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.

pharmacology

As a glucocorticoid agent, cortisone acetate changes genetic transcription levels causing varied metabolic effects and a modified immune response to varied stimuli. lucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.

mechanism of action

Cortisone acetate 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.

toxicity

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

route of elimination

Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

drug interactions

Acetylsalicylic acid: The corticosteroid, cortisone acetate, may decrease the effect of the salicylate, acetylsalicylic acid.

Fosphenytoin: The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, cortisone acetate.

Midodrine: Increased arterial pressure

Phenobarbital: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, cortisone acetate.

Phenytoin: The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, cortisone acetate.

Primidone: The barbiturate, primidone, may decrease the effect of the corticosteroid, cortisone acetate.

Pyridostigmine: The corticosteroid, cortisone acetate, may decrease the effect of the anticholinesterase, pyridostigmine.

Rifampin: The enzyme inducer, rifampin, may decrease the effect of the corticosteroid, cortisone acetate.

Tacrine: Tacrine and Cortisone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Vecuronium: Vecuronium may increase the adverse neuromuscular effects of systemic corticosteroids, such as Cortisone. Monitor for increased muscle weakness and signs of polyneuropathies and myopathy.