Meldonium - active substance popular medicine Mildronate (which will be written about here separately), which is also an independent drug produced by the domestic pharmaceutical plant Pharmstandard. Meldonium triggers at the cellular level a whole cascade of pharmacologically significant reactions, interactions and transformations that affect cellular metabolism and allow the use of this drug both in “solo” mode and as part of combination therapy in such seemingly completely unrelated areas, as treatment of cardiovascular and eye diseases, therapy of withdrawal syndrome and correction of asthenic conditions. The mechanism of action of this drug is unlikely to be completely clear to a person uninitiated in biochemical mysteries: meldonium suppresses the enzyme gamma-butyrobetaine hydroxygenase, which is involved in the synthesis of carnitine, as a result of which the production of gamma-butyrobetaine, which has vasodilating properties, increases. But this is not all the advantages of meldonium: it inhibits the movement of long-chain fatty acids through the cell membrane, actively counteracts the presence and multiplication in cells active forms unoxidized fatty acids, which are derivatives of acyl coenzyme A and acylcarnitine. And if it is not yet clear to most readers what the point of all this is, then you should be patient a little and continue reading. One of the main clinically significant effects of meldonium is the correction of the disturbed balance between the delivery of oxygen to cells and its consumption under unfavorable conditions of ischemia (the Great Soviet Encyclopedia gives a very apt and understandable definition of this pathological condition- local anemia).
The drug prevents disruption of the transport of the main energy substrate of the cell - ATP, while simultaneously activating anaerobic glycolysis. In case of ischemia of the heart muscle, meldonium slows down the formation of a zone of necrosis and shortens the rehabilitation period. In case of insufficiency of cardiac function, it increases the contractility of the heart muscle, gives the patient the ability to endure more impressive physical exertion, and reduces the frequency of angina pectoris. At the level of self-awareness, meldonium increases performance, tones the central nervous system, activates the immune system, and relieves physical and mental stress.
Meldonium is available in the form of capsules and solution for injection. The oral dosage form is taken before meals. The dose, frequency and duration of administration are determined by the specific disease and can vary over a fairly wide range: for example, the duration of taking meldonium for heart failure, stable angina or cerebrovascular accidents is 4-6 weeks, for cardialgia - 12 days, for alcohol withdrawal - 7- 10 days, with reduced performance and as an aid when playing sports - 10-21 days.
Pharmacology
A drug that improves metabolism, an analogue of gamma-butyrobetaine. Suppresses gamma-butyrobetaine hydroxinase, inhibits the synthesis of carnitine and the transport of long-chain fatty acids through cell membranes, and prevents the accumulation in cells of activated forms of unoxidized fatty acids - derivatives of acylcarnitine and acyl coenzyme A.
Under conditions of ischemia, it restores the balance of the processes of oxygen delivery and its consumption in cells, prevents disruption of ATP transport; At the same time, it activates glycolysis, which occurs without additional oxygen consumption. As a result of a decrease in carnitine concentration, gamma-butyrobetaine, which has vasodilating properties, is intensively synthesized. The mechanism of action determines the variety of its pharmacological effects: increased performance, reduced symptoms of mental and physical stress, activation of tissue and humoral immunity, cardioprotective effect.
In case of acute ischemic damage to the myocardium, it slows down the formation of the necrotic zone, shortens rehabilitation period. In heart failure, increases myocardial contractility, increases tolerance to physical activity, reduces the frequency of angina attacks. In acute and chronic ischemic disorders of cerebral circulation, it improves blood circulation in the ischemic area and promotes the redistribution of blood in favor of the ischemic area. Effective for vascular and dystrophic pathology of the fundus. Has a tonic effect on the central nervous system, eliminates functional disorders from nervous system in patients with chronic alcoholism with withdrawal syndrome.
Pharmacokinetics
After oral administration, it is quickly absorbed from the gastrointestinal tract. Bioavailability is about 78%. Cmax in plasma is achieved 1-2 hours after administration. It is biotransformed in the body to form two main metabolites, which are excreted by the kidneys. T1/2 is 3-6 hours and depends on the dose.
Release form
5 ml - ampoules (5) - plastic cell packaging (1) - cardboard packs.
5 ml - ampoules (10) - plastic cell packaging (1) - cardboard packs.
5 ml - ampoules (5) - plastic cell packaging (2) - cardboard packs.
5 ml - ampoules (5) - plastic cell packaging (15) - cardboard packs.
5 ml - ampoules (5) - plastic cell packaging (20) - cardboard packs.
Dosage
Due to the possibility of developing an stimulating effect, it is recommended to use it in the first half of the day. The dose is set individually depending on the indications and route of administration.
When taken orally, a single dose is 0.25-1 g, the frequency of administration and duration of treatment depend on the indications.
When administered intravenously, the dose is 0.5-1 g 1 time/day, the duration of treatment depends on the indications.
