<prompt> Which of the following is not an early adverse effect of methotrexate?Hepatic fibrosisMyelosupressionNauseaStomatitis  <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 Adverse Effects 10 Arachnoiditis with intrathecal administration Subacute toxicity with intrathecal administration paralysis of extremities, cranial nerve palsy, seizure or coma Demyelinating encephalopathy with cranial irradiation or other systemic chemotherapy Reddening of skin Hyperuricemia Ulcerative stomatitis Glossitis Gingivitis Nausea and vomiting Diarrhea Anorexia Intestinal perforation Mucositis dose-dependent Leukopenia Thrombocytopenia Renal failure Azotemia Nephropathy Pharyngitis 1-10 Alopecia Photosensitivity Rash Abdominal distress Malaise Fatigue Chills, fever Decreased resistance to infection Gastrointestinal hemorrhage Myelosuppression Disorders of lung, interstitial pneumonia acute, chronic Atrophy of liver, cirrhosis, hepatic fibrosis or necrosis, elevated liver function tests, hepatic failure REFERENCE: essentials of medical pharmacologyk.d.tripathi,sixth edition,page no:823 