MILDRONATE 250MG 40 CAPS - MADE IN LATVIA - FREE SHIPPING
(MILDRONATE 250 MG )
Pharmacodynamics. Meldonium is a precursor of carnitine, a structural analogue of gamma-butyrobetaine (GBB), in which one carbon atom is replaced by a nitrogen atom. its effect on the body can be explained in two ways.
1. Influence on carnitine biosynthesis.
Meldonium, by reversibly inhibiting gamma-butyrobetaine hydroxylase, reduces the biosynthesis of carnitine and therefore prevents the transport of long-chain fatty acids through the cell membranes, thus preventing the accumulation of a strong detergent in the cells - activated forms of unoxidized fatty acids. Thus, damage to cell membranes is prevented.
With a decrease in the concentration of carnitine under conditions of ischemia, beta-oxidation of fatty acids is delayed and oxygen consumption in cells is optimized, glucose oxidation is stimulated and the transport of ATP from the sites of its biosynthesis (mitochondria) to the sites of consumption (cytosol) is resumed. The cells are supplied with nutrients and oxygen, and the use of these substances is optimized.
In turn, with an increase in the biosynthesis of the precursor of carnitine, that is, GBB, NO-synthetase is activated, as a result of which the rheological properties of the blood improve, and the OPSS decreases.
With a decrease in the concentration of meldonium, the biosynthesis of carnitine increases again, and the amount of fatty acids in the cells gradually increases.
It is believed that the effectiveness of meldonium is based on an increase in tolerance to cell load (with a change in the amount of fatty acids).
2. Function of a mediator in a hypothetical GBD-ergic system.
A hypothesis has been put forward that there is a system for the transfer of neuronal signals in the body - the GBB-ergic system, which ensures the transfer of nerve impulses between cells. The mediator of this system is the latest precursor of carnitine, GBB ether. As a result of the action of GBB-esterase, the mediator gives the cell an electron, thus transferring an electrical impulse, and itself turns into GBB. Further, the hydrolyzed form of GBB is actively transported to the liver, kidneys and ovaries, where it is converted into carnitine. In response to stimulation, somatic cells again synthesize new GBB molecules, providing signal propagation.
With a decrease in the concentration of carnitine, GBB synthesis is stimulated, as a result of which the concentration of GBB ether increases.
Meldonium, as indicated earlier, is a structural analogue of GBB and can act as a mediator. In contrast, GBB hydroxylase “does not recognize” meldonium, so the concentration of carnitine does not increase, but decreases. Thus, meldonium itself, replacing the "mediator" and contributing to an increase in GBB concentration, leads to the development of a response in the body. As a result, the overall metabolic activity also increases in other systems, for example, in the central nervous system.
Effect on the central nervous system. In experiments on animals, the antihypoxic effect of meldonium and the effect that promotes cerebral circulation have been established. Meldonium optimizes the redistribution of cerebral circulation in favor of ischemic foci, increases the strength of neurons under hypoxic conditions.
Meldonium has a stimulating effect on the central nervous system - increased motor activity and physical endurance, stimulation of behavioral reactions, as well as an anti-stress effect - stimulation of the sympathoadrenal system, accumulation of catecholamines in the brain and adrenal glands, protection of internal organs from changes caused by stress.
Effectiveness in neurological diseases. The influence of meldonium on the process of rehabilitation of patients with neurological disorders (after suffering diseases of the blood vessels of the brain, operations on the brain, trauma, and suffering from tick-borne encephalitis) was studied.
The results of testing the therapeutic activity of meldonium indicate its dose-dependent positive effect on physical endurance and restoration of functional independence during the recovery period.
When analyzing the changes in individual and total intellectual functions after using the preparation, a positive effect on the recovery process of intellectual functions during the recovery period was established.
It was found that meldonium improves the convalescent quality of life (mainly due to the renewal of the physical function of the body), moreover, it helps to eliminate mental disorders.
Meldonia has a positive effect on the function of the nervous system - a decrease in impairments in patients with neurological deficit during the recovery period. The general neurological condition of patients improves (reduction of damage to the nerves of the brain and pathology of reflexes, regression of paresis, improvement of coordination of movements and autonomic functions).
