Pharmacort Mechanism of Action

Pharmacology: Pharmacodynamics: Hydrocortisone sodium succinate has the same metabolic and anti-inflammatory actions as hydrocortisone. When given parenterally and in equimolar quantities, the two compounds are equivalent in biologic activity.
Hydrocortisone is the principal glucocorticoid synthesized by the adrenal cortex in man. It influences carbohydrate, protein and lipid metabolism: In physiologic doses, its mineralocorticoid action is weak. Hydrocortisone's main therapeutic actions are its anti­-inflammatory and immunosuppressive effects. It inhibits the inflammatory response whatever the inciting agent, which is thought to be mediated by reduction in the formation of various vasoactive chemicals released during inflammation such as kinins, histamine, lyosomal enzymes, eicosanoids, and the complement system. Hydrocortisone inhibits the synthesis of prostaglandins through the synthesis of a family protein (lipocortin or macrocortin) that inhibits the activity of phospholipase A2. Lipocortin production also inhibits the synthesis of platelet activating factor. Hydrocortisone also modulates the immune response. The humoral response at therapeutic doses is inhibited only marginally. Cell mediated responses are not limited but their manifestations are prevented. These are affected by inhibition of macrophage production of tumor necrosis factor and IL-1, and response to IL-1, gamma­-interferon, migration inhibitory factor (MIF), and the T cell formation of IL-2.
Following intravenous administration demonstrable effects of hydrocortisone are evident within one hour and persist for a variable period.
Pharmacokinetics: Hydrocortisone sodium succinate is rapidly absorbed after parenteral administration.
After intramuscular injection. the absorption of the water soluble sodium succinate ester is rapid.
Hydrocortisone is extensively bound to plasma protein (90%) specifically, corticosteroid binding globulin (transcortin) and albumin.
Hydrocortisone is extensively metabolized in the liver and most body tissues to hydrogenated and degraded forms such as tetrahydrocortisone and tetrahydrocortisol. These are excreted in the urine, mainly conjugated as glucuronides, with a very small portion of unchanged hydrocortisone. Excretion of the administered dose is nearly complete within 12 hours. Hence, if constantly high blood levels are required, injection should be made every 4 to 6 hours. Negligible amounts are excreted in the bile; enterohepatic circulation does not occur. The metabolic clearance or hydrocortisone may be decreased in patients with hypothyroidism and increased in those with hyperthyroidism.