---

📚 RESPIRATORY PHARMACOLOGY - EXAM NOTES

(Shanbhag Pharmacology)

---

PART 1: DRUGS USED IN TREATMENT OF COUGH

Classification of Antitussive Drugs:

---

Types of Cough:

• Productive cough - Do NOT suppress; use expectorants + mucolytics + antibiotics
• Non-productive (dry) cough - Should be suppressed (use antitussives)

---

ANTITUSSIVES (Individual Drugs):

• Acts on cough centre in medulla (suppressant)
• Causes mild CNS depression, drowsiness
• Causes constipation (decreases intestinal movements)
• Has mild analgesic effect
• Less addiction liability than morphine
• Avoid in children <1 year and asthmatics

• Similar to codeine but NO analgesic effect, NO addiction liability
• Long duration of action
• Orally administered

• Opium alkaloid
• No analgesic, no constipation, no CNS depression, no addiction
• Useful in spasmodic cough
• Side effects: nausea, headache, bronchospasm (avoid in asthmatics)

• Centrally acting antitussive
• No analgesic, no constipation, no addiction
• May cause sedation and hallucinations
• Has mucociliary function in respiratory passages

• Useful in cough with allergic conditions
• Antiallergic + anticholinergic actions

• Acts peripherally on stretch receptors of airways

---

PHARYNGEAL DEMULCENTS:

• Syrups, lozenges, liquorice
• Increase salivation, produce soothing/protective effect on inflamed mucosa
• Lozenge - dissolves slowly, soothes irritated mucosa (e.g., dyclonine)
• Linctus - viscous liquid sipped slowly (e.g., linctus codeine)

---

EXPECTORANTS (Mucokinetics):

• Increase volume of bronchial secretion, decrease viscosity
• Cough becomes less tiring and productive
• Include: iodides, chlorides, bicarbonates, acetates, volatile oils

---

MUCOLYTICS:

• Semisynthetic, orally used
• Potent mucolytic + mucokinetic
• Mechanism: Bromhexine → liberates lysosomal enzymes → digest mucopolysaccharides → decreases viscosity → cough becomes less tiring
• Side effects: rhinorrhoea, lacrimation

• Acetylcysteine used as aerosol
• Mechanism: open disulphide bonds in mucoproteins → sputum becomes thin and less viscid
• Side effects: nausea, vomiting, bronchospasm
• Carbocisteine - oral; avoid in peptic ulcer patients (gastric irritation)

---

PART 2: DRUGS USED IN BRONCHIAL ASTHMA

Pathophysiology (Quick Recap):

• Bronchospasm + mucosal oedema + increased mucus secretion
• Mediators: Histamine, 5-HT, PGs, Leukotrienes (LTC₄, LTD₄), Proteases, PAF

Types of Asthma:

• Acute asthma - episodic dyspnoea + expiratory wheeze
• Chronic asthma - continuous wheeze, breathlessness, mucoid sputum
• Status Asthmaticus - prolonged severe intractable wheeze

---

CLASSIFICATION OF ANTIASTHMATIC DRUGS: ⭐⭐

---

SYMPATHOMIMETICS - MECHANISM OF ACTION: ⭐⭐

Sympathomimetics → β₂ receptor stimulation → ↑cAMP →
   • Bronchodilation
   • Inhibit release of histamine, SRS-A (LTC₄, LTD₄) from mast cells
   • Promote mucociliary clearance

• Rapid onset: 1-5 minutes
• Short duration of action
• Preferred for acute attack of asthma
• Route: Inhalation (MDI) 100-200 mcg every 6 hours; also oral, i.m., i.v.

