Antianginals: nitrate and PDE5 inhibitor interaction: practice question

A Pharmacology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pharmacology · Antianginals: nitrate and PDE5 inhibitor interaction

Sample item

A 62-year-old man with stable angina on isosorbide mononitrate takes sildenafil for erectile dysfunction and collapses with severe hypotension. Which mechanism underlies this interaction?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

C. Nitrate increases cyclic GMP formation while sildenafil prevents its breakdown, causing excessive vasodilatation

Nitrates release nitric oxide, which stimulates guanylyl cyclase to raise cGMP in vascular smooth muscle. Phosphodiesterase-5 inhibitors block cGMP degradation, so the combination produces an exaggerated, sometimes fatal, fall in blood pressure. Nitrates and PDE5 inhibitors must not be combined, and a nitrate-free interval is required after the PDE5 inhibitor.

Option by option

  • A. Nitrates inhibit hepatic metabolism of sildenafil, producing a toxic metabolite

    The interaction is pharmacodynamic and does not involve a toxic metabolite.

  • B. Sildenafil blocks L-type calcium channels, adding to nitrate-induced vasodilatation

    Sildenafil has no calcium channel blocking action.

  • C. Nitrate increases cyclic GMP formation while sildenafil prevents its breakdown, causing excessive vasodilatation (correct)

    Correct. Increased synthesis plus decreased breakdown of cGMP is additive.

  • D. Sildenafil inhibits nitric oxide synthase and causes rebound vasodilatation

    Sildenafil does not inhibit nitric oxide synthase; it amplifies the nitric oxide pathway downstream.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is C, Nitrate increases cyclic GMP formation while sildenafil prevents its breakdown, causing excessive vasodilatation. Nitrates release nitric oxide, which stimulates guanylyl cyclase to raise cGMP in vascular smooth muscle.

Why is "Nitrates inhibit hepatic metabolism of sildenafil, producing a toxic…" not the answer?

The interaction is pharmacodynamic and does not involve a toxic metabolite.

Why is "Sildenafil blocks L-type calcium channels, adding to nitrate-induced…" not the answer?

Sildenafil has no calcium channel blocking action.

Why is "Sildenafil inhibits nitric oxide synthase and causes rebound vasodila…" not the answer?

Sildenafil does not inhibit nitric oxide synthase; it amplifies the nitric oxide pathway downstream.

What concept does this question test?

It tests Antianginals: nitrate and PDE5 inhibitor interaction in Pharmacology. Phosphodiesterase-5 inhibitors block cGMP degradation, so the combination produces an exaggerated, sometimes fatal, fall in blood pressure. Nitrates and PDE5 inhibitors must not be combined, and a nitrate-free interval is required after the PDE5 inhibitor.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Antianginals: nitrate and PDE5 inhibitor interaction?

Learn drugs as classes, then the exception in each class that an examiner would pick. Then use the flashcards and the other Pharmacology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.