CNS drugs and antiepileptics: lamotrigine and oestrogen: 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: lamotrigine and oestrogen

Sample item

A 25-year-old woman has been seizure-free on lamotrigine alone. After she starts a combined oestrogen-progestin pill she has breakthrough seizures, and her lamotrigine level is low. What is the mechanism?

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

The answer and the reasoning

D. Oestrogen induces glucuronidation of lamotrigine

Lamotrigine is cleared mainly by glucuronidation, which oestrogen-containing contraceptives induce, so levels can fall by about half. The dose may need to rise, and then fall again in the pill-free week or when the pill is stopped. Valproate has the opposite effect by inhibiting glucuronidation.

Option by option

  • A. Progestin displaces lamotrigine from albumin

    Displacement would raise the free fraction and would not account for a fall in total level.

  • B. The pill reduces intestinal absorption of lamotrigine

    Lamotrigine is almost completely absorbed, and the pill does not alter this.

  • C. Oestrogen inhibits CYP3A4 and raises lamotrigine

    Lamotrigine is not a CYP3A4 substrate to any important extent, and inhibition would raise the level.

  • D. Oestrogen induces glucuronidation of lamotrigine (correct)

    Correct. Oestrogen induces UDP-glucuronosyltransferase and speeds lamotrigine clearance.

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 D, Oestrogen induces glucuronidation of lamotrigine. Lamotrigine is cleared mainly by glucuronidation, which oestrogen-containing contraceptives induce, so levels can fall by about half.

Why is "Progestin displaces lamotrigine from albumin" not the answer?

Displacement would raise the free fraction and would not account for a fall in total level.

Why is "The pill reduces intestinal absorption of lamotrigine" not the answer?

Lamotrigine is almost completely absorbed, and the pill does not alter this.

Why is "Oestrogen inhibits CYP3A4 and raises lamotrigine" not the answer?

Lamotrigine is not a CYP3A4 substrate to any important extent, and inhibition would raise the level.

What concept does this question test?

It tests CNS drugs and antiepileptics: lamotrigine and oestrogen in Pharmacology. The dose may need to rise, and then fall again in the pill-free week or when the pill is stopped. Valproate has the opposite effect by inhibiting glucuronidation.

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: lamotrigine and oestrogen?

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.