Glucocorticoids as Anti-inflammatory Agents

MOA & Basics - Inflammation Busters

• Synthetic analogs of endogenous cortisol; potent anti-inflammatory & immunosuppressive.
• Primary MOA (Genomic):
  • Bind cytosolic Glucocorticoid Receptors (GR).
  • GC-GR complex translocates to nucleus.
  • Modulates gene expression:
    • ↑ Synthesis of anti-inflammatory proteins (e.g., Lipocortin-1/Annexin A1, $I\kappa B\alpha$).
    • ↓ Synthesis of pro-inflammatory proteins (cytokines, chemokines, $COX_2$, $PLA_2$).
• Net effect: ↓ Leukocyte migration, adhesion, phagocytosis; ↓ Mast cell degranulation.

⭐ Glucocorticoids upregulate Annexin A1 (Lipocortin-1), which inhibits Phospholipase A2, thereby blocking arachidonic acid release and subsequent eicosanoid synthesis.

Classification & PK - Steroid Spectrum

• Duration of Action (DOA):
  • Short (8-12h): Hydrocortisone, Cortisone
  • Intermediate (12-36h): Prednisolone, Triamcinolone, Methylprednisolone
  • Long (36-72h): Dexamethasone, Betamethasone
• Potency (AI / MC):
  • Hydrocortisone: AI 1, MC 1 (Ref)
  • Prednisolone: AI 4, MC 0.8
  • Triamcinolone: AI 5, MC 0
  • Dexamethasone: AI 25-30, MC 0
  • Betamethasone: AI 25-30, MC 0
• Pharmacokinetics (PK):
  • Absorption: Oral, IV, IM, topical.
  • Metabolism: Hepatic. Prodrugs: Cortisone→Hydrocortisone, Prednisone→Prednisolone.
  • Excretion: Renal. High protein binding. Cross placenta.

⭐ Dexamethasone & Betamethasone: potent AI, negligible MC effect; preferred in cerebral edema.

Anti-inflammatory Uses - Clinical Toolkit

• Rheumatic Disorders: Rheumatoid arthritis, SLE, vasculitis, polymyalgia rheumatica, acute gout.
• Allergic States: Severe asthma, anaphylaxis, angioedema, drug hypersensitivity reactions.
• Respiratory Diseases: COPD exacerbations, sarcoidosis, aspiration pneumonitis.
• Gastrointestinal: Inflammatory bowel disease (Crohn's, UC).
• Renal Disorders: Nephrotic syndrome (esp. minimal change disease).
• Dermatological: Pemphigus vulgaris, severe contact dermatitis, exfoliative dermatitis.
• Ophthalmic: Uveitis, optic neuritis, allergic conjunctivitis.
• Neurological: Cerebral edema (vasogenic), multiple sclerosis acute flares.
• Organ Transplantation: Immunosuppression to prevent graft rejection.
• Hematological: Autoimmune hemolytic anemia (AIHA), idiopathic thrombocytopenic purpura (ITP).

⭐ In bronchial asthma, inhaled corticosteroids (ICS) are cornerstone long-term controllers; systemic steroids for acute severe exacerbations.

Adverse Effects - Steroid Perils

Many effects are dose & duration-dependent:

• Metabolic: Hyperglycemia, weight gain (central obesity), Cushingoid features (moon facies, buffalo hump), osteoporosis, dyslipidemia.
• CNS: Mood swings (euphoria, psychosis), insomnia.
• GI: Peptic ulcer, GI bleeding.
• CV: Hypertension, fluid retention, hypokalemia.
• Immune: Immunosuppression (↑ infections, latent TB reactivation), impaired wound healing.
• MSK: Myopathy (proximal), aseptic necrosis (femoral head).
• Ocular: Posterior subcapsular cataracts, glaucoma.
• Skin: Thinning, striae, acne, hirsutism.
• Endocrine: HPA axis suppression (tapering vital!), growth retardation (children).

⭐ Aseptic necrosis of the femoral head is a serious, often irreversible, complication of chronic steroid therapy.

Clinical Guidelines - Smart Steroids

• Routes: Oral, IV, IM, topical, intra-articular.
• Dosing: Lowest effective dose, shortest duration. Alternate-day therapy (ADT) for long-term use (↓ side effects).
• Interactions: Enzyme inducers (e.g., rifampicin) ↓ efficacy. NSAIDs ↑ GI bleed risk.
• Withdrawal: Taper gradually if used > 2-3 weeks to prevent adrenal insufficiency.

⭐ HPA axis suppression necessitates gradual tapering after prolonged use to prevent adrenal crisis.

High‑Yield Points - ⚡ Biggest Takeaways

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