Receptor regulation is a dynamic physiological process where the number or sensitivity of receptors on a cell surface or within a cell changes in response to various stimuli, including chronic exposure to drugs. For PharmD students and pharmacists, understanding these regulatory mechanisms—such as down-regulation, up-regulation, desensitization, and their roles in phenomena like drug tolerance and sensitization—is crucial for predicting and managing long-term drug therapy. These concepts directly impact medication effectiveness, the development of side effects, and withdrawal syndromes. This quiz will test your knowledge on the intricate processes of receptor regulation and their pharmacological implications.
1. Receptor regulation refers to the process by which cells can alter:
- a) The chemical structure of a drug.
- b) The number or sensitivity of their receptors in response to stimuli.
- c) The rate of drug absorption.
- d) The route of drug administration.
Answer: b) The number or sensitivity of their receptors in response to stimuli.
2. Prolonged or excessive exposure to an agonist drug often leads to:
- a) Up-regulation of receptors.
- b) Down-regulation or desensitization of receptors.
- c) Increased receptor sensitivity.
- d) Creation of new receptor types.
Answer: b) Down-regulation or desensitization of receptors.
3. Down-regulation of receptors typically involves a decrease in:
- a) The affinity of the drug for the receptor.
- b) The number of functional receptors available on the cell surface or within the cell.
- c) The rate of drug metabolism.
- d) The drug’s half-life.
Answer: b) The number of functional receptors available on the cell surface or within the cell.
4. Up-regulation of receptors often occurs in response to:
- a) Chronic administration of an agonist.
- b) Chronic administration of an antagonist or prolonged absence of an agonist.
- c) A single large dose of an agonist.
- d) Increased drug excretion.
Answer: b) Chronic administration of an antagonist or prolonged absence of an agonist.
5. Receptor desensitization is a phenomenon where:
- a) The number of receptors increases rapidly.
- b) A receptor becomes less responsive to stimulation by an agonist, even if the agonist is still present.
- c) The receptor binds more tightly to the agonist.
- d) The drug is metabolized more quickly.
Answer: b) A receptor becomes less responsive to stimulation by an agonist, even if the agonist is still present.
6. Homologous desensitization refers to the desensitization of:
- a) Multiple different types of receptors simultaneously.
- b) Only the specific receptor type that has been activated by an agonist.
- c) Receptors in a different tissue than where the agonist is acting.
- d) Receptors that have not been exposed to any agonist.
Answer: b) Only the specific receptor type that has been activated by an agonist.
7. Heterologous desensitization involves the desensitization of:
- a) Only the activated receptor type.
- b) A receptor to its specific agonist as well as the desensitization of other, non-activated receptors to their respective agonists, often via shared signaling pathways.
- c) Receptors due to genetic mutations only.
- d) Receptors that are located intracellularly.
Answer: b) A receptor to its specific agonist as well as the desensitization of other, non-activated receptors to their respective agonists, often via shared signaling pathways.
8. Receptor internalization or sequestration is a mechanism of down-regulation where:
- a) Receptors are permanently destroyed.
- b) Receptors are moved from the cell surface into the cell interior, making them unavailable for agonist binding.
- c) New receptors are synthesized at an increased rate.
- d) The receptor’s binding site is chemically altered.
Answer: b) Receptors are moved from the cell surface into the cell interior, making them unavailable for agonist binding.
9. Drug tolerance is a state characterized by:
- a) An increased response to the same dose of a drug over time.
- b) A decreased response to the same dose of a drug over time, requiring larger doses to achieve the same effect.
- c) The development of an allergic reaction to a drug.
- d) A rapid onset of action of the drug.
Answer: b) A decreased response to the same dose of a drug over time, requiring larger doses to achieve the same effect.
10. Pharmacokinetic tolerance involves changes in:
- a) Receptor sensitivity or number.
- b) The drug’s absorption, distribution, metabolism, or excretion, leading to lower concentrations of the drug at the site of action.
- c) The intrinsic activity of the drug.
