CNS drugs and antiepileptics: valproate and mitochondrial disease: 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 · CNS drugs and antiepileptics: valproate and mitochondrial disease

Sample item

A 14-month-old with developmental regression, intractable seizures and raised blood lactate is suspected to have a POLG mitochondrial disorder. Which antiepileptic should be avoided because it can precipitate fatal liver failure?

ALevetiracetamBSodium valproateCClobazamDPhenobarbitone

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

The answer and the reasoning

B. Sodium valproate

Valproate impairs mitochondrial beta-oxidation and carnitine handling. In children with POLG mutations, as in Alpers-Huttenlocher syndrome, it can cause rapidly fatal hepatic failure and is contraindicated.

Option by option

A. Levetiracetam
Levetiracetam is renally cleared and has little hepatic or mitochondrial toxicity.
B. Sodium valproate (correct)
Correct. Valproate is contraindicated in POLG-related mitochondrial disease because of fatal hepatotoxicity.
C. Clobazam
Clobazam has no known mitochondrial hepatotoxicity.
D. Phenobarbitone
Phenobarbitone, though sedating, is not specifically linked with fatal liver failure in POLG disease.

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 B, Sodium valproate. Valproate impairs mitochondrial beta-oxidation and carnitine handling.

Why is "Levetiracetam" not the answer?

Levetiracetam is renally cleared and has little hepatic or mitochondrial toxicity.

Why is "Clobazam" not the answer?

Clobazam has no known mitochondrial hepatotoxicity.

Why is "Phenobarbitone" not the answer?

Phenobarbitone, though sedating, is not specifically linked with fatal liver failure in POLG disease.

What concept does this question test?

It tests CNS drugs and antiepileptics: valproate and mitochondrial disease in Pharmacology. In children with POLG mutations, as in Alpers-Huttenlocher syndrome, it can cause rapidly fatal hepatic failure and is contraindicated.

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 CNS drugs and antiepileptics: valproate and mitochondrial disease?

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.