CARDIAC GLYCOSIDES — kardiotonnchesky means from group of steroid O-glycosides. In the nature This year contain in plants of 45 types relating to various families (to dogbane family, a lily family, a crowfoot family, bean, etc.), and also in skin poison of nek-ry toads.
The plants containing This year used as pharmaceuticals and ritual poisons in an extreme antiquity. Simple and galenova drugs of a foxglove are for the first time implemented in medical practice in the second half of 18 century by the English doctor W. Withering. The big contribution to studying was made This year by the Russian scientists E. V. Pelikan, S. P. Botkin, N. D. Strazhe-sko, etc.
To This year, the most widely used in modern medical practice, drugs belong foxgloves (see), napr, digitoxin (see), digoxin (see), acetyldigitoxin (see), Celanidum (see), lantosidum, etc., Strophanthus — strophanthin (see), lily of the valley (see) — Korglykonum and tincture of a lily of the valley, adonis (see) — Adonisidum and extract of an adonis dry.
Chemical constitution of cardiac glycosides
the Molecule consists of genin (aglikon) and glycanes This year. Genina represent steroid alcohols from group of derivatives of cyclopentanperhydrophenanthrene, at to-rogo in situation C17 there is unsaturated lactonic ring. The main are connected with existence in structure of genin pharmakol This year. properties of these substances. Rings of a cyclopentanperhydrophenanthrene kernel designate Latin letters 'And,
In, C and D. Existence cis-of communication between rings is characteristic of genin pharmacological active And yes This year In, C and D, and also a trance-svyazp between rings In and S. Besides, in a molecule of genin is available methyl group in situation C13 and hydroxylic group in situation C14.
Depending on the radical at C10 distinguish genina with aldehydic, spirit and methyl groups. Radicals at C5 and C17 can be presented by hydrogen or hydroxylic group, and at C16 — various chemical groups (fig. 1). Changes of any of perechnelenny radicals in genina define water solubility and lipophilicity and consequently, completeness of absorption, the speed of approach and duration of action corresponding This year. Depending on structure of lactonic ring (fig. 2) of a genina subdivide into kardenolida (with pentatomic nonlimiting 7-lactonic ring) and bufadiyenolida (with six-membered, twice unsaturated V-lactonic ring).
At saturation of lactonic ring activity decreases and development of pharmacological action accelerates This year, and disclosure of this ring is followed by an inactivation of genin.
In a molecule mean the remains of cyclic sugars connected through an oxygen linkage with genina in situation C3 by glycanes This year. Applied contain in medicine from one up to four remains of sugars This year, i.e. are mono - dio-, the trio - or tetrazidam. With increase in quantity of the remains of sugars biol. activity goes down This year. Depending on character of glycane subdivide by the following criteria This year. In a tautomeric form of the monosaccharides entering glycane divide into pyranosides (six-membered ring) and furanozida (pentatomic ring) This year. On and - or r-configurations of the hemiacetal hydroxyl connected with geniny distinguish alpha and beta glycosides. Depending on the nature of the sugar rest divide into pentazides, geksozida and biosides This year. More than 30 monosaccharides can be a part of glycanes This year, many from to-rykh are only a part of cardiac glycosides (D-digitalose, D - digitok-soza, D-cymarose, etc.), and others are eurysynusic in the nature (D-glucose, L-rhamnose, D-fukoza, etc.). Solubility, activity and toxicity This year, and also extent of their fixing in fabrics depends on character of glycane.
At hydrolysis from a molecule the remains of sugars are chipped off This year. Formation of so-called secondary glycosides from primary (genuinical), contained in vegetable raw materials is explained by it.
Properties and the mechanism of effect of cardiac glycosides
have direct selective effect on a myocardium This year and cause a positive inotropic effect (strengthening of cordial reductions), negative chronotropic effect (urezhe-ny cardiac rhythms), negative dromotropic effect (reduction of conductivity) and positive bathmotropic effect (increase in excitability of all elements of the carrying-out system of heart, except for a sinus node). At use This year in therapeutic doses the first three effects of these drugs and only partially positive bathmotropic effect are shown. Dromo-and bathmotropic effects are most expressed at intoxication This year. Positive inotropic action
shift up is the cornerstone This year of a curve force — speed. As a result of it ability of heart to perform work with this filling pressure, systolic pressure in ventricles, a stroke output and this expelled fraction of blood increases, the systole is shortened and the konech-but-systolic volume of ventricles decreases. Positive inotropic action is clinically expressed This year only in the conditions of heart failure when the stroke output is limited owing to decrease in contractility. At healthy faces signs of a positive inotropic effect can be revealed only by means of special hemodynamic researches This year.
