MSK drugs Flashcards
(18 cards)
What is the mechanism of action of methotrexate in musculoskeletal conditions?
Methotrexate inhibits dihydrofolate reductase (DHFR), leading to the reduced production of tetrahydrofolate. This disrupts purine and pyrimidine synthesis, inhibiting DNA synthesis and cell proliferation. In musculoskeletal conditions, this suppresses the immune response and reduces inflammation in diseases like rheumatoid arthritis.
Why is methotrexate used in musculoskeletal diseases?
Methotrexate is used in rheumatoid arthritis and other autoimmune diseases because it reduces joint inflammation, pain, and swelling by inhibiting T-cell proliferation and cytokine production. It is considered a disease-modifying anti-rheumatic drug (DMARD).
What are the common side effects of methotrexate?
- Gastrointestinal: Nausea, vomiting, mouth ulcers, diarrhea.
- Hematologic: Anemia, leukopenia, thrombocytopenia.
- Hepatotoxicity: Liver enzyme elevation, possible cirrhosis.
- Pulmonary toxicity: Pneumonitis, fibrosis (rare).
- Skin reactions: Rash, photosensitivity.
What is the mechanism of hepatotoxicity caused by methotrexate?
Methotrexate causes hepatotoxicity by accumulating in the liver, where it disrupts liver cell function. This can lead to elevated liver enzymes and, with chronic use, the potential for cirrhosis and fibrosis.
Why does methotrexate cause bone marrow suppression?
Methotrexate inhibits DNA synthesis in rapidly dividing cells, including bone marrow cells, leading to anaemia, leukopenia, and thrombocytopenia. This is due to its effect on the synthesis of purines and pyrimidines, which are essential for cell division
What is the role of folic acid in reducing methotrexate side effects?
Folic acid supplementation reduces the toxic effects of methotrexate by replenishing folate stores that are depleted by methotrexate’s inhibition of dihydrofolate reductase. It helps prevent gastrointestinal side effects, hematologic toxicity, and reduces the risk of mouth ulcers and fatigue
How does methotrexate affect the lungs?
Methotrexate can cause pulmonary toxicity in the form of pneumonitis (inflammation of lung tissue), which can lead to dyspnoea, cough, and fever. Long-term use may lead to fibrosis, although this is rare.
What is the significance of methotrexate-related gastrointestinal toxicity?
Gastrointestinal toxicity from methotrexate includes nausea, vomiting, mouth ulcers, and diarrhoea. This occurs due to its effect on rapidly dividing cells in the intestinal lining. Low-dose folic acid supplementation can help reduce these effects.
How can renal function be affected by methotrexate?
Methotrexate is primarily excreted via the kidneys. In patients with renal impairment, methotrexate clearance is reduced, leading to toxicity. Therefore, renal function should be monitored regularly, and dose adjustments may be needed.
What are the key risk factors for adverse effects from methotrexate?
- Pre-existing liver disease (e.g., cirrhosis, alcoholic liver disease)
- Renal impairment
- High-dose methotrexate therapy
- Alcohol consumption
- Advanced age
- Pregnancy (methotrexate is teratogenic)
What monitoring is required for patients on methotrexate?
- Liver function tests (LFTs): To detect hepatotoxicity.
- Renal function: Check creatinine and eGFR for kidney function.
- Full blood count (FBC): To detect bone marrow suppression (e.g., leukopenia, thrombocytopenia).
- Pulmonary function tests (if symptoms develop): To detect pneumonitis or fibrosis
How is methotrexate dosing adjusted for patients with renal impairment?
In patients with renal impairment, methotrexate dosing should be reduced or discontinued, as renal dysfunction can impair methotrexate elimination, leading to increased toxicity. Close monitoring of renal function is necessary, and the dose may need to be adjusted based on creatinine clearance.
What contraception advice should be given to patients on methotrexate?
Methotrexate is teratogenic, so patients (especially women) should be advised to use effective contraception during therapy and for at least 6 months after stopping methotrexate. Both male and female patients should be counselled on contraception during treatment.
What is the role of methotrexate in the management of rheumatoid arthritis?
Methotrexate is a first-line DMARD for rheumatoid arthritis, helping to reduce inflammation, pain, and joint damage. It modifies the disease course and improves long-term outcomes, slowing the progression of the disease.
How does methotrexate interact with other drugs?
- NSAIDs: Increase methotrexate toxicity by reducing renal clearance.
- Sulfonamides: Increase the risk of hematologic toxicity.
- Probenecid: Decreases methotrexate excretion, increasing toxicity.
- Penicillins: Increase methotrexate levels due to renal interactions.
What side effect is associated with methotrexate use in the skin?
Methotrexate can cause photosensitivity, increasing the risk of sunburn. It may also cause rash or alopecia in some patients, especially with higher doses.
What is the teratogenic effect of methotrexate?
Methotrexate is teratogenic, meaning it can cause birth defects if taken during pregnancy. It can cause miscarriage, fetal malformations, and neurodevelopmental issues. It is contraindicated during pregnancy.
What is the importance of folic acid supplementation in patients receiving methotrexate?
Folic acid supplementation helps reduce methotrexate-induced toxicity, including gastrointestinal symptoms, hematologic abnormalities, and mouth ulcers. It replenishes folate stores depleted by methotrexate and helps minimize side effects.
