Attention! The information is for reference purposes!
Before taking you should consult with a doctor!
SITE GUIDE ONLY. Not a pharmacy! We do not sell drugs! Nothing!

cardiac glycosides

The term "cardiac glycosides" firmly entrenched in medical terminology. These are specific chemical structure of the compounds contained in a number of plants and having characteristic cardiotonic activity. These are complex organic compounds such as esters, fissile during hydrolysis to sugars (glucones) and bessaharistuyu part (aglycone or Genins) .K this group are similar in structure and action of drugs derived semisynthetic or synthetically.
Aglycones have a steroid (tsiklopentapergidrofenantrenovuyu) structure with different radicals in different positions and with the core attached to the 17-position five-membered mono-unsaturated lactone ring at the most active cardiac glycosides. Some cardiac glycosides, isolated from the squill (stsillaren A stsillarenV) Helleborus (korelborin) et al., Instead of five-membered ring contains two six-membered unsaturated lactone ring. Glycosides with a five-membered lactone ring up cardenolides group with a six-membered ring - bufadienolides group.
The plants containing cardiac glycosides include various types of foxglove (Digitalis purpurea L., Digitalis Lanata Ehrh., Etc.), Adonis (Adonis vernalis L. et al.), Lily of the valley (Sonvallaria majalis L,.), Obvoynik (Reriploca graesa L.), different types of zheltushnik (Erysimum sanescens the Roth., Erusimum cheiranthoides L., et al.), strophanthus (strophanthus gratus, strophanthus Kombe), oleander (of Nerium oleander L.), hellebore (Nelleborusrurrurascens W. et K.), jute dlinnoplodny (Sorshorus L. The olitorius) hargkustarnikovy (Gomphocarpus fruticosus A. Br.) and others. The early used cardiac glycosides from obvoynika (periplotsin) zheltushnik (erizimin, erizimozid), oleander (neriolin, kornerin), hellebore (korelborin) kendyr Konoplev (tsimarin), jute dlinnoplodnogo (olitorizid, korhorozid), Kharga shrub (gomfotin) and konvallotoksiniz lily of the valley, are excluded from the range of medicines, because they do not have advantages over basic modern cardiac glycosides. Specific action cardiotonic glycosides contained in these plants, mainly due to the presence and nature of a part of their aglycones molecule. Some cardiac glycosides may imetodin same aglycone, but the remains of the different sugars; others - contain the same sugar, but different aglycones; individual glycosides characterized finally by others as part saccharina and aglycone. The molecule may be one (konvallotoksin), two (strophanthin, olitorizid et al.), Tri (digitoxin, digoxin, etc.) Or four parts sugar (digilanidy A, B and C) .u digilanidov A, B and C and atsetildigitoksina sugar residues attached to the residue acetic acid.
Residues sugars do not possess cardiotonic activity, but they affect the solubility of glycosides, their permeability through cell membrane, ability to bind to plasma proteins and tissues as well as natoksichnost.
The essential importance of physical and chemical properties of individual glycosides and their pharmacokinetic parameters.
By physico-chemical properties of cardiac glycosides are divided HA2 groups: polar and non-polar. The polar (hydrophilic) glycosides, which is the main representative of strophanthin (as well as part of the Korglikon konvallotoksin) sparingly soluble in lipids, and poorly absorbed from the gastrointestinal tract. Therefore, they are applied parenterally (intravenously). When administered intravenously strofantina effect develops quickly - in 5 - 10 minutes, the maximum effect - 25 - LP min. The biological half-life in plasma is srednem23 hours, and all the action is terminated after 2 - 3 days.
Polar glycosides derived largely kidneys in svyazis than violation of renal excretory function of dose (to avoid cumulation) should be reduced.
The non-polar (lipophilic) glycosides are readily soluble in lipids; They are well absorbed in the intestine rapidly bound to plasma proteins, mainly albumin. A significant amount of the dose absorbed in the intestine nonpolar glycoside to the liver and excreted in the bile, and then again reabsorbed in the gastrointestinal tract.
The main representative of the non-polar glycosides digitoxin is. Action digitoksina begins to appear after 2 - 4 hours after ingestion, reaches a maximum at 8 -. 12 hour plasma half-life period is an average of 5 days, and the action stops completely after 14 21 days.
Non-polar glycosides marginally excreted in the urine, a violation of renal excretory function has little effect on their excretion.
Due to the fact that they are well absorbed and are not destroyed in the gastro-intestinal tract, they are effective when taken orally. Because of the duration of the action, the non-polar glycosides relatively easily can cause cumulative effects.
If the impossibility of introducing this group of glycosides in a stomach (e.g., during vomiting) are sometimes administered rectally (as suppositories).
