Sodium and potassium channel blockers. Sodium channel blockers drugs Pills for cardiac arrhythmias: treatment features
(membrane stabilizing agents)
Sodium channel blockers are divided into 3 subgroups:
IA - quinidine, procainamide, disopyramide,
IB - lidocaine, mexiletine, phenytoin,
1C - flecainide, propafenone.
Subgroup IA drugs - quinidine, procainamide, disopyramide.
Quinidine- dextrorotatory isomer of quinine (an alkaloid of cinchona bark; genus Cinchona). Acting on cardiomyocytes, quinidine blocks sodium channels and therefore slows down the processes of depolarization. In addition, quinidine blocks potassium channels and therefore slows down repolarization.
The effect of quinidine on Purkinje fibers ventricles of the heart. In the action potential of Purkinje fibers, the following phases are distinguished:
Phase 0 - rapid depolarization,
Phase 1 - early repolarization,
Phase 2 - "plateau",
Phase 3 - late repolarization,
Phase 4 - spontaneous slow depolarization (diastolic depolarization); as soon as spontaneous slow depolarization reaches a threshold level, a new action potential is generated; the rate at which the threshold level is reached determines the frequency of the potentials, i.e. automatism of Purkinje fibers.
In connection with the slowdown in rapid depolarization, quinidine reduces excitability and conductivity, and due to the slowdown in spontaneous slow depolarization, it reduces the automaticity of Purkinje fibers.
Quinidine increases the duration of the action potential of Purkinje fibers.
On cells sinoatrial node quinidine has a weak inhibitory effect, since the resting potential in these cells is much lower than in Purkinje fibers and depolarization processes are mainly associated with the entry of Ca 2+ . At the same time, quinidine blocks the inhibitory effect of the vagus nerve on the sinoatrial node (vagolytic action) and therefore may cause a slight tachycardia.
in fibers working myocardium atrial and ventricular quinidine disrupts depolarization and weakens myocardial contractions. Quinidine reduces the excitability of the fibers of the working myocardium, which also prevents the pathological circulation of impulses.
Quinidine dilates peripheral blood vessels (α-adrenergic blocking action). Due to a decrease in cardiac output and a decrease in total peripheral vascular resistance, quinidine lowers blood pressure.
Assign quinidine inside with constant and paroxysmal forms of atrial fibrillation, ventricular and supraventricular paroxysmal tachycardia, ventricular and atrial extrasystoles.
Side effects of quinidine: decrease in the strength of heart contractions, decrease in blood pressure, dizziness, impaired atrioventricular conduction, cinchonism (ringing in the ears, hearing loss, dizziness, headache, visual disturbances, disorientation), nausea, vomiting, diarrhea, thrombocytopenia, allergic reactions. Quinidine, like many other antiarrhythmic drugs, in some patients (5% on average) can cause cardiac arrhythmias - an arrhythmogenic (proarrhythmic) effect.
Procainamide(novocainamide), unlike quinidine, has less effect on myocardial contractility, does not have a-adrenergic blocking properties. The drug is prescribed orally, and in emergency cases, administered intravenously or intramuscularly, mainly with ventricular, less often with supraventricular tachyarrhythmias (to stop flutter or atrial fibrillation) and extrasystoles.
Side effects of procainamide: arterial hypotension (associated with the ganglion-blocking properties of procainamide), flushing of the face, neck, atrioventricular conduction disturbances, nausea, vomiting, headache, insomnia. With prolonged use of procainamide, hemolytic anemia, leukopenia, agranulocytosis, the development of systemic lupus erythematosus syndrome (initial symptoms - skin rashes, arthralgia) are possible.
Disopyramide(ritmilen) is prescribed inside. It is effective in atrial and especially in ventricular tachyarrhythmias and extrasystoles. Of the side effects, the inhibitory effect of disopyramide on myocardial contractility and M-anticholinergic action (mydriasis, impaired near vision, dry mouth, constipation, difficulty urinating) are expressed. Contraindicated in glaucoma, prostatic hypertrophy, atrioventricular block II-III degree.
Subgroup IB drugs - lidocaine, mexiletine, phenytoin unlike drugs of the IA subgroup, they have less effect on conductivity, do not block potassium channels (“pure” sodium channel blockers), do not increase, but decrease the duration of the action potential (respectively, the ERP decreases).
Lidocaine(ksikain) - a local anesthetic and at the same time an effective antiarrhythmic agent. Due to low bioavailability, the drug is administered intravenously. The action of lidocaine is short-lived (t 1/2 1.5-2 hours), therefore, lidocaine solutions are usually administered intravenously by drip.
In Purkinje fibers, lidocaine slows down the rate of rapid depolarization (phase 0) to a lesser extent than quinidine. Lidocaine slows down diastolic depolarization (phase 4). Unlike drugs of subgroup IA, lidocaine does not increase, but reduces the duration of the action potential of Purkinje fibers. This is due to the fact that by blocking Na + channels in the "plateau" phase (phase 2), lidocaine shortens this phase; phase 3 (repolarization) starts earlier.
