💊 Methotrexate

Methotrexate is an antimetabolite, specifically a folic acid antagonist. It is used as an immunosuppressant and anti-inflammatory agent in rheumatology and dermatology, and as a cytotoxic agent in oncology.

Methotrexate inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purine nucleotides and thymidylate. This leads to a depletion of folate cofactors, thereby inhibiting DNA synthesis, repair, and cellular replication. In inflammatory conditions, its anti-inflammatory effects are thought to involve adenosine release and inhibition of T-cell proliferation.

In low doses, methotrexate is a cornerstone treatment for rheumatoid arthritis, psoriatic arthritis, and severe psoriasis. In higher doses, it is used in various malignancies, including acute lymphoblastic leukaemia, non-Hodgkin lymphoma, and choriocarcinoma. It is also used in the management of ectopic pregnancy.

Absolute contraindications include severe renal impairment, severe hepatic impairment, significant bone marrow suppression, active infection, and pregnancy/breastfeeding. Alcoholism or chronic liver disease are also contraindications. Live vaccines should be avoided during methotrexate therapy.

Common adverse effects include nausea, vomiting, stomatitis (mouth ulcers), and fatigue. Haematological toxicities such as myelosuppression (leukopenia, thrombocytopenia) are serious and dose-limiting. Hepatic fibrosis/cirrhosis and interstitial pneumonitis are rare but serious long-term complications. Renal toxicity can occur, especially with high doses or dehydration.

Regular monitoring of full blood count (FBC), liver function tests (LFTs), and renal function (creatinine, eGFR) is essential. FBC should be checked weekly initially, then less frequently. LFTs and renal function are typically monitored every 1-3 months. Patients should be monitored for signs of infection or pulmonary symptoms.

When prescribing, always confirm the dosing frequency (weekly for inflammatory conditions) and ensure folic acid is prescribed on a different day. Check for renal and hepatic impairment, and review concomitant medications for interactions (e.g., NSAIDs can increase methotrexate levels). Counsel patients on the serious nature of the drug, the importance of weekly dosing, folic acid, avoiding alcohol, and reporting any adverse effects immediately.

High-yield facts include its weekly dosing for inflammatory conditions and the mandatory co-prescription of folic acid to reduce side effects. Remember its dual role as an immunosuppressant and cytotoxic agent. Emphasise the severe toxicities (myelosuppression, hepatotoxicity, pneumonitis) and the need for rigorous monitoring. Pregnancy is an absolute contraindication.

SBA questions frequently test the correct dosing frequency (weekly for inflammatory conditions, not daily) and the importance of folic acid supplementation. Identifying signs of methotrexate toxicity (e.g., mouth ulcers, unexplained bruising, shortness of breath) and appropriate management (e.g., stopping methotrexate, administering folinic acid) are common themes. Contraindications like pregnancy and renal impairment are also high-yield.