What is ipratropium?

Ipratropium Bromide: An Anticholinergic Bronchodilator

Ipratropium bromide is a short-acting anticholinergic (antimuscarinic) bronchodilator that works by blocking the action of acetylcholine at muscarinic receptors in the airways, resulting in bronchodilation. 1

Mechanism of Action and Pharmacology

• Mechanism: Ipratropium bromide inhibits vagally mediated reflexes by antagonizing acetylcholine at muscarinic receptors on bronchial smooth muscle, preventing increases in intracellular cyclic guanosine monophosphate (cyclic GMP) 1
• Pharmacokinetics:
  • Only about 7% of inhaled dose is systemically absorbed 1, 2
  • Half-life of elimination is approximately 1.6 hours after intravenous administration 1
  • Minimally bound (0-9%) to plasma proteins 1
  • Does not cross the blood-brain barrier 1

Clinical Effects and Efficacy

• Onset and Duration:

  • Significant bronchodilation occurs within 15-30 minutes 1
  • Peak effect in 1-2 hours 1
  • Duration of action is 4-6 hours in most patients 1, 3

• Efficacy in COPD:

  • Produces significant improvements in pulmonary function (FEV1 increases of 15% or more) 1
  • At least as effective as beta-2 agonists in patients with chronic bronchitis 3
  • Less effective than long-acting anticholinergics like tiotropium in reducing exacerbations (RR, 0.77 [CI, 0.62 to 0.95]) 4
  • Not superior to placebo in reducing COPD exacerbations (RR, 0.95 [CI, 0.78 to 1.15]) 4

• Efficacy in Asthma:

  • Somewhat less effective than beta-2 agonists in asthmatic patients 3
  • May be useful as adjunctive therapy in asthma 5

Combination Therapy

• Combination with beta-2 agonists often produces greater bronchodilation than either agent alone 3, 5
• The combination of ipratropium plus long-acting beta-agonist may be more effective than long-acting beta-agonist alone in reducing exacerbations, though evidence is limited 4

Safety Profile

• Side Effects:

  • Generally well-tolerated at usual inhaled doses 3
  • Most common side effects are respiratory disorders 6
  • Anticholinergic side effects are rare (1.3% with HFA formulation, 0.7% with CFC formulation) 6
  • May cause increased wheezing in some individuals 2

• Precautions:

  • Should be used with caution in patients with:
    • Glaucoma
    • Prostatic hypertrophy
    • Bladder neck obstruction
    • Urinary retention 2

Clinical Positioning

• Current Role:
  • Primarily used as a short-acting bronchodilator in COPD management 4
  • Less commonly used than tiotropium (long-acting anticholinergic) which has replaced ipratropium as the preferred anticholinergic agent in COPD due to once-daily dosing and superior efficacy 7
  • May be useful for patients who experience troublesome side effects from beta-2 agonists (palpitations, tremor) 3
  • Often used in combination with other bronchodilators for enhanced effect 3, 5

Dosing

• Standard dosage is two inhalations (36 micrograms) four times daily 5
• Maximum recommended doses should not exceed 12 inhalations per day 5

Ipratropium represents an important therapeutic option for COPD patients, particularly when used in combination with other bronchodilators, though its role has diminished with the development of longer-acting anticholinergics like tiotropium that offer more convenient dosing and better efficacy in preventing exacerbations.