A pharmaceutical researcher is studying a new drug being developed for treatment of asthma that works by reversing irritant-induced bronchoconstriction. Laboratory guinea pigs are divided into 2 groups: a postvagotomy (complete transection of the vagus nerve) group and a normal study group. Both groups are exposed to irritants without receiving the study medication, and changes in bronchial diameters are recorded. Subsequently, both groups are exposed again to the irritants but are also given the study drug.
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The study drug is most likely similar to which of the following medications?
The figure on the left shows a decrease in bronchial diameter of normal lungs following administration of an irritant but minimal change in bronchial diameter of lungs without an intact vagus nerve. This implies that the bronchoconstriction is mediated by the parasympathetic nervous system. When the vagus nerve is stimulated (eg, via an inhaled irritant), acetylcholine is released and produces bronchoconstriction by acting on muscarinic receptors. The figure on the right demonstrates minimal decrease in bronchial diameter in normal lungs following administration of the irritant, suggesting that the study medication blocks the action of acetylcholine. Ipratropium, an anticholinergic and derivative of atropine, has this effect.
Ipratropium and other anticholinergic drugs used for obstructive lung disease (eg, tiotropium) are less potent bronchodilators than beta-2 adrenergic agonists but can enhance the bronchodilatory effect of these agents. In addition, ipratropium and similar drugs block the parasympathetic stimulation of tracheobronchial submucosal glands, decreasing mucus secretion and providing further benefit in treating asthma and chronic obstructive pulmonary disease (COPD).
(Choice A) Albuterol is a short-acting selective beta-2 adrenergic agonist that is the first-line treatment for asthma and COPD. The bronchodilatory effects of albuterol are independent of parasympathetic innervation.
(Choice B) Inhaled glucocorticoids (eg, flunisolide) have potent local anti-inflammatory effects in the airway and are used in the treatment of persistent asthma and COPD with frequent exacerbations.
(Choice D) Nifedipine causes bronchodilation by blocking calcium influx into bronchial smooth muscle cells; however, the drug is generally not used in treating obstructive lung disease.
(Choice E) Methylxanthines, such as theophylline and aminophylline, cause bronchodilation by blocking phosphodiesterase activity, thereby increasing the intracellular concentration of cyclic AMP.
(Choice F) Zileuton inhibits 5-lipoxygenase and thereby decreases the production of leukotrienes to reduce bronchoconstriction and improve asthma symptoms.
Educational objective:
Ipratropium, an anticholinergic agent and derivative of atropine, treats obstructive lung disease by blocking acetylcholine at muscarinic receptors, which prevents bronchoconstriction and reduces mucus secretion from tracheobronchial submucosal glands.