- d) The patient’s psychological response to the drug.
Answer: b) The drug’s absorption, distribution, metabolism, or excretion, leading to lower concentrations of the drug at the site of action.
11. Pharmacodynamic tolerance involves changes in:
- a) The rate of drug absorption.
- b) The responsiveness of the target receptors or cellular signaling pathways to the drug.
- c) The rate of drug excretion.
- d) The plasma protein binding of the drug.
Answer: b) The responsiveness of the target receptors or cellular signaling pathways to the drug.
12. Tachyphylaxis refers to:
- a) A very slow development of drug tolerance over months.
- b) A rapid decrease in response to a drug after repeated administration over a short period.
- c) An increased drug effect with repeated dosing.
- d) A type of allergic reaction.
Answer: b) A rapid decrease in response to a drug after repeated administration over a short period.
13. Drug sensitization (reverse tolerance) is a phenomenon where:
- a) The effect of a drug diminishes with repeated use.
- b) The effect of a drug increases with repeated administration of the same dose.
- c) The drug becomes less potent.
- d) The drug’s half-life decreases.
Answer: b) The effect of a drug increases with repeated administration of the same dose.
14. “Spare receptors” (receptor reserve) exist when:
- a) All receptors must be occupied to produce a maximal response.
- b) A maximal pharmacological response can be elicited by an agonist at a concentration that does not occupy all available receptors.
- c) There are no functional receptors for a particular drug.
- d) Receptors are only located inside the cell.
Answer: b) A maximal pharmacological response can be elicited by an agonist at a concentration that does not occupy all available receptors.
15. The presence of spare receptors can make a tissue:
- a) Less sensitive to an agonist.
- b) More sensitive to an agonist, as a maximal effect can be achieved with lower receptor occupancy.
- c) Prone to rapid desensitization.
- d) Resistant to all drug effects.
Answer: b) More sensitive to an agonist, as a maximal effect can be achieved with lower receptor occupancy.
16. Abrupt discontinuation of a drug that has caused receptor up-regulation (e.g., a beta-blocker) can lead to:
- a) No significant effect.
- b) An exaggerated response or withdrawal syndrome when endogenous agonists bind to the increased number of receptors.
- c) Continued tolerance to the drug.
- d) A decrease in receptor numbers.
Answer: b) An exaggerated response or withdrawal syndrome when endogenous agonists bind to the increased number of receptors.
17. Which of the following cellular processes can contribute to receptor down-regulation?
- a) Increased synthesis of new receptors.
- b) Decreased degradation of existing receptors.
- c) Increased rate of receptor endocytosis and degradation.
- d) Phosphorylation that increases receptor activity.
Answer: c) Increased rate of receptor endocytosis and degradation.
18. G protein-coupled receptor kinases (GRKs) play a role in:
- a) Activating G proteins directly.
- b) Phosphorylating agonist-occupied GPCRs, leading to arrestin binding and desensitization/internalization.
- c) Synthesizing new GPCRs.
- d) Degrading G proteins.
Answer: b) Phosphorylating agonist-occupied GPCRs, leading to arrestin binding and desensitization/internalization.
19. Arrestins are proteins that bind to phosphorylated GPCRs and promote:
- a) Increased receptor signaling.
- b) Receptor desensitization, internalization, and signaling via alternative pathways.
- c) Receptor synthesis.
- d) Prevention of agonist binding.
Answer: b) Receptor desensitization, internalization, and signaling via alternative pathways.
20. Chronic exposure to nicotine, an agonist at nicotinic acetylcholine receptors, can lead to:
- a) Down-regulation of these receptors in some brain areas.
- b) Up-regulation of these receptors in some brain areas, contributing to tolerance and dependence.
- c) No change in receptor number or sensitivity.
- d) Permanent destruction of these receptors.
Answer: b) Up-regulation of these receptors in some brain areas, contributing to tolerance and dependence. (Note: Nicotine receptor regulation is complex and can involve initial desensitization followed by up-regulation).
