MRCPsych Pharmacology Fundamentals 2

Question 1

Which cytochrome P450 enzyme is primarily responsible for the metabolism of clozapine?

Accepted Answer

CYP1A2

Answer

Clozapine is primarily metabolized by CYP1A2, which is why smoking (a CYP1A2 inducer) significantly lowers clozapine plasma levels.

Question 2

A patient on lithium develops polyuria and polydipsia. Which mechanism best explains lithium-induced nephrogenic diabetes insipidus?

Accepted Answer

Inhibition of aquaporin-2 (AQP2) channel insertion via reduced cAMP

Answer

Lithium inhibits adenylyl cyclase, reducing cAMP signaling and preventing ADH-stimulated AQP2 channel insertion in the collecting duct.

Question 3

Which pharmacokinetic parameter best predicts the risk of drug accumulation with repeated dosing?

Accepted Answer

Half-life

Answer

Half-life determines time to steady state and accumulation risk; steady state is reached after approximately 4–5 half-lives.

Question 4

Mirtazapine's antihistamine properties are primarily responsible for which side effect?

Accepted Answer

Sedation and weight gain

Answer

Mirtazapine's potent H1 receptor antagonism causes sedation and increased appetite, leading to weight gain.

Question 5

Which receptor mechanism underlies the therapeutic action of buspirone in generalised anxiety disorder?

Accepted Answer

5-HT1A partial agonism

Answer

Buspirone acts as a partial agonist at 5-HT1A receptors, providing anxiolytic effects without benzodiazepine-related dependence.

(MRCPsych) Member of the Royal College of Psychiatrists Practice Test