MCQ Quiz: Pharmacology of Non-Benzodiazepines

The development of non-benzodiazepine anxiolytics and hypnotics marked a significant step in psychopharmacology, aiming for more selective mechanisms of action to improve tolerability and safety. The Patient Care VII: Brain and Behavior curriculum dedicates specific focus to the pharmacology of these agents, distinguishing them from their benzodiazepine predecessors. This quiz will test your knowledge on the mechanisms, pharmacodynamic effects, and pharmacokinetic profiles of key non-benzodiazepine classes, including the “Z-drugs,” buspirone, melatonin receptor agonists, and orexin receptor antagonists.

1. The “Z-drugs,” such as zolpidem, are structurally different from benzodiazepines but share a similar mechanism of action by acting on which receptor complex?

• A. Dopamine D2 receptor
• B. Serotonin 5-HT2A receptor
• C. GABA-A receptor
• D. Orexin receptor

Answer: C. GABA-A receptor

2. How do Z-drugs modulate the GABA-A receptor?

• A. They are direct agonists that open the chloride channel without GABA.
• B. They bind to the same allosteric site as benzodiazepines, enhancing the effect of GABA.
• C. They are competitive antagonists at the GABA binding site.
• D. They increase the production of GABA in the presynaptic neuron.

Answer: B. They bind to the same allosteric site as benzodiazepines, enhancing the effect of GABA.

3. The Z-drugs’ primary hypnotic (sedative) effect with less anxiolytic and muscle relaxant activity is attributed to their relative selectivity for which GABA-A receptor alpha subunit?

• A. α1 subunit
• B. α2 subunit
• C. α3 subunit
• D. α5 subunit

Answer: A. α1 subunit

4. Buspirone is a non-benzodiazepine anxiolytic with a unique mechanism of action that involves:

• A. Positive allosteric modulation of the GABA-A receptor.
• B. Partial agonism at the serotonin 5-HT1A receptor.
• C. Antagonism of the orexin-1 receptor.
• D. Selective inhibition of serotonin reuptake.

Answer: B. Partial agonism at the serotonin 5-HT1A receptor.

5. A key pharmacological difference between buspirone and benzodiazepines is that buspirone:

• A. Has a rapid onset of action, providing immediate anxiety relief.
• B. Carries a high risk of physical dependence and withdrawal.
• C. Lacks hypnotic and anticonvulsant properties.
• D. Potentiates the effects of alcohol.

Answer: C. Lacks hypnotic and anticonvulsant properties.

6. Ramelteon (Rozerem) promotes sleep by acting as a selective agonist at which receptors?

• A. GABA-A receptors
• B. Dopamine D2 receptors
• C. Orexin OX1 and OX2 receptors
• D. Melatonin MT1 and MT2 receptors

Answer: D. Melatonin MT1 and MT2 receptors

7. Suvorexant (Belsomra) represents a novel pharmacological approach to treating insomnia. It works by:

• A. Enhancing GABAergic neurotransmission.
• B. Blocking wakefulness-promoting signals as an orexin receptor antagonist.
• C. Acting as a partial agonist at serotonin receptors.
• D. Blocking histamine H1 receptors.

Answer: B. Blocking wakefulness-promoting signals as an orexin receptor antagonist.

8. Which of the following non-benzodiazepine hypnotics has an ultra-short half-life, making it most suitable for patients who have difficulty with sleep onset but not sleep maintenance?

• A. Eszopiclone
• B. Zolpidem controlled-release
• C. Zaleplon
• D. Suvorexant

Answer: C. Zaleplon

9. The anxiolytic effects of buspirone are delayed for several weeks. This is because its mechanism requires:

• A. A slow and steady titration to a very high dose.
• B. Downregulation of 5-HT1A autoreceptors and other neuroadaptive changes.
• C. Accumulation in fat tissue before reaching the brain.
• D. Conversion to a more active metabolite.

Answer: B. Downregulation of 5-HT1A autoreceptors and other neuroadaptive changes.

10. Why is flumazenil, a benzodiazepine receptor antagonist, effective in reversing a zolpidem overdose?

• A. Because zolpidem is also a competitive antagonist.
• B. Because flumazenil stimulates the CNS.
• C. Because zolpidem, despite its different structure, binds to the BZD site on the GABA-A receptor.
• D. Because flumazenil enhances the metabolism of zolpidem.

