Antiarrhythmic drugs influence conduction and contractility. Antiarrhythmic drugs
Antiarrhythmic drugs (AADs) can correct serious disorders of the heart and significantly prolong the life of patients.
The drugs that are included in this group differ significantly in their mechanism of action, affecting different components of the process of cardiac contraction. All antiarrhythmic drugs of the new and old generation are available by prescription and are selected individually for each patient.
Classification of antiarrhythmics by mechanism of action
This classification is the most commonly used.
It characterizes medications according to their mechanism of action:
- membrane stabilizing agents;
- beta blockers;
- medications that slow down repolarization;
- calcium ion antagonists.
The process of heart contraction occurs by changing the polarization of cell membranes.
The correct charge is ensured by electrophysiological processes and ion transport. All antiarrhythmic drugs lead to the desired therapeutic effect by influencing cell membranes, but the process of influence differs for each subgroup.
Depending on what pathology caused the heart rhythm disturbance, the doctor decides to prescribe a certain pharmacological group of tablets against arrhythmia.
Membrane stabilizers
Membrane stabilizing agents combat arrhythmia by stabilizing the membrane potential in cardiac muscle cells.
These medications are further divided into three types:
- IA. They normalize heart contractions by activating ion transport through sodium channels. These include quinidine and procainamide.
- I.B. This includes drugs that are local anesthetics. They influence the membrane potential in cardiomyocytes by increasing membrane permeability for potassium ions. Representatives: phenytoin, lidocaine, trimecaine.
- IC. They have an antiarrhythmic effect by suppressing the transport of sodium ions (the effect is more pronounced than that of group IA) - Etatsizin, ajmaline.
Quinidine drugs of group IA also have other beneficial effects for normalizing heart rhythm. For example, they increase the threshold of excitability, eliminate the conduction of unnecessary impulses and contractions, and also slow down the restoration of membrane reactivity.
Beta blockers
These drugs can be divided into 2 more subgroups:
- Selective - block only beta1 receptors that are located in the heart muscle.
- Non-selective - additionally block beta2 receptors located in the bronchi, uterus and blood vessels.
Selective drugs are more preferable, since they directly affect the myocardium and do not cause side effects from other organ systems.
The functioning of the cardiac conduction system is regulated by various parts of the nervous system, including the sympathetic and parasympathetic. If the sympathetic mechanism is disrupted, incorrect arrhythmogenic impulses may arrive to the heart, which lead to the pathological spread of excitation and the appearance of arrhythmia. Drugs of the second class (from the group of beta blockers) eliminate the influence of the sympathetic system on the heart muscle and atrioventricular node, due to which they exhibit antiarrhythmic properties.
List of the best representatives of this group:
- metoprolol;
- propranolol (additionally has a membrane-stabilizing effect like class I antiarrhythmic drugs, which enhances the therapeutic effect);
- bisoprolol (Concor);
- timolol;
- betaxolol;
- sotalol (Sotagexal, Sotalex);
- atenolol
Beta blockers have a positive effect on heart function in several ways. By reducing the tone of the sympathetic nervous system, they reduce the flow of adrenaline or other substances into the myocardium that lead to excessive stimulation of cardiac cells. By protecting the myocardium and preventing electrical instability, drugs in this group are also effective in the fight against atrial fibrillation, sinus arrhythmia, and angina pectoris.
Most often, from this group, doctors prescribe medications based on propranolol (Anaprilin) or metoprolol. The drugs are prescribed for long-term regular use, but may cause side effects. The main ones are difficulty in bronchial obstruction, deterioration of the condition of patients with diabetes due to possible hyperglycemia.
Medicines that slow down repolarization
During the transport of ions across the cell membrane, an action potential occurs, which forms the basis for the physiological conduction of nerve impulses and contraction of myocardial tissue. After local excitation has occurred and a local response has arisen, the repolarization phase begins, which returns the membrane potential to its original level. Class 3 antiarrhythmics increase the duration of the action potential and slow the repolarization phase by blocking potassium channels. This leads to a prolongation of impulse conduction and a decrease in sinus rhythm, but overall myocardial contractility remains normal.
The main representative of this class is amiodarone (Cordarone). Cardiologists prescribe it most often due to its wide therapeutic effect. Amiodarone can be used to treat arrhythmias of any origin. It also acts as an emergency drug in case of emergency or deterioration of the patient's condition.
Amiodarone exhibits antiarrhythmic and bradycardic effects, slows nerve conduction in the atria, and increases the refractive period. Reducing myocardial oxygen demand and increasing coronary blood flow are also considered important properties. As a result, the heart is able to function more fully and is not susceptible to ischemia. The antianginal effect has found its use in the treatment of heart failure and ischemic heart disease.
In addition to Amiodarone, this group of drugs includes:
- ibutilide;
- bretylium tosylate;
- tedisamil.
Slow calcium channel blockers
Tablets for arrhythmia of the fourth group lead to the desired pharmacological effect due to their ability to block calcium channels. Calcium ions promote contraction of muscle tissue, therefore, when the channel is closed, excess myocardial conductivity is eliminated. The main representative is Verapamil. It is prescribed to relieve rapid heartbeat, treat extrasystole, and prevent increased frequency of ventricular and atrium contractions. All drugs with antiarrhythmic effect are prescribed only by a doctor.
In addition to Verapamil, this group includes diltiazem, bepridil, and nifedipine.
Choice of treatment depending on the type of arrhythmia
Arrhythmia is a disorder in the functioning of the heart. Its manifestations are rapid, slow or uneven contraction of the myocardium.
The causes of arrhythmia and the mechanisms of its occurrence may differ. Treatment tactics are selected individually after a detailed examination and determination of the localization of the process that led to improper myocardial contractility.
The treatment strategy includes the following steps:
- The doctor assesses the threat to hemodynamics from the presence of arrhythmia and decides on the need for treatment in principle.
- The risk of other complications due to arrhythmia is assessed.
- The patient’s subjective attitude towards arrhythmia attacks and his well-being at these moments are assessed.
- The degree of aggressiveness of therapy is determined - mild, conservative, radical.
- A thorough examination of the patient is carried out to identify the cause of the disease. After this, the doctor evaluates whether etiotropic therapy is possible. A detailed examination of some patients reveals that the cause of the disease is psychological, so the treatment tactics will change dramatically (sedatives will be used).
