Singapore Drugs Database

Indication

For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease.

Mechanism of Action

Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.

Pharmacokinetics

Absorption

Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption.

Distribution

Metabolism

Primarily hepatic via CYP3A4

Elimination

Toxicity

Side effects include inhibition of bone formation, suppression of calcium absorption and delayed wound healing

Active Ingredient/Synonyms

(11alpha,14beta)-11,17,21-trihydroxypregn-4-ene-3,20-dione | (11beta)-11,17,21-Trihydroxypregn-4-ene-3,20-dione | 11beta-hydrocortisone | 11beta,17alpha,21-Trihydroxy-4-pregnene-3,20-dione | 11β-hydrocortisone | 17-Hydroxycorticosterone | 4-Pregnen-11beta,17alpha,21-triol-3,20-dione | Cortisol | Hidrocortisona | Hydrocortisone | Hydrocortisonum | Kendall's compound F | Reichstein's substance M | Hydrocortisone |