Local anaesthetics: pKa and onset: practice question

A Anaesthesia 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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Anaesthesia · Local anaesthetics: pKa and onset

Sample item

Why does lignocaine have a faster onset than bupivacaine at physiological pH?

AIt binds plasma proteins more stronglyBIt has a higher molecular weightCIt is more lipid solubleDIts pKa is closer to tissue pH, so more of the drug is in the unionised form

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

The answer and the reasoning

D. Its pKa is closer to tissue pH, so more of the drug is in the unionised form

Lignocaine has a pKa of 7.9 and bupivacaine 8.1, so at pH 7.4 a larger fraction of lignocaine is unionised and crosses the nerve membrane. Onset is also influenced by concentration and dose, but pKa is the main molecular determinant.

Option by option

A. It binds plasma proteins more strongly
Bupivacaine binds proteins more strongly and acts for longer.
B. It has a higher molecular weight
Molecular weight is not the reason.
C. It is more lipid soluble
Bupivacaine is more lipid soluble.
D. Its pKa is closer to tissue pH, so more of the drug is in the unionised form (correct)
Correct. A lower pKa increases the unionised fraction.

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 Anaesthesia question

What is the answer to this Anaesthesia question?

The best answer is D, Its pKa is closer to tissue pH, so more of the drug is in the unionised form. Lignocaine has a pKa of 7.

Why is "It binds plasma proteins more strongly" not the answer?

Bupivacaine binds proteins more strongly and acts for longer.

Why is "It has a higher molecular weight" not the answer?

Molecular weight is not the reason.

Why is "It is more lipid soluble" not the answer?

Bupivacaine is more lipid soluble.

What concept does this question test?

It tests Local anaesthetics: pKa and onset in Anaesthesia. 9 and bupivacaine 8.1, so at pH 7.4 a larger fraction of lignocaine is unionised and crosses the nerve membrane. Onset is also influenced by concentration and dose, but pKa is the main molecular determinant.

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 Local anaesthetics: pKa and onset?

Make a table of each agent, its key advantage and its main side effect. Then use the flashcards and the other Anaesthesia 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.