Cytotoxic agents azathioprine

The treatment of collagen disease is based on immunosuppressive therapies. Immunosuppressive agents, such as corticosteroids, are widely used. In addition, cytotoxic agents (azathioprine, cyclophosphamide, and methotrexate) have also been administered. 

Cytotoxic agents which are exclusively used to achieve immunosuppression are azathioprine and mycophenolate mofetil, although their over all mechanism of action is similar to that of the antitumor dmgs, i.e. inhibition of lymphocyte proliferation after antigen exposure. 

Azathioprine also has applications in certain disorders with autoimmune components, most commonly rheumatoid arthritis. It is as effective as cyclophosphamide in the treatment of Wegener s granulomatosis. It has largely been replaced by cyclosporine in immunosuppressive therapy. Relative to other cytotoxic agents, the better oral absorption of azathioprine is the reason for its more widespread clinical use. 

Cytotoxic agents such as azathioprine are effective immunosuppressants because they... 

C. Azathioprine is a phase-specific cytotoxic agent that functions by inhibiting purine synthesis. The other answers are wrong because azathioprine is nonspecific, is not an alkylating agent, has no effect on immune complexes, and does not induce antibody synthesis. 

Azathioprine, cyclophosphamide, methotrexate, leflunomide Lymphocyte-specific cytotoxic agents Mycophenolate mofetil... 

Clinical Use. Azathioprine (Imuran) is a cytotoxic agent that is structurally and functionally similar to certain anticancer drugs, such as mercaptopurine.22,30 Azathioprine is primarily used to prevent the rejection of transplanted organs, especially in patients with kidney transplants. Azathioprine may also be used to suppress immune responses in a wide range of other conditions, such as systemic lupus erythematosus, dermatomyositis, inflammatory myopathy, hepatic disease, myasthenia gravis, and ulcerative colitis. As presented in Chapter 16, azathioprine is also used as an antiarthritic disease-modifying agent. 

Cytotoxic agents destroy immimologically competent cells. Azathioprine, a prodrug for the purine antagonist mercaptopurine, is used in autoimmune disease because it provides enhanced immunosuppressive activity. Cyclophosphamide is a second choice. Bone marrow is depressed as is to be expected. 

Allopurinol inhibits the enzymatic inactivation of mercaptopurine and its derivative azathio-prine by xanthine oxidase. Thus, when allopurinol is used concomitantly with oral mercaptopurine or azathioprine, dosage of the antineoplastic agent must be reduced by 25-33% (see Chapters 38 and 51). This is of importance when treating gout in the transplant recipient. The risk of bone marrow suppression also is increased when allopurinol is administered with cytotoxic agents that are not metabolized by xanthine oxidase, particularly cyclophosphamide. 

The answer is b. (Hardmanr pp 1296-1299.) Cyclosporine is the preferred agent because it is a specific T cell inhibitor, and its success rate in protecting against rejection is considerably better than that of any other agent. All of the other agents listed in the question are cytotoxic. Because of the severe adverse reactions with cyclosporine, it is used in conjunction with azathioprine, which reduces the required dose. Prednisone is also used in conjunction with cyclosporine. 

Azathioprine is a prodrug of mercaptopurine and, like mercaptopurine, functions as an antimetabolite (see Chapter 54). Although its action is presumably mediated by conversion to mercaptopurine and further metabolites, it has been more widely used than mercaptopurine for immunosuppression in humans. These agents represent prototypes of the antimetabolite group of cytotoxic immunosuppressive drugs, and many other agents that kill proliferative cells appear to work at a similar level in the immune response. 

---