In addition, all fetuses between 24 and 34 week gestation at risk of preterm delivery should be considered as candidates for antenatal treatment with GCs. Acute pharmacologic doses of GCs can be used in a small number of nonendocrine diseases, such as for patients suffering from acute traumatic spinal cord injury, with severe neurological deficits and bone pain even after surgery and critical illness-related cortisol insufficiency. They are also used for some diagnostic purposes, such as in establishing Cushing’s syndrome. SGCs administered as replacement therapy in primary or secondary adrenal insufficiency (AI), and as adrenal suppression therapy in glucocorticoid resistance and congenital adrenal hyperplasia.
Also GCs are used in renal, intestinal, liver, eye, and skin diseases and in the suppression of the host-vs.-graft or graft-vs.-host reactions following organ transplantation. GCs represent the standard therapy for reducing inflammation and immune activation in asthma, as well as allergic, rheumatoid, collagen, vascular, hematological, neurological disorders, and inflammatory bowel diseases. GCs are used in nearly all medical specialties for systemic therapies. The mechanisms of actions of GCs are shown in Figure 1. The half-lives of synthetic GCs are generally longer than that of cortisol, which is approximately 80 minutes. Exogenous GCs have the same metabolic processes as endogenous GCs. The kidney excretes 95% of the conjugated metabolites, and the remainder is lost in the gut. Binding of the GCs to this receptor creates a complex, which then translocates into the nucleus, where it can interact directly with specific DNA sequences (glucocorticoid-responsive elements ) and other transcription factors.
GCs perform most of their effects owing to specific, immanent distributed intracellular receptors.
Conversely synthetic GCs other than prednisolone either bind weakly to albumin or circulate as free steroids, because they have little or no affinity for CBG. The free form of the GCs can easily diffuse through the membrane and can bind with high affinity to intracytoplasmic glucocorticoid receptors. Approximately 90% of endogenous cortisol in serum is bound to proteins, primarily corticosteroid-binding globulin (CBG) and albumin. The delta-4,3-keto-11-beta,17-alpha,21-trihydroxyl configuration is required for glucocorticoid activity and is present in all natural and synthetic GCs. The main SGCs used in clinical practice together with their relative biological potencies and their plasma and biological half-lives are listed in Table 1. In addition to these, some variations increase SGCs’ water solubility for parenteral administration or decrease their water solubility to improve topical potency. Structural variations reduce the natural cross-reactivity of SGCs with the mineralocorticoid receptor (MR), eliminating the offending salt-retaining effect. These include gastrointestinal or parenteral absorption, plasma half-life, and metabolism in the liver, fat, or target tissues-and their abilities to interact with the glucocorticoid receptor and to modulate the transcription of glucocorticoid-responsive genes. These structural variations may affect the bioavailability of SGCs. The differences between pharmacologic effects of synthetic GCs (SGCs) result from structural variations of their basic steroid nucleus and its side groups. Since the successful use of hydrocortisone (cortisol), the principal glucocorticoid of the human adrenal cortex, in the suppression of the clinical manifestations of rheumatoid arthritis, many synthetic compounds with glucocorticoid activity have been manufactured and tested. The term “glucocorticoids” (GCs) represents both naturally secreted hormones by adrenal cortex and anti-inflammatory and immunosuppressive agents.