Introduction: Non-competitive antagonists MCQs With Answer provide B.Pharm students a focused review of how non-competitive antagonists alter receptor function, dose–response curves, and clinical outcomes. This topic covers mechanisms (allosteric modulation, irreversible orthosteric blockade), pharmacodynamic signatures (reduced Emax, insurmountable inhibition), experimental identification (Schild analysis, washout studies), and therapeutic relevance (e.g., NMDA receptor blockers). Understanding receptor reserve, signal transduction interference, and differences from competitive antagonists is essential for rational drug design and safe prescribing. These MCQs emphasize mechanism, kinetics, examples, and clinical implications to deepen conceptual and applied knowledge. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the hallmark effect of a non-competitive antagonist on a drug’s dose–response curve?
- A parallel rightward shift without change in maximal response
- A decrease in maximal response (Emax) often without parallel shift
- An increase in potency with higher Emax
- No change in either potency or efficacy
Correct Answer: A decrease in maximal response (Emax) often without parallel shift
Q2. Which mechanism best describes an allosteric non-competitive antagonist?
- Competes with agonist at the orthosteric binding site
- Binds to a different site altering receptor conformation and function
- Enhances agonist binding affinity
- Irreversibly degrades the agonist
Correct Answer: Binds to a different site altering receptor conformation and function
Q3. Which of the following is a classic example of a non-competitive NMDA receptor antagonist used clinically?
- Propranolol
- Ketanserin
- Ketamine
- Atropine
Correct Answer: Ketamine
Q4. How does an irreversible (covalent) antagonist typically affect receptor availability?
- Increases receptor density
- Temporarily blocks receptors but leaves them intact
- Permanently reduces available receptors until new receptors are synthesized
- Enhances receptor internalization and recycling immediately
Correct Answer: Permanently reduces available receptors until new receptors are synthesized
Q5. Which experimental observation suggests non-competitive antagonism rather than competitive antagonism?
- Rightward parallel shift in dose–response that is reversed by higher agonist concentration
- No change in Emax but decreased potency
- Reduction of maximal response even with increasing agonist concentrations
- Enhanced agonist binding affinity
Correct Answer: Reduction of maximal response even with increasing agonist concentrations
Q6. In presence of a non-competitive antagonist, how is EC50 generally affected?
- EC50 always decreases
- EC50 always increases proportionally to Emax decrease
- EC50 may be unchanged, increased, or appear altered depending on receptor reserve
- EC50 becomes zero
Correct Answer: EC50 may be unchanged, increased, or appear altered depending on receptor reserve
Q7. Which term best describes a non-competitive antagonist that binds reversibly to an allosteric site?
- Irreversible orthosteric antagonist
- Non-surmountable covalent antagonist
- Allosteric negative modulator
- Functional agonist
Correct Answer: Allosteric negative modulator
Q8. Which pharmacological technique helps distinguish competitive from non-competitive antagonism?
- Schild regression analysis and observation of parallel shifts
- Measuring half-life of the drug in plasma
- Assessing renal clearance
- Measuring blood–brain barrier permeability
Correct Answer: Schild regression analysis and observation of parallel shifts
Q9. A non-competitive antagonist that blocks ion channel function typically interacts with which part of the receptor?
- Extracellular orthosteric ligand-binding pocket only
- Intracellular signaling proteins exclusively
- The ion conduction pore or a site that stabilizes closed state
- Lipid bilayer with no receptor contact
Correct Answer: The ion conduction pore or a site that stabilizes closed state
Q10. Which clinical implication is most consistent with non-competitive antagonism?
- Effects are easily reversed by increasing agonist dose
- Antagonist effects may persist until receptor turnover or antagonist dissociation
- There is no impact on therapeutic index
- Non-competitive antagonists always have fewer side effects
Correct Answer: Antagonist effects may persist until receptor turnover or antagonist dissociation
Q11. How does receptor reserve (spare receptors) influence the effect of a non-competitive antagonist?
