Methotrexate should be given with which of the following to decrease its side effects?
Ans. d (Folinic acid). (Ref. Harrison 18th/Chapter 326. The Vasculitis Syndromes)To 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/ DrugANTIDOTE/TREATMENT1AcetaminophenA/-acetylcysteine2SalicylatesAlkalinize urine, dialysis3Anticholinesterases, organophosphatesAtropine, pralidoxime4Antimuscarinic, anticholinergic agentsPhysostigmine salicylate5b-blockersGlucagon6DigitalisStop dig, normalize K+, lidocaine, anti-dig Fab fragments, Mg2+7IronDeferoxamine8LeadCaEDTA, dimercaprol, succimer, penicillamine9Arsenic, mercury, goldDimercaprol (BAL), succimer10Copper, arsenic, goldPenicillamine11CyanideNitrite, hydroxocobalamin, thiosulfate12MethemoglobinMethylene blue13Carbon monoxide100% O2, hyperbaric O214Methanol, ethylene glycol (antifreeze)Ethanol, dialysis, fomepizole15OpioidsNaloxone/naltrexone16BenzodiazepinesFlumazenil17TCAsNaHCO3 (nonspecific)18HeparinProtamine19WarfarinVitamin K, fresh frozen plasma20tPA, streptokinaseAminocaproic acid21CisplatinAmifostine22CyclophosphamideMESNA23DoxorubicinDexrozoxazone
Folic acid
Cyanocobalamin
Thiamine
Folinic acid
Anti-Cancer