Diprosone Mechanism of Action

Pharmacology: Topical corticosteroids, such as betamethasone dipropionate, are effective in the treatment of corticosteroid-responsive dermatoses primarily because of their anti-inflammatory, anti-pruritic and vasoconstrictive actions. While the physiologic, pharmacologic, and clinical effects of the corticosteroids are well known, the exact mechanisms of their actions in each disease are uncertain. However, corticosteroids are thought to act by the induction of phospholipase A₂ inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation, such as prostaglandins and leukotrienes, by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A. The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.
While topical corticosteroids can be absorbed from normal intact skin, dermal inflammation and/or other dermatologic disease processes may increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids.
After dermal absorption, topical corticosteroids enter pharmacokinetic pathways similar to those of systemically administered corticosteroids. In varying degrees, corticosteroids are bound to plasma proteins. They are metabolized primarily in the liver and excreted by the kidneys. Some topical corticosteroids and their metabolites undergo biliary excretion.
Toxicology: Preclinical Information: Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term animal studies have not been performed to evaluate the carcinogenic potential of betamethasone dipropionate or the effect of fertility of topically applied corticosteroids.
Betamethasone dipropionate was negative in the bacterial mutagenicity assay (Salmonella typhimurium and Escherichia coli), and in the mammalian cell mutagenicity assay (CHO/HGPRT). It was positive in the in vitro human lymphocyte chromosome aberration assay, and equivocal in the in vivo mouse bone marrow micronucleus assay. This pattern of response is similar to that of dexamethasone and hydrocortisone.
Betamethasone dipropionate has been shown to be fetotoxic (increased incidence of resorptions) and teratogenic in rabbits when given by the intramuscular route at doses of 0.015 and 0.05 mg/kg. The abnormalities observed included umbilical hernias (0.015 and 0.05 mg/kg), cephalocele and cleft palate (0.05 mg/kg); an increased incidence of resorptions also was observed at both levels.
Other corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels, and some corticosteroids have been shown to be teratogenic after dermal application.