Lidocaine reduces excitability and conductivity (less than quinidine), reduces automatism and reduces the ERP of Purkinje fibers (the ratio of ERP to action potential duration increases).
Lidocaine does not have a significant effect on the sinoatrial node; on the atrioventricular node has a weak inhibitory effect. In therapeutic doses, lidocaine has little effect on myocardial contractility, blood pressure, and atrioventricular conduction.
Lidocaine is used only for ventricular tachyarrhythmias and extrasystoles. Lidocaine is the drug of choice for the treatment of ventricular arrhythmias associated with myocardial infarction. At the same time, long-term administration of lidocaine is considered inappropriate for the prevention of arrhythmias in myocardial infarction (possibly a proarrhythmic effect of lidocaine, weakening of heart contractions, impaired atrioventricular conduction).
Side effects of lidocaine: moderate inhibition of atrioventricular conduction (contraindicated in atrioventricular block II-III degree), irritability, dizziness, paresthesia, tremor.
With an overdose of lidocaine, drowsiness, disorientation, bradycardia, atrioventricular block, arterial hypotension, respiratory depression, coma, cardiac arrest are possible.
Meksiletin- an analogue of lidocaine, effective when taken orally.
Phenytoin(difenin) is an antiepileptic drug that also has antiarrhythmic properties similar to those of lidocaine. Phenytoin is especially effective in arrhythmias caused by cardiac glycosides.
Preparations of subgroup 1C - propafenone, flecainide - significantly slow down the rate of fast depolarization (phase 0), slow down spontaneous slow depolarization (phase 4) and have little effect on repolarization (phase 3) of Purkinje fibers. Thus, these substances significantly inhibit excitability and conduction, with little effect on the duration of the action potential. By reducing excitability, the ERP of Purkinje fibers and fibers of the working myocardium are increased. Inhibit atrioventricular conduction.
Propafenone has a weak adrenoblocking activity.
The drugs are effective in supraventricular arrhythmias, with ventricular extrasystoles and tachyarrhythmias, but they have pronounced arrhythmogenic properties (they can cause arrhythmias in 10-15% of patients), reduce myocardial contractility. Therefore, they are used only when other antiarrhythmic drugs are ineffective. Assign inside and intravenously.
β -Adrenoblockers
From p-blockers as antiarrhythmic drugs use propranolol, metoprolol, atenolol and etc.
β-blockers, blocking β-adrenergic receptors, eliminate the stimulating effect of sympathetic innervation on the heart and therefore reduce: 1) automatism of the sinoatrial node, 2) automatism and conductivity of the atrioventricular node, 3) automatism of Purkinje fibers.
B-blockers are used mainly for supraventricular tachyarrhythmias and extrasystoles. In addition, these drugs may be effective in ventricular extrasystoles associated with increased automatism.
Side effects of β-blockers: heart failure, bradycardia, impaired atrioventricular conduction, increased fatigue, increased bronchial tone (contraindicated in bronchial asthma), peripheral vasoconstriction, increased action of hypoglycemic agents (elimination of the hyperglycemic action of adrenaline).
Drugs that increase the duration of the action potential (drugs that slow down repolarization; potassium channel blockers)
The drugs in this group include amiodarone, sotalol, bretylium, ibutilide, dofetilide.
Amiodarone(kordaron) - an iodine-containing compound (similar in structure to thyroid hormones). It is highly effective in various forms of tachyarrhythmia and extrasystole, including those resistant to other antiarrhythmic drugs. In particular, amiodarone is highly effective in converting atrial fibrillation and flutter into sinus rhythm and in preventing ventricular fibrillation. The drug is prescribed orally, less often - intravenously.
Amiodarone blocks K + channels and slows down repolarization in the fibers of the conduction system of the heart and in the fibers of the working myocardium. In this regard, the duration of the action potential and ERP increase.
In addition, amiodarone has some inhibitory effect on Na + channels and Ca 2+ channels, and also has non-competitive β-blocking properties. Therefore, amiodarone can be attributed not only to III, but also to 1a, II and IV classes of antiarrhythmic drugs.
β-blockers
Amiodarone has non-competitive a-blocking properties and dilates blood vessels.
In connection with the blockade of Ca 2+ channels and β-adrenergic receptors, amiodarone weakens and slows down contractions of the heart (reduces the heart's need for oxygen), and due to the blockade of a-adrenergic receptors, it dilates the coronary and peripheral vessels, moderately lowers blood pressure. Therefore, amiodarone is effective in angina pectoris, for the prevention of exacerbations of coronary insufficiency after myocardial infarction.
Amiodarone is highly lipophilic, is deposited in tissues for a long time (adipose tissue, lungs, liver) and is very slowly excreted from the body, mainly with bile ( t 60-100 days). With prolonged systematic use of amiodarone, light brown deposits (promelanin and lipofuscin) are noted around the perimeter of the cornea (usually do not disturb vision), as well as deposits in the skin, due to which the skin acquires a gray-blue tint and becomes highly sensitive to ultraviolet rays (photosensitivity) .
