Glucocorticoid Pulse Therapy Research Articles

Pulse glucocorticoid therapy. The 'big shot' revisited

Pulse glucocorticoid therapy. The 'big shot' revisited

Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates.

Glucocorticoids are pleiotropic hormones that at pharmacologic doses prevent or suppress inflammation and other immunologically mediated processes. At the molecular level, glucocorticoids form complexes with specific receptors that migrate to the nucleus where they interact with selective regulatory sites within DNA; this results in positive and negative modulation of several genes involved in inflammatory and immune responses. At the cellular level, glucocorticoids inhibit the access of leukocytes to inflammatory sites; interfere with the functions of leukocytes, endothelial cells, and fibroblasts; and suppress the production and the effects of humoral factors involved in the inflammatory response. Clinically, several modes of glucocorticoid administration are used, depending on the disease process, the organ involved, and the extent of involvement. High doses of daily glucocorticoids are usually required in patients with severe diseases involving major organs, whereas alternate-day regimens may be used in patients with less aggressive diseases. Intravenous glucocorticoids (pulse therapy) are frequently used to initiate therapy in patients with rapidly progressive, immunologically mediated diseases. The benefits of glucocorticoid therapy can easily be offset by severe side effects; even with the greatest care, side effects may occur. Moreover, for certain complications (for example, infection diathesis, peptic ulcer, osteoporosis, avascular necrosis, and atherosclerosis), other drug toxicities and pathogenic factors overlap with glucocorticoid effects. Minimizing the incidence and severity of glucocorticoid-related side effects requires carefully decreasing the dose; using adjunctive disease-modifying immunosuppressive and anti-inflammatory agents; and taking general preventive measures.

Classification of Eye Changes of Graves' Disease

Classification of Eye Changes of Graves' Disease

Nonspecific action of glucocorticosteroids after high-dose pulse therapy?

The original view of glucocorticoid effects as being divided into physiological and pharmacological ones is no longer acceptable, i.e. all glucocorticoid effects are apparently mediated by receptor occupation which triggers RNA protein synthesis. The concentrations needed for receptor-mediated effects are low, e.g. the KD value for dexamethasone is in the nanomolar range. The high-dose pulse glucocorticoid therapy results in blood concentrations much higher than those necessary for receptor saturation. This makes sense only when nonspecific effects may be expected to occur which necessitate concentrations higher than 10(-6) mol.l-1. In this paper the question of nonspecific glucocorticoid effects in adjuvant arthritis and carrageenin paw edema of rats was investigated using the glucocorticoid receptor antagonist RU 38486 and by injecting the RNA/protein synthesis inhibitors actinomycin D or cycloheximide. We did not find convincing evidence for nonspecific glucocorticoid mechanisms.