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Pharmacotherapy for Lower Respiratory Conditions: Asthma & COPD

Pharmacotherapy for Lower Respiratory Conditions

Asthma and COPD Overview

  • Asthma: Chronic lung disease involving airflow limitation and airway hyperresponsiveness. Triggered by external stimuli (allergens/irritants), leading to an inflammatory response and mediator release (histamine, leukotrienes), causing wheezing, coughing, and shortness of breath.

  • COPD: Chronic lung disease characterized by small airway obstruction, persistent airflow limitations, and reduced expiratory flow rate.

Inhaled Medication Formulations

  • Metered-Dose Inhalers (MDIs): Pressurized canisters, require hand-breath coordination (use with spacer).

  • Dry Powder Inhalers (DPIs): Inhaled dry powder, requires rapid/forceful breath (RespiClick: breath-activated, Digihaler: tracks usage).

  • Nebulizers: Convert liquid to fine mist, for dexterity issues or larger doses, longer treatment time.

Bronchodilators
Beta2-Adrenergic Agonists (SABAs & LABAs)

  • Mechanism of Action (MOA): Selectively activate β_2 receptors in bronchial smooth muscle, increasing cAMP and signaling relaxation, relieving bronchoconstriction.

  • Short-Acting Beta2 Agonists (SABAs) - e.g., albuterol, levalbuterol:

    • Indications: "Rescue inhaler" for acute bronchospasm (Asthma, COPD), exercise-induced asthma prevention.

    • Black Box Warning (Asthma): Increased risk of asthma-related death/hospitalization if used without Inhaled Corticosteroids (ICS); not for monotherapy.

    • Side Effects: Tachycardia, increased BP, tremor, headache, hypokalemia, hyperglycemia.

    • Contraindications: Caution with underlying cardiovascular disease, seizure disorders, hyperthyroidism. Interactions with TCAs, MAOIs, beta-blockers.

  • Long-Acting Beta2 Agonists (LABAs) - e.g., salmeterol, formoterol:

    • Indications: Long-term maintenance.

      • Asthma: Always in combination with ICS; never monotherapy, not for acute exacerbations.

      • COPD: Can be monotherapy or combined; not for acute exacerbations.

    • Black Box Warning (Asthma): Increased risk of asthma-related death/hospitalization if used without ICS.

    • Side Effects: Similar to SABAs.

    • Contraindications: Not for acute exacerbations, not alone for asthma. Avoid concurrent LABA use or exceeding dosage. Caution with strong CYP450 3A4 inhibitors, CVD.

Muscarinic Agonists (Anticholinergics) (SAMAs & LAMAs)

  • MOA: Inhibit muscarinic acetylcholine receptors in bronchial smooth muscle, causing relaxation and preventing inflammatory mediator release.

  • Short-Acting Muscarinic Antagonists (SAMAs) - e.g., ipratropium:

    • Indications: Maintenance treatment for COPD.

    • Side Effects: Anticholinergic effects (restlessness, dizziness, headache, blurred vision, urinary obstruction, cough).

    • Contraindications: Narrow-angle glaucoma, BPH, bladder neck obstruction. Allergy to atropine, soy, peanuts.

  • Long-Acting Muscarinic Antagonists (LAMAs) - e.g., tiotropium, aclidinium, umeclidinium:

    • Indications: Maintenance treatment for COPD (once daily dosing). Asthma (adjunct therapy for severe cases, not first-line). Exercise-induced bronchospasm.

    • Side Effects: Similar anticholinergic effects (xerostomia).

    • Contraindications: Caution with narrow-angle glaucoma, BPH, bladder neck obstruction, CrCl < 60 mL/min.

Methylxanthines - e.g., theophylline

  • MOA: Inhibits phosphodiesterase, increasing cAMP, relaxing smooth muscle, and preventing inflammatory mediator release.

  • Indications: Maintenance for COPD (alternative). Not recommended for Asthma or COPD (2024) due to slow onset, less effectiveness, and more adverse effects.

  • Side Effects: Arrhythmia (life-threatening), nausea, insomnia, headache, seizures. Narrow therapeutic index (monitor serum levels for toxicity).

  • Contraindications: Allergy to corn products. Not for acute asthma exacerbations or children < 12 years.

Anti-Inflammatory Agents
Glucocorticoids (Corticosteroids) (Inhaled & Systemic)

  • Inhaled Glucocorticoids (ICS) - e.g., fluticasone, budesonide, mometasone:

    • MOA: Inhibits muscarinic cholinergic receptors (inflammatory cytokines), modulates inflammation.

    • Indications: Essential maintenance for asthma. Used in combination for COPD. Takes ~2 weeks for maximal effectiveness.

    • Side Effects: Oropharyngeal candidiasis (thrush, rinse mouth after use), hoarseness, dry mouth. Risk of growth suppression in children.

    • Contraindications: Not for acute relief.

  • Systemic Glucocorticoids - e.g., prednisone, methylprednisolone, dexamethasone:

    • MOA: Modulate mast cell mediator release, prevent histamine/inflammatory mediator release.

    • Indications: Essential for acute severe asthma exacerbations. COPD exacerbations. Short-course "burst" treatment (lowest effective dose for shortest duration).

    • Side Effects: Anaphylaxis, adrenal insufficiency, Cushing syndrome, edema, osteoporosis, weight gain, increased infection risk.

    • Contraindications: Untreated infections. Taper gradually if high dose/long-term.

Leukotriene Modifiers - e.g., montelukast, zafirlukast

  • MOA: Blocks leukotriene binding to receptors, reducing smooth muscle contraction, vascular permeability, and mucus secretions.

  • Indications: Maintenance treatment for asthma (alternative, not first-line). Less effective than ICS.

  • Side Effects: Headache, infection, nausea, abdominal pain, liver enzyme elevation. Neuropsychiatric adverse events (monitor for nightmares, behavioral problems).

  • Contraindications: Not for acute bronchospasms. Increased bleeding risk if on anticoagulants.

Mast Cell Stabilizers - e.g., cromolyn sodium

  • MOA: Modulates mast cell mediator release, preventing histamine and other inflammatory mediator release.

  • Indications: Maintenance for asthma (alternative, not first-line). Exercise-induced asthma.

  • Side Effects: Mild (unpleasant taste, throat irritation, cough). Good safety profile, but less commonly used now.

  • Contraindications: Not for acute bronchospasms. Caution with renal/hepatic impairment.

Monoclonal Antibodies - e.g., omalizumab

  • MOA: Targets and neutralizes molecules in the inflammatory process, reducing inflammatory cell recruitment and mediator release.

  • Indications: Add-on therapy for severe asthma with specific criteria (e.g., IgE levels 30 to 700 IU/mL, failed high-dose ICS).

  • Black Box Warning: Anaphylaxis.

  • Side Effects: Injection site reaction, headache.

  • Contraindications: History of anaphylaxis. Not for acute bronchospasms. Administered SC every 2-4 weeks, supervised administration preferred.

Phosphodiesterase-4 (PDE4) Inhibitors - e.g., roflumilast

  • MOA: Inhibits PDE4, increasing cAMP in inflammatory cells; relaxes smooth muscle, reduces inflammation.

  • Indications:

    • COPD: Maintenance for chronic COPD with frequent exacerbations.

    • Asthma: Alternative for severe asthma failed high-dose ICS.

  • Side Effects: Diarrhea, nausea, weight loss, headache, insomnia, anxiety, depression.

  • Contraindications: Hepatic impairment. Caution with depression, suicidal ideation. Monitor for weight/behavior changes.