PHRM 825: Inflammation Flashcards
When does inflammation occur?
When there is infection of noxious stimuli
What does inflammation do?
- Eliminates harmful agents and necrotic cells
- Initiates healing process
Signs of inflammation
- Heat
- Redness
- Swelling
- Pain
- Loss of function (like in arthritis)
What cells accumulate in acute inflammation?
Neutrophils
What cells accumulate in chronic inflammation?
Lymphocytes and macrophages
What cytokines cause acute inflammation?
Tumor necrosis factor (TNF)
IL-1
Chemokines
What cytokines cause chronic inflammation?
Interferon-gamma (IFN-gamma) by T cells
IL-12 by macrophages
What are eicosanoids?
Short-lived mediators (seconds-minutes) that act in autocrine and paracrine signaling and bind to G-protein coupled receptors
What does generation of cAMP by eicosanoids cause?
Dilation
What does release of calcium by eicosanoids cause?
Constriction
What doe PGE2 cause in the blood vessels?
Dilation
What does PGF2alpha cause in the blood vessels?
Constriction
What does PGI2 cause in the blood vessels?
Dilation
What does PGI2 do in regards to platelets?
Inhibits aggregation
What does TXA2 cause in the blood vessels?
Constriction
What does TXA2 do in regards to platelets?
Causes aggregation
How many carbons do eicosanoids have?
20
What is the most abundant and important precursor to eicosanoids?
Arachidonic acid
What are the 4 pathways of oxygenation of arachidonic acid?
- PGH synthase (COX) pathway
- Lipoxygenase pathway
- Epoxygenase (CYP450) pathway
- Isoprostane pathway (free radical reaction)
What enzyme has housekeeping functions such as GI cytoprotection?
COX-1
What do NSAIDs block?
Synthesis of prostaglandins and thromboxane
They do NOT block the synthesis of leukotrienes
What do PGH2alpha, PGE2, PGI2, and TXA all arise from?
PGH2
What are 4 ways to block eicosanoid activity?
- Corticosteroids
- NSAIDs
- Selective inhibition of thromboxane
- Inhibition of leukotriene
What do lipocortins inhibit?
Phospholipase A2
What is pannus?
Proliferating synovial cells mixed with immune cells and connective tissue
What is ankylosis and when does it occur?
Joint fusion - Rheumatoid arthritis
What does DMARD stand for?
Disease modifying anti-rheumatic drug
How is RA commonly treated?
Aggressive treatment with DMARDs right after diagnosis
