Understanding screening models for diuretics is essential for B.Pharm students because it links renal physiology, pharmacology and drug discovery. This concise overview highlights common in vivo and in vitro diuretic screening approaches: saline-load and metabolic-cage tests in rats/mice, acute versus chronic protocols, isolated perfused kidney and tubular microperfusion, plus cellular transporter assays for NKCC2, NCC and ENaC. Important endpoints include urine volume, natriuresis, kaliuresis, osmolar and free-water clearance, lithium clearance and dose–response (ED50). Practical topics cover assay techniques (flame photometry, ion-selective electrodes), positive controls (furosemide, thiazides), data interpretation, toxicity and ethical 3R principles. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which in vivo model is most commonly used for initial acute diuretic screening and urine collection in B.Pharm preclinical studies?
- Dog metabolic cage test
- Rat saline-load/metabolic-cage test
- Isolated rabbit kidney perfusion
- Human volunteer open-label study
Correct Answer: Rat saline-load/metabolic-cage test
Q2. Which primary endpoint directly measures natriuretic effect in diuretic screening?
- Urine glucose concentration
- Urine sodium excretion (natriuresis)
- Plasma ALT levels
- Urine creatinine clearance
Correct Answer: Urine sodium excretion (natriuresis)
Q3. Which laboratory method is most appropriate for quantifying urinary sodium during diuretic screening?
- Flame photometry
- ELISA for sodium
- Mass spectrometry for proteins
- pH meter
Correct Answer: Flame photometry
Q4. Lithium clearance is used in diuretic studies primarily to estimate which renal process?
- Glomerular filtration rate (GFR)
- Proximal tubular sodium reabsorption
- Collecting duct potassium secretion
- Renin release
Correct Answer: Proximal tubular sodium reabsorption
Q5. Which diuretic class acts predominantly at the thick ascending limb by inhibiting the NKCC2 transporter?
- Thiazide diuretics
- Loop diuretics
- Carbonic anhydrase inhibitors
- Potassium-sparing diuretics
Correct Answer: Loop diuretics
Q6. In an acute diuretic test, why is a positive control drug like furosemide used?
- To increase animal stress
- To validate assay sensitivity and compare efficacy
- To decrease urine production artificially
- To neutralize the test compound chemically
Correct Answer: To validate assay sensitivity and compare efficacy
Q7. Which in vitro approach helps identify direct interaction of a candidate diuretic with renal transporters?
- Metabolic cage urine collection
- Expression of transporters in Xenopus oocytes or transfected cell lines
- Whole-animal blood pressure monitoring
- Renal ultrasound imaging
Correct Answer: Expression of transporters in Xenopus oocytes or transfected cell lines
Q8. Free water clearance (CH2O) is most useful to assess which diuretic effect?
- Natriuresis
- Osmotic or aquaretic effects on water handling
- Proteinuria
- GFR elevation
Correct Answer: Osmotic or aquaretic effects on water handling
Q9. Which measurement is essential to differentiate natriuretic versus aquaretic diuretic actions?
- Urine sodium-to-water ratio and osmolar clearance
- Serum glucose
- Platelet count
- Liver enzyme profile
Correct Answer: Urine sodium-to-water ratio and osmolar clearance
Q10. Which diuretic class acts on the distal convoluted tubule by inhibiting the NCC transporter?
- Loop diuretics
- Thiazide diuretics
- Osmotic diuretics
- Carbonic anhydrase inhibitors
Correct Answer: Thiazide diuretics
Q11. In isolated perfused kidney studies, what advantage is obtained compared to whole-animal models?
- Elimination of ethical considerations
- Direct control of perfusate composition and mechanistic insight without systemic influences
- Long-term chronic dosing assessment
- Measurement of central nervous system effects
Correct Answer: Direct control of perfusate composition and mechanistic insight without systemic influences
Q12. Which electrolyte disturbance is a common adverse effect of loop and thiazide diuretics in screening studies?
- Hyperkalemia
- Hypokalemia
- Hypermagnesemia
- Hypoglycemia
Correct Answer: Hypokalemia
Q13. Which parameter is used to calculate diuretic potency (ED50) during dose–response screening?
- Dose producing 50% of maximal diuretic effect
- Dose producing 50% mortality
- Dose required to change urine pH by 50%
- Time to maximum concentration (Tmax)
Correct Answer: Dose producing 50% of maximal diuretic effect
Q14. What is the primary rationale for using metabolic cages in chronic diuretic screening?
- To force animals to drink more water
- To collect accurate timed urine samples and monitor long-term changes
- To increase animal social interaction
- To reduce animal feed consumption
Correct Answer: To collect accurate timed urine samples and monitor long-term changes
Q15. Which assay would best quantify urinary potassium excretion (kaliuresis) in diuretic tests?