0.5 ml of injection solution with a concentration of 500 mg/5 ml is administered parabulbarically for 10 days.
Interaction
When used together, meldonium enhances the effect of antianginal drugs, some antihypertensive drugs, and cardiac glycosides.
With simultaneous use of meldonium with nitroglycerin, nifedipine, alpha-blockers, antihypertensive drugs and peripheral vasodilators, moderate tachycardia may develop, arterial hypotension(Caution is required with these combinations).
Side effects
From the outside cardiovascular system: rarely - tachycardia, changes in blood pressure.
From the side of the central nervous system: rarely - psychomotor agitation.
From the digestive system: rarely - dyspeptic symptoms.
Allergic reactions: rarely - skin itching, redness, rash, swelling.
Indications
For oral or intravenous administration: as part of complex therapy for coronary artery disease (angina pectoris, myocardial infarction), chronic heart failure, dyshormonal cardiomyopathy; as part of complex therapy of acute and chronic disorders cerebral circulation (stroke and cerebrovascular insufficiency); decreased performance, physical overstrain (including among athletes), postoperative period to speed up rehabilitation; withdrawal syndrome in chronic alcoholism (in combination with specific therapy for alcoholism).
For parabulbar administration: acute circulatory disorders in the retina, hemophthalmos and retinal hemorrhages of various etiologies, thrombosis central vein retina and its branches, retinopathy of various etiologies (including diabetic and hypertensive) - only for parabulbar administration.
Contraindications
Increased intracranial pressure (including in cases of impaired venous outflow, intracranial tumors), pregnancy, lactation (breastfeeding), childhood and adolescence under 18 years of age, increased sensitivity to meldonium.
Features of application
Use during pregnancy and breastfeeding
During pregnancy and lactation (breastfeeding), the use of the drug is contraindicated.
Use for liver dysfunction
Use with caution in case of liver diseases, especially for a long time.Use for renal impairment
Use with caution in case of kidney disease, especially for a long time.
Use in children
In children and adolescents under 18 years of age, the effectiveness and safety of meldonium have not been established.
Meldonium in capsule form is contraindicated for use in children and adolescents under 18 years of age; in syrup form - in children under 12 years of age.
Special instructions
Use with caution in case of liver and/or kidney disease, especially for a long time.
Many years of experience in the treatment of acute myocardial infarction and unstable angina in cardiology departments show that meldonium is not a first-line treatment for acute coronary syndrome.
As I already wrote, meldonium or mildronate (there are several other names abroad, but they are not so important) is, roughly speaking, which until recently was very widely used in the sports field. Why was it used? Yes, I note that since the beginning of 2016, he was included in the “black list” of drugs prohibited by the Doping Agency.
Just imagine how many amateurs and simply experienced athletes “used” it (used it, if anything), even if the world-famous “burned” using this drug.
Why is it so attractive?
Okay, let me try to explain as simply as possible why so many athletes from the CIS countries like this simple drug. First answer the question: what muscle in the human body never rests? Perhaps the heart immediately came to mind? Then you were not mistaken - the heart really works constantly, without rest, breaks or days off. Only during training it begins to beat more often. What about hard training, where you need to run long distances, lift tons of iron, squeeze all the juices out of the body, burning its reserves?
Such cases are not uncommon not only for, but even for the majority of amateurs aimed at achieving results. And how can you protect your health in such situations and not get a stroke (at best)?
Yes, it’s very simple - start taking meldonium, which will help get rid of a number of problems, unless, of course, you are an athlete on the Olympic team and you need to undergo a doping test in a week. I’ll tell you exactly what the problems are below.
Effects on the human body
You know, before writing this article, I went through a lot of information, where many sources provided not exactly the opposite information, but still inconsistent with the official statements of the creator of this drug. Therefore, I will rely solely on the statements of the author himself, Ivars Kalvins.
He said that the medicine was initially developed for military purposes, and only then passed into civilian use.
Judge for yourself, a soldier is the same all-around athlete, which involves running, lifting weights, moving them, physical labor and much more. Imagine that during a training exercise, soldiers need to cover a forced march of 20–30 kilometers, which is a decent distance.
No, this is not just running - it’s running in full uniform (body armor, machine gun, ammunition, walkie-talkie, well, you know what I mean). And if it comes to real combat operations, where it is necessary, after covering the distance, to still fight with the real enemy? Few people can withstand such loads without consequences for the body. So we turned to pharmacology for help.
According to the author himself, meldonium not only prevents heart disease due to excessive physical exertion, but also allows you to adapt to subsequent stressful situations (physically and psychologically). Yes, exactly psychological.
After all, you can often come across an athlete who uses meldonium in order to overcome anxiety at competitions. Imagine that you are in a stadium and tens of thousands of fans are watching you. Wouldn't you be worried? If not, then you are a confident person, of which there are few. So it turns out that the drug helps fight stress in order to properly demonstrate your physical qualities.
