Pharmacodynamics: tachyphylaxis: 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 · Pharmacodynamics: tachyphylaxis

Sample item

During spinal anaesthesia a man is given ephedrine boluses every few minutes for hypotension, and each successive dose produces a smaller rise in blood pressure. What is the most likely mechanism?

ADevelopment of neutralising antibodies against ephedrineBInduction of hepatic enzymes that accelerate ephedrine metabolismCGenetic loss of beta receptors over minutesDDepletion of releasable noradrenaline stores in sympathetic nerve terminals

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

The answer and the reasoning

D. Depletion of releasable noradrenaline stores in sympathetic nerve terminals

Ephedrine acts mainly indirectly by displacing noradrenaline from vesicles. With rapid repeated dosing the releasable store is exhausted and the response falls within minutes, which is termed tachyphylaxis. A direct agonist such as phenylephrine does not show this because it does not depend on stored transmitter.

Option by option

A. Development of neutralising antibodies against ephedrine
Ephedrine is a small molecule and does not provoke neutralising antibodies on this timescale.
B. Induction of hepatic enzymes that accelerate ephedrine metabolism
Enzyme induction takes days and cannot explain a fall within minutes.
C. Genetic loss of beta receptors over minutes
Receptor gene expression cannot change over minutes, and the effect depends on transmitter release.
D. Depletion of releasable noradrenaline stores in sympathetic nerve terminals (correct)
Correct. An indirectly acting amine loses effect when its transmitter store is depleted.

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.

Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is D, Depletion of releasable noradrenaline stores in sympathetic nerve terminals. Ephedrine acts mainly indirectly by displacing noradrenaline from vesicles.

Why is "Development of neutralising antibodies against ephedrine" not the answer?

Ephedrine is a small molecule and does not provoke neutralising antibodies on this timescale.

Why is "Induction of hepatic enzymes that accelerate ephedrine metabolism" not the answer?

Enzyme induction takes days and cannot explain a fall within minutes.

Why is "Genetic loss of beta receptors over minutes" not the answer?

Receptor gene expression cannot change over minutes, and the effect depends on transmitter release.

What concept does this question test?

It tests Pharmacodynamics: tachyphylaxis in Pharmacology. With rapid repeated dosing the releasable store is exhausted and the response falls within minutes, which is termed tachyphylaxis. A direct agonist such as phenylephrine does not show this because it does not depend on stored transmitter.

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 Pharmacodynamics: tachyphylaxis?

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.