An 18-year-old woman comes to the clinic due to intermittent dry cough, wheezing, and shortness of breath. She recently began practicing twice a day for her college track team and has been experiencing these symptoms with running. Her symptoms have been limiting her ability to complete practice but usually resolve after several minutes of rest. Medical history includes childhood asthma that has not required treatment for the past 5 years. The patient is prescribed a medication that reduces bronchoconstriction by inhibiting the interaction of inflammatory mediators with cell surface receptors. Which of the following drugs was most likely used in this patient?
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Exercise-induced bronchoconstriction is common in patients with underlying asthma. Asthma occurs due to a complex inflammatory response to the environment that involves Th2 lymphocytes, eosinophils, and mast cells. Eosinophils and mast cells synthesize and release leukotrienes, which are inflammatory mediators that induce bronchial smooth muscle contraction (bronchoconstriction), bronchial mucus secretion, and bronchial edema. The leukotrienes mainly responsible for these responses are the cysteinyl-containing leukotrienes such as leukotriene C4, D4, and E4.
Leukotriene receptor antagonists (eg, montelukast, zafirlukast) effectively treat asthma by binding to leukotriene receptors on bronchial smooth muscle cells and blocking the effects of cysteinyl-containing leukotrienes.
(Choice A) Albuterol causes short-acting bronchodilation via selective stimulation of beta 2 receptors. It is typically used as an as-needed rescue inhaler in patients with asthma.
(Choice B) Dextromethorphan suppresses cough via stimulation of sigma opioid receptors in the CNS (it does not stimulate mu or delta opioid receptors and therefore does not cause other typical opioid effects). It is commonly used in cold medication but is not effective for treatment of asthma.
(Choice C) Inhaled corticosteroids (eg, fluticasone, budesonide) help treat asthma by inhibiting nuclear transcription of inflammatory genes leading to widespread anti-inflammatory effects. One effect is reduced activity of the enzyme phospholipase A2 to decrease the production of leukotrienes. Corticosteroids do not block cell surface receptors.
(Choice D) Ipratropium stimulates bronchodilation via blockade of the binding of acetylcholine (a neurotransmitter) to muscarinic receptors. Inhaled ipratropium is sometimes used in the treatment of asthma but is more commonly used for chronic obstructive pulmonary disease.
(Choice F) Zileuton is a 5-lipoxygenase enzyme inhibitor that reduces the production of leukotrienes (it does not block leukotriene cell surface receptors). It can be used for treatment of asthma, but it is often avoided due to concerns about toxicity.
Educational objective:
The cysteinyl-containing leukotrienes (ie, leukotriene C4, D4, and E4) are inflammatory mediators that stimulate bronchoconstriction, bronchial mucus secretion, and bronchial edema to contribute to the pathogenesis of asthma. Leukotriene receptor antagonists (eg, montelukast, zafirlukast) treat asthma by binding to leukotriene receptors on bronchial smooth muscle cells and blocking these effects.