USMLE PRACTICE QUESTION #117
TOPIC: Medication Side Effects
USMLE practice question #117 will test your understanding of the underlying cause of a common medication side effect.
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A 52-year-old woman presents to her primary care physician with a persistent dry cough for the past 2 weeks. She denies fever, wheezing, chest pain, or dyspnea. She was recently started on lisinopril for hypertension 1 month ago. Physical examination reveals no abnormalities and the chest X-ray is unremarkable. Laboratory tests, including a complete blood count and basic metabolic panel, are within normal limits. Which of the following best explains the pathophysiology of this patient’s symptom?
A) Increased activation of the kallikrein-kinin system
B) Reduced degradation of bradykinin and substance P
C) Inhibition of nitric oxide synthase in pulmonary endothelial cells
D) Increased cyclooxygenase-2 (COX-2) activity in airway epithelium
E) Enhanced prostacyclin synthesis by pulmonary macrophages
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “Which of the following best explains the pathophysiology of this patient’s symptom?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Recognize the cause of the side effect; 2nd: Identify the underlying cause of the side effect.
Step 3: Read the vignette carefully and ask yourself: “The underlying cause of ACE inhibitor-induced cough is what?”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
This vignette describes a 52-year-old woman with a persistent dry cough for the past two weeks. She was recently started on lisinopril, an angiotensin-converting enzyme inhibitor (ACE inhibitor), for hypertension. The cough is nonproductive and has been present for about a month, which is consistent with one of the most common side effects of ACE inhibitors: ACE inhibitor-induced cough.
ANSWER CHOICES:
CHOICE A: Increased activation of kallikrein-kinin system
Explanation: The kallikrein-kinin system involves the production of bradykinin, which is degraded by ACE. ACE inhibitors do not increase the activation of this system; they block the degradation of bradykinin.
CHOICE B: Reduced degradation of bradykinin and substance P
Explanation: ACE normally degrades bradykinin and substance P. When ACE is inhibited (as with lisinopril), these substances accumulate, leading to irritation in the respiratory tract and causing a persistent dry cough.
CHOICE C: Inhibition of nitric oxide synthase in pulmonary endothelial cells
Explanation: Nitric oxide synthase produces nitric oxide, a vasodilator. Inhibition of nitric oxide synthase would reduce nitric oxide production, but this mechanism is not related to ACE inhibitor-induced cough.
CHOICE D: Increased cyclooxygenase-2 (COX-2) activity in airway epithelium
Explanation: COX-2 is an enzyme involved in inflammation and pain pathways, producing prostaglandins. Increased COX-2 activity can lead to inflammation but is not related to ACE inhibitor-induced cough.
CHOICE E: Enhanced prostacyclin synthesis by pulmonary macrophages
Explanation: Prostacyclin is a vasodilator produced by endothelial cells and macrophages. It plays a role in vascular homeostasis but does not contribute to the mechanism behind an ACE inhibitor-induced cough.
FINAL VERDICT…
The patient's persistent dry cough after starting lisinopril (an ACE inhibitor) is most likely due to the accumulation of bradykinin and substance P, which are normally degraded by angiotensin-converting enzyme (ACE). When ACE is inhibited, these substances accumulate in the respiratory tract, leading to irritation and triggering a persistent dry cough. This side effect typically resolves after discontinuation or switching to another class of antihypertensive medication, such as an angiotensin II receptor blocker (ARB), which does not affect bradykinin metabolism.
KEY CONCEPTS:
ACE inhibitors, such as lisinopril, are commonly used to treat hypertension and heart failure.
One of the well-known side effects of ACE inhibitors is a persistent dry cough, which occurs in approximately 5-20% of patients.
This cough is thought to be caused by the accumulation of bradykinin and substance P, which ACE normally degrades. When ACE is inhibited, these substances accumulate in the respiratory tract, leading to irritation and cough.
CORRECT ANSWER: B) Reduced degradation of bradykinin and substance P
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