21. Tolerance to opioid analgesics is a significant clinical challenge and is primarily an example of:
- a) Pharmacokinetic tolerance.
- b) Pharmacodynamic tolerance involving receptor desensitization, down-regulation, and other adaptive changes.
- c) Allergic reaction.
- d) Increased drug absorption.
Answer: b) Pharmacodynamic tolerance involving receptor desensitization, down-regulation, and other adaptive changes.
22. Receptor recycling refers to the process where internalized receptors are:
- a) Immediately degraded in lysosomes.
- b) Returned to the cell surface to become functional again.
- c) Permanently stored within the cell.
- d) Converted into different types of receptors.
Answer: b) Returned to the cell surface to become functional again.
23. The process of receptor regulation is important because it allows cells to:
- a) Respond identically to all stimuli.
- b) Adapt to varying levels of stimulation and protect against overstimulation.
- c) Only decrease their responsiveness.
- d) Ignore all external signals.
Answer: b) Adapt to varying levels of stimulation and protect against overstimulation.
24. Altered receptor regulation can contribute to the pathophysiology of certain diseases. For example, insulin resistance in type 2 diabetes involves:
- a) Up-regulation of insulin receptors.
- b) Down-regulation and desensitization of insulin receptors or post-receptor defects.
- c) Increased insulin receptor sensitivity.
- d) Absence of insulin receptors.
Answer: b) Down-regulation and desensitization of insulin receptors or post-receptor defects.
25. Objective 9 of the PHA5515 syllabus is to “Describe the process of receptor regulation under conditions of under and over stimulation.” Over-stimulation by an agonist typically leads to:
- a) Receptor up-regulation.
- b) Receptor down-regulation or desensitization.
- c) Increased receptor synthesis.
- d) Decreased receptor degradation.
Answer: b) Receptor down-regulation or desensitization.
26. Objective 10 of the PHA5515 syllabus is to “List alternative mechanisms that contribute to drug tolerance and sensitization.” Besides receptor changes, pharmacokinetic tolerance can occur due to:
- a) Increased receptor binding.
- b) Induction of drug-metabolizing enzymes (e.g., cytochrome P450).
- c) Decreased drug excretion.
- d) Changes in receptor structure.
Answer: b) Induction of drug-metabolizing enzymes (e.g., cytochrome P450).
27. If a patient develops tolerance to a drug, the prescriber might need to:
- a) Decrease the dose.
- b) Increase the dose or frequency, or switch to another medication.
- c) Discontinue the drug immediately without tapering.
- d) Administer the drug by a different route.
Answer: b) Increase the dose or frequency, or switch to another medication.
28. Cross-tolerance occurs when tolerance to one drug:
- a) Increases sensitivity to another drug.
- b) Confers tolerance to another pharmacologically similar drug.
- c) Has no effect on the response to other drugs.
- d) Reverses the effects of another drug.
Answer: b) Confers tolerance to another pharmacologically similar drug.
29. The clinical implication of spare receptors is that a maximal effect can be produced even when:
- a) Only a very high concentration of agonist is present.
- b) Only a fraction of the total receptor pool is occupied by the agonist.
- c) All receptors are desensitized.
- d) The drug is a partial agonist.
Answer: b) Only a fraction of the total receptor pool is occupied by the agonist.
30. If a drug causes depletion of a neurotransmitter necessary for its action, this can lead to a form of tolerance or tachyphylaxis. This is a mechanism that is:
- a) Directly related to receptor number change.
- b) An alternative mechanism to receptor regulation, affecting the availability of an endogenous signaling molecule.
- c) Related to pharmacokinetic changes.
- d) A type of receptor up-regulation.
Answer: b) An alternative mechanism to receptor regulation, affecting the availability of an endogenous signaling molecule.
31. Receptor supersensitivity can occur after:
- a) Prolonged exposure to an agonist.
- b) Chronic blockade of receptors by an antagonist or denervation.
- c) A single dose of a drug.