Answer: C. Because zolpidem, despite its different structure, binds to the BZD site on the GABA-A receptor.

11. A significant counseling point for all Z-drugs is the risk of “complex sleep-related behaviors.” This refers to:

• A. The patient sleeping more deeply than usual.
• B. Engaging in activities like driving or eating while not fully awake, with no memory of the event.
• C. Experiencing vivid dreams.
• D. Waking up frequently during the night.

Answer: B. Engaging in activities like driving or eating while not fully awake, with no memory of the event.

12. The pharmacology of ramelteon is distinct from other hypnotics because it:

• A. Carries a high risk of abuse and dependence.
• B. Has no direct GABAergic or histaminergic activity.
• C. Causes significant muscle relaxation.
• D. Is a Schedule IV controlled substance.

Answer: B. Has no direct GABAergic or histaminergic activity.

13. A patient taking buspirone should be advised that:

• A. It will provide immediate relief for a panic attack.
• B. It must be taken on a scheduled basis to be effective.
• C. It is safe to drink large amounts of alcohol with it.
• D. It is highly addictive.

Answer: B. It must be taken on a scheduled basis to be effective.

14. The primary advantage of buspirone over benzodiazepines for the management of Generalized Anxiety Disorder (GAD) is its:

• A. Rapid onset of action.
• B. Potent hypnotic effect.
• C. Lack of potential for physical dependence and abuse.
• D. Efficacy in treating panic attacks.

Answer: C. Lack of potential for physical dependence and abuse.

15. Which Z-drug is available as a controlled-release formulation designed to help with both sleep onset and sleep maintenance?

• A. Zaleplon
• B. Zolpidem
• C. Triazolam
• D. Ramelteon

Answer: B. Zolpidem

16. The metabolism of most Z-drugs and buspirone proceeds primarily through which enzyme, making them susceptible to drug interactions?

• A. Aldehyde oxidase
• B. CYP2D6
• C. CYP3A4
• D. UGT1A1

Answer: C. CYP3A4

17. Orexin A and B are neuropeptides that are central to which physiological process?

• A. Regulating mood and emotions.
• B. Promoting and maintaining wakefulness.
• C. Controlling appetite and satiety.
• D. Mediating pain perception.

Answer: B. Promoting and maintaining wakefulness.

18. Eszopiclone (Lunesta) is the S-enantiomer of zopiclone. Isolating the active enantiomer is a medicinal chemistry strategy known as:

• A. Prodrug design.
• B. Chiral switching.
• C. Bioisosterism.
• D. Drug repurposing.

Answer: B. Chiral switching.

19. Why would flumazenil be ineffective for reversing an overdose of ramelteon or suvorexant?

• A. Because flumazenil has a very short half-life.
• B. Because neither ramelteon nor suvorexant acts on the GABA-A receptor complex.
• C. Because these drugs are not CNS depressants.
• D. Because they are metabolized by a different pathway.

Answer: B. Because neither ramelteon nor suvorexant acts on the GABA-A receptor complex.

20. The term “partial agonist,” which describes buspirone’s action at the 5-HT1A receptor, means that it:

• A. Produces the maximum possible response at the receptor.
• B. Binds to the receptor but produces a submaximal response compared to a full agonist.
• C. Blocks the receptor completely.
• D. Binds irreversibly to the receptor.

Answer: B. Binds to the receptor but produces a submaximal response compared to a full agonist.

21. A patient taking zolpidem should be counseled to take it immediately before bed and only if they have at least how many hours to sleep?

• A. 2-3 hours
• B. 4-5 hours
• C. 7-8 hours
• D. 10-12 hours

Answer: C. 7-8 hours

22. Which of the following non-benzodiazepines lacks significant potential for drug-drug interactions with other CNS depressants like alcohol?

• A. Zolpidem
• B. Eszopiclone
• C. Buspirone
• D. Zaleplon

Answer: C. Buspirone

23. The development of non-benzodiazepines that target novel systems like melatonin and orexin is an example of:

• A. A focus on creating less selective drugs.
• B. A rational drug design approach based on the neurobiology of sleep-wake cycles.
• C. An outdated approach to pharmacology.
• D. A strategy to make medications more expensive.

