Notes on Drugs for Asthma and COPD

Objectives

• Discuss medications used for Asthma and COPD.
• Distinguish the differences in routes and methods of delivery for medications.

Asthma

• Definition: A chronic inflammatory disorder of the airway.
• Characteristic Signs and Symptoms:
  • Sense of breathlessness
  • Tightening of the chest
  • Wheezing
  • Dyspnea (shortness of breath)
  • Cough
• Cause: Immune-mediated airway inflammation.

Pathophysiology of Asthma

• Symptoms arise from a combination of:
  • Inflammation
  • Bronchoconstriction.
• Treatment must address both components.

Chronic Obstructive Pulmonary Disease (COPD)

• Definition: A chronic, progressive, irreversible disorder characterized by airflow restrictions, inflammation, cough, sputum production, wheezing, and dyspnea.
• Components of COPD:
  • Chronic bronchitis: Chronic cough and excessive sputum, with hypertrophy of mucus-secreting glands in the airways.
  • Emphysema: Enlarged air spaces in bronchioles and alveoli.
• Common Cause: Smoking cigarettes.

Overview of Drugs for Asthma & COPD

• Two Main Pharmacologic Classes:
  1. Anti-inflammatory agents:
  • Glucocorticoids (e.g., prednisone)
  • Leukotriene Modifiers (e.g., Zafirlukast)
  • Mast Cell Stabilizers (e.g., Cromolyn)
  1. Bronchodilators:
  • Beta2 agonists (e.g., albuterol)
  • Methylxanthines (e.g., Theophylline)
  • Anticholinergics (e.g., Atrovent)

Inhalation Drug Therapy

• Advantages:
  • Enhanced therapeutic effects
  • Minimized systemic effects
  • Rapid relief of acute attacks
• Types:
  • Metered-dose inhalers (MDIs)
  • Respimats
  • Dry-powder inhalers (DPIs)
  • Nebulizers

Anti-Inflammatory Drugs

• Foundation of Asthma Therapy: Taken daily for long-term control.
• Glucocorticoids:
  • Examples: Budesonide (Pulmicort) and Fluticasone (Flovent).
  • Most effective anti-asthma drugs available.
  • Mechanism of Action:
  • Suppress inflammation.
  • Reduce bronchial hyperreactivity and airway mucus production.
  • Increase the number of bronchial beta2 receptors and their responsiveness to beta2 agonists.
  • Mainly administered by inhalation, but IV and oral forms are available.
  • Adverse Effects:
  • Inhaled: Oropharyngeal candidiasis; dysphonia.
  • Oral: Adrenal suppression, osteoporosis, hyperglycemia, peptic ulcer disease (PUD).

Leukotriene Modifiers

• Function: Suppress effects of leukotrienes, reducing bronchoconstriction and inflammation.
• Agents: Zileuton (Zyflo), Zafirlukast (Accolate), Montelukast (Singulair).
• Adverse Effects: Neuropsychiatric effects including depression, suicidal thinking, and behavior.

Cromolyn

• Type: Mast Cell Stabilizer used for prophylaxis (not for quick relief).
• Therapeutic Use: Chronic asthma and exercise-induced bronchospasm (EIB).
• Adverse Effects: Cough, bronchospasm.

Monoclonal Antibodies

• Examples:
  • Omalizumab (Xolair): Anti-IgE
  • Dupilumab (Dupixent): Interleukin-4 receptor antagonist
  • Benralizumab (Fasenra): Interleukin-5 receptor antagonist
• Not approved as first-line agents for acute asthma; very expensive.

Bronchodilators

• Function: Provide symptomatic relief but do not alter the underlying disease process.
• Types:
  • Beta2-Adrenergic Agonists (e.g., albuterol, salmeterol): Most effective for relief of acute bronchospasm.
  • Mechanism of Action:
  • Activate beta2 receptors in lung smooth muscle, promoting bronchodilation.
• Adverse Effects:
  • Tachycardia, angina, tremor.

Management of Asthma and COPD

• Tests of Lung Function:
  • Forced Expiratory Volume in 1 Second (FEV1)
  • Forced Vital Capacity (FVC)
  • Peak Expiratory Flow (PEF)
• Goals for Chronic Asthma Management:
  • Reducing impairment and risk.
• Drugs for Acute Severe Exacerbations:
  • Oxygen, systemic glucocorticoids, and nebulized high-dose SABA.
• Management Strategy for COPD:
  • Stable: Bronchodilators, glucocorticoids, phosphodiesterase-4 inhibitors.
  • Acute: SABAs preferred for bronchodilation during exacerbations.