MRCPsych Pharmacology Fundamentals 2 — Questions and Answers
Question 1: Which cytochrome P450 enzyme is primarily responsible for the metabolism of clozapine?
- CYP2D6
- CYP1A2 (Correct answer)
- CYP3A4
- CYP2C19
Correct answer: CYP1A2
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?
- Blockade of ADH receptors in the collecting duct
- Inhibition of aquaporin-2 (AQP2) channel insertion via reduced cAMP (Correct answer)
- Direct tubular damage reducing GFR
- Increased aldosterone secretion
Correct answer: Inhibition of aquaporin-2 (AQP2) channel insertion via reduced cAMP
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?
- Volume of distribution
- Bioavailability
- Half-life (Correct answer)
- Peak plasma concentration (Cmax)
Correct answer: Half-life
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?
- Sexual dysfunction
- Sedation and weight gain (Correct answer)
- QTc prolongation
- Hepatotoxicity
Correct answer: Sedation and weight gain
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?
- GABA-A positive allosteric modulation
- 5-HT1A partial agonism (Correct answer)
- D2 receptor blockade
- Noradrenaline reuptake inhibition
Correct answer: 5-HT1A partial agonism
Buspirone acts as a partial agonist at 5-HT1A receptors, providing anxiolytic effects without benzodiazepine-related dependence.
Question 6: A patient taking phenelzine eats a tyramine-rich meal and develops a hypertensive crisis. Which enzyme is phenelzine inhibiting?
- Catechol-O-methyltransferase (COMT)
- Tyrosine hydroxylase
- Monoamine oxidase (MAO) (Correct answer)
- Dopamine beta-hydroxylase
Correct answer: Monoamine oxidase (MAO)
Phenelzine irreversibly inhibits MAO, preventing tyramine breakdown and leading to massive noradrenaline release and hypertensive crisis.
Question 7: Which statement about the pharmacology of sodium valproate is correct?
- It primarily acts by blocking dopamine D2 receptors
- It enhances GABA activity and inhibits sodium channels (Correct answer)
- It is a selective serotonin reuptake inhibitor
- It acts solely via NMDA receptor antagonism
Correct answer: It enhances GABA activity and inhibits sodium channels
Valproate has multiple mechanisms including GABA transaminase inhibition (increasing GABA) and voltage-gated sodium channel blockade.
MRCPsych Pharmacology Fundamentals 2
Which cytochrome P450 enzyme is primarily responsible for the metabolism of clozapine?