- Having chosen a treatment strategy, the doctor selects the most suitable medication. This takes into account the mechanism of action, the likelihood of complications, and the type of detected arrhythmia.
Beta blockers are prescribed mainly for supraventricular arrhythmias, class IB medications are prescribed for ventricular imbalances, calcium channel blockers are effective for extrasystoles and paroxysmal tachycardias. Membrane stabilizers and antiarrhythmics of class 3 are considered more universal and are used for arrhythmias of any origin.
The first couple of weeks of treatment need to be especially careful to monitor the patient's condition. After a few days, a control ECG is performed, which is then repeated several more times. If the dynamics are positive, the interval of control studies may increase.
The choice of dose does not have a universal solution. More often, the dosage is selected practically. If a therapeutic amount of the drug causes side effects, the doctor may use a combination treatment regimen in which the dose of each arrhythmia drug is reduced.
With tachycardia
Treatment methods for tachycardia depend on the etiology of the latter. Indications for continuous use of antiarrhythmic drugs are cardiac reasons. However, before starting treatment, it is necessary to exclude neurological causes (home problems, stress at work) and hormonal disorders (hyperthyroidism).
Medications that help reduce rapid heart rate:
- Diltiazem.
- Sotahexal.
- Bisoprolol.
- Adenosine.
Most drugs come in the form of tablets or capsules. They are inexpensive and are taken by the patient at home, usually in combination with blood thinners. For paroxysms (powerful attacks of rapid heartbeat or pulse), injectable forms of drugs are used.
With extrasystole
If systolic contractions occur up to 1200 per day, and they are not accompanied by dangerous symptoms, the disease is considered potentially safe. To treat extrasystole, a group of membrane stabilizers can be prescribed. In this case, the doctor can prescribe drugs from any subgroup, in particular, class IB drugs are used primarily for the treatment of ventricular extrasystoles.
There has also been a positive effect of calcium channel blockers, which can relieve tachyarrhythmia or excessive heart contractions.
- Ethacizin.
- Propaphenone.
- Propanorm.
- Allapinin.
- Amiodarone.
If the removal of extrasystoles with modern medications is ineffective, as well as if the frequency of extrasystolic contractions is more than 20,000 per day, non-drug methods can be used. For example, radiofrequency ablation (RFA) is a minimally invasive surgical procedure.
For atrial fibrillation and flutter
When a person has atrial flutter or fibrillation, they usually have an increased risk of blood clots. The treatment regimen includes drugs for arrhythmia and.
List of drugs that stop excessive atrial fibrillation and flutter:
- Quinidine.
- Propaphenone.
- Ethacizin.
- Allapinin.
- Sotalol.
Anticoagulants such as aspirin or indirect anticoagulants are added to them.
For atrial fibrillation
For atrial fibrillation, the main drugs should also be combined with anticoagulant drugs. It is impossible to cure the disease forever, so to maintain normal heart rate you will have to take medications for many years.
For treatment the following are prescribed:
- Ritmonorm, Cordarone - to normalize heart rhythm.
- Verapamil, Digoxin - for a reduced frequency of ventricular contractions.
- Non-steroidal drugs, anticoagulants - for the prevention of thromboembolism.
There is no universal cure for all arrhythmias. Amiodarone has the widest therapeutic effect.
Possible side effects
Pacemakers, adrenergic agonists, and antiarrhythmic drugs can cause a number of undesirable effects. They are determined by a complex mechanism of action that affects not only the heart, but also other systems of the body.
According to patient reviews and pharmacological studies, antiarrhythmic drugs provoke the following side effects:
- bowel disorder, nausea, anorexia;
- fainting, dizziness;
- change in blood picture;
- impaired visual function, numbness of the tongue, noise in the head;
- bronchospasm, weakness, cold extremities.
The most popular drug, Amiodarone, also has a fairly wide range of undesirable manifestations - tremor, dysfunction of the liver or thyroid gland, photosensitivity, visual impairment.
The manifestation of arrhythmogenic effects in old age is another side effect, in which the patient, on the contrary, is provoked arrhythmias, fainting occurs and blood circulation is impaired. It is most often caused by ventricular tachycardia or due to taking a drug that has a proarrhythmic effect. That is why treatment of any cardiac diseases should be carried out only by a doctor, and all such drugs belong to the prescription group.
Contraindications to most drugs:
- use in pediatrics;
- prescription for pregnant women;
- presence of AV block;
- bradycardia;
- deficiency of potassium and magnesium.
Interaction with other drugs
Acceleration of the metabolism of antiarrhythmic drugs is observed when taken simultaneously with inducers of microsomal liver enzymes or alcohol. A slowdown in metabolism occurs when combined with liver enzyme inhibitors.
Lidocaine enhances the effect of anesthetics, sedatives, hypnotics and muscle relaxants.
When taking drugs for arrhythmia in combination, they enhance each other's effects.
Combining drugs with non-steroidal drugs is possible (for example, with Ketorol in ampoules or tablets, as well as Aspirin Cardio), in order to obtain a blood-thinning effect or treat concomitant pathologies.
Before starting treatment, you must inform your doctor about all medications the patient is taking.
Other groups of drugs for the treatment of rhythm disorders
There are drugs that can regulate heart rate directly or indirectly, but they belong to other pharmacological groups. These are preparations of cardiac glycosides, adenosine, magnesium and potassium salts.
Cardiac glycosides affect the conduction system of the heart by regulating autonomic activity. They often become the drugs of choice in patients with heart failure or hypertension. Adenosine triphosphate is a substance that takes part in many important electrophysiological processes in the human body. In the atrioventricular node, it helps slow impulse conduction and successfully fights tachycardia. This group includes the drug Riboxin, a precursor of ATP.
Tranquilizers with sedatives are prescribed for the neurogenic etiology of arrhythmia.
Magnesium and potassium preparations (Panangin) are also used to treat arrhythmias and fibrillation due to the participation of these elements in the mechanism of muscle contraction. They are called "vitamins for the heart." Normalization of ion concentrations inside and outside the cell has a positive effect on myocardial contractility and metabolism.
Antiarrhythmic drugs are used to eliminate or prevent heart rhythm disturbances of various etiologies. They are divided into drugs that eliminate tachyarrhythmias. and drugs effective for bradyarrhythmias.