Other side effects of amiodarone:
bradycardia;
Decreased myocardial contractility;
Difficulty atrioventricular conduction;
Arrhythmias torsade de pointes (“twisting peaks”; ventricular tachyarrhythmia with periodic changes in the direction of the QRS teeth; associated with a slowdown in repolarization and the occurrence of early post-depolarization - before the end of the 3rd phase) in 2-5% of patients;
Increased bronchial tone; :
Tremor, ataxia, paresthesia;
Hyperthyroidism or hypothyroidism (amiodarone disrupts the conversion of T 4 to T 3);
Liver dysfunction;
Interstitial pneumonitis (associated with the formation of toxic oxygen radicals, inhibition of phospholipases and the development of lipophospholipidosis); possible pulmonary fibrosis;
Nausea, vomiting, constipation.
Sotalol (betaspace)- β-blocker, which at the same time increases the duration of the action potential, i.e. refers to II and III classes of antiarrhythmic drugs. It is used for ventricular and supraventricular tachyarrhythmias (in particular, for atrial fibrillation and flutter to restore the sinus rhythm of atrial contractions), as well as for extrasystoles. Deprived of many side effects characteristic of amiodarone, but exhibits side effects characteristic of β-blockers. When using the drug, arrhythmias torsade de pointes (1.5-2%) are possible.
Bretylium(ornid) increases the duration of the action potential mainly in ventricular cardiomyocytes and is used for ventricular tachyarrhythmias (can be administered intravenously to stop arrhythmias). It also has sympatholytic properties.
Means that increase the duration of the action potential and, accordingly, the ERP in the atria, are effective for the translation (conversion) of atrial fibrillation into sinus rhythm.
Compounds have been synthesized that selectively block K + channels and increase the duration of the action potential and ERP without affecting other properties of cardiomyocytes - "pure" drugs III class ibutilide And dofetilide. These drugs have a selective antifibrillatory effect. They are used to convert atrial fibrillation to sinus rhythm and to prevent atrial fibrillation in the future. When using ibutilide and dofetilide, torsade de pointes arrhythmias are possible.
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A characteristic property of drugs of this class is their ability to significantly slow down repolarization without changing the rate of depolarization. Class III drugs are able to influence these processes in the atria, AV node and ventricles. The slowing down of repolarization under the influence of these drugs leads to an increase in the duration of the action potential and refractory periods. At the same time, "pure" drugs of this class do not slow down conduction, since they do not affect the rate of depolarization. This mechanism of action is realized through the blockade of outgoing potassium currents. Class III drugs increase the duration of the QT interval on the ECG, which predisposes to the development of polymorphic "pirouette" VT (trosade de pointes).
Currently, three drugs of this class are prescribed in Russia: amiodarone, sotalol and nibentan*, however, there are other promising drugs belonging to this class, in particular ibutilide and others.
Amiodarone
The drug is produced in ampoules of 150 mg and tablets of 200 mg.
Pharmacological effects
In addition to the ability to slow down repolarization, amiodarone can block adrenergic α- and β-receptors, sodium and calcium channels, that is, it has the property of all four classes of antiarrhythmic drugs. It lengthens the action potential, increasing the effective refractory period of the atria, AV node, bundle of His, Purkinje fibers, and accessory pathways. It has an effect characteristic of sodium channel blockers, but slows down intraventricular conduction to a lesser extent. Due to its ability to block slow calcium channels, amiodarone reduces the frequency of sinus rhythm and slows down conduction through the AV node. Amiodarone is chemically similar to thyroid hormones. Due to the significant content of iodine, it blocks the conversion of T4 to T3, and weakens the stimulating effect of thyroid hormones on the heart.
Pharmacokinetics
After oral administration, amiodarone is slowly absorbed by 30-50%. Bioavailability ranges from 30 to 80%, averaging 50%. In plasma, more than 90% is protein bound. After a single dose, the maximum concentration in the blood is reached after 3-7 hours. It is concentrated in adipose tissue, kidneys, liver, and lungs. Metabolized in the liver to form an active metabolite. It has a long half-life (20-110 days). With intravenous administration of amidarone, its activity reaches a maximum after 15 minutes and persists for 4 hours after injection. It is excreted by 85-95% with bile.
Indications for use and dosage
Indications. Amiodarone is considered one of the drugs of choice for the relief of paroxysmal VT, as well as for the prevention of recurrence of this arrhythmia. The drug is also effective for stopping and preventing paroxysmal supraventricular tachycardia. Amiodarone is a first-line drug for restoring sinus rhythm in paroxysmal and persistent forms of AF and for the prevention of relapses. It is also possible to use the drug to reduce the frequency of excitation of the ventricles with persistent AF with tachyarrhythmia. Amiodarone is also used to stop and prevent paroxysms of atrial flutter. The drug is effective in the prevention of recurrence of ventricular fibrillation in resuscitated patients. In addition, the drug can be used to treat patients with supraventricular and ventricular extrasystoles. Amiodarone is indicated for the treatment of arrhythmias in patients with ventricular preexcitation syndrome, coronary artery disease, including acute forms, and heart failure.