Some glycosides are intermediate between the most polar (strofantinom) and nonpolar (digitoxin) glycosides. Thus digoxin is well absorbed from the gastrointestinal tract, binds to plasma proteins otnositelnomalo largely (about 3O%) excreted by the kidneys. Like strofantinu, it has a rapid effect when administered intravenously; its effect when administered 30 begins after 20 minutes and the introduction of non - 5 - 20 min.
After blood in the heart tissues glycosides fiksiruyutsyav suction and receipt, including the heart muscle. The duration of action depends on the strength of the binding proteins, the destruction rate and excretion from the body. These factors determine the ability of the drug to accumulate in the body (the degree of cumulation). From the preparations of digitalis, most closely associated with proteins and has the most lasting effect and the cumulative effect of digitoxin, somewhat less pronounced, these properties have atsetildigitoksina, tselanida, digoxin. Less bind to other proteins will appear and have a relatively small effect of cumulative strophanthin and some other glycosides.
Selecting the mode of administration and the drug is dependent on the indication. In acute cardiovascular collapse and sudden decompensation occurred willows other cases where immediate assistance is needed, resort to intravenous medications that provide fast, strong, although relatively short, action (strofantin, Korglikon). In chronic heart failure, on the basis of long-term illness, as well as for maintenance treatment after the removal of the phenomena of acute cardiovascular insufficiency, usually used cardiac glycosides, which have full effect after oral administration (digitoxin, digoxin and others.).
For the treatment of chronic heart failure glycosides are used in dosages that will provide the establishment of stable therapeutic concentration in the blood. In the phase I treatment ( "saturation") reach the compensation of cardiac activity, and in phase II ( "maintenance"), cardiac glycosides administered in small doses, sufficient to maintain the achieved compensation. For some patients, "maintenance" phase can be very long, sometimes lifelong. In phase I drugs are administered: parenterally (intravenously) or into, and in phase II, - usually inside.
There are 3 digitizing method:. A) The fast digitalization, designed for the creation of "saturating" the concentration of the drug within pervyh24 - P6 h This requires large doses of the drug, which is associated with the danger of overdose. Due to the frequent occurrence of toxic side effects, this method is used only in rare cases (only in a clinical setting); b) moderately rapid digitalization, involves the use of medium-dose with the onset of the effect of 2 - 5 - 7 days; drug prescribed fractionally, gradually picking up the optimal dose for a given patient; c) the method of slow digitalization in small doses.
The most common method of digitizing a moderately fast pace.
When administered intravenously, the required amount of cardiac glycoside solution is usually diluted in 10 - 20 ml of 5%, 20% or 40% glucose solution, and if there are contraindications to the use of glucose - in the same volume of isotonic sodium chloride solution. Enter slowly. For drip infusion diluted glycoside solution in 5% glucose solution or isotonic sodium chloride solution.
The action of cardiac glycosides appears to change all the main functions of the heart. Under the influence of therapeutic doses of cardiac glycosides observed: a) strengthening of systolic contractions of the heart; the duration of systole is reduced, this effect is mainly due to a direct effect on the heart; b) extending the diastole; heart rate slows down, improving blood flow to the ventricles; due to the simultaneous amplification systolic contraction increases stroke volume. Deceleration rate is largely due to increased tone of the vagus nerve center; it is not observed after atropine. Increasing center vagal tone is a reaction to the excitement of vascular reflex zones occurring in the amplification of the pulse wave as a result of systolic cardiac glycosides; c) lowering the excitability of cardiac conduction system; slows conductivity bundle branch block, lengthening the interval between contractions of the atria and ventricles (atrioventricular conduction slowing).
The main therapeutic effect of cardiac glycosides heart failure manifests itself. Causes of strengthening myocardial contraction, helps expel blood received by the chambers of the heart during diastole, and improved circulation. It should be borne in mind that the optimum effect depends on the correct selection of the dose. Optimal dosages to improve the energy balance of the myocardium, inadequate doses can lower it.
Cardiac glycosides are effective for different types of heart failure (left and right ventricular), especially in heart failure due to overloading of the myocardium in hypertension, valvular heart disease and atherosclerotic cardiosclerosis.
The use of cardiac glycosides at the initial or latent heart failure is not only preventive but also therapeutic interventions, with which you can rectify the existing functional disorders and prevent the development of overt heart failure.
In connection with the action of bradycardic, some cardiac glycosides are effective for atrial fibrillation, atrial flutter, paroxysmal atrial tachycardia and atrioventricular node. However, please note that in high doses can cause cardiac glycosides supraventricular paroxysmal tachycardia with partial atrioventricular block, in connection with which these drugs are dangerous to take, if not established the cause of the arrhythmia. If ventricular tachycardia cardiac glycosides increase the risk of ventricular fibrillation.
