budesonide

Budesonide is a synthetic glucocorticoid with potent local anti-inflammatory activity and relatively low systemic bioavailability due to extensive first-pass metabolism by CYP3A4 in the liver, making it a preferred corticosteroid when systemic steroid side effects need to be minimized. Mechanism: binds glucocorticoid receptors, translocates to the nucleus, and modulates gene transcription—upregulating anti-inflammatory proteins (e.g., lipocortin-1, which inhibits phospholipase A2) and downregulating pro-inflammatory cytokines, COX-2, and adhesion molecules. Clinical uses include: (1) Inhaled budesonide for persistent asthma (controller therapy) and COPD maintenance, often combined with a long-acting beta-agonist (e.g., budesonide-formoterol, used in SMART therapy for asthma); (2) Intranasal budesonide for allergic rhinitis; (3) Oral enteric/pH-release budesonide (Entocort) targeted to the ileum and proximal colon for mild-to-moderate Crohn's disease and microscopic (lymphocytic/collagenous) colitis; (4) Nebulized budesonide for croup. Adverse effects: local effects include oral candidiasis and dysphonia with inhaled use (reduced by rinsing mouth after use); systemic effects (adrenal suppression, growth suppression in children, osteoporosis) are less common than with systemic steroids but can occur especially with high doses or hepatic impairment (which reduces first-pass metabolism and increases systemic exposure). It does not significantly inhibit CYP3A4 interactions but its own metabolism can be affected by CYP3A4 inhibitors (e.g., ketoconazole), increasing systemic steroid effects. Boards often test budesonide's targeted-release oral formulation as first-line for mild-moderate ileocecal Crohn's disease due to fewer systemic steroid side effects compared to prednisone, and its role in asthma/COPD as an inhaled corticosteroid.