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Bronchial Asthma - Pharmacology Viva Rapid Revision

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1. Definition (Quick Opener)

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2. Pathophysiology (Know for Mechanism Questions)

• Early phase (0-30 min): Allergen activates mast cells via IgE → releases histamine, leukotrienes (LTC4, LTD4, LTE4), and prostaglandins → immediate bronchoconstriction
• Late phase (4-8 hrs): Eosinophil and T-lymphocyte infiltration → sustained inflammation, mucus, airway remodeling
• Key mediators: Histamine, LTs, PGD2, PAF, TNF-α, IL-4, IL-5, IL-13
• cAMP ↑ → bronchodilation; cGMP ↑ → bronchoconstriction

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3. Drug Classification

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4. Key Drug Mechanisms (Most Asked in Viva)

Beta-2 Agonists

• MOA: Bind β2 receptors on airway smooth muscle → activate adenylyl cyclase → ↑cAMP → bronchodilation. Also inhibit mast cell mediator release.
• SABA onset: 5 min; duration: 4-6 hrs
• SABA (Salbutamol): Drug of choice for acute attack; metered dose inhaler (MDI) preferred
• LABA (Salmeterol): Onset 15-30 min; duration 12 hrs. Long lipophilic side chain anchors it in membrane.
• Formoterol: LABA with fast onset (like SABA) - can be used for both relief and maintenance (SMART regimen with budesonide)
• SE: Tachycardia (β1), tremor, hypokalemia (K+ shift into cells), tolerance with overuse

Corticosteroids (ICS)

• MOA: Bind glucocorticoid receptor → nuclear translocation → inhibit transcription of inflammatory cytokines (IL-4, IL-5, IL-13, TNF-α). Reduce eosinophil and mast cell infiltration. Reduce bronchial hyperreactivity. Do NOT directly relax smooth muscle.
• ICS drugs: Beclomethasone, budesonide, fluticasone, mometasone, ciclesonide
• SE of ICS: Oral candidiasis, dysphonia (hoarseness) - prevented by rinsing mouth after use
• Systemic steroids (IV hydrocortisone, oral prednisolone): Used in severe acute attacks and status asthmaticus

Theophylline

• MOA: PDE inhibitor → prevents cAMP breakdown → bronchodilation. Also adenosine receptor antagonist (blocks adenosine-induced bronchoconstriction).
• Narrow therapeutic index: 10-20 mcg/mL (therapeutic); >20 mcg/mL toxic
• SE: Nausea/vomiting (early), arrhythmias, seizures (toxic levels)
• Drug interactions: Cimetidine, erythromycin, ciprofloxacin INCREASE levels (inhibit CYP1A2). Smoking, rifampicin DECREASE levels.
• Aminophylline: Water-soluble theophylline salt; given IV in acute severe asthma

Anticholinergics

• MOA: Block M3 muscarinic receptors on bronchial smooth muscle → inhibit acetylcholine-induced bronchoconstriction
• Ipratropium bromide (SAMA): Quaternary ammonium - poor systemic absorption, no CNS effects. Used as add-on in acute severe asthma (combined with salbutamol nebulization)
• Tiotropium (LAMA): 24-hr duration; now approved for asthma maintenance (add-on to ICS). Dissociates rapidly from M2 receptors (preserving ACh feedback inhibition).
• SE: Dry mouth, urinary retention (rare), worsening glaucoma if sprayed in eye

Leukotriene Modifiers

• Montelukast, zafirlukast: CysLT1 receptor blockers → block LTC4, LTD4, LTE4 effects
• Zileuton: 5-lipoxygenase inhibitor → blocks ALL leukotriene synthesis (including LTB4)
• Uses: Mild persistent asthma, aspirin-sensitive asthma (ASA exacerbates via 5-LOX shunting), exercise-induced asthma, allergic rhinitis with asthma
• Montelukast SE: Neuropsychiatric effects (nightmares, depression, suicidal ideation - black box warning)

Cromolyn Sodium / Nedocromil

• MOA: Stabilize mast cell membranes → prevent degranulation → no mediator release. Block Cl- channels. Also inhibit sensory nerve activation.
• Only prophylactic - no bronchodilator effect, useless in acute attack
• Best indication: Exercise-induced asthma (inhaled before exercise), allergen-induced asthma
• SE: Very safe; minor throat irritation

Omalizumab (Anti-IgE)

• MOA: Monoclonal antibody that binds free serum IgE → prevents IgE binding to mast cell FcεRI receptors → blocks allergic cascade
• Use: Moderate-to-severe allergic asthma not controlled by ICS+LABA
• Given: SC injection every 2-4 weeks
• SE: Injection site reactions; rare anaphylaxis (observe for 30-60 min after each dose)

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5. Stepwise Management (GINA-based)

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6. Status Asthmaticus Management

1. Oxygen - maintain SpO2 >94%
2. Nebulized salbutamol (2.5-5 mg) + ipratropium (0.5 mg) - repeat every 20 min x3
3. IV/oral corticosteroids - hydrocortisone 100-200 mg IV or prednisolone 40-60 mg oral
4. IV aminophylline - if no response (load 5 mg/kg over 20 min, then infusion)
5. IV magnesium sulfate (2 g IV) - bronchodilation via Ca2+ channel blockade
6. Heliox, intubation - in life-threatening cases

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7. High-Yield Viva Points

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8. Quick Mechanism Diagram (Memorize)

Allergen → IgE on mast cells → Mast cell activation
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Histamine, LTs, PGD2 → Bronchoconstriction + inflammation
       ↓
β2 agonists → ↑cAMP → Smooth muscle relaxation (RELIEF)
ICS → ↓Cytokines, ↓eosinophils (CONTROL)
Anticholinergics → Block M3 → ↓ACh bronchoconstriction
Montelukast → Block CysLT1 → ↓LT-mediated bronchoconstriction
Theophylline → ↓PDE → ↑cAMP → Bronchodilation

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