Corticosteroids in Respiratory Disorders

MoA & Classification - Steroid Superpowers

• Mechanism of Action (MoA): Potent anti-inflammatory.
  • Genomic (slow): Bind cytosolic Glucocorticoid Receptors (GR) → complex to nucleus:
    • ↑ Lipocortin-1 (Annexin A1) → inhibits $PLA_2$ → ↓ PGs, LTs.
    • ↓ Pro-inflammatory genes ($NF-\kappa B$, AP-1 blocked).
  • Non-Genomic (rapid): Via membrane GRs.
• Types: Glucocorticoids (anti-inflammatory) vs. Mineralocorticoids (salt-retaining). Focus: Glucocorticoids.
• Classification (Glucocorticoids):
  • Systemic (Oral/IV):
    • Short (8-12h): Hydrocortisone.
    • Intermediate (12-36h): Prednisolone, Methylprednisolone.
    • Long (36-72h): Dexamethasone.
  • Inhaled (ICS): Beclomethasone, Budesonide, Fluticasone (local action, ↓ systemic SEs). 📌 Potency: Hydrocortisone (1) < Prednisolone (4) < Methylprednisolone (5) < Dexamethasone (25).

⭐ Corticosteroids upregulate $\beta_2$-adrenergic receptors, enhancing bronchodilator responsiveness.

Inhaled Corticosteroids (ICS) - Puff Power

• Common ICS: Beclomethasone, Budesonide, Fluticasone, Ciclesonide, Mometasone.
• Delivery Devices:
  • MDI: Adv: Portable. Disadv: Needs coordination. Spacer improves delivery, ↓ local S/E.
  • DPI: Adv: Breath-actuated. Disadv: Needs good inspiratory flow.
  • Nebulizers: Adv: For severe attacks/uncooperative patients. Disadv: Less portable.
• Pharmacokinetics:
  • High first-pass metabolism (e.g., Fluticasone, Budesonide) crucial for low systemic effects.
  • Ciclesonide: Prodrug activated in lungs, minimizing local and systemic side effects.
• Local Side Effects & Prevention:
  • Oropharyngeal candidiasis (thrush), dysphonia (hoarseness).
  • Prevention: Use spacer with MDI; rinse mouth thoroughly with water and spit after inhalation.

⭐ Ciclesonide is a prodrug activated in the lungs, minimizing local side effects like candidiasis.

Systemic Steroids: Indications - System Savers

Systemic corticosteroids (Oral - OCS; Intravenous - IVCS) are vital for managing acute and severe respiratory conditions.

• Core Indications (OCS/IVCS):

  • Acute Severe Asthma: Rapidly reduces airway inflammation and obstruction.
  • COPD Exacerbations: Shortens recovery time, improves FEV1 & PaO2, reduces relapse risk.
  • Chronic Severe Asthma (Refractory): For patients not controlled on high-dose ICS/LABA.
  • Sarcoidosis: Symptomatic pulmonary disease (e.g., Stage II/III with significant symptoms/lung function impairment).
  • Interstitial Lung Diseases (ILDs):
    • Cryptogenic Organizing Pneumonia (COP)
    • Nonspecific Interstitial Pneumonia (NSIP) (especially cellular variant)
  • ARDS (Acute Respiratory Distress Syndrome): Selected cases (e.g., early moderate-severe ARDS, COVID-19 related), benefits controversial, dose & timing critical.

• Dosing Principles & Examples:

  • "Burst" Therapy (Acute Exacerbations):
    • Prednisolone (Oral): 40-50 mg/day for 5-7 days (Asthma/COPD). No tapering needed for short courses.
  • Longer Courses (>2-3 weeks): Gradual tapering is essential to prevent adrenal insufficiency.
  • Route Selection:
    • Oral (PO): Prednisolone is preferred if patient can tolerate oral intake.
    • Intravenous (IV): Methylprednisolone (e.g., 60-128 mg/day in divided doses for severe asthma), Hydrocortisone (e.g., 100-200 mg IV stat then q6h for status asthmaticus). Use for severe cases or if unable to take orally.

⭐ For acute asthma exacerbations, oral corticosteroids are as effective as intravenous corticosteroids if the patient can tolerate oral intake and there are no concerns about absorption.

Flowchart: Steroid Use in Acute Asthma Exacerbation

Adverse Effects & Management - Steroid Alerts

Key Cautions:

• Active untreated infections (esp. TB, fungal), live vaccines (with high dose systemic), peptic ulcer disease, uncontrolled diabetes/hypertension.

Steroid Withdrawal Syndrome:

• Abrupt cessation: fatigue, myalgia, arthralgia, hypotension. Taper dose.

⭐ Alternate day therapy with short-acting oral corticosteroids like prednisolone can reduce HPA axis suppression in long-term use.

High‑Yield Points - ⚡ Biggest Takeaways

• Inhaled Corticosteroids (ICS) like Budesonide & Fluticasone are first-line for persistent asthma.
• Systemic corticosteroids (e.g., Prednisolone) manage acute asthma/COPD exacerbations.
• MOA: Broad anti-inflammatory effects, ↓ cytokines & eosinophils.
• ICS adverse effects: Oral thrush, dysphonia; mitigate with spacer & mouth rinsing.
• Systemic risks: Hyperglycemia, osteoporosis, HPA axis suppression, immunosuppression.
• Budesonide is the safest ICS during pregnancy.
• Also indicated for ABPA and pulmonary sarcoidosis.