Method of application and dose. For the relief of acute arrhythmias, amiodarone is administered intravenously in a stream at a dose of 150-300 mg over 3 minutes or drip at a dose of 5 mg/kg (with heart failure 2.5 mg/kg) for 20-120 minutes and then as an infusion until daily dose of 1200-1800 mg. With planned therapy, the drug is prescribed orally at a dose of 600-800 mg / day for 5-15 days, then the dose is reduced to 400 mg / day for 5-7 days, and then switched to a maintenance dose of 200 mg / day (5 days a day). week with two days off). There are more intensive amiodarone regimens, but they are rarely used.
Contraindications
Amiodarone is contraindicated in SSSU and AV block II-III degree (in the absence of a pacemaker), prolongation of the Q-T interval on the ECG, hypersensitivity to iodine, interstitial lung disease, hypokalemia. Caution must be observed when prescribing the drug to patients with thyroid dysfunction (hypo- and hyperthyroidism), liver failure, bronchial asthma, as well as during pregnancy and lactation.
Side effects
On the part of the cardiovascular system, side effects may include the development of sinus bradycardia, impaired sinoatrial, atrioventricular and occasionally intraventricular conduction, as well as prolongation of the Q-T interval with the possible development of VT of the "pirouette" type (the frequency of the latter does not exceed 0.5%). On the part of the endocrine system, one of the frequent side effects is a violation of the function of the thyroid gland, more often in the form of its decrease. According to the ATMA meta-analysis, the incidence of hypothyroidism in the treatment of amiodarone is 6%. On the part of the respiratory system, there may be side effects such as dry cough, shortness of breath; with prolonged continuous use of high doses of the drug, interstitial pneumonia, alveolitis and pulmonary fibrosis may develop - although rare (no more than 1%), but one of the most serious side effects of amiodarone.
From the side of the nervous system, headache, dizziness, paresthesia, depression may occur, and with prolonged use - peripheral neuropathy, extrapyramidal disorders, optic neuritis. From the digestive system can be: anorexia, nausea, vomiting, constipation, diarrhea. With prolonged use, the development of toxic hepatitis is possible. Other undesirable effects should include skin pigmentation, photosensitivity, deposition of lipofuscin in the cornea, which may cause minor visual impairment.
Clinically Significant Interactions
Among the drugs that interact with amiodarone, a number of groups potentiate the prolongation of the Q-T interval, predisposing to the development of "pirouette" VT, in particular sotalol, subclass IA antiarrhythmics, phenothiazines, glucocorticoids, tricyclic antidepressants, loop and thiazide diuretics, laxatives, amphotericin B. With Combining amiodarone with other antiarrhythmic drugs increases the risk of developing bradycardia, sinoatrial and AV blockade. When combined with warfarin, cyclosporine, cardiac glycosides, it is possible to increase the concentration of these drugs in plasma.
Doshchitsin V.L.
Antiarrhythmic drugs
Sodium channel blockers ("fast")- These are drugs that block the sodium channels of cardiomyocyte membranes (reducing the rate of depolarization of the heart fiber) and have membrane-stabilizing and antiarrhythmic effects.
This group includes class I antiarrhythmic drugs (A, B and C):
- A - Aimaline, disopyramide, procainamide (Novocainamide), quinidine (Kinidin Durules).
- B - lidocaine (lidocaine hydrochloride, mexiletine, phenytoin.
- C - lippaconitine hydrobromide (Allapinin), propafenone (Propanorm, Ritmonorm).
-
Sodium channel blockers are not prescribed simultaneously with antiarrhythmic drugs of other classes.
When this group of drugs is combined with other drugs, the following reactions are possible:- With antihypertensive drugs - the hypotensive effect of these drugs is enhanced.
- With anticholinesterase agents, the effectiveness of these drugs decreases.
- With m-anticholinergics - the anticholinergic effect of these drugs is enhanced.
- With amiodarone and cisapride - the QT interval is prolonged and the risk of developing ventricular arrhythmia of the "pirouette" type is increased.
- With rifampicin, the concentration of sodium channel blockers in the blood plasma decreases.
- With phenobarbital - the concentration of sodium channel blockers in the blood plasma decreases.
- With verapamil - the risk of arterial hypotension and collapse increases.
- With antibiotics of the macrolide group (erythromycin, clarithromycin, azithromycin, josamycin), the concentration of disopyramide in the blood plasma increases, there is a risk of lengthening the QT interval, the development of ventricular arrhythmia of the "pirouette" type.
- With β-blockers - the risk of developing severe bradycardia, an increase in the QT interval increases.
