CNS drugs and antiepileptics: clozapine and smoking cessation: 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.

Try it

Pharmacology · CNS drugs and antiepileptics: clozapine and smoking cessation

Sample item

A man with treatment-resistant schizophrenia has been stable for a year on a fixed dose of clozapine. After admission to a smoke-free ward he stops smoking, and within a week he is sedated, hypotensive and has a seizure. What is the explanation?

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

The answer and the reasoning

C. Loss of CYP1A2 induction raised clozapine levels

Polycyclic hydrocarbons in tobacco smoke induce CYP1A2, which metabolises clozapine. Stopping smoking removes the induction, so levels can rise sharply, causing sedation, hypotension and seizures. The dose is usually reduced and levels are checked.

Option by option

  • A. Tolerance to the antipsychotic effect has developed

    Tolerance would reduce the effect, whereas this patient shows signs of excess.

  • B. Clozapine is now cleared more slowly by the kidney

    Clozapine is cleared mainly by hepatic metabolism, not by renal excretion.

  • C. Loss of CYP1A2 induction raised clozapine levels (correct)

    Correct. Without smoke-induced CYP1A2, clozapine clearance falls and levels rise.

  • D. Nicotine withdrawal directly caused the seizure

    Nicotine withdrawal causes irritability and craving and is not a standard cause of seizures here.

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.

More Pharmacology questions

Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is C, Loss of CYP1A2 induction raised clozapine levels. Polycyclic hydrocarbons in tobacco smoke induce CYP1A2, which metabolises clozapine.

Why is "Tolerance to the antipsychotic effect has developed" not the answer?

Tolerance would reduce the effect, whereas this patient shows signs of excess.

Why is "Clozapine is now cleared more slowly by the kidney" not the answer?

Clozapine is cleared mainly by hepatic metabolism, not by renal excretion.

Why is "Nicotine withdrawal directly caused the seizure" not the answer?

Nicotine withdrawal causes irritability and craving and is not a standard cause of seizures here.

What concept does this question test?

It tests CNS drugs and antiepileptics: clozapine and smoking cessation in Pharmacology. Stopping smoking removes the induction, so levels can rise sharply, causing sedation, hypotension and seizures. The dose is usually reduced and levels are checked.

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: clozapine and smoking cessation?

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.