• Preferred for moderate to severe persistent asthma
• NOT suitable for acute attack (slow onset)
• Dose: Inhalation 50 mcg twice daily

• Rapid onset (unlike salmeterol)
• Preferred for moderate to severe persistent asthma
• Dose: Inhalation 12-24 mcg twice daily

• Prodrug of terbutaline
• Oral, once daily dose
• Long duration of action

• Useful in acute attack not responding to other drugs
• 0.2-0.5 mL of 1:1000 solution SC
• Use has declined due to cardiac side effects

---

METHYLXANTHINES: ⭐⭐

Theophylline/Aminophylline → Inhibit Phosphodiesterase (PDE) → ↑cAMP →
   • Bronchodilation
   • Inhibit histamine & SRS-A release from mast cells
   • Improve mucociliary clearance
   Also: competitive antagonism at adenosine receptors → bronchodilation

• Well absorbed orally and parenterally
• Food delays absorption of theophylline
• Cross placental and blood-brain barrier
• Metabolized in liver, excreted in urine

• Theophylline - poorly water soluble; only oral; NOT for injection
• Aminophylline - water soluble, highly irritant; oral or slow IV
• Etophylline - water soluble; oral, i.m., or i.v.
• Doxophylline - oral (once/twice daily); less GI and CNS side effects

• CNS: Restlessness, insomnia, headache, tremors, convulsions
• GI: Nausea, vomiting, gastritis, aggravation of peptic ulcer
• CVS: Tachycardia, palpitation, hypotension, sudden death due to cardiac arrhythmias
• Also causes diuresis
• Narrow therapeutic index

1. Sympathomimetics × Methylxanthines:
   • Bronchodilatation (beneficial)
   • Cardiac stimulation (harmful)
2. Phenytoin/Rifampicin/Phenobarbitone × Theophylline: enzyme inducers → decrease theophylline effect
3. Cimetidine/Ciprofloxacin/Erythromycin × Theophylline: enzyme inhibitors → potentiate theophylline toxicity

1. Bronchial asthma + COPD (theophylline as additional drug)
2. Apnoea in premature infants - Aminophylline/Caffeine IV (caffeine is safer)

---

ANTICHOLINERGICS: ⭐

• Ipratropium bromide, Tiotropium bromide (atropine substitutes)
• Block acetylcholine effects in bronchial smooth muscle → bronchodilation
• Do NOT affect mucociliary clearance
• Slow onset; less effective than sympathomimetics
• Preferred bronchodilators in COPD
• Act primarily on larger airways
• Tiotropium is longer acting, more efficacious than ipratropium
• Combined with β₂ agonists in acute severe asthma (greater and prolonged bronchodilation)

---

LEUKOTRIENE RECEPTOR ANTAGONISTS: ⭐

Montelukast/Zafirlukast → block cysteinyl LT-receptors ← Leukotrienes LTC₄ & LTD₄
→ Bronchodilation + suppress bronchial inflammation + decrease hyperreactivity

• Well absorbed orally; highly protein bound; metabolized in liver
• Prophylactic treatment of mild and moderate persistent asthma
• Well tolerated; side effects: headache, skin rashes, rarely eosinophilia

• Inhibits 5-lipoxygenase (orally)
• Hepatotoxicity restricts its use

---

MAST CELL STABILIZERS: ⭐⭐

• Stabilize mast cell membrane → inhibit release of histamine, SRS-A, PGs, LTs, PAF, etc.
• Reduce bronchial hyperreactivity
• NOT bronchodilators
• Onset of action is slow; AG:AB reaction is NOT affected

• Poorly absorbed orally → given by inhalation in bronchial asthma
• Uses:
  1. Prophylaxis of allergic asthma (prevent bronchospasm)
  2. Allergic conjunctivitis, allergic rhinitis, allergic dermatitis (topical)
• Side effects: local irritation - cough, bronchospasm, headache, nasal congestion

• Similar mechanism to sodium cromoglycate
• Has additional H₁-blocking effect
• Orally effective; slow onset of action

