Inhaled verapamil-induced bronchoconstriction in mild asthma

Area of Science:

• Pharmacology
• Respiratory Medicine
• Clinical Trials

Background:

• Asthma is a chronic respiratory disease characterized by airway inflammation and hyperresponsiveness.
• Verapamil, a calcium channel blocker, has been investigated for potential anti-inflammatory and bronchodilatory effects.
• The safety and efficacy of inhaled verapamil in asthma management remain areas of interest.

Purpose of the Study:

• To evaluate the effect of inhaled verapamil on airway responsiveness in subjects with mild asthma.
• To assess the safety and tolerability of increasing doses of inhaled verapamil.
• To determine if verapamil mitigates exercise-induced bronchoconstriction.

Main Methods:

• Single-blind, randomized crossover study involving methacholine challenges before and after placebo or inhaled verapamil (5-160 mg).
• Double-blind, randomized crossover study assessing inhaled verapamil (placebo, 10 mg, highest tolerated dose) prior to standardized exercise challenge.
• Measurements included FEV1 (Forced Expiratory Volume in 1 second) and PC20 (provocative concentration of methacholine causing a 20% fall in FEV1).

Main Results:

• A 10 mg dose of inhaled verapamil modestly increased the provocative concentration (PC20) of methacholine, indicating improved airway responsiveness (2.1x baseline vs. 1.1x for placebo, p<0.001).
• Doses of 20 mg or higher of inhaled verapamil paradoxically induced bronchoconstriction in 70% of subjects, with adverse effects like cough and wheezing.
• Inhalation of higher verapamil doses before exercise challenge led to bronchospasm in 3 subjects, though the highest tolerated dose significantly reduced exercise-induced FEV1 decline (-6.4% vs. -17.1% for placebo, p<0.05).

Conclusions:

• Inhaled verapamil at 10 mg demonstrates a modest benefit in airway responsiveness for mild asthma.
• Higher doses of inhaled verapamil (≥20 mg) are associated with paradoxical bronchoconstriction and should be used cautiously in asthmatic individuals.
• The potential for verapamil to induce bronchospasm necessitates careful consideration, particularly with oral or intravenous administration in asthma patients.