NSAIDS Flashcards
what pathways do NSAIDs block?
Cyclooxygenase 1 and 2 (and thus prostanoids)
what do eicosanoids bind to?
prostaglandins, thrombaxanes, leukotrienes
enzyme expression seen with Cox-1
TXA2 in platelets
enzyme expression seen with Cox-2
PGE/TXA2 in activated macrophages
For COX-1 and COX-2: which is constitutively expressed and which is induced?
COX-1 is constitutive
COX-2 is induce by stress
Major side effect of inhibition of COX-1
GI related problems
Prostaglandins regulate stomach acids- inhibition can cause bloody stools, stomach bleeding, anemia…
Major difference between aspirin and other NSAIDs
aspirin is an irreversible inhibitor
NSAID uses
analgesia, anti-pyretic
only at high doses is it anti-inflammatory
one potential good side effect of NSAIDs, now being researched?
cancer prevention
common NSAID side effects
GI- pain, nausea, diarrhea, ulcers, perforation
Renal- insufficiency, failure, low efficacy of HTN Rx
MI !!! black box warning
can you use NSAIDs in pregnancy
No- prostaglandins involved in uterin fxn
prolonged gestation, post-partum hemorrhage
what is acetylsalicylic acid and why is it special?
aspirin
non-selective for COX-1 and and COX-2
Irreversible- acetylates serine- kills enzyme
contraindication of aspirin
use in children- Reye’s syndrome
antipyretic effect of aspirin
only works at low doses
high doses can induce pyretic effect
therapeutics of aspirin
cardioprotective- decreases platelet aggregation for 4-7 days
decrease MI risk (only in at-risk individuals)
where is aspirin secreted
proximal tubule and glomerular filtration
need to adjust dose in renal failure
how to prevent GI problems (drug)
co-formulation with misoprostol (or other proton-pump inhibitor)
aspirin hypersensitivity
induced effect- neoantigen formation
common in people with nasal polyps
cross sensitivity with NSAIDs
side effects with toxic doses of aspirin
tinnitus
respiratory and metabolic acidosis
only NSAIDs for IV use
ibuprofen and ketorolac
half-life of ibuprofen
2 hours
max daily dose of ibuprofen
2400mg
half life of naproxen
14 hours
patients have more GI effects on ibuprofen or naproxen?
naproxen
half life of celebrex
11 hours
which pathway does celebrex inhibit
cox-2
side effect not seen with celebrex that is seen with other NSAIDs
GI problems
who is contraindicated for celebrex
CAD or cerebrovascular disease
sulfa allergies
what does a COX-2 inhibitor prevent
vasodilation, inhibition of platelet aggregation (i.e. celebrex causes more platelet aggregation)
when is misoprostol contraindicated
used to induce labor- don’t use in early pregnancy- causes termination
toxicity of acetaminophen
liver (depletion of GSH)
therapeutic effects of acetaminophen
anti-pyretic
analgesic
NOT an anti-inflammatory
which pathways are inhibited by acetaminophen (irreversibly)
cox-1, cox-2 and possibly cox-3? (unknown)
when to not take acetaminophen
when drinking alcohol
favors toxic pathway for acetaminophen metabolism
treatment for acetaminophen OD
N-acetylcysteine (stops liver damage)
