Musculoskeletal system - Methotrexate Flashcards
1
Q
Musculoskeletal system
Methotrexate
Common indications
A
- As a disease-modifying treatment for rheumatoid arthritis.
- As part of chemotherapy regimens for cancers including leukaemia, lymphoma and some solid tumours.
- To treat severe psoriasis (including psoriatic arthritis) that is resistant to other therapies.
2
Q
Musculoskeletal system
Methotrexate
MOA
A
- Methotrexate inhibits dihydrofolate reductase, which converts dietary folic acid to tetrahydrofolate (FH4). FH4 is required for DNA and protein synthesis, so lack of FH4 prevents cellular replication
- Actively dividing cells are particularly sensitive to the effects of methotrexate, accounting for its efficacy in cancer
- Methotrexate also has anti-inflammatory and immunosuppressive effects
- These are mediated in part by inhibition of inflammatory mediators such as interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α
3
Q
Musculoskeletal system
Methotrexate
Adverse effects
A
- Dose-related adverse effects of methotrexate include mucosal damage (e.g. sore mouth, gastrointestinal upset) and bone marrow suppression (resulting most significantly in neutropenia and an increased risk of infection)
- Long-term use can cause hepatic cirrhosis or pulmonary fibrosis
- Neurological effects such as headache, seizures and coma may also occur
- Treatment is with folinic acid, which ‘rescues’ normal cells from methotrexate effects, and with hydration and urinary alkalinisation to enhance methotrexate excretion
4
Q
Musculoskeletal system
Methotrexate
Warnings
A
- Methotrexate is teratogenic and must be avoided in pregnancy
- As methotrexate is renally excreted, it is contraindicated in severe renal impairment.
- As it can cause hepatotoxicity, methotrexate should be avoided in patients with abnormal liver function.
5
Q
Musculoskeletal system
Methotrexate
Important interactions
A
- Methotrexate toxicity is more likely if it is prescribed with drugs that inhibit its renal excretion
- e.g. NSAIDs, penicillins other folate antagonists, e.g. trimethoprim and phenytoin, increases the risk of haematological abnormalities.
- The risk of neutropenia is increased if methotrexate is combined with clozapine.
6
Q
Musculoskeletal system
Methotrexate
Practical prescribing
A
- For autoimmune disease, methotrexate is prescribed for oral administration.
- A typical dose would be 7.5–20 mg once weekly, adjusted according to response and adverse effects (which are more common at higher doses)
- Folic acid 5 mg can be prescribed to be taken on the 6 days where methotrexate is not taken
- For cancer, methotrexate may be given by IV, IM or intrathecal routes to induce remission, then orally for maintenance treatment
7
Q
Musculoskeletal system
Methotrexate
Monitoring
A
- Efficacy should be monitored by symptoms, examination (e.g. of inflamed joints) and blood tests (e.g. inflammatory markers)
- Safety monitoring is essential as adverse effects can be life threatening, but may be reversible if detected early and treatment is stopped
- Measure full blood count, liver and renal function before starting treatment, then 1–2 weekly until treatment is established and 2–3 monthly thereafter
