<prompt> Methotrexate should be given with which of the following to decrease its side effects?Folic acidCyanocobalaminThiamineFolinic acid  <response>: Ans. d Folinic acid. Ref. Harrison 18thChapter 326. The Vasculitis SyndromesTo lessen toxicity, methotrexate is often given together with folic acid, 1 mg daily, or folinic acid, 5-10 mg once a week 24h following methotrexate.METHOTREXATE acts by inhibiting hydrofolate reductase - blocking the conversion of dihydrofolate to tetrahydrofolate, which is an essential coenzyme required for one carbon atom transfer reactions in de novo purine synthesis and amino acid interconversions. It has cell specific action and acts on the S phase of cell cycle.- USES:- It is apparently curative in choricarcinoma.- It is also useful in acute leukemias, rheumatoid arthritis, psoriasis and as an immunosupressant.- High dose methotrexate is used in management of osteosarcoma and Histiocytosis X. Its toxicity cannot be overcomed by folic acid, because it will not be converted to active co-enzyme form. However, folinic acid citrovorum factor rapidly reverses its effect. Thymidine also counteracts its toxicity.Antidotes for some drug toxicities Toxin DrugANTIDOTETREATMENT1AcetaminophenA-acetylcysteine2SalicylatesAlkalinize urine, dialysis3Anticholinesterases, organophosphatesAtropine, pralidoxime4Antimuscarinic, anticholinergic agentsPhysostigmine salicylate5b-blockersGlucagon6DigitalisStop dig, normalize K, lidocaine, anti-dig Fab fragments, Mg27IronDeferoxamine8LeadCaEDTA, dimercaprol, succimer, penicillamine9Arsenic, mercury, goldDimercaprol BAL, succimer10Copper, arsenic, goldPenicillamine11CyanideNitrite, hydroxocobalamin, thiosulfate12MethemoglobinMethylene blue13Carbon monoxide100 O2, hyperbaric O214Methanol, ethylene glycol antifreezeEthanol, dialysis, fomepizole15OpioidsNaloxonenaltrexone16BenzodiazepinesFlumazenil17TCAsNaHCO3 nonspecific18HeparinProtamine19WarfarinVitamin K, fresh frozen plasma20tPA, streptokinaseAminocaproic acid21CisplatinAmifostine22CyclophosphamideMESNA23DoxorubicinDexrozoxazone 