Tier 2 safety pharmacology: GI, renal and other systems MCQs With Answer

Introduction: This blog presents a focused set of Tier 2 safety pharmacology multiple-choice questions designed for M.Pharm students preparing in-depth for preclinical safety evaluation of gastrointestinal (GI), renal and related systems. The questions emphasize experimental methods, in vivo and in vitro models, biomarkers, and regulatory-relevant endpoints used to detect organ-specific liabilities beyond the core cardiovascular, respiratory and CNS battery. Each MCQ targets practical assay selection, interpretation of physiological and biochemical readouts, and contemporary biomarkers (e.g., KIM‑1, NGAL), along with imaging and telemetry approaches. Use these questions to consolidate knowledge of study design, sensitive endpoints and translational considerations for nonclinical safety testing.

Q1. Which classical in vivo assay is commonly used to measure gastric emptying and small intestinal transit in rodents?

• Charcoal meal test
• Ussing chamber assay
• Inulin clearance
• Pylorus ligation ulcer test

Correct Answer: Charcoal meal test

Q2. What primary parameter does an Ussing chamber measure when applied to intestinal tissues in safety pharmacology?

• Transepithelial ion transport and electrical resistance (short-circuit current/TEER)
• Glomerular filtration rate
• Gastric acid secretion rate
• Systemic blood pressure changes

Correct Answer: Transepithelial ion transport and electrical resistance (short-circuit current/TEER)

Q3. Which urinary biomarker is most sensitive for early detection of proximal tubular injury in preclinical studies?

• KIM-1 (Kidney Injury Molecule-1)
• ALT (alanine aminotransferase)
• Plasma creatine kinase
• Serum albumin

Correct Answer: KIM-1 (Kidney Injury Molecule-1)

Q4. Which method is considered the gold standard for measuring glomerular filtration rate (GFR) in experimental animals?

• Inulin clearance
• Urine dipstick protein test
• Plasma ALT measurement
• Ussing chamber assessment

Correct Answer: Inulin clearance

Q5. For evaluating colonic transit in rodents, which assay is most appropriate?

• Colonic bead expulsion test
• Charcoal meal gastric emptying
• Telemetry ECG recording
• Inulin clearance

Correct Answer: Colonic bead expulsion test

Q6. The pylorus ligation (Shay) model in rodents is primarily used to assess which safety-relevant endpoint?

• Gastric acid secretion and ulcerogenic potential
• Glomerular filtration rate
• Colonic transit time
• Hepatocellular enzyme induction

Correct Answer: Gastric acid secretion and ulcerogenic potential

Q7. Which biomarker rises very early (hours) after acute kidney injury and is useful for rapid detection in safety studies?

• NGAL (neutrophil gelatinase-associated lipocalin)
• Serum bilirubin
• Alkaline phosphatase
• Fasting glucose

Correct Answer: NGAL (neutrophil gelatinase-associated lipocalin)

Q8. Which in vitro technique is best suited to study drug effects on renal tubular transport function directly?

• Isolated perfused tubule technique
• Whole-animal telemetry
• Charcoal meal transit
• Hepatocyte suspension assay

Correct Answer: Isolated perfused tubule technique

Q9. Which observation most clearly indicates a loss of renal concentrating ability in an animal study?

• Low urine osmolality despite fluid restriction
• Decreased plasma creatinine with low urine volume
• High urine osmolality and low urine volume
• Reduced urine sodium with normal osmolality

Correct Answer: Low urine osmolality despite fluid restriction

Q10. Which ICH guidance document provides the primary recommendations for safety pharmacology core battery and follow-up studies?

• ICH S7A
• ICH Q3C
• ICH M7
• ICH E14

Correct Answer: ICH S7A

Q11. Which non-radioactive plasma marker is commonly used as an alternative to inulin for measuring GFR in preclinical studies?

• Iohexol clearance
• ALT activity
• Serum troponin
• Ussing chamber current

Correct Answer: Iohexol clearance

Q12. In an Ussing chamber study of small intestine, which readout corresponds to net secretory or absorptive ion movement?

• Short-circuit current (Isc)
• Serum creatinine concentration
• Gastric motility index
• Urine specific gravity

Correct Answer: Short-circuit current (Isc)

Q13. Which urinary measurement is the most direct indicator of glomerular (not tubular) dysfunction in preclinical screening?

• Albuminuria / urinary albumin
• Urinary KIM-1
• Urinary NGAL
• Urinary NAG (N-acetyl-β-D-glucosaminidase)

Correct Answer: Albuminuria / urinary albumin

Q14. Which technology allows simultaneous, continuous measurement of gastric pH and motor activity in conscious animals for safety studies?

• Implantable telemetric pH and motility probes
• Ussing chamber
• Inulin clearance via catheter
• HPLC analysis of plasma drugs

Correct Answer: Implantable telemetric pH and motility probes

Q15. A fractional excretion of sodium (FENa) greater than 2% in a preclinical study most likely indicates which condition?

• Intrinsic renal tubular damage
• Pre-renal azotemia due to hypovolemia
• Obstructive uropathy with intact tubules
• Increased gastric acid secretion

Correct Answer: Intrinsic renal tubular damage

Q16. Which compound is commonly used as a positive control to induce experimental constipation in rodents when validating constipation assays?

• Loperamide
• Bethanechol
• Cisapride
• Isoproterenol

Correct Answer: Loperamide

Q17. KIM-1, an early tubular injury biomarker, is predominantly expressed in which renal cell population?

• Proximal tubular epithelial cells
• Glomerular podocytes
• Distal collecting duct intercalated cells
• Renal endothelial cells only

Correct Answer: Proximal tubular epithelial cells

Q18. Which nuclear medicine technique is used to noninvasively estimate GFR and renal perfusion in translational safety studies?

• Renal scintigraphy with 99mTc-DTPA
• Ussing chamber flux assay
• Charcoal meal transit imaging
• Plasma ALT clearance

Correct Answer: Renal scintigraphy with 99mTc-DTPA

Q19. Drug-induced increases in GI smooth muscle contraction are primarily mediated by activation of which receptor subtype?

• M3 muscarinic receptor
• Beta-2 adrenergic receptor
• Histamine H2 receptor
• Alpha-1 adrenergic receptor

Correct Answer: M3 muscarinic receptor

Q20. In safety screening for hematopoietic toxicity, which laboratory parameter typically provides the earliest sign of bone marrow suppression?

• Decline in reticulocyte count
• Elevated serum creatinine
• Increased ALT
• High urinary osmolality

Correct Answer: Decline in reticulocyte count

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