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Potassium and magnesium aspartate

The drug is included in the list of vital and essential drugs (VED).

The drug produced by LLC "IST-PHARM" and LLC "Pharmasyntez-Tyumen" under the name "Potassium and Magnesium asparaginate" contains the following components: potassium and magnesium, respectively.

The human body contains almost all the chemical elements of the periodic table (injection solution “Glucose”). However, some trace elements are present in significantly higher quantities and their role is well studied. With potassium deficiency, hypokalemia develops (laboratory determination of the microelement Potassium is mandatory in ICU conditions according to indications). Hypokalemia is accompanied by the following, often life-threatening, symptoms: heart rhythm disturbances; frequent cramps, pain; irritability; tremor of hands, feet; coordination problems; muscle weakness, constant drowsiness; fast fatiguability. The role of potassium ions is to maintain osmotic pressure and cell volume, acid-base balance, and regulate enzyme activity. The concentration of potassium inside cells exceeds its extracellular level by 20-40 times. Potassium ions affect cardiac conductivity (the ability of the heart to transmit a signal about the need to contract the heart muscle) and regulate heart function, increase the tone and strength of smooth and striated muscles, and take part in the activity of the nervous system.

Magnesium, along with calcium, sodium and potassium, is one of the first four minerals in the body, and in terms of content inside the cell it ranks second after potassium. Magnesium is especially actively involved in processes that are associated with energy utilization, in particular, with the breakdown of glucose and the removal of waste waste and toxins from the body (see “Glucose 5%” infusion solution for more details). It has been confirmed that the vitamins thiamine (B1), pyridoxine (B6) and vitamin C (necessary for the full functioning of the body, for example, a lack of Vitamin C leads to scurvy) are fully absorbed in the presence of such a microelement as Magnesium. It is thanks to Magnesium that during the process of cell growth, their structure becomes more stable, regeneration (the ability of living organisms to restore damaged tissue over time) and cell renewal of tissues and organs is more effective. Magnesium stabilizes the bone structure and gives bones strength.

The drug "Potassium and Magnesium aspartate" is used as prescribed by a doctor based on the results of studies of trace elements in blood serum and the specific clinical situation.

E.L.Bulanova, A.Yu.Bulanov, M.Yu.Krasnoselsky First Moscow State Medical University named after. I.M. Sechenov Federal State Budgetary Institution Hematological Research Center of the Ministry of Health and Social Development of the Russian Federation.

Currently, a wide range of infusion solutions is presented in clinical practice, which implies the possibility of their selection depending on the tasks and characteristics of the patient. A popular representative of the group of crystalloids is a solution of potassium and magnesium aspartate (KMA). Infusion of CMA solution is a highly effective, efficient and safe method of replenishing intracellular ion deficiency. It is known that many infusion solutions, in addition to the main function assigned to them - maintaining the volume of circulating blood, correcting water and electrolyte disorders - have additional properties that are in demand in the clinic. Being an infusion electrolyte solution, CMA is also an effective antiarrhythmic agent. Key words: infusion therapy, Potassium and magnesium aspartate, antiarrhythmic therapy.

Potassium-magnesium asparaginate – infusion solution with antiarrhythmic properties ELBulanova, A.Yu.Bulanov, M.Yu.Krasnoselsky IMSechenov FMSMU Hematology Science Center, Moscow

There are many infusion solutions available to date, so it provides the possibility of choice, according to treatment targets and patient characteristics. Potassium-magnesium asparaginate (PMA) solution belongs to wildly used crystalloids. PMA infusion is considered to be highly effective and safe method of intracellular ion deficiency replenishment. It is known that many infusion solutions in addition to basic functions – blood volume maintaining, fluid and electrolyte disturbances correction – have some extra useful properties. As electrolyte solution, PMA is also an effective antiarrhythmic agent. Key words: infusion therapy, potassium-magnesium asparaginate, antiarrhythmic therapy.

Information about the author: Bulanova Ekaterina Lvovna – Associate Professor of the Department of Anesthesiology - Reanimatology 1st State Medical University named after. Sechenova, candidate of medical sciences. Bulanov Andrey Yulievich – Candidate of Medical Sciences, senior researcher at the Clinical Department of Anesthesiology and Reanimation of the Federal State Budgetary Institution Hematological Research Center of the Ministry of Health and Social Development of the Russian Federation.