Ventricular fibrillation followed by asystole is responsible for 60-85% of cases of sudden death, primarily in cardiac patients. In many of them, the heart is still quite capable of contractile activity and could work for many years. At least 75% of patients with myocardial infarction and 52% of patients with heart failure suffer from progressive heart rhythm disturbances.
Chronic, recurrent forms of arrhythmias accompany heart diseases (valvular defects, myocarditis, coronary insufficiency, cardiosclerosis, hyperkinetic syndrome) or occur against the background of disorders of the neuroendocrine regulation of cardiac activity (thyrotoxicosis, pheochromocytoma). Arrhythmias develop during intoxication with nicotine, ethyl alcohol, cardiac glycosides, diuretics, caffeine, anesthesia with halogen-containing general anesthetics, operations on the heart, blood vessels, and lungs. Heart rhythm disturbances are often a vital indication for emergency treatment with antiarrhythmic drugs. In recent years, the paradoxical fact has been established that antiarrhythmic drugs can cause dangerous arrhythmias. This limits their use for arrhythmias with minimal clinical manifestations.
In 1749, it was proposed to take quinine for “persistent palpitations.” In 1912 to Karl Friedrich Wenckebach (1864-1940), a famous German cardiologist who described Wenckebach's block. A merchant contacted him about a heart attack. Wenckebach diagnosed atrial fibrillation, but explained to the patient that it was not possible to relieve it with medications. The merchant expressed doubts about the medical competence of cardiologists and decided to undergo treatment on his own. He took 1 g of quinine powder, which in those days had a reputation as a cure for all diseases. After 25 minutes, the heart rhythm returned to normal. Since 1918, the dextrorotatory isomer of quinine, quinidine, was introduced into medical practice on the recommendation of Wenckebach.
Under normal conditions, the function of the heart pacemaker is performed by the sinus node. His P-cells (the name is from the first letter of the English word racemaker) have automaticity - the ability to spontaneously. during diastole generate an action potential. The resting potential of β cells ranges from -50 to -70 mV, and depolarization is caused by incoming flows of calcium ions. The following phases are distinguished in the structure of the membrane potential of β-cells:
Phase 4 - slow spontaneous diastolic calcium-type depolarization; phase 0 - development of a positive action potential +20-30 mV after reaching the depolarization threshold in phase 4;
Phase 1 - rapid repolarization (input of chlorine ions);
Phase 2 - slow repolarization (output of potassium ions and slow influx of calcium ions);
Phase 3 - final repolarization with restoration of the negative resting potential.
During the resting potential, the ion channels are closed (the external activation and internal inactivation gates are closed), during depolarization the channels open (both types of gates are open), during the repolarization period the ion channels are in an inactivated state (the external gates are open, the internal gates are closed).
Action potentials from the β-cells of the sinus node propagate through the atrial conduction system, the atrioventricular node, and the intraventricular His-Purkinje fiber system (in the direction from the endocardium to the epicardium). In the conduction system of the heart, the cells are long and thin, contact each other in the longitudinal direction, and have rare lateral connections. Action potentials are conducted 2-3 times faster along cells than in the transverse direction. The speed of impulse conduction in the atria is -1 m/s, in the ventricles - 0.75-4 m/s.
ECG wave R corresponds to atrial depolarization, complex ORS - ventricular depolarization (phase 0), segment ST - repolarization phases 1 and 2, wave T - repolarization phase 3.
In the conduction system of a healthy heart, distal to the sinus node, spontaneous depolarization occurs much more slowly than in the sinus node, and therefore is not accompanied by an action potential. There is no spontaneous depolarization in the contractile myocardium. The cells of the conduction system and contractile myocardium are excited by impulses from the sinus node. In the atrioventricular node, spontaneous depolarization is caused by the entry of calcium and sodium ions, in the Purkinje fibers - the entry of only sodium ions (“sodium” potentials).
The rate of spontaneous depolarization (phase 4) is regulated by the autonomic nervous system. With increased sympathetic influences, the entry of calcium and sodium ions into cells increases, which accelerates spontaneous depolarization. With an increase in parasympathetic activity, potassium ions are released more intensely, slowing down spontaneous depolarization.
During an action potential, the myocardium is in a state of refractory to stimulation. With absolute refractoriness, the heart is not capable of excitation and contraction, regardless of the strength of stimulation (phase 0 and the beginning of repolarization); at the beginning of the relative refractory period, the heart is excited in response to a strong stimulus (the final stage of repolarization); at the end of the relative refractory period, the excitation is accompanied by contraction.
The effective refractory period (ERP) covers the absolute refractory period and the initial part of the relative refractory period, when the heart is capable of weak excitation, but does not contract. On the ECG, the ERP corresponds to the complex QRS and the ST segment.
PATHOGENESIS OF ARRHYTHMIAS
Tachyarrhythmias arise due to disturbances in impulse formation or circulation of a circular excitation wave.
Impulse formation disorder
In patients with arrhythmia, heterotopic and ectopic pacemakers appear in the myocardium, which have greater automatism than the sinus node.
Heterotopic foci are formed in the conduction system distal to the sinus node.
Ectopic lesions appear in the contractile myocardium.
Impulses from additional foci cause tachycardia and extraordinary contractions of the heart.
A number of factors contribute to the “unleashing” of abnormal automatism:
The occurrence or acceleration of spontaneous depolarization (the entry of calcium and sodium ions is facilitated under the influence of catecholamines, hypokalemia, stretching of the heart muscle);
Reducing the negative diastolic resting potential (myocardial cells contain excess calcium and sodium ions during hypoxia, blockade Na/TO-ATPase and calcium-dependent ATPase);
Reduction of ERP (potassium and calcium conductivity increases in phase 2. development of the next action potential is accelerated);
Weakness of the sinus node with rare generation of impulses;
Release of the conduction system from the control of the sinus node during conduction block (myocarditis, cardiosclerosis).
Trigger activity is manifested by early or late trace depolarization. Early trace depolarization, interrupting phases 2 or 3 of the transmembrane potential, occurs with bradycardia, low content of potassium and magnesium ions in the extracellular fluid, and excitation of beta-adrenergic receptors. It causes polymorphic ventricular tachycardia (torsades de pointes). Late trace depolarization develops immediately after the end of repolarization. This type of trigger activity is caused by overload of myocardial cells with calcium ions during tachycardia, myocardial ischemia, stress, and poisoning with cardiac glycosides.