- Large receptor reserve makes a non-competitive antagonist more likely to eliminate response immediately
- Large receptor reserve can mask the loss of receptors, maintaining Emax until reserve is depleted
- Receptor reserve only affects pharmacokinetics, not antagonism
- Receptor reserve converts non-competitive antagonists into agonists
Correct Answer: Large receptor reserve can mask the loss of receptors, maintaining Emax until reserve is depleted
Q12. Which statement about surmountability is true for non-competitive antagonists?
- Their inhibition is always fully surmountable by increased agonist concentration
- Their inhibition is often insurmountable, meaning maximal response cannot be restored
- They convert agonists into inverse agonists
- Surmountability depends solely on the antagonist’s molecular weight
Correct Answer: Their inhibition is often insurmountable, meaning maximal response cannot be restored
Q13. Which laboratory finding supports irreversible non-competitive antagonism?
- Complete recovery of response after washout
- Permanent rightward parallel shift that reverses with more agonist
- Persistent reduction in Emax even after extensive washout
- No change in receptor number on biochemical assay
Correct Answer: Persistent reduction in Emax even after extensive washout
Q14. A drug that reduces signaling downstream of the receptor without blocking ligand binding is best described as:
- An orthosteric competitive antagonist
- A functional (physiological) non-competitive antagonist
- A pharmacokinetic antagonist
- A prodrug activator
Correct Answer: A functional (physiological) non-competitive antagonist
Q15. Which of the following is a pharmacodynamic consequence of non-competitive antagonism on tissue response?
- Increased maximal tissue response to agonist
- Reduced efficacy and possible altered sensitivity depending on spare receptors
- Enhanced receptor synthesis immediately
- Elimination of all receptor-mediated signaling permanently
Correct Answer: Reduced efficacy and possible altered sensitivity depending on spare receptors
Q16. Memantine is clinically used for Alzheimer’s disease. Its action as a non-competitive NMDA antagonist primarily provides what benefit?
- Permanent inhibition of glutamate release
- Reduction of excitotoxicity by blocking excessive NMDA receptor activity
- Complete blockade of all CNS NMDA signaling
- Enhancement of long-term potentiation
Correct Answer: Reduction of excitotoxicity by blocking excessive NMDA receptor activity
Q17. Which experimental approach would indicate an antagonist is acting at an allosteric site?
- Complete displacement of radioligand from the orthosteric site in binding assay
- No change in binding affinity but a change in agonist efficacy or kinetics
- Immediate receptor degradation on Western blot
- Identical effects to a high-affinity competitive ligand in Schild plot
Correct Answer: No change in binding affinity but a change in agonist efficacy or kinetics
Q18. In drug development, why might a reversible allosteric non-competitive antagonist be preferred over an irreversible one?
- Irreversible antagonists are always more selective
- Reversible allosteric antagonists allow finer temporal control and reduced long-term toxicity
- Reversible antagonists permanently eliminate receptor function
- Irreversible antagonists cannot be synthesized reliably
Correct Answer: Reversible allosteric antagonists allow finer temporal control and reduced long-term toxicity
Q19. Which property is typical of an orthosteric irreversible antagonist?
- Forms a covalent bond with the receptor, reducing Bmax
- Increases agonist potency without affecting Bmax
- Acts exclusively through downstream second messengers
- Is always water-soluble and rapidly reversible
Correct Answer: Forms a covalent bond with the receptor, reducing Bmax
Q20. How can washout experiments differentiate reversible from irreversible antagonists?
- Reversible antagonists show persistent effect after washout
- Irreversible antagonists’ effects persist after extensive washout, while reversible ones recover
- Both reversible and irreversible antagonists always recover after washout
- Washout experiments are not informative for antagonism type
Correct Answer: Irreversible antagonists’ effects persist after extensive washout, while reversible ones recover
Q21. A non-competitive antagonist that stabilizes an inactive receptor conformation is called:
- A positive allosteric modulator
- An inverse agonist or negative allosteric modulator depending on context
- An agonist at the orthosteric site
- A competitive enhancer
Correct Answer: An inverse agonist or negative allosteric modulator depending on context
Q22. Which is a functional (physiological) non-competitive antagonism example?