The problem of choosing infusion solutions in clinical practice is one of the pressing issues in intensive care, especially in modern conditions of a wide range of drugs presented on the pharmaceutical market. The choice of crystalloid solutions is determined by the biochemical composition of the blood plasma, the degree of hydration of the body, and the presence of concomitant pathology. One of the representatives of the group of crystalloids, which stands out somewhat from the mass of others, is a solution of potassium and magnesium aspartate. Analysis of the features of its therapeutic properties was the purpose of this work. The main reactions of the body's vital activity: generation of excitation, regulation of cellular metabolism, water-salt metabolism, response to stress are determined by the basic electrolyte composition, in particular, the level of potassium, and are impossible without the presence of a difference in the concentrations of cations on the cell membrane. The process of ensuring the difference in concentrations - polarization of the plasma membrane - occurs actively using the energy of ATP with the assistance of the enzyme of the outer membrane of cells of all animal tissues - Na / K-ATPase. The enzyme has a specific ion recognition mechanism and selectively removes Na+ from the cell and accumulates K+ in it. This enzyme was first described in 1957 by Jens Christian Skou, a Danish scientist who received the Nobel Prize in Chemistry in 1997 for his discovery. The asymmetric arrangement of monovalent cations is a property inherent only to living organisms, necessary for the formation of membrane potential, the electrical stability of the cell, the ability of the cell to be excited under the influence of an impulse, the transport of metabolites through the membrane, and the regulation of intracellular metabolic reactions. Potassium, magnesium and 11 other basic structural elements of the body were first isolated by the English chemist Humphry Davy in 1808. Potassium was obtained from caustic potassium, and caustic potash was obtained from potash isolated from plant ash, hence the English name “potassium”. But the word “potassium” is of Arabic origin, “al-kali” is plant ash. The name “potassium” was introduced into Russian chemical nomenclature in 1831 by G.I. Hess. The history of the discovery of magnesium went beyond the time of alchemical searches and began in 1695: by evaporating the mineral water of the Epsom spring (England), N. Gros obtained salt, which has a bitter taste and a laxative effect. A few years later it turned out that when this salt reacted with “permanent alkali” (as soda and potash were called in those days), a white powder was formed. The same powder was obtained by calcining a mineral discovered in the vicinity of the Greek city of Magnesia. This similarity earned Epsom salt the name white magnesia. In 1808, Humphry Davy, by electrolysis of moistened white magnesia with mercury oxide, obtained an amalgam of a new metal, which was soon isolated from it and named magnesium. But purified magnesium was first obtained by A. Bussy in 1829 [1]. The adult human body contains about 160–250 g of potassium, which is present mainly inside the cell. The daily requirement for an adult is 2–5 g, for a child – 16–30 mg per 1 kg of body weight. Potassium is found in all plants, mainly bananas, potatoes, dried fruits, apricots, spinach, broccoli, and legumes. An interesting fact is that natural potassium consists of two stable isotopes, 39K and 41K, and one radioactive isotope, 40K, with a half-life of about 1.3 billion years. This isotope is found in living organisms and, through its radiation, makes a significant contribution to the overall radiation background of the planet. In the cell, K+ ions bind to proteins, creatinine, and phosphate. Various processes and conditions change the quantitative ratio of potassium inside and outside the cell. Thus, the influence of stress, phosphorylation of adenylic acid, glycolysis, catecholamines contribute to the release of K+ from the cell, provoking hyperkalemia; during dephosphorylation, glycogenolysis, the action of aldosterone and insulin, K+ rushes into the cell, leading to hypokalemia. Hyperkalemia accompanies shock, hypoxia, acidosis, the predominance of protein catabolism over anabolism, and dehydration. A high extracellular concentration of K+ accelerates its elimination and vice versa. Potassium is eliminated mainly in the urine in the distal parts of the renal tubules under the influence of aldosterone; to a lesser extent through the gastrointestinal tract and through sweating. Intracellular K+ deficiency is possible even with normal levels of kalemia, especially against the background of acidosis. The potassium balance is determined by the following mechanisms: • acidosis leads to the exchange of intracellular K+ for hydrogen cations, contributing to the occurrence of hyperkalemia, alkalosis favors hypokalemia; • insulin favors the transition of K+ into the cell; • mineralocorticoids reduce the reabsorption of potassium ions and accelerate its transition into the intracellular space; • in the distal tubules in the same cells two differently directed processes function simultaneously: reabsorption and secretion of potassium, which ensures the extraction of potassium from the urine in case of hypokalemia, and in case of excess, the excretion of potassium; • with hyperkalemia, as well as in response to angiotensin II and ACTH, the zona glomerulosa of the adrenal cortex increases the secretion of aldosterone, stimulates its secretion in the nephrons. The most common reasons for a decrease in potassium in the blood are the following: • insufficient potassium intake due to impaired consciousness of the patient, the use of special diets, long-term parenteral administration of unbalanced fluid containing a low concentration of potassium; • treatment with ion exchange resins; • decreased absorption due to diseases of the gastrointestinal tract or after operations; • increased urinary losses due to primary or secondary hyperaldosteronism: malignant hypertension, heart failure, liver cirrhosis with ascites, nephrotic syndrome, juxtaglomerular hyperplasia, Itsenko-Cushing syndrome, polyuria, de Toni-Debreu-Fanconi syndrome, tubular acidosis, acute renal failure in the stage of polyuria, treatment with diuretics, corticosteroids; • increased losses with diarrhea, vomiting, through an intestinal fistula; • movement of K+ from the extracellular to the intracellular environment during uncontrolled treatment with insulin, alkalosis. Magnesium ranks fourth after sodium, potassium, and calcium among other cations in the body; it is found mainly inside the cell, occupying second place there after potassium [2]. The average adult human body contains 20–28 g (850–1100 mmol) of magnesium, the daily requirement is about 0.25–0.5 g. Bone tissue contains 60% of the total amount of magnesium, if necessary 20–30% of this amount can be quickly mobilized, the remaining magnesium is distributed between the cells of the heart, brain, kidneys and other organs [1]. Magnesium is involved in many biochemical processes: oxidative phosphorylation reactions, protein synthesis, steroid hormones, urea, glucose, citric acid cycles, nucleic acid and lipid metabolism, formation of energy-rich phosphates; provides the ability to metabolize about 300 enzymes: creatine kinase, adenylate cyclase, phosphofructokinase, MAO kinase, Na/K-ATPase, Ca-ATPase [3, 4]. Magnesium helps normalize the intracellular content of potassium and calcium and thereby affects vascular tone, prevents cell necrosis and electrical instability, and reduces spasm of smooth muscles. Another effect of magnesium on vascular tone is indirect: as a result of the release of nitric oxide by the endothelium, endothelium-dependent vascular relaxation under the influence of acetylcholine improves. Magnesium homeostasis is regulated by a number of mechanisms: thyrocalcitonin and vasopressin stimulate magnesium excretion, which increases with overhydration and hypercalcemia. Parathyroid hormone suppresses magnesiumuria. The kidneys are predominantly involved in the elimination of magnesium: the loop of Henle regulates the reabsorption of magnesium; to a lesser extent, gastrointestinal tract, sweating. Absorption of magnesium occurs throughout the intestine up to the sigmoid colon, however, the main zone of its absorption is the duodenum. Therefore, the most important reasons for the development of magnesium deficiency include the following: • increased losses through the gastrointestinal tract due to vomiting and diarrhea; through the kidneys with nephrotic syndrome, renal acidosis, during therapy with loop diuretics, verapamil, treatment with cyclosporine, cisplatin, etc.; • endocrine disorders: hyperthyroidism, hyperparathyroidism, hyperaldosteronism; • increased need for magnesium during pregnancy, breastfeeding, stress, increased sweating; during the period of convalescence, growth; • reduced intake: dietary habits, alcoholism, parenteral or natural nutrition low in magnesium. The fast food diet, consumption of alcohol and drinks containing caffeine increase the excretion of magnesium through the kidneys; the use of refined products interferes with the absorption of magnesium. By analogy with iodine-deficient areas, magnesium-deficient areas have already appeared in our country: endemic hypomagnesemia was discovered in the Kursk region [5]. • reduced intestinal resorption: enteropathy, condition after extensive intestinal resections, malabsorption syndrome, diarrhea. Normal levels of magnesemia do not always exclude magnesium deficiency in body tissues: for example, with deficiency, magnesium can be released from the bones, preventing a decrease in its serum concentration. In this regard, it makes sense to determine magnesium in formed elements, erythrocytes, mononuclear cells, recalculated per unit mass of the material under study, or loss of magnesium in the urine [3]. When we talk about “magnesium deficiency,” we mean a decrease in the total magnesium content in the body; “hypomagnesemia” defines a decrease in the concentration of magnesium in the serum (normally 0.8–1.2 µmol/l). Given the importance of magnesium metabolism, the International Classification of Diseases ICD-10 provides a separate diagnosis code - “Magnesium deficiency” - E61.2. Magnesium ions are a physiological antagonist of calcium, and magnesium competes with calcium on the same channel of the cell membrane of the contractile apparatus, helping to normalize the intracellular calcium content and thereby reducing vascular tone [1]. Magnesium has a specific mild antiarrhythmic quality. The mechanism of this action is the stabilization of the membrane and the presence of antagonistic properties towards Ca2+, which corresponds to antiarrhythmic drugs of classes I and IV. Since the metabolism of potassium and magnesium is closely interconnected, the clinical manifestations of disturbances in the homeostasis of these cations in the body are similar to each other and manifest themselves and complement each other at the level of almost all organs and systems. At the cellular level, these disorders are based on: deficiency of functional activity of enzymes, disruption of energy-intensive membrane transport, development of generalized inflammation, quantitative changes in other electrolytes. It has long been well known that magnesium is an important cofactor in ensuring optimal levels of intracellular potassium [6], simultaneous deficiency of potassium and magnesium can lead to hypokalemia, resistant to treatment in the absence of correction of magnesium deficiency. Clinical manifestations of magnesium deficiency are as follows: • psycho-neurological: fear, anxiety, depression, decreased concentration, increased irritability, hyperreflexia, mnestic disorders, dizziness, sleep disturbance, chronic fatigue syndrome; • cardiovascular: vasospasm, electrical instability of the myocardium - various disturbances of heart rhythm and conduction: extrasystole, ventricular and supraventricular tachycardia, torsades de pointes, atrial fibrillation, long QT syndrome on the electrocardiogram; • visceral: bronchospasm, laryngospasm, stool disorders, abdominal pain, nausea, vomiting, pylorospasm; • muscular: paresthesia, skeletal muscle cramps, increased uterine tone, spontaneous miscarriages, premature birth. Hypokalemia is manifested by the following symptom complexes: • psycho-neurological: increased fatigue, depression, indifference to the environment; • cardiovascular: increased sensitivity of the myocardium to digitalis drugs, cardiac rhythm disturbances: extrasystole, ventricular and supraventricular tachycardia, atrial and ventricular fibrillation, characteristic ECG pattern: depression of the ST segment, flattening and widening of the T wave, appearance of the U wave; • visceral: nausea, vomiting, intestinal atony, constipation, bladder atony; • muscular: paresthesia, weakness, muscle spasm of the lower extremities, hyporeflexia and adynamia. Considering the high role of disturbances in the metabolism of potassium and magnesium in the development of various pathologies, the importance of maintaining normal levels of these electrolytes, and, if necessary, prompt correction of both cations, becomes obvious. The combination of potassium and magnesium ions in one preparation is of great importance and is justified by the following reasons: • potassium deficiency often accompanies magnesium deficiency; • with simultaneous correction an additive effect may be observed; • the ability to avoid excessive administration of fluid as a solvent in patients at risk of developing hypervolemia. The pharmaceutical market offers a number of drugs to compensate for the deficiency of these ions. As already mentioned, potassium and magnesium are mainly intracellular ions. In this regard, it is advisable to compensate for their deficiency with solutions containing components that facilitate the penetration of these ions into the intracellular space. Thus, the advantage of infusion of a mixture containing glucose, insulin, potassium, and magnesium becomes obvious. In Russia they use the so-called “polarizing mixture” or “polarizing cocktail”, or more precisely, “repolarizing”. The recipe was described and proposed by Henri Laborit [4] (1914–1995), a French physiologist, writer and philosopher. There are no official recommendations on its composition. Typically, this is an infusion of 5% glucose solution; 1.2 g KCl; 2.5 g MgSO4; insulin calculated for glucose volume. This composition facilitates the myocardium’s transition from the uneconomical oxidation of free fatty acids to glucose, which is more energetically favorable under hypoxic conditions, especially in the presence of an ischemically damaged cardiomyocyte. A number of domestic and foreign authors propose the introduction of the proposed mixture to prevent, in particular, catecholamine-induced non-coronarogenic myocardial micronecrosis. When acute coronary syndrome occurs, as well as any other stress, potassium and magnesium deficiency may develop due to the specific effect of hypercatecholaminemia, hypercortisolism, and hyperaldosteronism. In addition, in a number of patients in critical condition, subclinical hypothyroidism is detected as an adaptation reaction to stress. The antithyroid properties of magnesium salts have been described, the use of which in a critical situation will allow the body to optimally adapt to damage [7]. Another component that facilitates the penetration of the discussed ions into the cell is aspartate. Aspartic acid is present in the body as part of proteins and in free form, plays a huge role in the metabolism of proteins and carbohydrates, and is involved in the formation of pyrimidine bases and urea. By eliminating ammonia, it protects the central nervous system and normalizes the processes of excitation and inhibition. Stimulates the immune system: accelerates the synthesis of immunoglobulins, antibodies, participates in the synthesis of the main carriers of genetic information - DNA, RNA. Promotes the conversion of carbohydrates into glucose and the subsequent storage of glycogen [2]. L- and D-enantiomers of aspartic acid are known. D-enantiomers of amino acids are inactive for most of the body's enzyme systems and are practically not absorbed. It is L-aspartate, due to its slight dissociation, that binds metal ions and transports them into the cell in the form of complex compounds through its own transport system. By increasing the permeability of cell membranes to potassium and magnesium, it has a positive effect on the activity of synthetic processes in cells. L-aspartate takes an active part in amino acid metabolism, being the starting material for the synthesis of non-essential amino acids, which should be taken into account when choosing nutritional support; improves myocardial metabolism, increasing the tolerance of cardiac glycosides. A mixture of potassium and magnesium salts of aspartic acid activates anabolic processes in muscle tissue. The optimal combined infusion drug containing these components is KMA (potassium-magnesium asparaginate) (Berlin-Chemie AG/Menarini Group, Germany). The ratio of potassium and magnesium in the KMA preparation is 2:1. Thus, indications for infusion of CMA solution are all of the above states of electrolyte deficiency. Most often, the drug is used in cardiological practice: as an addition to amiodarone therapy in order to preserve the sinus rhythm in patients with various types of arrhythmias [8], with an adverse prognosis of the course of acute myocardial infarction: if it is impossible to perform angioplasty, contraindications for thrombolytic therapy [9–11 [9–11 ], in operations with artificial blood circulation [12]. KMA strictly speaking does not apply to antiarrhythmics according to the most common classification of Vogen -VILAMS, dividing antiarrhythmics into 4 classes: I - membrane -stabilizing agents; II-beta-blockers; III - drugs that slow down repolarization; IV - blockers of "slow" calcium channels. A number of authors preparations that have a mechanism of action, different from drugs of the I - IV classes, include V classes. These drugs have the most diverse effect on the myocardium, are used mainly for arrhythmias caused by hypokalemia, as well as for overdose of cardiac glycosides. The leading role in the mechanism of action of all antiarrhythmics is played by their influence on cell membranes, the transport of ions (Na+, K+, Ca2+), and the interconnected changes in depolarization, an increase in the magnitude of the membrane potential of cardiomyocytes, a decrease in the excitability and automatism of myocardium. Classes of antiarrhythmic agents and individual drugs differ in effect on these processes. There are functional and organic arrhythmias. Functional arrhythmias can be physiological in excessive physical exertion, psycho -emotional excitement, fever, etc., the adrenaline and norepinephrine, which are distinguished under these conditions, increase the current of sodium ion and calcium into conductive cardiomyocytes. This leads to a decrease in the membrane potential of cells, an increase in their excitability and the occurrence of ectopic foci of automatism. Arrhythmias associated with organic heart lesions more often occur according to the RENTRY mechanism. It follows that the drugs containing K, MG can contribute to the antiarrhythmic effect of true antiarrhythmics, or restore the rhythm with functional arrhythmias. The drug KMA according to the mechanism of antiarrhythmic action can be attributed to the IB or IV class. Preparations related to the IB class (activators of potassium channels) - KMA - slightly block sodium channels and activate potassium. The zero phase of the action potential leans slightly, the third phase - the repolarization phase - is shortened. Thus, the potential of action and the effective refractory period are shortened (Fig. 1). However, the degree of shortening of repolarization is greater than the degree of decrease in refractoryness: in fact, the refractory period increases relatively. Activation of potassium channels lengthens slow diastolic depolarization (except for nodes), which leads to a weakening of ectopic automatism, the negative battropic effect on the myocardium of ventricles and atrial, as well as on the conductive system below the atrioventricular node. As a drug that has antagonistic properties in relation to calcium ion, KMA can be attributed to grade IV. Normally, in the conducting system of the heart of calcium, it takes part in the generation of the potential of the action of syno) and atrioventricular nodes. He is responsible for slow diastolic depolarization and phase of quick depolarization. The heart rate and the speed of atrioventricular conduction depend on the degree of activity of calcium channels in the nodes. Calcium activates the assets-miosin complex, leading to a reduction in cardiomyocytes. The action of the KMA is based on the blockade of slow calcium channels in the sinus node, which conducts the atrial and ventricular system. Magnesium ions activate the Na+/K+enzyme- ATF-Azu and potassium channels. Magnesium sulfate is used to stop the attack of ventricular tachycardia type “Piruet”: QRS complexes are continuously changing in shape, direction, amplitude and duration - “dance” around the isolin. This option of arrhythmia can be idiopathic or occurs against the background of extension of the QT interval due to electrolyte disorders, taking the drugs lengthening the QT interval: antiarrhythmics of the class IA and IC, phenotiazins, tricyclic antidepressants. Contraindication to the use of potassium-magnesium mixtures is the presence of acute and chronic renal failure; hyperkalemia; hypermagnesemia; insufficiency of the adrenal cortex; shock; AV blockade; myasthenia gravis; dehydration; increased sensitivity to Xility. We bring to your attention a clinical example. Patient T., 60 years old, complaints about interruptions in the heart. From the anamnesis it is known that for 5 years is observed by a cardiologist about coronary heart disease, stable angina of functional class II, hypertension of the II degree, at the ECG, paroxysm of atrial fibrillation (Fig. 2) has been recorded. Against the background of infusion of the solution of KMA, a sinus rhythm was restored (Fig. 3). Subsequently, during the examination, there was no expansion of heart chambers, against the background of selected therapy with B-blockers, the sinus rhythm remains. This example illustrates the possibility of restoring the sinus rhythm against the background of infusion of KMA with the subsequent selection of antiarrhythmic therapy. A variety of forms of rhythm disorders that occur against the background of the absence of electrolyte blood disorders should be started with the administration or against the background of the administration of the drug KMA (if there are no contraindications) - a balanced electrolyte solution. Conducting an infusion of a solution of KMA is a highly -effective, effective and with a high security profile by replenishing intracellular ion deficiency. Thus, it is known that many infusion solutions, in addition to the main functions assigned to them (maintaining the volume of circulating blood, correction of water-electrolyte disorders) have additional properties that, for example, the effect on hemostasis, modeling of a systemic inflammatory response, noted for a series hydroxyethylated starch. Being an infusion electrolyte solution, KMA is also an effective antiarrhythmic agent.

