Non-Opioid Analgesics - NSAIDs/APAP Flashcards
major target for NSAIDs
COX 2
how is PG synthesis inhibited
inhibiting COX 1 AND COX 2
beneficial and risky
3 eicosanoids
PG
thromboxanes
LT
3 non selective COX inhibitors
ibuprofen
naproxen
ketorolac (toradol)
2 selective COX 2 inhibitors
celecoxib
APAP
harmful actions mediated by COX 2 eicosanoids that are mediated by NSAIDs
pain
inflammation
fever
beneficial actions of COX-1 eicosanoids that are diminished by NSAID use
kidney -> diuresis
secretions -> GI
platetelets -> pro -> clotting
inhibitory effects of NSAIDs on beneficial effects of COX 2 (5)
GI ulceration/bleeding
renal dysfxn
increased risk of thrombotic events
delayed labor
bad effects of NSAIDs are most critical in
elderly pt’s w. deteriorating renal fxn
2 main ways non opioid analgesics classified
selectivity → COX 1 vs COX 2
reversible vs irreversible inhibition
4 major groups of non opioid analgesics
NSAIDs
celecoxib
APAP
ASA
which non opioid analgesics are reversible
NSAIDs
celecoxib
APAP
which non opioid analgesic is irreversible
ASA
which non opioid analgesics inhibit COX 1 AND COX 2
NSAIDs → reversible
ASA → irreversible
celecoxib and APAP inhibit
COX 2
reversible
where does APAP inhibit COX 2
CNS
major dose dependent therapeutic uses of COX -2 inhibitors
analgesia
antipyretic
AI
which effect of COX-2 inhibitors requires the highest dose
anti-inflammatory
effect of COX-1 inhibitors that requires low daily dosing
antithrombotic
common s.e of COX inhibitors
GI ulceration → COX 1
increased bleeding risk → COX 1
delayed labor → COX 2
increased thrombotic events → COX 2
renal dysfxn → COX 1 and COX 2
which COX are found in the kidney
COX 1 AND COX 2
3 clinical uses of NSAIDs (NS COX inhibitors)
pain
antipyretic
anti-inflammatory
t/f: NSAIDs are as effective or superior to ASA and APAP for pain of inflammatory origin (muscle/dental/arthritis)
T!
what NSAID is available IM/IV for postop pain
ketorolac
which NSAID is available as a solution for pediatric fever
ibuprofen
APAP
t/f: NSAIDs are as effective or superior to ASA/APAP for antipyretic effects
T!
t/f: efficacies of NSAIDs/APAP/ASA are similar for anti-inflammatory effects
F!
is absorption of NSAIDs affected by food
no
NSAIDs are distributed to __ after repeated dosees
synovial fluid
metabolism/elimination of NSAIDs
metabolism: liver (CYP enzymes) →
elimination: renal
list NSAIDs in order of shortest to longest t½
ibuprofen
celecoxib
naproxen
3 relative contraindications for NSAIDs
PUD → interfere w. gastric cytoprotection via COX-1
antiplatelet/anticoagulant use
ASA/NSAID triad
HTN
DM
CKD
HF
2 meds to manage mild dyspepsia
antacids
PPI (omeprazole)
education for pt taking low dose ASA for cardioprotective effect who also needs to take NSAIDs for pain/inflammation
ASA
1 hr later -> NSAID
is renal insufficiency caused by NSAIDs reversible
yes
all __,
along with __ cause fluid retention
and should be used cautiously in pt’s w. __
NSAIDs
celecoxib
CVD
what is the ASA/NSAID triad
hypersensitivity to ASA/NSAIDs
chronic rhinosinusitis w. nasal polyps
bronchial asthma
why are GC better for asthmatics
decrease LT AND PGs
why are NSAIDs bad for asthmatics
decrease PGs
increase LTs
3 indications for celecoxib (selective COX 2 inhibitor)
inflammation
acute pain
primary dysmenorrhea
2 inflammatory conditions French pointed out for celecoxib
RA
ankylosing spondylitis
benefits of celecoxib outweigh risks in pt’s who can not tolerate NSAIDs due to __,
but risks outweigh benefits in pt’s w. __
GI s.e
CVD
5 pt pops who might benefit from celecoxib
age > 65 yo
anticoag use
prior GI bleed
active PUD
concurrent use of oral GC
besides celecoxib, 2 other safe options for pt’s at high risk for GI s.e w. NSAIDs
NSAID PLUS PPI
NSAID PLUS misoprostol
what class of drug is misoprostol
PG analog
does celecoxib alter platelet fxn or increase bleeding risk
no! → does not inhibit COX 1
celecoxib increases the risk of (2)
ischemic CVD
HF
how does celecoxib increase risk for ischemic CVD and HF
blocks COX 2 →
elevates bp
decreases renal fxn
black box warning for celecoxib
adverse CV thrombotic events (similar risk to NS NSAIDs)
hypersensitivity rxn dt sulfa moiety
GI risk: higher w. inhibition of COX 1 or COX 2
higher w. COX 1
GI risk is lowest w. __
and highest w. __
lowest: ibuprofen (followed by celecoxib)
highest: naproxen
CV risk: higher w. inhibition of COX 1 or COX 2
equal!
renal risk: higher w. inhibition of COX 1 or COX 2
equal!
alternative for pt w. HTN, DM, HF, CKD
APAP
tramadol
opioids
t/f: APAP is less effective than NSAIDs for pain
F
t/f: for antipyretic effects, APAP is effective or superior to ASA/NSAIDs
T!
does APAP have anti-inflammatory action
no!
may have some use in OA
why doesn’t APAP have anti inflammatory action
it inhibits central cytokine release, but not peripheral inflammation
absorption rate of APAP is related to __
and is faster w. __
gastric emptying
liquid preps
APAP is metabolized to (2)
sulfate
glucuronide
a small % of APAP is metabolized to __
hepatotoxic metabolite
ellimination/metabolism of APAP is unaffected by
renal fxn
when you think elimination/metabolism of APAP, think phase
2
t/f: APAP has few-no s.e when compared to NSAIDs
T!
bc it doesn’t work on peripheral COX 1 or COX 2
major concern w. APAP
hepatotoxicity
at what dose is risk of hepatotoxicity increased w. APAP
1000mg
does 1000 mg of APAP provide greater analgesia
no!
chronic ethanol induces __
and depletes protective __
CYP2E1
GSH
be aware of APAP in __ products
opioid combo →
percocet
vicodin
risk of APAP in opioid products
tolerance develops → need higher doses → hepatotoxicity
tx for APAP overdose
N-acetylcysteine → replenishes GSH and inactivates Ac directly
Phase 1 rxns
oxidation
hydrolysis
reduction
phase 1 enzyme to know
CYP450
inducing/inhibiting action of CYP450
significant
saturability of CYP450
minimal
phase II rxns
conjugations →
n-acetylation
glutathione
glucoronidation
sulfation
phase II enzyme to know
transferase
saturability of transferase
substantial
