious myocarditis. It is impossible to use drugs of this spectrum if there is a record in the patient's history that he has suffered SG poisoning. Relative contraindications are pregnancy and lactation, liver and kidney failure, thyroid disease.