By the way, on many resources and sources I came across information that the product supposedly increases endurance. In fact, this is how it turns out, but the definition is not entirely correct. I will not go into detail about how and what happens in the body at the cellular level, but I will only say that athletes who take it for a certain time have increased their performance.
Absorption, excretion, side effects
The drug is absorbed by 78%, which indicates a great impact. It begins to work to its maximum within two hours after administration. Absorption of the drug occurs through gastrointestinal tract, but elimination occurs (half-life) through the kidneys within 3 to 6 hours.
downright critical side effects not noticed, but some had skin itching, agitation, tachycardia and dyspepsia. To be honest, I don’t fully understand the meaning of the last two terms, but if you are interested, then Google it. Surely you will find it.
Conclusion
So, let’s summarize what effects this drug has on a person: increasing endurance, adapting to heavy physical activity, preserving the heart, preventing and overcoming anxiety and stress. By the way, this is not the entire list of effects exerted by the drug, because what I described is of interest exclusively to athletes. But for patients with certain diseases, the drug also contains many benefits.
Best regards, Vladimir Manerov
Subscribe and be the first to know about new articles on the site, right in your email.
Composition and release form of the drug
Solution for injection in the form of a clear, colorless liquid.
Excipients: water for injection - up to 1 ml.
5 ml - ampoules (5) - contour cell packaging (1) - cardboard packs.
5 ml - ampoules (5) - contour cell packaging (2) - cardboard packs.
5 ml - ampoules (5) - contour cell packaging (50) - cardboard boxes (for hospitals).
5 ml - ampoules (5) - contour cell packaging (100) - cardboard boxes (for hospitals).
Pharmacological action
A drug that improves metabolism, an analogue of gamma-butyrobetaine. Suppresses gamma-butyrobetaine hydroxinase, inhibits the synthesis and transport of long-chain fatty acids through cell membranes, and prevents the accumulation in cells of activated forms of unoxidized fatty acids - derivatives of acylcarnitine and acyl coenzyme A.
Under conditions of ischemia, it restores the balance of the processes of oxygen delivery and its consumption in cells, prevents disruption of ATP transport; At the same time, it activates glycolysis, which occurs without additional oxygen consumption. As a result of a decrease in carnitine concentration, gamma-butyrobetaine, which has vasodilating properties, is intensively synthesized. The mechanism of action determines the variety of its pharmacological effects: increased performance, reduced symptoms of mental and physical stress, activation of tissue and humoral immunity, cardioprotective effect.
In case of acute ischemic damage to the myocardium, it slows down the formation of the necrotic zone and shortens the rehabilitation period. In heart failure, it increases myocardial contractility, increases exercise tolerance, and reduces the frequency of attacks. In acute and chronic ischemic disorders of cerebral circulation, it improves blood circulation in the ischemic area and promotes the redistribution of blood in favor of the ischemic area. Effective for vascular and dystrophic pathology of the fundus. It has a tonic effect on the central nervous system, eliminates functional disorders of the nervous system in patients with chronic alcoholism with withdrawal syndrome.
Pharmacokinetics
After oral administration, it is quickly absorbed from the gastrointestinal tract. Bioavailability is about 78%. Cmax is reached 1-2 hours after administration. It is biotransformed in the body to form two main metabolites, which are excreted by the kidneys. T1/2 is 3-6 hours and depends on the dose.
Indications
For oral or intravenous administration: as part of complex therapy for coronary artery disease (angina pectoris), chronic heart failure, dyshormonal cardiomyopathy; as part of complex therapy for acute and chronic cerebrovascular accidents (stroke and cerebrovascular insufficiency); decreased performance, physical overstrain (including in athletes), postoperative period to speed up rehabilitation; chronic withdrawal syndrome (in combination with specific therapy for alcoholism).
For parabulbar administration: acute circulatory disorders in the retina, hemophthalmos and retinal hemorrhages of various etiologies, thrombosis of the central retinal vein and its branches, retinopathy of various etiologies (including diabetic and hypertensive) - only for parabulbar administration.
Contraindications
Increased intracranial pressure (including in cases of impaired venous outflow, intracranial tumors), pregnancy, lactation (breastfeeding), children and adolescents under 18 years of age, increased sensitivity to meldonium.
Dosage
Due to the possibility of developing an stimulating effect, it is recommended to use it in the first half of the day. The dose is set individually depending on the indications and route of administration.
When taken orally, a single dose is 0.25-1 g, the frequency of administration and duration of treatment depend on the indications.
When administered intravenously, the dose is 0.5-1 g 1 time/day, the duration of treatment depends on the indications.
0.5 ml of injection solution with a concentration of 500 mg/5 ml is administered parabulbarically for 10 days.
