-
inflammatory mediator
vasodilator, increases permeability
histamine
-
inflammatory mediator
potent mediator of pain
bradykinin
-
inflammatory mediator
vasodilator, chemotactic
prostaglandin
-
inflammatory mediator
increases permeability, chemotactic
leukotriene
-
4 main effects of chronic inflammation meidators
- cell activation
- PG-production
- fibroblast
- chemotaxis
- proliferation
-
what is stimulated by inflammation that causes leukocytes to slow and start rolling
E-selectin
-
mediates sticking of the leukocytes to the endothelial wall
-
leukocyte migration through the edothelial wall
diapedesis
-
chemotaxis
chemokines, leukotrienes, cytokines, f-MLP
-
housekeeping enzyme
maintains integrity of gastric mucosa
maintains renal function
COX 1
-
inducible enzyme for inflammation
COX 2
-
inhibition of COX 1 results in what 3 things
- gastric ulcer
- renal failure
- protection against acute MI
-
inhibition of COX 2 results in what 3 things
- antiinflammatory
- antipyretic
- analgesic action
-
thromboxane (TxA2) causes
vasoconstriction
-
prostacyclin (PGI2) causes
vasodilation
-
Prostaglandins (PGD2, PGE2, PGF2) causes (3)
- inflammation
- fever
- gastroprotection
-
drug class that inhibits COX
NSAIDS
-
drug group that inhibits Phospholipase A2
steroids
-
phospholipase A2 acts on the cell membrane and produces what
arachidonic acid
-
converts arachidonic acid to leukotrienes
lipoxygenase
-
drug that inhibits lipoxygenase
zileuton
-
leukotriene responsible for chemotaxis
LTB4
-
drug to inhibit LTB4
colchicine
-
drug to inhibit LTD4 from receptor binding
montelukast
-
leukotriene binding causes what
bronchoconstriction
-
what converts arachidonic acid to prostaglandin H2
cyclooxygenase
-
where are thromboxanes produced from
platelets
-
where are protacyclins produced from
endothelium
-
where are prostaglandins (PGD2, PGE2, PGF2) located
blood stream
-
why does low dose aspirin work on platelets and not endothelium
platelets don't have DNA, it is for the life of the cell - 7 days
-
how do NSAIDS induce asthma
by inhibiting COX you shift the mechanism to the LOX side which is bronchoconstriction
-
MOA of aspirin
irreversible non-selective inhibitor of both COX - covalent
-
absorption of aspirin
- rapidly from stomach and small intestine
- hydrolyzed to salicylic acid
-
how does aspirin reduce fever
inhibition of pyrogen-induced PG synthesis
-
what is aspirin inhibiting that causes adverse GI effects
prostaglandins
-
drug to treat aspirin induced GI ulcer
misoprostol (cytotec)
-
doses of > 4g/day can cause what
stones
-
severe side effect of aspirin in children
reye's syndrome
-
aspirin and warfarin
increased bleeding
-
aspirin and glucocorticoids
increased risk of gastric ulcer
-
aspirin and alcohol
increased risk of gastric ulcer
-
aspirin and ibuprofen
reduces platelet effect of aspirin
-
sign of plain aspirin tablets gone bad
odor of vinegar
-
2 differences of aspirin and other first generation NSAIDS
- reversible inhibition of COX
- does not protect against MI
-
4 nonacetylated salicylates (first generation NSAIDS)
- choline salicylate (arthropan)
- magnesium salicylate (magan)
- sodium salicylate
- salsalate (disalcid, mono-gesic)
-
prodrug NSAID
hydrolyzed in alkaline medium to release 2 molecules of salicylates
salsalate (disalcid, mono-gesic)
-
first generation NSAID
propionic acid derivative
ibuprofen (advil, motrin)
-
drug of choice to promote closure of ductus arteriosus in preterm infants
ibuprofen
-
intravenous ibuprofen
caldolor
-
first generation NSAID not metabolized to salicylic acid
T1/2 of 11-15h
diflunical (dolobid)
-
first generation NSAID for gouty arthritis
indomethacin (indocin)
-
first generation NSAID given post-surgery
not to be taken longer than 5 days
more peripheral
ketorolac (Toradol)
-
first generation NSAID with T 1/2 of 50h
piroxicam (Feldene)
-
first generation NSAID
undergoes extensive enterohepatic circulation
prodrug
SE - steven johnson syndrome
sulindac (clinoril)
-
first generation NSAID
approved for rheumatoid arthritis and osteoarthritis (not fever or inflammation)
tolmetin (tolectin)
-
first generation NSAID
more cox 2 inhibition
indicated for osteoarthritis
meloxicam (mobic)
-
2 2nd generation NSAID
- celecoxib (celebrex)
- acetaminophen (tylenol)
-
antidote for acetaminophen overdose and what does it mimic
- acetylcysteine (mucomyst)
- G-SH
-
what metabolizes toxic metabolites of acetominphen to non-toxic
G-SH (glutathione)
-
how does alcohol stimulate acetominophen toxicity
- increase toxic metabolites
- inhibits G-SH
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