MRCPsych Pharmacology Fundamentals 3 — Questions and Answers
Question 1: Which antipsychotic is most associated with QTc prolongation and carries the highest risk of torsades de pointes?
- Aripiprazole
- Quetiapine
- Thioridazine (Correct answer)
- Amisulpride
Correct answer: Thioridazine
Thioridazine has the greatest QTc-prolonging effect among antipsychotics and has been withdrawn in many countries due to fatal arrhythmia risk.
Question 2: The Maudsley Prescribing Guidelines recommend plasma level monitoring for which drug primarily to assess adherence and toxicity?
- Sertraline
- Quetiapine
- Clozapine (Correct answer)
- Aripiprazole
Correct answer: Clozapine
Clozapine plasma level monitoring (target 0.35–0.60 mg/L) is recommended to confirm adherence and reduce toxicity risk.
Question 3: A patient develops rigidity, hyperthermia, autonomic instability, and elevated CK after starting haloperidol. What is the most likely diagnosis?
- Serotonin syndrome
- Neuroleptic malignant syndrome (Correct answer)
- Anticholinergic toxicity
- Malignant hyperthermia
Correct answer: Neuroleptic malignant syndrome
Neuroleptic malignant syndrome (NMS) presents with the tetrad of hyperthermia, rigidity, autonomic instability, and altered consciousness after antipsychotic exposure.
Question 4: Which of the following best describes the concept of 'receptor occupancy' in antipsychotic prescribing?
- The proportion of drug absorbed from the GI tract
- The percentage of target receptors bound by a drug at a given plasma level (Correct answer)
- The ratio of drug in plasma to drug in tissue
- The time for 50% of the drug to be eliminated
Correct answer: The percentage of target receptors bound by a drug at a given plasma level
Receptor occupancy describes the fraction of receptors occupied by a drug, with D2 occupancy of 60–80% associated with antipsychotic efficacy and <80% minimising EPS.
Question 5: Which SSRI is considered safest in overdose due to its relatively flat dose-response curve and low cardiac toxicity?
- Citalopram
- Fluoxetine (Correct answer)
- Paroxetine
- Fluvoxamine
Correct answer: Fluoxetine
Fluoxetine has a very wide therapeutic index; in overdose it rarely causes serious cardiac effects, unlike citalopram which prolongs QTc in high doses.
Question 6: Which mechanism explains the use of propranolol for lithium-induced tremor?
- Alpha-1 adrenergic blockade reducing peripheral vasoconstriction
- Beta-adrenergic blockade reducing peripheral tremor amplitude (Correct answer)
- Inhibition of lithium renal reabsorption
- GABA-B agonism in the cerebellum
Correct answer: Beta-adrenergic blockade reducing peripheral tremor amplitude
Propranolol, a non-selective beta-blocker, reduces the amplitude of action (physiological) tremor by blocking peripheral beta-2 adrenergic receptors in muscle.
Question 7: Which pharmacodynamic interaction explains why combining SSRIs with tramadol increases the risk of serotonin syndrome?
- Both inhibit monoamine oxidase
- Tramadol inhibits serotonin reuptake AND is a weak mu-opioid agonist, with SSRIs adding additive serotonergic load (Correct answer)
- SSRIs increase tramadol bioavailability via CYP2D6 inhibition
- Both block 5-HT3 receptors
Correct answer: Tramadol inhibits serotonin reuptake AND is a weak mu-opioid agonist, with SSRIs adding additive serotonergic load
Tramadol inhibits serotonin and noradrenaline reuptake; combined with an SSRI, the additive serotonergic effect raises serotonin syndrome risk.
MRCPsych Pharmacology Fundamentals 3
Which antipsychotic is most associated with QTc prolongation and carries the highest risk of torsades de pointes?