On modern representations, do not influence education, stocks and release of energy in a myocardium This year, and also do not make direct impact on sokratitelny proteins. Linkng of their lactonic ring with the Na+-SH groups, K+ - dependent ATP-ase of cells of a myocardium is the cornerstone of action This year. There is a direct correlation between braking of activity of this key enzyme potassium sodium pompe and expressiveness of an inotropic effect This year. It is proved also that donators of SH-group, napr, Unithiolum (see), reduce cardiotonic action This year. Oppression of activity of Na+-, Independent ATP-ase under influence leads to decrease in intensity of the transmembrane movement of ions of Na + This year and K+ in this connection ion concentration of Na + in a cell increases. At the expense of yet not identified mechanisms growth of intracellular ion concentration of Na + leads to increase in consumption by cardiomyocytes of Sa2 + and promotes allocation of this ion from tanks of a sarcoplasmic reticulum. Ions of Sa2+, interacting with protein of troponi-nomas, activate actomyosin that is followed by strengthening of contractility of a myocardium.
Increase under the influence of This year force and speed of cordial reductions leads to nek-rum to increase in oxygen consumption by healthy heart. However at insufficiency blood circulations (see) these effects are not followed This year by increase in oxygen consumption and substrates of oxidation as This year significantly unload a myocardium and transfer it to energetically more favorable level of work, reducing the volume of heart and tension developed by it.
Compensating increase in intracellular concentration of sodium and calcium by criterion of isowasps-motichnosti, ions of K+ leave cardiomyocytes. The gradient of ion concentration of K+ on a membrane decreases therefore the rest potential of cells moves closer to a threshold of depolarization. In low concentrations change the size of rest potential a little This year, in high — considerably reduce it. In this regard at poisonings automatism of all elements increases This year the carrying-out system of heart (see) the pbyavleniye of ectopic activity is also provoked. The adverse positive bathmotropic effect is aggravated at a hypercalcemia, a hypopotassemia, effect of sympathomimetic amines and an Euphyllinum This year. Reduction of rest potential is followed by shortening of action potential. According to it the effective refractory period is shortened that promotes developing of atrial and nodal arrhythmias (see. Arrhythmias of heart ).
Negative dromotropic effect is shown by reduction of speed of atrioventricular conductivity and the corresponding shortening of an interval of PQ This year. This phenomenon is caused both by direct action on a myocardium, and activation of a vagus nerve This year. The negative dromotropic effect is the reason of development of an incomplete, and then and total atrioventricular block in the beginning This year (see. Heart block ) and arrhythmias on the mechanism of a repeated entrance of excitement. At the same time delay of atrioventricular conductivity provides therapeutic effect This year at supraventricular tachycardias, including at a ciliary takhisistoliya (see. Ciliary arrhythmia ). The intra ventricular conductivity on Purki-nye fibers measured on duration of the QRS complex, cardiac glycosides are not worsened significantly.
In small doses have negative chronotropic effect as a result of activation of influences of a vagus nerve on a myocardium This year. This effect is eliminated atropine (see). At use of high doses direct negative dromotropic effect on sinuatrial connection prevails This year. Activation of a vagus nerve at influence is carried out reflex from baroreceptors of sinocarotid and aortal zones (a sinokardial-ny reflex) and from stretch receptors of a myocardium This year (so-called effect of Betsold, or a cardio-cardial reflex of Betsold — Yarisha). At the same time intensity of a Bainbridge reflex decreases (see. Reflexogenic zones) owing to reduction of stretching of receptors of mouths of venas cava. Thus, at heart failure (see) cardiac glycosides in therapeutic doses slow down a sinoatrial rate of hl. obr. as a result of improvement of blood circulation.
This year cause more bystry relaxation of a myocardium and change the direction of process of repolarization in this connection amplitude of a tooth of T decreases by an ECG, and the segment of ST decreases below the isoline. These changes are not eliminated with atropine and are not a sign of toxic action.