Side effects
From the cardiovascular system: rarely - tachycardia, changes in blood pressure.
From the side of the central nervous system: rarely - psychomotor agitation.
From the digestive system: rarely - dyspeptic symptoms.
Allergic reactions: rarely - skin itching, redness, rash, swelling.
Drug interactions
When used together, meldonium enhances the effect of antianginal drugs, some antihypertensive drugs, and cardiac glycosides.
With simultaneous use of meldonium with nifedipine, alpha-blockers, antihypertensive drugs and peripheral vasodilators, the development of moderate tachycardia and arterial hypotension is possible (with these combinations, caution is required).
Midolat.
Composition and release form
Meldonium dihydrate. Hard gelatin capsules (250 mg).
Pharmacological action
A drug that improves metabolism and energy supply to tissues. Meldonium dihydrate is an analogue of gamma-butyrobetaine, inhibits gamma-butyrobetaine hydroxinase, reduces the synthesis of carnitine and the transport of long-chain fatty acids through cell membranes, and prevents the accumulation in cells of activated forms of unoxidized fatty acids - derivatives of acylcarnitine and acyl coenzyme A.
Under conditions of ischemia, it restores the balance of oxygen delivery and consumption in cells, prevents disruption of transport, and at the same time activates glycolysis, which occurs without additional oxygen consumption. As a result of a decrease in carnitine concentration, the synthesis of gamma-butyrobetaine, which has vasodilating properties, increases.
The mechanism of action determines the variety of pharmacological effects of the drug: increased performance, reduced symptoms of mental and physical stress, activation of tissue and humoral immunity, cardio-protective effect. In case of acute ischemic damage to the myocardium, it slows down the formation of the necrotic zone and shortens the rehabilitation period.
In heart failure, it increases myocardial contractility, increases exercise tolerance, and reduces the frequency of angina attacks.
In acute and chronic ischemic conditions, NMC improves blood circulation in the ischemic area and promotes the redistribution of blood in favor of the ischemic area. Effective in cases of vascular and dystrophic pathology of the fundus. It is also characterized by a tonic effect on the central nervous system, elimination of functional disorders of the somatic and autonomic nervous system in patients with chronic alcoholism during the period of abstinence.
Pharmacokinetics
After oral administration, it is quickly absorbed, bioavailability is 78%. Cmax in blood plasma is achieved 1-2 hours after oral administration. Metabolized in the body to form two main metabolites, which are excreted by the kidneys. T1/2 when taken orally depends on the dose and is 3-6 hours.
Indications
- in neurology in complex therapy: ischemic, hemorrhagic stroke in recovery period, transient cerebrovascular accidents, chronic failure cerebral circulation;
— in cardiology in complex therapy: (angina pectoris, myocardial infarction), CHF, dyshormonal cardiomyopathy;
- decreased performance, physical overstrain, including in athletes, postoperative period to speed up rehabilitation, alcohol withdrawal syndrome (in combination with specific therapy).
Application
The drug is prescribed orally. For NMC in the acute phase, an injection form of the drug is used for
10 days, after which the drug is prescribed orally at 500 mg/day. The course of treatment is 4-6 weeks. For chronic cerebrovascular accidents - 500 mg
1 r/day, preferably in the morning. The course of treatment is 4-6 weeks. Repeated courses - 2-3 times a year.
In cardiology in complex therapy - 0.5-1 g/day. The course of treatment is 4-6 weeks. For cardialgia against the background of dyshormonal myocardial dystrophy - 250 mg 2 times a day (morning and evening). The course of treatment is 12 days.
For mental and physical overload (including athletes), adults - 250 mg 4 times a day. Course of treatment - 10-14 days. If necessary, treatment is repeated after 2-3 weeks. Before training - 0.5-1 g 2 times a day, preferably in the first half of the day.
The duration of the course during the preparatory period is 14-21 days, during the competition period - 10-14 days. For alcohol withdrawal syndrome - 500 mg 4 times a day. The course of treatment is 7-10 days.
Side effect
AR (skin itching, rashes, redness and swelling of the face), dyspepsia, tachycardia, agitation, decreased blood pressure.
Contraindications
Increased intracranial pressure (due to impaired venous outflow and intracranial tumors), pregnancy, lactation ( breast-feeding), childhood under 18 years of age, hypersensitivity to the components of the drug.
Interaction with other drugs
Do not use simultaneously with others dosage forms containing meldonium (risk of developing side effects). Enhances the effect of coronary dilatants and some antihypertensive drugs, cardiac glycosides.
Due to the possible development of moderate tachycardia and arterial hypotension, caution should be exercised when combined with alpha-blockers, antihypertensive agents and peripheral vasodilators. Can be combined with antianginal drugs, anticoagulants, antiplatelet agents, antiarrhythmic drugs, diuretics, bronchodilators.