Mechanism of Action: How Steroids Block Inflammation
Glucocorticoids act at the genomic level. Upon entering the target cell, the hormone binds to an intracellular receptor in the cytoplasm. This complex then translocates to the nucleus, where it interacts with chromatin, stimulating or suppressing the synthesis of specific proteins.
The primary anti-inflammatory effect is mediated through the arachidonic acid pathway in a cascade:
- The drugs induce the synthesis of lipocortin proteins.
- Lipocortin inhibits the enzyme phospholipase A2.
- This halts the release of arachidonic acid from the phospholipids of damaged cell membranes.
- Deprived of this substrate, the synthesis of inflammatory mediators ceases across two pathways simultaneously: the cyclooxygenase pathway (decreasing prostaglandins) and the lipoxygenase pathway (decreasing leukotrienes).
Additionally, these hormones suppress the transcription of genes encoding proinflammatory cytokines (such as interleukins and tumor necrosis factor) and tissue-destroying enzymes (e.g., collagenases).
Main Pharmacological Effects
In clinical practice, these drugs are utilized for their potent extra-metabolic properties (pathogenetic therapy):
- Anti-inflammatory effect: Rapidly reduces pain, swelling, heat, and redness. They inhibit the expression of adhesion molecules on the vascular endothelium, preventing leukocytes from emigrating from blood vessels into the site of inflammation.
- Immunosuppressive and antiallergic effect: Suppresses tissue macrophage activity, reduces antibody production, and redistributes lymphocytes from the blood into lymphoid tissue.
- Antishock effect: Reduces the synthesis of platelet-activating factor and potentiates the vasoconstrictive effect of catecholamines (epinephrine), thereby maintaining blood pressure.
Clinical pearl: A complete blood count in a patient receiving glucocorticoids typically shows neutrophilic leukocytosis. Neutrophils are released from the bone marrow but are prevented from migrating into tissues, remaining in circulation within the vascular bed.
Classification of Drugs
Glucocorticoids are classified by origin, chemical structure, and route of administration. The addition of a fluorine atom to the chemical structure significantly enhances the anti-inflammatory potency while minimizing mineralocorticoid effects.
| Group | Characteristics | Representatives |
|---|---|---|
| Natural | Analogues of human hormones | Hydrocortisone (Hydrocortisone) |
| Synthetic (non-fluorinated) | More potent than natural, less fluid retention | Prednisolone, methylprednisolone |
| Synthetic (fluorinated) | Maximum activity, minimal sodium retention | Dexamethasone, triamcinolone |
| Topical | Ointments and creams for dermatology | Betamethasone, clobetasol |
| Inhaled | For pulmonology (asthma, COPD) | Budesonide, beclomethasone |
Side Effects of Long-Term Therapy
Prolonged use of high doses leads to iatrogenic Cushing's syndrome—a state of artificial hormone excess affecting all types of metabolism.
- Carbohydrate metabolism: Stimulation of gluconeogenesis and decreased glucose uptake by peripheral tissues lead to hyperglycemia and steroid-induced diabetes mellitus.
- Protein metabolism: Enhanced protein catabolism causes muscle atrophy and skin thinning.
- Lipid metabolism: Fat is redistributed in a dysplastic pattern. The face becomes rounded ("moon facies") and plethoric, fat accumulates on the trunk, and the extremities become thin. Purple abdominal striae appear.
- GI tract and bones: "Steroid" peptic ulcers can form (due to stimulation of hydrochloric acid secretion), osteoporosis develops, and bone growth is stunted in children.
- CNS: Direct excitatory effects can trigger steroid psychoses with mood swings ranging from euphoria to deep depression.