“How does leucovorin rescue methotrexate toxicity?”

追加: 2026-06-03

[00:00:00]How does leucovorin rescue methotrexate toxicity? It's a great question. So, what's the mechanism of action of methotrexate? I'm asking you.

[00:00:10]It's a dihydrofolate reductase inhibitor. So, past level and that's normally that enzyme going to convert what to what?

[00:00:19]So, dihydrofolate, DHF, into tetrahydrofolate, THF, and we need tetrahydrofolate for what?

[00:00:30]DNA synthesis. So, what are the three highest yield use cases on USMLE for methotrexate?

[00:00:41]So, the highest yield use case is it's the first-line DMARD for rheumatoid arthritis, disease-modifying antirheumatic drug. Second highest yield use case is it's used for systemic psoriasis. Let's say patient has psoriatic arthritis or they've failed topical agents for plaque psoriasis. Third is it can be used as a chemotherapeutic agent {slash} non-specific immunosuppressant. Fine.

[00:01:04]So, students ask about leucovorin.

[00:01:07]I'm asking you, what is the other name for leucovorin?

[00:01:14]Folinic acid, not folic acid. Holy [ __ ] okay? So, folic acid, what vitamin is that?

[00:01:23]So, folic acid, folate, vitamin B9, should know that. So, folic acid is often given to patients on methotrexate, but it still requires dihydrofolate reductase for conversion into tetrahydrofolate for DNA synthesis. Now, folinic acid is closely associated with THF structurally. So, in other words, folinic acid is already on the THF side of the equation. So, we bypass tetrahydrofolate.

[00:01:54]What the [ __ ] am I saying? We bypass dihydrofolate reductase.

[00:02:00]because we're already on the THF side of the equation, you understand? So, patients who have methotrexate toxicity, what would be three major toxicities of methotrexate masking?

[00:02:13]Mouth ulcers, they really like that, so that's mucositis.

[00:02:17]Pancytopenia, you got to knock out the bone marrow, so myelosuppression. Three is hepatotoxicity. So, patients who have methotrexate toxicity, we can rescue them, quote unquote, with leucovorin, folinic acid.