Tier 1 safety pharmacology: CVS, CNS, respiratory assessments MCQs With Answer

Introduction

This blog presents a concise, exam-focused question bank on Tier 1 safety pharmacology — cardiovascular (CVS), central nervous system (CNS) and respiratory assessments — tailored for M.Pharm students. Questions cover regulatory essentials (ICH S7A), experimental design, instrumentation (telemetry, plethysmography, EEG), common endpoints (QT/QTc, heart rate, tidal volume, locomotor activity), data interpretation and typical positive controls. Each MCQ is designed to deepen understanding of preclinical screening methods, study limitations, and translational relevance, helping students prepare for both exams and practical research. Answers are provided to reinforce learning and clarify why particular measures are chosen in core safety pharmacology studies.

Q1. What is the primary objective of Tier 1 (core battery) safety pharmacology studies?

• To determine the therapeutic efficacy of a compound in disease models
• To identify adverse effects on vital functions (CVS, CNS, respiratory) before human exposure
• To establish chronic toxicity profiles over months of dosing
• To replace clinical trials with animal data

Correct Answer: To identify adverse effects on vital functions (CVS, CNS, respiratory) before human exposure

Q2. Which international guideline specifically outlines the core battery for safety pharmacology?

• ICH M3(R2)
• ICH S7A
• OECD Guideline 407
• GLP OECD 170

Correct Answer: ICH S7A

Q3. Which ECG parameter is most commonly used as an indicator of proarrhythmic risk in preclinical studies?

• PR interval
• QT/QTc interval
• QRS axis
• ST segment height

Correct Answer: QT/QTc interval

Q4. What is the main advantage of using telemetry for cardiovascular assessments in animals?

• Lower equipment cost compared with surface ECG
• Allows continuous recording in conscious, freely moving animals over extended periods
• Requires no surgical implantation
• Eliminates all motion artifacts automatically

Correct Answer: Allows continuous recording in conscious, freely moving animals over extended periods

Q5. In unrestrained whole-body plethysmography, which derived parameter has been used controversially as a surrogate for airway resistance?

• Minute volume
• Tidal volume
• Enhanced pause (Penh)
• Respiratory frequency

Correct Answer: Enhanced pause (Penh)

Q6. Which domains are commonly evaluated in the Functional Observation Battery (FOB) for CNS safety pharmacology?

• Sensory, motor, autonomic and behavioral functions
• Only memory and learning tests
• Only electrophysiology and EEG
• Only respiratory rate and tidal volume

Correct Answer: Sensory, motor, autonomic and behavioral functions

Q7. The rotarod test in rodents is primarily used to assess which CNS function?

• Sensory perception
• Memory retention
• Motor coordination and balance
• Depressive-like behavior

Correct Answer: Motor coordination and balance

Q8. Which drug is commonly used as a positive control for CNS depressant effects in safety pharmacology screens?

• Fluoxetine
• Diazepam
• Caffeine
• Kainic acid

Correct Answer: Diazepam

Q9. Which QT correction formula is often preferred in preclinical cardiovascular telemetry to account for heart rate effects?

• Bazett’s formula
• Fridericia’s formula
• Fick’s correction
• Garcia’s method

Correct Answer: Fridericia’s formula

Q10. ICH S7A recommends safety pharmacology evaluations in which species selection strategy?

• Only one rodent species is sufficient
• Only non-rodent species are required
• At least one rodent and one non-rodent species
• Human volunteers before animal studies

Correct Answer: At least one rodent and one non-rodent species

Q11. Which respiratory parameter is directly measured (not derived) by plethysmography in conscious small animals?

• Arterial oxygen tension (PaO2)
• Tidal volume (via pressure changes in plethysmograph)
• Alveolar-arterial gradient
• Pulmonary vascular resistance

Correct Answer: Tidal volume (via pressure changes in plethysmograph)

Q12. Which technique is most appropriate to detect drug-induced seizure activity in preclinical CNS safety studies?

• Open field test
• Electroencephalography (EEG)
• Rotarod
• Forced swim test

Correct Answer: Electroencephalography (EEG)

Q13. Why are baseline (pre-dose) measurements critical in safety pharmacology studies?

• They allow for higher dosing on the first day
• To account for inter-animal variability and use each animal as its own control
• They eliminate the need for control groups
• They calibrate instruments but are not used in data analysis

Correct Answer: To account for inter-animal variability and use each animal as its own control

Q14. Which electrolyte disturbance commonly prolongs the QT interval and increases proarrhythmic risk?

• Hypercalcemia
• Hypokalemia
• Hypernatremia
• Hypomagnesemia without affecting QT

Correct Answer: Hypokalemia

Q15. Which respiratory assessment provides direct and quantitative information about gas exchange and acid-base status?

• Plethysmography
• Arterial blood gas (ABG) analysis
• Pulse oximetry alone
• Enhanced pause (Penh)

Correct Answer: Arterial blood gas (ABG) analysis

Q16. In telemetry recordings from conscious animals, what is a common source of artifact affecting ECG quality?

• Proper electrode implantation
• Animal movement and muscle activity
• Using too low sampling rate
• Complete absence of electrical noise

Correct Answer: Animal movement and muscle activity

Q17. In the Functional Observation Battery, which finding typically indicates CNS sedation?

• Increased startle response
• Markedly decreased locomotor activity
• Improved motor coordination
• Increased exploratory behavior

Correct Answer: Markedly decreased locomotor activity

Q18. When selecting doses for Tier 1 safety pharmacology studies, what principle is generally recommended?

• Use only doses expected in therapeutic human plasma levels
• Include clinically relevant exposures and higher multiples to define safety margins
• Always use a single fixed low dose
• Base doses solely on in vitro potency without in vivo tolerability data

Correct Answer: Include clinically relevant exposures and higher multiples to define safety margins

Q19. Which of the following is NOT part of the Tier 1 core battery in safety pharmacology?

• Cardiovascular assessments
• Central nervous system assessments
• Respiratory assessments
• Comprehensive renal function testing

Correct Answer: Comprehensive renal function testing

Q20. Continuous telemetry in a safety pharmacology study typically allows simultaneous monitoring of which parameters?

• ECG, arterial blood pressure, core body temperature, and activity
• Only behavioral endpoints like grooming
• Arterial blood gas continuously without sampling
• Only respiratory flow parameters in real time

Correct Answer: ECG, arterial blood pressure, core body temperature, and activity

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