ANTIARRHYTHMIC MEANS (synonym antiarrhytmic means) — group of the pharmaceuticals applied to the prevention and stopping of disturbances of a rhythm of cordial activity.
The item of page according to the classification offered in 1971 — 1972 by Singh and Williams (V. of N. Singh, V. E. M. of Williams), divide into 4 groups.
To the first group carry the drugs having membrane stabilizing properties: quinidine (see), novokainamid (see), Disopyramidum (a synonym Rythmodanum), Ajmalinum (see), Ethmosinum , see), meksitit, lidocaine, Trimecainum (see) and dipheninum (see). In the concentration necessary for identification of antiarrhytmic action, they exert comparable impact on Electrophysiologic harakteri-stpk of fibers of a myocardium. Drugs of this group have ability to reduce the maximum speed of depolarization of cells of a myocardium due to disturbance of functions of so-called bystry natrium channels of a cellular membrane. In therapeutic concentration this action is shown by increase in an excitation threshold, oppression of conductivity p increase in the effective refractory period. At the same time there is no considerable change of rest potential of a cell membrane and duration of action potential, but suppression of spontaneous diastolic depolarization of cells of the carrying-out system of heart constantly is registered.
The therapeutic effect of P. of page of this group is observed at arrhythmias (see. Arrhythmias of heart ), arising as a result of circulation of an excitation wave on a vicious circle as a result of change of the effective refractory period, and at arrhythmias which cornerstone the mechanism of strengthening of automatism or reduction of an excitation threshold is — as a result of suppression of spontaneous diastolic depolarization.
Second group The item of page includes propranolol (see) and other β-adrenoblockers, which have antiarrhytmic effect of hl. obr. due to blockade of the sympathetic influences on heart which are carried out through β-adrenoceptors.......... Blockers of β-adrenoceptors, suppressing activity of adenylatecyclase of cellular membranes, slow down formation of cyclic AMF which is the intracellular transmitter of effects of the catecholamines participating in certain conditions in genesis of arrhythmias. Electrophysiologically effect of drugs of this group in therapeutic doses is characterized by oppression of the fourth phase of depolarization. However value of this phenomenon in the mechanism of their antiarrhytmic action is still not clear. β-adrenoblockers increase duration of action potential of cells of a myocardium.
Third group The item of page is submitted by Amiodaronum (kordaron) and Ornidum (see). Amiodaronum moderately oppresses a sympathetic innervation, but does not interact with β-adrenoceptors.......... In experimental works it was shown that Amiodaronum has no membrane stabilizing effect and has extremely poorly expressed properties inherent in the first group P. of page.
Ornidum has antiarrhythmic effect, the mechanism to-rogo remains not clear. Consider that it is caused by the oppressing influence of this drug on release of noradrenaline from the terminations of sympathetic nerves.
In the fourth group P. of page inhibitors of transmembrane transport of calcium ions enter. The most active is verapamil (see). By means of electrophysiologic methods of a research it is established that it causes lengthening of the 1st and 2nd phase of action potential owing to blockade of calcium channels of a cellular membrane that is followed by antiarrhytmic action. About it experimental data confirm a role of disturbances of slow calcic current through membranes of cells of a myocardium in genesis of some types of arrhythmias to a takyasa. At such arrhythmias the ectopic center appears as a result of activation of the ionic mechanism as «the slow answer» which is normal characteristic of cells of sinus and atrioventricular nodes. Assume that this mechanism participates in developing of the arrhythmias connected both with circulation of an excitation wave, and with strengthening of automatism.
Thus, the antiarrhytmic effect can be gained as a result of influence of antiarrhythmic funds for various electrophysiologic properties of cells of a myocardium.
By efficiency at different forms of arrhythmias the page can distinguish from P. preferential effective at supraventricular disturbances of a rhythm (e.g., verapamil), hl. obr. at ventricular arrhythmias (lidocaine, Trimecainum), at supraventricular and ventricular arrhythmias (Ajmalinum, quinidine, novokainamid, Disopyramidum, etc.).
During the definition of indications to P.'s appointment pages shall be considered the form of arrhythmia, character of a basic disease, conditions promoting developing of arrhythmia and also character and features of effect of drugs.
Verapamil appoint at the supraventricular extrasystoles and supraventricular Bouveret's diseases resulting from circulation of an excitation wave in sinuatrial area, auricles, an atrioventricular node. However at patients with a syndrome of premature excitement of ventricles, at Krom during a paroxysm of tachycardia (especially atrial fibrillations) impulses in the anterograde direction are carried out on Kent bunch, verapamil can, having improved conductivity, to worsen the course of arrhythmia.
Use lidocaine and Trimecainum it is limited to parenteral administration of these drugs for the purpose of suppression of ventricular arrhythmias at an acute myocardial infarction, surgeries on heart, intoxications cardiac glycosides. In case of the arrhythmias connected from Hypaque of l by an iyemiya, the specified drugs are ineffective. Lidocaine sometimes renders also stopping effect at supraventricular tachycardias at which the circle of circulation of an excitation wave joins additional ways.
Dipheninum appoint hl. obr. at the ventricular arrhythmias arising at intoxications cardiac glycosides and hypopotassemias. The patient with the expressed heart failure and disturbance of atrioventricular conductivity usually appoint only lidocaine (in small doses) or dipheninum; P.'s most to page is contraindicated to them.
At heart failure without disturbance of conductivity it is possible to appoint, except these drugs, also an Ethmosinum and Amiodaronum.
At syndrome of a braditakhikardiya (sick sinus syndrome) can lead use of Disopyramidum, quinidine, verapamil or blockers R-ad-renoretseptorov to increase in duration of an asystolia in this connection it is necessary to appoint them with care.
