What is ipratropium?

What is Ipratropium?

Ipratropium bromide is a short-acting anticholinergic (parasympatholytic) bronchodilator that works by blocking acetylcholine at muscarinic receptors in the airways, thereby preventing vagally-mediated bronchoconstriction and producing bronchodilation primarily in large and intermediate-size airways. 1

Mechanism of Action

• Ipratropium inhibits vagally mediated reflexes by antagonizing acetylcholine, the transmitter agent released from the vagus nerve, preventing increases in intracellular cyclic GMP that cause bronchoconstriction 1
• The drug acts primarily on large- and intermediate-size airways, in contrast to beta-adrenergic agents which act primarily on smaller airways 2
• It is a quaternary ammonium compound (synthetic derivative of atropine), which means it is ionized in aqueous solutions and does not cross the blood-brain barrier, avoiding central nervous system side effects 1

Pharmacokinetics and Onset

• Bronchodilation begins within 15-30 minutes, reaches peak effect in 1-2 hours, and persists for 4-6 hours in most patients 1, 3
• Only 7% of an inhaled dose is absorbed systemically (from lung surface or GI tract), with the remainder swallowed but not absorbed 1
• The elimination half-life is approximately 1.6 hours after intravenous administration, with minimal plasma protein binding (0-9%) 1

Clinical Efficacy and Limitations

In COPD:

• Ipratropium is NOT superior to placebo in reducing COPD exacerbations (RR 0.95, CI 0.78-1.15), unlike long-acting anticholinergics such as tiotropium 4
• It produces significant improvements in FEV1 (15% or more increases) in the majority of patients with chronic bronchitis and emphysema, though it does not consistently improve subjective symptom scores 1
• Tiotropium is more effective than ipratropium in reducing exacerbations (RR 0.77, CI 0.62-0.95) and is now considered superior for COPD maintenance therapy 4, 5, 6

In Acute Asthma Exacerbations:

• Ipratropium provides additive benefit when combined with short-acting beta-agonists (SABAs) in moderate to severe asthma exacerbations, particularly in emergency settings 7, 8
• The combination produces a 7.3% improvement in FEV1 (95% CI 3.8-10.9%) and 22.1% improvement in peak expiratory flow (95% CI 11.0-33.2%) compared to beta-agonist alone 8
• It is not recommended as monotherapy for acute asthma due to delayed onset of action compared to SABAs 7, 9

Clinical Role and Positioning

• Ipratropium is primarily used as rescue medication or adjunctive therapy, not as first-line maintenance treatment for COPD 5
• For COPD maintenance therapy, long-acting muscarinic antagonists (LAMAs) like tiotropium are preferred over ipratropium due to superior efficacy in reducing exacerbations and hospitalizations 5, 6
• Combined therapy with beta-agonists produces greater bronchodilation than either agent alone, with median duration of 15% FEV1 improvement extending to 5-7 hours versus 3-4 hours with beta-agonist alone 1

Safety Profile

• Ipratropium is well-tolerated with minimal systemic side effects due to poor systemic absorption and inability to cross the blood-brain barrier 1, 2
• Common adverse effects are mild and include dry mouth, cough, nausea, and dizziness, without the cardiovascular effects (palpitations, tremor) associated with beta-agonists 3, 9
• Does not affect mucociliary function, heart rate, urinary bladder, or eye function at therapeutic doses, unlike systemic atropine 2

Dosing

• Standard dosing is 2 inhalations (36 mcg) four times daily for maintenance therapy, with a maximum of 12 inhalations per day 9
• For acute exacerbations, multiple high doses are administered via nebulizer (typically 0.5 mg/2.5 mL) in combination with beta-agonists 7