Mast Cell Stabilizers

Intro & MOA - The Calm Keepers

• Prophylactic anti-inflammatory agents; prevent/reduce allergic reaction severity.
• Target mast cells, key in Type I hypersensitivity reactions.
• Not bronchodilators; ineffective for acute asthma attacks/anaphylaxis.
• Mechanism of Action (MOA):
  • Stabilize mast cell membranes, preventing degranulation upon allergen exposure.
  • Inhibit release of inflammatory mediators:
    • Histamine
    • Leukotrienes (e.g., LTC₄, LTD₄)
    • Prostaglandins (e.g., PGD₂)
    • Cytokines
  • Modulate delayed chloride ($Cl^−$) channels in the cell membrane, reducing $Ca^{2+}$ influx essential for exocytosis.
  • 📌 Mnemonic: "Keep the CALM": Chloride channel ALteration Mast cell stabilization.

⭐ Cromolyn sodium & Nedocromil are classic examples; primarily used for prophylaxis of mild persistent asthma, especially exercise-induced or allergen-induced asthma in children, and allergic rhinitis/conjunctivitis.

Pharmacokinetics - Journey of Stabilizers

• Absorption (A):
  • Oral: Very poor (<1%); not for systemic use.
  • Inhalation: Main route for local lung effect. Small systemic absorption.
  • Topical: Nasal/ophthalmic for local action.
• Distribution (D):
  • Acts locally (airways, nose, eyes). Minimal systemic distribution.
• Metabolism (M):
  • Not metabolized; excreted unchanged.
• Excretion (E):
  • Absorbed fraction: Urine and bile (equal).
  • Unabsorbed oral: Feces.
  • Half-life (Cromolyn): ~80-90 min.

⭐ Low systemic absorption (~8-10%) via inhalation is key, minimizing systemic adverse effects.

Key Drugs & Uses - Stabilizer Superstars

• Cromolyn Sodium (Disodium Cromoglycate)
  • Mechanism: Stabilizes mast cell membranes, preventing degranulation and release of inflammatory mediators (histamine, leukotrienes).
  • Uses:
    • Prophylaxis of bronchial asthma (allergic, exercise-induced, irritant-induced). Not for acute bronchospasm.
    • Allergic rhinitis (nasal solution).
    • Allergic conjunctivitis (ophthalmic solution).
    • Food allergy (oral, for GI symptoms).
    • Systemic mastocytosis.
  • Dosage Forms: Metered-dose inhaler (MDI), nebulizer solution, nasal spray, eye drops (2-4%), oral capsules.
  • 📌 Mnemonic: "Cromolyn keeps mast cells from cryin' (degranulating)".
• Nedocromil Sodium
  • Mechanism: Similar to cromolyn, inhibits mast cell degranulation and release of mediators. May also inhibit other inflammatory cells.
  • Uses:
    • Prophylaxis of mild to moderate asthma.
    • Allergic conjunctivitis (ophthalmic solution).
  • Dosage Forms: MDI, eye drops.
• Ketotifen
  • Mechanism: Mast cell stabilizer with potent H1-antihistaminic activity.
  • Uses:
    • Long-term prophylaxis of asthma (oral).
    • Allergic rhinitis (oral, nasal spray).
    • Allergic conjunctivitis (ophthalmic solution 0.025%).
  • Dosage Forms: Tablets, syrup, eye drops, nasal spray.

⭐ Ketotifen is unique as it combines mast cell stabilizing properties with significant H1-receptor antagonism, making it particularly useful for allergic conditions with prominent itching or sneezing.

Side Effects & Cautions - Stabilizer Setbacks

• General: Usually mild & transient.
• Inhaled (Cromolyn, Nedocromil):
  • Common: Throat irritation, cough, bronchospasm (paradoxical).
  • Nedocromil: Unpleasant taste.
  • Headache.
• Oral (Ketotifen):
  • Sedation (H1-blocking effect). 📌 K for Knockout.
  • Increased appetite, weight gain, dry mouth.
• Ocular Preparations: Local irritation, stinging.
• Serious (Rare):
  • Hypersensitivity reactions (e.g., anaphylaxis).
  • Cromolyn: Eosinophilic pneumonia, laryngeal edema.
• Cautions & Contraindications:
  • Known hypersensitivity.
  • ⚠️ Acute asthma/bronchospasm: Ineffective; for prophylaxis ONLY.
  • Ketotifen: Caution with tasks requiring alertness (driving).
  • Abrupt withdrawal may precipitate symptoms.

⭐ Mast cell stabilizers are primarily prophylactic; they do not provide immediate relief in an acute asthma attack.

High‑Yield Points - ⚡ Biggest Takeaways

• Mechanism: Inhibit mast cell degranulation, preventing histamine/leukotriene release.
• Key Drugs: Cromolyn sodium, Nedocromil; Ketotifen (also H1 blocker).
• Primary Use: Prophylaxis of allergic asthma (esp. exercise-induced) & allergic rhinitis.
• Not for Acute Attacks: For long-term prevention, not acute relief.
• Administration: Mainly inhalation; Ketotifen also oral/ophthalmic.
• Safety: Excellent safety profile, minimal side effects; safe in children.
• Onset: Slow; benefits in 2-4 weeks with regular use.