Azathioprine is a cornerstone immunomodulator used in the management of complex inflammatory conditions, most notably Inflammatory Bowel Disease (IBD). Its pharmacology serves as a classic example of the intricate relationship between prodrug metabolism, pharmacogenomics, and clinically significant drug interactions, a topic explored in depth in the Patient Care 4 curriculum. A pharmacist’s understanding of azathioprine is critical for patient safety, requiring vigilance in monitoring, knowledge of the TPMT enzyme, and patient counseling. This quiz will test your comprehension of this important anti-inflammatory agent.
1. Azathioprine exerts its immunosuppressive effect by first being converted to which active compound?
- a. Allopurinol
- b. 6-mercaptopurine (6-MP)
- c. Thiouric acid
- d. Mesalamine
Answer: b. 6-mercaptopurine (6-MP)
2. The active metabolites of azathioprine, thioguanine nucleotides (TGNs), work by what mechanism?
- a. They inhibit TNF-alpha.
- b. They incorporate into DNA and RNA, disrupting lymphocyte proliferation.
- c. They block the H+/K+ ATPase pump.
- d. They antagonize histamine-2 receptors.
Answer: b. They incorporate into DNA and RNA, disrupting lymphocyte proliferation.
3. Azathioprine is best described as a:
- a. Biologic agent
- b. Prodrug
- c. Stool softener
- d. Saline laxative
Answer: b. Prodrug
4. A patient deficient in the enzyme Thiopurine S-methyltransferase (TPMT) is at a very high risk for what severe, life-threatening toxicity when taking azathioprine?
- a. Hepatotoxicity
- b. Nephrotoxicity
- c. Myelosuppression (bone marrow suppression)
- d. Cardiotoxicity
Answer: c. Myelosuppression (bone marrow suppression)
5. What is the recommended action before initiating azathioprine therapy to mitigate toxicity risk?
- a. Administer a test dose.
- b. Check the patient’s blood pressure.
- c. Perform TPMT genotype or phenotype testing.
- d. Obtain a baseline ECG.
Answer: c. Perform TPMT genotype or phenotype testing.
6. A patient who is a TPMT “poor metabolizer” should receive what dose of azathioprine?
- a. A higher dose than standard.
- b. The standard dose.
- c. A drastically reduced dose or avoid the drug altogether.
- d. A loading dose followed by a standard dose.
Answer: c. A drastically reduced dose or avoid the drug altogether.
7. A patient stabilized on azathioprine is newly prescribed allopurinol for gout. What is the concern with this combination?
- a. Allopurinol will decrease the effectiveness of azathioprine.
- b. Allopurinol inhibits xanthine oxidase, a key enzyme in azathioprine metabolism, leading to a high risk of severe toxicity.
- c. The combination increases the risk of GERD.
- d. There is no significant interaction.
Answer: b. Allopurinol inhibits xanthine oxidase, a key enzyme in azathioprine metabolism, leading to a high risk of severe toxicity.
8. If a patient must take allopurinol and azathioprine concurrently, the azathioprine dose should typically be:
- a. Increased by 50%.
- b. Doubled.
- c. Reduced by approximately 66-75%.
- d. Switched to every other day.
Answer: c. Reduced by approximately 66-75%.
9. What is the primary role of azathioprine in the management of Inflammatory Bowel Disease (IBD)?
- a. For rapid induction of remission in an acute flare.
- b. As a first-line agent for mild disease.
- c. For maintaining remission and as a steroid-sparing agent.
- d. For treating extra-intestinal manifestations only.
Answer: c. For maintaining remission and as a steroid-sparing agent.
10. How long does it typically take for azathioprine to exert its full therapeutic effect in IBD?
- a. 24-48 hours
- b. 1-2 weeks
- c. 3-6 months
- d. Immediately upon administration.
Answer: c. 3-6 months
11. The pharmacology of azathioprine is a specific topic within the Patient Care 4 curriculum.
- a. True
- b. False
Answer: a. True
12. Which of the following lab parameters must be monitored regularly in a patient taking azathioprine?
- a. Serum electrolytes
- b. Blood glucose
- c. Complete Blood Count (CBC) with differential and Liver Function Tests (LFTs)
- d. International Normalized Ratio (INR)
Answer: c. Complete Blood Count (CBC) with differential and Liver Function Tests (LFTs)
13. Azathioprine is an analog of which endogenous purine?
- a. Adenine
- b. Guanine
- c. Xanthine
- d. Hypoxanthine
Answer: b. Guanine
14. A patient on azathioprine develops a fever and a severe sore throat. The pharmacist should recognize this as a potential sign of:
- a. An expected therapeutic effect.
- b. Myelosuppression (specifically, leukopenia).
- c. Pancreatitis.
- d. A common, mild side effect.
Answer: b. Myelosuppression (specifically, leukopenia).
15. Besides TPMT, genetic variations in which other enzyme have been associated with thiopurine intolerance, especially in Asian populations?
