Screening models for cardiovascular drugs – diuretics MCQs With Answer

Introduction

Screening models for cardiovascular drugs—diuretics MCQs With Answer introduces B. Pharm students to essential experimental and clinical approaches used to evaluate diuretics. This concise guide covers in vitro assays (cell-based transport studies, isolated nephron segments), in vivo animal models (rodent urine-volume and electrolyte excretion tests), key targets (NCC, NKCC2, ENaC), pharmacodynamics, pharmacokinetics, biomarkers, safety assessments and translational challenges. Emphasis is placed on interpreting endpoints, selecting appropriate models, assay design and species differences for effective drug screening and development. The content is practical, exam-oriented and rich in relevant keywords to strengthen learning and retention. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which transporter is the primary target of thiazide diuretics in renal screening models?

• NKCC2 cotransporter
• NCC (Na+-Cl− cotransporter)
• ENaC (epithelial sodium channel)
• Na+/K+ ATPase

Correct Answer: NCC (Na+-Cl− cotransporter)

Q2. In in vitro screening of diuretics, which cell line is commonly used to model renal epithelial transport?

• HepG2 hepatocytes
• MDCK (Madin-Darby Canine Kidney) cells
• PC12 neuronal cells
• RAW 264.7 macrophages

Correct Answer: MDCK (Madin-Darby Canine Kidney) cells

Q3. Which physiological endpoint is most directly measured in acute in vivo diuretic screening studies?

• Mean arterial pressure
• Urine volume and electrolyte excretion
• Cardiac output
• Serum liver enzymes

Correct Answer: Urine volume and electrolyte excretion

Q4. Loop diuretics primarily inhibit which renal transporter in screening assays?

• NCC in the distal convoluted tubule
• NKCC2 in the thick ascending limb
• ENaC in the collecting duct
• Proximal tubule transporter NHE3

Correct Answer: NKCC2 in the thick ascending limb

Q5. Which screening model is best suited to study chronic diuretic effects and compensatory mechanisms?

• Acute isolated kidney perfusion
• Short-term cell culture transport assay
• Long-term rodent dosing with metabolic cage urine collection
• Isolated membrane vesicle assay

Correct Answer: Long-term rodent dosing with metabolic cage urine collection

Q6. In transporter inhibition assays, what is a common direct readout used to indicate diuretic activity?

• Cell proliferation rate
• Radioisotope or fluorescent tracer uptake/flux
• ATP concentration in plasma
• Serum creatinine clearance

Correct Answer: Radioisotope or fluorescent tracer uptake/flux

Q7. Which diuretic class acts by inhibiting carbonic anhydrase in proximal tubules?

• Thiazides
• Loop diuretics
• Carbonic anhydrase inhibitors (e.g., acetazolamide)
• Potassium-sparing diuretics

Correct Answer: Carbonic anhydrase inhibitors (e.g., acetazolamide)

Q8. For early safety screening of diuretics, which parameter is most important to monitor in animal studies?

• Hematocrit changes only
• Electrolyte disturbances and renal function markers
• Behavioral activity counts only
• Fecal microbiome composition

Correct Answer: Electrolyte disturbances and renal function markers

Q9. Which model is particularly useful to measure drug effects on glomerular filtration rate (GFR) during diuretic screening?

• In vitro renal epithelial monolayer
• In situ isolated perfused kidney and in vivo clearance studies
• Hollow-fiber bioreactor
• Cell-free enzyme assay

Correct Answer: In situ isolated perfused kidney and in vivo clearance studies

Q10. Spironolactone is classified as which type of diuretic and what model target is most relevant for screening?

• Loop diuretic; NKCC2
• Thiazide; NCC
• Potassium-sparing (aldosterone antagonist); mineralocorticoid receptor in collecting duct models
• Osmotic diuretic; proximal tubule osmotic flux

Correct Answer: Potassium-sparing (aldosterone antagonist); mineralocorticoid receptor in collecting duct models

Q11. Which biomarker in urine is commonly assessed to evaluate natriuretic effect of test diuretics in rodents?

• Urinary glucose concentration
• Urinary sodium and potassium concentrations
• Urinary bilirubin
• Urinary albumin alone

Correct Answer: Urinary sodium and potassium concentrations

Q12. What limitation must be considered when extrapolating diuretic results from rodent models to humans?

• Rodents lack kidneys
• Renal transporter expression and nephron segment physiology differ between species
• Rodents have identical pharmacokinetics to humans
• Rodents do not respond to any diuretics

Correct Answer: Renal transporter expression and nephron segment physiology differ between species

Q13. In screening for ENaC inhibitors, which functional assay is most appropriate?

• Measurement of NKCC2-mediated Cl− flux
• Ussing chamber measurement of amiloride-sensitive Na+ current
• Assessment of carbonic anhydrase activity
• Renal clearance of inulin

Correct Answer: Ussing chamber measurement of amiloride-sensitive Na+ current

Q14. Which assay helps distinguish diuretics that act proximally versus distally in the nephron?

