| Mechanism of action |
Fluocinolone Acetonide is a corticosteroid that 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. Cyclooxygenase (both COX-1 and COX-2) expression
is also suppressed, potentiating the effect. In another 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. Like
other glucocorticoid agents Fluocinolone acetonide acts as a
physiological antagonist to insulin by decreasing glycogenesis
(formation of glycogen). It also promotes the breakdown of lipids
(lipolysis), and proteins, leading to the mobilization of extrahepatic
amino acids and ketone bodies. This leads to increased circulating
glucose concentrations (in the blood). There is also decreased glycogen
formation in the liver. |
