Introduction: Screening models for local anaesthetics are essential in B. Pharm training to evaluate potency, onset, duration, toxicity and mechanism of action. Common keywords include in vitro nerve preparations, patch‑clamp, Langendorff heart, IC50/EC50, pharmacokinetics, pharmacodynamics, structure‑activity relationship (SAR), ester versus amide metabolism, lipophilicity and cardiotoxicity. These models range from isolated nerve or tissue assays and molecular ion‑channel screens to in vivo analgesia and toxicity tests, enabling formulation and safety optimization. Understanding model selection, endpoints and limitations helps predict clinical behavior and guide drug design. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which in vitro preparation is classically used to assess nerve conduction block by local anaesthetics?
- Isolated frog sciatic nerve
- Isolated guinea pig atrium
- Rat liver microsomes
- Isolated rabbit kidney
Correct Answer: Isolated frog sciatic nerve
Q2. Which assay directly measures sodium channel blockade by local anaesthetics at the molecular level?
- Patch‑clamp electrophysiology
- Tail‑flick test
- Langendorff heart perfusion
- Hot‑plate test
Correct Answer: Patch‑clamp electrophysiology
Q3. The Langendorff perfused heart model is primarily used to evaluate which adverse effect of local anaesthetics?
- Cardiotoxicity and arrhythmogenic potential
- Hepatotoxicity
- Renal clearance
- Local tissue irritation
Correct Answer: Cardiotoxicity and arrhythmogenic potential
Q4. In screening local anaesthetics, EC50 or IC50 values indicate what property?
- Potency of effect (concentration for half‑maximal response)
- Maximum efficacy achievable
- Rate of metabolism
- Toxic dose in humans
Correct Answer: Potency of effect (concentration for half‑maximal response)
Q5. Which physicochemical parameter most strongly affects onset of action of local anaesthetics?
- pKa relative to tissue pH
- Molecular weight only
- Color of the solution
- Melting point
Correct Answer: pKa relative to tissue pH
Q6. Ester local anaesthetics are primarily metabolized by which pathway?
- Plasma pseudocholinesterases (esterases)
- CYP450 hepatic oxidation
- Glomerular filtration unchanged
- Conjugation with glutathione
Correct Answer: Plasma pseudocholinesterases (esterases)
Q7. Which in vivo assay measures sensory blockade and is commonly used to screen analgesic potency of local anaesthetics?
- Tail‑flick latency test
- Rotarod performance test
- Forced swim test
- Open field locomotion
Correct Answer: Tail‑flick latency test
Q8. Lipophilicity of a local anaesthetic influences which clinical property most directly?
- Duration of action due to tissue binding
- pKa value
- Color of the drug
- Route of renal excretion
Correct Answer: Duration of action due to tissue binding
Q9. Which parameter is used to compare safety margin between nerve block and systemic toxicity in screening?
- Therapeutic index (safety index)
- Log P only
- Onset time measured in seconds
- Protein binding percentage alone
Correct Answer: Therapeutic index (safety index)
Q10. High‑throughput screening for local anaesthetics often uses which surrogate endpoint?
- Block of sodium currents in automated patch‑clamp assays
- Tail diameter measurement
- Animal body weight change
- Colorimetric pH shift
Correct Answer: Block of sodium currents in automated patch‑clamp assays
Q11. Which structural change typically increases potency of an amide local anaesthetic?
- Increased lipophilicity of the aromatic moiety
- Shortening the alkyl chain to reduce size
- Replacing amide with ester bond
- Removing tertiary amine
Correct Answer: Increased lipophilicity of the aromatic moiety
Q12. A lower pH at the injection site (e.g., inflamed tissue) affects local anaesthetic how?
- Reduces fraction of non‑ionized drug and slows onset
- Increases non‑ionized fraction and speeds onset
- No effect on onset or potency
- Causes immediate systemic toxicity
Correct Answer: Reduces fraction of non‑ionized drug and slows onset
Q13. Which animal preparation is useful to study differential block of motor versus sensory fibers?
- Isolated peripheral nerve with compound action potential recording
- Isolated kidney slice
- Hepatocyte culture
- Isolated pancreatic islet
Correct Answer: Isolated peripheral nerve with compound action potential recording
Q14. Stereoisomerism in local anaesthetics can influence which attributes?
- Potency, toxicity and metabolic profile
- Only the color of the drug
- Only the pKa value
- None; stereoisomers are identical in effect
Correct Answer: Potency, toxicity and metabolic profile
Q15. Which method assesses cardiotoxicity by measuring contractile force and conduction in an isolated heart?