Literature 1. Semigolovsky N.Yu. Magnesium deficiency as a general medical problem. Difficult patient. 2008; 7:6:8–11. 2. Kostyuchenko L.N. Disturbances of potassium-magnesium homeostasis and its correction during nutritional support for gastroenterological patients. Difficult patient. 2007; 6–7: 3–7. 3. Sviridov S.V. Balanced and special electrolyte solutions. Difficult patient. 2007; 8:5:32–35. 4. Postnikova S.L., Kasatova T.B., Vereshchagina G.S., Malysheva N.V. Magnesium and cardiovascular diseases. Russian medical journal. Cardiology. 2007; 15:20:1-4. 5. Tereshchenko I.V. Magnesium deficiency in the practice of an endocrinologist. Clinical medicine. 2008; 7:47–51. 6. Whang R., Whang DD, Ryan MP Refractory potassium repletion. A consequence of magnesium deficiency. Arch. Intern. Med. 1992; 152(1):40–45. 7. Semigolovsky N.Yu. Polarizing mixture and Potassium-magnesium aspartate in the treatment of cardiac patients. Difficult patient. 2006; 8:4:33–35. 8. Semigolovsky N.Yu. On the treatment of patients with atrial fibrillation (reflections on international Recommendations). Difficult patient. 2006; 4:4:3–6. 9. Merai I.A., Pavlikova E.P., Alexandria L.G., Teraz Y.M. Potassium and magnesium aspartate in restoring and maintaining sinus rhythm in patients with a stable form of atrial fibirillation. CONSILIUM MEDICUM. Arterial hypertension. 9:11:37–39. 10. Antman EM Magnesium in Acute MI. Circulation. 1995; 92:2367–2372. 11. Zipes DP, CammA..J, Borggrefe M., Buxton AE, Chaitman B., Fromer M., Gregoratos G., Klein G., Moss A..J, Myerburg RJ, Priori SG, Quinones MA, Roden DM , Silka MJ, Tracy C. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol. 2006; 48: 247–346. 12. Trekova N.A., Andrianova M.Yu., Tolstova I.A., Akselrod B.A., Zaitseva S.V., Morozov Yu.A. The use of a solution of potassium and magnesium aspartate to maintain the balance of potassium and magnesium during cardiac surgery under conditions of artificial circulation. Anesthesiology and resuscitation. 2008; 5:17–21. 13. Bulanov A.Yu., Gorodetsky V.M., Serebriysky I.I. Volume-substituting solutions in intensive care protocols: principles of drug selection. Bulletin of Intensive Care. 2005; 5: 104–106.

