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Rheumatrex: profile and news
Research Suggests Arthritis Drug Needs Second Chance Apr 24, 2006 Other information Indication For the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole; Severe psoriasis; Severe, active, classical or definite rheumatoid arthritis; Pharmacology Methotrexate is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Methotrexate inhibits folic acid reductase which is responsible for the conversion of folic acid to tetrahydrofolic acid. At two stages in the biosynthesis of purines and at one stage in the synthesis of pyrimidines, one-carbon transfer reactions occur which require specific coenzymes synthesized in the cell from tetrahydrofolic acid. Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it quite strongly and inhibits the enzyme. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Methotrexate selectively affects the most rapidly dividing cells (neoplastic and psoriatic cells). Methotrexate is also indicated in the management of severe, active, classical, or definite rheumatoid arthritis. Mechanism Of Action Methotrexate anti-tumor activity is a result of the inhibition of folic acid reductase, leading to inhibition of DNA synthesis and inhibition of cellular replication. The mechanism involved in its activity against rheumatoid arthritis is not known. Drug Category Antirheumatic Agents; Immunosuppressive Agents; Dermatologic Agents; Antimetabolites; Abortifacient Agents; Antineoplastic Agents; ATC:L01BA01; ATC:L04AX03 Brand Names/Synonyms Abitrexate; Amethopterin; Amethopterine; Antifolan; Arbitrexate; Emtexate; Folex; Folex Pfs; HDMTX; L-Amethopterin; Ledertrexate; MTX; Metatrexan; Methopterin; Methotextrate; Methotrate; Methotrexat; Methotrexate; Methotrexate Lpf; Methotrexate Preservative Free; Methotrexate Sodium; Methotrexate for Injection; Methotrexate, Usp Grade; Methylaminopterin; Methylaminopterinum; Mexate; Mexate-Aq; Mexate-Aq Preserved; N-Bismethylpteroylglutamic Acid; NSC 740; R 9985; Rheumatrex; Rheumatrex Dose Pack; Trexall; X 133 Dosage Forms Tablets Absorption Well absorbed <30 mg/mē, 20% Interactions Interactions for Methotrexate: Concomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity. Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate. These drugs have been reported to reduce the tubular secretion of methotrexate in an animal model and may enhance its toxicity. Despite the potential interactions, studies of methotrexate in patients with rheumatoid arthritis have usually included concurrent use of constant dosage regimens of NSAIDs, without apparent problems. It should be appreciated, however, that the doses used in rheumatoid arthritis (7.5 to 15 mg/week) are somewhat lower than those used in psoriasis and that larger doses could lead to unexpected toxicity. Methotrexate is partially bound to serum albumin, and toxicity may be increased because of displacement by certain drugs, such as salicylates, phenylbutazone, phenytoin, and sulfonamides. Renal tubular transport is also diminished by probenecid; use of methotrexate with this drug should be carefully monitored. Oral antibiotics such as tetracycline, chloramphenicol, and nonabsorbable broad spectrum antibiotics, may decrease intestinal absorption of methotrexate or interfere with the enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria. Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with high and low dose methotrexate. Use of methotrexate with penicillins should be carefully monitored. The potential for increased hepatotoxicity when methotrexate is administered with other Vitamin preparations containing folic acid or its derivatives may decrease responses to systemically administered methotrexate. Preliminary animal and human studies have shown that small quantities of intravenously administered leucovorin enter the CSF primarily as 5-methyltetrahydrofolate and in humans, remain 1 - 3 orders of magnitude lower than the usual methotrexate concentrations following intrathecal administration. However, high doses of leucovorin may reduce the efficacy of intrathecally administered methotrexate. Folate deficiency states may increase methotrexate toxicity. Trimethoprim/sulfamethoxazole has been reported rarely to increase bone marrow suppression in patients receiving methotrexate, probably by an additive antifolate effect. Chemical IUPAC Name 2-[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]aminopentanedioicacid Chemical Formula C20H22N8O5 Half Life 0.7-5.8 hours Drug Type Approved Drug # Accession No APRD00353 CAS Registry Number 59-05-2 |
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