The concept of spare receptors, also known as receptor reserve, is an important principle in pharmacology that explains why a maximal biological response can often be achieved even when not all available receptors are occupied by an agonist. For PharmD students and pharmacists, understanding spare receptors is key to comprehending drug potency, the effects of antagonists, and how tissues can maintain sensitivity to signaling molecules. This phenomenon deviates from simple interpretations of the law of mass action and has significant implications for drug design and therapeutic strategies. This quiz will test your knowledge on the definition, characteristics, and pharmacological significance of spare receptors.
1. “Spare receptors” or “receptor reserve” exists in a system when:
- a) All receptors must be occupied by an agonist to elicit a maximal pharmacological response.
- b) A maximal pharmacological response can be elicited by an agonist at a concentration that does not occupy all of the available receptors.
- c) There are no functional receptors present for a particular drug.
- d) The drug has very low potency.
Answer: b) A maximal pharmacological response can be elicited by an agonist at a concentration that does not occupy all of the available receptors.
2. The presence of spare receptors implies that the number of receptors in a tissue is:
- a) Less than the number of drug molecules needed for a maximal effect.
- b) Exactly equal to the number of drug molecules needed for a maximal effect.
- c) Greater than the number that needs to be occupied to produce a maximal response.
- d) Constantly changing and cannot be determined.
Answer: c) Greater than the number that needs to be occupied to produce a maximal response.
3. In a system with spare receptors, a full agonist can produce a maximal response by occupying:
- a) 100% of the receptors.
- b) Only a small fraction of the available receptors.
- c) Receptors in a different tissue.
- d) No receptors, acting through a different mechanism.
Answer: b) Only a small fraction of the available receptors.
4. The Law of Mass Action, in its simplest form applied to drug-receptor binding, might not fully explain drug effects in systems with spare receptors because:
- a) It assumes drug effects are always directly proportional to the number of occupied receptors up to 100% occupancy for maximal effect.
- b) It only applies to antagonists.
- c) It ignores the concentration of the drug.
- d) It does not consider receptor desensitization.
Answer: a) It assumes drug effects are always directly proportional to the number of occupied receptors up to 100% occupancy for maximal effect.
5. The presence of spare receptors primarily affects an agonist’s apparent:
- a) Efficacy (maximal effect).
- b) Potency (concentration needed for a given effect).
- c) Half-life.
- d) Route of elimination.
Answer: b) Potency (concentration needed for a given effect).
6. In a system with spare receptors, the EC50 (concentration for 50% of maximal effect) for a full agonist will be _________ its KD (dissociation constant for receptor binding).
- a) Greater than
- b) Less than
- c) Equal to
- d) Unrelated to
Answer: b) Less than
7. How do spare receptors influence the sensitivity of a tissue to an agonist?
- a) They decrease the sensitivity.
- b) They increase the sensitivity, allowing a response at lower agonist concentrations.
- c) They have no effect on sensitivity.
- d) They only affect the duration of action.
Answer: b) They increase the sensitivity, allowing a response at lower agonist concentrations.
8. For a partial agonist in a system with a large receptor reserve, it is possible for the partial agonist to:
- a) Act as a full antagonist.
- b) Produce a maximal response similar to a full agonist, even if its intrinsic activity is lower.
- c) Never produce any response.
- d) Only bind to spare receptors.
Answer: b) Produce a maximal response similar to a full agonist, even if its intrinsic activity is lower. (This depends on the degree of “spareness” and the intrinsic activity of the partial agonist.)
9. When an irreversible antagonist is added to a system with spare receptors, what is typically observed initially as the antagonist concentration increases?
- a) An immediate decrease in the maximal response of a full agonist.
- b) A parallel rightward shift of the agonist dose-response curve with no change in the maximal response, until the spare receptors are exhausted.
- c) An increase in the agonist’s potency.
- d) No effect on the agonist’s action.
Answer: b) A parallel rightward shift of the agonist dose-response curve with no change in the maximal response, until the spare receptors are exhausted.
10. Once all spare receptors are occupied by an irreversible antagonist, further addition of the antagonist will cause:
- a) A continued parallel rightward shift of the agonist dose-response curve.
- b) A decrease in the maximal response achievable by the full agonist.
- c) An increase in the agonist’s maximal response.
- d) The agonist to become a partial agonist.
Answer: b) A decrease in the maximal response achievable by the full agonist.
11. In a system with NO spare receptors, an irreversible antagonist will:
- a) Cause a parallel rightward shift in the agonist dose-response curve.
- b) Immediately decrease the maximal response of a full agonist with increasing antagonist concentration.