Cardiovascular diseases

1.1. Arrhythmias.

Aspartic acid is a carrier of K+ and Mg2+ ions. It easily penetrates into cells, increases the concentration of K+, Mg2+ ions and performs a stabilizing function. Magnesium is an activator of sodium-potassium adenosine triphosphatase (Na/K-ATPase), so increasing magnesium is the most effective means of increasing potassium levels. In addition, magnesium is a calcium antagonist and helps reverse afterdepolarization caused by increased calcium influx. In recent years, a large number of clinical studies have been conducted confirming that potassium and magnesium aspartate plays an important role in the treatment of heart rhythm disorders. For example, in a study by Xie Ronglu[1], 170 patients with arrhythmia due to various causes were randomly divided into two groups; In the study group, potassium and magnesium aspartate and an energy mixture were added to standard therapy. The results showed a marked increase in serum potassium and magnesium levels in patients in the study group. Holter monitoring confirmed that the incidence of arrhythmia compared to the control group decreased significantly.

Xie Yumei et al.[2] achieved improved performance when introducing potassium and magnesium aspartate into the treatment regimen for persistent arrhythmia in children. As a result, for ventricular extrasystole, pronounced effectiveness was established in 14 cases, effectiveness in 5 cases, the overall effectiveness rate was 86.4%; for atrial extrasystole, pronounced effectiveness - in 6 cases, efficiency - in 3 cases, the overall effectiveness rate is 90%. Pronounced effectiveness has also been established in the treatment of atrial and ventricular paroxysmal tachycardia.

Thus, research proves that potassium and magnesium aspartate is highly effective in the treatment of cardiac arrhythmias of various origins, both when administered intravenously and when taken orally. In addition, it increases the effectiveness of other antiarrhythmic drugs.

1.2. Myocardial infarction.

In acute myocardial infarction (AMI), magnesium forms insoluble chelate complexes with fatty acids; in addition, increased levels of catecholamines can lead to increased excretion of magnesium, which contributes to the development of hypomagnesemia. Hypomagnesemia and hypokalemia are associated with the development of arrhythmias and increased mortality in AMI. For this reason, the use of potassium and magnesium aspartate may be beneficial in AMI. For example, Liu Tong [3] treated 48 cases of AMI with intravenous infusion of potassium and magnesium aspartate at a dose of 50 ml in 500 ml of 5% glucose solution for 7-14 days. The control group received standard treatment. According to the study results, the incidence of early ventricular tachycardia and angina in the group taking potassium and magnesium aspartate was significantly reduced, and there was a greater improvement in cardiac function than in the control group. However, mortality in both groups was not statistically different. In the study by Sun Shuang et al.[4] potassium and magnesium aspartate were used in the treatment of 30 cases of AMI; the control group received the energy mixture. According to the study results, the incidence of ventricular arrhythmia in the study group was significantly lower, and there was greater improvement in cardiac function than in the control group. There was 1 death in the study group, and 7 in the control group. The differences between the two groups reached statistical significance (P<0.05).

1.3. Heart failure.

Most drugs for the treatment of congestive heart failure (CHF) cause electrolyte imbalances, thereby interfering with the therapeutic effect, increasing the adverse reactions of digitalis glycosides and antiarrhythmic drugs, worsening heart failure and increasing the incidence of sudden death. Aspartic acid is the best carrier of K+ and Mg2+ ions, since it has a high affinity for cells and is also capable of reducing oxygen consumption by the myocardium. Therefore, potassium and magnesium aspartate is the best drug for maintenance therapy of heart failure. For example, in the study by Chen Dan et al.[5] 128 patients with CHF were divided into two groups: in the study group, in addition to standard treatment, patients received potassium and magnesium aspartate intravenously for 15 days, and then for another 15 days orally in tablet form, and patients in the control group received only standard treatment . The results of the study showed that in the study group the frequency of arrhythmias and malignant arrhythmias decreased compared to the control group. During clinical examination for 1 year, 10 deaths were recorded in the therapeutic group, and 25 cases in the control group, and the differences reached statistical significance (P<0.05). In a study conducted by Zhou Chu et al.[6], 38 patients in the study group took potassium and magnesium aspartate orally, 2 tablets 3 times a day, daily for 10 days, in addition to standard treatment, and 38 patients in the control group received only standard treatment . After 1 course of treatment, the effectiveness rate in the therapeutic group was 84.21%, in the control group - 63.16%. In the study by Yan Yuquan et al.[7] 80 patients in the study group with refractory heart failure received cyclic adenosine monophosphate (cAMP), potassium and magnesium aspartate, nitroglycerin and dobutamine, while 78 patients in the control group received only nitroglycerin and dobutamine. According to the study results, the overall effectiveness rate in the study group was 88.75%, and in the control group - 73.1%. Hemodynamic parameters in the study group improved to a greater extent than in the control group.

