Corticosteroids

Mechanism of Action - Gene-Switching Steroids

• Genomic Effects: Steroids modulate gene transcription, a process taking hours to days.
• Pathway: Lipophilic steroid crosses cell membrane → binds cytosolic glucocorticoid receptor (GR) → complex translocates to the nucleus.
• Gene Regulation: Steroid-GR complex binds Glucocorticoid Response Elements (GREs) on DNA.

• Transactivation (Upregulation): ↑ synthesis of anti-inflammatory proteins like Annexin A1 (Lipocortin-1), which inhibits Phospholipase A2.
• Transrepression (Downregulation): ↓ synthesis of pro-inflammatory proteins by inhibiting transcription factors (e.g., NF-κB, AP-1).

⭐ High-Yield: The cornerstone of the anti-inflammatory effect is inhibiting the NF-κB transcription factor. This broadly suppresses pro-inflammatory cytokines (e.g., IL-1, TNF-α), chemokines, and adhesion molecules.

Clinical Uses - The Inflammation Tamers

• Autoimmune & Inflammatory Disorders:
  • Rheumatoid arthritis, SLE, IBD (Crohn's, UC)
  • Vasculitides (e.g., Giant Cell Arteritis)
  • Multiple Sclerosis (acute flares)
  • Sarcoidosis
• Allergic Reactions:
  • Asthma (acute & chronic), Anaphylaxis (adjunct)
  • Allergic rhinitis, Urticaria, Atopic dermatitis
• Hematologic Malignancies:
  • Part of chemotherapy for leukemias & lymphomas (e.g., ALL, Hodgkin's)
• Other Major Uses:
  • Organ transplant rejection (prophylaxis & treatment)
  • Adrenal insufficiency (replacement therapy, e.g., Addison's disease)
  • Gout (acute attacks)
  • Cerebral edema (vasogenic, e.g., from tumors)

⭐ Used to promote fetal lung maturation in preterm labor (<34 weeks gestation). Betamethasone/Dexamethasone stimulates surfactant production, reducing the risk of Neonatal Respiratory Distress Syndrome (NRDS).

Adverse Effects - The Double-Edged Sword

Widespread, dose-dependent effects. 📌 Remember CUSHINGOID side effects.

• Endocrine & Metabolic:
  • Iatrogenic Cushing's syndrome (moon facies, central obesity, buffalo hump, purple striae).
  • Hyperglycemia/steroid-induced diabetes, weight gain, fluid retention (→ hypertension).
  • HPA axis suppression (requires slow tapering after >2-3 weeks of use).
• Musculoskeletal:
  • Osteoporosis from ↓ osteoblast activity and ↑ osteoclast activity → ↑ fracture risk.
  • Steroid-induced myopathy (proximal muscle weakness).
• Immunologic & GI:
  • Immunosuppression → ↑ infection risk (Candida), reactivation of latent TB.
  • Gastritis and peptic ulcer formation, especially with concurrent NSAID use.
• CNS & Ocular:
  • Insomnia, agitation, psychosis ('steroid psychosis').
  • Posterior subcapsular cataracts and ↑ intraocular pressure (glaucoma).

⭐ Avascular necrosis (osteonecrosis) of the femoral head is a severe, often irreversible complication. It can occur even with short courses and presents with insidious onset of hip pain.

Equivalency & Tapering - Switching & Stopping Safely

• Glucocorticoid Dose Equivalents:
  • Hydrocortisone 20 mg
  • Prednisone 5 mg
  • Methylprednisolone 4 mg
  • Dexamethasone 0.75 mg
• Tapering Goal: Prevent iatrogenic adrenal insufficiency by allowing HPA axis recovery. Abrupt cessation after prolonged use can be fatal.

⭐ HPA axis suppression risk ↑ significantly after >2-3 weeks of supraphysiologic doses, mandating a gradual taper.

High‑Yield Points - ⚡ Biggest Takeaways

• Corticosteroids inhibit NF-κB, blocking transcription of pro-inflammatory cytokines like IL-2.
• They broadly suppress both cell-mediated and humoral immunity, causing lymphopenia.
• A key effect is inducing apoptosis in T-cells and eosinophils.
• Paradoxically, they cause neutrophilia by preventing neutrophil adhesion to vessel walls.
• Chronic use leads to iatrogenic Cushing's syndrome and osteoporosis.
• Abrupt cessation can trigger acute adrenal insufficiency; always taper the dose.