• Measuring urinary glucose only
• Fractional excretion of sodium and lithium clearance
• Hepatic microsome stability test
• Platelet aggregation assay

Correct Answer: Fractional excretion of sodium and lithium clearance

Q15. Osmotic diuretics like mannitol are best evaluated using which experimental endpoint?

• ENaC activity assay
• Urine osmolality and diuresis measurement
• Renal prostaglandin synthesis only
• Plasma cholesterol levels

Correct Answer: Urine osmolality and diuresis measurement

Q16. Which pharmacokinetic parameter is most critical for interpreting diuretic time-course in screening studies?

• Volume of distribution for lipophilic drugs only
• Oral bioavailability and renal clearance
• Plasma protein glycosylation
• Skin permeability

Correct Answer: Oral bioavailability and renal clearance

Q17. In high-throughput screening of diuretic candidates, what is a major advantage of cell-based transport assays?

• They perfectly replicate whole-organ physiology
• They allow rapid mechanistic profiling of transporter interactions
• They measure blood pressure directly
• They require no controls

Correct Answer: They allow rapid mechanistic profiling of transporter interactions

Q18. Which parameter would indicate potassium-sparing activity during an in vivo diuretic test?

• Marked hypokalemia
• Reduced urinary potassium excretion compared to loop diuretics
• Increased urinary glucose excretion
• Lowered GFR only

Correct Answer: Reduced urinary potassium excretion compared to loop diuretics

Q19. When designing a diuretic screen, why is vehicle and time-matched control important?

• Controls are not necessary for diuretic studies
• To account for circadian and handling effects on urine output and electrolyte excretion
• To increase variability intentionally
• To measure liver toxicity only

Correct Answer: To account for circadian and handling effects on urine output and electrolyte excretion

Q20. Which assay would best detect off-target inhibition of Na+/K+ ATPase by a diuretic candidate?

• ENaC current assay
• Cell viability and ATPase activity assay in renal tubular epithelial cells
• Urinary sodium measurement only
• Platelet aggregation assay

Correct Answer: Cell viability and ATPase activity assay in renal tubular epithelial cells

Q21. In screening diuretics for heart failure use, which additional parameter is often monitored in animal models?

• Pulmonary edema and body weight change
• Hair color change
• Fur density only
• Bone mineral density

Correct Answer: Pulmonary edema and body weight change

Q22. Which experimental approach helps identify whether a diuretic effect is prostaglandin-mediated?

• Co-administration with a cyclooxygenase inhibitor and observing attenuation of effect
• Measuring plasma insulin
• Using a beta-blocker challenge
• Measuring gastric pH

Correct Answer: Co-administration with a cyclooxygenase inhibitor and observing attenuation of effect

Q23. What is a common limitation of isolated perfused kidney models in diuretic screening?

• They mimic whole-animal neurohormonal regulation perfectly
• They lack integrated endocrine and systemic regulation that affects renal handling
• They always overestimate drug toxicity
• They cannot measure urine output

Correct Answer: They lack integrated endocrine and systemic regulation that affects renal handling

Q24. For screening a novel NCC inhibitor, which genetic model could provide strong mechanistic evidence?

• NCC knockout mice showing no additional natriuretic effect of the compound
• Liver-specific transgenic mice unrelated to kidney
• Cardiac myocyte knockout mice for beta-adrenergic receptor
• Skin fibroblast culture model

Correct Answer: NCC knockout mice showing no additional natriuretic effect of the compound

Q25. Which analytical technique is commonly used to quantify urinary electrolytes in diuretic studies?

• HPLC for large proteins only
• Ion-selective electrodes or flame photometry
• Western blotting for sodium
• Mass spectrometry for DNA

Correct Answer: Ion-selective electrodes or flame photometry

Q26. During preclinical screening, which finding would raise concern for diuretic-induced renal injury?

• Stable serum creatinine and BUN
• Marked rise in serum creatinine and BUN with oliguria
• Transient mild increase in urine volume only
• Reduced body weight due to less edema alone

Correct Answer: Marked rise in serum creatinine and BUN with oliguria

Q27. In pharmacodynamic modeling of diuretics, what does a leftward shift in dose–response curve indicate?

• Reduced potency
• Increased potency (lower ED50)
• No change in efficacy
• Decreased maximum effect only

Correct Answer: Increased potency (lower ED50)

Q28. Which experimental readout helps assess diuretic effect on calcium handling relevant for thiazide screening?

• Urinary calcium excretion and serum calcium levels
• Blood glucose only
• Serum bilirubin
• Urinary urea nitrogen only

Correct Answer: Urinary calcium excretion and serum calcium levels

Q29. When evaluating drug–drug interactions in diuretic screening, which co-administered drug class is most important to consider for increased risk of hyperkalemia?

• Loop diuretics
• ACE inhibitors or ARBs
• Thiazide diuretics
• Beta-2 agonists

Correct Answer: ACE inhibitors or ARBs

Q30. Which property of candidate diuretics is crucial to optimize to ensure renal exposure without systemic toxicity?

• High lipophilicity and CNS penetration only
• Renal clearance and tissue selectivity toward renal transporters
• Inability to be excreted
• Strong inhibition of hepatic cytochromes only

Correct Answer: Renal clearance and tissue selectivity toward renal transporters

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

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