ASPPB Psychopharmacology 3 — Questions and Answers
Question 1: Which of the following benzodiazepines is most appropriate for a patient with severe hepatic impairment?
- Diazepam
- Chlordiazepoxide
- Lorazepam (Correct answer)
- Clonazepam
Correct answer: Lorazepam
Lorazepam (along with oxazepam and temazepam) undergoes direct glucuronidation rather than hepatic oxidation, making it safer in liver disease.
Question 2: A patient on carbamazepine experiences double vision and ataxia after a new medication is added. The new drug most likely inhibited CYP3A4, causing:
- Reduced carbamazepine levels leading to breakthrough seizures
- Elevated carbamazepine levels producing toxicity (Correct answer)
- Induction of carbamazepine's own metabolism
- Displacement of carbamazepine from protein binding sites
Correct answer: Elevated carbamazepine levels producing toxicity
Carbamazepine is a CYP3A4 substrate; CYP3A4 inhibition raises its plasma concentration and produces dose-dependent toxicity.
Question 3: The discontinuation syndrome most associated with paroxetine, characterized by dizziness, 'brain zaps,' and flu-like symptoms, is attributable primarily to:
- Rebound norepinephrine excess
- Rapid decrease in synaptic serotonin following abrupt cessation (Correct answer)
- Dopamine D2 receptor upregulation
- Cholinergic rebound due to paroxetine's anticholinergic properties
Correct answer: Rapid decrease in synaptic serotonin following abrupt cessation
Abrupt SSRI withdrawal rapidly drops serotonin availability at synapses, producing a characteristic discontinuation syndrome; paroxetine's short half-life worsens this.
Question 4: Which mood stabilizer is first-line for acute bipolar mania and also has the strongest evidence for suicide prevention in bipolar disorder?
- Valproate
- Lamotrigine
- Lithium (Correct answer)
- Quetiapine
Correct answer: Lithium
Lithium has robust evidence for both acute mania and long-term suicide risk reduction in bipolar disorder.
Question 5: Tardive dyskinesia risk is highest with which class of antipsychotics?
- Second-generation antipsychotics with high 5-HT2A affinity
- First-generation high-potency D2 blockers such as haloperidol (Correct answer)
- Partial D2 agonists such as aripiprazole
- Clozapine and quetiapine with low D2 occupancy
Correct answer: First-generation high-potency D2 blockers such as haloperidol
High-potency first-generation antipsychotics (e.g., haloperidol) produce sustained nigrostriatal D2 blockade, the mechanism underlying tardive dyskinesia.
Question 6: Buprenorphine for opioid use disorder is formulated with naloxone primarily to:
- Enhance analgesic potency through opioid synergism
- Deter intravenous misuse by precipitating withdrawal if injected (Correct answer)
- Reduce buprenorphine's ceiling effect on respiratory depression
- Accelerate buprenorphine absorption sublingually
Correct answer: Deter intravenous misuse by precipitating withdrawal if injected
Sublingual naloxone has negligible bioavailability, but if the tablet is injected, naloxone absorbs systemically and precipitates acute opioid withdrawal.
Question 7: Patients taking warfarin who are started on fluoxetine should be monitored closely because fluoxetine:
- Induces CYP2C9, increasing warfarin clearance
- Inhibits CYP2C9, reducing warfarin metabolism and raising INR (Correct answer)
- Displaces warfarin from albumin, increasing free fraction transiently
- Promotes vitamin K absorption, antagonizing warfarin's effect
Correct answer: Inhibits CYP2C9, reducing warfarin metabolism and raising INR
Fluoxetine inhibits CYP2C9, the primary enzyme metabolizing S-warfarin, leading to elevated warfarin levels and bleeding risk.
ASPPB Psychopharmacology 3
Which of the following benzodiazepines is most appropriate for a patient with severe hepatic impairment?