Autonomic nervous system: linaclotide mechanism: 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 · Autonomic nervous system: linaclotide mechanism

Sample item

A woman with irritable bowel syndrome with constipation has not responded to fibre and an osmotic laxative. She is started on linaclotide. Which mechanism lies behind its effect?

ABlockade of peripheral mu opioid receptors in the gut wallBAgonism at 5-HT4 receptors to stimulate peristalsisCOpening of ClC-2 chloride channels by a prostaglandin E1 derivativeDGuanylate cyclase C activation, raising cGMP and luminal chloride and bicarbonate secretion

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

The answer and the reasoning

D. Guanylate cyclase C activation, raising cGMP and luminal chloride and bicarbonate secretion

Linaclotide is a peptide that acts on the luminal surface of enterocytes as a guanylate cyclase C agonist. The rise in cGMP increases chloride and bicarbonate secretion and also reduces visceral pain signalling. Lubiprostone acts on ClC-2 channels, and prucalopride on 5-HT4 receptors.

Option by option

A. Blockade of peripheral mu opioid receptors in the gut wall
Peripheral mu receptor blockade is used for opioid-induced constipation and not for irritable bowel syndrome.
B. Agonism at 5-HT4 receptors to stimulate peristalsis
5-HT4 agonism is the mechanism of prucalopride.
C. Opening of ClC-2 chloride channels by a prostaglandin E1 derivative
ClC-2 channel activation is the mechanism of lubiprostone.
D. Guanylate cyclase C activation, raising cGMP and luminal chloride and bicarbonate secretion (correct)
Correct. Guanylate cyclase C agonism with raised cGMP drives fluid secretion.

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, Guanylate cyclase C activation, raising cGMP and luminal chloride and bicarbonate secretion. Linaclotide is a peptide that acts on the luminal surface of enterocytes as a guanylate cyclase C agonist.

Why is "Blockade of peripheral mu opioid receptors in the gut wall" not the answer?

Peripheral mu receptor blockade is used for opioid-induced constipation and not for irritable bowel syndrome.

Why is "Agonism at 5-HT4 receptors to stimulate peristalsis" not the answer?

5-HT4 agonism is the mechanism of prucalopride.

Why is "Opening of ClC-2 chloride channels by a prostaglandin E1 derivative" not the answer?

ClC-2 channel activation is the mechanism of lubiprostone.

What concept does this question test?

It tests Autonomic nervous system: linaclotide mechanism in Pharmacology. The rise in cGMP increases chloride and bicarbonate secretion and also reduces visceral pain signalling. Lubiprostone acts on ClC-2 channels, and prucalopride on 5-HT4 receptors.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. 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 Autonomic nervous system: linaclotide mechanism?

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.