- With hypoglycemic agents - the risk of developing hypoglycemia increases.
- With cyclosporine - the risk of developing nephrotoxicity increases and the anticholinergic effects of disopyramide increase.
- With laxatives - a decrease in the concentration of quinidine in the blood plasma and a decrease in its effectiveness.
- With sodium bicarbonate, acetazolamide - the likelihood of developing the toxic effects of quinidine increases.
- With tricyclic antidepressants - the excretion of desipramine, imipramine, nortriptyline, trimipramine from the body decreases, which leads to an increase in their concentration in the blood plasma.
- With amiloride - the effectiveness of quinidine decreases.
- With warfarin - the anticoagulant effect of this drug is enhanced.
- With haloperidol - the concentration of this drug in the blood plasma increases and the risk of side effects increases.
- With hydroxyzine - the risk of developing severe cardiac arrhythmias increases.
- With dextromethorphan - the concentration of this drug in the blood plasma increases.
- With digoxin - the concentration of this drug in the blood serum increases.
- With disopyramide - the concentration of quinidine in the blood plasma increases, the QT interval lengthens.
- With dicumarol - the concentration of its effectiveness increases.
- With itraconazole, ketoconazole - the concentration of quinidine in the blood plasma increases.
- With codeine - the concentration of the analgesic effect of this drug increases.
- With mefloquine - the QT interval is lengthened.
- With propranolol - the β-adrenergic blocking effect of this drug is enhanced, the risk of developing orthostatic hypotension increases.
- With captopril - increased risk of developing leukopenia.
- With ofloxacin - an increase in the concentration of procainamide in the blood plasma.
- With cimetidine - an increase in the concentration of procainamide in the blood plasma and the risk of increasing its side effects.
- With diamondylate, atropine and morphine - slowing down the absorption of mexiletin.
- With metoclopramide - acceleration of the absorption of mexiletin.
- With theophylline - an increase in the concentration of this drug in the blood plasma and an increase in its side effects.
- With β-blockers, tricyclic antidepressants, local anesthetics - increased antiarrhythmic action of propafenone in ventricular arrhythmias.
- With indirect anticoagulants - potentiation of the action of these drugs.
- With propranolol, metoprolol, cyclosporine, digoxin - an increase in the concentration of these drugs in the blood.
- With theophylline - an increase in the concentration of this drug in the blood and an increase in the likelihood of developing its toxic effects.
- With cimetidine - an increase in the concentration of propafenone in the blood plasma and the expansion of the QRS complex on the ECG.
- With erythromycin - inhibition of the metabolism of propafenone.
Class IA
Disopyramide
Quinidine, procainamide chloride (Novocainamide), disopyramide (Ritmodan, Ritmilen).
Quinidine is an alkaloid from cinchona bark (a dextrorotatory isomer of quinine). Quinidine blocks fast sodium channels of the cell membrane and therefore reduces the rate of rapid depolarization in phase 0, as a result of which it reduces the conductivity of Purkinje fibers, contractile myocardium and, to a lesser extent, atrioventricular conduction. By blocking sodium channels, quinidine slows down the slow spontaneous depolarization in phase 4 and therefore reduces automaticity in Purkinje fibers.
Quinidine blocks potassium channels, as a result of which it slows down the process of repolarization (the release of K + ions from the cell) and increases the duration of the action potential. This leads to a lengthening of the effective refractory period.
Quinidine has practically no direct effect on the sinoatrial node, in which depolarization both in phase 0 and in phase 4 is determined by the entry of Ca2+ ions, but it inhibits the transmission of excitation from the vagus nerve to the heart (anticholinergic effect) and thus can cause an increase in automatism of the sinoatrial node and moderate tachycardia. In therapeutic doses, quinidine only moderately reduces the rate of excitation through the atrioventricular node.
Quinidine reduces myocardial contractility and dilates peripheral vessels (blocks a-adrenergic receptors), resulting in a moderate decrease in blood pressure.
Quinidine is effective in both ventricular and supraventricular arrhythmias. It is prescribed orally for constant and paroxysmal
small forms of atrial fibrillation, paroxysmal tachycardia, extrasystole.
In medical practice, quinidine is used in the form of quinidine sulfate, administered orally. Quinidine is almost completely absorbed from the gastrointestinal tract. Bioavailability averages 70-80%. The maximum plasma concentration is reached after 2-3 hours. Plasma protein binding is 60-80%. Metabolized in the liver, excreted by the kidneys (about 20% unchanged); t) / 2 is 6-7 hours. Renal excretion of the drug increases when the reaction of urine changes to the acid side.
Side effects of quinidine - reduced myocardial contractility, arterial hypotension, intracardiac block; nausea, vomiting, diarrhea, dizziness, tinnitus, hearing impairment, visual impairment; thrombocytopenia. In some patients (an average of 5%), quinidine, like many other antiarrhythmic drugs, has an arrhythmogenic effect (ventricular arrhythmias of the "pirouette" type are possible).
