Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1    Pharmacodynamic properties
Pharmacotherapeutic group: Corticosteroids for systemic use, glucocorticoids, ATC code: H02A B01.

Betamethasone is a synthetic glucocorticoid (9 alpha-fluoro-16 beta-methylprednisolone).
Betamethasone has strong anti-inflammatory, immunosuppressive and anti-allergic activity.

Betamethasone has no clinically significant mineralocorticoid effect. Glucocorticoids diffuse across cell membranes and form complexes with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin) and stimulate the transcription of messenger RNA and the protein synthesis of various enzymes. These are finally responsible for the effects observed in systemic glucocorticoid use. In addition to their significant effect on the inflammatory and immune processes, glucocorticoids also influence the metabolism of carbohydrates, proteins and lipids. Finally, they also have an effect on the cardiovascular system, skeletal muscles and the central nervous system.

Effect on inflammatory and immune processes:
The anti-inflammatory, immunosuppressive and anti-allergic properties of glucocorticoids are responsible for a very substantial part of their therapeutic applications. The main aspects of these properties are: reduction in the number of immuno-active cells at the inflammatory site, reduced vasodilation, stabilization of lysosomal membranes, inhibition of phagocytosis, reduced production of prostaglandins and related substances.

The anti-inflammatory activity is about 25 times greater than that of hydrocortisone, and 8 to 10 times greater than that of prednisolone (on a weight basis).
Effect on the metabolism of carbohydrates and proteins:
Glucocorticoids stimulate protein catabolism. In the liver, the released amino acids are converted into glucose and glycogen by the process of gluconeogenesis. Glucose uptake in peripheral tissues decreases, which leads to hyperglycemia and glucosuria, especially in patients with a diabetic predisposition.

Effect on lipid metabolism:
Glucocorticoids have lipolytic activity. This lipolysis is more pronounced in the limbs. Glucocorticoids also have a lipogenic effect that occurs mainly in the trunk, neck and head. As a whole, these effects lead to a redistribution of fat deposits.

The maximum pharmacological activity of corticosteroids appears later than the peak serum levels, suggesting that most effects of these medications are not based on direct activity of the medicinal product, but on the modification of enzyme activity.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

Betamethasone sodium phosphate and betamethasone dipropionate are resorbed from the injection site and induce therapeutic effects and other pharmacological effects, both locally and systemically.

Betamethasone sodium phosphate is highly soluble in water and is metabolized in the body into betamethasone, the biologically active steroid. 2.63 mg of betamethasone sodium phosphate is equivalent to 2 mg of betamethasone.

Prolonged activity is obtained using betamethasone dipropionate. This practically insoluble product constitutes a deposit, so that it is less rapidly resorbed and relieves symptoms longer.

Blood levels                        Intramuscular injection
Betamethasone natrii phosphas                      Dipropionas
Maximum plasma concentration        1 hour after administration          Slow absorption 
Plasma half-life after a single     from 3 to 5 hours                    Progressive metabolism dose

Excretion                           24 hours                             More than 10 days 
Biological half-life                36 to 54 hours

Betamethasone is metabolized in the liver. Betamethasone binds primarily to albumin. In patients with a liver disorder, its clearance is slower or delayed.