Overview
Clinical Meaning
Systemic glucocorticoids are among the most commonly prescribed medications, with profound anti inflammatory and immunosuppressive effects that make them invaluable across numer...
Systemic glucocorticoids are among the most commonly prescribed medications, with profound anti-inflammatory and immunosuppressive effects that make them invaluable across numerous conditions — but their extensive adverse effect profile requires careful prescribing. Mechanism: Glucocorticoids cross the cell membrane and bind cytoplasmic glucocorticoid receptors (GR), forming a GR-steroid complex that translocates to the nucleus. Genomic effects (hours to days): transactivation (inducing anti-inflammatory genes: lipocortin-1, IL-10, IκBα) and transrepression (suppressing pro-inflammatory genes: NF-κB and AP-1 pathways → reducing TNF-α, IL-1, IL-6, COX-2, iNOS, adhesion molecules). Non-genomic effects (seconds to minutes): membrane stabilization, rapid immunosuppression. Pharmacokinetic considerations: relative potency (hydrocortisone = 1, prednisone = 4, methylprednisolone = 5, dexamethasone = 25-30), half-life (short-acting: hydrocortisone 8-12 hrs; intermediate: prednisone/prednisolone 12-36 hrs; long-acting: dexamethasone 36-72 hrs), and mineralocorticoid activity (hydrocortisone has significant sodium retention; dexamethasone has none). HPA axis suppression: exogenous glucocorticoids suppress CRH and ACTH production via negative feedback. Doses equivalent to >7.5 mg prednisone daily for >3 weeks can suppress the HPA axis sufficiently that abrupt discontinuation causes adrenal crisis (hypotension, hypoglycemia, shock). Tapering is essential — the rate depends on dose, duration,...