NSAIDS

Question 1

what pathways do NSAIDs block?

Answer 1

Cyclooxygenase 1 and 2 (and thus prostanoids)

Question 2

what do eicosanoids bind to?

Answer 2

prostaglandins, thrombaxanes, leukotrienes

Question 3

enzyme expression seen with Cox-1

Answer 3

TXA2 in platelets

Question 4

enzyme expression seen with Cox-2

Answer 4

PGE/TXA2 in activated macrophages

Question 5

For COX-1 and COX-2: which is constitutively expressed and which is induced?

Answer 5

COX-1 is constitutive

COX-2 is induce by stress

Question 6

Major side effect of inhibition of COX-1

Answer 6

GI related problems

Prostaglandins regulate stomach acids- inhibition can cause bloody stools, stomach bleeding, anemia…

Question 7

Major difference between aspirin and other NSAIDs

Answer 7

aspirin is an irreversible inhibitor

Question 8

NSAID uses

Answer 8

analgesia, anti-pyretic

only at high doses is it anti-inflammatory

Question 9

one potential good side effect of NSAIDs, now being researched?

Answer 9

cancer prevention

Question 10

common NSAID side effects

Answer 10

GI- pain, nausea, diarrhea, ulcers, perforation
Renal- insufficiency, failure, low efficacy of HTN Rx
MI !!! black box warning

Question 11

can you use NSAIDs in pregnancy

Answer 11

No- prostaglandins involved in uterin fxn

prolonged gestation, post-partum hemorrhage

Question 12

what is acetylsalicylic acid and why is it special?

Answer 12

aspirin
non-selective for COX-1 and and COX-2
Irreversible- acetylates serine- kills enzyme

Question 13

contraindication of aspirin

Answer 13

use in children- Reye’s syndrome

Question 14

antipyretic effect of aspirin

Answer 14

only works at low doses

high doses can induce pyretic effect

Question 15

therapeutics of aspirin

Answer 15

cardioprotective- decreases platelet aggregation for 4-7 days
decrease MI risk (only in at-risk individuals)

Question 16

where is aspirin secreted

Answer 16

proximal tubule and glomerular filtration

need to adjust dose in renal failure

Question 17

how to prevent GI problems (drug)

Answer 17

co-formulation with misoprostol (or other proton-pump inhibitor)

Question 18

aspirin hypersensitivity

Answer 18

induced effect- neoantigen formation
common in people with nasal polyps
cross sensitivity with NSAIDs

Question 19

side effects with toxic doses of aspirin

Answer 19

tinnitus

respiratory and metabolic acidosis

Question 20

only NSAIDs for IV use

Answer 20

ibuprofen and ketorolac

Question 21

half-life of ibuprofen

Answer 21

2 hours

Question 22

max daily dose of ibuprofen

Answer 22

2400mg

Question 23

half life of naproxen

Answer 23

14 hours

Question 24

patients have more GI effects on ibuprofen or naproxen?

Answer 24

naproxen

Question 25

half life of celebrex

Answer 25

11 hours

Question 26

which pathway does celebrex inhibit

Answer 26

cox-2

Question 27

side effect not seen with celebrex that is seen with other NSAIDs

Answer 27

GI problems

Question 28

who is contraindicated for celebrex

Answer 28

CAD or cerebrovascular disease | sulfa allergies

Question 29

what does a COX-2 inhibitor prevent

Answer 29

vasodilation, inhibition of platelet aggregation (i.e. celebrex causes more platelet aggregation)

Question 30

when is misoprostol contraindicated

Answer 30

used to induce labor- don't use in early pregnancy- causes termination

Question 31

toxicity of acetaminophen

Answer 31

liver (depletion of GSH)

Question 32

therapeutic effects of acetaminophen

Answer 32

anti-pyretic analgesic NOT an anti-inflammatory

Question 33

which pathways are inhibited by acetaminophen (irreversibly)

Answer 33

cox-1, cox-2 and possibly cox-3? (unknown)

Question 34

when to not take acetaminophen

Answer 34

when drinking alcohol | favors toxic pathway for acetaminophen metabolism

Question 35

treatment for acetaminophen OD

Answer 35

N-acetylcysteine (stops liver damage)