Pharmacokinetics: high extraction drugs in portal shunting: 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 · Pharmacokinetics: high extraction drugs in portal shunting

Sample item

A 55-year-old man with cirrhosis and extensive portosystemic shunting is given the usual oral dose of propranolol and develops marked bradycardia and hypotension. Which explanation best accounts for this?

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

The answer and the reasoning

A. Shunting bypasses first-pass metabolism, so oral bioavailability of this high extraction drug rises

Propranolol has a high hepatic extraction ratio, so a large fraction is removed on first pass and its oral bioavailability is normally low. With portosystemic shunts, portal blood bypasses hepatocytes and bioavailability can rise several-fold, so oral doses must be lowered. Clearance of such drugs depends mainly on hepatic blood flow.

Option by option

  • A. Shunting bypasses first-pass metabolism, so oral bioavailability of this high extraction drug rises (correct)

    Correct. Reduced first-pass extraction makes the standard oral dose behave like a much larger one.

  • B. Ascites reduces the volume of distribution of the lipophilic drug, raising plasma levels

    Ascites enlarges the volume of distribution of water-soluble drugs, and propranolol is lipophilic, so this is not the main factor.

  • C. Renal clearance of the drug falls because of hepatorenal physiology

    Propranolol is eliminated almost entirely by hepatic metabolism, not by the kidney.

  • D. Hypoalbuminaemia increases hepatic clearance by raising the free fraction

    A higher free fraction would help clearance only of low extraction drugs, and does not explain the large bioavailability change.

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 A, Shunting bypasses first-pass metabolism, so oral bioavailability of this high extraction drug rises. Propranolol has a high hepatic extraction ratio, so a large fraction is removed on first pass and its oral bioavailability is normally low.

Why is "Ascites reduces the volume of distribution of the lipophilic drug, ra…" not the answer?

Ascites enlarges the volume of distribution of water-soluble drugs, and propranolol is lipophilic, so this is not the main factor.

Why is "Renal clearance of the drug falls because of hepatorenal physiology" not the answer?

Propranolol is eliminated almost entirely by hepatic metabolism, not by the kidney.

Why is "Hypoalbuminaemia increases hepatic clearance by raising the free frac…" not the answer?

A higher free fraction would help clearance only of low extraction drugs, and does not explain the large bioavailability change.

What concept does this question test?

It tests Pharmacokinetics: high extraction drugs in portal shunting in Pharmacology. With portosystemic shunts, portal blood bypasses hepatocytes and bioavailability can rise several-fold, so oral doses must be lowered. Clearance of such drugs depends mainly on hepatic blood flow.

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 Pharmacokinetics: high extraction drugs in portal shunting?

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.