Non-Opioid Analgesics - NSAIDs/APAP

Question 1

major target for NSAIDs

Answer 1

COX 2

Question 2

how is PG synthesis inhibited

Answer 2

inhibiting COX 1 AND COX 2

beneficial and risky

Question 3

3 eicosanoids

Answer 3

PG

thromboxanes

LT

Question 4

3 non selective COX inhibitors

Answer 4

ibuprofen

naproxen

ketorolac (toradol)

Question 5

2 selective COX 2 inhibitors

Answer 5

celecoxib

APAP

Question 6

harmful actions mediated by COX 2 eicosanoids that are mediated by NSAIDs

Answer 6

pain

inflammation

fever

Question 7

beneficial actions of COX-1 eicosanoids that are diminished by NSAID use

Answer 7

kidney -> diuresis

secretions -> GI

platetelets -> pro -> clotting

Question 8

inhibitory effects of NSAIDs on beneficial effects of COX 2 (5)

Answer 8

GI ulceration/bleeding

renal dysfxn

increased risk of thrombotic events

delayed labor

Question 9

bad effects of NSAIDs are most critical in

Answer 9

elderly pt’s w. deteriorating renal fxn

Question 10

2 main ways non opioid analgesics classified

Answer 10

selectivity → COX 1 vs COX 2

reversible vs irreversible inhibition

Question 11

4 major groups of non opioid analgesics

Answer 11

NSAIDs

celecoxib

APAP

ASA

Question 12

which non opioid analgesics are reversible

Answer 12

NSAIDs

celecoxib

APAP

Question 13

which non opioid analgesic is irreversible

Answer 13

ASA

Question 14

which non opioid analgesics inhibit COX 1 AND COX 2

Answer 14

NSAIDs → reversible

ASA → irreversible

Question 15

celecoxib and APAP inhibit

Answer 15

COX 2

reversible

Question 16

where does APAP inhibit COX 2

Answer 16

CNS

Question 17

major dose dependent therapeutic uses of COX -2 inhibitors

Answer 17

analgesia

antipyretic

AI

Question 18

which effect of COX-2 inhibitors requires the highest dose

Answer 18

anti-inflammatory

Question 19

effect of COX-1 inhibitors that requires low daily dosing

Answer 19

antithrombotic

Question 20

common s.e of COX inhibitors

Answer 20

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

Question 21

which COX are found in the kidney

Answer 21

COX 1 AND COX 2

Question 22

3 clinical uses of NSAIDs (NS COX inhibitors)

Answer 22

pain

antipyretic

anti-inflammatory

Question 23

t/f: NSAIDs are as effective or superior to ASA and APAP for pain of inflammatory origin (muscle/dental/arthritis)

Answer 23

T!

Question 24

what NSAID is available IM/IV for postop pain

Answer 24

ketorolac

Question 25

which NSAID is available as a solution for pediatric fever

Answer 25

ibuprofen APAP

Question 26

t/f: NSAIDs are as effective or superior to ASA/APAP for antipyretic effects

Answer 26

T!

Question 27

t/f: efficacies of NSAIDs/APAP/ASA are similar for anti-inflammatory effects

Answer 27

F!

Question 28

is absorption of NSAIDs affected by food

Answer 28

no

Question 29

NSAIDs are distributed to __ after repeated dosees

Answer 29

synovial fluid

Question 30

metabolism/elimination of NSAIDs

Answer 30

metabolism: liver (CYP enzymes) → elimination: renal

Question 31

list NSAIDs in order of shortest to longest t½

Answer 31

ibuprofen celecoxib naproxen

Question 32

3 relative contraindications for NSAIDs

Answer 32

**PUD** → *interfere w. gastric cytoprotection via COX-1* ## Footnote **antiplatelet/anticoagulant use** **ASA/NSAID triad** **HTN** **DM** **CKD** **HF**

Question 33

2 meds to manage mild dyspepsia

Answer 33

antacids PPI (omeprazole)

Question 34

education for pt taking low dose ASA for cardioprotective effect who also needs to take NSAIDs for pain/inflammation

Answer 34

ASA 1 hr later -\> NSAID

Question 35

is renal insufficiency caused by NSAIDs reversible

Answer 35

yes

Question 36

all \_\_, along with __ cause fluid retention and should be used cautiously in pt's w. \_\_

