Glucocorticoids

Glucocorticoids are a class of corticosteroids that include the endogenous hormone cortisol and a range of synthetic analogs used as medications. They act by binding to the glucocorticoid receptor, a transcription factor that modulates gene expression in many tissues, leading to metabolic effects and widespread anti-inflammatory and immunosuppressive actions.

The anti-inflammatory effects arise from suppression of proinflammatory genes and mediators, including cytokines, adhesion molecules, and enzymes such as COX-2 and inducible nitric oxide synthase. Glucocorticoids also induce anti-inflammatory proteins and inhibit phospholipase A2, reducing prostaglandin and leukotriene synthesis. They influence leukocyte distribution and function, decreasing immune responses. Metabolic effects include increased gluconeogenesis, protein catabolism, lipolysis, and redistribution of body fat, contributing to potential long-term adverse effects with systemic exposure.

Pharmacologically, glucocorticoids can be administered orally, topically, by inhalation, or via local injections. They vary in potency and duration of action: short-acting examples include hydrocortisone; intermediate-acting include prednisone and prednisolone; long-acting include dexamethasone and betamethasone. They are widely metabolized in the liver and excreted renally; many are highly lipophilic and bind to plasma proteins. Drug effects depend on dose, duration, and route of administration, with higher systemic exposure carrying greater risk of adverse outcomes.

Therapeutically, glucocorticoids are used for autoimmune and inflammatory diseases (such as rheumatoid arthritis, lupus, inflammatory bowel disease), allergic and dermatologic conditions, respiratory diseases (asthma, COPD), and organ transplantation. Inhaled or topical forms provide targeted therapy with lower systemic exposure. Long-term use requires careful tapering to minimize withdrawal and HPA axis suppression. Common adverse effects include hyperglycemia, osteoporosis, infection risk, hypertension, mood changes, cataracts, and growth retardation in children.