Treatment Options for RA Flashcards
What are DMARDs?
Disease modifying anti-rheumatic drugs
What parts of the body does RA affect?
- joints
- tendon sheaths
- other body organs
Why does RA affect body organs?
- affects any membrane with similar structure to synovium so serous membranes around heart/GI system are affected
How is RA symmetrical?
- cytokine disease
- spreads from distal to proximal joints
- vertebral bodies damaged frequently as midline
What are the 2 main methods of management?
- pain relief -> same guidelines as OA
- DMARDs to modify disease progression
What is the gold standard DMARD?
Methotrexate
- cannot give in pregnancy
- start within 3 months of symptoms starting
- combined with other for mild RA
- combined with TNFa inhibitor for moderate
- combined with rituximab for severe
What are some additional therapies?
- physiotherapy
- occupational therapy
- podiatry
- therapy (stress management, relaxation, coping)
What is methotrexate? Mechanism of action
- folic acid antagonist
- enters the cell polyglutamated
- prevents production of DNA and RNA synthesis during cell mitosis by inhibiting dihydrofolate reductase and thymidylate synthase
- used in chemotherapy
- blocks production of pro-inflammatory cytokines
- stops production of additional synoviocytes
What are the side effects of methotrexate?
- liver problems
- affects blood count
What is the dosage for methotrexate?
- orally once a week on same day
- loading dose = 5-10mg a week
- maintenance dose = 2.5mg tablet
- if oral ineffective -> subcutaneous or IM injection
What is sulfasalazine?
- DMARD
- old sulphur antibiotic
What is the mechanism of action of sulfasalazine?
- not well understood
- not well absorbed across gut
- metabolised by gut bacteria to 5-ASA
- inhibits COX, cytokines, IL-1 and TNFa in gut modulating travel sites where they produce joint inflammation
What is 5-ASA?
- metabolite of sulfasalazine
- treats ulcerative colitis and relieves arthritic symptoms
- role in the gut
What is hydroxychloroquine?
- anti-malarial
- DMARD
What is the mechanism of action of hydroxychloroquine?
- accumulates in lysosomes increasing pH -> decrease protein modifications of precursors which are secreted with cytokines
- block TLR9 decreasing dendritic cell activation which signal to B cells and lymphocytes
What are the side effects from hydroxychloroquine?
- rash
What is the dosage for hydroxychloroquine?
- 400mg daily
- reduced to 2-3 times a week
What is leflunomide?
- similar efficacy to methotrexate
- DMARD
What is the mechanism of action of leflunomide?
- inhibits DNA and RNA synthesis through inhibiting pyrimidine biosynthesis
What are gold salts?
- IM injectiosn once a week
- 4-6 months before effects seen
- unknown mechanism of action
- side effects
What are some examples of TNFa blockers?
- etanercept
- infliximab (monoclonal antibody against TNFa)
- adalimumab (TNFa monoclonal antibody binding TNF soluble and bound)
What are some examples of IL-1 blockers?
- anankinra (human recombinant IL-1 receptor antagonist)
- canakinumab (human monoclonal antibody IL-1 beta)
- rilonacept
Who are B cells blockers for?
- patients who fail to respond to one or more anti-TNF alpha agents
What is an example of a B cell blocker?
- rituximab
- destroys both normal and malignant B cells
- in combination with methotrexate
- effects seen around 3 months after infusions
What is an example of a T cell blocker?
- abatacept
(activates negative switch of CTLA-4 signal stopping T cell) - betalacept
What is an example of an IL-6 inhibitor?
- tocilizumab
