NSAIDs Flashcards
______ are inflammatory mediators that can cause bronchospasm.
Leukotrienes, PGs, TXA
______ is a potent vasodilator and platelet inhibitor generated mostly by COX-2
prostacyclin
_______ is a potent vasoconstrictor and platelet aggregator generated mostly by COX-1
TXA2
This drug is a nonselective, irreversible COX1 and COX2 inhibitor
ASA
describe the kinetics of ASA at high doses above 600mg…
zero order
________ of urine promotes excretion of ASA
Alkalinization
acids ionize in basic soln., ionized cannot cross membranes
4 effects of ASA
analgesic
antipyretic
anti-inflammatory
anti-platelet
how long does ASA last? why?
8-10 days… until new platelets
Long term use of ASA decreases risk of…
CRC
Progression of ASA metabolic adverse effects…
low dose respiratory alkalosis
THEN
high dose metabolic/resp acidosis
A single dose of ASA ______ bleeding time
doubles
ASA should be stopped _______ before elective surgery
1 week
______ doses of ASA decrease uric acid excretion, _______ doses increase uric acid excretion
Low ASA = decreased
High ASA = increased
ASA competes with uric acid at the ______ receptor
OAT-2
ASA asthma occurs due to…
increased leukotrienes (COX inhibition –> 5-LOX activity)
Is ASA teratorgenic?
no
Which NSAID should be avoided with these conditions?
• gastric ulcer • severe hepatic damage • hypoprothrombinemia • Vitamin K deficiency • hemophilia
ASA
Fatal dose of ASA is…
20g
This is a salicylic acid derivative that is NOT metabolized to salicylic acid…
diflunisal
does diflunisal have CNS action and therefore antipyretic action?
no
Reverse COX-2 inhibitor with less gastropathy/GI risk
Celecoxib
What increases the risk fo cardiovascular disease with celecoxib?
increased TXA2 = platelet aggregation
COX-2 Inhibition shifts to favor TXA2 production from COX-1
the below are contraindications for which drug?
GI disease, asthma, breast feeding,
pregnancy, renal failure,
celecoxib
Nonspecific, reversible inhibitor of COX-1 and COX 2 w. lowest SE profile
ibuprofen
ibuprofen has metabolites that produce free radicals… what severe SE can occur due to this?
agranylocytosis, aplastic anemia
This NSAID reduces PMN migration via PLA inhibition
indomethacin
This NSAID has very potent anti-inflammatory effects but has high incidence of SEs-
indomethacin
which NSAID is used for PDA?
indomethacin
This is a potent COX inhibitor that decreases AA bioavailability
diclofenac
what can be combined with NSAIDs to limit GI toxicity?
misoprostol
This is an NSAID that is used as an analgesic in post-op pain, and may be combined with opiates to reduce opiate burden
ketorolac
combining _____ with ASA reduces effects on platelets
ibuprofen
What is the mean half-life of naproxen?
13 hours
does naproxen cross the placental barrier?
yes
what NSAID is bound to plasma proteins, where displacement can cause drug interactions? (particularly warfarin)
naproxen
These two NSAIDs inhibit PMN migration and lymphocyte function. They also decrease ROS production
“-oxicams”
piroxicam, meloxicam
This is an NSAID not on the market in the US, it has serious SEs but is very potent
phenylbutazone
3 side effects of acetaminophen…
skin rash
ASA cross-sensitivity
neutropenia
major serious SE of acetamiophen
hepatic necrosis
What is the dose of acetaminophen that can cause hepatotoxicity?
10-15g
what dose of acetaminophen can be fatal?
25g
2 labs that can show acetaminophen toxicity
serum transaminase
lactic acid dehydrogenase
acetaminophen toxicity can progress to what three things?
encephalopathy, coma, death
______ is responsible for acetaminophen’s liver damage
intermediate metabolite
When does toxicity occur biochemically in acetaminophen administration?
when metabolites exceed reduced glutathione
specific antidote for acetaminophen poisoning and timeline
N-acetylcysteine w/in 10 hours
Which NSAID?
Hx of PUD, but not active
celecoxib
NSAIDs + misoprostol or prazols
Which Analgesic?
active PUD
acetaminophen or opioids
COX1 or COX2?
produces G protective PG production
promotes platelet aggregation and vasoconstriction
COX-1
COX1 or COX2?
Promotes inflammation
inhibits platelet aggregation
promotes vasodilation
COX-2