Answer: B. A rational drug design approach based on the neurobiology of sleep-wake cycles.

24. The pharmacologic effect of zolpidem is more likely to be prolonged and pronounced in which patient population?

• A. Young male adults
• B. Athletes
• C. Women and elderly patients
• D. Adolescents

Answer: C. Women and elderly patients

25. A patient taking a potent CYP3A4 inhibitor, such as itraconazole, should use caution if prescribed which of the following?

• A. Lithium
• B. Gabapentin
• C. Eszopiclone
• D. Levetiracetam

Answer: C. Eszopiclone

26. Unlike Z-drugs, ramelteon is not a federally controlled substance. This is based on its pharmacological profile, which shows a lack of:

• A. Efficacy for insomnia.
• B. Evidence of abuse potential or physical dependence.
• C. CNS activity.
• D. Oral bioavailability.

Answer: B. Evidence of abuse potential or physical dependence.

27. The selectivity of Z-drugs for the α1-subunit of the GABA-A receptor results in less ________ compared to non-selective benzodiazepines.

• A. Sedation
• B. Amnesia
• C. Muscle relaxant and anxiolytic effects
• D. Hypnotic effect

Answer: C. Muscle relaxant and anxiolytic effects

28. Which non-benzodiazepine is specifically indicated for the treatment of GAD and is not effective for other anxiety subtypes like panic disorder or OCD?

• A. Zolpidem
• B. Buspirone
• C. Eszopiclone
• D. Ramelteon

Answer: B. Buspirone

29. The pharmacology of the orexin system involves two key receptors, OX1R and OX2R. Suvorexant is referred to as a DORA because it:

• A. Selectively antagonizes only OX1R.
• B. Selectively antagonizes only OX2R.
• C. Antagonizes both orexin receptors.
• D. Is a partial agonist at both receptors.

Answer: C. Antagonizes both orexin receptors.

30. Which pharmacokinetic parameter best explains why zaleplon is primarily effective for reducing sleep latency (time to fall asleep)?

• A. Its long half-life
• B. Its high volume of distribution
• C. Its ultra-short half-life
• D. Its high degree of protein binding

Answer: C. Its ultra-short half-life

31. The term “hypnotic” in pharmacology refers to a drug that:

• A. Reduces anxiety.
• B. Induces sleep.
• C. Relieves pain.
• D. Elevates mood.

Answer: B. Induces sleep.

32. The absorption of zolpidem can be delayed and its peak concentration decreased if taken with:

• A. Water on an empty stomach.
• B. A high-fat meal.
• C. Grapefruit juice.
• D. Another CNS depressant.

Answer: B. A high-fat meal.

33. As a 5-HT1A partial agonist, buspirone can be thought of as a “serotonin modulator.” This mechanism is fundamentally different from which class of anxiolytics?

• A. SSRIs
• B. SNRIs
• C. Benzodiazepines
• D. TCAs

Answer: C. Benzodiazepines

34. The primary therapeutic use of non-benzodiazepine receptor agonists (Z-drugs) is:

• A. The long-term management of generalized anxiety disorder.
• B. The short-term treatment of insomnia.
• C. The treatment of seizures.
• D. The management of alcohol withdrawal.

Answer: B. The short-term treatment of insomnia.

35. A key difference in the withdrawal potential between buspirone and Z-drugs is that:

• A. Buspirone has a high risk of severe withdrawal.
• B. Z-drugs have no withdrawal risk.
• C. Buspirone is not associated with a significant withdrawal syndrome, whereas Z-drugs can cause rebound insomnia.
• D. Both have identical, severe withdrawal syndromes.

Answer: C. Buspirone is not associated with a significant withdrawal syndrome, whereas Z-drugs can cause rebound insomnia.

36. The pharmacology of eszopiclone differs from zaleplon in that eszopiclone has a longer half-life, making it more effective for:

• A. Inducing sleep only.
• B. Sleep maintenance throughout the night.
• C. PRN use during the day for anxiety.
• D. Treating cataplexy.

Answer: B. Sleep maintenance throughout the night.