Circular wave of excitation
Excitation wave circulation reentry - repeated admission) contributes to heterochronism - a mismatch in the time of the refractory period of myocardial cells. A circular excitation wave encountering refractory depolarized tissue in the main conduction path. is sent along an additional route. but can return in the antidromic direction along the main path. if the refractory period has ended. Pathways for the circulation of excitation are created in the border zone between scar tissue and intact myocardium. The main circular wave breaks up into secondary waves that excite the myocardium, regardless of impulses from the sinus node. The number of extraordinary contractions depends on the period of wave circulation before attenuation.
CLASSIFICATION OF ANTIARRYTHMIC DRUGS
Antiarrhythmic drugs are classified according to their effect on the electrophysiological properties of the myocardium (E.M. Vaughan Williams, 1984; D.C. Hamson. 1985) (Table 38.2).
Antiarrhythmic drugs used for cerebrovascular accidents, venotropic drugs. Antiarrhythmic drugs.
This is a group of drugs used for arrhythmias - conditions characterized by disturbances in the rhythm of heart contractions. Arrhythmias are the most important cause of death in sick people, which makes it important to study this group of cardiovascular drugs. Arrhythmias can accompany many pathological conditions: for example, 1) metabolic disorders due to circulatory disorders; 2) accompany many hormonal disorders; 3) are a consequence of various intoxications; 4) are a consequence of the development of side effects of many medications, etc.
Regardless of the above reasons, heart rate disturbances directly arise from pathological changes in cardiac functions such as automaticity, conductivity, incl. and their combined disorders. Pharmacocorrection of arrhythmias is aimed at normalizing these impaired functions. Considering that the automaticity and conductivity of the corresponding cells of the conduction system of the heart directly depend on the ion flows that form the action potential of the cells - pacemakers and cells of the conduction system of the heart, this formed the basis for the classification of antiarrhythmic drugs.
The mechanism of formation of the action potential of pacemaker cells and cells of the conduction system of the heart, see the physiology course: what ion flows are what phases of the action potential and where they are formed, on what phases of the action potential the functions of automaticity and conductivity depend, how the phases of the action potential fit into the electrocardiogram.
Classification of antiarrhythmic drugs. Medicines used for tachyarrhythmias and extrasystoles.
1. Sodium channel blockers:
A. Slowing down depolarization and repolarization: quinidine, procainamide, propafenone, etmosin, etatsizin, allapinin .
B. Accelerating repolarization: lidocaine.
2. Calcium channel blockers : verapamil.
3. Agents that prolong repolarization: amiodarone, sotalol.
4. β-adrenergic receptor blockers: propranolol, metoprolol.
5. Cardiac glycosides: digoxin.
6. Potassium preparations: panangin, asparkam.
Medicines used for bradyarrhythmias and blockades.
1. Adrenergic agonists: isoprenaline, ephedrine, adrenaline.
2. M-anticholinergics: atropine.
Group 1A drugs have a non-selective membrane-stabilizing effect, thereby suppressing the flow of all ions through their channels of cell membranes. This leads to a lengthening of all phases of the action potential, and the refractory period of the cells of the cardiac conduction system also lengthens. As a result, both the automaticity function and the conductivity function are simultaneously suppressed in them. This makes the drugs of this group universal, used for both atrial and ventricular tachyarrhythmias.
Quinidine sulfate - Available in tablets of 0.1 and 0.2.
The drug is well absorbed when administered orally. In the blood, 87% binds to plasma proteins, incl. with albumin and acidic α 1 - glycoprotein. Therefore, in case of myocardial infarction, the dose of the drug should be increased. Most of the prescribed dose is oxidized in the liver, and only 20% is excreted unchanged in the urine. It should be taken into account that quinidine significantly inhibits the IID6 isoenzyme of cytochrome P450. T ½ is about 8 hours. The drug is prescribed orally in 2 stages. At the saturation stage, it can be prescribed up to 6 times a day; to maintain the effect, the daily dose is prescribed 3 times a day.
For the mechanism of action, see above. In addition to the above, quinidine in a patient can also block α-adrenergic receptors and cause an M-cholinergic blocking effect. This contributes to a drop in blood pressure and the development of so-called torsade de pointes. As treatment continues and the antiarrhythmic effect of the drug develops, the tachycardia effect disappears. It should also be taken into account that in case of atrial tachyarrhythmias, the M - anticholinergic effect can improve conduction in the A-V node, increasing the rhythm of ventricular contractions.
O.E. Antiarrhythmic, decrease in heart rate, prolongation of AP and RP, suppression of automaticity and conduction.
P.P. 1) Prevention and chronic treatment of patients with atrial tachyarrhythmias: flicker, flutter, tachycardia, paroxysmal tachycardia in the interictal period.
2) Prevention and chronic treatment of patients with ventricular tachyarrhythmias: tachycardia, paroxysmal tachycardia in the interictal period, extrasystole.
P.E. At the beginning of treatment, the development of deadly complications is possible: torsade de pointes (due to a drop in blood pressure and M - the anticholinergic effect of quinidine), thromboembolism of vital vessels, especially when treating patients with atrial tachyarrhythmias. This should be anticipated and prevented.
In addition, it is possible to develop bradycardia, a decrease in cardiovascular system, a decrease in blood pressure, ringing in the ears, decreased hearing acuity, vestibular disorders, headache, diplopia, nausea, vomiting, diarrhea, allergies, sometimes hepatotoxicity, suppression of hematopoiesis. Possible development of cumulation.
Procainamide hydrochloride (novocainamide) - available in tablets of 0.25 and 0.5; in ampoules 10% solution in an amount of 5 ml.
The drug acts and is used similarly quinidine , differences: 1) much weaker, approximately 20%, binds to plasma proteins, therefore it acts faster and is used for acute atrial and ventricular tachyarrhythmias; 2) eliminates faster, T ½ is about 3 - 4 hours; 3) is metabolized in the liver by the reaction of N - acetylation, so you need to remember about fast and slow acetylators, it is excreted mainly in the urine; 4) does not have α-adrenergic blocking and M-cholinergic blocking effects, but due to the ability to lower blood pressure, the drug is still capable of provoking tachycardia at the beginning of treatment, accumulates less, therefore is generally better tolerated, but unlike quinidine, it can more often cause severe allergies up to before the formation of drug-induced lupus erythematosus syndrome, but this more often occurs in patients with low activity of acetylating enzymes.