Data on influence on coronary circulation are contradictory This year. In therapeutic doses This year usually do not worsen it. However cases of provocation of attacks are described stenocardias (see) under influence This year.
Cardiotonic action of all in comparable doses is identical This year. Separate drugs differ from each other in generally pharmacokinetic parameters This year (see articles devoted to separate drugs This year).
Indications and contraindications to use of cardiac glycosides
the Main indication to use is This year heart failure (see). This year are most effective at the heart failure caused by overloads, napr at arterial hypertension, valve heart diseases, an atherosclerotic cardiosclerosis. In other cases, napr, at a prelum a tumor of mouths of venas cava or a calciphied pericardium when the kontraktilnost of heart is normal, do not render significant This year to lay down. effect.
This year are a little effective at the majority myocardial dystrophies (see), cardiomyopathies (see), myocardites (see), and also at aortal insufficiency, especially syphilitic etiology (see. acquired ), and thyrotoxicosis (see) if the sinoatrial rate is kept, at a pulmonary heart (see) without therapy of a basic disease. However This year are not contraindicated at these diseases since have a nek-swarm medical effect, reducing symptoms of a cordial decompensation. At acute myocardites appoint only in the reduced doses This year.
At attacks of Bouveret's supraventricular disease give good preventive and medical, effect This year, but supraventricular paroxysmal tachycardia (see) with an atrioventricular block can appear also at intoxication This year. Therefore it is possible to appoint This year, only precisely knowing that earlier patients with the specified pathology did not accept these drugs. This year are highly effective at a takhisistolichesky form of blinking or an atrial flutter in combination with a fluid lungs. Ventricular premature ventricular contraction (see), arisen against the background of treatment This year, is one of symptoms of intoxication and demands drug withdrawal. At the same time premature ventricular contraction connected with an overload of ventricles at heart failure after adequate therapy can disappear This year.
At ventricular tachycardia it is possible to apply with care to treatment of the accompanying circulatory unefficiency This year. However at emergence of ventricular tachycardia against the background of therapy it is necessary to cancel This year the used drug since disturbance of a rhythm can be a consequence of intoxication This year
This year are moderately effective at an acute left ventricular failure of the different degree caused by an acute myocardial infarction, but are contraindicated at cardiogenic shock (see). At an acute myocardial infarction (see) This year apply in reduced doses as ischemic areas of a myocardium of an aritmogenna. At careful use in cases of an acute myocardial infarction This year statistically authentically do not increase either mortality, or quantity of arhythmic complications.
At the stenocardia which arose against the background of heart failure and carat a diomega of l of AI, render positive effect This year. However in the absence of heart failure they can aggravate a wedge, displays of stenocardia also in some cases provoke emergence of its attacks. Therefore at unstable stenocardia these drugs are inexpedient to be used.
This year are contraindicated at an idiopathic subaortal stenosis since strengthening of cordial reductions caused by them increases extent of disturbance of outflow of blood from a left ventricle. At an atrioventricular block of the second degree are contraindicated owing to danger of development of total cross block, especially against the background of attacks of Morganyi This year — Adams — Stokes (see. Morganyi — Adams — Stokes a syndrome ). It is not necessary to apply This year at a syndrome Wolf-fa — Parkinson — Whyte (see. Wolff — Parkinson — Whyte a syndrome ).
During pregnancy and feeding a breast it is necessary to appoint This year with care since they rather easily get through a placental barrier and are allocated with maternal milk.
Side and toxic effect of cardiac glycosides
is Distinguished by cordial and extracardiac manifestations of toxic action This year. Cordial displays of intoxication are caused by features of the mechanism of action on a myocardium This year.
So, the reduction of amplitude of rest potential caused This year which is followed by shortening of the refractory period can be one of the reasons of fatal fibrillation of ventricles, ventricular and atrial extrasystoles which are often proceeding as allorhythmias (up to a bigeminal pulse). Due to the negative dromotropic effect can cause an atrioventricular block of various degree This year. Also not Bouveret's supraventricular Bouveret's diseases with an atrioventricular block are characteristic of intoxication This year. The sinus arrhythmia, sinuatrial blockade, a stop of a sinus node, tachycardia from atrioventricular connection and polytopic ventricular tachycardia is possible. Electrocardiographic symptoms of intoxication are the sinus bradycardia, atrioventricular dissociation, ventricular arrhythmias and supraventricular arrhythmias with an atrioventricular block.
