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Anti-inflammatory Respiratory Agents

Anti-inflammatory Respiratory Agents

Anti-inflammatory Respiratory Agents

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Corticosteroids - Steroid Power Puffs

Potent anti-inflammatory; cornerstone of asthma/COPD therapy.

  • MOA: Bind intracellular glucocorticoid receptors → modulate gene expression → ↓ inflammatory mediators (cytokines, PGs, LTs) & ↓ inflammatory cell activity.
  • Key Examples:
    • ICS (Inhaled): Beclomethasone, Budesonide, Fluticasone.
    • Systemic: Prednisolone, Hydrocortisone.
  • Major Indications:
    • Asthma: First-line controller for persistent disease.
    • COPD: Exacerbations, severe disease (often with LABA).
  • Side Effects & Pearls:
    • ICS: Oral candidiasis (thrush), dysphonia. 💡 Pearl: Use spacer; rinse mouth post-ICS to prevent.
    • Systemic (long-term): Cushingoid features, osteoporosis, hyperglycemia, PUD, immunosuppression. 📌 Mnemonic for systemic effects: CUSHINGOID (multiple features).

⭐ Inhaled corticosteroids (ICS) are the most effective long-term control therapy for persistent asthma. Factors affecting glucocorticoid sensitivity in asthmaoka

Leukotriene Modifiers - Leukotriene Block Party

Leukotriene synthesis pathway and drug targets

  • Overview: Target leukotrienes, key inflammatory mediators in asthma.
  • Classes & MOA:
    • Zileuton: 5-Lipoxygenase (5-LOX) inhibitor. Blocks synthesis of all leukotrienes.
      • Indication: Chronic asthma.
      • ⚠️ Side Effect: Hepatotoxicity (monitor LFTs).
    • Montelukast, Zafirlukast: Cysteinyl Leukotriene Receptor Antagonists (LTRAs). Block CysLT1 receptors. 📌 LUKasts block LeUKotriene receptors.
      • Indications: Add-on asthma therapy, Aspirin-Exacerbated Respiratory Disease (AERD), exercise-induced bronchoconstriction.
      • ⚠️ Side Effects: Montelukast: Neuropsychiatric events. Zafirlukast: Hepatotoxicity, Churg-Strauss (rare).

⭐ Montelukast is particularly useful in patients with aspirin-exacerbated respiratory disease (AERD) due to its effect on cysteinyl leukotrienes.

Mast Cell Stabilizers & Anti-IgE - Allergy Avengers

  • Mast Cell Stabilizers: Cromolyn, Nedocromil
    • MOA: Stabilize mast cells → ↓ degranulation & mediator release.
    • Use: Prophylaxis (mild asthma/allergic rhinitis). Not for acute attacks. Limited efficacy.
  • Anti-IgE Antibody: Omalizumab (📌 OMA binds IgE)
    • MOA: Monoclonal Ab; binds free IgE → prevents mast cell activation.
    • Indication: Severe allergic asthma (IgE 30-700 IU/mL), ≥6 yrs.
    • Route: Subcutaneous. ⚠️ Key SE: Anaphylaxis.
FeatureCromolynsOmalizumab
MOA Detail↓ Mediator release↓ IgE binding to mast cells
EfficacyLimitedEffective for severe IgE-mediated asthma
AdminInhalation/NasalSubcutaneous

⭐ Omalizumab is a monoclonal antibody that binds to free IgE, preventing its interaction with mast cells, and is used in severe, persistent allergic asthma.

PDE4 Inhibitors & Novel Agents - COPD's New Guard

  • Roflumilast (PDE4 Inhibitor):
    • MOA: $↑cAMP$ in inflammatory cells.
    • Indication: Severe COPD + chronic bronchitis & exacerbations.
    • Side Effects: GI distress, weight loss, mood changes (📌 Roflumilast: Mood, Intestinal, Loss of weight).
  • Novel Biologics (Anti-IL5 for Eosinophilic Asthma):
    • Mepolizumab, Reslizumab, Benralizumab.

⭐ Roflumilast: oral PDE4 inhibitor for severe COPD (chronic bronchitis, frequent exacerbations), reduces exacerbations.

High‑Yield Points - ⚡ Biggest Takeaways

  • Inhaled Corticosteroids (ICS) are first-line therapy for persistent asthma control.
  • Oropharyngeal candidiasis, dysphonia: key local ICS adverse effects; prevent with spacer use & mouth rinsing.
  • Systemic corticosteroids are vital for acute severe asthma exacerbations, reducing airway inflammation.
  • Montelukast (LTRA) is key for AERD and exercise-induced bronchoconstriction (EIB).
  • Mast cell stabilizers (e.g., Cromolyn) prevent mediator release, for asthma prophylaxis only.
  • Omalizumab (anti-IgE MAb) treats severe, persistent IgE-mediated allergic asthma.
  • Anti-IL-5 biologics (e.g., Mepolizumab) target eosinophils in severe eosinophilic asthma.

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_____ and Nedocromil prevent mast cell degranulation (used for asthma prophylaxis)

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_____ and Nedocromil prevent mast cell degranulation (used for asthma prophylaxis)

Cromolyn sodium

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