Ethmozin and its more active derivative etacizin act and apply similarly quinidine , differences: 1) dilates coronary vessels, improving cardiac metabolism; 2) are available in tablets and solutions for injection, and are used for both acute and chronic atrial and ventricular tachyarrhythmias; 3) better tolerated.
Propaphenone Available in both tablets and solution for injection. Absorbed from the gastrointestinal tract by 100%, but bioavailability due to the pronounced presystemic elimination of this route of administration is 3.4 - 10.6%, which is why oral administration of propafenone is practically not used. In the blood, almost all of it binds to plasma proteins. Metabolized in the liver with the participation of cytochrome P450. Excreted in bile and urine. T ½ is very individual, and varies from 5.5 to 17.2 hours in different patients, which in combination with the above makes the drug very inconvenient to dosage. In addition, the drug is very poorly tolerated, causing many very serious side effects. Therefore, this drug is rarely used, only for severe ventricular tachyarrhythmias resistant to the use of other antiarrhythmic drugs.
Allapinin - available in tablets 0.025 each.
The oral bioavailability of the drug is about 40% due to pronounced presystemic elimination. The drug penetrates well through the BBB into the central nervous system. Excreted in urine. T ½ is about 1 hour.
For the mechanism of action, see above. In general, it can be noted that, relative to the above-mentioned remedies, it is not very potent in terms of action, but it is also a less toxic herbal medicine, a derivative of aconitine.
O.E. 1) decrease in heart rate.
2) dilates coronary vessels, thereby improving cardiac metabolism.
3) sedative.
P.P. 1) Prevention and chronic treatment of patients with atrial tachyarrhythmias.
2) Prevention and chronic treatment of patients with ventricular tachyarrhythmias: tachycardia, paroxysmal tachycardia in the interictal period, extrasystole..
P.E. Dizziness, headache, diplopia, ataxia, tachyarrhythmias at the beginning of treatment, facial hyperemia, allergies.
Lidocaine hydrochloride (lidocard) - available in ampoules of a 2% solution in an amount of 10 ml.
It is prescribed intravenously, usually by infusion. It is well absorbed from the gastrointestinal tract, but bioavailability due to the pronounced presystemic elimination of this route of administration is almost 0%, which is why oral administration of lidocaine is practically not used. The drug is prescribed mainly intravenously, preferably by drip infusion. This is due to the fact that T ½ the drug with a single intravenous administration is about 8 minutes, and therefore a rapid relapse of the pathology occurs. In the blood, 70% binds to plasma proteins, incl. with acidic α 1 - glycoprotein, therefore, in case of myocardial infarction, the dose of the drug should be increased. The drug is metabolized in the liver and excreted mainly in bile. Final T ½ of the drug and active metabolites is about 2 hours.
The mechanism of action is associated with a block of Na + - channel activity and some activation of K + - channels, resulting in the formation of a state of hyperpolarization of the cell membrane of cells of the cardiac conduction system. This leads to a prolongation of the phase of diastolic depolarization, which leads to a pronounced suppression of the automaticity function. Due to some activation of K + channels, phase 3 of the action potential is accelerated, which, in turn, can lead to a shortening of the refractory period of the cells of the cardiac conduction system. This, firstly, does not allow suppression of the conductivity function, and secondly, in some cases this function can even improve. This action limits the use of lidocaine for atrial tachyarrhythmias due to fear of the spread of the abnormal atrial rhythm to the ventricles, which has an extremely unfavorable prognosis.
O.E. Decrease in heart rate due to prolongation of the action potential and suppression of automaticity. It should be remembered that the refractory period is shortened, which does not suppress, but may even improve conduction function.
P.P. Acute, life-threatening ventricular tachyarrhythmias, especially those arising against the background of myocardial infarction.
P.E. Bradycardia, decrease in blood pressure, reactions of excitation or depression of the central nervous system, depending on the initial condition of the patient, allergies.
Amiodarone (cordarone) - available in tablets of 0.2; in ampoules containing a 5% solution in an amount of 3 ml.
It is prescribed orally, intravenously 1 time per day, more often when prescribing a saturation dose. The bioavailability of oral administration of the drug is about 30%, due to incomplete absorption. In the blood it is almost 100% bound to plasma proteins. Pronouncedly deposited in lipids. Metabolized in the liver by isoenzyme IIIA4 of cytochrome P450. Amiodarone inhibits the activity of liver microsomal enzymes (cytochrome P450 isoenzymes IIIA4 and IIC9), so the elimination of co-administered drugs may be significantly suppressed. T ½ the drug in adults is about 25 hours, and after discontinuation of the drug it can last for weeks, months; in children - less. Considering the above, the drug should be prescribed in 2 stages. For example, the drug is prescribed 5 days a week followed by a break of 2 days. Other treatment regimens are also possible. Due to the pronounced connection with plasma proteins and deposition, the effects of the drug develop slowly (weeks, sometimes months), it is prone to accumulation, which makes its correct use difficult.
The mechanism of action of the drug is not exactly clear. It is believed that the drug affects the lipid environment and blocks ion channels of cell membranes. K + and Ca 2+ channels are blocked to a greater extent, which leads to the most pronounced prolongation of the repolarization phase of the action potential of cells of the cardiac conduction system. The block of Na + - channels is short and insignificant. As a result, the functions of both automaticity and conductivity are simultaneously suppressed. In addition, the drug dilates the coronary vessels. There are also assumptions about its α - or β - adrenergic component of action.
O.E. Decrease in heart rate due to prolongation of the action potential and refractory period, suppression of automaticity and slowing of conduction.
P.P. 1) Chronic treatment of patients with atrial tachyarrhythmias: flicker, flutter, tachycardia, paroxysmal tachycardia in the interictal period.
2) Chronic treatment of patients with ventricular tachyarrhythmias: tachycardia, paroxysmal tachycardia in the interictal period, extrasystole.
P.E. Bradycardia, some decrease in CVS, decrease in blood pressure, nausea, vomiting, bluish discoloration of the skin, changes in the color of the iris, photodermatitis, hypo- or hyperthyroidism (a structural analogue of thyroid hormones), neurotoxicity, damage to muscle tissue, and allergies may be observed. Sometimes fatal complications occur due to necrosis of hepatocytes and pulmonary pneumosclerosis. The drug accumulates markedly, there is a high risk of overdose and intoxication.
