1. Introduction
Adrenergic bronchodilators are a class of drugs that relax bronchial smooth muscle by stimulating adrenergic receptors, primarily β2-adrenergic receptors. They are central in the management of asthma, chronic obstructive pulmonary disease (COPD), and other obstructive airway diseases.
These agents are divided into short-acting (SABAs) and long-acting (LABAs), each with distinct pharmacokinetics and clinical indications.
2. Classification and Examples
2.1 Short-Acting Beta-2 Agonists (SABAs)
- Examples: Salbutamol (Albuterol), Terbutaline, Fenoterol
- Onset: Rapid (5–15 minutes)
- Duration: 4–6 hours
- Use: Acute relief of bronchospasm (“rescue inhalers”)
2.2 Long-Acting Beta-2 Agonists (LABAs)
- Examples: Salmeterol, Formoterol, Indacaterol, Olodaterol
- Onset: Formoterol rapid (5–10 min), Salmeterol slower (10–20 min)
- Duration: 12–24 hours
- Use: Maintenance therapy for asthma and COPD; never used as monotherapy in asthma due to risk of severe exacerbations
2.3 Ultra-Long-Acting Beta-2 Agonists (ULABAs)
- Examples: Vilanterol (in combination inhalers)
- Duration: 24 hours
- Use: Once-daily maintenance therapy for COPD and asthma (in combination with corticosteroids)
3. Mechanism of Action
- Stimulate β2-adrenergic receptors in bronchial smooth muscle
- Activation → adenylate cyclase → ↑ cAMP → protein kinase A activation
- Result: Phosphorylation of myosin light-chain kinase → smooth muscle relaxation → bronchodilation
- Additional effects:
- Inhibit mast cell mediator release
- Promote mucociliary clearance
- Minimal cardiac β1 stimulation at therapeutic doses, but higher doses can increase heart rate
4. Pharmacokinetics
| Property | SABAs | LABAs |
|---|---|---|
| Onset | 5–15 min | 10–20 min (Salmeterol), 5–10 min (Formoterol) |
| Duration | 4–6 h | 12 h |
| Metabolism | Liver (CYP2C19, CYP2D6 for some), conjugation | Liver via CYP3A4 |
| Route | Inhalation (preferred), oral, subcutaneous | Inhalation (preferred) |
Note: Inhaled route maximizes pulmonary effect while minimizing systemic side effects.
5. Clinical Uses
- Asthma
- SABAs: Rescue therapy for acute exacerbations
- LABAs: Maintenance therapy combined with inhaled corticosteroids
- Chronic Obstructive Pulmonary Disease (COPD)
- Both SABAs and LABAs used for symptom relief and maintenance
- ULABAs improve compliance due to once-daily dosing
- Other Indications
- Prevention of exercise-induced bronchospasm (SABAs)
- Adjunct therapy in status asthmaticus (IV or subcutaneous forms)
6. Adverse Effects
6.1 Common
- Tremor
- Palpitations / tachycardia
- Nervousness or anxiety
- Headache
- Mild hypokalemia (due to β2-mediated K+ shift)
6.2 Rare but Serious
- Paradoxical bronchospasm (with inhaler)
- Cardiac arrhythmias, especially in patients with underlying heart disease
- Worsening of hypokalemia at high doses
- Tolerance with chronic overuse → reduced bronchodilator efficacy
7. Drug Interactions
- Non-selective β-blockers: Can antagonize bronchodilator effect
- Diuretics: May worsen hypokalemia
- MAOIs / Tricyclic antidepressants: Increase cardiovascular side effects
- CYP3A4 inhibitors: May increase plasma concentration of LABAs like salmeterol or formoterol
8. Clinical Pearls
- SABAs should be used as needed; overuse indicates poor asthma control and need for therapy adjustment
- LABAs must never be used as monotherapy in asthma; always combine with inhaled corticosteroids
- Monitor heart rate, blood pressure, and serum potassium in patients on frequent or high-dose therapy
- Inhaled route is preferred to maximize pulmonary delivery and minimize systemic adverse effects
9. Special Populations
- Children: Dosing adjusted; inhaler technique critical
- Pregnancy: SABAs considered relatively safe; LABAs used only if benefits outweigh risks
- Elderly: Increased susceptibility to cardiovascular effects; start low dose
- Cardiac disease: Use with caution; monitor for arrhythmias
10. Summary
Adrenergic bronchodilators are cornerstone therapy in asthma and COPD, offering rapid relief (SABAs) or long-term maintenance (LABAs/ULABAs). They act through β2-adrenergic receptor stimulation to relax bronchial smooth muscle. While generally safe, careful monitoring is required for cardiovascular side effects, electrolyte disturbances, and tolerance. Combining LABAs with inhaled corticosteroids improves safety and efficacy in asthma.
