Untitled Quiz

Drug Therapy of Bronchial Asthma

• Bronchial asthma is a chronic inflammatory airway disease characterized by increased responsiveness to various stimuli. Airways narrow, causing inflammation and changes in severity.

• Asthma attacks involve recurrent reversible airway obstruction triggered by different stimuli. Symptoms include coughing, wheezing, and difficulty breathing.

Pathogenesis of Asthma

• Asthma involves contracted smooth muscle in the airways.
• Blood vessels in the airways are infiltrated by immune cells.
• Inflammation and swelling occur.
• Excess mucus is produced.
• Reduced airway diameter.

Management of Asthma

• General Measures:

  • Stop smoking
  • Avoid triggers (antigens, severe exercise, stress, certain medications like aspirin)
  • Treat related conditions like chest infections and use immunotherapy where appropriate

• Drug Treatment:

  • Bronchodilators:

    • Beta-2 adrenergic agonists (short-acting: e.g., salbutamol; long-acting: e.g., salmeterol)
    • Methylxanthines (e.g., theophylline)
    • Anticholinergics (e.g., ipratropium bromide)

  • Anti-inflammatory Agents:

    • Glucocorticoids
    • Leukotriene receptor antagonists (e.g., zafirlukast, montelukast)
    • Anti-IgE monoclonal antibodies

  • Supportive Therapy:

    • Expectorants and mucolytics
    • Treatment of respiratory infections
    • Sedatives and tranquilizers
    • Oxygen therapy and fluid therapy
    • Desensitization

Bronchodilators

• Mechanisms of Action (Beta-2 Agonists): Beta-2 agonists increase cyclic AMP (cAMP), leading to relaxation of bronchial smooth muscle.

• Mechanisms of Action (Methylxanthines): Methylxanthines (like theophylline) inhibit phosphodiesterase (PDE), increasing intracellular cAMP and relaxing smooth muscles. They also reduce the release of bronchospasm mediators.

• Mechanisms of Action (Anticholinergics): Anticholinergics (like ipratropium bromide) block acetylcholine's effect on airways, preventing bronchoconstriction.

Beta-2 Agonists

• Classification:

  • Selective (e.g., salbutamol): Fewer side effects
  • Non-selective (e.g., adrenaline, isoprenaline, ephedrine)

• Short-acting (e.g., salbutamol): Effective during acute attacks. Lasts 4-6 hours.

• Long-acting (e.g., salmeterol): Prophylactic for preventing future attacks; last 12 hours.

• Dynamics (of Beta-2 agonists): Increased cAMP, leading to relaxation of smooth muscles, reduced mucociliary transport, reduced release of bronchospasm mediators and reduced microvascular permeability

• Salbutamol: Synthetic, sympathomimetic catecholamine that works via inhalation, oral, or parenteral routes. Causes bronchodilation, reduced bronchial secretion, mast cell stabilization, and uterine relaxation.

Methylxanthines

• Examples: Theophylline, theobromine, caffeine
• Kinetics: Oral, sustained release, intravenous, inhalation, rectal
• Dynamics: Inhibits phosphodiesterase (PDE), increasing cyclic AMP (cAMP), leading to smooth muscle relaxation. Reduced adenosine receptors, inhibition of antigen-histamine release, and increased catecholamine release from the adrenal medulla.
• Narrow therapeutic index: Careful monitoring of serum levels is crucial.

Adverse Effects of Theophylline

• Cardiovascular (tachycardia, arrhythmia)
• Central Nervous System (convulsions, nervousness)
• Gastrointestinal (heartburn, vomiting, abdominal pain, peptic ulcer)

Precautions of Theophylline

• Intravenous administration should be slow to avoid cardiac arrhythmias, hypotension, and arrest.
• Lower infusion rates in patients with heart failure, liver dysfunction, or elderly individuals.
• Avoid a loading dose if theophylline has been taken recently.
• Oral preparations should be taken with food to prevent gastric irritation.
• Serum levels should be checked regularly (eg, approximately every 6-12 months).

Anticholinergic Agents

• Ipratropium Bromide: A quaternary amine; fewer side effects (inhalation).
• Mechanism of Action: Blocks vagal-mediated bronchoconstriction.
• Use: COPD, chronic bronchitis, emphysema, psychogenic asthma, asthma induced by beta blockers.

Leukotriene Antagonists

• Ziluton: Inhibits 5-lipoxygenase, preventing leukotriene synthesis.
• Zafirlukast & Montelukast: Block leukotriene receptors.
• Use: Effective in exercise, antigen, and aspirin-induced asthma.

Anti-IgE Monoclonal Antibodies

• Mechanism of Action: Inhibits mast cell degranulation, also might inhibit IgE synthesis by B lymphocytes
• Use: Decreases asthma severity and reduces corticosteroid needed by patients with moderate-to-severe asthma.