Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1. Pharmacodynamic properties
Dexamethasone Panpharma belongs to the H02AB02 therapeutic group.

Dexamethasone is a long-acting fluorinated corticosteroid with a high anti- inflammatory and immunosuppressive potency and a low mineralocorticoid activity.
Glucocorticoids cause profound and varied metabolic effects. They also modify immune response to different stimuli.

This medicine inhibits the synthesis of prostaglandins and leukotrienes, substances that mediate the vascular and cell processes involved in inflammation and immune response. They therefore reduce vasodilation and the fluid exudate typical of inflammatory processes, leukocyte activity, neutrophil aggregation and degranulation, the release of hydrolytic enzymes by lysosomes, etc. Both actions are due to the inhibition of the synthesis of phospholipase A2, the enzyme responsible for releasing the polyunsaturated fatty acids that are precursors of prostaglandins and leukotrienes.

Dexamethasone, like all glucocorticoids, binds to cytoplasmic glucocorticoid receptors and activates them. As a result, different neutral endopeptidases, plasminogen activator inhibitors, lipocortin, etc. are mobilised.

Glucocorticoids reduce the stability of certain RNA-messenger molecules, altering gene transcription. The genes affected by this action include the synthesis of collagenase, elastase, plasminogen activator, type II cyclooxygenase, cytokines and chemokines.

Other actions

Pharmacological doses of exogenous corticosteroids suppress the hypothalamic- pituitary- adrenal (HPA) axis through a negative feedback mechanism.

Glucocorticoids stimulate protein catabolism and induce the enzymes responsible for the metabolism of amino acids.

Glucocorticoids increase the availability of glucose for different actions that increase the hepatic reserves of glycogen, concentrations of blood glucose and insulin resistance.

Glucocorticoids increase lipolysis and mobilise fatty acids from adipose tissue, leading to an increase in fatty acid plasma concentrations. They also reduce bone formation and increase bone resorption.

Dexamethasone, the active substance of Dexamethasone Panpharma, is 30 times more potent than cortisone, 25 times more potent than hydrocortisone, 6 times more potent than prednisone and prednisolone and 5 times more potent than methylprednisolone and triamcinolone.

Pharmacokinetic Properties

5.2. Pharmacokinetic properties

Dexamethasone is a long-acting corticosteroid, since its effects are maintained for up to 72 hours, its total clearance ranges between 2.8 and 3.5 mg/minute/kg, its elimination half-life is 3-4 hours (limits of 3 to 6 hours for adults, 2.8-7.5 hours for 8-16 year olds and 2.3-9.5 hours for children less than 2 years old) and its biological half-life is 36-54 hours.

Following intramuscular administration, peak serum levels are reached within one hour, it is widely distributed in the organism with a degree of plasma protein binding of 70%, it crosses the placental and blood-milk barriers, the volume of distribution is 2 l/kg, it is metabolised in the liver (hydroxylation) and is eliminated in urine, 8% in unchanged form and to a lesser extent in bile.