Procainamide on the electrophysiological parameters of the heart acts like quinidine. Unlike quinidine, it reduces myocardial contractility less, has less pronounced anticholinergic properties, does not block a-adrenergic receptors, but has a moderate ganglioblocking effect. Just like quinidine, procainamide is used for ventricular and supraventricular tachyarrhythmias, extrasystoles. The drug is prescribed not only inside, but also intravenously (if necessary, to quickly achieve the effect).
When taken orally, procainamide is absorbed faster than quinidine. Bioavailability - 75-95%, slightly associated with plasma proteins (15-20%). It is metabolized in the liver to form an active metabolite, N-acetylprocainamide. According to the rate of metabolism of procainamide, slow and fast "acetylators" are distinguished, in which the duration of the drug's action differs significantly. Procainamide is excreted by the kidneys unchanged and as metabolites. The active metabolite is excreted more slowly than procainamide; in case of impaired renal function, it can accumulate in the body.
Side effects - lowering blood pressure (due to ganglion-blocking action), impaired conduction; nausea, vomiting, diarrhea, convulsions, allergic reactions, manifested in the form of fever, joint and muscle pain, skin rash, and less often in the form of a syndrome similar to systemic lupus erythematosus, agranulocytosis; neuropsychiatric disorders are possible.
Disopyramide has a pronounced antiarrhythmic effect, similar in properties to quinidine. Reduces myocardial contractility, has pronounced m-anticholinergic properties.
Indications for use are the same as for quinidine, the drug is administered orally. It is well absorbed from the intestine (bioavailability of about 80%), binds to plasma proteins, and is metabolized in the liver. It is excreted mainly by the kidneys (t1 / 2 6-8 hours).
Side effects - a significant decrease in myocardial contractility, atrioventricular block, arrhythmogenic effect. In connection with the pronounced m-anticholinergic activity, side effects such as dry mouth, accommodation paralysis, constipation (constipation), urinary retention occur.
Class IB
Lidoc aina hydrochloride (Xycaine, Xylocaine), mexiletine (Mexitil), phenytoin (Difenin).
Lidocaine hydrochloride
Class IB drugs reduce conductivity to a lesser extent than class IA drugs; they reduce the duration of the action potential, as a result of which the effective refractory period is shortened.
Lidocaine is used as a local anesthetic and antiarrhythmic agent. Both effects are associated with the blockade of sodium channels in cell membranes. Lidocaine reduces the conductivity in the Purkinje fibers and reduces the automatism of the Purkinje fibers and the working myocardium. Suppresses ectopic foci of excitation. Unlike quinidine, lidocaine does not lengthen, but shortens the action potential and the effective refractory period. Lidocaine is prescribed only for ventricular arrhythmias (tachyarrhythmias, extrasystoles). It is the drug of choice for ventricular arrhythmias associated with myocardial infarction. Since lidocaine has a low bioavailability when administered orally, it is administered intravenously (drip). It binds to plasma proteins (by 50-80%), is metabolized mainly in the liver. Rapidly disappears from blood plasma; X - about 2 hours. With liver pathology, the metabolic rate of lidocaine decreases.
Lidocaine is well tolerated, but side effects are possible: CNS disorders (drowsiness, confusion, convulsive reactions), arterial hypotension, decreased atrioventricular conduction.
Mexiletine is a structural analog of lidocaine that is effective when taken orally. Mexiletin is effective when taken orally (bioavailability is 90-100%), it acts for a long time. The drug can also be administered intravenously. Used for ventricular arrhythmias. Side effects - bradycardia, arterial hypotension, impaired atrioventricular conduction, possible arrhythmias, nausea, vomiting, neurological disorders.
Phenytoin was synthesized as an anticonvulsant (antiepileptic) agent. Then, the drug was found to have antiarrhythmic activity, similar in electrophysiological characteristics to the activity of lidocaine. Phenytoin is used for ventricular arrhythmias, including those caused by cardiac glycosides. Phenytoin is administered orally and intravenously (in the form of sodium salt).
Phenytoin is slowly absorbed from the gastrointestinal tract, binds to plasma proteins in the blood (by 80-96%); metabolized in the liver, metabolites are mainly excreted by the kidneys. Due to the delayed excretion from the body (X - more than 24 hours), cumulation is possible.
With intravenous administration of phenytoin, acute reactions in the form of hypotension and arrhythmias are possible. With prolonged oral administration, side effects occur on the part of the central nervous system (ataxia, nystagmus, confusion), hematopoietic organs, and the gastrointestinal tract. The drug causes gingival hyperplasia.
Class 1C
Propafenone (Ritmonorm), flecainide, moracizin hydrochloride (Etmozin), etacizin.
fO-HCI
"cho-s2n5
Drugs of this class reduce the rate of depolarization in phase 0 and phase 4 by inhibiting the transport of sodium ions, have little effect on the duration of the action potential and the effective refractory period.
