MCQ Quiz: Pharmacology of Addiction Treatment: Ethanol

Alcohol Use Disorder (AUD) is a complex, chronic brain disease that requires a multi-faceted treatment approach, where pharmacotherapy plays a vital role. For the modern pharmacist, a deep understanding of the pharmacology of medications used to treat AUD is essential for optimizing patient outcomes, ensuring safety, and providing effective counseling. This involves not only knowing the drugs used for relapse prevention, such as naltrexone, acamprosate, and disulfiram, but also the agents used to manage acute withdrawal. This quiz, based on topics from the Patient Care VII curriculum, will test your knowledge of the mechanisms of action, pharmacokinetics, and clinical application of these critical medications.

1. What is the primary neurochemical mechanism of ethanol that produces its acute sedative and anxiolytic effects?

• a) It is a potent agonist at the dopamine D2 receptor.
• b) It is a positive allosteric modulator of GABA-A receptors.
• c) It blocks the reuptake of serotonin.
• d) It irreversibly inhibits monoamine oxidase (MAO). Answer: b) It is a positive allosteric modulator of GABA-A receptors.

2. Chronic ethanol consumption leads to what neuroadaptive change in the NMDA receptor system?

• a) Downregulation of NMDA receptors
• b) Upregulation of NMDA receptors
• c) No change in NMDA receptors
• d) Conversion of NMDA receptors to AMPA receptors Answer: b) Upregulation of NMDA receptors

3. The hyperexcitability seen in acute alcohol withdrawal (e.g., seizures, delirium tremens) is primarily caused by:

• a) A surge in dopamine release.
• b) The combination of reduced GABAergic inhibition and enhanced glutamatergic excitation.
• c) Sudden downregulation of opioid receptors.
• d) Inhibition of aldehyde dehydrogenase. Answer: b) The combination of reduced GABAergic inhibition and enhanced glutamatergic excitation.

4. Which class of medication is the first-line treatment for managing the symptoms of acute alcohol withdrawal?

• a) Antipsychotics
• b) Antidepressants
• c) Benzodiazepines
• d) Opioid antagonists Answer: c) Benzodiazepines

5. What is the pharmacological mechanism of action for disulfiram in the treatment of AUD?

• a) It blocks mu-opioid receptors to reduce alcohol craving.
• b) It modulates NMDA receptors to stabilize neuronal activity.
• c) It irreversibly inhibits the enzyme aldehyde dehydrogenase.
• d) It is a partial agonist at the nicotinic acetylcholine receptor. Answer: c) It irreversibly inhibits the enzyme aldehyde dehydrogenase.

6. A patient taking disulfiram who consumes alcohol will experience an accumulation of which toxic metabolite?

• a) Acetic acid
• b) Formaldehyde
• c) Acetaldehyde
• d) Methanol Answer: c) Acetaldehyde

7. Naltrexone is an effective treatment for AUD. Its mechanism involves antagonism of which receptors?

• a) GABA-A receptors
• b) NMDA receptors
• c) Serotonin 5-HT3 receptors
• d) Mu-opioid receptors Answer: d) Mu-opioid receptors

8. By blocking mu-opioid receptors, naltrexone is thought to reduce which aspect of drinking?

• a) The unpleasant withdrawal symptoms.
• b) The rewarding or pleasurable effects of alcohol.
• c) The metabolism of alcohol in the liver.
• d) The sedative effects of alcohol. Answer: b) The rewarding or pleasurable effects of alcohol.

9. A crucial counseling point for a patient starting naltrexone is that they must be free from what class of drugs before initiation?

• a) Benzodiazepines
• b) SSRIs
• c) Opioids
• d) Antipsychotics Answer: c) Opioids

10. What is the proposed mechanism of action for acamprosate?

• a) It is a potent dopamine reuptake inhibitor.
• b) It is thought to normalize glutamate and GABA neurotransmission, which is dysregulated by chronic alcohol use.
• c) It inhibits alcohol dehydrogenase.
• d) It blocks the rewarding effects of alcohol by acting on opioid receptors. Answer: b) It is thought to normalize glutamate and GABA neurotransmission, which is dysregulated by chronic alcohol use.

11. Which AUD medication is primarily eliminated by the kidneys and is often preferred in patients with significant liver disease?