- a. NUDT15
- b. CYP2C9
- c. UGT1A1
- d. SLCO1B1
Answer: a. NUDT15
16. Which of the following is NOT a potential long-term risk of azathioprine therapy?
- a. Increased risk of non-Hodgkin lymphoma.
- b. Increased risk of non-melanoma skin cancer.
- c. Increased risk of infection.
- d. Increased risk of hypertension.
Answer: d. Increased risk of hypertension.
17. The medicinal chemistry of azathioprine is a topic covered in the Patient Care 4 curriculum.
- a. True
- b. False
Answer: a. True
18. Why is azathioprine considered a “steroid-sparing” agent?
- a. It has the same mechanism of action as steroids.
- b. It allows for the dose of chronic corticosteroids to be reduced or discontinued while maintaining disease remission.
- c. It increases the metabolism of steroids.
- d. It prevents all side effects of steroids.
Answer: b. It allows for the dose of chronic corticosteroids to be reduced or discontinued while maintaining disease remission.
19. A common GI side effect that can occur when initiating azathioprine is:
- a. Constipation
- b. Nausea and vomiting
- c. Black stools
- d. Heartburn
Answer: b. Nausea and vomiting
20. A patient with normal TPMT activity will primarily metabolize 6-mercaptopurine via which two pathways?
- a. TPMT and Xanthine Oxidase (XO)
- b. HGPRT and UGT1A1
- c. CYP3A4 and CYP2D6
- d. Aldehyde dehydrogenase and alcohol dehydrogenase
Answer: a. TPMT and Xanthine Oxidase (XO)
21. The management of Inflammatory Bowel Disease is an active learning session in the Patient Care 4 course.
- a. True
- b. False
Answer: a. True
22. Azathioprine can be classified as a(n):
- a. Antimetabolite
- b. Alkylating agent
- c. Topoisomerase inhibitor
- d. Monoclonal antibody
Answer: a. Antimetabolite
23. A patient with Crohn’s Disease is in remission on infliximab and azathioprine. This is an example of:
- a. Monotherapy
- b. Combination therapy
- c. Induction therapy
- d. Palliative therapy
Answer: b. Combination therapy
24. The active thioguanine nucleotides (TGNs) are structurally similar to which natural purines, allowing them to be incorporated into DNA/RNA?
- a. Cytosine and Thymine
- b. Guanine and Adenine
- c. Uracil
- d. All of the above
Answer: b. Guanine and Adenine
25. A pharmacist’s role in managing azathioprine therapy includes:
- a. Verifying the appropriateness of the dose based on TPMT status.
- b. Counseling the patient on the need for routine lab monitoring.
- c. Screening for the allopurinol drug interaction.
- d. All of the above.
Answer: d. All of the above.
26. Why isn’t azathioprine effective for treating an acute flare of IBD?
- a. Because of its slow onset of action.
- b. Because it is not an anti-inflammatory drug.
- c. Because it cannot be given orally.
- d. Because it has too many side effects.
Answer: a. Because of its slow onset of action.
27. In a patient with zero TPMT activity, the 6-mercaptopurine is shunted towards which metabolic pathway?
- a. The xanthine oxidase pathway, producing more thiouric acid.
- b. The HGPRT pathway, producing dangerously high levels of active TGNs.
- c. The CYP3A4 pathway.
- d. It is not metabolized and is excreted unchanged.
Answer: b. The HGPRT pathway, producing dangerously high levels of active TGNs.
28. A key counseling point for a patient starting azathioprine is to immediately report:
- a. Mild fatigue
- b. Signs of infection, such as fever or chills.
- c. Occasional headache
- d. Decreased appetite
Answer: b. Signs of infection, such as fever or chills.
29. Febuxostat is another xanthine oxidase inhibitor used for gout. What interaction would you expect with azathioprine?
- a. No interaction.
- b. A similar, severe interaction as seen with allopurinol.
- c. It would decrease azathioprine levels.
- d. It would cause a mild rash.
Answer: b. A similar, severe interaction as seen with allopurinol.
30. The primary use of azathioprine in GI disorders is for:
- a. GERD
- b. Irritable Bowel Syndrome (IBS)
- c. Inflammatory Bowel Disease (IBD)
- d. Peptic Ulcer Disease (PUD)
Answer: c. Inflammatory Bowel Disease (IBD)
31. The immunosuppressive effects of azathioprine are mediated by its impact on which cells?
- a. Red blood cells
- b. Platelets
- c. T-lymphocytes and B-lymphocytes
- d. Neutrophils
Answer: c. T-lymphocytes and B-lymphocytes
32. Can a patient with intermediate TPMT activity be treated with azathioprine?
- a. No, it is absolutely contraindicated.
- b. Yes, but typically at a reduced starting dose with careful monitoring.
- c. Yes, at the standard dose without any changes.
- d. Yes, but only if they are also taking allopurinol.
Answer: b. Yes, but typically at a reduced starting dose with careful monitoring.
