Pharmacology Central Nervous System Agents 3 — Questions and Answers
Question 1: A patient taking clozapine develops a fever, sore throat, and absolute neutrophil count of 400/mm³. What is the immediate action?
- Continue clozapine and start prophylactic antibiotics
- Permanently discontinue clozapine and notify the registry (Correct answer)
- Reduce the clozapine dose by 50% and recheck ANC in 3 days
- Switch to olanzapine and monitor weekly
Correct answer: Permanently discontinue clozapine and notify the registry
ANC below 500/mm³ indicates severe agranulocytosis; clozapine must be permanently discontinued and the REMS registry notified immediately.
Question 2: Which opioid is contraindicated in patients with renal failure due to accumulation of an active neurotoxic metabolite?
- Fentanyl
- Hydromorphone
- Meperidine (Correct answer)
- Buprenorphine
Correct answer: Meperidine
Meperidine's active metabolite normeperidine accumulates in renal failure and causes CNS excitation, tremors, and seizures.
Question 3: A depressed patient starts an SSRI. Which adverse effect should be specifically discussed during the first 1-2 weeks of therapy?
- Agranulocytosis requiring weekly blood draws
- Increased suicidal ideation, especially in patients under 25 (Correct answer)
- Irreversible sexual dysfunction requiring drug discontinuation
- Tardive dyskinesia developing within the first month
Correct answer: Increased suicidal ideation, especially in patients under 25
The FDA black box warning for antidepressants highlights increased suicidal thinking and behavior in patients under 25, most prominent in the first few weeks.
Question 4: Which drug combination is most likely to cause serotonin syndrome?
- Haloperidol + lithium
- Phenelzine + meperidine (Correct answer)
- Clonazepam + amitriptyline
- Clozapine + valproate
Correct answer: Phenelzine + meperidine
Phenelzine (MAO inhibitor) combined with meperidine (which also inhibits serotonin reuptake) causes dangerous serotonin excess.
Question 5: A patient receiving haloperidol develops sustained muscle rigidity, hyperthermia of 40°C, and autonomic instability. What is the diagnosis?
- Tardive dyskinesia
- Neuroleptic malignant syndrome (Correct answer)
- Serotonin syndrome
- Acute dystonic reaction
Correct answer: Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is characterized by the tetrad of hyperthermia, rigidity, autonomic instability, and altered consciousness from dopamine blockade.
Question 6: Carbidopa is combined with levodopa in Parkinson's treatment primarily to:
- Enhance levodopa's effect on D2 receptors in the basal ganglia
- Inhibit peripheral DOPA decarboxylase, reducing peripheral dopamine conversion (Correct answer)
- Prevent levodopa degradation by MAO-B in the CNS
- Block COMT to extend levodopa's half-life systemically
Correct answer: Inhibit peripheral DOPA decarboxylase, reducing peripheral dopamine conversion
Carbidopa inhibits peripheral DOPA decarboxylase, preventing levodopa conversion to dopamine outside the CNS and reducing peripheral side effects while increasing CNS availability.
Question 7: A patient reports taking a medication for neuropathic pain that works by binding to alpha-2-delta subunits of voltage-gated calcium channels. This drug is most likely:
- Carbamazepine
- Amitriptyline
- Gabapentin (Correct answer)
- Duloxetine
Correct answer: Gabapentin
Gabapentin (and pregabalin) bind to the alpha-2-delta subunit of voltage-gated calcium channels, reducing neuronal excitability and neuropathic pain signaling.
Pharmacology Central Nervous System Agents 3
A patient taking clozapine develops a fever, sore throat, and absolute neutrophil count of 400/mm³.
What is the immediate action?