Anti-inflammatories - NSAIDs

Question 1

Which level do NSAIDs works?

perception, projection, modulation, transmission, transduction?

Answer 1

transduction (skin, muscle, bone, joint, viscera) - reduces inflammation that causes the pain

Question 2

Inflammation can be caused by insults to the body. What is the common insult?

Answer 2

disruption of cell membrane integrity. Membrane phospholipids are exposed to enzymatic attack

Question 3

Name the types of stimuli for inflammation…

Answer 3

physical trauma
thermal
ichhaemia
Ag-Ab interaction
infection

Question 4

Draw ‘review of Inflammation 1-3 flow chart… It forms the basis of the whole lecture!

Answer 4

slide 9…

Question 5

NSAIDs are most effective during which phases?

Answer 5

acute & subacute phases

Question 6

Isoform COX-1 is also known as …? what are its functions?

Answer 6

‘constitutive’ - functions as ‘house-keeping’ and protective roles in blood vessels, GASTROintestinal mucosa & kidney
PGE2 & PGI2

Question 7

Isoform COX-2 is also known as …? what are its functions?

Answer 7

‘induced’ - after insult (ischaemia, infection…) -> mediators of inflammation, pain & pyrexia

Question 8

Most NSAIDs inhibit COX-?

Answer 8

COX-2

Question 9

How does inhibition of COX-2 reduce side effects?

Answer 9

by sparing “good” COX-1

Question 10

How does a drug “know” the difference between a COX-2 & COX-1?…

Answer 10

COX-2 channel is a little wider than COX-1, allowing NSAID to enter & bind to COX-selective site

Question 11

Why is nanna’s knee not cured after admin. of celecoxib when she says she feels better?

Answer 11

The drug (NSAID) stops further ACUTE inflammation via COX-2 -> knee feels better….but….damage from chronic pain is almost permanent -> this treatment aka -> “bandaid solution” in terms of chronic arthritis

Question 12

Firocoxib vs Carprofen…Which NSAID is more potent? Which is more effective as an NSAID? Which is safer?

Answer 12

firocoxib more potent, effective & safer as it is more selective for COX-2

Question 13

Paracetamol pros & cons…

Answer 13

pros - inhibits COX via arachadonic acid, no GIT ulceration

cons - peroxides inactivate paracetamol; only works in brain or mild inflammation; can cause hepatic necrosis in cats

Question 14

How many human deaths in US due to NSAIDs?

Answer 14

16.5k

Question 15

Side effects of NSAIDs are commonly seen where?

Answer 15

1. GI tract
2. Altered PLATELET FUNCTION
3. kidney

Question 16

NSAID side effects are nearly entirely related to the inadvertent inhibition of COX-?

Answer 16

COX-1

Question 17

How do NSAIDs cause side effects in the GI tract…?

Answer 17

inhibiting “good” PGs which inhibit acid secretion, increase mucosal blood flow & mucous production -> erosion, ulceration & haemorrhage

Question 18

Re. side effects in the GI tract…how can they be alleviated? 3 methods…

Answer 18

1. H-2 blockers (ranitidine) & PPI (omeprazole) - GOLD STANDARD FOR TREATING ULCERS -> decreases acid secretion
2. PGE1 analogue (misoprostol) (ulcer prevention)
3. sucralfate (protects ulcers already formed)

Question 19

How do NSAIDs cause ALTERED PLATELET FUNCTION…?

Answer 19

NSAIDs decrease thromboxane & PGI2 -> a net decrease in platelet aggregation potentially resulting in abnormal bleeding

Question 20

How do NSAIDs cause side effects in the kidney…?

Answer 20

PGE2 & PGI2 (increase salt & water excretion & blood flow to kidney) & when NSAIDs inhibits them -> Water retention → hypertension & decreased renal blood flow papillary → necrosis and nephritis

Question 21

Safest NSAID & why?

Answer 21

celecoxib as it targets COX-2 moreso than COX-1

Question 22

List the NSAID indications…

Answer 22

• analgesia: sx (desexing, orthopedics), trauma, arthritis

- anti-inflammatory

Question 23

NSAIDs commonly used in small animals…List & briefly discuss their clinical use and potential side-effects (SE)

Answer 23

• meloxicam: good analgesic (peri-operative); good for exotics; cat-friendly preps [low]
• firocoxib: lowest SEs (COX-2 selective); good analgesia (esp chronic therapy)
• carprofen: very commonly used, good analgesia (peri-op)

Question 24

NSAIDs commonly used in production animals…List & briefly discuss their clinical use and potential side-effects (SE)

Answer 24

• flunixin: old, cheap, established WHPs, trusted

- tolfenamic acid: more $, possibly fewer SEs than flunixin, established WHPs

Question 25

NSAIDs commonly used in equines…List & briefly discuss their clinical use and potential side-effects (SE)

Answer 25

• flunixin: VERY COMMONLY USED; EXCELLENT analgesic for COLIC horses
• phenylbutazone: VERY COMMONLY USED; no COX-1/ COX-2 selectivity -> causes SEs

Question 26

What are the clinical role of Dietary Fatty Acids (FAs)? What are the 2 clinically significant FAs? MOA?

Answer 26

• clinically used for arthritis, allergic skin conditions
• DHA; omega-3 & EPA; omega-3
• MOA: competitive inhibition at phospholipase region

Question 27

List some non-NSAID anti-arthritis drugs (chondroprotectives)…

Answer 27

• glucosamine
• chondroitin sulphate
• shark cartilage
• green-lipped mussel
• hyaluronan
• polysulfated glycosaminoglycans

Question 28

Admin, MOA & safety of glucosamine…?

Answer 28

oral for human & animals
MOA: stim. of hyaluronic acid prod. & collagen & proteoglycan synthesis -> improves cartilage matrix
safe

Question 29

Admin, MOA & safety of chondroitin sulphate…?

Answer 29

oral for human & animals (many contain glucosamine)
MOA: main glycosaminoglycan in cartilage
safe

Question 30

Admin, MOA & safety of shark cartilage…?

Answer 30

shit & ethics associated

Question 31

Admin, MOA & safety of green-lipped mussel…?

Answer 31

combo of glycosaminoglycans, omega-3 FAs, AAs & vits & minerals
safe

Question 32

Admin, MOA & safety of Hyaluronan…?

Answer 32

Essential component of synovial fluid, a lubricant - associated with poor studies (no positive effects & no mention of SEs)

Question 33

Admin, MOA & safety of Polysulfated Glycosaminoglycans…?

Answer 33

Inhibition of soluble mediators (eg proteases, collagenase, elastase) of inflammation..