<prompt> Methotrexate is used for the management of all of these conditions except:Rheumatoid ahritisPsoriasisSickle cell anemiaOrgan transplantation  <response>: Methotrexate Mtx It is one of the oldest and highly efficacious antineoplastic drugs; inhibits dihydrofolate reductase DHFRase-blocking the conversion of dihydrofolic acid DHFA to tetrahydrofolic acid THFA which is an essential coenzyme required for one carbon transfer reactions in de novo purine synthesis and amino acid interconversions. The inhibition is pseudoirreversible because Mtx has 50,000 times higher affinity for the enzyme than the normal substrate. Methotrexate has cell cycle specific actionkills cells in S phase; primarily inhibits DNA synthesis, but also affects RNA and protein synthesis. It exes major toxicity on bone marrow-low doses given repeatedly cause megaloblastic anaemia, but high doses produce pancytopenia. Desquamation and bleeding may occur in g.i.t. Methotrexate is apparently curative in choriocarcinoma: 15-30 mg day for 5 days orally or 2G-40 mgm2 BSA i.m. or i.v. twice weekly.It is highly effective in maintaining remission in children with acute leukaemias, but not good for inducing remission: 2.5-15 mgday. It is also useful in other malignancies, rheumatoid ahritis, psoriasis and as immunosuppressant. Essentials of medical pharmacology K D Tripathi Sixth edition Pg no 823 