3 DMARDs Flashcards
How long does it take for DMARDs to take clinical effects?
6 weeks to 6 months
Some within 2 weeks
What is the first choice to treat rheumatoid arthritis?
Methotrexate
What is the MOA for methotrexate?
Inhibits AICAR transformylase
What does AICAR transformylase do?
Catalyzes the penultimate and final steps in de novo purine biosynthesis which leads to synthesis of IMP
Inhibition of AICAR transformylase results in the accumulation and release of what?
Adenosine
How does adenosine act as a potent anti-inflammatory mediator?
Acts on A2b receptors and suppresses NF-kB activation induced by TNF and other inflammatory stimuli
Besides blocking IMP, what other pathway does Methotrexate affect?
Thymidylate synthase pathway
What are the MOST COMMON adverse effects of Methotrexate?
Nausea and mucosal ulcers
How is Methotrexate toxicity reduced?
Leucovorin or folic acid
Can methotrexate be used in pregnancy?
No.
Contraindicated
Cyclosporine binds to what?
Cyclophilin (an immunophilin)
Cyclosporin-Cyclophilin complex inhibits what?
Calcineurin
What is the dose limiting adverse affect of cyclosporine?
Nephrotoxicity
Which drug is a purine antimetabolite?
Azathioprine
What is Azathioprine converted to?
6-mercaptopurine
What is the action of 6-mercaptopurine?
inhibits de novo synthesis if purine synthesis
What is azathioprine used for?
Refractory rheumatoid arthritis
What is the MOA of cyclophophamide?
Cross links DNA, thereby preventing cell replication
What are the gold compounds?
- Gold sodium thiomalate
- Auranofin
Gold salts are taken up by what? Resulting in?
- Macrophages
- Supress phagocytosis and lysosomal enzymes
Which are the anti-TNF drugs?
1) Adalimumab
2) Infliximab
3) Entanercept
What must be done before putting a patient on a anti-TNF drug?
Screen for TB
before and during treatment
Which is the anti-interleukin drug?
Anakinra
What is the MOA of anakinra?
IL-1 receptor antagonist?
Leflunomide in combination with methotrexate increases risk of what?
Hepatotoxicity
The combination of different biological agents increases risk of what?
Neutropenia and infections
