MChem Master of Chemistry Master of Chemistry: Pharmaceutical Chemistry 5 — Questions and Answers
Question 1: Which formulation strategy is used to achieve zero-order release kinetics in an oral controlled-release dosage form?
- Immediate-release granules
- Osmotic pump (OROS) technology (Correct answer)
- Enteric coating
- Spray-dried dispersion
Correct answer: Osmotic pump (OROS) technology
Osmotic pump systems (OROS) deliver drug at a rate controlled by osmotic pressure, approximating zero-order (constant rate) release independent of GI conditions.
Question 2: In target identification using affinity-based proteomics, what role does the immobilized drug analog play?
- It acts as a competitive inhibitor to block off-target binding
- It captures protein targets from cell lysates for subsequent identification by mass spectrometry (Correct answer)
- It serves as a fluorescent probe for live-cell imaging
- It delivers siRNA to knockdown candidate genes
Correct answer: It captures protein targets from cell lysates for subsequent identification by mass spectrometry
Immobilized drug analogs function as bait to pull down protein binding partners from complex cell lysates, which are then identified by LC-MS/MS proteomics.
Question 3: Which type of Phase I clinical trial design uses a Bayesian continual reassessment method (CRM)?
- Randomized controlled trial
- Dose-escalation study to find maximum tolerated dose (Correct answer)
- Bioequivalence study
- Crossover efficacy trial
Correct answer: Dose-escalation study to find maximum tolerated dose
CRM is a model-based adaptive design used in Phase I dose-escalation oncology trials to estimate the MTD more efficiently than traditional 3+3 designs.
Question 4: Which endogenous enzyme system is the primary target of proton pump inhibitors (PPIs) like omeprazole?
- Na⁺/K⁺-ATPase in cardiac muscle
- H⁺/K⁺-ATPase in gastric parietal cells (Correct answer)
- Ca²⁺-ATPase in smooth muscle
- Carbonic anhydrase in renal tubules
Correct answer: H⁺/K⁺-ATPase in gastric parietal cells
PPIs irreversibly inhibit the H⁺/K⁺-ATPase (proton pump) in gastric parietal cells, blocking the final step of gastric acid secretion.
Question 5: Which analytical technique is used to quantify drug-plasma protein binding by separating bound from unbound drug?
- Equilibrium dialysis (Correct answer)
- UV-Vis spectrophotometry
- Infrared spectroscopy
- Mass spectrometry direct injection
Correct answer: Equilibrium dialysis
Equilibrium dialysis separates protein-bound drug from free drug across a semipermeable membrane, allowing accurate determination of fraction unbound (fu).
Question 6: What is the significance of the therapeutic index (TI) in pharmaceutical development?
- It measures the rate of drug absorption
- It quantifies the ratio between toxic dose and effective dose, indicating the safety margin (Correct answer)
- It predicts the duration of drug action in plasma
- It ranks the potency of drugs within the same pharmacological class
Correct answer: It quantifies the ratio between toxic dose and effective dose, indicating the safety margin
The therapeutic index (TD50/ED50) describes the safety margin of a drug; a narrow TI (e.g., warfarin, digoxin, lithium) requires careful therapeutic drug monitoring.
Question 7: Which regulatory designation expedites development of drugs for serious conditions with unmet medical need in the US?
- Orphan Drug Designation
- Breakthrough Therapy Designation (Correct answer)
- Fast Track Designation
- Accelerated Approval
Correct answer: Breakthrough Therapy Designation
Breakthrough Therapy Designation provides intensive FDA guidance and faster review for drugs showing substantial improvement over existing therapies on clinically significant endpoints.
MChem Master of Chemistry Master of Chemistry: Pharmaceutical Chemistry 5
Which formulation strategy is used to achieve zero-order release kinetics in an oral controlled-release dosage form?