USMLE PRACTICE QUESTION #77
TOPIC: Pharmacology MOA.
Today’s question will test your ability to recognize the mechanism of action of a commonly tested pharmaceutical drug.
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A 43-year-old man with a history of heart transplantation presents to the clinic for a routine follow-up. He has been taking several medications as part of his immunosuppressive therapy, including mycophenolate mofetil. Which of the following best describes the mechanism of action of mycophenolate mofetil?
A. Inhibition of purine synthesis by incorporating into DNA and RNA
B. Inhibition of inosine monophosphate dehydrogenase
C. Inhibition of mTOR, leading to reduced T-cell activation
D. Inhibition of COX-2, leading to reduced prostaglandin synthesis
E. Inhibition of microtubule polymerization
F. Blockade of the IL-2 receptor alpha chain (CD25) on T cells
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
The MENTAL MODEL used to answer this question comes from our detailed test-taking skills masterclass (check it out if you want to boost your USMLE test-taking skills). Here’s how to think through this question:
Step 1. Read the last line to determine the actual question: “Which of the following best describes the mechanism of action of mycophenolate mofetil?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 1st order. 1st: Identify the MOA of the drug in question.
Step 3: Read the vignette carefully and ask yourself: “What’s the MOA of mycophenolate mofetil?”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
This rare 1st-order question allows us to quickly and easily collect a point on exam day. We must be able to identify a 1st-order question so we don’t waste time reading the vignette; it wastes time without adding anything of importance. In this case, the last line of the vignette poses the question along with the only piece of information needed to answer.
ANSWER CHOICES:
CHOICE A: Inhibition of purine synthesis by incorporating into DNA and RNA
Explanation: This mechanism involves antimetabolites that incorporate into nucleic acids, disrupting their synthesis. This is the mechanism of action of drugs like azathioprine and 6-mercaptopurine. Mycophenolate mofetil does not incorporate into DNA/RNA.
CHOICE B: Inhibition of inosine monophosphate dehydrogenase
Explanation: This correctly describes the MOA of Mycophenolate mofetil. It is converted to mycophenolic acid, which inhibits inosine monophosphate dehydrogenase (IMPDH), which is crucial for de novo guanosine nucleotide synthesis.
CHOICE C: Inhibition of mTOR, leading to reduced T-cell activation
Explanation: mTOR inhibitors block a key signaling pathway necessary for T-cell proliferation. This is performed by drugs like sirolimus (rapamycin) and everolimus. Mycophenolate mofetil does not inhibit mTOR.
CHOICE D: Inhibition of COX-2, leading to reduced prostaglandin synthesis
Explanation: COX-2 inhibitors reduce inflammation by blocking prostaglandin production. This is accomplished with drugs like celecoxib and other NSAIDs. This is not part of mycophenolate mofetil’s MOA.
CHOICE E: Inhibition of microtubule polymerization
Explanation: This mechanism disrupts cell division by preventing microtubule formation, as is seen with drugs like colchicine, vincristine, and vinblastine. Mycophenolate mofetil does not affect microtubules.
CHOICE F: Blockade of the IL-2 receptor alpha chain (CD25) on T cells
Explanation: This prevents IL-2-mediated T-cell activation, which is accomplished with drugs like basiliximab and daclizumab, not mycophenolate mofetil.
FINAL VERDICT…
The correct mechanism of action for mycophenolate mofetil is the inhibition of inosine monophosphate dehydrogenase (IMPDH), which selectively affects lymphocyte proliferation by depleting guanosine nucleotides.
CORRECT ANSWER: B) Inhibition of inosine monophosphate dehydrogenase
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That’s it for question 77!
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