MTX

Methotrexate (MTX, chemical structure shown in Fig. 1.) competitively inhibits the dehyrofolate reductase, an enzyme that plays an essential role in purine synthesis. The dehydrofolate reductase regenerates reduced folates when thymidine monophosphate is formed from deoxyuridine monophosphate. Without reduced folates cells are unable to synthesize thymine. Administration of N-5 tetrahydrofolate or N-5 formyl-tetrahydrofolate (folinic acid) can bypass this block and rescue cells from methotrexate activity by serving as antidote. 

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

The miscellaneous drugp are used to treat a variety of musculoskeletal disorders. Ffenicillamine, methotrexate (MTX), and hydroxychloroquine are used to treat rheumatoid arthritis in patients who have had an insufficient therapeutic response to or are intolerant of other antirheumatic drugp such as the sailcylates and NSAIDs. The Summary Drug Table Drug s Used to Tream Musculoskeletal Disorders provides additional information about these and other drug s. One compound, hylan G-F 20, listed in the Summary Drug Table is not used for rheumatoid arthritis, but rather, for osteoarthritis knee pain. It is a viscous, elastic... 

The mechanism of action of penicillamine, MTX, and hydroxychloroquine in the treatment of rheumatoid arthritis is unknown. 

MTX is a potentially toxic dmg that is also used in the treatment of malignancies and psoriasis. Nausea, vomiting, a decreased platelet count, leukopenia (decreased white blood cell count), stomatitis (inflammation of the oral cavity), rash, pruritus, dermatitis, diarrhea, alopecia (loss of hair), and diarrhea may be seen with the administration of this dmg. 

These dru are contraindicated in patients with known hypersensitivity. Hydroxychloroquine is contraindicated in patients with porphyria (a group of serious inherited disorders affecting the bone marrow or the liver), psoriasis (chronic skin disorder), and retinal disease (may cause irreversible retinal damage). MTX is contraindicated during pregnancy because it is a Pregnancy Category X dmg and may cause birth defects... 

There is an increased risk of toxicity of MTX when administered with the NSAIDs, salicylates, oral antidiabetic drugs, phenytoin, tetracycline, and probenecid. There is an additive bone marrow depressant effect when administered with other drug known to depress the bone marrow or with radiation therapy. There is an increased risk for nephrotoxicity when MTX is administered with other drug that cause nephrotoxicity. When penicillamine is administered with digoxin, decreased blood levels of digoxin may occur. There is a decreased absorption of penicillamine when the dmg is administered with food, iron preparations, and antacids. 

MTX is potentially toxic. Therefore, the nurse observes closely for development of adverse reactions, such as thrombocytopenia (see Nursing Alert in Gold Compounds section) and leukopenia (see discussion of adverse reactions associated with hydroxychloroquine). Hematology, liver, and renal function studies are monitored every 1 to 3 months with MTX therapy. The primary care provider is notified of abnormal hematology, liver function, or kidney function finding. The nurse immediately brings all adverse reactions or suspected adverse reactions to the attention of the primary health care provider. 

The above indicates the importance of the equilibrium in Eq. (18) for the termination of a polymeric chain. The halide transfer from the complex counterion to the cationic chain end was experimentally investigated using the model system Ph3C+MtX +1... 

DOX, doxorubicine TAX, taxol MTX, methotrexate DDPt, cisplatin 5PU, flurouracil ETO, etoposide. 

MTX exceeds any other marine toxins known in the mouse lethality (0.13 ig/kg) and is 80 times more potent than commercial saponin (Merck) in hemolytic activity. According to Terao (72), MTX induced severe pathomorphological change in the stomach, heart and lymphoid tissues in mice and rats by i.p. injection of 200... 

Mechanical Response. At concentrations above 10 g/mL, MTX caused a sustained contraction in the rabbit aorta. The MTX-induced contraction lasted for at least 3... 

The application of high concentrations (above 5 x 10 g/mL) of MTX caused a biphasic inotropic change and gradual rise in diastolic tension of the atria. Furthermore, MTX produced various arrhythmic movements and cardiac arrest in the guinea pig left and right atria (Figure 4). 

Figure 1. The log cx)ncentration-cx)ntractile response curves for maitotoxin (MTX) in the rabbit aorta in the presence ( ) or absence (o) of verapamil (10" M). Verapamil was administered 15 min before the application of MTX. The maximum response to MTX (3 x 10 g/mL) is expressed as 100%. Vertical lines indicate the standard error of mean (n=7). (Reproduced with permission from Ref. 13. Copyright 1983 Press Syndicate of the University of Cambridge)...

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