Anticholinergic bronchodilators

Introduction

Anticholinergic bronchodilators, also known as antimuscarinic bronchodilators, are a cornerstone in the management of chronic obstructive pulmonary disease (COPD) and are also used as adjunctive therapy in asthma. These drugs act by blocking muscarinic receptors (mainly M3) in the airway smooth muscle, thereby reducing parasympathetic-mediated bronchoconstriction and mucus secretion.

They are generally categorized into short-acting muscarinic antagonists (SAMAs) and long-acting muscarinic antagonists (LAMAs), with LAMAs forming the backbone of COPD maintenance therapy.

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Mechanism of Action

• Normal physiology: Vagal stimulation → acetylcholine release → muscarinic receptor activation (M3) → bronchoconstriction + mucus secretion.

• Anticholinergic bronchodilators: Block muscarinic M3 receptors on airway smooth muscle → bronchodilation and decreased mucus production.

• Additional effects: Inhibition of reflex bronchospasm induced by irritants.

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Classification

1. Short-Acting Muscarinic Antagonists (SAMAs)

• Generic: Ipratropium bromide.

• Onset/Duration: Onset within 15 minutes, duration 4–6 hours.

• Uses:

  • Acute relief in COPD (often combined with short-acting β2-agonists, e.g., albuterol).

  • Off-label for asthma exacerbations (especially in emergency settings).

• Adverse Effects: Dry mouth, cough, mild systemic anticholinergic effects (rare).

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2. Long-Acting Muscarinic Antagonists (LAMAs)

• Generics:

  • Tiotropium (once daily).

  • Aclidinium bromide (twice daily).

  • Umeclidinium (once daily).

  • Glycopyrrolate inhalation (twice daily).

• Onset/Duration: Slower onset than SAMAs but provide 24-hour bronchodilation.

• Uses:

  • Maintenance therapy in moderate-to-severe COPD.

  • Tiotropium is also approved for asthma maintenance in patients not controlled with ICS/LABA.

• Adverse Effects: Dry mouth, constipation, urinary retention (rare systemic effects).

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Clinical Indications

1. Chronic Obstructive Pulmonary Disease (COPD):

   • First-line maintenance therapy (LAMAs preferred over LABAs for reducing exacerbations).

   • SAMAs used for symptom relief in acute exacerbations.

2. Asthma:

   • Ipratropium: used acutely in combination with SABA in severe asthma attacks.

   • Tiotropium: add-on therapy for patients uncontrolled on inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs).

3. Other Uses:

   • Off-label for bronchospasm induced by irritants (e.g., smoke, cold air).

   • Used perioperatively to reduce airway secretions (though systemic anticholinergics are more common here).

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Contraindications

• Hypersensitivity to atropine derivatives or formulation components.

• Caution in:

  • Narrow-angle glaucoma (risk of increased intraocular pressure if drug contacts the eyes).

  • Prostatic hyperplasia and bladder neck obstruction (urinary retention risk).

  • Elderly patients sensitive to systemic anticholinergic effects.

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Adverse Effects

• Local/Respiratory: Dry mouth, throat irritation, cough.

• Systemic (rare with inhaled forms): Constipation, urinary retention, blurred vision (if sprayed into eyes), tachycardia.

• Serious: Paradoxical bronchospasm (rare).

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Clinical Considerations

1. Choice of agent:

   • COPD: LAMAs (tiotropium, umeclidinium) preferred for maintenance.

   • Asthma: LAMAs are add-on therapy, not first-line; ipratropium used in acute exacerbations.

2. Combination therapy:

   • SAMA + SABA (e.g., ipratropium + albuterol): synergistic in acute COPD/asthma exacerbations.

   • LAMA + LABA or LAMA + LABA + ICS combinations widely used in COPD for maintenance.

3. Delivery systems: Available as metered-dose inhalers (MDIs), dry powder inhalers (DPIs), and nebulized solutions (ipratropium, glycopyrrolate).

4. Safety in elderly: Preferred over systemic anticholinergics due to minimal CNS penetration (quaternary ammonium structure).

5. Monitoring: Clinical response (symptom improvement, reduced exacerbations), not plasma levels.