Answer 36

NSAIDs celecoxib CVD

Question 37

what is the ASA/NSAID triad

Answer 37

**hypersensitivity** to ASA/NSAIDs chronic rhinosinusitis w. **nasal polyps** **bronchial asthma**

Question 38

why are GC better for asthmatics

Answer 38

decrease LT AND PGs

Question 39

why are NSAIDs bad for asthmatics

Answer 39

decrease PGs ## Footnote **increase LTs**

Question 40

3 indications for celecoxib (selective COX 2 inhibitor)

Answer 40

inflammation acute pain primary dysmenorrhea

Question 41

2 inflammatory conditions French pointed out for celecoxib

Answer 41

RA ankylosing spondylitis

Question 42

benefits of celecoxib outweigh risks in pt's who can not tolerate NSAIDs due to \_\_, but risks outweigh benefits in pt's w. \_\_

Answer 42

GI s.e CVD

Question 43

5 pt pops who might benefit from celecoxib

Answer 43

age \> 65 yo anticoag use prior GI bleed active PUD concurrent use of oral GC

Question 44

besides celecoxib, 2 other safe options for pt's at high risk for GI s.e w. NSAIDs

Answer 44

NSAID PLUS PPI NSAID PLUS misoprostol

Question 45

what class of drug is misoprostol

Answer 45

PG analog

Question 46

does celecoxib alter platelet fxn or increase bleeding risk

Answer 46

no! → does not inhibit COX 1

Question 47

celecoxib increases the risk of (2)

Answer 47

ischemic CVD HF

Question 48

how does celecoxib increase risk for ischemic CVD and HF

Answer 48

blocks COX 2 → elevates bp decreases renal fxn

Question 49

black box warning for celecoxib

Answer 49

adverse CV thrombotic events (similar risk to NS NSAIDs) hypersensitivity rxn dt **sulfa moiety**

Question 50

GI risk: higher w. inhibition of COX 1 or COX 2

Answer 50

higher w. COX 1

Question 51

GI risk is lowest w. \_\_ and highest w. \_\_

Answer 51

lowest: ibuprofen (followed by celecoxib) highest: naproxen

Question 52

CV risk: higher w. inhibition of COX 1 or COX 2

Answer 52

equal!

Question 53

renal risk: higher w. inhibition of COX 1 or COX 2

Answer 53

equal!

Question 54

alternative for pt w. HTN, DM, HF, CKD

Answer 54

APAP tramadol opioids

Question 55

t/f: APAP is less effective than NSAIDs for pain

Answer 55

F

Question 56

t/f: for antipyretic effects, APAP is effective or superior to ASA/NSAIDs

Answer 56

T!

Question 57

does APAP have anti-inflammatory action

Answer 57

no! *may have some use in OA*

Question 58

why doesn't APAP have anti inflammatory action

Answer 58

it **inhibits central cytokine release**, but not peripheral inflammation

Question 59

absorption rate of APAP is related to \_\_ and is faster w. \_\_

Answer 59

gastric emptying liquid preps

Question 60

APAP is metabolized to (2)

Answer 60

sulfate glucuronide

Question 61

a small % of APAP is metabolized to \_\_

Answer 61

hepatotoxic metabolite

Question 62

ellimination/metabolism of APAP is unaffected by

Answer 62

renal fxn

Question 63

when you think elimination/metabolism of APAP, think phase

Answer 63

2

Question 64

t/f: APAP has few-no s.e when compared to NSAIDs

Answer 64

T! *bc it doesn't work on peripheral COX 1 or COX 2*

Question 65

major concern w. APAP

Answer 65

hepatotoxicity

Question 66

at what dose is risk of hepatotoxicity increased w. APAP

Answer 66

1000mg

Question 67

does 1000 mg of APAP provide greater analgesia

Answer 67

no!

Question 68

chronic ethanol induces \_\_ and depletes protective \_\_

Answer 68

CYP2E1 GSH

Question 69

be aware of APAP in __ products

Answer 69

opioid combo → percocet vicodin

Question 70

risk of APAP in opioid products

Answer 70

tolerance develops → need higher doses → hepatotoxicity

Question 71

tx for APAP overdose

Answer 71

**N-acetylcysteine** → replenishes GSH and inactivates Ac directly

Question 72

Phase 1 rxns

Answer 72

oxidation hydrolysis reduction

Question 73

phase 1 enzyme to know

Answer 73

CYP450

Question 74

inducing/inhibiting action of CYP450

Answer 74

significant

Question 75

saturability of CYP450

Answer 75

minimal

Question 76

phase II rxns

Answer 76

**conjugations** → n-acetylation glutathione glucoronidation sulfation

Question 77

phase II enzyme to know

Answer 77

transferase

Question 78

saturability of transferase

Answer 78

substantial