Prednisolone (Prednisolonum)

It has anti-allergic, anti-inflammatory, immunosuppressive and anti-shock effects.

Interaction with intracellular glucocorticoid receptors leads to the formation of dimers of the glucocorticoid-glucocorticoid receptor complex.

The steroid hormone complex with the receptor is transported to the nucleus of the cell.In the nucleus this complex interacts with effector elements localized on the acceptor sites of the chromatin (genes). As a result of the interaction, stimulation or inhibition of gene expression occurs; this leads to a change in the synthesis of matrix RNA and proteins.

The anti-inflammatory effect of prednisolone is due to several factors.

1. The drug induces the synthesis of lipocortin, which inhibits the activity of phospholipase A2. Inhibition of phospholipase-mediated A2 hydrolysis of membrane phospholipids of damaged tissues prevents the formation of arachidonic acid. The disruption of the formation of arachidonic acid actually means inhibition of the synthesis of prostaglandins, since arachidonic acid is a substrate for further metabolism along the cyclooxygenase pathway, and also along the lipoxygenase pathway, with appropriate inhibition of leukotriene synthesis.

2. The anti-inflammatory effect of glucocorticoids is potentiated by their ability to inhibit the expression of COX-2 genes, which also leads to a decrease in the synthesis of prostaglandins in the inflammatory focus, including pro-inflammatory prostaglandins E₂ and I₂.

3. Prednisolone inhibits the expression of molecules of intercellular adhesion in the endothelium of blood vessels, violating the penetration of neutrophils and monocytes into the focus of inflammation. After the introduction of glucocorticoids, an increase in the concentration of neutrophils in the blood (due to their entry from the bone marrow and the restriction of migration from the blood vessels) is noted. This causes a decrease in the number of neutrophils in the site of inflammation.

Glucocorticoids inhibit the transcription of cytokine genes that stimulate the inflammatory and immune response (IL-1, IL-2, IL-6, IL-8), as well as tumor necrosis factor (and some others). Also, a decrease in the transcription rate and an increase in the degradation of the receptor genes for IL-1 and IL-2, inhibition of transcription of the metalloproteinase (collagenase, elastase, etc.) genes involved in the increase permeability of the vascular wall, in the processes of scarring and destruction of cartilaginous tissue in diseases of the joints.

Immunosuppressive action is due to inhibition of transcription of DNA encoding the main histocompatibility complex, pro-inflammatory cytokines and inhibition of proliferation of T lymphocytes. It leads to a decrease in the number of T-lymphocytes and their influence on B-lymphocytes, inhibits the production of immunoglobulins.Reduces formation and increases the breakdown of the components of the compliment system.

The antiallergic effect is associated with the inhibition of the synthesis of mediators of allergy, degranulation of mast cells and release of mediators of allergy, in connection with what it is effective for allergic reactions of immediate type.

Restores the sensitivity of adrenoreceptors to catecholamines. Accelerates the breakdown of proteins and reduces their concentration in the plasma, inhibits the utilization of glucose by peripheral tissues and stimulates gluconeogenesis in the liver, potentiates the formation of enzyme proteins in the liver, erythropoietin, fibrinogen, surfactant, lipomodulin. It leads to the redistribution of fat, increases the formation of triglycerides and higher fatty acids. Reduces absorption and potentiates the excretion of calcium; delays sodium and water.

The mechanism of the antishock effect of prednisolone is associated with a decrease in the synthesis of the platelet activating factor (a shock mediator), as well as a decrease in extra-neuronal capture and an increase in the pressor effect of catecholamines.