• a) Disulfiram
• b) Naltrexone
• c) Chlordiazepoxide
• d) Acamprosate Answer: d) Acamprosate

12. Why are long-acting benzodiazepines like chlordiazepoxide or diazepam often preferred for alcohol withdrawal protocols?

• a) They have a higher abuse potential.
• b) They provide a smoother, more stable withdrawal with a lower risk of breakthrough seizures.
• c) They are less sedating than short-acting agents.
• d) They do not require any liver metabolism. Answer: b) They provide a smoother, more stable withdrawal with a lower risk of breakthrough seizures.

13. In a patient with severe alcoholic hepatitis or cirrhosis, which benzodiazepines might be preferred for withdrawal management due to their simpler metabolism pathway?

• a) Diazepam and chlordiazepoxide
• b) Alprazolam and triazolam
• c) Lorazepam, oxazepam, and temazepam (LOT)
• d) Clonazepam and clorazepate Answer: c) Lorazepam, oxazepam, and temazepam (LOT)

14. What is a significant risk of using flumazenil, the benzodiazepine antidote, in a patient with co-dependence on alcohol and benzodiazepines during withdrawal?

• a) It can precipitate life-threatening seizures.
• b) It can cause severe hypertension.
• c) It can induce a disulfiram-like reaction.
• d) It can lead to opioid overdose. Answer: a) It can precipitate life-threatening seizures.

15. Thiamine (Vitamin B1) is administered to patients undergoing alcohol withdrawal to prevent which neurological complication?

• a) Parkinson’s disease
• b) Wernicke-Korsakoff syndrome
• c) Guillain-Barré syndrome
• d) Huntington’s disease Answer: b) Wernicke-Korsakoff syndrome

16. Which off-label medication for AUD has a mechanism that involves enhancing GABAergic activity and antagonizing glutamate?

• a) Ondansetron
• b) Topiramate
• c) Prazosin
• d) Gabapentin Answer: b) Topiramate

17. The primary pathway for ethanol metabolism involves alcohol dehydrogenase converting ethanol to acetaldehyde, followed by aldehyde dehydrogenase converting acetaldehyde to:

• a) Acetate
• b) Methanol
• c) Formic acid
• d) Water Answer: a) Acetate

18. Which cytochrome P450 enzyme is induced by chronic heavy drinking and contributes to the metabolic tolerance of alcohol?

• a) CYP3A4
• b) CYP2D6
• c) CYP2E1
• d) CYP1A2 Answer: c) CYP2E1

19. A patient taking disulfiram must be counseled to avoid hidden sources of alcohol, such as:

• a) Certain mouthwashes and liquid medications.
• b) Grapefruit juice.
• c) Dairy products.
• d) Caffeinated beverages. Answer: a) Certain mouthwashes and liquid medications.

20. The primary goal of using benzodiazepines during acute alcohol withdrawal is to:

• a) Reduce cravings for alcohol.
• b) Treat the underlying cause of AUD.
• c) Safely manage the symptoms of CNS hyperexcitability.
• d) Provide a long-term maintenance therapy. Answer: c) Safely manage the symptoms of CNS hyperexcitability.

21. A patient on naltrexone for AUD is in a car accident and requires emergency surgery. What is the pharmacological challenge?

• a) The patient will have an exaggerated response to general anesthetics.
• b) Naltrexone will prevent the patient from forming blood clots.
• c) Standard doses of opioid analgesics will be ineffective due to receptor blockade.
• d) The patient is at high risk for a hypertensive crisis. Answer: c) Standard doses of opioid analgesics will be ineffective due to receptor blockade.

22. Which AUD medication is typically initiated after the patient has already achieved abstinence to help maintain it?

• a) Naltrexone
• b) Diazepam
• c) Acamprosate
• d) Lorazepam Answer: c) Acamprosate

23. The “thirst” or craving for alcohol is a key target for which medications?

• a) Only disulfiram
• b) Only thiamine
• c) Naltrexone and acamprosate
• d) Only benzodiazepines Answer: c) Naltrexone and acamprosate

24. The pharmacological basis for using gabapentin off-label for AUD is its ability to:

• a) Block dopamine receptors.
• b) Modulate GABAergic and glutamatergic systems, potentially reducing withdrawal symptoms and cravings.
• c) Inhibit the metabolism of alcohol.
• d) Act as a powerful antidepressant. Answer: b) Modulate GABAergic and glutamatergic systems, potentially reducing withdrawal symptoms and cravings.