1.4. Arterial hypertension.

Epidemiological and laboratory studies have shown a negative correlation between body magnesium levels and the risk of developing hypertension. Potassium and magnesium aspartate is metabolized to form urea and potassium and magnesium ions, increasing osmotic pressure and inhibiting water reabsorption, thereby increasing diuresis and lowering blood pressure. For example, Hu Yiwen[8] conducted a randomized controlled trial of the therapeutic effect of potassium and magnesium aspartate and nifedipine in the treatment of essential arterial hypertension. In the study group, patients took potassium and magnesium aspartate orally, 2 tablets 3 times a day daily, in the control group - nifedipine at a dose of 10 mg 3 times a day, daily. The course of treatment was 2 months. The results showed that the overall effectiveness and expressed effectiveness in the study group reached 90% and 65%, respectively, significantly exceeding those in the control group (70% and 50%, respectively). Particularly high effectiveness was noted in the treatment of mild arterial hypertension. At the same time, it was found that the level of total cholesterol and triglycerides in patients in the study group decreased significantly. The differences between the two groups reached statistical significance (P<0.01). In the study by Wei Zongde et al.[9] 60 patients with mild arterial hypertension were randomly divided into two groups. In the study group, patients were prescribed 6 tablets of potassium and magnesium aspartate orally daily, as well as a behavioral intervention; The control group received only behavioral intervention. The course of treatment was 3 months. According to the results of the study, indicators such as the degree of reduction in blood pressure, the effectiveness of treatment and the concentration of potassium and magnesium in the blood serum after treatment were significantly higher than in the control group.

