What is the effect of inhaled ipratropium (Ipratropium bromide)?

From the Guidelines

Inhaled ipratropium bromide is recommended as a treatment option for chronic obstructive pulmonary disease (COPD) due to its effectiveness in reducing exacerbations and improving lung function, as evidenced by a meta-analysis published in 2015 1. The standard dosage for adults is typically 2 inhalations (36 mcg) four times daily using a metered-dose inhaler, or 500 mcg via nebulizer 3-4 times daily.

Key Points

• Ipratropium works by blocking muscarinic acetylcholine receptors in the lungs, which prevents bronchial smooth muscle contraction and reduces mucus secretion, thereby opening airways and improving breathing.
• Common side effects include dry mouth, throat irritation, and headache.
• The medication begins working within 15-30 minutes and effects last for 4-6 hours.
• Ipratropium is often combined with albuterol (a short-acting beta-agonist) for enhanced bronchodilation in products like Combivent Respimat.
• Unlike beta-agonists, ipratropium has minimal cardiac effects, making it particularly useful for patients with heart conditions or those who experience tachycardia with beta-agonists.

Evidence

A study published in 2007 found that long-acting inhaled therapies, used alone or in combination, reduced exacerbations more than placebo by 13% to 25% and had similar effectiveness to each other 1. However, the 2015 study provides more recent and relevant evidence for the use of inhaled ipratropium bromide in COPD management, and its findings support the recommendation for its use in reducing exacerbations and improving lung function 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Ipratropium bromide is an anticholinergic (parasympatholytic) agent that, based on animal studies, appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve The bronchodilation following inhalation of ipratropium bromide is primarily a local, site-specific effect, not a systemic one In controlled 12-week studies in patients with bronchospasm associated with chronic obstructive pulmonary disease (chronic bronchitis and emphysema) significant improvements in pulmonary function (FEV1 increases of 15% or more) occurred within 15 to 30 minutes, reached a peak in 1 to 2 hours, and persisted for periods of 4 to 5 hours in the majority of patients, with about 25% to 38% of the patients demonstrating increases of 15% or more for at least 7 to 8 hours.

The primary mechanism of action of inhaled ipratropium is as an anticholinergic agent, which causes bronchodilation by inhibiting the action of acetylcholine on the muscarinic receptor on bronchial smooth muscle.

• The onset of action is within 15 to 30 minutes.
• The peak effect is reached in 1 to 2 hours.
• The duration of action is 4 to 5 hours in the majority of patients, with some patients experiencing effects for at least 7 to 8 hours 2.

From the Research

Inhaled Ipratropium

• Inhaled ipratropium is used in the treatment of chronic obstructive pulmonary disease (COPD) and has been compared to short-acting beta-2 agonists and long-acting beta-2 agonists in various studies 3, 4, 5, 6, 7.
• A study published in 2006 found that ipratropium bromide had small benefits over short-acting beta-2 agonists in terms of lung function outcomes and quality of life 3.
• Another study published in 1994 found that a combination of ipratropium and albuterol was more effective than either agent alone in patients with COPD 4.
• A 2006 study comparing ipratropium bromide to long-acting beta-2 agonists found that there was little difference between the two in terms of improving COPD symptoms and exercise tolerance, but long-acting beta-2 agonists were more effective in improving lung function variables 5.
• A study published in 2006 found that formoterol resulted in greater immediate improvement in lung function compared to ipratropium bromide, but both drugs were equally effective in improving lung function and reducing dyspnea 6.
• A 2001 study found that inhaled short-acting beta2-agonists and ipratropium both produced small improvements in FEV1, but there was no difference between the two treatments 7.

Comparison to Other Treatments

• Ipratropium bromide has been compared to short-acting beta-2 agonists, such as albuterol and metaproterenol, and long-acting beta-2 agonists, such as salmeterol and formoterol 3, 4, 5, 6, 7.
• Combination therapy with ipratropium and a short-acting beta-2 agonist or long-acting beta-2 agonist has been found to be more effective than either agent alone in some studies 4, 5.

Efficacy and Safety

• The efficacy and safety of inhaled ipratropium have been evaluated in various studies, with results showing small benefits in terms of lung function outcomes and quality of life 3, 4, 5, 6, 7.
• The safety profile of ipratropium has been found to be similar to that of other bronchodilators, with common side effects including dry mouth and cough 3, 4, 5, 6, 7.