25. A patient’s adherence to which AUD medication is paramount due to the severe consequences of drinking alcohol while on it?

• a) Acamprosate
• b) Naltrexone
• c) Disulfiram
• d) Vitamin B12 Answer: c) Disulfiram

26. The pharmacology of addiction treatment often combines medication with which other modality for best outcomes?

• a) A high-protein diet
• b) Intense physical exercise only
• c) Psychosocial support and counseling (e.g., AA, cognitive behavioral therapy)
• d) Herbal supplements Answer: c) Psychosocial support and counseling (e.g., AA, cognitive behavioral therapy)

27. The development of tolerance to the sedative effects of ethanol occurs more rapidly than tolerance to which other effect?

• a) The anxiolytic effects
• b) The euphoric effects
• c) The respiratory depressant effects
• d) The diuretic effects Answer: c) The respiratory depressant effects

28. From a medicinal chemistry perspective, the two sulfur atoms in the disulfiram molecule are key to its ability to:

• a) Bind to opioid receptors.
• b) Inactivate the aldehyde dehydrogenase enzyme.
• c) Cross the blood-brain barrier easily.
• d) Mimic the structure of GABA. Answer: b) Inactivate the aldehyde dehydrogenase enzyme.

29. The CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol, revised) scale is used to:

• a) Diagnose Alcohol Use Disorder.
• b) Objectively score the severity of alcohol withdrawal to guide benzodiazepine dosing.
• c) Predict the likelihood of relapse.
• d) Determine a patient’s blood alcohol concentration. Answer: b) Objectively score the severity of alcohol withdrawal to guide benzodiazepine dosing.

30. Which AUD medication is available as a long-acting intramuscular injection?

• a) Acamprosate
• b) Disulfiram
• c) Naltrexone
• d) Lorazepam Answer: c) Naltrexone

31. The primary advantage of a long-acting injectable formulation of naltrexone is:

• a) It is less expensive than the oral form.
• b) It overcomes issues with daily medication adherence.
• c) It has a faster onset of action.
• d) It does not require the patient to be opioid-free. Answer: b) It overcomes issues with daily medication adherence.

32. What is the pharmacological rationale for the “cross-tolerance” observed between ethanol and benzodiazepines?

• a) They are both metabolized by the same CYP450 enzyme.
• b) They both act on the GABA-A receptor complex.
• c) They both block NMDA receptors.
• d) They both inhibit aldehyde dehydrogenase. Answer: b) They both act on the GABA-A receptor complex.

33. The main difference between a symptom-triggered and a fixed-dose schedule for benzodiazepine administration during alcohol withdrawal is that the symptom-triggered approach:

• a) Uses higher total doses of benzodiazepines.
• b) Is associated with a longer treatment duration.
• c) Tailors the dose to the patient’s withdrawal severity, often resulting in lower total doses and shorter treatment.
• d) Is more complicated and rarely used. Answer: c) Tailors the dose to the patient’s withdrawal severity, often resulting in lower total doses and shorter treatment.

34. A patient stabilized on naltrexone for AUD complains it is not reducing their cravings. An appropriate pharmacological consideration would be:

• a) Doubling the dose of naltrexone immediately.
• b) Switching to disulfiram without patient consent.
• c) Assessing adherence and considering a switch to or addition of acamprosate.
• d) Concluding that no medication will work for this patient. Answer: c) Assessing adherence and considering a switch to or addition of acamprosate.

35. The pharmacological goal of maintenance therapy for AUD is to:

• a) Cure the underlying brain disease.
• b) Prevent relapse and support long-term recovery.
• c) Allow the patient to engage in controlled drinking.
• d) Manage only the acute withdrawal phase. Answer: b) Prevent relapse and support long-term recovery.

36. A significant drug-drug interaction to be aware of with disulfiram is with metronidazole, which can cause:

• a) Reduced efficacy of both drugs.
• b) A psychotic reaction.
• c) Severe hypertension.
• d) Rapid clearance of disulfiram. Answer: b) A psychotic reaction.

37. How does naltrexone’s pharmacology make it useful for a patient whose goal is to reduce heavy drinking rather than achieve complete abstinence?