Application of KMA (Berlin Chemie) in cardiac intensive care

On the other hand, in the recommendations section “Metabolic therapy and control of blood glucose levels” we read: “the introduction of “polarizing mixtures” containing high concentrations of glucose, potassium and large doses of insulin did not justify itself, as did the use of antioxidants... “So is it necessary, can or cannot mixtures containing potassium and magnesium be used in the treatment of patients with acute myocardial infarction? Is their use justified? The answer to these questions may be the results of the long-awaited recent randomized placebo-controlled trial (RCT) IMMEDIATE [2]. The objective of this original RCT was to test the hypothesis that prehospital administration of glucose-potassium-insulin (GKIS) to patients diagnosed with acute coronary syndrome can reduce the incidence of myocardial infarction in the first 24 hours (endpoint 1) and the incidence of cardiac arrest. development of heart failure (HF), mortality and size of MI after 30 days. Paramedics from Boston (USA) randomized 911 patients using ECG data. The RCT did not include patients with severe heart failure and renal failure, as well as the inability to sign informed consent. Diagnosis of MI was based on ECG dynamics and determination of biomarkers. The GKIS contained 30% glucose, 50 U/L insulin and 80 mEq of potassium chloride, and a 5% glucose solution served as a placebo. According to the results of RCTs, the proportions of patients with the development of MI in the groups did not differ significantly, as did the 30-day mortality rate, which was 4.4% (GKIS) and 6.1% (placebo) (p = 0.27), but the summary point of the frequency Cardiac arrest + hospital mortality was significantly lower in the GKIS group (4.4% vs. 8.7%, p=0.01). In small subgroups (49 patients with GKIS and 61 placebo), myocardial scintigraphy with technetium 99m revealed a significant reduction in the size of myocardial infarction when using GKIS (2% versus 10%, p = 0.01). As expected, free fatty acid levels were lower in the GCI group than in the placebo group (p=0.001). Thus, 50 years after the first publication of the Mexicans, D. Sodi-Pallares et al. (1962) about the effectiveness of GKIS [3] in the West, the feasibility of early administration of the mixture to acute coronary patients was proven! Meanwhile, many evidence-based RCTs and meta-analyses on GKIS were conducted back in the so-called pre-thrombolytic era. The largest among them, a meta-analysis in 1997 [4], summing up data on 1932 patients, showed that GCIS can reduce mortality in MI by 28–48%, depending on the dose and time of administration. The largest RCT of the thrombolytic era, the Latin American ECLA, assessed the effectiveness of GCIs of various concentrations in 407 patients admitted to the hospital within 24 hours of the onset of MI [5]. The introduction of GCIS was accompanied by a 66% reduction in the risk of hospital mortality in 252 patients receiving reperfusion therapy (95% thrombolysis, 5% angioplasty). Moreover, treatment of GKIS, which was not started immediately in this RCT, but 10–11 hours after the onset of the disease, was accompanied by a gain even in 1-year survival of patients, and this pattern was dose-dependent (those receiving low-concentrated solutions had intermediate mortality rates). The latter, however, does not agree with the data of a Dutch study from 2007 (GKIS - 20% glucose with 80 mmol/l KCl - in 444 patients with STEMI without HF compared with traditional treatment in 445 patients during a subsequent one-year follow-up) [6], not revealed the effect of therapy on either the short-term or long-term prognosis. It is also interesting that a group of 155 patients in ECLA treated without reperfusion also did not benefit from the introduction of GCI (their in-hospital mortality rate was 8.4%). The obvious contradiction with the above meta-analysis [4], performed on almost 10 times more patients, is explained by commentators precisely by the small number of the analyzed group and the presence of the possibility of spontaneous thrombolysis [7]. By the way, the author of this commentary, K. Epstein, head of the Boston Laboratory for Myocardial Research (Boston again!), was a great enthusiast of the GKIS. Citing the results of the DIGAMI RCT (1996) [8] on the administration of a glucose-insulin mixture to diabetics with MI, which reduced the relative risk of death by 29–58%, he concludes that the thrombolytic era has finally proven the effectiveness of GCIs in acute coronary syndromes, as well as in RCTs in cardiogenic shock [9] and coronary artery bypass surgery [10, 11]. At the same time, a Polish study of the effectiveness of GKIS in 1997 myocardial infarction [12], which was soon conducted, also had the opposite results and was even terminated early due to an increase in the overall mortality of patients compared to the control group. Thus, clinical data on the use of GCIs in AMI are still quite contradictory. This may be due to the need for individual selection of the concentration of GKIS ingredients. It is also necessary to more clearly define safe infusion volumes that can significantly influence myocardial preload. The beneficial effect of glucose is not always obvious, especially in patients with diabetes, of which, as is known, there are many among coronary patients, and insulin, which in case of overdose does not improve the condition of the ischemic myocardium. Even in the first monograph in the USSR “Acute Myocardial Infarction” by D.M. Grotel (1940) [13], the author recommended intravenous administration of concentrated glucose in the acute period of MI (25 ml of 40–50% glucose daily) to restore the glycogen content in the myocardium, which decreases during “anoxia”. He immediately provided data on the need for careful administration of insulin to diabetics with a description of cases of natural deterioration in the condition of coronary patients “due to insulin hypoglycemia.” Among the mechanisms of the protective effect of GCI are an increase in the uptake and oxidation of glucose by the myocardium, a decrease in circulation and the uptake of toxic free fatty acids [14]. It was found that the disturbance of local myocardial contractility, which under the conditions of dopamine administration is interpreted as hibernating myocardium, disappears against the background of the administration of GCIS, which is why the use of GCIS is considered very promising in the treatment of patients with severe heart failure [15]. On the other hand, in addition to potassium deficiency during MI, magnesium deficiency also develops under the influence of hypercatecholaminemia, hypercortisolism and hyperaldosteronism - natural reactions of the body to any stress. It is known that magnesium helps to normalize the intracellular content of potassium and calcium and thereby reduces vascular tone, prevents cell necrosis and their electrical instability. It is no coincidence that many researchers recommend the use of magnesium as part of a polarizing mixture in patients with MI [16, 17]. A meta-analysis of RCTs in 1301 patients with MI once revealed a beneficial effect of magnesium on hospital mortality [18]. The English LIMIT-2 study confirmed the effectiveness of magnesium use in patients with MI who were not subject to thrombolysis [19]. It has been shown that intravenous administration of magnesium sulfate reduces mortality in MI by 24% and reduces the incidence of heart failure by 25%. Magnesium salts are also used as an antiarrhythmic agent, combining the qualities of class I and IV antiarrhythmics (membrane stabilizing and calcium antagonists, respectively). Magnesium has the ability to prevent cell potassium loss and reduce the dispersion of the QT interval duration on the ECG, which is considered as an unfavorable prognostic factor in terms of the development of fatal arrhythmias. The positive effect of magnesium administration during MI was also proven by M. Shechter et al. (1995), who used magnesium sulfate in patients for whom thrombolysis was contraindicated [20]. The hospital mortality of these patients was 4%, which is significantly lower than that in the control group (17%), which received glucose as a comparison drug. According to the same researchers [21], the use of oral magnesium and potassium supplements in patients with coronary artery disease led to a significant increase in endothelium-dependent dilation of the brachial artery by 15.5% compared to placebo, while a linear correlation was revealed between the intracellular concentration of magnesium and the degree of vasodilation. It has been established that, taking into account the antiatherogenic effects of magnesium preparations, correction of its deficiency can help slow the progression of coronary artery disease. The ARIC (The Atherosclerosis Risk in Communities) study, after 4–7 years of follow-up of a cohort of 13,922 people, showed an association between the development of coronary artery disease and hypomagnesemia [22]. The most pronounced magnesium deficiency, as established [23], occurs in patients with elevated levels of atherogenic lipids. It has also been shown that the use of magnesium supplements in patients with metabolic syndrome improves insulin-dependent glucose utilization [24]. The drug potassium and magnesium aspartate - KMA (Berlin Chemie/Menarini), which includes sufficient doses of potassium and magnesium, as well as xylitol and aspartic acid, does not have a number of disadvantages of GKIS. Aspartic acid, as is known, belongs to the active glucoplastic amino acids, easily penetrating the cell and participating in intermediate metabolism and also as a transporter of electrolytes. Its combination with potassium and magnesium was proposed by G. Selye in 1958 for the treatment and prevention of acute ischemic, hypoxic and necrotic processes in the myocardium [25]. At the same time, A. Labori’s works appeared on the high effectiveness of the potassium-magnesium salt of aspartic acid in hypoxia, ischemia, intoxication, as well as in conditions accompanied by the accumulation of ammonia and under-oxidized metabolic products in the body. These works show that aspartic acid, being included in the Krebs cycle, normalizes the disturbed ratios of tricarboxylic acids, actively participates in the synthesis of ATP, promotes the entry of potassium and magnesium into the cell and restores the adequate functioning of ion pumps under hypoxic conditions. Aspartic acid is an aliphatic amino acid present in the body as part of proteins, and in its free form plays an important role in the metabolism of nitrogenous substances, participates in the formation of pyrimidine bases, as well as urea. By reducing the ammonia content, aspartate protects the central nervous system, is able to normalize the processes of excitation and inhibition in it, and stimulates the immune system. Aspartic acid helps increase glycogen stores, which is important for nutritional support to ensure protein-energy homeostasis. Salts of aspartic acid increase endurance and the body’s resistance to various influences, i.e. have an adaptation effect [26]. The active use of potassium and magnesium aspartate in clinical practice began in the 1970s. The effectiveness of CMA has been shown in patients with MI, HF, and intoxication with cardiac glycosides [27–29]. The drug is successfully used in open heart surgery [30, 31]. The advantages of CMA for cardiac surgical patients operated on under artificial circulation include the absence of sodium and glucose in the solution. And xylitol, used as an energy substrate, can be used in patients with diabetes. The dose of CMA is selected individually, depending on the indications. The average recommended daily dose is 1-2 intravenous injections of 500 ml of infusion solution. The rate of administration is 15–45 drops/min. depending on individual tolerance. A week before cardiac surgery and for a week after cardiac surgery, 500 ml of the drug is administered once a day. The KMA drug is successfully packaged so that if you want to limit the infusion load of a cardiac surgery patient or a patient with MI, you can choose small bottles of 250 ml of solution. If the recommended rate of drip administration of the drug was observed, no adverse reactions were observed, which makes the use of CMA a reliable tool for metabolic effects on the myocardium, suggesting accelerated healing, antiarrhythmic effect, moderate hypotensive and reactive effects. With rapid intravenous administration or overdose, symptoms of hyperkalemia (muscle hypotonicity, paresthesia of the extremities, slowing of AV conduction, arrhythmias, cardiac arrest) and hypermagnesemia (facial hyperemia, thirst, marked decrease in blood pressure, impaired neuromuscular transmission, depression of the respiratory center) may develop. , arrhythmia, seizures). This effect is reversible by administering a 10% calcium gluconate solution and carrying out symptomatic therapy to correct the resulting cardiovascular disorders. If necessary, hemodialysis is performed, which we have never encountered in 12 years of working with CMA. Our experience with the use of CMA indicates a high degree of effectiveness and, when used correctly, a high safety profile of this product. Working according to modern standards of management of patients with AMI using thrombolytic therapy, early cardiac catheterization to determine indications for coronary angioplasty, stenting or coronary artery bypass grafting, using modern pharmacotherapy regimens with mandatory individualization of prescriptions, we have achieved a very modest hospital mortality rate for patients with MI, amounting to 2.9– 4.2% with an average age of deaths of 77–80 years. The contribution of KMA to this final result is undeniable, but it is quite difficult to isolate it. In our practice, we have positive experience in using the drug to eliminate potassium and magnesium deficiency as part of combination therapy for various manifestations of coronary heart disease, including acute myocardial infarction, for chronic circulatory failure, cardiac arrhythmias, for preparation for coronary angioplasty and coronary artery bypass surgery and for postoperative management of such patients; intoxication with cardiac glycosides; previous and current use of saluretics; profuse sweating (“country”, “bath” heart attacks); dyspeptic disorders. Literature 1. National clinical guidelines. Diagnosis and treatment of patients with acute myocardial infarction with ST segment elevation ECG. – M.: Silicea-Poligraf, 2008. P. 240–330. 2. Selker HP, Beshansky JR, Sheehan PR et al. Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial // JAMA. 2012. Vol. 9 (307). R. 1925–1933. 3. Sodi-Pallares D., Testelli M., Fishleder F. Effects of an intravenous infusion of a potassium-insulin-glucose solution on the electrocardiographic signs of myocardial infarction // Am. J. Cardiol. 1962. Vol. 9. R. 66–181. 4. Fath-Ordoubadi F., Beatt KJ Glucose-insulin-potassium therapy for the treatment of acute myocardial infarction. An overview of randomized placebo – controlled trials // Circulation. 1997. Vol. 96. P. 1152–1156. 5. Diaz R, Paolasso EC, Piegas LS et al. On behalf of the ECLA (Estudios Cardiologicos Latinoamerica) collaborative group. Metabolic modulation of acute myocardial infarction. The ECLA glucose-insulin-potassium pilot trial // Circulation. 1998. Vol. 98. P. 2227–2234. 6. Rasoul S., Ottervanger JP, Timmer JR et al. One year outcomes after glucose-insulin-potassium in ST elevation myocardial infarction. The Glucose-insulin-potassium study II // Int. J. Cardiol. 2007. Vol.31. 122(1). P. 52–55. 7. Apstein S.S. Remarkable Results From a New Prospective, Randomized Trial // Circulation. 1998. Vol. 98. R. 2223–2226. 8. Malmberg K., Ryden L., Hamsten A. et al. Effects of insulin treatment on cause-specific one-year mortality and morbidity in diabetic patients with acute myocardial infarction: DIGAMI study group: Diabetes Insulin-Glucose in Acute Myocardial Infarction // Eur. Heart J. 1996. Vol. 17. R. 1337–1344. 9. Coven DL, Suter TM, Eberli FR, Apstein CS Dobutamine and glucose-insulin-potassium (GIK) improve cardiac function and survival in a randomized trial of cardiogenic shock // Circulation. 1994. Vol. 90 (Suppl. I). R.I–480. 10. Coleman GM, Gradinac S, Taegtmeyer H et al. Efficacy of metabolic support with glucose-insulin-potassium for left ventricular pump failure after aortocoronary bypass surgery // Circulation. 1989. Vol. 80(Suppl. I). PI-91–I-96. 11. Lazar HL, Philippides G., Fitzgerald C. et al. Glucose-insulin-potassium solutions enhance recovery after urgent coronary artery bypass grafting // J. Thorac. Cardiovasc. Surg. 1997. Vol. 113. R. 354–362. 12. Ceremuzynski L., Budaj A., Czepiel A. et al. Low-dose polarizing mixture (Glucose-Insulin-Kalium) in acute myocardial infarction. Pol-GIK Multicenter Trial (abstract) // Circulation. 1997. Vol. 96 (Suppl.). P. 206. 13. Grotel D.M. Acute myocardial infarction. – L.: Leningrad Medical Institute named after. acad. I.P. Pavlova, 1940. 220 p. 14. Oliver MF, Opie LH Effects of glucose and fatty acids on myocardial ischemia and arrhythmias // Lancet. 1994. Vol. 343. R. 155–158. 15. Shlyakhto E.V. Myocardial metabolism in patients with coronary artery disease // Heart failure. 2003. T. 4. No. 1. P. 19–21. 16. Ruda M.Ya., Zysko A.P. Myocardial infarction. – M.: Medicine, 1981. 288 p. 17. Ruksin V.V. Emergency cardiology. – St. Petersburg: Nevsky Dialect, 1997. 471 p. 18. Teo KK, Yusuf S, Collins R et al. Effects of intravenous magnesium in suspected acute myocardial infarction. Overview of randomized trials // Brit. Med. J. 1991. Vol. 303. P. 1499–1503. 19. Woods KL, Fletcheer S., Foffe C., Haider Y. Intravenous magnesium sulphate in suspected acute myocardial infarction. Results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) // Lancet. 1992. Vol. 343. P. 816–819. 20. Shechter M., Hod H., Chouraqui P. et al. Magnesium therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy // Am. J. Cardiol. 1995. Vol. 75. P. 321–323. 21. Shechter M., Sharir M., Labrador M. J. et al. Oral magnesium therapy improves endothelial function in patients with coronary artery disease // Circulation. 2000. Vol. 102(19). R. 2353–2358. 22. Liao F., Folsom AR, Brancati FL Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study // Am. Heart J. 1998. Vol. 136(3). R. 480–490. 23. Ueshima K. Magnesium and ischemic heart disease: a review of epidemiological, experimental, and clinical evidence // Magnes Res. 2005. Vol. 18 (4). pp. 275–284 24. Lima Mde L., Cruz T., Rodrigues LE et al. Serum and intracellular magnesium deficiency in patients with metabolic syndrome-evidences for its relation to insulin resistance // Diabetes Res. Clin. Pract. 2009. Vol. 83(2). R. 257–262. 25. Selye H. The Chemical Prevention of Cardiac Necrosis. – New York: Ronald Press, 1958. 26. Kosarev V.V., Babanov S.A. Clinical pharmacology of drugs used in cardiovascular diseases. – Samara: Etching, 2010. 140 p. 27. Kabelitz HJ On infusion therapy with potassium-magnesium aspartate in acute myocardial infarct, chronically insufficient heart and digitalis intoxication // Med. Klin. 1968. Vol. 63(32). R. 1267–1271. 28. Grujic M., Perinovic M. Treatment of acute myocardial infarct and chronic heart failure using potassium-magnesium aspartate // Med. Welt. 1974. Vol. 13. R. 25(50). R. 2124–2126. 29. Zola-Sleczek E., Mochalski W. Potassium magnesium aspartate (K-Mg-aspartate) in the treatment of digitalis glycoside poisoning // Folia Med. Cracov. 1979. Vol. 21(2). R. 323–331. 30. Trekova N.A., Andrianova M.Yu., Tolstova I.A. and others. The use of a solution of potassium and magnesium aspartate to maintain the balance of potassium and magnesium during cardiac surgery under artificial circulation // Anesthesiology and Reanimatology. 2008. No. 5. pp. 17–21. 31. Akselrod B.A., Tolstova I.A., Andrianova M.Yu., Trekova N.A. The role of magnesium in the implementation of vascular reactions during anesthesia in cardiac surgery patients // Anesthesiology and Reanimatology. 2011. No. 3. pp. 8–13.

