MPharm Master of Pharmacy Master of Pharmacy: Pharmacology and Therapeutics 4 — Questions and Answers
Question 1: In a patient with Parkinson's disease, which mechanism explains levodopa-induced dyskinesias after long-term use?
- Upregulation of dopamine D2 receptors in the caudate
- Pulsatile dopaminergic stimulation causing sensitization of striatal neurons (Correct answer)
- Accumulation of dopamine metabolites causing oxidative stress
- Downregulation of dopamine transporters in the nigrostriatal pathway
Correct answer: Pulsatile dopaminergic stimulation causing sensitization of striatal neurons
Non-physiologic pulsatile dopamine receptor stimulation from intermittent levodopa dosing causes maladaptive plasticity and sensitization in striatal circuits, producing dyskinesias.
Question 2: A patient on tacrolimus post-renal transplant is started on fluconazole. What is the expected outcome?
- Decreased tacrolimus levels due to increased renal clearance
- Increased tacrolimus levels due to CYP3A4 inhibition (Correct answer)
- No interaction; tacrolimus is not CYP metabolized
- Decreased tacrolimus levels due to CYP3A4 induction
Correct answer: Increased tacrolimus levels due to CYP3A4 inhibition
Fluconazole potently inhibits CYP3A4, the primary enzyme metabolizing tacrolimus, leading to significantly elevated tacrolimus levels and nephrotoxicity risk.
Question 3: Which pharmacodynamic principle explains why combining a bactericidal and bacteriostatic antibiotic may reduce efficacy?
- The bacteriostatic drug increases bacterial efflux pumps
- Bactericidal drugs (e.g., beta-lactams) require actively dividing bacteria; stasis prevents this (Correct answer)
- The bacteriostatic drug inhibits protein synthesis needed for beta-lactam targets
- Combining antibiotics always leads to pharmacokinetic antagonism
Correct answer: Bactericidal drugs (e.g., beta-lactams) require actively dividing bacteria; stasis prevents this
Beta-lactams target cell wall synthesis during active bacterial growth; bacteriostatic agents halt growth, preventing the cell division needed for beta-lactam-mediated killing.
Question 4: A Type 2 diabetic with established cardiovascular disease is prescribed empagliflozin. Beyond glycemic control, what is its primary evidence-based benefit?
- Significant reduction in HbA1c compared to other agents
- Reduction in cardiovascular death and hospitalization for heart failure (Correct answer)
- Prevention of diabetic retinopathy progression
- Reduction in peripheral neuropathy symptoms
Correct answer: Reduction in cardiovascular death and hospitalization for heart failure
The EMPA-REG OUTCOME trial demonstrated empagliflozin significantly reduces cardiovascular death and heart failure hospitalization in patients with T2DM and established CVD.
Question 5: A patient receiving vancomycin develops red man syndrome during infusion. What is the mechanism?
- IgE-mediated type I hypersensitivity reaction
- Direct mast cell degranulation causing histamine release independent of IgE (Correct answer)
- Type III immune complex hypersensitivity in skin vessels
- Complement activation by vancomycin binding to red cell membranes
Correct answer: Direct mast cell degranulation causing histamine release independent of IgE
Red man syndrome is caused by direct, non-IgE-mediated mast cell degranulation from rapid vancomycin infusion, releasing histamine and causing flushing and urticaria.
Question 6: Which parameter determines whether a drug follows first-order or zero-order elimination kinetics?
- The drug's protein binding affinity
- Whether drug concentration exceeds the capacity of elimination pathways (saturation kinetics) (Correct answer)
- The drug's lipophilicity and volume of distribution
- The route of administration
Correct answer: Whether drug concentration exceeds the capacity of elimination pathways (saturation kinetics)
At low concentrations, most drugs follow first-order kinetics; when drug concentration saturates metabolic enzymes, zero-order kinetics occur (constant amount eliminated per unit time).
Question 7: In the treatment of status epilepticus, why is lorazepam preferred over diazepam for initial IV management?
- Lorazepam has faster onset of action than diazepam
- Lorazepam has longer duration of action due to less rapid CNS redistribution (Correct answer)
- Lorazepam has fewer respiratory depression adverse effects
- Lorazepam does not require hepatic metabolism unlike diazepam
Correct answer: Lorazepam has longer duration of action due to less rapid CNS redistribution
Although both have similar onset, lorazepam is less lipophilic and redistributes more slowly out of the CNS, providing a longer anticonvulsant effect (12-24 hours vs 20-30 minutes).
MPharm Master of Pharmacy Master of Pharmacy: Pharmacology and Therapeutics 4
In a patient with Parkinson's disease, which mechanism explains levodopa-induced dyskinesias after long-term use?