fluticasone

Fluticasone is a potent glucocorticoid receptor agonist that diffuses into cells, binds cytoplasmic glucocorticoid receptors, and translocates to the nucleus to modulate gene transcription. It upregulates anti-inflammatory proteins (e.g., lipocortin-1/annexin A1, which inhibits phospholipase A2) and downregulates pro-inflammatory cytokines (IL-4, IL-5, IL-13), COX-2, and adhesion molecules, thereby decreasing eosinophilic and mast cell-mediated airway inflammation. Clinically, inhaled fluticasone (e.g., Flovent, or combined with salmeterol as Advair, or with vilanterol as Breo) is a cornerstone of asthma step-therapy per GINA/NAEPP guidelines and is also used in COPD to reduce exacerbation frequency in patients with frequent exacerbations or eosinophilia. Intranasal fluticasone (Flonase) is first-line for allergic rhinitis, reducing sneezing, congestion, and rhinorrhea. Topical fluticasone treats eczema and other inflammatic dermatoses. Because of high first-pass metabolism and low systemic bioavailability, inhaled/intranasal fluticasone has fewer systemic side effects than oral steroids, though local adverse effects include oral candidiasis (thrush)-mitigated by rinsing mouth after use-dysphonia, and epistaxis (nasal form). High-dose or long-term use can still cause HPA axis suppression, growth suppression in children, cataracts, and osteoporosis. It does not provide immediate bronchodilation and should not be used for acute asthma exacerbations; it is a controller, not a rescue medication. Important boards points: know the mechanism (glucocorticoid receptor, gene transcription modulation), the distinction between ICS (controller) vs SABA (reliever), and step-up therapy for asthma control (ICS first-line for persistent asthma, combined with LABA for moderate-severe disease).