Sotalol amiodarone , differences: 1) has a different mechanism of action, it is a non-selective β-adrenergic blocker; 2) can cause torsades de pointes due to concomitant hypoK + emia, see other side effects propranolol .
Propranolol - See above for more detailed description. The antiarrhythmic effect is associated with the removal of the heart from the influence of sympathetic innervation and with a compensatory increase in the influence of parasympathetic innervation on the heart. As a result of this, the action potential and refractory period are lengthened, the automaticity function is suppressed and conduction slows down, especially pronounced at the level of the A - V node. The drug is used for both acute and chronic atrial tachyarrhythmias. In case of ventricular rhythm disturbances, it is recommended only with a concomitant increase in the tone of the sympathetic innervation, for example, against the background of hyperthyroidism, with pheochromocytoma, etc.
Metopranolol acts and is applied similarly propranolol , differences: 1) cardioselective drug, better tolerated.
Digoxin - See above for more detailed description. The drug slows down conduction at the level of the A - V node, acting directly and reflexively. But at the same time, due to the +batmotropic effect, digoxin can stimulate the function of automaticity. Therefore, it is used only for atrial tachyarrhythmias in order to prevent the spread of abnormal atrial rhythm to the ventricles, which has an extremely unfavorable prognosis, which is why the drug is strictly contraindicated for ventricular tachyarrhythmias.
Panangin - produced in dragees; in ampoules containing a solution in an amount of 10 ml.
It is a combination drug that is prescribed using the official prescription form. It contains potassium aspartate (contains 0.158 in the dragee) and magnesium aspartate (contains 0.14 in the dragee). The ampoule contains: K + - 0.1033 and Mg + - 0.0337.
Panangin is prescribed orally, intravenously up to 3 times a day. The IV is administered as slowly as possible. Absorbed into the gastrointestinal tract completely and quickly enough, excreted in the urine by the kidneys.
In the patient's body it replenishes the deficiency of K + and Mg + ions. Such a drug is especially relevant in cases where the traditional pathway of K + ions entering the cell is blocked, for example, when exposed to cardiac glycoside drugs. In this case, alternative Mg + -dependent K + - channels are activated, delivering K + into the cell. In the cells of the conduction system of the heart, this leads to an extension of the depolarization phase, which prolongs their action potential and refractory period, suppresses the function of automaticity, and conduction slows down.
O.E. 1) Replenishes the lack of K + and Mg + ions in the body.
2) Reduces heart rate due to prolongation of the action potential and refractory period, suppression of automaticity and slowdown of conduction.
3) improves metabolism in the myocardium.
P.P. 1) Prevention and chronic treatment of patients with hypoK + emia that occurs, for example, due to the use of K + - excreting drugs: saluretics, cardiac glycosides, glucocorticoid hormones, etc.
2) Acute manifestations of hypocemia.
3) Prevention and chronic treatment of patients with atrial and ventricular tachyarrhythmias.
4) Complex treatment of patients with acute atrial and ventricular tachyarrhythmias.
5) Chronic combination treatment of patients with ischemic heart disease.
P.E. Bradycardia, extrasystole, decreased blood pressure, nausea, vomiting, diarrhea, heaviness in the epigastrium, symptoms of hyperK + - and hyperMg 2+ - emia, depression of the central nervous system to the point of coma, incl. respiratory depression, convulsions.
Asparkam acts and is applied similarly Panangina , differences: 1) domestic, cheaper product.
For bradycardia, pharmacotherapy is almost never practiced; in some cases, the technique of implanting pacemakers is used. Medicines are used as emergency aid for severe manifestations of A-V blockades. It should be remembered that with the development of such a pathology against the background of a pronounced increase in parasympathetic influences, for example, with intoxication with cardiac glycoside drugs, it is more appropriate to use atropine sulfate. For a more detailed description of the drugs named in the classification, see the previous lectures.
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Diseases of the cardiovascular system are a fairly common problem among many of our fellow citizens of mature age. They are the ones that most often cause death and also provoke the development of other serious conditions.
Arrhythmia is considered to be one of the most common diseases of this kind. It can develop for various reasons, but it must be treated under the supervision of a specialist. Therapy can be carried out using a number of medications, among which not the least are herbal preparations. So let's talk about antiarrhythmic drugs of plant origin, we will briefly describe them.
Valerian – tincture, tablets and other remedies
Valerian preparations are often prescribed to patients suffering from various types of arrhythmia. They can be taken in the form of a tincture - twenty thirty drops three times a day. Tablets are usually prescribed one or two three to four times a day.
You can also purchase ready-made herbal raw materials at the pharmacy and prepare the medicine yourself. To do this, take a tablespoon of crushed valerian roots and brew them with one glass of cold water. Place the container with the medicine on the fire, bring to a boil and simmer for five minutes. Consume one tablespoon of the strained broth two to three times a day.
Motherwort
At the pharmacy you can buy an alcoholic tincture of motherwort or herbal raw materials for making your own infusion. The tincture should be consumed thirty to fifty drops per dose two to three times a day. To make your own medicine, take a tablespoon of chopped herbs and brew it with a glass of boiling water. Soak this product in a water bath for twenty minutes, then leave for another forty minutes. Consume the strained mixture in a third of a glass three times a day shortly before meals.
Altalex
An excellent remedy for the treatment of arrhythmia is a herbal-based pharmaceutical drug called Altalex. It has a rather complex composition, which combines essential oils of lemon balm and peppermint, as well as fennel and nutmeg, cloves and thyme, pine needles and anise, as well as sage, cinnamon and lavender. Altalex is available as an extract in a bottle, which must be used to prepare a therapeutic infusion. To do this, you should dilute ten to twenty drops of the drug in a glass of hot tea, you can also drop the drug onto a piece of sugar.
Antares
This drug, like the other drugs already listed for arrhythmia, has an excellent calming effect. It is based on an extract obtained from the rhizomes of Kava-Kava. This drug should be consumed in the amount of one or two tablets every day immediately after a meal. The medicine should be taken with a sufficient amount of plain water.
Nervoflux
This medicinal composition is intended for making tea. In the treatment of arrhythmia, it is used as a sedative. Nervuflox contains dehydrated extracts of plants such as orange and lavender flowers, mint leaves, valerian and licorice root, as well as hop cones. A teaspoon of dry matter should be brewed with one cup of hot water and mixed thoroughly. The resulting drink can be sweetened a little with honey. Consume this volume of drink three times a day.
