Pharmacology: Phamacodynamics: Mode or Mechanisms of Action: Hydrocortisone is the principal glucocorticosteroid synthesised by the adrenal cortex in man. Its mineralocorticoid action is weak (0.1% of aldosterone).
Corticosteroids: Diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA, and stimulate transcription of messenger RNA (mRNA) and subsequent protein synthesis of various enzymes thought to be ultimately responsible for two categories of effects of systemic corticosteroids. However, these agents may suppress transcription of mRNA in some cells (e.g. lymphocytes).
Anti-inflammatory (steroidal): Glucocorticoids decrease or prevent tissue responses to inflammatory processes, thereby reducing development of symptoms of inflammation without affecting the underlying cause. Glucocorticoids inhibit accumulation of inflammatory cells, including macrophages and leukocytes, at sites of inflammation. They also inhibit phagocytosis, lysosomal enzyme release, and synthesis and/or release of several chemical mediators of inflammation. Immunosuppressant actions may also contribute significantly to the anti- inflammatory effect.
lmmunosuppressant: May involve prevention or suppression of cell-mediated (delayed hypersensitivity) immune reactions as well as more specific actions affecting the immune response. Glucocorticoids reduce the concentration of thymus-dependent lymphocytes (T-lymphocytes), monocytes, and eosinophils. They also decrease binding of immunoglobulin to cell surface receptors and inhibit the synthesis and/or release of interleukins, thereby decreasing T-lymphocyte blastogenesis and reducing expansion of the primary immune response. Glucocorticoids may also decrease passage of immune complexes through basement membranes and decrease concentrations of complement components and immunoglobulins.
Other actions/effects: Pharmacologic (supra-physiologic) doses of erogenous corticosteroids produce hypothalamic-pituitary-adrenal (HPA) axis suppression via a negative feedback mechanism, i.e., they inhibit pituitary ACTH secretion, thereby reducing ACTH-mediated production of corticosteroids and androgens in the adrenal cortex.
Glucorticoids also: Stimulate protein catabolism and induce enzymes responsible for metabolism of amino acids; Increase glucose availability by inducing hepatic enzymes involved in gluconeogenesis, stimulating protein catabolism and decreasing peripheral utilization of glucose; Increase lipolysis and mobilize fatty acids from adipose tissues, leading to increased plasma fatty acid concentrations; Decrease bone formation and increase bone resorption.
Pharmacokinetics: Absorption: Rapidly absorbed.
Time to peak concentration: About one hour.
Bio-transformation: Primarily hepatic (slow and rather limited); also renal and tissue; mostly to inactive metabolites.
Duration of action: Depends upon the solubility of the dosage form as well as the biological (tissue) half-life (about 190 minutes).
Protein binding: >90% bound to plasma proteins.
Elimination: Renal mainly as inactive metabolites.