- d) Increased drug metabolism.
Answer: b) Chronic blockade of receptors by an antagonist or denervation.
32. The time course for the development of tolerance or sensitization can vary greatly depending on:
- a) Only the drug’s color.
- b) The specific drug, dose, frequency of administration, and individual patient factors.
- c) The pharmacy where the drug was dispensed.
- d) The time of day the drug is taken.
Answer: b) The specific drug, dose, frequency of administration, and individual patient factors.
33. Understanding receptor regulation is important for pharmacists when counseling patients on:
- a) The price of the medication.
- b) The importance of adherence, potential for decreased effect over time, and risks of abrupt discontinuation of certain drugs.
- c) The best time to pick up refills.
- d) How to store the medication only.
Answer: b) The importance of adherence, potential for decreased effect over time, and risks of abrupt discontinuation of certain drugs.
34. The phenomenon of withdrawal symptoms upon cessation of certain drugs (e.g., opioids, benzodiazepines) is often related to:
- a) The drug still being highly effective.
- b) Adaptive changes in receptor systems (e.g., down-regulation with agonists, up-regulation with antagonists) that are unmasked when the drug is removed.
- c) The drug causing permanent receptor damage.
- d) An allergic reaction to drug cessation.
Answer: b) Adaptive changes in receptor systems (e.g., down-regulation with agonists, up-regulation with antagonists) that are unmasked when the drug is removed.
35. Phosphorylation of receptors is a common post-translational modification that can rapidly:
- a) Increase the number of receptors.
- b) Alter receptor activity, promote desensitization, or target them for internalization.
- c) Change the drug’s chemical structure.
- d) Decrease drug metabolism.
Answer: b) Alter receptor activity, promote desensitization, or target them for internalization.
36. If a drug is a partial agonist, it binds to the receptor and produces a submaximal response. Chronic administration of a partial agonist might lead to what kind of receptor regulation compared to a full agonist?
- a) Always more profound down-regulation.
- b) Potentially less pronounced down-regulation or desensitization than a full agonist.
- c) Only up-regulation.
- d) No receptor regulation.
Answer: b) Potentially less pronounced down-regulation or desensitization than a full agonist.
37. The presence of spare receptors can protect a tissue from the effects of:
- a) Agonist overdose.
- b) Irreversible antagonists, up to a certain concentration, as a maximal response can still be achieved by occupying the remaining functional receptors.
- c) All types of drug interactions.
- d) Drug metabolism.
Answer: b) Irreversible antagonists, up to a certain concentration, as a maximal response can still be achieved by occupying the remaining functional receptors.
38. Some drugs, like certain antidepressants, may take weeks to exert their full therapeutic effect. This delay may be related to:
- a) Slow absorption of the drug.
- b) Slow adaptive changes in receptor numbers, sensitivity, or gene expression.
- c) The drug needing to accumulate to very high concentrations.
- d) The pharmacist dispensing the drug slowly.
Answer: b) Slow adaptive changes in receptor numbers, sensitivity, or gene expression.
39. Which of these is NOT a primary mechanism of receptor regulation discussed?
- a) Change in receptor number (up-regulation or down-regulation).
- b) Change in receptor sensitivity (desensitization).
- c) Change in the drug’s chemical structure by the receptor.
- d) Covalent modification of the receptor (e.g., phosphorylation).
Answer: c) Change in the drug’s chemical structure by the receptor.
40. Understanding receptor regulation helps in designing dosing strategies. For example, “drug holidays” or intermittent dosing for some drugs might be an attempt to:
- a) Increase the cost of therapy.
- b) Minimize the development of tolerance or receptor down-regulation.
- c) Ensure the patient never misses a dose.
- d) Speed up drug elimination.
Answer: b) Minimize the development of tolerance or receptor down-regulation.
41. Receptor trafficking refers to the:
- a) Illicit sale of receptors.
- b) Movement of receptors within the cell, including their synthesis, insertion into membranes, internalization, recycling, or degradation.
