Screening models for cardiovascular drugs – antiarrhythmics MCQs With Answer

Screening models for cardiovascular drugs – antiarrhythmics MCQs With Answer

This concise introduction covers screening models for cardiovascular drugs, focusing on antiarrhythmics and translational safety pharmacology for B. Pharm students. You will learn key concepts like ion channel assays (hERG, Nav1.5, Cav1.2), patch‑clamp and automated electrophysiology, hiPSC‑derived cardiomyocytes, MEA and optical mapping, isolated tissue and Langendorff hearts, in vivo telemetry, and regulatory frameworks (ICH S7B, E14, CiPA). Emphasis is on mechanism of action, proarrhythmia risk, QT/APD assessment, dose–response metrics (IC50, selectivity), and experimental design considerations. This will build applied knowledge for drug screening, interpretation of electrophysiological data, and safety decision‑making. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which in vitro assay is considered the gold standard for measuring hERG (IKr) channel block and risk of QT prolongation?

• Microelectrode array (MEA) recording in cardiomyocytes
• Manual patch‑clamp on heterologous cells expressing hERG
• Langendorff perfused heart action potential recording
• Telemetry ECG in conscious animals

Correct Answer: Manual patch‑clamp on heterologous cells expressing hERG

Q2. What is the main advantage of hiPSC‑derived cardiomyocytes (hiPSC‑CMs) in antiarrhythmic screening?

• They provide high‑throughput ionic current recordings identical to adult myocytes
• They offer human genetic background and multicellular electrophysiology for translational insights
• They eliminate the need for any electrophysiology validation
• They always display mature adult action potential morphology

Correct Answer: They offer human genetic background and multicellular electrophysiology for translational insights

Q3. What does IC50 represent in ion channel screening of antiarrhythmic drugs?

• The concentration at which 50% of the drug is metabolized
• The concentration at which 50% inhibition of a specific ion current is observed
• The time required for a drug to reach 50% of peak plasma level
• The percentage of cells showing action potential changes at a fixed dose

Correct Answer: The concentration at which 50% inhibition of a specific ion current is observed

Q4. Which technique allows simultaneous extracellular field recordings from networks of cardiomyocytes to detect conduction changes and arrhythmic events?

• Optical mapping with voltage‑sensitive dyes
• Microelectrode array (MEA)
• Isolated Purkinje fiber recording
• Langendorff isolated heart monophasic action potential

Correct Answer: Microelectrode array (MEA)

Q5. Which regulatory initiative integrates multiple ion channel data and in silico models to improve proarrhythmia prediction?

• ICH E14 alone
• Thorough QT (TQT) study only
• CiPA (Comprehensive in vitro Proarrhythmia Assay)
• Good Laboratory Practice (GLP) guidelines

Correct Answer: CiPA (Comprehensive in vitro Proarrhythmia Assay)

Q6. Which ion current blockade is most directly associated with QT interval prolongation and torsades de pointes risk?

• INa (fast sodium current)
• IKr (hERG potassium current)
• ICa,L (L‑type calcium current)
• IKs (slow delayed rectifier potassium current)

Correct Answer: IKr (hERG potassium current)

Q7. In patch‑clamp experiments, what does use‑dependence of a sodium channel blocker imply?

• Block increases with more frequent channel activation (higher stimulation rate)
• Block decreases with increasing drug concentration
• Block is independent of channel state or frequency
• Block only occurs in resting channels

Correct Answer: Block increases with more frequent channel activation (higher stimulation rate)

Q8. Which in vivo model is commonly used for telemetry ECG studies to assess QT and arrhythmia liability in conscious animals?

• Isolated guinea pig papillary muscle
• Conscious telemetry in dogs or rabbits
• Langendorff perfused rat heart
• In vitro HEK293 cell line assays

Correct Answer: Conscious telemetry in dogs or rabbits

Q9. Optical mapping primarily measures which of the following parameters in cardiac tissues?

