Arthritis and Gout Flashcards
1
Q
What is Rheumatoid Arthritis?
Describe the Pathophysiology of RA
A
- Due to inflammation of synovial membrane
- joint inflammation involves massive leukocyte infiltration
- important role of macrophages, neutrophils, T and B lymphocytes, plasma cells, cytokines (IL-1, TNFa)
- damage occurs where the synovium contacts cartilage and bone
- both bone and cartilage become damaged
- joint inflammation involves massive leukocyte infiltration
2
Q
What is the role of NSAIDs (also paracetamol and codeine) in RA?
A
- Symptomatic relief only
3
Q
What is the role of Glucocorticoids in RA?
A
- Corticosteroids may be used systemically or as intra-articular injection (limited)
4
Q
What is the role of DMARDs in RA?
A
- Drugs that control the disease and not just treat symptoms
- Delayed action and more toxic
5
Q
What is the role of Dihydrofolate Reductase (DHFR)?
A
- Enzyme that participates in the tetrahydrofolate synthesis
6
Q
What is tetrahydrofolate needed for?
A
The synthesis of the nucleotides
7
Q
What is dihydroorotate dehydrogenase?
A
- Rate-limiting enzyme in de novo synthesis of pyrimidines
8
Q
What are Common DMARD combinations?
A
- Triple Therapy
- Methotrexate, sulfasalazine, hydroxychloroquine
- Double Therapy
- Methotrexate and Leflunomide
- Methotrexate and Sulfasalazine
- Methotrexate and Hydroxychloroquine
9
Q
Describe Tumour Necrosis Factor (TNFa)
A
- Potent pro-inflammatory cytokine
- Produced mainly by macrophages and monocytes
- Major contributor to the inflammatory and destructive changes that occur in RA
- Blockade of TNFa results in a reduction in a number of other pro-inflammatory cytokines (IL-1, IL-6 and IL-8)
10
Q
Describe Receptor Antagonist to IL-1
A
- Recombinant human IL-1 receptor antagonist (IL-1 ra)
- prevents IL-1 from binding to receptor
- decreases IL-1 mediated activity
11
Q
Describe the characteristics of IL-1RA
A
- IL-IRA is a member of the IL-1 cytokine family
- IL-IRA is secreted by various types of cells including immune cells, epithelial cells and adipocytes and is a natural inhibitor of the pro-inflammatory effect of IL1beta
12
Q
Describe Other Immunodulatory and Cytotoxic agents
A
- Additional immunomodulatory drugs are also used in RA sometimes, including azathioprine and cyclosporin A
- These are highly toxic and so are used for life-threatening extra-artricular manifestations of RA such as systemic vasculitis or with severe articular disease that is refractory to other therapy
13
Q
What is gout?
A
- Arthritic-related disease
- a peripheral arthritis resulting from the deposition of sodium urate crystals in one or more joints
- Metabolic disorder: hyperuricemia
- Excess uric acid
- Immune reaction to crystals
14
Q
Describe the characteristics of excess uric acid in Gout
A
- Deposit in joints
- Lactate in sinovial joint > decrease pH
- Favours urate crystallisation
15
Q
Describe the characteristics of Immune Reaction to Crystals in Gout
A
- Activation of complement, kinin systems
- Generation of leukotrienes (B4)
- Accumulation of neutrophils
- >50% of immune cells in sinovial fluid
- Chemotactic mediators, eicosanoids, IL-1, TNF-a
- Toxic oxygen radicals
- Lysosomal proteolytic enzyme