Modern Pharmaceuticals of Russia

Asparkam, tablets 175 mg + 175 mg

Trade name: Asparkam International non-proprietary or generic name:
Potassium and magnesium aspartate.
Dosage form:
Tablets
Description:
Round flat-cylindrical tablets of white color with a chamfer and a score.
ATC code:
A12СХ
Pharmacotherapeutic group:
Potassium and magnesium preparation.
Pharmacological action:
The most important intracellular cations of potassium (K+) and magnesium (Mg++) play a key role in the functioning of numerous enzymes, in the formation of bonds between macromolecules and intracellular structures and in the mechanism of muscle contractility.
The intra- and extracellular ratio of potassium, calcium, sodium and magnesium ions affects myocardial contractility. Endogenous aspartate acts as a conductor of ions: it has a high affinity for cells, due to the slight dissociation of its salts, ions in the form of complex compounds penetrate into the cell. Magnesium aspartate and potassium aspartate improve myocardial metabolism. Lack of magnesium/potassium predisposes to the development of arterial hypertension, atherosclerosis of the coronary arteries, arrhythmias and metabolic changes in the myocardium. Pharmacokinetics
Potassium and magnesium aspartates are intensively absorbed in the intestine, mainly in the small intestine.
Excreted by the kidneys. Indications for use:
To eliminate potassium and magnesium deficiency as part of combination therapy for various manifestations of coronary heart disease (including acute myocardial infarction);
chronic heart failure; heart rhythm disturbances (including arrhythmias caused by an overdose of cardiac glycosides). Contraindications:
Hypersensitivity to any of the constituent components of the drug, acute and chronic renal failure, hyperkalemia, hypermagnesemia, Addison's disease, atrioventricular block I-III degree, shock (including cardiogenic) (blood pressure less than 90 mm Hg), violation amino acid metabolism, myasthenia gravis, hemolysis, acute metabolic acidosis, dehydration state, age under 18 years (efficacy and safety have not been established).
With caution:
Pregnancy (especially in the first trimester of pregnancy) and breastfeeding.
Use during pregnancy and breastfeeding:
Use is possible if the potential benefit to the mother outweighs the possible risk to the fetus.

