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,...