37. Which non-benzodiazepine is a useful alternative for GAD in patients with a history of substance abuse?

• A. Zolpidem
• B. Eszopiclone
• C. Buspirone
• D. Triazolam

Answer: C. Buspirone

38. The FDA has issued warnings and required lower recommended doses for certain hypnotics, especially for women, due to the risk of:

• A. Hypertensive crisis.
• B. Severe liver damage.
• C. Next-morning impairment and drowsiness.
• D. Agranulocytosis.

Answer: C. Next-morning impairment and drowsiness.

39. Ramelteon is a good pharmacological choice for sleep-onset insomnia in a patient for whom abuse potential is a major concern, such as a patient in recovery from:

• A. Hypertension.
• B. Diabetes.
• C. A substance use disorder.
• D. Hyperlipidemia.

Answer: C. A substance use disorder.

40. The pharmacologic principle of “affinity” describes:

• A. The maximum effect of a drug.
• B. The strength of the binding between a drug and its receptor target.
• C. The rate of drug metabolism.
• D. The oral bioavailability of a drug.

Answer: B. The strength of the binding between a drug and its receptor target.

41. The primary side effects of buspirone, such as dizziness and headache, are related to its action at which receptors?

• A. GABA-A receptors
• B. Histamine H1 receptors
• C. Serotonin and, to some extent, dopamine receptors
• D. Muscarinic receptors

Answer: C. Serotonin and, to some extent, dopamine receptors

42. Which of the following is NOT a controlled substance?

• A. Zolpidem
• B. Eszopiclone
• C. Zaleplon
• D. Ramelteon

Answer: D. Ramelteon

43. The “hangover” effect from a hypnotic is pharmacologically related to:

• A. The drug having a short half-life.
• B. The presence of significant drug concentrations upon waking.
• C. A drug-food interaction.
• D. An allergic reaction.

Answer: B. The presence of significant drug concentrations upon waking.

44. The pharmacology of orexin receptor antagonists is unique because they promote sleep by:

• A. Enhancing an inhibitory neurotransmitter system.
• B. Inhibiting a wakefulness-promoting neurotransmitter system.
• C. Modulating circadian rhythms.
• D. Blocking serotonin reuptake.

Answer: B. Inhibiting a wakefulness-promoting neurotransmitter system.

45. Why is it important for a pharmacist to counsel a patient not to drink alcohol when taking a Z-drug?

• A. It will cause a hypertensive crisis.
• B. It will prevent the Z-drug from working.
• C. It causes an additive pharmacodynamic effect, leading to excessive CNS and respiratory depression.
• D. It will damage the liver.

Answer: C. It causes an additive pharmacodynamic effect, leading to excessive CNS and respiratory depression.

46. A patient reports that zolpidem is no longer working as well as it used to. This phenomenon is known as:

• A. An idiosyncratic reaction.
• B. Anaphylaxis.
• C. Tolerance.
• D. An inverse agonist effect.

Answer: C. Tolerance.

47. Which non-benzodiazepine would you NOT recommend to a patient who complains of waking up at 3 a.m. and being unable to fall back asleep?

• A. Zolpidem CR
• B. Eszopiclone
• C. Zaleplon
• D. Suvorexant

Answer: C. Zaleplon

48. The pharmacology of non-benzodiazepines is covered in the PHA5789C syllabus under which module?

• A. Module 3: Psychotic Spectrum Disorders
• B. Module 4: Mood Disorders
• C. Module 5: Anxiety and Sleep-Wake Disorders
• D. Module 6: Epilepsy

Answer: C. Module 5: Anxiety and Sleep-Wake Disorders

49. The development of non-benzodiazepines with different mechanisms (GABAergic, melatonergic, orexin-based) illustrates what key concept in pharmacology?

• A. That all drugs must have the same mechanism to achieve the same effect.
• B. That a therapeutic outcome like “sleep” can be achieved by modulating different biological pathways.
• C. That older drugs are always better than newer drugs.
• D. That drug development is purely a matter of chance.

Answer: B. That a therapeutic outcome like “sleep” can be achieved by modulating different biological pathways.

50. An understanding of the pharmacology of non-benzodiazepines is essential for a pharmacist to:

• A. Recommend the appropriate agent based on a patient’s specific symptoms (e.g., sleep onset vs. sleep maintenance).
• B. Counsel on appropriate administration and potential side effects.
• C. Screen for drug interactions.
• D. All of the above.

Answer: D. All of the above.