Leucovorin to the Rescue​

A 78-year-old man was advised to go to the emergency department by his rheumatologist after reporting symptoms of nausea, severe fatigue, and feeling "off" for two days. The patient had recently been prescribed methotrexate for his polymyalgia rheumatica, and was instructed to take 5 mg once a week, but he misunderstood and took 5 mg daily for six days.The patient's heart rate was 80 beats per minute, his blood pressure was 155/75 mm Hg, his pulse ox was 98% on room air, and his temperature was 98°F. His initial labs included a CBC with no abnormalities, but his creatinine was 2.5 mg/dL with a GFR of 25. Baseline levels from previous visits were creatinine 1.2 mg/dL and GFR >50.​What is the mechanism of methotrexate toxicity?As a structural analog of folate, methotrexate competitively inhibits dihydrofolate reductase. (Figure below.) This ultimately leads to interference with DNA and RNA synthesis so rapidly proliferating cells are most sensitive to this effect. Renal toxicity is associated with the precipitation of methotrexate and its metabolites in the renal tubules causing acute tubular necrosis. Most reported toxicity occurs with chronic oral administration, but other routes of reported toxicity include inadvertent high-dose intrathecal, intravenous, and intramuscular administration. Toxicity from acute intentional overdose is mostly benign. Clinical Manifestations of Methotrexate ToxicityMucositis manifesting as stomatitis, esophagitis, or diarrheaD...
Source: The Tox Cave - Category: Emergency Medicine Tags: Blog Posts Source Type: blogs