Then, these complexes enter the cell nucleus, binds (chromatin) and stimulate the transcription and subsequent synthesis of various enzymes, which explains the effect of corticosteroids for systemic use. Not only have a significant impact on the inflammatory and immune response, but also affect the carbohydrate, protein and fat metabolism.
Most of the indications for use of equipoisedue to their anti-inflammatory, immunosuppressive and anti-allergic properties. Because of these properties are achieved following therapeutic effects:
- reducing the number of immunoactive cells near the inflammation focus;
- reduction in vasodilation;
- stabilization of the lysosomal membranes;
- inhibition of phagocytosis;
- decrease in production of prostaglandins and related compounds.
Methylprednisolone has a strong anti-inflammatory action, and its activity is higher than that of prednisolone, and the ability to cause water retention and sodium ions is reduced compared to prednisolone.Metabolism and mechanism of anti-inflammatory action of methylprednisolone sodium succinate are similar to those for methylprednisolone. For parenteral administration of equivalent amounts of the biological activity of both compounds identical. The on / in the introduction of activity ratio of methylprednisolone sodium succinate and hydrocortisone sodium succinate, designed to reduce the number of eosinophils was not less than 4: 1. This correlates well with data on the relative potency equipoise of methylprednisolone and hydrocortisone when administered orally. A dose of 4 mg of methylprednisolone has the same glucocorticosteroid (anti-inflammatory) effect as 20 mg of hydrocortisone. Methylprednisolone has only negligible mineralocorticoid activity (equivalent to 200 mg methylprednisolone deoxycorticosterone 1 mg).
Exert catabolic action on proteins. The released amino acids are converted into hepatic gluconeogenesis and glycogen into glucose. Glucose uptake in peripheral tissues is reduced, which may lead to hyperglycaemia and glycosuria, especially in patients at risk of developing diabetes.
Maximum pharmacological activity of corticosteroids appears not at the peak plasma concentration, and after it, therefore, the action of corticosteroids is primarily due to their effect on the enzyme activity.
In any method of methylprednisolone sodium succinate injection is largely and rapidly hydrolyzed by the action of cholinesterase with the formation of the active form – free methylprednisolone. After the on / in infusion of 30 mg / kg for 20 minutes, or 1 g for about 30-60 min after 15 min methylprednisolone achieved peak plasma concentration (20 ug / ml). After about 25 min after i / v bolus 40 mg methylprednisolone reached its peak in the plasma concentration equal to 42-47 g / 100 ml. When the / m 40 min 120 mg methylprednisolone achieved plasma level equal to 34 g / 100 ml. When the / m achieves a low peak value than on / in. The average maximum plasma concentration C max is reached after 1 hour / m administration of 40 mg of methylprednisolone sodium succinate and is 454 ng / mL.After 12 hours methylprednisolone concentration in plasma decreased to 31.9 ng / ml and after 18 hours -metilprednizolon not detected in the blood. Comparing equipoise the areas under the curve “concentration – time” refers to the equal effectiveness of the drug in / in and / m the introduction of equivalent doses of sodium succinate methylprednisolone.
After the / m of the drug present in the blood plasma for a more extended period than after in / in the introduction, if you have entered the equivalent amount of methylprednisolone. Considering the mechanism of action of corticosteroids, it can be assumed that these differences have minimal clinical significance. The clinical effect is usually seen after 4-6 hours after administration. In the treatment of bronchial asthma first positive results identified after 1-2 h. The half-life of methylprednisolone sodium succinate in blood plasma is 2.3-4 hour, and probably does not depend on the route of administration.Methylprednisolone – glucocorticosteroids with an intermediate duration of action. Its half-life in the human body is 12-36 hours. Due to the intracellular activity revealed a pronounced difference between the half-life of the SSC and plasma half-life of the whole organism. Pharmacotherapeutic effects is maintained even when the drug is no longer in the blood is determined. The duration of anti-inflammatory activity of corticosteroids is approximately equal to the duration of suppression of the hypothalamic-pituitary-adrenal equipoise system.
Methylprednisolone Contact proteins (albumin and transcortin) – about 40 -. 90%
Metabolism of methylprednisolone in the liver, and this process is qualitatively similar to the metabolism of cortisol. The main metabolites are 20β-gidroksimetilprednizolon and 20β-hydroxy-6α-metilprednizon.Metabolites are mainly in urine in free form or in the form of glucuronides and sulfates which are produced primarily in the liver and partially – in the kidneys. After the on / in the methylprednisolone labeled with carbon- 14 C, 75% of the total radioactivity excreted in the urine within 96 hours, and 9% excreted in the feces within 5 days and 20% found in the bile.