NSAIDs

Question 1

Define pharmacokinetics

Answer 1

What the body does to the drug

Question 2

Define pharmacodynamics

Answer 2

What the drug does to the body

Question 3

What is the therapeutic window of NSAIDs?

Answer 3

Narrow

Question 4

What do NSAIDs block?

Answer 4

Prostaglandins

Question 5

Where do NSAIDs act? (2)

Answer 5

• Periphery
• Spinal cord

Question 6

Where do steroids act in the pathway? What is the negative of this?

Answer 6

At phospholipase, which is one stage higher than NSAIDs and you therefore get more side effects

Question 7

Where do NSAIDs act in the pathway?

Answer 7

Cyclooxygenase

Question 8

Name 5 things NSAIDs have been shown to inhibit in horses (7)

Answer 8

–Inflammation

–Fever

–Oedema

–‘Endotoxaemia’ (??)

–Ileus

–Adhesion formation

–(thrombosis formation)

Question 9

Which NSAID can we use in inflammatory visceral disease in equine?

Answer 9

Flunexin

Question 10

What can occur with poor IV administration of phenylbutazone?

Answer 10

Thrombophlebitis and necrosis

Question 11

What must you do if you give a horse phenylbutazone?

Answer 11

Sign the horse passport out of the food chain

Question 12

What should you do if you want to give phenylbutazone but there is no passport available?

Answer 12

Use meloxicam as this can go into food chain

Question 13

Compared with opioids, what is NSAIDS:

A) Better for?

B) Less good for?

Answer 13

A) MSK Pain

B) Visceral pain

Question 14

Name 2 reasons we would rather use NSAIDs than opioids in horses?

Answer 14

Side effects

Don’t want to dispense too many opioids (horse owners are dodge)

Question 15

Name 7 pracitcal considerations when it comes to NSAID use (9)

Answer 15

• Non-scheduled (still POM-V)
• Cheaper vs opioids
• Effective per-os
• Little long-term decrease in efficacy
• Longer duration of action
• Side effects
• Compliance (owner)
• Cost
• Co-morbidities

Question 16

Where are NSAIDs metabolised?

Answer 16

Liver

Question 17

Where are NSAIDs excreted?

Answer 17

Kidneys

Question 18

What is the protein binding of NSAID?

Answer 18

High

Question 19

What is the volume of distribution of NSAIDs?

Answer 19

Low

Question 20

What is the wash out period?

Answer 20

–If you want to change from one NSAIDs to another. There is advice to allow a number of half life wash out before we start the next one. May need bridging medication to tide them over e.g. adjuncts – paracetamol. Not currently done in horses.

Question 21

What should you do if you have a problem with an NSAID?

Answer 21

Yellow form or online reporting to VMD

Question 22

What is the “housekeeping” pathway?

Answer 22

Cox 1 - constitutive

Question 23

What is the inflammatory pathway?

Answer 23

COX 2 - inducible

Question 24

Why can NSAIDs cause problems with the kidneys?

Answer 24

• Renal blood flow mediated by prostaglandins (PG) in medullary circulation (Therefore PG inhibition by NSAIDS can cause problems)
• Hypotension + NSAID = renal damage hence concern peri-operatively

Question 25

What is the effect of prostaglandins in the GIT?

Answer 25

They are cytoprotective ## Footnote –Decrease the volume, acidity and pepsin content in the stomach –Stimulate bicarbonate secretion –Promote mucosal blood flow and repair and turnover of cells

Question 26

Name 5 side effects of NSAIDs (7)

Answer 26

–Vomiting (small ans) –Colic –Inappetance - D++ –PLE -2° anaemia, –Ulceration –Death

Question 27

What are young horses more susceptible to with NSAIDs?

Answer 27

Gastric ulceration

Question 28

What are adult horses with NSAIDs more susceptible to?

Answer 28

Right dorsal colitis

Question 29

What is the relative ulcerogenicity with: Flunixin Phenylbutazone Ketoprofen?

Answer 29

Phenylbutazone \> flunixin \> ketoprofen

Question 30

Name 2 long term adaptations of the GI tract to NSAIDs (3)

Answer 30

* Increased mucosal blood flow * Increased mucosal cell regeneration * Decreased inflammatory cell infiltrate

Question 31

How many days on NSAIDs does it take for there to be long term adaptation?

Answer 31

14 days

Question 32

What is enterohepatic recycling?

Answer 32

Excretion into intestine from bile – repeated exposure of the duodenum to drug

Question 33

What does enterohepatic recycling directly correlate to?