Influence of cardiac glycosides on the blood pressure is not constant. When stagnation and reduced blood pressure, it increases with the improvement of cardiac function, with increased blood pressure, significant changes in its value is usually not observed. The pressure in peripheral veins while improving blood circulation usually decreases. abdominal vessels are narrowed, renal vessels dilate slightly. Cardiac glycosides increase tonuskoronarnyh arteries. This effect is due to the fact that cardiac glycosides are synergistic calcium ions. Therefore, in patients with coronary artery disease and with atherosclerotic lesions of the coronary vessels in the application of cardiac glycosides may aggravate angina pectoris. The deterioration of the patients can also be explained by the increase of the shock of the heart and increased myocardial oxygen demand. In recent years, in order to prevent these effects are recommended antianginal drugs from the group of calcium antagonistovionov.
Urine output under the influence of cardiac glycosides is enhanced; This effect is mainly due to the general improvement of blood circulation.
Data on the effect on blood clotting contradictory, but it is advisable in the treatment of cardiac glycosides monitor coagulation indicators.
Cardiac glycosides also have an effect on the central nervous system. Preparations adonis and lily of the valley is often used together with bromides and valerian preparations as a means of calming and improving heart function.
In high doses, cardiac glycosides can cause nausea and vomiting, which is due to their direct impact on the vomiting center and chemosensitivity receptor area (See. Emetics), as well as reflections caused (by ingestion) irritating effect on the gastric mucosa. Emetic effect is partly due to reflections that occur when excited cardiac receptors.
In high doses, possible loss of appetite, diarrhea, disorders of the central nervous system (headache, anxiety, insomnia, depressive effects, visual disturbances).
With an overdose of cardiac glycosides may lead to severe bradycardia, arrhythmia politopnye, bigemia or trigeminy, slow down atrioventricular conduction. Toxic doses can cause ventricular fibrillation and cardiac arrest.
In connection with the ability to cumulation, the toxic effect may in some degree manifest long-term use heart glikozidovv normal doses.
When intoxication associated with an overdose of cardiac glycosides, make a break in their application, the duration of which depends on the cumulative properties of the preparation used and the clinical picture; if necessary, give the preparations of potassium and antiarrhythmic drugs (See. Difenin) .Kaly especially indicated for concomitant use of cardiac glikozidovi diuretics (saluretiki).
When administered in subcutaneous adipose tissue, cardiac glycosides solutions are irritating.
General contraindications to the use of cardiac glycosides: bradycardia, atrioventricular block of varying degrees, Adams syndrome - Stokes - Morgan, angina (angina use is possible only in the presence of heart failure). Caution is needed in myocardial infarction (use is possible only with severe heart failure with dilatation of the myocardium); in shock or absence of signs of heart failure, cardiac glycosides are contraindicated.
Biochemical and physico-chemical elements of the mechanism of action of cardiac glycosides include a number of interrelated processes. Small doses increase the content of catecholamines in the myocardium, stimulate "Na + - K + - pump" and have a positive inotropic effect, which correlates with an increase in catecholamine concentrations. Higher doses inhibit Na + - K + - ATPase sarcolemma and "Na + - K + - Pump", increase the intracellular content of Na + and activate transsarkolemmnuyu + Na exchange system - Ca ~ +, causing an increase in revenues in the Ca ion cells, which contributes to further positive inotropic effect. In addition, under the influence cardiotonic agents is inhibited enzyme activity of phosphodiesterase (PDE mainly III), which leads to inhibition of disintegration of cyclic adenosine monophosphate (cAMP) - "secondary mediator" participating in the energy supply of the contractile process in myocardial cells.
A certain importance is given to the influence of cardiac glycosides on adenosine receptors and antagonism of endogenous adenosine has a negative inotropic effect (see. Theophylline).
Toxic doses cause inhibition of cardiac glycosides "Na + - K + pump" intracellular potassium loss, which can lead to the arrhythmogenic effects of these drugs.
In medical practice currently employed individual cardiac glycosides (isolated from plants) and their semisynthetic derivatives, and neogalenic and galenical preparations (powders, infusions, tinctures, extracts). Because these drugs are powerful substances, they need to be standardized. For this purpose, physico-chemical and biological methods, providing the definition of activity in animal studies (frogs, cats, pigeons).
When using biological methods activity is assessed by comparison with the standard crystalline drug and expressed in units. One ICE (frog unit of action) corresponds to a dose of the standard drug, causing in certain experimental conditions, cardiac arrest in systole in most standard experimental frogs. Under one cat or pigeon unit of action (1 CUD 1 EDG) imply standard dose of the drug per 1 kg of body weight, causing in certain experimental conditions, heart failure cats and pigeons.
Необходимо учитывать, что величина терапевтической дозы для разных сердечных гликозидов зависит не только от их биологической активности, устанавливаемой указанными способами, но и от их всасывания из желудочнокишечного тракта, стойкости в организме и способности к кумулиции при повторном применении.

<<< Back in the subgroup Cardiac

Subgroup Cardiac drugs include: