Rheumatoid arthritis chemotherapy

The answer is c. (Katzung, pp 608-609, 932-9.13.) Methotrexate is classified as an anti metabolite with therapeutic uses in cancer chemotherapy and as an immunosuppressive agent indicated in the treatment of severe active classical rheumatoid arthritis. Leucovorin is related to methotrexate in that it is an antagonist of its actions. It can supply a source of reduced folate for the methylation reactions that are prevented by methotrexate. 

Cyclophosphamide (Cytotoxin) Alkylating agent cancer chemotherapy transplant rejection rheumatoid arthritis Decreased Ts cells, B cells, and NK cells... 

Methotrexate is one of the few anticancer drugs that can be safely administered intrathecally for the treatment of meningeal metastases. Its routine use as prophylactic intrathecal chemotherapy in acute lymphoblastic leukemia has greatly reduced the incidence of recurrences in the CNS and has contributed to the cure rate in this disease. Daily oral doses of methotrexate are used for severe cases of the nonneoplastic skin disease psoriasis (see Chapter 41), and methotrexate has been used as an immunosuppressive agent in severe rheumatoid arthritis. 

Originally developed for chemotherapy, azathioprine is used today mainly as an immunosuppressive agent and rarely as an antineoplastic drug. It was introduced as an immunosuppressive agent by a British pioneer of tissue transplantation, Roy Caine. Azathioprine was used to prevent rejection after tissue transplantation as a replacement for 6-mercaptopurine because it was less toxic. In addition to tissue transplantation, it is also used for rheumatoid arthritis and Crohn s disease. Azathioprine is a prodrug which in the body is converted to its active metabolites 6-mercaptopurine and 6-thioinosinic acid. Until the discovery of cyclosporine, azathioprine in combination with steroids was the standard treatment to prevent rejection after tissue transplantation. 

Methotrexate is now considered the first DMARD of choice in the treatment of rheumatoid arthritis and is used in up to 60% of patients. It is active in this condition at much lower doses than those needed in cancer chemotherapy (see Chapter 55 Cancer Chemotherapy). 

Originally developed as part of a large-scale effort headed by the United States National Cancer Institute to investigate chemotherapeutic agents from natural sources, paclitaxel was approved by the FDA in 1992 as an antineoplastic agent to treat metastatic ovarian cancer after failure of first-line or subsequent chemotherapy (37). Further studies demonstrated efficacy in other solid tumors (38). In addition, paclitaxel was shown to inhibit T- and B-cell proliferation when tested for transplant-rejection application (39,40) and has demonstrated inhibition of matrix-metalloproteinase synthesis in studies conducted to test its utility for rheumatoid arthritis (41). 

The bleomycin assay has been applied to assess the levels of available, nontransferrin-bound iron in plasma samples in patients with iron overload disease (Peters et al., 1985), with acute leukaemia before and after drug chemotherapy (Halliwell et al., 1988), as well as patients with rheumatoid arthritis (Winyard et al., 1987). 

A 55-year-old man with chronic lymphocytic leukemia and rheumatoid arthritis took methotrexate for 4 years and developed a B cell non-Hodgkin s lymphoma in the shoulder and axillary lymph nodes he had Epstein-Barr viral antigens in the serum. After radiation and chemotherapy had failed, complete remission was achieved with a combination of rituximab and EPOCH (etoposide -I- prednisone -I- vincristine -I-cyclophosphamide + doxorubicin). 

Similarly, replacement of the hydroxyl group of ptcroyl-glutamic acid (folic acid) by the amino gntup leads to ami-nopterin, a folate antimetubulite. Addition of the methyl group to the/>-aminobcn/.oatc nitrogen produced methotrexate. which is used in cancer chemotherapy, for psoriasis, and as an immunosuppressant in rheumatoid arthritis. 

Atropine - emergency treatment of hypotension with bradycardia Azathioprine - immunosuppressant cancer chemotherapy, rheumatoid arthritis Baclofen - skeletal muscle relaxant spasticity Barbiturate - hypnotic (little therapeutic use)... 

Persistent or recurrent cutaneous T-cell lymphoma Prevention of severe chemotherapy-induced thrombocytopenia Moderate to severe active rheumatoid arthritis Moderate to severe active rheumatoid arthritis Anemia related to AZT therapy in HIV-infected patients Anemia associated with chronic renal failure... 

Anti-inflammatory systemic lupus erythematosus leukemias rheumatoid arthritis breast cancer Synthetic estrogen cancer chemotherapy... 

Cytotoxin) chemotherapy transplant rejection rheumatoid arthritis NK cells... 

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