Aymalin
This drug is made from an alkaloid that is present in some varieties of rauwolfia. This medication is a fairly effective drug that copes with various types of arrhythmia. It can be administered both intramuscularly and intravenously, for example, to eliminate acute attacks. So take orally in the amount of 0.05-0.1g three or four times a day.
Novo-passit
This remedy is also quite often used in the treatment of arrhythmia. Like many of the drugs already described, it has an excellent antiarrhythmic effect. Novo-passit contains guaifenesin, as well as several extracts of plants such as hawthorn, hops, St. John's wort, as well as lemon balm, black elderberry, valerian and hop cones. This medication is usually taken five milliliters (exactly how much is contained in one teaspoon) three times a day.
Persen
This is a common sedative drug that is often used to treat arrhythmia. It contains active ingredients such as valerian extracts, as well as peppermint and lemon mint. This medication comes in the form of tablets, which should be consumed in a pair of tablets two or three times a day.
Sanosan
This medicinal composition is also very common in the treatment of arrhythmia; it has excellent sedative properties due to the presence of hop extracts and valerian in its composition. It can be purchased in the form of tablets, which should be consumed in two or three pieces about an hour before resting at night.
Ziziphora
This common medicinal plant is included in many pharmaceutical preparations, but it can also be consumed on its own, making medicinal compositions with your own hands. So you can boil three tablespoons of raw material in half a liter of water and simmer over low heat for five minutes. Next, leave in the thermos for another hour, then strain. Consume a third of a glass three times a day for two to three weeks.
Heart arythmy is a heart rhythm disorder: a disturbance in the normal sequence or frequency of heartbeats.
Heart rhythm disturbances are an independent and important section in cardiology. Occurring in various cardiovascular diseases (Coronary heart disease, myocarditis, myocardial dystrophy and myocardiopathy), arrhythmias often cause heart and circulatory failure and aggravate the work and life prognosis. Treatment of arrhythmias requires strict individualization.
It can be considered generally accepted that arrhythmias arise mainly as a result of two processes - a disturbance in the formation or a disturbance in the conduction of an impulse (or a combination of both processes). In accordance with this, they are divided into groups.
Classification of cardiac arrhythmias:
I. Cardiac arrhythmias caused by impaired impulse formation:
– A. Automatic disorders:
1. Changes in the automaticity of the sinus node (sinus tachycardia, sinus bradycardia, sinus node arrest).
2. Ectopic rhythms or impulses caused by the predominance of automatism of the underlying centers.
– B. Other (besides automatism) mechanisms for disrupting the formation of impulses (extrasystoles, paroxysmal tachycardias).
II. Cardiac arrhythmias caused by impaired impulse conduction:
These are different types of blockade, as well as rhythm disturbances caused by the phenomenon of semi-blockade with return of excitation (re entry phenomenon).
III. Cardiac arrhythmias caused by combined disturbances in the formation and conduction of impulses.
IV. Fibrillation (atrial, ventricular).
Heart rhythm disturbances have an adverse effect on the body as a whole and primarily on the cardiovascular system. Cardiac arrhythmias can be a clinical manifestation, sometimes the earliest, of coronary heart disease, inflammatory myocardial diseases, and extracardiac pathology. The appearance of arrhythmia requires examination of the patient to determine the causes of the arrhythmia.
Rhythm disturbances often lead to the appearance or worsening of circulatory failure, a drop in blood pressure up to arrhythmic collapse (shock). Finally, certain types of ventricular arrhythmias may herald the onset of sudden death from ventricular fibrillation; these include ventricular paroxysmal tachycardia, ventricular extrasystole (polytopic, group, paired, early).
Treatment of cardiac arrhythmias:
When treating cardiac arrhythmias, etiological and pathogenetic therapy should be carried out. However, its importance should not be overestimated, especially in urgent cases. The lack of a reliable antiarrhythmic effect in most cases of such therapy dictates the need for the use of special antiarrhythmic drugs.
Drugs used to treat cardiac arrhythmias:
Antiarrhythmic drugs exert their effect mainly by changing the permeability of the cell membrane and the ionic composition of the myocardial cell.
According to the basic electrophysiological mechanisms of cardiac arrhythmia, antiarrhythmic drugs can have a therapeutic effect if they have the following properties:
a) the ability to have a suppressive effect on increased (pathological) automatism by reducing the slope of the diastolic (spontaneous) depolarization curve in phase 4;
b) the ability to increase the value of the resting transmembrane potential;
c) the ability to lengthen the action potential and the effective refractory period.
The main antiarrhythmic drugs can be divided into three classes:
I class. Membrane stabilizing agents:
Their action is based on the ability to inhibit the passage of electrolytes through a semi-permeable cell membrane, leading primarily to a slowdown in the entry of sodium ions during the depolarization period and the release of potassium ions during the repolarization period. Depending on the effect on the conduction system of the heart, drugs of this class can be divided into two subgroups (A and B).
– A. A group of drugs that have an inhibitory effect on myocardial conductivity (quinidine, novocainamide, ajmaline, etmozin, disopyramide).
Quinidine has the most pronounced inhibitory effect on automatism, excitability, conductivity and contractility; is one of the most antiarrhythmic drugs. However, due to the presence of significant side effects, its use is currently limited. Quinidine is prescribed mainly to restore sinus rhythm in cases of persistent atrial fibrillation, prolonged attacks of atrial fibrillation, and for prophylaxis in patients with frequent attacks of atrial fibrillation (flutter).
Quinidine sulfate (Chinidinum sulfas) is usually prescribed orally to restore sinus rhythm in atrial fibrillation. There are various schemes for using the drug. Old regimens involved the administration of quinidine 0.2-0.3 g every 2-4 hours (except at night) with a gradual increase in dose to the maximum over 3-7 days. The daily dose should not exceed 2 g, in some cases the maximum dose is 3 g. Currently, treatment is often started with a loading dose of 0.4 g, followed by 0.2 g of quinidine every 2 hours. In subsequent days, the dose is gradually increased. After restoration of sinus rhythm, maintenance doses are 0.4–1.2 g/day for a long period under regular electrocardiographic monitoring. For atrial extrasystole, 0.2-0.3 g of quinidine is prescribed 3-4 times a day, for attacks of ventricular tachycardia - 0.4-0.6 g every 2-3 hours.
