Nonopioid Analgesics

Question 1

__________ are released from injured cells.

Answer 1

Alarmins

Question 2

____________ can produce ‘degranulation’ of mast cells.

Answer 2

Alarmin IL-33

Question 3

What is the mast cells response to IL-33?

Answer 3

Release histamine

Leads to local vasodilation and edema

Question 4

What type of receptor does histamine act through in the endothelium?

Answer 4

GPCR

Gq -> increased PLC -> IP3 -> increased calcium

Gq -> increased PLA -> increased NO and increased MLCK activity -> NO causes smooth muscle to relax & MLCK causes leaky endothelium

Question 5

T/F: If pain is managed by opioids, anti-inflammation has no value.

Answer 5

False

Still beneficial to reduce inflammation and attenuate production of prostaglandins

Question 6

____________ lead to pain sensitization and more inflammation.

Answer 6

Prostaglandins

Question 7

What are all prostaglandins derived from?

Answer 7

Arachidonic acid

Question 8

Which enzymes send the arachidonic acid down the pathway leading to prostaglandin production?

Answer 8

COX1 and COX2

Question 9

T/F: COX1 leads to inflammation and is a target of NSAIDS.

Answer 9

False

COX2 leads to inflammation

COX1 leads to homeostatic functions

Question 10

Which inflammatory mediators activate and inhibit COX2?

Answer 10

Activate - IL-1, TNF, growth factors

Inhibit - glucocorticoids, IL-4

Question 11

Prostaglandins react with __________.

Answer 11

GPCR

Question 12

T/F: Prostaglandins play a key role in the inflammatory response and pain sensitization.

Answer 12

True

Question 13

T/F: Prostaglandins only act to sensitize pain response at the periphery.

Answer 13

False

Also sensitize pain response centrally making it more likely for a threshold to be reached

Question 14

How do all NSAIDS work?

Answer 14

Inhibit COX enzymes -> less PG production

Question 15

Why is aspirin one of the worst NSAIDS?

Answer 15

It is 100x more selective for COX1 over COX2

Question 16

Which NSAID has the best selectivity for COX2?

Answer 16

Naproxen

Question 17

What effects are seen with aspirin (acetylsalicylic acid)?

Answer 17

Decreased pain, fever, inflammation, and thrombosis

Question 18

What effects are seen with ibuprofen and naproxen?

Answer 18

Decreased pain, fever, and inflammation

Question 19

What effects are seen with acetaminophen (Tylonal)?

Answer 19

Decreased pain and fever

Question 20

Why might aspirin lead to a decrease in thrombosis?

Answer 20

NSAIDS inhibit COX enzymes -> inhibit TXA2 production -> inhibits platelet aggregation

Aspirin is an irreversible inhibitor making it better at preventing thrombosis

Question 21

What are the two major factors that make aspirin an anti thrombotic drug?

Answer 21

1) Platelets have no nucleus (cant make new COX enzymes)
2) Aspirin is an irreversible inhibitor

Inhibits COX irreversibly and cell cant make more COX

Question 22

T/F: Acetaminophen (tylonal) is a good anti-inflammatory.

Answer 22

False

Question 23

What is one of the biggest adverse effects of NSAIDS?

Answer 23

Inhibit mucus secretion in the stomach - stomach less effective at producing bicarb lining

Question 24

T/F: NSAIDS may cause increased bleeding times, kidney problems, increased BP, and heart failure.

Answer 24

True

Question 25

What is Reye’s Syndrome?

Answer 25

Normally seen in children - toxic reaction to nontoxic levels of aspirin

Question 26

What are some contraindications for aspirin?

Answer 26

Ulcer, diabetes, gout, and hypocoagulation conditions

Question 27

T/F: Selective COX-2 inhibitors are heavily backed with research.

Answer 27

False

Side effects are not well understood.

Celebrex is the only approved one

Question 28

What is the most effective therapy for analgesia?

Answer 28

Optimum does of NSAID and additional opioid

Question 29

Which NSAID is the most susceptible to liver toxicity?

Answer 29

High doses of acetaminophen