• a) It makes alcohol taste bad.
• b) It reduces the reinforcing effects, making it easier to stop after one or two drinks.
• c) It causes a severe reaction with any amount of alcohol.
• d) It has no effect on heavy drinking. Answer: b) It reduces the reinforcing effects, making it easier to stop after one or two drinks.

38. The FDA-approved AUD medications primarily work by targeting:

• a) Neurotransmitter systems to reduce cravings and reinforcement, or by creating an aversive reaction.
• b) The social determinants of health.
• c) The liver’s ability to regenerate.
• d) The patient’s psychological desire for social interaction. Answer: a) Neurotransmitter systems to reduce cravings and reinforcement, or by creating an aversive reaction.

39. Before starting disulfiram, it is essential to confirm that the patient has:

• a) Been abstinent from alcohol for at least 12 hours.
• b) Normal kidney function.
• c) A prescription for an opioid analgesic.
• d) A co-occurring anxiety disorder. Answer: a) Been abstinent from alcohol for at least 12 hours.

40. A patient experiences severe nausea, vomiting, flushing, and tachycardia after having one beer. They likely have been taking which medication?

• a) Acamprosate
• b) Naltrexone
• c) Lorazepam
• d) Disulfiram Answer: d) Disulfiram

41. The induction of CYP2E1 by chronic alcohol use can increase the toxicity of which other common drug?

• a) Aspirin
• b) Acetaminophen
• c) Lisinopril
• d) Metformin Answer: b) Acetaminophen

42. Why is patient motivation and education so critical for the success of disulfiram therapy?

• a) The medication is very expensive.
• b) The therapy relies on the patient’s commitment to avoid alcohol to prevent the aversive reaction.
• c) The medication has to be taken 6 times a day.
• d) The medication is only effective if taken with food. Answer: b) The therapy relies on the patient’s commitment to avoid alcohol to prevent the aversive reaction.

43. Which AUD medication has a dosing schedule of two tablets three times a day, which can be a barrier to adherence?

• a) Naltrexone
• b) Disulfiram
• c) Acamprosate
• d) Topiramate Answer: c) Acamprosate

44. The pharmacological treatment of AUD in a pregnant patient is complex, but the most important intervention is:

• a) Starting disulfiram immediately.
• b) Achieving abstinence from alcohol to prevent fetal alcohol syndrome.
• c) Prescribing naltrexone without an assessment.
• d) Using high-dose benzodiazepines throughout the pregnancy. Answer: b) Achieving abstinence from alcohol to prevent fetal alcohol syndrome.

45. What is the role of the pharmacist when dispensing a medication like naltrexone for the first time?

• a) To refuse the fill if the patient has a history of AUD.
• b) To counsel the patient on the mechanism, goals, side effects, and importance of carrying a medical alert card.
• c) To simply label the bottle and dispense it without comment.
• d) To tell the patient the medication will cure their addiction. Answer: b) To counsel the patient on the mechanism, goals, side effects, and importance of carrying a medical alert card.

46. The pharmacological opposite of alcohol withdrawal (CNS hyperexcitability) is acute alcohol intoxication, which presents as:

• a) CNS stimulation
• b) CNS depression
• c) No change in CNS activity
• d) A sympathomimetic crisis Answer: b) CNS depression

47. Which of the following is NOT a primary pharmacological target for the current FDA-approved AUD medications?

• a) Opioid system
• b) Glutamate system
• c) Aldehyde dehydrogenase
• d) Serotonin reuptake system Answer: d) Serotonin reuptake system

48. The primary advantage of pharmacotherapy in AUD is that it can:

• a) Replace the need for counseling and support groups.
• b) Help reduce cravings and support abstinence, making psychosocial interventions more effective.
• c) Cure the genetic predisposition to addiction.
• d) Work for every single patient who tries it. Answer: b) Help reduce cravings and support abstinence, making psychosocial interventions more effective.

49. A patient taking naltrexone should be monitored for which potential adverse effect?

• a) Hypertensive crisis
• b) Severe sedation
• c) Hepatotoxicity (liver injury)
• d) Renal failure Answer: c) Hepatotoxicity (liver injury)

50. The successful pharmacological treatment of AUD ultimately depends on:

• a) The price of the medication.
• b) A combination of the right medication for the right patient and strong psychosocial support.
• c) The pharmacist’s opinion alone.
• d) The patient’s ability to tolerate side effects. Answer: b) A combination of the right medication for the right patient and strong psychosocial support.