Review Question - QID 101884

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Cholinomimetic Agents Direct agonists Direct Agonists Uses Mechanism of Action Methacholine • Challenge test for bronchial airway hyperactivity/asthma • Rapid onset of contraction of smooth muscles in the airways and increases tracheobronchial secretions• Slightly resistant to QID: 101884 (M1.PH.14.218)

QID 101884 (Type "101884" in App Search)

A 16 year-old female is being evaluated for shortness of breath. For the last year she has had shortness of breath and subjective wheezing with exercise and intermittent coughing at night. She reports waking up from sleep coughing 1-2 times per month. She now skips gym class because of her symptoms. She denies any coughing, chest tightness, or shortness of breath on the day of her visit. On exam, her lungs are clear to auscultation bilaterally, with normal inspiratory to expiratory duration ratio. Her pulmonary function tests (PFTs) show normal FEV1 and FVC based on her age, gender, and height. She is told to inhale a medication, and her PFTs are repeated, now showing a FEV1 79% of her previous reading. The patient is diagnosed with asthma. Which of the following medications was used to diagnose the patient?

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Methacholine

82%

194/238

Pilocarpine

5/238

Bethanechol

16/238

Carbachol

7/238

Physostigmine

8/238

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The patient is suffering from asthma. Methacholine is a direct cholinergic agonist used to diagnose asthma in a currently asymptomatic patient.

Methacholine, pilocarpine, bethanchol, and carbachol are all direct cholinomimetic agents, meaning that they are agonists of muscarinic and nicotinic receptors. Pilocarpine, bethanchol, and carbachol are more resistant to degradation by acetylcholinesterase than methacholine. The rapid onset and metabolism of methacholine make it an ideal agent to induce an obstructive pattern on PFTs in an asthma patient currently without PFT findings.

In a review of work-related asthma, Youakim reviews bronchodilator response and methacholine challenge tests for asthma. A positive bronchodilator response is an increase in FEV1 12% over baseline or an absolute increase of 200mL. In patients with normal FEV1 at the time of evaluation, a methacholine challenge test should be considered. A drop in FEV1 of greater than 20% after inhalation of 8mg/mL or less of methacholine is considered a positive result.

In an evaluation of the methacholine challenge test, Sumino et al. found that with a positive result cut off set at a 20% decrease in FEV1 after 8mg/ml methacholine, the sensitivity of the test is 77%, and the specificity is 96%. However, the sensitivity was lower in caucasian subjects than in African American subjects (69% vs 95%).

Illustration A lists relative and absolute contraindications for methacholine bronchoprovocation testing.
Illustration B lists possible causes of false-negatives in methacholine bronchoprovocation testing.

Incorrect Answers:
Answer 2: Pilocarpine is a direct cholinergic agonist used for the treatment of glaucoma.
Answer 3: Bethanechol is a direct cholinergic agonist used for the treatment of iatrogenic urinary retention.
Answer 4: Carbachol is a direct cholinergic agonist used for the treatment of glaucoma.
Answer 5: Physostigmine is used for the treatment of glaucoma, atropine overdoes, and nightshade poisoning.

ILLUSTRATIONS: