What are the adverse effects of methotrexate?

• A. Hyperglycemia
• B. Renal toxicity
• C. Increased platelet production
• D. Bone marrow suppression, hepatotoxicity, and GI irritation

Answer: (D)

Methotrexate disrupts DNA synthesis by inhibiting dihydrofolate reductase, so rapidly dividing cells are hit hardest. That explains the main adverse effects: bone marrow suppression, which leads to decreased blood cell counts (anemia, leukopenia, and thrombocytopenia); hepatotoxicity from liver cell injury, especially with longer use or higher doses; and GI irritation from damage to the mucosal lining, causing stomatitis, mucositis, nausea, vomiting, and diarrhea. Hyperglycemia isn’t a typical effect of methotrexate, and increased platelet production would contradict the expected marrow suppression. Nephrotoxicity can occur with high-dose therapy, but the classic triad centers on marrow suppression, liver toxicity, and GI mucosal irritation.