NSAIDs and gout Flashcards
what are the molecular inflammatory mediators?
- kinins, neuropeptides, vasoactive amines
- arachadonic metabolites
- cytokines, free radicals, proteases
what are the arachadonic acid metabolites?
PGs, thromboxanes, prostacyclin
what are the functional characteristics of NSAIDs?
analgesia
antipyretic
anti-inflammatory
primary target - PG production via COX1 and COX2
is acetaminophen an NSAID?
no
which COX enzyme is constitutively expressed?
COX1
what role do PGE2 and PGI2 play in inflammation?
edema and vascular permeability
what is the role of COX1?
homeostasis
PGs in stomach mucosa (protective)
what is the role of COX2?
production of inflammatory molecules
essential for normal kidney function
what are the nonselective NSAIDs?
acetylsalicylic acid (aspirin) ibuprofen indomethacin
what is the selective NSAID? is it for COX1 or COX2?
celecoxib
COX2
once in the blood, aspirin is hydrolyzed to what?
salicylic acid
what is the MOA of salicylic acid?
reversible COX inhibitor
does aspirin have a potential for drug interactions? why or why not?
yes
80% bound to plasma proteins
what are the low dose effects of aspirin?
analgesic, antipyretic
what are the high dose effects of aspirin?
antiinflammatory
is the acetylation (an inhibition) of COX reversible or irreversible?
irreversible
the antiinflammatory effects of aspirin come from inhibition of what COX enzyme?
COX2
the analgesic effects of aspirin come from inhibition of what COX enzyme?
COX2
what is the MOA of the antipyretic effects of aspirin?
blocks production of PGs in CNS to reset temperature control at hypothalamus
fall in temperature due to dilation of superficial blood vessels
what is the effect of aspirin on bleeding time?
prolongs
what are the adverse effects of aspirin?
GI tract upset
GI irritation
platelet inhibition
GI tract upset from aspirin use is mediated by the inhibition of what COX enzyme?
COX1
keterolac, naproxen, oxaprozin, piroxicam, and sulindac are what class of drug?
NSAID
which NSAIDs have less GI adverse effects?
COX2 selective inhibitors
what is the main adverse effect of the COX2 selective inhibitors?
CV thrombotic events
what are the COX2 selective inhibitors?
celecoxib
etoricoxib
meloxicam
which COX2 selective inhibitor is approved for rheumatoid arthritis?
celecoxib (celebrex)
what are the actions of acetaminophen? does it have antiinflammatory properties?
analgesic and antipyretic
no
what are the drug interactions for acetaminophen? why?
ethanol, isoniazid
metabolism by cyp450
what is the MOA of capsaicin?
release of substance P leading to depletion and prevention of reaccumulation
gout is characterized by accumulations of what type of crystals?
monosodium urate (uric acid)
what is the primary NSAID used to treat severe gout?
indomethacin
what is the role of colchicine? what is the MOA?
used to be primary gout agent
inhibits leukocyte migration and phagocytosis
what are the xanthine oxidase inhibitors?
allopurinol
febuxostat
what are the uricosuric agents?
probenecid
sulfinpyrazone
allopurinol and febuxostat are what type of drug for gout?
xanthing oxidase inhibitors
probenecid and sulfinpyrazone are what type of drug for gout?
uricosuric