Answer 33

Toxcitiy

Question 34

Name 4 ways GI safety with NSAIDs can be improved (6)

Answer 34

–Protective strategy – case by case basis –Sucralfate (sucrose aluminum sulphate) –H2 antagonists –Proton pump-inhibitors –? Newer Coxibs ? –Different formulation of NSAIDs sometimes

Question 35

What is the effect of some NSAIDs on cartilage and what is the mechanism of this?

Answer 35

Worsen cartilage degeneration in arthritic animals – decreased GAG synthesis

Question 36

What is the effect of carprofn on equine cartilage cells? (2)

Answer 36

* Increased GAG at therapeutic doses * Increase proteoglycan metabolism

Question 37

What type of reactions happen with NSAIDs causing hepatotoxciity?

Answer 37

Type 1 and type 3

Question 38

What is the breed predisposition of dogs getting hepatotoxcity with NSAIDs?

Answer 38

There isn't one

Question 39

What is the difference between cats and dogs having NSAIDs?

Answer 39

They have a lower clearance of salicylates

Question 40

Name 5 of the possible effects cats may get with NSAIDs (7)

Answer 40

* Hyperthermia * Respiratory alkalosis * Metabolic acidosis * Methaemoglobinaemia * Haemorrhagic gastro-enteritis * Renal failure * Hepatic injury

Question 41

What is Robenacoxib (onsior)?

Answer 41

A tissue selective NSAID

Question 42

Name 5 guidelines for safe use of NSAIDs? (7)

Answer 42

–No hypovolaemia (but what about colic sx?) –No concurrent administration of another NSAID OR a steroid – possibly allow washout (4-5 half lives?? in dogs), but this is not performed in horses.. –No hepatic or renal insufficiency –Dog – high confidence in absence of renal failure –Cats – no margin of safety ! –Routine biochemistry? For long term use? YES –Screening biochemistry? Before starting in some cases of long term therapy? YES IF POSSIBLE

Question 43

What is acetaminophen?

Answer 43

Paracetamol

Question 44

Where is paracetamol licensed?

Answer 44

Pigs

Question 45

When is paracetamol most commonly used?

Answer 45

As a bridgng mechanism

Question 46

Where is sodium salicylate licensed?

Answer 46

Catlle and pigs

Question 47

What is the mechanism of paracetamol action?

Answer 47

–Unknown mechanism of action – central ?, 5-HT3, **TPRV1**, Cox, cannabinoid pathways possibly involved?

Question 48

Where should you look for off licence use of NSAIDs?

Answer 48

BSAVA formulary

Question 49

What is the issue of using NOAH for drugs?

Answer 49

Not all drugs are in there - companies have to pay to be in there

Question 50

Name 4 licensed NSAIDs in horses (6)

Answer 50

* Phenylbutazone, * Suxibuzone, * Flunixin, * Meloxicam, * Vedaprofen, * Firocoxib

Question 51

Name 3 licensed NSAIDs in cats (4)

Answer 51

* Meloxicam, * Robenacoxib, * Ketoprofen, * Tolfenamic acid

Question 52

Name 7 licensed NSAIDs in dogs (10)

Answer 52

* Meloxicam, * Carprofen, * Robenacoxib, * Mavacoxib, * Paracetamol (with codeine), * Tolfenamic acid, * Ketoprofen, (tepoxalin - expired ) * Firocoxib, * Phenylbutazone, * Cimicoxib

Question 53

Name 4 licensed NSAIDs in pigs (6)

Answer 53

* Ketoprofen, * Meloxicam, * Tolfenamic acid, * Flunixin, * Salicylic acid, * Paracetamol

Question 54

Name 3 licensed NSAIDs in cows (4)

Answer 54

* Ketoprofen, * Meloxicam, * Flunixin, * Salicylic acid

Question 55

Name licensed drugs in sheep and goats

Answer 55

Nothing licensed – use cascade as for other food producing animals

Question 56

What is the benefit of mavacoxib?

Answer 56

Duration up to a month

Question 57

Name 6 therapeutic decsions of using NSAIDs (8)

Answer 57

* Consider Efficacy * Consider Safety * Address compliance (see suggestions in the OA NSAID booklet for improvements) * Consider the formulation – route of admin * Cost ? * Duration of action * Support packages? * EBM

Question 58

Name 8 "other" therapies to NSAIDs for MSK disease (10)

Answer 58

* Exercise management * Weight control & diet (may need additional analgesics * Modifications to lifestyle (ramps, rugs, claws) * Hydrotherapy & physiotherapy * Chondroprotectives * Joint replacement * IRap * Stem cell therapies * Other ‘drugs’ :Isoxsuprine hydrochloride (Navilox), vegetable tablets, garlic & fenugreek, sodium hyaluronate (Hyonate), prednoleucotropin (PLT) * EP4 receptor blockers (galliprant –USA only, UK 2018/19)