Since these drugs have pronounced arrhythmogenic properties (arrhythmias occur in 10-15% of patients), they are used mainly for rhythm disturbances refractory to the action of other antiarrhythmic drugs.
Propafenone is a typical Class 1C antiarrhythmic agent; in addition to a pronounced blockade of sodium channels, it has some (3-adrenergic blocking activity and weakly blocks calcium channels. It is used both for ventricular and supraventricular arrhythmias with the ineffectiveness of other antiarrhythmic drugs. It is administered orally and intravenously.
When administered orally, propafenone is well absorbed from the intestine, but undergoes intensive metabolism during the first passage through the liver (bioavailability varies from 4 to 40%). More than 90% of patients belong to the phenotype of fast metabolism of propafenone, and about 10% - to the phenotype of slow metabolism. Differences in metabolic rate are due to genetic factors. In the process of metabolism, 2 pharmacologically active substances are formed.
Of the side effects noted: nausea, vomiting, constipation, dry mouth, sleep disturbance, bradycardia, bronchospasm. The drug has pronounced arrhythmogenic properties, and therefore it is used for ineffectiveness or intolerance of other antiarrhythmic drugs.
Flecainide, in connection with the blockade of sodium channels, reduces the rate of rapid depolarization (phase 0), as a result of which it slows down conduction in the Purkinje fibers, in the atrioventricular node, and the His bundle. It has little effect on the rate of repolarization, slightly reduces myocardial contractility. Applied in the form of flecainide acetate for ventricular arrhythmias in case of ineffectiveness of other antiarrhythmic drugs. Enter inside, sometimes intravenously. Side effects include nausea, headache, dizziness, blurred vision. The arrhythmogenic effect of the drug was noted in 5-15% of cases.
Moratsizin - a derivative of phenothiazine, a drug of a mixed type of action, exhibits the properties of sodium channel blockers of three classes 1C, IB, 1A. Moratsizin inhibits conduction in the atrioventricular node, His bundle and Purkinje fibers, practically does not affect the rate of repolarization. Myocardial contractility does not change significantly. Moracizin is effective in both ventricular and supraventricular arrhythmias, due to arrhythmogenic properties, it is used in arrhythmias refractory to other antiarrhythmic drugs. The drug can be administered orally and intravenously.
Side effects: arrhythmogenic effect, palpitations, headache, fatigue and weakness, diarrhea, etc.
Ethacizin is similar in chemical structure to moratsizin, blocks not only sodium, but also calcium channels. Indications for use are the same as for Moracizin. The drug is administered orally and intravenously. Side effects
Chapter 19 F Antiarrhythmic drugs ❖ 277
the effects are more pronounced and occur more frequently than that of moracizin (especially when administered intravenously).
Antiarrhythmic drugs are drugs used to normalize the rhythm of heart contractions. These chemical compounds belong to various pharmacological classes and groups. They are designed to treat and prevent their occurrence. Antiarrhythmics do not increase life expectancy, but are used to control clinical symptoms.
Antiarrhythmic drugs are prescribed by cardiologists if the patient has a pathological arrhythmia, which worsens the quality of life and can lead to the development of severe complications. Antiarrhythmic drugs have a positive effect on the human body. They should be taken for a long time and only under the control of electrocardiography, which is carried out at least once every three weeks.
The cell wall of cardiomyocytes is permeated with a large number of ion channels through which potassium, sodium, and chloride ions move. This movement of charged particles leads to the formation of an action potential. Arrhythmia is caused by abnormal propagation of nerve impulses. To restore the rhythm of the heart, it is necessary to reduce activity and stop the circulation of the impulse. Under the influence of antiarrhythmic drugs, ion channels close and the pathological effect on the heart muscle of the sympathetic nervous system decreases.
The choice of an antiarrhythmic agent is determined by the type of arrhythmia, the presence or absence of structural pathology of the heart. When the necessary safety conditions are met, these drugs improve the quality of life of patients.
Antiarrhythmic therapy is primarily carried out to restore sinus rhythm. Patients are treated in a cardiological hospital, where they are intravenously or orally administered antiarrhythmic drugs. In the absence of a positive therapeutic effect, go to. Patients without concomitant chronic heart disease can restore sinus rhythm on their own on an outpatient basis. If attacks of arrhythmia occur rarely, are short and oligosymptomatic, patients are shown dynamic observation.
Classification
The standard classification of antiarrhythmic drugs is based on their ability to influence the production of electrical signals in cardiomyocytes and their conduction. They are divided into four main classes, each of which has its own path of exposure. The effectiveness of drugs for different types of arrhythmia will be different.
- Membrane stabilizing sodium channel blockers - Quinidine, Lidocaine, Flecainide. Membrane stabilizers affect the functionality of the myocardium.
- - "Propranolol", "Metaprolol", "Bisoprolol". They reduce mortality from acute coronary insufficiency and prevent recurrence of tachyarrhythmias. Medicines of this group coordinate the innervation of the heart muscle.