Extra care is demanded by P.'s choice by the village for patients with additional ways of carrying out excitement in the anterograde direction on Kent bunch. This results from the fact that separate drugs from number P. of page stop attacks of arrhythmia, but to a ta are capable to prevent their emergence. Besides, some P. of page can promote developing of tachycardia. So, at patients with Wolff's syndrome — Parkinson — Whyte and wide ventricular complexes during a paroxysm use of glycosides or verapamil can lead to improvement of conductivity on Kent bunch, and during the trembling or atrial fibrillation to cause fibrillation of ventricles. In such cases for stopping of an attack it is recommended to appoint lidocaine, novokainamid, Ajmalinum or Amiodaronum.
At nodal atrioventricular Bouveret's disease it is the most reasonable to apply verapamil, Obsidanum, Amiodaronum, and also the cardiac glycosides having ability to slow down the speed of carrying out excitement in an atrioventricular node. At such arrhythmias novokainamid and quinidine are ineffective since they do not influence conductivity in this node. However novokainamid and quinidine can be used for the prevention of attacks as they suppress premature ventricular contraction which is in certain conditions a starting factor in emergence of a paroxysm of tachycardia.
For stopping ciliary arrhythmia intravenous administration of a novokainamid, Ajmalinum, Amiodaronum is recommended; at satisfactory portability of an attack inside appoint quinidine, Disopyramidum or novokainamid in the corresponding doses. Verapamil and cardiac glycosides use only for the purpose of an urezheniye of a rhythm of ventricles.
At patients with ventricular tachycardia the most effective for interruption of an attack is lidocaine which if necessary it is possible to appoint in the maximum therapeutic dose (before emergence of moderately expressed symptoms from c. item of page). In the absence of effect of lidocaine use other drugs (taking into account contraindications).
Tactics of treatment of P. of page is defined by weight of a course of a disease and predictive value of the available disturbances of a heart rhythm. Does not raise doubts need for the purpose of prevention of constant administration of drugs at the paroxysms which are often repeating (several times a week), the frequent premature ventricular contraction which are followed by the expressed disturbances of a hemodynamics and bad' health p causing disability or life-threatening. Patients with rare attacks of tachycardia (tachyarrhythmia) or with rather frequent, but proceeding without sharp disturbance of the general state attacks which are easily stopped can recommend P.'s reception by the village only for the purpose of their interruption.
Tactics of the doctor at treatment of patients with ekstrasistoliya, proceeding asymptomatically or with insignificant a wedge, manifestations, is defined by predictive value of extrasystoles. Prospective observations showed that at almost healthy faces supraventricular or ventricular extrasystoles are not life-threatening therefore accidental identification at them asymptomatically the proceeding disturbance of a cordial rhythm (without heart disease) shall not serve as the indication to P.'s use by the village. At the same time at hron, coronary heart disease ventricular extrasystoles considerably worsen the forecast for life in this connection patients should appoint the drugs having anti-anginal and antiarrhytmic effect.
There is development, this, testimonial of a possibility, in certain cases of aritmogenny action of all active P. of page. In this regard at Wolff's syndrome — Parkinson — Whyte, individual selection of P. of page by acute medicinal tests is necessary for ventricular tachycardia and fibrillation of ventricles (intravenous or peroral administration of P. of page since small doses which bring to the most admissible) under careful electrocardiographic control at rest and at an exercise stress or against the background of artificially imposed heart rhythm that allows to reveal timely aritmogenny action of P. of page and if necessary to give the emergency help.
In the absence of effect of purpose of any one drug use P.'s combinations of page from various groups. The most rational is co-administration of beta adrenoblockers with quinidine or with cardiac glycosides. However it is not recommended to combine P. the pages having the identical mechanism of action or exerting opposite impact on Electrophysiologic properties of a myocardium and the carrying-out system of heart.
The Kliniko-pharmakologichesky characteristic of the main P. of page is provided in the table.
Bibliography: Masur N. A. Current state and perspectives of studying of disturbances of a heart rhythm, Cardiology, t. 18, No. 4, page 5, 1978; it e, Questions of terminology, classification of disturbances of a cordial rhythm and tactics of their treatment, Bulletin Vsesoyuz. kardiol. nauch. USSR Academy of Medical Sciences center, t. 3, No. 2, page 8, 1980; Sumarokov A. V. and Mikhaylov A. A. Arrhythmias of heart, M., 1976; H and z about in E. I. and Bogolyubov V. M. Disturbances of a heart rhythm, M., 1972; Krone R. J. and. To 1 e i g e of R. E. Prevention and treatment of supraventricular arrhythmias, Heart a. Lung, v. 6, p. 79, 1977; Opie L. H. Drugs and the heart, Lancet, v. 1, p. 861, 1980; Rosen M. R. a. Hoffman B. F. Mechanisms of action of antiarrhythmic drugs, Circulat. Res., v. 32, p. 1, 1973; Singh B. N. a. Vaughan Williams E. M. Effect of altering potassium concentration on the action of lidocaine and diphenylthydantoin on rabbit atrial and ventricular muscle, ibid., v. 29, p. 286, 1971; they, A fourth class of anti-dysrhythmic action? Effect of verapamil on ouabain toxicity, on atrial and ventricular intracellular potentials, and on other features of cardiac function, Cardiovasc. Res., v. 6. p. 109, 1972; Singh B. N. Collett J. T. a. Chew Ch. Y. C. New perspectives in pharmacologic therapy of cardiac arrhythmias, Progr. cardiovasc. Dis., v. 22, p. 243, 1980; Winkle R. A., G I a n t z S. A. a. Harrison D. C. Pharmacologic therapy of ventricular arrhythmias, Amer. J. Cardiol., v. 36, p. 629,1975.
H. A. Masur.