Methotrexate Corticosteroids

Altered immune function increases infection, which should be considered, particularly in patients taking azathioprine, methotrexate, corticosteroids, or other drugs that may produce myelosuppression. 

METHOTREXATE CORTICOSTEROIDS t risk of bone marrow toxicity Additive effect Monitor FBC regularly... 

CNS prophylaxis relies on intrathecal chemotherapy (e.g., methotrexate, cytarabine, and corticosteroids), systemic... 

Drugs that may affect aspirin include activated charcoal, ammonium chloride, ascorbic acid or methionine, antacids and urinary alkalinizers, carbonic anhydrase inhibitors, corticosteroids, and nizatidine. Drugs that may be affected by aspirin include alcohol, ACE inhibitors, anticoagulants (oral), beta-adrenergic blockers, heparin, loop diuretics, methotrexate, nitroglycerin, NSAIDs, probenecid and sulfinpyrazone, spironolactone, sulfonylureas and exogenous insulin, and valproic acid. 

Drugs that may affect cyclosporine include allopurinol, amiodarone, androgens (eg, danazol, methyltestosterone), anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), azole antifungals (eg, fluconazole, ketoconazole), beta-blockers, bosentan, bromocriptine, calcium channel blockers, colchicine, oral contraceptives, corticosteroids, fluoroquinolones (eg, ciprofloxacin), foscarnet, HMG-CoA reductase inhibitors, imipenem-cilastatin, macrolide antibiotics, methotrexate, metoclopramide, nafcillin, nefazodone, orlistat, potassium-sparing diuretics, probucol, rifamycins (rifampin, rifabutin), serotonin reuptake inhibitors (SSRIs eg, fluoxetine, sertraline),... 

The present primary mode of therapy for these diseases involves the use 5-amino-salicylate (5-ASA) products. Often patients require additional medications, including corticosteroids, to help induce remission and various immune modulators, such as azathioprine, 6-mercaptopurine or methotrexate, to maintain remission. In Crohn s disease certain antibiotics, such as metronidazole and ciprofloxacin, and infliximab Remi-cade), an anti-tumor necrosis factor-a(TNFa) antibody, also have been used. The pharmacology of antibiotics, immunosuppressive drugs, and corticosteroids is discussed in Chapters 43,57, and 60, respectively. 

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. 

B. Indications and nse Remicade is indicated for the reduction of the symptoms of moderate to severe Crohn s disease in patients who have not responded well to traditional treatments, including corticosteroids and other immunosuppressants, and antibiotics, and to close enterocuta-neous fistulas. Remicade, with concomitant methotrexate, is indicated for the reduction in signs and symptoms, and inhibiting the progression of structural damage due to RA in patients who have had an inadequate response to methotrexate alone. 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

Advantage is taken of the properties of antimctabolitcs in chemotherapy. In cancer chemotherapy, several antimetabolites are used. These include methotrexate, 6-mercaptopunne, 6-thioguanine, 5-fluorouracil, and cystine arabinoside. In the chemotherapy of metastatic breast cancer, 5-fluorouracil and methotrexate, in combination with cyclophosphamide, have been used. Antimetabolites, sometimes along with corticosteroids, are used in the therapy of various autoimmune diseases, such as thrombocytenic purpura, thyroiditis, Goodpasture s syndrome, among others. 

A number of toxic effects on the blood have been documented, including agranulocytosis caused by chlorpromazine, hemolytic anemia caused by methyldopa, and megaloblastic anemia caused by methotrexate. Toxic effects on the eye have been noted and range from retinotoxicity caused by thioridazine to glaucoma caused by systemic corticosteroids. 

The management of cancer includes treatment with alkylating agents (nitrogen mustards and alkyl sulfonates), antimetabolites (methotrexate and purine analogs), natural products (vinca alkaloids and antibiotics), miscellaneous compounds (hydroxyurea, procarbazine, and cis-platinum), hormones (estrogens and corticosteroids), and radioactive isotopes (see Chapter 62). 

Methotrexate can be helpful in controlling relapses of Crohn s disease unresponsive to corticosteroid or azathioprine. It has also been used with benefit in ulcerative colitis. Its short- and long-term use are limited by a wide profile of adverse effects including bone marrow suppression and pulmonary and hepatic fibrosis (see p. 291). 

Te use of NSAIDS and other anti-inflammatory therapies are similar to those used in other autoimmune arthritic disorders. Corticosteroid injections for severe pain and inflammation at specific joints are standard therapy. For severe forms of the disease immunomodulating anti-rheumatic drugs such as methotrexate and sulfasalazine are effective. As with other similar disorders, the biologic TNF a inhibitors are currently prescribed for severe Reiter s syndrome. 

Wallace JR, Luchi M. Fatal cytomegalovirus pneumonia in a patient receiving corticosteroids and methotrexate for mixed connective tissue disease. South Med J 1996 89(7) 726-8. 

Lafforgue P, Monjane 1-Mouterde S, Durand A, Catalin J, Acquaviva PC. Is there an interaction between low doses of corticosteroids and methotrexate in patients with rheumatoid arthritis A pharmacokinetic study in 33 patients. J Rheumatol 1993 20(2) 263-7. 

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