ABCN Pharmacology Fundamentals 3 — Questions and Answers
Question 1: Which benzodiazepine is preferred for elderly patients because it does not undergo hepatic oxidation and lacks active metabolites?
- Diazepam
- Clonazepam
- Lorazepam (Correct answer)
- Alprazolam
Correct answer: Lorazepam
Lorazepam undergoes direct glucuronidation (the LOT rule: Lorazepam, Oxazepam, Temazepam) and is safer in elderly patients with impaired hepatic oxidative metabolism.
Question 2: A patient on valproate develops tremor, weight gain, and elevated ammonia levels without liver disease. The elevated ammonia is best explained by valproate's effect on:
- Inhibition of urea cycle enzymes via carnitine depletion (Correct answer)
- Increased renal ammonia excretion
- Enhanced glutamate decarboxylase activity
- Blockade of hepatic glutamine synthetase
Correct answer: Inhibition of urea cycle enzymes via carnitine depletion
Valproate depletes carnitine and inhibits urea cycle function, leading to hyperammonemia independent of hepatotoxicity.
Question 3: Which atypical antipsychotic is most associated with metabolic syndrome, weight gain, and new-onset diabetes?
- Aripiprazole
- Ziprasidone
- Clozapine (Correct answer)
- Lurasidone
Correct answer: Clozapine
Clozapine has the highest risk of metabolic syndrome among antipsychotics due to potent H1, muscarinic, and 5-HT2C antagonism.
Question 4: A neuropsychologist is informed that a patient's phenytoin level is within normal range but the patient has symptoms of toxicity. Which condition would most likely explain this discrepancy?
- Concurrent use of an enzyme inducer
- Hypoalbuminemia shifting the free fraction upward (Correct answer)
- Increased renal clearance
- Hepatic enzyme deficiency increasing total drug
Correct answer: Hypoalbuminemia shifting the free fraction upward
Phenytoin is ~90% protein-bound; hypoalbuminemia increases the free (active) fraction without changing total measured levels, causing toxicity at 'normal' concentrations.
Question 5: Memantine's mechanism of action in Alzheimer's disease involves:
- Acetylcholinesterase inhibition
- Selective serotonin reuptake inhibition
- Non-competitive NMDA receptor antagonism (Correct answer)
- GABA-A receptor potentiation
Correct answer: Non-competitive NMDA receptor antagonism
Memantine blocks NMDA receptors non-competitively, reducing excitotoxic glutamate activity implicated in Alzheimer's neurodegeneration.
Question 6: Which drug interaction principle explains why adding fluoxetine to a stable dose of tricyclic antidepressant (TCA) can cause TCA toxicity?
- Fluoxetine displaces TCAs from plasma proteins
- Fluoxetine inhibits CYP2D6, reducing TCA metabolism (Correct answer)
- Fluoxetine increases renal TCA clearance
- Fluoxetine induces CYP3A4, increasing TCA production
Correct answer: Fluoxetine inhibits CYP2D6, reducing TCA metabolism
Fluoxetine is a potent CYP2D6 inhibitor, blocking the primary metabolic pathway for TCAs and causing plasma levels to rise to toxic concentrations.
Question 7: The therapeutic index is calculated as:
- ED50 / LD50
- LD50 / ED50 (Correct answer)
- Cmax / Cmin
- Vd / Cl
Correct answer: LD50 / ED50
The therapeutic index (TI) = LD50 / ED50; a narrow TI (e.g., lithium, digoxin) means the toxic dose is close to the therapeutic dose.
ABCN Pharmacology Fundamentals 3
Which benzodiazepine is preferred for elderly patients because it does not undergo hepatic oxidation and lacks active metabolites?