Treat extracardiac displays of intoxication went. - kish., neurologic and nek-ry other frustration. Disturbances of functions went. - kish. a path (anorexia, nausea, vomiting) most often develop at the patients accepting This year orally. However in some cases these disturbances are noted also at intravenous administration of drugs. To nevrol. to the disturbances caused This year neuralgia, headaches, etc. belong.
At long reception it is possible This year bradycardia (see), aggravation of heart failure, a lose of weight, disturbance of color sight (scotoma, vision in yellow or green color, white auras around objects), development of a delirium (see. Delirious syndrome ), slackness, sleeplessness (see), dizziness (see).
Treat number of the rare complications caused This year gynecomastia (see), skin allergic reactions, immune thrombocytopenia (see). One of the main reasons of intoxication is the overdose of drugs This year. Development of intoxication is promoted by change of pharmacokinetics This year at nek-ry patol. states, napr, at a hypothyroidism, a renal or liver failure. Sensitivity to This year is increased at elderly people, and also at kardiomiopa-tiya, a hypoxia of a myocardium (e.g., at an acute heart attack), disturbances of an acid-base state, especially at alkalosis (see), hypomagnesiemia and hypercalcemias (see). Most often development of intoxication is promoted by exhaustion of reserves of potassium under the influence of saluretics and in connection with secondary This year hyper aldosteronism (see). It is possible to refer also electric cardioversion to the factors provoking arrhythmias.
Development of intoxication is promoted by prescription of medicines, strengthening action This year, napr, drugs of calcium, or the means increasing ion concentration of calcium in blood, napr, quinidine against the background of therapy by digoxin. Cancellation of the drugs weakening effects This year, napr of phenobarbital, Butadionum, a holesti-ramin, drugs of potassium, can also be the cause of strengthening of toxicity This year.
At intoksikatsionny tachyarrhythmias cancel This year and appoint drugs of potassium, dipheninum, a xycain, p-adrenoblockers, napr, ana-prilin. In the presence hypopotassemias (see) appoint drugs of potassium, napr, potassium chloride inside (to 4 — 7 g a day) or intravenously (to 5% solution of glucose with a speed of 40 mekv / hour during 1 — 3 hour). It is not recommended to appoint potassium at an atrioventricular block or a hyperpotassemia. In such cases it is reasonable to apply dipheninum.
The xycain is very effective at the ventricular tachyarrhythmias arising at v of intoxication This year. However it can be used only in the absence of an atrioventricular block. In the latter case use of an artificial pacemaker can be required (see. Cardiostimulation ). For therapy of the ventricular arrhythmias caused This year it is impossible to use electric cardioversion since it can lead to fibrillation of ventricles. At emergence of fibrillation electric defibrillation (see) is method of the choice.
At intoxications also donators of sulphhydryl groups, napr, Unithiolums, and the drugs connecting calcium ions and reducing their content in blood serum, napr, disodium salt ethylene diamine tetraacetic to - you are effective This year.
Bibliography: Votchal B. E. and Slutsk M: E. Cardiac glycosides, M., 1973, bibliogr.; Gatsura V. V. and Kudrin A. N. Cardiac glycosides in complex pharmacotherapy of insufficiency of heart, M., 1983; M and sh to about fi-of a ska y M. D. Pharmaceuticals, p.1, page 341, M., 1977; Sivkov I. I. and Kukes V. G. Chronic circulatory unefficiency, D., 1973; Sycheva I. M. and Vinogradov A. V. Chronic circulatory unefficiency, page 72, M., 1977; Cardiac diagnosis and treatment, ed. by N. O. Fowler, p. 1009, Hagerstown, 1976; Harrison’s principles of internal medicine, ed. by K. J. Is-selbacher a. o., p. 1064, N. Y., 1980; The heart, ed. by J. W. Hurst a. o., p. 1942, N. Y. a. o., 1978; Heart disease, ed. by E. Braunwald, p. 509; Philadelphia a. o., 1980; The pharmacological basis of therapeutics, ed. by A. G. Gilman and. lake, N. Y., 1980.
Century of H. Uranov.