- c) Increase the potency of the full agonist.
- d) Have no effect.
Answer: b) Immediately decrease the maximal response of a full agonist with increasing antagonist concentration.
12. The concept of spare receptors is relevant to understanding the action of drugs that target:
- a) Enzymes only.
- b) G protein-coupled receptors (GPCRs) and other receptor types where amplification of signal can occur.
- c) Ion channels exclusively.
- d) DNA.
Answer: b) G protein-coupled receptors (GPCRs) and other receptor types where amplification of signal can occur.
13. Physiologically, spare receptors can be advantageous because they:
- a) Reduce the efficiency of signaling.
- b) Allow a cell to respond to low concentrations of a hormone or neurotransmitter and provide a safety margin.
- c) Ensure that drugs always have a long duration of action.
- d) Prevent drug tolerance.
Answer: b) Allow a cell to respond to low concentrations of a hormone or neurotransmitter and provide a safety margin.
14. Experimentally, the presence of spare receptors can be demonstrated by comparing:
- a) The drug’s cost with its efficacy.
- b) The agonist’s EC50 for producing a response with its KD for receptor binding.
- c) The drug’s half-life in different patient populations.
- d) The route of administration with the onset of action.
Answer: b) The agonist’s EC50 for producing a response with its KD for receptor binding.
15. If EC50 < KD for a full agonist, it suggests:
- a) The absence of spare receptors.
- b) The presence of spare receptors.
- c) The drug is a non-competitive antagonist.
- d) The drug has poor absorption.
Answer: b) The presence of spare receptors.
16. Receptor down-regulation (a decrease in receptor number) in a system with a large receptor reserve might initially lead to:
- a) An increase in the maximal response to an agonist.
- b) A decrease in agonist potency (EC50 increases) with little or no change in the maximal response, until the reserve is significantly depleted.
- c) An immediate loss of all response to the agonist.
- d) The agonist becoming an antagonist.
Answer: b) A decrease in agonist potency (EC50 increases) with little or no change in the maximal response, until the reserve is significantly depleted.
17. The degree of “spareness” can vary between:
- a) Different drugs acting on the same receptor.
- b) Different tissues for the same receptor and agonist.
- c) Different routes of administration for the same drug.
- d) Only different species.
Answer: b) Different tissues for the same receptor and agonist.
18. The phenomenon of spare receptors is one condition where the Law of Mass Action is not followed in its simplest interpretation for dose-response relationships because:
- a) The maximal effect does not require 100% receptor occupancy.
- b) Drugs do not bind to receptors.
- c) The effect is always directly proportional to dose.
- d) All receptors are identical.
Answer: a) The maximal effect does not require 100% receptor occupancy.
19. From a clinical perspective, the presence of spare receptors can mean that:
- a) Higher doses of antagonists are always needed.
- b) A tissue can still respond effectively to an agonist even if a certain fraction of its receptors is non-functional or blocked.
- c) All drugs will exhibit tachyphylaxis.
- d) Partial agonists will always behave like full antagonists.
Answer: b) A tissue can still respond effectively to an agonist even if a certain fraction of its receptors is non-functional or blocked.
20. Which type of drug interaction is most directly influenced by the presence or absence of spare receptors when considering antagonists?
- a) Pharmacokinetic interactions affecting metabolism.
- b) The ability of an irreversible antagonist to reduce the maximal effect of a full agonist.
- c) Interactions involving plasma protein binding.
- d) Interactions affecting drug excretion.
Answer: b) The ability of an irreversible antagonist to reduce the maximal effect of a full agonist.
21. If a tissue loses a significant number of spare receptors due to a disease state, the potency of an agonist acting on that tissue is likely to:
- a) Increase.
- b) Decrease.
- c) Remain unchanged.
- d) Become unpredictable.
Answer: b) Decrease.
22. The concept of spare receptors helps explain why some potent agonists can elicit a maximal response at very low concentrations, far below their KD values.
- a) True
- b) False
Answer: a) True
23. The intrinsic activity of a drug is directly related to the presence of spare receptors.
- a) True
- b) False (Intrinsic activity relates to the ability of the drug-receptor complex to produce a response; spare receptors relate to the number of receptors vs. response).
Answer: b) False (Intrinsic activity relates to the ability of the drug-receptor complex to produce a response; spare receptors relate to the number of receptors vs. response).
24. A system that exhibits a high degree of receptor reserve for a particular agonist will be relatively resistant to the effects of:
- a) A competitive antagonist at low concentrations.
- b) An irreversible antagonist, until a large proportion of receptors are inactivated.