- c) Binding of drugs to transport proteins.
- d) The speed at which an agonist binds to a receptor.
Answer: b) Movement of receptors within the cell, including their synthesis, insertion into membranes, internalization, recycling, or degradation.
42. If a patient taking a beta-blocker (antagonist) for hypertension stops it abruptly, they might experience rebound hypertension. This is likely due to:
- a) Down-regulation of beta-adrenergic receptors during therapy.
- b) Up-regulation of beta-adrenergic receptors during therapy, leading to an exaggerated response to endogenous catecholamines when the blocker is removed.
- c) The drug remaining in their system for weeks.
- d) A pharmacokinetic interaction.
Answer: b) Up-regulation of beta-adrenergic receptors during therapy, leading to an exaggerated response to endogenous catecholamines when the blocker is removed.
43. Mechanisms contributing to drug tolerance can be diverse. “Exhaustion of mediators” means:
- a) Receptors are tired of binding the drug.
- b) The drug depletes an endogenous substance necessary for its effect (e.g., amphetamines depleting neurotransmitters).
- c) The patient is tired of taking the medication.
- d) All spare receptors have been used up.
Answer: b) The drug depletes an endogenous substance necessary for its effect (e.g., amphetamines depleting neurotransmitters).
44. Which statement best describes the clinical relevance of understanding receptor regulation?
- a) It is only relevant for researchers, not practicing pharmacists.
- b) It helps explain variability in drug response, the development of tolerance, and withdrawal phenomena, guiding safer and more effective drug use.
- c) It simplifies drug therapy by making all responses predictable.
- d) It means that all drugs eventually stop working.
Answer: b) It helps explain variability in drug response, the development of tolerance, and withdrawal phenomena, guiding safer and more effective drug use.
45. A patient reports that their nitroglycerin patches for angina are not working as well as they used to. This could be an example of:
- a) Drug sensitization.
- b) Development of tolerance due to receptor desensitization or other adaptive mechanisms.
- c) An allergic reaction.
- d) The drug becoming more potent.
Answer: b) Development of tolerance due to receptor desensitization or other adaptive mechanisms.
46. The video lecture “Watch: Receptor Regulation” in PHA5515 likely covers:
- a) How to synthesize receptors in a lab.
- b) The molecular mechanisms by which receptor number and function are altered in response to drugs and other stimuli.
- c) The history of receptor discovery.
- d) Only pharmacokinetic tolerance.
Answer: b) The molecular mechanisms by which receptor number and function are altered in response to drugs and other stimuli.
47. The body’s natural adaptive responses involving receptor regulation are generally aimed at:
- a) Maximizing drug effects at all times.
- b) Maintaining homeostasis.
- c) Making all drugs less effective.
- d) Increasing the number of available receptors indefinitely.
Answer: b) Maintaining homeostasis.
48. Genetic variations in genes encoding receptors or signaling proteins can influence an individual’s baseline receptor expression and their propensity to:
- a) Only experience pharmacokinetic drug interactions.
- b) Develop tolerance or sensitization, or experience different levels of drug response and receptor regulation.
- c) Adhere to medication regimens.
- d) Choose a specific pharmacy.
Answer: b) Develop tolerance or sensitization, or experience different levels of drug response and receptor regulation.
49. If a drug relies on active transport into a cell to reach an intracellular receptor, tolerance could develop if:
- a) The receptor becomes more sensitive.
- b) The active transport system becomes saturated or down-regulated.
- c) The drug’s solubility increases.
- d) The drug is administered intravenously.
Answer: b) The active transport system becomes saturated or down-regulated.
50. Understanding the principles of receptor regulation underpins the rationale for:
- a) Using the highest possible dose of every medication.
- b) Tapering doses when discontinuing certain chronic medications to avoid withdrawal or rebound effects.
- c) Never adjusting drug doses once initiated.
- d) Administering all drugs by the same route.
Answer: b) Tapering doses when discontinuing certain chronic medications to avoid withdrawal or rebound effects.