Surgery>>>>>Transplantation
Question 2#

The mechanism of action of azathioprine (AZA) is:

A) Inhibition of calcineurin
B) Interference with DNA synthesis
C) Binding of FK- 506 binding proteins
D) Inhibition ofP7056 kinase

Correct Answer is B

Comment:

An antimetabolite, azathioprine (AZA) is converted to 6-mercaptopurine and inhibits both the de novo purine synthesis and salvage purine synthesis. AZA decreases T-lymphocyte activity and decreases antibody production. It has been used in transplant recipients for more than 40 years, but became an adjunctive agent after the introduction of cyclosporine. With the development of newer agents such as mycophenolate mofetil (MMF), the use of AZA has decreased significantly. However, it is preferred in recipients who are considering conceiving a child, because MMF is teratogenic in females and can cause birth defects. AZA might be an option for recipients who cannot tolerate the gastrointestinal (GI) side effects of MMF.

The most significant side effect of AZA, often dose-related, is bone marrow suppression. Leukopenia is often reversible with dose reduction or temporary cessation of the drug. Other significant side effects include hepatotoxicity, pancreatitis, neoplasia, anemia, and pulmonary fibrosis. Its most significant drug interaction is with allopurinol, which blocks AZJ's metabolism, increasing the risk of pancytopenia. Recommendations are to not use AZA and allopurinol together, or if doing so is unavoidable, to decrease the dose of AZA by 75%.