---

GLUCOCORTICOIDS: ⭐⭐

• Induce synthesis of 'lipocortin' → inhibits phospholipase A₂ → prevent formation of PGs, TXA₂, SRS-A
• Antiallergic + anti-inflammatory + immunosuppressant
• Actions:
  1. Suppress inflammatory response to AG:AB reaction
  2. Decrease mucosal oedema
  3. Reduce bronchial hyperreactivity
• Do NOT have direct bronchodilating effect
• Potentiate β₂-adrenergic agonists
• Prevent development of tolerance to β₂ agonists

• Used as prophylactic agents
• For persistent asthma requiring frequent β₂ agonists
• Ciclesonide is a prodrug (activated by esterases in bronchial epithelium)
• Side effects: hoarseness, dysphonia, oropharyngeal candidiasis
• Reduced by: spacer + rinsing mouth after each dose; oral thrush treated with nystatin/hamycin

• Fluticasone + Salmeterol
• Budesonide + Formoterol
• Used in moderate and severe persistent asthma + COPD

• Acute severe asthma and chronic severe asthma
• Long-term side effects: gastric irritation, Na⁺/water retention, hypertension, muscle weakness, osteoporosis, HPA axis suppression

---

ANTI-IgE MONOCLONAL ANTIBODY: ⭐

• Prevents binding of IgE to mast cells → prevents mast cell degranulation
• No effect on IgE already bound to mast cells
• Parenteral administration
• Used in moderate to severe asthma + allergic disorders (nasal allergy, food allergy)
• Approved for patients >12 years
• Side effects: redness, stinging, itching, induration (local)

---

INHALATIONAL DEVICES: ⭐

---

TREATMENT OF STATUS ASTHMATICUS: ⭐⭐

1. Humidified oxygen inhalation
2. Nebulized β₂ agonist (salbutamol 5 mg / terbutaline 10 mg) + anticholinergic (ipratropium 0.5 mg)
3. Systemic glucocorticoids: IV hydrocortisone 200 mg stat → 100 mg q6h or oral prednisolone 30-60 mg/day
4. Inj. salbutamol 0.4 mg i.m.
5. IV fluids (correct dehydration)
6. Potassium supplements (correct hypokalaemia from salbutamol/terbutaline)
7. Sodium bicarbonate (treat acidosis)
8. Antibiotics (treat infection)

---

DRUGS TO AVOID IN BRONCHIAL ASTHMA: ⭐⭐

1. NSAIDs - Aspirin, Ibuprofen, Diclofenac (Paracetamol CAN be used)
2. β-Adrenergic blockers
3. Cholinergic agents

---

---

⭐ IMPORTANT EXAM QUESTIONS (Frequently Asked)

SHORT NOTES / ESSAYS:

1. Classify antitussive drugs. Write the pharmacology of codeine / dextromethorphan / noscapine.
2. Write a note on mucolytics. / Compare bromhexine and acetylcysteine.
3. Classify antiasthmatic drugs with examples.
4. Mechanism of action of salbutamol (selective β₂ agonist) in bronchial asthma.
5. Compare short-acting and long-acting β₂ agonists.
6. Mechanism of action of methylxanthines. Adverse effects. Drug interactions.
7. Why is theophylline not used parenterally? / Aminophylline vs Theophylline.
8. Write a note on sodium cromoglycate / mast cell stabilizers.
9. Mechanism of action of glucocorticoids in asthma. Inhaled vs systemic steroids.
10. Omalizumab - mechanism, uses, side effects.
11. Treatment of Status Asthmaticus (acute severe asthma).
12. Drugs to be avoided in bronchial asthma and why.
13. Write a note on leukotriene receptor antagonists (montelukast).
14. Ipratropium bromide - mechanism, uses, why preferred in COPD.
15. Inhalational devices used in asthma treatment (pMDI, nebulizer, dry powder inhaler).

ONE-LINERS / MCQ TARGETS:

---

Note: All ⭐ marked topics are high-yield for university exams. Topics marked ⭐⭐ are most frequently asked in long essays or repeated MCQs.