Suction. After a single oral administration of meldonium in doses of 25; 50; 100; 200; 400; 800 or 1500 mg Cmax in blood plasma and AUC increases in proportion to the dose applied. The time to reach Cmax is 1–2 hours. When the doses are repeated, the equilibrium plasma concentration is reached 72–96 hours after the first dose. Accumulation of meldonium in blood plasma is possible. Food slows down the absorption of meldonium without changing the Cmax and AUC values.
Distribution. Meldonium from the bloodstream quickly spreads into tissues. Plasma protein binding increases with time after dose. Meldonium and its metabolites partially pass through the placental barrier. In animal studies, it has been proven that meldonium is excreted in breast milk.
Biotransformation. In studies of metabolism in experimental animals, it was found that meldonium is mainly metabolized in the liver.
Excretion. In the elimination of meldonium and its metabolites from the body, renal excretion is important. T1 / 2 of meldonium is approximately 4 hours. When repeated doses are used, the T1 / 2 is different.
Special patient groups
Elderly patients. Elderly patients with impaired liver or kidney function, who have increased bioavailability, should reduce the dose of meldonium.
Renal dysfunction. Patients with impaired renal function in whom bioavailability increases, the dose of meldonium should be reduced. Non-clinical studies have shown that when administered orally to rats, meldonium in doses of 20; 100 and 500 mg / kg of body weight is low-toxic and does not affect the activity of the kidneys. There is an interaction between renal reabsorption of meldonium or its metabolites (for example 3-hydroxymeldonium) and carnitine, as a result of which the renal clearance of carnitine increases. There is no direct effect of meldonium, GBB and the combination of meldonium / GBB on the renin-angiotensin-aldosterone system.
Liver dysfunction. Patients with impaired liver function, in whom bioavailability increases, the dose of meldonium should be reduced. In the study of toxicity in rats when using meldonium at a dose of more than 100 mg / kg, liver staining in yellow and fat denaturation was established. Histopathological studies on animals after the use of meldonium in high doses (400 and 1600 mg / kg) showed the accumulation of lipids in liver cells. Changes in liver function indicators in humans after high doses (400-800 mg) were not observed. The possible infiltration of fats into liver cells cannot be ruled out.
Children. There is no data on the safety and efficacy of meldonium in children (under the age of 18 years), therefore, the use of the preparation in this category of patients is contraindicated.
In complex therapy in the following cases:
decreased performance, physical and psycho-emotional overstrain;
during the recovery period after cerebrovascular disorders, head trauma and encephalitis.
For oral administration. the capsules are swallowed with water. the preparation is used regardless of food intake. due to the possible stimulating effect, the preparation is recommended to be used in the morning.
Adults. The dose is 500 mg / day (2 capsules of 250 mg). The daily dose can be applied all at once or divided into two single doses. The maximum daily dose is 500 mg.
Patients with a history of mild or moderate hepatic and / or renal dysfunction should be careful when using the preparation (it is necessary to monitor liver and / or kidney function).
Application during pregnancy or lactation
Pregnancy. Animal studies are insufficient to assess the effects of meldonium on pregnancy, embryo / fetal development, childbirth and postpartum development. The potential risk to humans is unknown, therefore meldonium is contraindicated during pregnancy.
Lactation. The available animal data indicate the penetration of meldonium into mother's milk. It is not known whether Meldonium passes into human breast milk. The risk to newborns / babies cannot be excluded, therefore, during breastfeeding, meldonium is contraindicated.
The ability to influence the reaction rate when driving or working with other mechanisms. No studies have been carried out to assess the effect on the ability to drive and maintain machinery.
Meldonium can be used together with long-acting nitrates and other antianginal agents, cardiac glycosides and diuretic preparations. it can also be combined with anticoagulants, antiplatelet agents, antiarrhythmics and other preparations that improve microcirculation.
Meldonium can enhance the effect of preparations containing glyceryl trinitrate, nifedipine, β-adrenergic receptor blockers, other antihypertensive preparations and peripheral vasodilators.
With the simultaneous use of meldonium with lisinopril, a positive effect of combination therapy was revealed (vasodilation of the main arteries, improvement of peripheral circulation and quality of life.
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