Anti-inflammatory agents Flashcards
(35 cards)
What is the role of interleukin-1 (IL-1) in inflammation?
IL-1 activates phospholipase, leading to prostaglandin synthesis, and promotes IL-8 and E-selectin production.
What is the function of IL-8 (CXCL8) during inflammation?
IL-8 is a chemotactic factor that attracts neutrophils to the site of injury.
What is the role of leukotrienes in inflammation?
Leukotrienes are chemotactic factors that attract neutrophils to the site of injury.
How do prostaglandins contribute to inflammation?
Prostaglandins cause vasodilation and sensitize nerve endings, contributing to pain.
How do histamines affect inflammation?
Histamines increase the permeability of capillary endothelial cells.
Why do NSAIDs have limited effectiveness in reducing inflammation?
They do not block leukotriene synthesis, which also contributes to inflammation.
How do NSAIDs reduce inflammation?
NSAIDs inhibit cyclooxygenase (COX), blocking prostaglandin synthesis.
What happens in normal inflammation?
Neutrophils phagocytose the foreign agent, and inflammation subsides as the stimulus is removed.
What distinguishes chronic inflammation from acute inflammation?
Chronic inflammation occurs when the inflammatory stimulus is not removed, causing continued neutrophil activation and tissue damage.
Why must chronic inflammation be controlled pharmacologically?
Chronic inflammation can cause prolonged tissue damage and maladaptive responses.
What is the initiating event of rheumatoid arthritis?
The initiating event is unknown, but there is a genetic predisposition.
What is the role of Rheumatoid Factor (RF) in RA?
RF is an IgM antibody against IgG, produced by B-cells in the synovial fluid, and triggers the complement system, causing tissue damage and attracting neutrophils and macrophages.
How do IL-1 and TNF-α contribute to RA?
IL-1 and TNF-α produced by pannus promote bone resorption and joint destruction through osteoclast activation.
What is pannus in RA?
Pannus is scar-like tissue formed by neutrophils, macrophages, and fibroblasts that accumulates in the joint.
How do DMARDs differ from NSAIDs in RA treatment?
DMARDs can arrest or slow the progression of RA (e.g., joint erosion), while NSAIDs only manage pain.
How do NSAIDs help in the treatment of RA?
NSAIDs inhibit COX, block prostaglandin synthesis, and reduce pain sensitivity but do not affect joint disease progression.
What are the differences between the generations of NSAIDs?
1st generation: Aspirin (irreversible COX inhibition, GI side effects).
2nd generation: Ibuprofen (reversible COX inhibition, fewer GI effects).
3rd generation: Naproxen (longer half-life, less frequent dosing).
4th generation: Celecoxib (COX-2 selective inhibitor).
What are examples of first-generation DMARDs?
Gold compounds (e.g., aurothioglucose), which accumulate in monocytes and macrophages, interfering with migration and phagocytosis.
What are examples of second-generation DMARDs?
B/T cell inhibitors such as methotrexate and leflunomide.
What is the mechanism of methotrexate in RA treatment?
Methotrexate increases adenosine production, signaling through adenosine receptors, which reduces inflammation, including T cell inhibition.
What is the mechanism of leflunomide in RA treatment?
Leflunomide blocks pyrimidine synthesis, leading to cytotoxic effects on T cells.
What are third-generation DMARDs (“biologics”) in RA treatment?
TNF-α inhibitors (e.g., etanercept, infliximab), IL-6 inhibitors (e.g., tocilizumab), and JAK inhibitors (e.g., tofacitinib).
What was the old paradigm for treating RA?
Treat conservatively with NSAIDs, and switch to DMARDs only when necessary in later stages.
What is the new paradigm for treating RA?
Treat aggressively with DMARDs as soon as RA is diagnosed to take advantage of the “window of opportunity.”