Quinidine bisulfate is used at a dose of 0.25 g 2 times a day (1-2 tablets), to restore sinus rhythm, you can give 6 tablets a day.
Aymalin (gilurythmal, tahmalin) is an alkaloid found in the roots of the Indian plant Rauwolfia serpentina (Snake Rauwolfia). Used for the prevention and treatment of atrial and ventricular extrasystole. When administered intravenously, ajmaline gives a good effect against paroxysms of tachyarrhythmia. It is also used for Wolff-Parkinson-White syndrome. The drug is available in tablets of 0.05 g and in ampoules of 2 ml of 2.5% solution. Aymalin is prescribed intramuscularly, intravenously and orally. Initially, up to 300–500 mg/day is used orally in 3–4 doses, with maintenance doses of 150–300 mg/day. Usually 50 mg (2 ml of a 2.5% solution) is administered intravenously in 10 ml of a 5% glucose solution or isotonic sodium chloride solution slowly over 3–5 minutes. 50–150 mg/day is administered intramuscularly.
– B. A group of membrane-stabilizing drugs that do not have a significant effect on myocardial conductivity (lidocaine, trimecaine, mexitil, diphenine).
Unlike quinidine, they somewhat shorten (or do not lengthen) the refractory period, due to which myocardial conductivity is not impaired, and according to some data, it is improved.
Lidocaine (Lidocaini) is one of the most effective and safest means for stopping ventricular paroxysmal tachycardias and prognostically unfavorable ventricular extrasystoles.
II class. Antiadrenergic drugs:
– A. Blockers of β-adrenergic receptors (anaprilin, oxprenolol, amiodarone, etc.).
The antiarrhythmic effect of drugs in this group consists of their direct antiadrenergic effect, as well as the quinidine-like effect exerted by most drugs in this group. Beta blockers are indicated in the treatment of extrasystoles (atrial and ventricular), as a course of treatment for paroxysms of atrial fibrillation and flutter, supraventricular and ventricular tachycardia, as well as persistent sinus tachycardia (not associated with heart failure).
Beta blockers are contraindicated in cases of severe circulatory failure, atrioventricular block of I–III degree, and bronchial asthma. Caution is required when treating extrasystole, paroxysmal atrial fibrillation due to sick sinus syndrome, as well as diabetes mellitus.
III class. Calcium antagonists:
The antiarrhythmic effect of drugs in this group is explained mainly by inhibition of calcium entry and potassium exit from myocardial cells. The most effective and widely used is verapamil. When administered intravenously, verapamil (isoptin) stops attacks of supraventricular paroxysmal tachycardia; effective for atrial fibrillation and flutter. Orally prescribed for the prevention of extrasystoles (usually atrial), paroxysms of atrial fibrillation.
Potassium preparations give a positive result mainly in arrhythmias caused by digitalis intoxication, as well as in cases accompanied by significant hypokalemia and hypokaligistia.
Cardiac glycosides may have an antiarrhythmic effect. They are used mainly for rhythm disturbances (extrasystoles, paroxysms of atrial fibrillation) associated with obvious or hidden heart failure. Sometimes cardiac glycosides are combined with quinidine to prevent the negative inotropic effect of quinidine.
Heart rhythm disturbances caused by a slowdown in the conduction of impulses through the conduction system pose a serious therapeutic problem. This occurs with sinoatrial block, atrioventricular block, and Adams-Stokes-Morgagni syndrome.
Herbal medicine for cardiac arrhythmias:
Among herbal medicines for cardiac arrhythmias, ephedrine hydrochloride (Ephedrinum hydrochloridum) is used orally or subcutaneously in a single dose of 0.025–0.05 g. The highest single dose orally and subcutaneously is 0.05 g, daily – 0.15 g. The drug is produced in tablets of 0.025 g and in ampoules of 1 ml of 5% solution.
Atropine sulfate (Atropinum sulfatis) is most often used intravenously or subcutaneously at a dose of 0.25–0.5 mg. Available in tablets of 0.0005 g and in ampoules of 1 ml of 0.1% solution.
Caffeine-sodium benzoate (Coffeinum-natrii benzoas) is prescribed in a single dose of 0.05 to 0.2 g 2-4 times a day. Available in tablets of 0.1–0.2 g and in ampoules of 1 and 2 ml of 10% and 20% solution.
An auxiliary agent in the treatment of atrial fibrillation and paroxysmal tachycardia with antiarrhythmic drugs are hawthorn fruits (Fruct. Crataegi). Prescribe liquid extract (Extr. Crataegi fluidum) 20-30 drops 3-4 times a day before meals or tincture (T-rae Crataegi) 20 drops 3 times a day.
For extrasystolic arrhythmia associated with functional neurotic reactions, the following mixture is indicated: T-rae Valerianae, T-rae Convallariae aa 10.0, Extr. Crataegi fluidi 5.0, Mentholi 0.05. Take 20–25 drops 2–3 times a day.
It is necessary to normalize sleep, its depth and duration. For this purpose, the following fees are recommended:
1. Three-leaf leaves (Fol. Trifolii fibrini 30.0), peppermint leaves (Fol. Menthae piperitae 30.0), valerian root (Rad. Valerianae 30.0). The infusion is prepared at the rate of 1 tablespoon per glass of boiling water. Take 1 glass of infusion 30–40 minutes before bedtime.
2. Buckthorn bark (Cort. Frangulae 40.0), chamomile flowers (Flor. Chamomillae 40.0). The infusion is prepared at the rate of 1 tablespoon of the mixture per glass of boiling water. In the evening, drink 1-2 glasses of infusion.
3. Three-leaf leaves (Fol. Trifolii fibrini 20.0), peppermint leaves (Fol. Menthae piperitae 20.0), angelica root (Rad. Archange 30.0), valerian root (Rad. Valerianae 30.0). The infusion is taken 1/3 cup 3 times a day.
4. Chamomile flowers (Flor. Chamomillae 25.0), peppermint leaves (Fol. Menthae piperitae 25.0), fennel fruits (Fruct. Foeniculi 25.0), valerian root (Rad. Valerianae 25.0), fruits caraway (Rad. Carvi 25.0). The decoction is taken in the evening, 1 glass.