- c) A different agonist acting on a separate receptor system.
- d) Pharmacokinetic drug interactions.
Answer: b) An irreversible antagonist, until a large proportion of receptors are inactivated.
25. The “operational model” of receptor theory incorporates the concept of spare receptors by considering:
- a) Only the affinity of the drug for the receptor.
- b) Both drug affinity and the efficiency of the stimulus-response coupling, which can be influenced by receptor number.
- c) Only the intrinsic activity of the drug.
- d) The rate of drug absorption.
Answer: b) Both drug affinity and the efficiency of the stimulus-response coupling, which can be influenced by receptor number.
26. Which statement accurately describes the relationship between full agonists and spare receptors?
- a) Full agonists require 100% receptor occupancy even with spare receptors.
- b) Full agonists can take advantage of spare receptors to produce a maximal response without occupying all receptors.
- c) Spare receptors reduce the maximal effect of full agonists.
- d) Full agonists do not interact with spare receptors.
Answer: b) Full agonists can take advantage of spare receptors to produce a maximal response without occupying all receptors.
27. For a system with spare receptors, if a competitive antagonist is added, the dose-response curve for a full agonist will shift to the right, but the maximal response:
- a) Will decrease.
- b) Can still be achieved by increasing the agonist concentration.
- c) Will increase.
- d) Will be achieved at a lower agonist concentration.
Answer: b) Can still be achieved by increasing the agonist concentration.
28. The efficiency of coupling between receptor activation and downstream signaling pathways can influence the apparent:
- a) Chemical stability of the drug.
- b) Degree of receptor spareness.
- c) Route of drug administration.
- d) Plasma protein binding of the drug.
Answer: b) Degree of receptor spareness.
29. Conditions where the Law of Mass Action (simple model) is not followed regarding receptor theory include spare receptors and:
- a) First-order kinetics.
- b) Receptor cooperativity.
- c) Passive diffusion.
- d) Zero-order kinetics.
Answer: b) Receptor cooperativity.
30. Receptor cooperativity refers to a situation where:
- a) Receptors from different tissues cooperate.
- b) The binding of one ligand molecule to a multi-subunit receptor influences the binding of subsequent ligand molecules.
- c) All drugs cooperate to produce a greater effect.
- d) Receptors only bind one drug at a time.
Answer: b) The binding of one ligand molecule to a multi-subunit receptor influences the binding of subsequent ligand molecules.
31. If a tissue has very few or no spare receptors for a particular agonist, it implies that:
- a) The agonist is extremely potent in that tissue.
- b) A nearly 100% receptor occupancy is required to achieve a maximal response.
- c) The tissue is highly sensitive to antagonists.
- d) Receptor desensitization will not occur.
Answer: b) A nearly 100% receptor occupancy is required to achieve a maximal response.
32. The term “receptor number” is a key determinant in the phenomenon of:
- a) Drug solubility.
- b) Spare receptors and receptor regulation (down-regulation/up-regulation).
- c) Drug’s chemical class.
- d) Drug’s taste.
Answer: b) Spare receptors and receptor regulation (down-regulation/up-regulation).
33. Consider a drug that is a full agonist. In a tissue with many spare receptors versus a tissue with few spare receptors for this drug, the EC50 will likely be:
- a) Higher in the tissue with many spare receptors.
- b) Lower in the tissue with many spare receptors.
- c) The same in both tissues.
- d) Dependent only on the drug’s KD.
Answer: b) Lower in the tissue with many spare receptors.
34. The concept of spare receptors is most relevant for understanding the actions of:
- a) Drugs that do not bind to receptors.
- b) Agonists and their interaction with antagonists.
- c) Drugs that only affect enzymes.
- d) Drugs that are eliminated renally.
Answer: b) Agonists and their interaction with antagonists.
35. If a drug requires a high level of receptor occupancy to achieve its effect, it suggests that in that particular system, there are:
- a) Many spare receptors.
- b) Few or no spare receptors.
- c) Only intracellular receptors.
- d) Only ion channel-linked receptors.
Answer: b) Few or no spare receptors.
36. Spare receptors can “buffer” the system against:
- a) Increases in agonist concentration.
- b) A partial loss of receptor number, allowing a maximal response to still be achievable.
- c) All types of drug toxicity.
- d) Changes in drug metabolism.
Answer: b) A partial loss of receptor number, allowing a maximal response to still be achievable.
37. The existence of spare receptors means that the relationship between receptor occupancy and response is often:
- a) Linear.
- b) Non-linear.
- c) Inversely proportional.
- d) Non-existent.
Answer: b) Non-linear.