- Langendorff perfusion model
- Pooled plasma protein assay
- Whole blood clotting time
- Isolated lymphocyte proliferation
Correct Answer: Langendorff perfusion model
Q16. In vitro assays often evaluate reversibility of block. Why is reversibility important?
- Predicts potential for prolonged motor/sensory deficits and safety
- Indicates color stability of the formulation
- Determines the taste of the drug
- Shows whether drug is fluorescent
Correct Answer: Predicts potential for prolonged motor/sensory deficits and safety
Q17. Adding epinephrine to a local anaesthetic formulation is screened for what effect?
- Prolongation of local effect via vasoconstriction
- Accelerated hepatic metabolism
- Increased renal excretion rate
- Neutralization of drug pKa
Correct Answer: Prolongation of local effect via vasoconstriction
Q18. QSAR and molecular modelling in screening primarily help with what?
- Predicting structure‑activity relationships and guiding design
- Measuring in vivo analgesic duration directly
- Replacing all animal toxicity studies
- Providing definitive clinical dosing
Correct Answer: Predicting structure‑activity relationships and guiding design
Q19. Which toxic effect is commonly monitored in animal models at high systemic concentrations of local anaesthetics?
- Central nervous system excitation followed by depression
- Hyperglycemia only
- Increased hair growth
- Enhanced renal filtration
Correct Answer: Central nervous system excitation followed by depression
Q20. When measuring onset of block in isolated nerve preparations, what is a typical measurable endpoint?
- Time to 50% reduction in compound action potential amplitude
- Time to color change of solution
- pH shift in perfusate
- Change in tissue weight
Correct Answer: Time to 50% reduction in compound action potential amplitude
Q21. Which ion channel subtype is a primary molecular target for most local anaesthetics?
- Voltage‑gated sodium channels (Nav)
- Ligand‑gated nicotinic receptors
- Potassium leak channels only
- Chloride channels exclusively
Correct Answer: Voltage‑gated sodium channels (Nav)
Q22. In tissue binding studies, high protein binding of a local anaesthetic typically causes:
- Longer duration of action due to depot effect
- Faster renal elimination
- Decreased potency at the target site
- Immediate hypersensitivity reactions always
Correct Answer: Longer duration of action due to depot effect
Q23. Which experimental control is essential when comparing two local anaesthetic formulations in vitro?
- Vehicle (placebo) control with identical solvent conditions
- Using different temperatures for each group
- Changing pH only in the test group
- Varying tissue source randomly without record
Correct Answer: Vehicle (placebo) control with identical solvent conditions
Q24. The tail‑flick and hot‑plate tests primarily measure which modality of nociception?
- Thermal nociception
- Mechanical nociception
- Inflammatory edema
- Auditory reflexes
Correct Answer: Thermal nociception
Q25. Which factor is least relevant when selecting an animal model for local anaesthetic screening?
- Color of the animal’s fur
- Similarity of nerve anatomy to humans
- Ethical and regulatory considerations
- Reproducibility of endpoints
Correct Answer: Color of the animal’s fur
Q26. In vitro models using artificial lipid membranes help to study which property of local anaesthetics?
- Membrane partitioning and lipid interactions
- Renal clearance mechanisms
- Hepatic enzyme induction
- Behavioral side effects
Correct Answer: Membrane partitioning and lipid interactions
Q27. Which screening outcome would indicate a candidate has undesirably high systemic potency relative to local effect?
- Low therapeutic index with systemic toxicity at near‑effective concentrations
- Very high pKa only
- Poor solubility in water only
- Slow onset exclusively
Correct Answer: Low therapeutic index with systemic toxicity at near‑effective concentrations
Q28. Why are metabolic stability assays important in screening local anaesthetics?
- They predict duration, systemic exposure and risk of accumulation
- They change the color of the final product
- They determine the taste of oral formulations
- They are unnecessary for injectable drugs
Correct Answer: They predict duration, systemic exposure and risk of accumulation
Q29. Which result from a nerve conduction velocity study would suggest preferential block of small pain fibers?
- Greater reduction in conduction of thin, small‑diameter fibers than large fibers
- Equal reduction across all fiber types
- Faster conduction in small fibers
- No change in any fiber conduction
Correct Answer: Greater reduction in conduction of thin, small‑diameter fibers than large fibers
Q30. Ethical considerations in screening models require which action before animal studies?
- Approval from an institutional animal ethics committee and adherence to 3Rs
- Immediate publication without approval
- Random selection of endpoints without justification
- Use of highest possible dose to save time
Correct Answer: Approval from an institutional animal ethics committee and adherence to 3Rs
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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