A 28-year-old woman comes to the clinic for follow-up after recent hospitalization due to autoimmune hepatitis. High-dose glucocorticoids improved the hepatitis, and on discharge, the patient continued prednisone therapy. Today, she feels well and has no other medical concerns. Physical examination shows no abdominal tenderness or jaundice. Prednisone is tapered and azathioprine is prescribed for continued management of autoimmune hepatitis. Which of the following should be periodically monitored while the patient is taking this new medication?

Question

A 28-year-old woman comes to the clinic for follow-up after recent hospitalization due to autoimmune hepatitis.  High-dose glucocorticoids improved the hepatitis, and on discharge, the patient continued prednisone therapy.  Today, she feels well and has no other medical concerns.  Physical examination shows no abdominal tenderness or jaundice.  Prednisone is tapered and azathioprine is prescribed for continued management of autoimmune hepatitis.  Which of the following should be periodically monitored while the patient is taking this new medication?

Quizplus · Accepted Answer

11ec160b_3c79_3352_9249_b772869c727d_MD0001_00 Azathioprine is an immunosuppressant used in the prevention of organ transplant rejection and the treatment of autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, and autoimmune hepatitis. It functions via inhibition of purine synthesis pathways. Following ingestion, azathioprine is converted to 6-mercaptopurine, which is then converted to 6-thioguanine metabolites; these metabolites are pharmacologically active and mediate both the therapeutic and adverse effects of azathioprine. The 6-thioguanine metabolites reduce cellular proliferation via 2 methods of purine synthesis inhibition: These effects are exerted preferentially on rapidly dividing cells (eg, activated lymphocytes in the setting of organ transplant or autoimmune disease) but are otherwise nonspecific and disrupt other hematologic cell lines, including neutrophils, erythrocytes, and platelets. Therefore, pancytopenia (ie, leukopenia, anemia, and thrombocytopenia) is a common adverse effect that must be monitored with periodic complete blood count testing. (Choices B and C) Unlike glucocorticoids, azathioprine has no adverse effects on glucose or lipid metabolism, an advantage of this medication over chronic glucocorticoid therapy. (Choice D) Azathioprine has no known effect on lung function. The chemotherapeutic agent bleomycin may cause pulmonary fibrosis and therefore requires periodic monitoring of pulmonary function. (Choice E) The anemia caused by azathioprine and other antimetabolite drugs (eg, methotrexate) is typically macrocytic (due to impaired DNA synthesis), but this macrocytic effect is independent of vitamin B₁₂ levels. Proton pump inhibitors and histamine 2 blockers can disrupt absorption of vitamin B₁₂ and may cause or contribute to its deficiency. Educational objective: Azathioprine is an immunosuppressant that functions via inhibition of purine synthesis by its pharmacologically active 6-thioguanine metabolites. In addition to the desired effect of reduced lymphocyte proliferation, the proliferation of other hematologic cell lines (eg, neutrophils, erythrocytes, platelets) is reduced, leading to a common adverse effect of pancytopenia. __________ References: Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. (http://www.ncbi.nlm.nih.gov/pubmed/8174958)

A 28-Year-Old Woman Comes to the Clinic for Follow-Up After