• Single‑channel ionic currents with picoampere resolution
• Membrane potential propagation, action potential duration and conduction velocity using dyes
• Plasma drug concentration over time
• Genomic expression of ion channel mRNA

Correct Answer: Membrane potential propagation, action potential duration and conduction velocity using dyes

Q10. Which experimental model best assesses drug effects on atrial selectivity and potential for atrial fibrillation suppression?

• Ventricular Purkinje fiber isolated preparations
• Isolated atrial tissue or atrial trabeculae preparations
• hERG channel assay alone
• In vivo renal clearance study

Correct Answer: Isolated atrial tissue or atrial trabeculae preparations

Q11. What is a primary limitation of heterologous expression systems (e.g., HEK293 cells) for ion channel screening?

• They always reproduce adult human cardiomyocyte electrophysiology faithfully
• They lack the full complement of cardiac ion channel interplay and accessory proteins
• They are too expensive for routine screening
• They cannot express hERG channels

Correct Answer: They lack the full complement of cardiac ion channel interplay and accessory proteins

Q12. Which metric integrates multiple ion channel effects into a predicted proarrhythmia risk score in CiPA?

• QTc measured in isolated hearts
• hERG IC10 value alone
• In silico computer model derived proarrhythmia score using multi‑ion channel data
• Peak plasma concentration without pharmacodynamics

Correct Answer: In silico computer model derived proarrhythmia score using multi‑ion channel data

Q13. Which antiarrhythmic class primarily blocks L‑type calcium channels and is useful for supraventricular tachycardias?

• Class I (sodium channel blockers)
• Class II (beta‑blockers)
• Class III (potassium channel blockers)
• Class IV (calcium channel blockers)

Correct Answer: Class IV (calcium channel blockers)

Q14. In Langendorff isolated heart preparations, which parameter is commonly measured to evaluate repolarization changes?

• QT interval on surface ECG only
• Action potential duration at 90% repolarization (APD90)
• Hepatic clearance rate of the drug
• Resting membrane potential of single isolated myocytes only

Correct Answer: Action potential duration at 90% repolarization (APD90)

Q15. Which phenomenon describes early afterdepolarizations (EADs) and their relation to drug screening?

• EADs are late sodium current increases unrelated to repolarization
• EADs are depolarizations during phase 2 or 3 that can precipitate torsades and are monitored in models prone to APD prolongation
• EADs refer to conduction block in atrioventricular node only
• EADs are purely mechanical contractile abnormalities

Correct Answer: EADs are depolarizations during phase 2 or 3 that can precipitate torsades and are monitored in models prone to APD prolongation

Q16. Why are guinea pig cardiomyocytes often used in preclinical screening for repolarization?

• They lack any potassium currents
• Their repolarization currents resemble human cardiac electrophysiology, especially IKs/IKr balance
• They are identical to human atrial cells in all respects
• They are the only species that express hERG channel

Correct Answer: Their repolarization currents resemble human cardiac electrophysiology, especially IKs/IKr balance

Q17. Which measurement differentiates between QT prolongation due to direct hERG block versus multichannel effects?

• Comparing hERG IC50 alone without other assays
• Multi‑ion channel profiling (INa, ICa,L, IKr, IKs) and in silico modeling
• Only measuring heart rate changes in vivo
• Plasma protein binding percentage

Correct Answer: Multi‑ion channel profiling (INa, ICa,L, IKr, IKs) and in silico modeling

Q18. What is the key goal of safety pharmacology studies for antiarrhythmic drug candidates?

• To identify the marketed price of the drug
• To assess potential adverse effects on cardiac electrophysiology and proarrhythmia liability
• To exclusively measure drug solubility
• To replace clinical ECG monitoring completely

Correct Answer: To assess potential adverse effects on cardiac electrophysiology and proarrhythmia liability

Q19. Which parameter from ECG telemetry is corrected for heart rate to assess drug effects on repolarization?