- Potassium channel blockers - Amiodarone, Sotalol, Ibutilide.
- - Verapamil, Diltiazem.
- Others:, sedatives, tranquilizers, neurotropic agents have a combined effect on myocardial function and its innervation.
Table: division of antiarrhythmics into classes
Representatives of major groups and their action
1A class
The most common class 1A antiarrhythmic drug is " Quinidine" which is made from the bark of the cinchona tree.
This drug blocks the penetration of sodium ions into cardiomyocytes, lowers the tone of arteries and veins, has an irritating, analgesic and antipyretic effect, and inhibits brain activity. Quinidine has a pronounced antiarrhythmic activity. It is effective in various types of arrhythmias, but causes side effects when dosed and applied incorrectly. Quinidine has an effect on the central nervous system, blood vessels and smooth muscles.
When taking the drug, it should not be chewed, so as not to get irritation of the gastrointestinal mucosa. For a better protective effect, it is recommended to take Quinidine with meals.
the effect of drugs of various classes on the ECG
1B class
Antiarrhythmic 1B class - "Lidocaine". It has antiarrhythmic activity due to its ability to increase membrane permeability to potassium and block sodium channels. Only significant doses of the drug can affect the contractility and conduction of the heart. The drug stops attacks of ventricular tachycardia in the postinfarction and early postoperative period.
To stop an arrhythmic attack, it is necessary to inject 200 mg of "Lidocaine" intramuscularly. In the absence of a positive therapeutic effect, the injection is repeated after three hours. In severe cases, the drug is administered intravenously in a stream, and then proceed to intramuscular injections.
1C class
Class 1C antiarrhythmics prolong intracardiac conduction, but have a pronounced arrhythmogenic effect, which currently limits their use.
The most common means of this subgroup is "Ritmonorm" or "Propafenone". This medicine is intended for the treatment of extrasystole, a special form of arrhythmia caused by premature contraction of the heart muscle. "Propafenone" is an antiarrhythmic drug with a direct membrane-stabilizing effect on the myocardium and a local anesthetic effect. It slows down the influx of sodium ions into cardiomyocytes and reduces their excitability. "Propafenone" is prescribed to persons suffering from atrial and ventricular arrhythmias.
Grade 2
Class 2 antiarrhythmics - beta-blockers. Influenced "Propranolol" blood vessels dilate, blood pressure decreases, bronchial tone increases. In patients, the heart rhythm normalizes, even in the presence of resistance to cardiac glycosides. At the same time, the tachyarrhythmic form is transformed into a bradyarrhythmic form, the heartbeat and interruptions in the work of the heart disappear. The drug is able to accumulate in tissues, that is, there is a cumulation effect. Because of this, when using it in the elderly, doses must be reduced.
3rd grade
Class 3 antiarrhythmics are potassium channel blockers that slow down electrical processes in cardiomyocytes. The brightest representative of this group - "Amiodarone". It dilates the coronary vessels, blocks adrenoreceptors, lowers blood pressure. The drug prevents the development of myocardial hypoxia, reduces the tone of the coronary arteries, reduces heart rate. The dosage for admission is selected only by the doctor on an individual basis. Due to the toxic effect of the drug, its intake must be constantly accompanied by control of pressure and other clinical and laboratory parameters.
4th grade
Antiarrhythmic class 4 - "Verapamil". This is a highly effective remedy that improves the condition of patients with severe forms of angina pectoris, hypertension and arrhythmias. Under the influence of the drug, the coronary vessels expand, the coronary blood flow increases, the resistance of the myocardium to hypoxia increases, the rheological properties of the blood normalize. "Verapamil" accumulates in the body, and then excreted by the kidneys. It is produced in the form of tablets, dragees and injections for intravenous administration. The drug has few contraindications and is well tolerated by patients.
Other drugs with antiarrhythmic activity
Currently, there are many drugs that have an antiarrhythmic effect, but are not included in this pharmaceutical group. These include:
- Cholinolytics, which are used to increase the heart rate in bradycardia - "Atropine".
- Cardiac glycosides designed to slow down the heart rate - "Digoxin", "Strophanthin".
- "Magnesium sulfate" used to stop an attack of a special ventricular tachycardia, called "pirouette". It occurs with severe electrolyte disturbances, as a result of long-term use of certain antiarrhythmic drugs, after a liquid protein diet.
Antiarrhythmic agents of plant origin
Herbal medicines have an antiarrhythmic effect. List of modern and most common drugs:
Side effects
The negative effects of antiarrhythmic therapy are represented by the following effects:
Cardiovascular diseases are a common cause of death, especially among middle-aged and elderly people. Heart disease provokes the development of other life-threatening conditions, such as arrhythmia. This is a serious enough health condition that does not allow self-treatment. At the slightest suspicion of the development of this disease, it is necessary to seek medical help, undergo a full examination and a full course of antiarrhythmic treatment under the supervision of a specialist.