- Flame photometry or ion-selective electrode for potassium
- Western blot for potassium channels
- Histology of kidney
- Urine sediment microscopy
Correct Answer: Flame photometry or ion-selective electrode for potassium
Q16. Which experimental factor can confound diuretic screening results by altering baseline urine output?
- Ambient room temperature and hydration status
- Color of animal cage bedding
- Brand of pipettes used
- Time of year only
Correct Answer: Ambient room temperature and hydration status
Q17. Spironolactone and amiloride are examples of which diuretic category tested in screening models?
- Loop diuretics
- Thiazide diuretics
- Potassium-sparing diuretics
- Osmotic diuretics
Correct Answer: Potassium-sparing diuretics
Q18. What is the primary mechanism of osmotic diuretics like mannitol in renal models?
- Inhibition of carbonic anhydrase
- Increasing tubular osmolarity to reduce water reabsorption
- Blocking ENaC channels
- Stimulating aldosterone secretion
Correct Answer: Increasing tubular osmolarity to reduce water reabsorption
Q19. Which biomarker is commonly measured to assess GFR during diuretic screening?
- Serum albumin
- Creatinine clearance
- Urine bilirubin
- Plasma amylase
Correct Answer: Creatinine clearance
Q20. Why is randomization and blinding important in animal diuretic screening studies?
- To reduce cost of experiments
- To minimize bias and improve validity of results
- To shorten the study duration
- To enhance drug potency artificially
Correct Answer: To minimize bias and improve validity of results
Q21. Which technique allows measurement of single nephron or tubular segment transport properties ex vivo?
- Patch-clamp of neurons
- Micropuncture and tubular microperfusion
- ELISA for hormone levels
- Whole-body plethysmography
Correct Answer: Micropuncture and tubular microperfusion
Q22. In transporter-based in vitro assays, which readout indicates inhibition of NKCC2/NCC activity?
- Increased ATP production
- Reduced ion uptake (Na+, K+, Cl−) into cells or oocytes
- Higher cell proliferation
- Increased mRNA for transporter
Correct Answer: Reduced ion uptake (Na+, K+, Cl−) into cells or oocytes
Q23. Which outcome defines diuretic resistance in screening or clinical contexts?
- Enhanced natriuresis despite increasing doses
- Failure to achieve expected natriuretic/diuretic response at usual doses
- Loss of drug appearance in plasma
- Immediate hypersensitivity reaction
Correct Answer: Failure to achieve expected natriuretic/diuretic response at usual doses
Q24. Which statistical approach is most appropriate for comparing urine output across multiple dose groups?
- Chi-square test for categorical data
- ANOVA followed by post hoc multiple comparisons
- Spearman correlation only
- Kaplan–Meier survival analysis
Correct Answer: ANOVA followed by post hoc multiple comparisons
Q25. Which ethical principle should guide animal diuretic screening to reduce numbers and suffering?
- Maximize animal use for statistical power
- 3Rs: Replacement, Reduction and Refinement
- Ignore anesthesia to save time
- Use only wild-caught animals
Correct Answer: 3Rs: Replacement, Reduction and Refinement
Q26. During screening, which combination therapy rationale might be explored to improve diuretic efficacy?
- Combining two drugs with identical sites of action
- Combining agents acting at different nephron sites (e.g., loop + thiazide)
- Combining a diuretic with an antiemetic
- Combining diuretic with high-salt diet
Correct Answer: Combining agents acting at different nephron sites (e.g., loop + thiazide)
Q27. Which measurement helps detect volume contraction after diuretic administration in screening models?
- Hemoglobin/hematocrit increase and plasma urea rise
- Decrease in urinary sodium
- Increase in urine glucose
- Reduction in body temperature
Correct Answer: Hemoglobin/hematocrit increase and plasma urea rise
Q28. What is a key limitation of in vitro transporter assays when extrapolating to whole-animal diuretic effects?
- They fully replicate neurohormonal and systemic compensatory mechanisms
- They may not reflect absorption, distribution, metabolism and systemic feedback
- They always overestimate toxicity
- They are cheaper than animal studies
Correct Answer: They may not reflect absorption, distribution, metabolism and systemic feedback
Q29. Which endpoint would best indicate a carbonic anhydrase inhibitor effect in screening?
- Increased urine bicarbonate and alkaline urine pH
- Pronounced kaliuresis only
- Selective proteinuria
- Decreased urine glucose
Correct Answer: Increased urine bicarbonate and alkaline urine pH
Q30. When designing a diuretic screening study, why is selecting an appropriate vehicle control important?
- Vehicle controls are unnecessary if using high doses
- To ensure observed effects are due to the test compound, not solvent or administration method
- To enhance the test compound potency
- To blind the investigators only
Correct Answer: To ensure observed effects are due to the test compound, not solvent or administration method
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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