• PR interval only
• QTc (corrected QT interval)
• QRS amplitude
• ST segment elevation exclusively

Correct Answer: QTc (corrected QT interval)

Q20. Automated patch‑clamp platforms are beneficial in drug screening mainly because they:

• Provide manual control over every seal formation
• Enable higher throughput and standardized ion current measurements compared with manual patch clamp
• Can only measure action potential in intact hearts
• Eliminate need for data quality control

Correct Answer: Enable higher throughput and standardized ion current measurements compared with manual patch clamp

Q21. Which class of antiarrhythmic drugs is most associated with sodium channel blockade and slowed conduction velocity?

• Class III agents
• Class I agents
• Class IV agents
• Class II agents

Correct Answer: Class I agents

Q22. What is the purpose of using positive and negative controls in electrophysiology screening assays?

• To calibrate instruments for metabolic assays
• To validate assay sensitivity, reproducibility and dynamic range for detecting channel block or absence thereof
• To increase the rate of false positives intentionally
• To eliminate the need for replicates

Correct Answer: To validate assay sensitivity, reproducibility and dynamic range for detecting channel block or absence thereof

Q23. Which antiarrhythmic characteristic is tested by measuring effective refractory period (ERP) in isolated tissue?

• Renal excretion rate
• Ability to suppress reentrant arrhythmias by prolonging refractoriness
• Plasma protein binding
• Hepatic metabolism pathway

Correct Answer: Ability to suppress reentrant arrhythmias by prolonging refractoriness

Q24. How does blockade of late sodium current (INa,L) affect action potential and arrhythmia risk?

• INa,L blockade typically shortens APD and may reduce EADs and arrhythmia risk in some settings
• INa,L blockade always increases QT interval dramatically
• INa,L blockade has no effect on calcium handling
• INa,L blockade increases heart rate directly

Correct Answer: INa,L blockade typically shortens APD and may reduce EADs and arrhythmia risk in some settings

Q25. What is a translational challenge when moving from animal cardiac models to human clinical prediction?

• Animal hearts are identical to human hearts in ion channel expression
• Species differences in ion channel composition, heart rate and drug metabolism can limit predictivity
• Animals do not have action potentials
• Human trials do not require prior safety data

Correct Answer: Species differences in ion channel composition, heart rate and drug metabolism can limit predictivity

Q26. Which measurement from isolated ventricular wedge preparations helps predict transmural dispersion of repolarization?

• APD90 in endocardial, midmyocardial (M cell) and epicardial layers
• Hepatic clearance only
• Single hERG current at one holding potential
• QTc in conscious rodents only

Correct Answer: APD90 in endocardial, midmyocardial (M cell) and epicardial layers

Q27. Which assay can measure calcium transient amplitude and kinetics to assess proarrhythmic calcium handling disturbances?

• hERG patch‑clamp only
• Calcium imaging in cardiomyocytes using fluorescent dyes
• Serum electrolyte measurements
• Microsomal metabolic stability test

Correct Answer: Calcium imaging in cardiomyocytes using fluorescent dyes

Q28. Why is concentration‑response (dose–response) testing important in preclinical screening of antiarrhythmics?

• It identifies the range of concentrations where target engagement and off‑target risk occur and allows IC50/EC50 estimation
• It determines taste and smell of the drug
• It eliminates the need for any in vivo testing
• It is only required for marketed drugs, not candidates

Correct Answer: It identifies the range of concentrations where target engagement and off‑target risk occur and allows IC50/EC50 estimation

Q29. Which guideline specifically addresses nonclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation)?

• ICH S7B
• ICH Q1A
• ICH M4
• GLP only

Correct Answer: ICH S7B

Q30. When interpreting screening data, which combined approach yields the most robust prediction of proarrhythmia risk?

• Single hERG assay without context
• Multi‑ion channel in vitro assays, hiPSC‑CM/MEA or optical mapping, in silico modeling, and confirmatory in vivo telemetry
• Only clinical TQT study without preclinical evaluation
• Randomized selection of assays without predefined endpoints

Correct Answer: Multi‑ion channel in vitro assays, hiPSC‑CM/MEA or optical mapping, in silico modeling, and confirmatory in vivo telemetry

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.

Mail- Sachin@pharmacyfreak.com