38. For a partial agonist, the presence of spare receptors may allow it to produce a response that is:
- a) Always equal to its intrinsic activity relative to a full agonist.
- b) Greater than what its intrinsic activity would predict if it can occupy enough receptors to activate downstream signaling sufficiently.
- c) Always zero.
- d) Toxic at all doses.
Answer: b) Greater than what its intrinsic activity would predict if it can occupy enough receptors to activate downstream signaling sufficiently.
39. Receptor regulation and the concept of spare receptors are interconnected because:
- a) Receptor regulation eliminates spare receptors.
- b) Changes in receptor number due to regulation will impact the functional reserve of spare receptors and thus alter drug responsiveness.
- c) Spare receptors prevent any form of receptor regulation.
- d) They are completely independent concepts.
Answer: b) Changes in receptor number due to regulation will impact the functional reserve of spare receptors and thus alter drug responsiveness.
40. Why is understanding spare receptors important for drug development?
- a) It helps in designing drugs that are always less potent.
- b) It can inform strategies for developing drugs with desired sensitivity profiles and understanding how receptor density in target tissues might affect response.
- c) It ensures all developed drugs will have spare receptors.
- d) It primarily relates to marketing strategies.
Answer: b) It can inform strategies for developing drugs with desired sensitivity profiles and understanding how receptor density in target tissues might affect response.
41. If two full agonists act on the same receptor system with spare receptors, but Agonist A has a lower KD than Agonist B, then Agonist A will likely appear:
- a) Less potent than Agonist B.
- b) More potent than Agonist B (lower EC50).
- c) To have a lower maximal effect than Agonist B.
- d) To be a partial agonist compared to Agonist B.
Answer: b) More potent than Agonist B (lower EC50).
42. The functional consequence of spare receptors is that a cell can be highly responsive to an agonist even when the actual number of agonist-receptor complexes is low.
- a) True
- b) False
Answer: a) True
43. Tissues with a high proportion of spare receptors may be more resistant to the effects of receptor down-regulation in terms of maintaining a maximal response, at least initially.
- a) True
- b) False
Answer: a) True
44. Which of the following systems is well-known to often exhibit spare receptors?
- a) Systems with very limited signal amplification.
- b) Insulin receptors in certain tissues.
- c) Systems where one receptor binding event leads to only one downstream molecule activation.
- d) Systems involving direct binding to DNA.
Answer: b) Insulin receptors in certain tissues.
45. The concept of spare receptors applies primarily to the actions of:
- a) Antacids.
- b) Agonists that elicit a biological response via receptor interaction.
- c) Drugs that are eliminated by zero-order kinetics.
- d) Osmotic diuretics.
Answer: b) Agonists that elicit a biological response via receptor interaction.
46. When an irreversible antagonist reduces the maximal effect of a full agonist, it indicates that:
- a) There were no spare receptors, or the spare receptors have been overcome.
- b) The agonist has become a partial agonist.
- c) The antagonist has increased the agonist’s affinity.
- d) The system has up-regulated receptors.
Answer: a) There were no spare receptors, or the spare receptors have been overcome.
47. The “margin of safety” provided by spare receptors means that:
- a) The drug will never cause side effects.
- b) A significant number of receptors can be lost or inactivated before the maximal physiological or pharmacological response is compromised.
- c) The drug can be given at any dose.
- d) Tolerance will never develop.
Answer: b) A significant number of receptors can be lost or inactivated before the maximal physiological or pharmacological response is compromised.
48. The “stimulus” generated by an agonist-receptor complex is amplified by downstream signaling pathways. This amplification is a key reason for the existence of:
- a) Pharmacokinetic tolerance.
- b) Spare receptors.
- c) Drug-drug interactions affecting metabolism.
- d) Non-specific drug binding.
Answer: b) Spare receptors.
49. If receptor desensitization occurs in a system with spare receptors, the agonist’s dose-response curve might show:
- a) An increase in maximal effect.
- b) A shift to the left (increased potency).
- c) A shift to the right (decreased potency) and/or a decrease in maximal effect, depending on the extent of desensitization and spareness.
- d) No change.
Answer: c) A shift to the right (decreased potency) and/or a decrease in maximal effect, depending on the extent of desensitization and spareness.
50. Understanding spare receptors helps pharmacists appreciate why:
- a) All drugs have the same potency.
- b) The relationship between drug dose, receptor occupancy, and tissue response can be complex and non-linear.
- c) Generic drugs are always less effective.
- d) Patients never develop tolerance to medications.
Answer: b) The relationship between drug dose, receptor occupancy, and tissue response can be complex and non-linear.