33. Azathioprine is on the NIOSH list of hazardous drugs, requiring careful handling by pharmacy and nursing staff.
- a. True
- b. False
Answer: a. True
34. A patient has been stable on azathioprine for 2 years. How often should their CBC be monitored?
- a. It is no longer necessary.
- b. Weekly.
- c. Monthly.
- d. Every 3-6 months, or per institutional protocol.
Answer: d. Every 3-6 months, or per institutional protocol.
35. A patient on azathioprine should be counseled on the importance of:
- a. Sun protection, due to an increased risk of skin cancer.
- b. A high-purine diet.
- c. Avoiding all vaccinations.
- d. Taking the medication on an empty stomach.
Answer: a. Sun protection, due to an increased risk of skin cancer.
36. The therapeutic effect of azathioprine relies on its ability to suppress:
- a. Gastric acid production.
- b. The inflammatory immune response.
- c. Peristalsis.
- d. Histamine release.
Answer: b. The inflammatory immune response.
37. If TPMT testing is not available, a common practice is to:
- a. Start at the highest possible dose of azathioprine.
- b. Start at a very low dose and titrate up slowly with frequent CBC monitoring.
- c. Avoid using azathioprine altogether.
- d. Use allopurinol concurrently.
Answer: b. Start at a very low dose and titrate up slowly with frequent CBC monitoring.
38. Which of the following drugs can inhibit TPMT activity, potentially increasing the risk of azathioprine toxicity?
- a. Acetaminophen
- b. Metformin
- c. Mesalamine
- d. Lisinopril
Answer: c. Mesalamine
39. The ultimate goal of azathioprine therapy in IBD is to:
- a. Cure the disease.
- b. Provide rapid symptom relief in an acute flare.
- c. Maintain long-term, steroid-free remission.
- d. Treat constipation.
Answer: c. Maintain long-term, steroid-free remission.
40. Understanding how prodrugs result in drug action is a key objective in the Medicinal Chemistry curriculum.
- a. True
- b. False
Answer: a. True
41. Pancreatitis is a potential, serious idiosyncratic adverse effect of azathioprine.
- a. True
- b. False
Answer: a. True
42. A patient calls the pharmacy and says they missed their daily dose of azathioprine this morning. What is the best advice?
- a. “Take the missed dose now, and take your next dose at the regular time.”
- b. “Double your dose tomorrow.”
- c. “Skip today’s dose and resume your normal schedule tomorrow.”
- d. “Stop taking the medication and call your doctor.”
Answer: c. “Skip today’s dose and resume your normal schedule tomorrow.”
43. Why is routine CBC monitoring essential during the first few months of azathioprine therapy?
- a. To check for efficacy.
- b. Because the risk of myelosuppression is highest during initiation.
- c. To monitor for pancreatitis.
- d. To check for drug interactions.
Answer: b. Because the risk of myelosuppression is highest during initiation.
44. The conversion of azathioprine to 6-mercaptopurine is what kind of reaction?
- a. An enzymatic reaction in the liver.
- b. A non-enzymatic reaction involving glutathione.
- c. An acid-catalyzed reaction in the stomach.
- d. A reaction that only occurs in the colon.
Answer: b. A non-enzymatic reaction involving glutathione.
45. A patient should be counseled that they should not receive which type of vaccine while on azathioprine?
- a. Inactivated vaccines (e.g., standard flu shot)
- b. Live attenuated vaccines (e.g., MMR, varicella)
- c. Recombinant vaccines (e.g., Shingrix)
- d. All vaccines are contraindicated.
Answer: b. Live attenuated vaccines (e.g., MMR, varicella)
46. A decrease in which cell line on a CBC would be the most concerning sign of azathioprine-induced myelosuppression?
- a. Red blood cells
- b. Eosinophils
- c. White blood cells (leukocytes)
- d. Basophils
Answer: c. White blood cells (leukocytes)
47. The pharmacology of azathioprine is covered under the module for selected anti-inflammatory agents.
- a. True
- b. False
Answer: a. True
48. Is azathioprine safe to use during pregnancy for IBD?
- a. It is absolutely contraindicated.
- b. It is considered a relatively safe and often necessary option, as the risk of an active IBD flare outweighs the risk of the medication.
- c. It is only safe in the first trimester.
- d. It is only safe in the third trimester.
Answer: b. It is considered a relatively safe and often necessary option, as the risk of an active IBD flare outweighs the risk of the medication.
49. If a patient experiences nausea when starting azathioprine, the pharmacist can recommend:
- a. Discontinuing the medication immediately.
- b. Taking the medication with food or in divided doses.
- c. Taking an OTC antiemetic 30 minutes before each dose.
- d. Both b and c are reasonable recommendations.
Answer: d. Both b and c are reasonable recommendations.
50. The complex pharmacology and pharmacogenomics of azathioprine underscore the pharmacist’s critical role in:
- a. Dispensing medications quickly.
- b. Ensuring patient safety through monitoring, education, and drug interaction screening.
- c. Only managing over-the-counter medications.
- d. Recommending surgical interventions.
Answer: b. Ensuring patient safety through monitoring, education, and drug interaction screening.