Test 2: 25 antiinflam Flashcards
5 signs of inflammation
heat
redness
swelling
pain
loss of function
chronic inflammation results in formation of
fibrous tissue
why treat inflammation
reduce pain
prevent loss of function
accelerate resolution of inflammation
limit fibrosis and degeneration
what are some mediators of acute inflammation
prostaglandins
leukotrienes
bradykinin
serotonin
histamine
what are some mediators of chronic inflammation
PDF3- stimulate fibrosis
TNF ⍺, interleukins, interferons
all stimulate acute inflammation factors and cell activation
prostaglandins and leukotrienes are made from
arachoidonic acid
(increased Ca, TNF, interleukins and interferons can all increase production)
what is rate limiting step to make leukotrienes and prostandlandins
PLA2= phospholipase A2
takes membrane phospholipids and turns it into Arachidonic acid
from there AA can become
* (5-LOX) →Leukotreines
* (COX1 and COX2) → prostanoids
leukoteienes are produced by — cells
leukocytes: neutrophils, mast cells, monocytes, macrophages
lungs
mediate inflammation and bronchoconstriction and mucus production in airways →asthma
what do leukotrienes do?
mediate inflammation and bronchoconstriction and mucus production in airways →asthma
arachidonic acid (—)→ leukotrenes
5-LOX (5-lipoxygenase)
NSAID and aspirin block what part of inflammation cascade
COX1 and CO2
prevenets arachidonic acid →prostanoids
Prostaglandins sensitize — to other inflammatory mediators (—)
nociceptors
i.e. bradykinin
inflammation associated pain
prostacyclin
made by vascular endoethial cells
inhibits platelet aggregation
causes vasodilation/ inhibits smooth muscle contraction
thromboxane is made by — and does —
platelets and macrophages
Promotes platelet aggregation (antagonist for PGI2(prostacyclin))
Vasoconstriction- causes smooth muscle contraction
— causes platelet aggregation and vasoconstriction
— inhibits platelet aggregation, and causes vasodilation
TXA2 (thromboxane)
* synthesized by platelets + macrophages
* Promotes platelet aggregation (antagonist for PGI2)
* Vasoconstriction- causes smooth muscle contraction
PGI2 (prostacyclin)
* synthesized by vascular endothelial cells
* Inhibits platelet aggregation
* Vasodilation -inhibits smooth muscle contraction
how do eicosanoids work
bind to GPCR and induce changed in intracellular calcium levels
eicosanoids = prostaglandins
grapiprant/galliprant works by
inhibit EP4 receptors
prostaglandin receptor
blocks pain stimuli from inflammation
COX1 is found in— cells and does —
platelets and other cell
housekeeping enzyme- required for cell-cell signaling, tissue homeostasis and gastric cytoprotection
PGEs stimulate bicarbonate and mucous secretions in gastric mucosa
how does COX1 cause gastric cytoprotection
PGEs stimulate bicarbonate and mucous secretions in gastric mucosa
this is why you can get gastric ulcers with NSAID cause it blocks COX1
COX2 main function
is expressed during inflammation and causes inflammatory response
— transcription factor is a major regulator of the immune response
NK κB
how does NFκB work during inflammation
will activate and enter nucleus and cause formation of COX2, iNOS and cytokines
does a lot of other stuff
how to stop formation of AA from membrane phospholipids
corticosteroids
blocks Phopholipase A2 (PLA2)
Asprin and NSAID block what part of arachidonic pathway
inhibits COX 1 and 2
stops production of prostaglandins
— is a Non-selective Cox inhibitors
classic NSAIDS: aspirin, ibuprofen
— is a Weakly Cox2-selective drug
carprofen
— Strongly Cox2-selective drugs
coxibs
— is a EP4 receptor inhibitors
Grapiprant/Gallaprant
EP4 is a prostaglandin receptor that leads to pain stimuli from inflammation