Potassium and magnesium aspartate passes into breast milk.
If it is necessary to take the drug during breastfeeding, breastfeeding should be stopped. Directions for use and dosage:
Before use, you should consult your doctor.

Take orally, without chewing and with plenty of water.

Asparkam should be taken after meals, because... the acidic environment of the stomach reduces its effectiveness.

Adults are prescribed 1-2 tablets 3 times a day.
The course of treatment is 3-4 weeks. If necessary, the course is repeated. Side effects:
Possible nausea, vomiting, diarrhea, discomfort or burning sensation in the epigastric region (in patients with anacid gastritis or cholecystitis), atrioventricular block, paradoxical reaction (increased number of extrasystoles), hyperkalemia (nausea, vomiting, diarrhea, paresthesia), hypermagnesemia (facial redness, thirst, decreased blood pressure, hyporeflexia, respiratory depression, convulsions).
Overdose
The risk of symptoms of hyperkalemia and hypermagnesemia increases.

Symptoms of hyperkalemia:

increased fatigue, myasthenia gravis, paresthesia, confusion, heart rhythm disturbances (bradycardia, atrioventricular block, arrhythmias, cardiac arrest).

Symptoms of hypermagnesemia:

decreased neuromuscular excitability, nausea, vomiting, lethargy, decreased blood pressure.
With a sharp increase in the content of magnesium ions in the blood: inhibition of deep tendon reflexes, respiratory paralysis, coma. Treatment: symptomatic therapy - intravenous administration of calcium chloride at a dose of 100 mg/min, if necessary - hemodialysis. Interaction with other drugs:
Pharmacodynamic interactions.

When used together with potassium-sparing diuretics (triamterene, spironolactone), beta-blockers, cyclosporine, heparin, angiotensin-converting enzyme (ACE) inhibitors, and non-steroidal anti-inflammatory drugs, the risk of developing hyperkalemia up to the development of arrhythmia and asystole increases. The simultaneous use of potassium supplements with glucocorticosteroids eliminates the hypokalemia caused by the latter. Potassium reduces the undesirable effects of cardiac glycosides. Asparkam enhances the negative dromo- and bathmotropic effects of antiarrhythmic drugs. Magnesium reduces the effects of neomycin, polymyxin B, tetracycline and streptomycin. Anesthetics increase the inhibitory effect of magnesium preparations on the central nervous system; when used simultaneously with atracuronium, decamethonium, succinyl chloride and suxamethonium, neuromuscular blockade may be enhanced. Calcitriol increases the content of magnesium in the blood plasma, calcium supplements reduce the effects of magnesium supplements.

Pharmacokinetic interaction.

Medicines that have an astringent and enveloping effect reduce the absorption of magnesium and potassium aspartate in the gastrointestinal tract, therefore it is necessary to maintain a three-hour interval between oral administration of Asparka with the above medications.
Special instructions:
Patients with diseases accompanied by hyperkalemia require special attention: regular monitoring of potassium levels in the blood plasma is necessary.
Effect on the ability to drive vehicles and machinery:
No studies have been conducted.
No effect is expected on the ability to drive vehicles or operate mechanisms that require increased concentration and speed of psychomotor reactions. Release form:
Release form. Tablets, 175 mg + 175 mg.

8, 10, 20, 25 tablets in a blister pack (blister) made of polyvinyl chloride film and aluminum foil.

10 tablets in a contour-free packaging made of polyethylene-coated packaging paper.

50, 100 tablets in polyethylene jars.

Labels made of label or writing paper or labels made of self-adhesive paper are glued onto polyethylene cans.

1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 contour packages or 1 polyethylene jar together with instructions for medical use are placed in a box of cardboard.

It is allowed to pack 500, 700 or 1000 contour packages together with an equal number of instructions for medical use in corrugated cardboard boxes (for hospitals).
Storage conditions:
At a temperature not exceeding 25 °C.
Keep out of the reach of children. Shelf life:
3 years.

Do not use the drug after the expiration date indicated on the package.
Dispensing conditions:
Without a prescription.

Liver diseases

Aspartic acid is a precursor of oxaloacetate, plays an important role in the tricarboxylic acid cycle, participates in the ornithine cycle, accelerates the formation of urea from ammonia and carbon dioxide, thereby promoting their excretion. Potassium and magnesium aspartate improves liver function by reducing the concentration of bilirubin in the blood serum, and can be used in the treatment of viral hepatitis, liver cirrhosis, and hepatic encephalopathy. Guo Fengkun[11] reported the combined use of glycerrizinic acid diamine and potassium and magnesium aspartate in the treatment of 82 cases of chronic cholestatic hepatitis. Treatment was carried out at a dose of 300–500 mg of glycerrizinic acid diamine in 400 ml of 10% glucose solution, 30 ml of potassium and magnesium aspartate in 250 ml of 5% glucose solution, intravenously, 1 time per day, daily for 6 weeks, and showed a pronounced therapeutic effect.

In addition, potassium and magnesium aspartate has a pronounced effect in the prevention and treatment of bronchial asthma, migraine, ischemic cerebrovascular diseases, toxic damage to the myocardium and liver, and malignant diseases.

References: 1 Xie Ronglu. Evaluation of the effectiveness of potassium and magnesium aspartate in the treatment of arrhythmia [J]. Clinical Medicine China, 2000, 3(2): 102–104. 2 Xie Yumei, Li Yufen. Experience with the use of Panangin in the treatment of persistent cardiac arrhythmias in children [J]. Guangdong Medicine, 1998, 19(2): 145–146. 3 Liu Tong. Clinical efficacy of potassium and magnesium aspartate in the treatment of acute myocardial infarction [J]. Chinese Journal of Misdiagnosis, 2002, 2(7): 1017–1018. 4 Sun Shuang, Liu Huiming, Chen Yanxiang. Clinical efficacy of potassium and magnesium aspartate in the treatment of acute myocardial infarction [J]. Railway Medical Journal, 2001, 29 (5): 323–324. 5 Chen Dan, Xue Jing, Xi Lin et al. Clinical efficacy of potassium and magnesium aspartate in the treatment of heart failure [J]. Journal of the Military Medical College of the Fourth Jilin Military Medical University, 2002, 24 (2): 79–80, 88. 6 Zhou Chu, Yu Jilun, Dong Zhichun, et al. Clinical observation of 38 cases of treatment of heart failure with potassium and magnesium aspartate [ J]. Chinese Journal of Interventional Cardiology, 2000, 8(2): 80. 7 Yan Yuquan, Yang Chuangjun, Guo Li. Clinical efficacy of cyclic adenosine monophosphate and potassium magnesium aspartate in the treatment of refractory heart failure [J]. Henan Medical News, 2000, 8(1): 37–38. 8 Hu Yiwen. Randomized controlled trial of the effectiveness of potassium and magnesium aspartate and nifedipine in the treatment of essential hypertension [J]. Journal of Pharmacoepidemiology, 1998, 7(1): 5–6. 9 Wei Zongde, Yang Xiaolin, Zhang Zhi, et al. Clinical efficacy of potassium and magnesium aspartate in the treatment of moderate hypertension [J]. Journal of Luzhou Medical Institute, 1998, 21(3): 211–213. 10 Li Yingmei, Li Xingguang. The use of dopamine and potassium and magnesium aspartate in the treatment of 57 cases of multiple organ failure in pulmonary heart failure [J]. Clinical Digest, 1997, 12(2): 79–80. 11 Guo Fengkun. Clinical efficacy of glycyrrhizic acid diamine and potassium magnesium aspartate in the treatment of chronic cholestatic hepatitis [J]. Pharmacology Tianjin, 2001, 13(3): 53–54. China Library Classification System Number: R972+.2 R975+. 5 Literary identifier: A Article serial number: 1009-0878(2003) 04-0282-02