- Alpha-adrenergic antagonist binding to receptor orthosteric site
- Administration of a drug that lowers intracellular ATP, reducing channel activity independently of ligand binding
- Direct agonist binding to receptor causing response
- Competitive inhibition at the enzyme active site
Correct Answer: Administration of a drug that lowers intracellular ATP, reducing channel activity independently of ligand binding
Q23. When performing a Schild plot, what pattern suggests non-competitive antagonism?
- A straight line with slope equal to 1
- No simple parallel shifts; inability to fit a straight line with slope 1 indicating non-competitive action
- A linear relationship with negative slope exactly −1
- Complete overlap of agonist dose–response curves
Correct Answer: No simple parallel shifts; inability to fit a straight line with slope 1 indicating non-competitive action
Q24. Which safety consideration is particularly important for irreversible non-competitive antagonists?
- They are always safe because effects are short-lived
- Dose selection is critical because prolonged receptor blockade can cause long-lasting toxicity
- They never cross the blood–brain barrier, so CNS effects are irrelevant
- No monitoring required after administration
Correct Answer: Dose selection is critical because prolonged receptor blockade can cause long-lasting toxicity
Q25. Which pharmacological effect would suggest a drug is acting as a channel-blocking non-competitive antagonist?
- Increased single-channel open time and conductance
- Use-dependent block where inhibition increases with channel activation
- Enhanced agonist binding to the extracellular domain
- Acceleration of receptor recycling
Correct Answer: Use-dependent block where inhibition increases with channel activation
Q26. Which experimental observation indicates the presence of spare receptors when a non-competitive antagonist is applied?
- Immediate loss of all function with minimal receptor occupancy
- No change in maximal response until a threshold of receptor blockade is reached
- Emax falls instantly with any antagonist concentration
- Potency increases while efficacy decreases dramatically
Correct Answer: No change in maximal response until a threshold of receptor blockade is reached
Q27. In clinical toxicology, why are non-competitive channel blockers often more dangerous in overdose?
- Their effects are always easily reversed by antidotes
- They may produce profound physiological block that cannot be overcome by endogenous agonists
- They increase metabolic elimination of toxins
- They only affect peripheral tissues with no CNS involvement
Correct Answer: They may produce profound physiological block that cannot be overcome by endogenous agonists
Q28. Which property differentiates a non-competitive antagonist from a pharmacokinetic antagonist?
- Non-competitive antagonists alter drug concentrations in plasma
- Non-competitive antagonists act at the receptor or signaling pathway, while pharmacokinetic antagonists change drug availability
- Pharmacokinetic antagonists bind covalently to receptors
- There is no difference; both are the same
Correct Answer: Non-competitive antagonists act at the receptor or signaling pathway, while pharmacokinetic antagonists change drug availability
Q29. Which statement about partial agonists and non-competitive antagonists is accurate?
- Partial agonists always act as non-competitive antagonists
- Partial agonists can behave as functional antagonists in presence of full agonists by reducing maximal response
- Partial agonists increase Emax when combined with full agonists
- Partial agonists irreversibly inactivate receptors
Correct Answer: Partial agonists can behave as functional antagonists in presence of full agonists by reducing maximal response
Q30. Which therapeutic strategy might overcome some effects of reversible non-competitive antagonists?
- Increasing agonist concentration always fully restores Emax
- Using allosteric positive modulators or alternative signaling pathway agonists to restore function
- Administering a different irreversible antagonist
- Reducing agonist concentration to lower receptor activation
Correct Answer: Using allosteric positive modulators or alternative signaling pathway agonists to restore function
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