Adrenergic bronchodilators

Introduction

Adrenergic bronchodilators, also known as sympathomimetic bronchodilators, are a major drug class used in the treatment of asthma, chronic obstructive pulmonary disease (COPD), and other conditions with reversible airway obstruction. They act by stimulating β-adrenergic receptors in bronchial smooth muscle, leading to relaxation, bronchodilation, and improved airflow.

They are often categorized by receptor selectivity (β2-selective vs. non-selective) and duration of action (short-acting, long-acting, ultra-long-acting). These medications form the backbone of acute and maintenance therapy in obstructive airway diseases.

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Mechanism of Action

• Adrenergic bronchodilators bind to β2-adrenergic receptors on bronchial smooth muscle.

• This activates adenylate cyclase, increasing cyclic AMP (cAMP) levels.

• Elevated cAMP activates protein kinase A (PKA), which phosphorylates and inactivates myosin light chain kinase, reducing intracellular calcium and producing smooth muscle relaxation.

• Additional effects:

  • Inhibition of mast cell mediator release (histamine, leukotrienes).

  • Improved mucociliary clearance.

  • Reduced vascular permeability in the airways.

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Classification

1. Short-Acting β2 Agonists (SABAs)

• Rapid onset, short duration (4–6 hours).

• Used as rescue medications for acute bronchospasm.

Examples and Typical Doses:

• Albuterol (Salbutamol):

  • Inhalation: 90–100 mcg per puff; 1–2 puffs every 4–6 hours as needed.

  • Nebulizer: 2.5 mg every 4–6 hours.

• Levalbuterol: 45 mcg per puff; 2 puffs every 4–6 hours PRN.

• Terbutaline: Subcutaneous injection 0.25 mg every 20 min for up to 3 doses (used in acute severe asthma).

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2. Long-Acting β2 Agonists (LABAs)

• Duration: ~12 hours.

• Used in maintenance therapy for asthma (always with inhaled corticosteroids) and COPD.

• Not suitable for monotherapy in asthma due to risk of asthma-related death.

Examples and Typical Doses:

• Salmeterol: 50 mcg inhaled every 12 hours.

• Formoterol: 12 mcg inhaled every 12 hours.

• Arformoterol: Nebulizer solution, 15 mcg twice daily.

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3. Ultra-Long-Acting β2 Agonists (Ultra-LABAs)

• Duration: ≥24 hours.

• Allow once-daily dosing, mainly for COPD.

Examples and Typical Doses:

• Indacaterol: 75 mcg once daily by inhalation.

• Olodaterol: 5 mcg once daily by inhalation.

• Vilanterol: Available only in fixed-dose combinations (e.g., with fluticasone or umeclidinium).

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4. Non-Selective Adrenergic Agents

• Stimulate both β1 and β2 receptors, sometimes α receptors.

• Limited use today due to systemic side effects.

Examples and Typical Doses:

• Epinephrine:

  • Subcutaneous injection 0.3–0.5 mg every 20 min for up to 3 doses in severe asthma or anaphylaxis.

• Isoproterenol: Rarely used; historically inhaled or IV for bronchospasm, but non-selectivity causes cardiac stimulation.

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Therapeutic Uses

• Asthma: SABAs for acute relief, LABAs with ICS for maintenance.

• COPD: LABAs and Ultra-LABAs as part of long-term management, often combined with antimuscarinic agents and/or inhaled corticosteroids.

• Exercise-induced bronchospasm: Albuterol inhaled 5–20 minutes before exercise.

• Anaphylaxis: Epinephrine (IM) is life-saving.

• Hyperkalemia (off-label use): High-dose nebulized albuterol can temporarily lower serum potassium.

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Adverse Effects

• Cardiovascular: Tachycardia, palpitations, hypertension, arrhythmias (more with non-selective agents).

• Neurological: Tremor, nervousness, headache, insomnia.

• Metabolic: Hypokalemia (due to intracellular potassium shift), hyperglycemia.

• Respiratory: Paradoxical bronchospasm (rare).

• Tolerance and tachyphylaxis with chronic overuse.

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Contraindications and Precautions

• Caution in patients with cardiac arrhythmias, uncontrolled hypertension, or hyperthyroidism.

• Avoid LABA monotherapy in asthma—must be combined with ICS.

• Use with caution in pregnancy (though albuterol is considered relatively safe).

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Drug Interactions

• Beta-blockers (especially non-selective like propranolol) blunt bronchodilatory effect.

• MAO inhibitors and tricyclic antidepressants: Increase risk of hypertensive crisis with adrenergic agonists.

• Other sympathomimetics: Additive cardiovascular effects.

• Diuretics: May enhance hypokalemia risk.

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Clinical Considerations

• Inhaled delivery is preferred—maximizes local effect, minimizes systemic side effects.

• Stepwise asthma management: SABAs are rescue-only; LABAs and Ultra-LABAs used for persistent disease in combination with controllers.

• COPD: LABAs/Ultra-LABAs are essential; often combined with long-acting muscarinic antagonists (LAMAs).

• Anaphylaxis: Epinephrine is first-line, not LABAs