Rational Use of NSAIDs Flashcards
How do NSAIDs reduce inflammation?
inhibit the production of prostaglandins released by damaged tissue by inhibiting cyclo-oxygenase
When are NSAIDs indicated?
- controlling pain and inflammation in NON ALLERGIC disorders e.g. degenerative joint disease
- Peri-operative pain management
- Decreasing platelet aggregation e.g. heartworm disease, thromboembolism
What is the name of the pathway that NSAIDs act on and what are the products of these pathways?
Cyclooxygenase pathway
COX-1 (physiologic COX)
COX-2 (the inducible COX)
What is the role of COX-1?
Physiologic roles- mucosal protection, renal blood flow & haemostasis
What is the role of COX-2?
Inducible behaviours- inflammation, pain & fever
How does inhibiting COX-2 helps with tumours?
Tumours produce COX-2 so inhibiting can slow the growth of these tumours
What are the three types of NSAIDs?
- Non selective
- Preferential (mainly inhibit COX-2 with some COX-1 inhibition)
- Selective (inhibit COX-2 without inhibiting COX-1)
How do Corticosteroids reduce inflammation?
Block the production of Phospholipase from the membrane
Phospholipase is usually used to make arachnoid acid which is needed to make COX-1 / COX-2
Therefore Corticosteroids block both COX-1 and COX-2
Why are some NSAIDs more toxic than others?
Their COX-1 : COX-2 ratios differ so have different levels of safety depending on their inhibition of COX-1 (the physiological one)
Give two examples of non selective COX inhibitors?
Aspirin
Phenylbutazone
Ketoprofen
Tolfenamic acid
What are Preferential COX-2 inhibitors good for but what is the risk?
Good for analgesic and anti-inflammatory activity by blocking COX-2
BUT some COX-1 inhibition is possible at elevated doses
Preferential COX-2 inhibitors also includes drugs known as…..
Why?
Coxibs- COX-2 selective in humans but NOT in animals
Give two examples of Preferential inhibitors of COX-2?
Meloxicam / Metacam
Carprofen
Mavacoxib
Cimicoxib
What is the duration of action like for Mavacoxib?
VERY long!- can be given as an NSAID once a month
Give two examples of selective inhibitors of COX-2?
Firocoxib
Robenocoxib
How do non NSAID Osteoarthritis drugs work?
Prostaglandin (PGE2)- binds to 4 receptors- the EP4 receptor is responsible for pain and inflammation associated with osteoarthritis- inhibiting this receptor inhibits the pain
Give an example of a non NSAID Osteoarthritis drug?
Grapiprant / Galliprant
Which two NSAIDs are preferred to administer to dogs and what is their mechanism of action?
Carprofen (the COX-2 preferential)
Firocoxib (COX-2 selective)
What is the risk of using Carprofen in cats?
Daily dosing leads to GI disaster!- think holes in the intestine
Can we use Firocoxib in Cats?
How does its inhibition differ in cats than dogs?
Technically no- not licensed in cats
Acts as a COX-2 preferential in cats rather than selective
Which NSAIDs are preferred in Horses and what is their mechanism of action?
Carprofen (non selective)
Firocoxib (selective)
How/ Where are NSAIDs best absorbed?
from stomach & small intestine
well absorbed after subcutaneous or intramuscular injection
How do the biological properties of NSAIDs make them effective in targeting inflamed tissue?
Weak acids to readily penetrate inflamed tissue
Highly protein bound so readily accumulate in protein rich inflammatory exudate
Which route of elimination do NSAIDs follow?
Hepatic
Can we give Paracetamol to companion animals?
Cats- NO
Dogs- Yes
What are some potential side effects of NSAIDs?
GI damage
Renal toxicity
Haematological such as blood clotting
When there is no pre existing GI injury, are NSAIDs still a risk?
Depends on the NSAID- Non selective ones are higher risk as COX-1 and COX-2 need to be inhibited to generate a mucosal injury in the absence of a pre existing one
How do NSAIDs cause GI damage?
Disrupt the mucosal gel layer of the GI tract meaning acid is let in
Why do COX-2 selective drugs have higher GI risks in dogs?
Dogs have a higher requirement for COX-2 in the duodenum (both COX have protective roles in the duodenum but COX-2 has a bigger role) so COX-2 inhibitors cause a higher degree of duodenal ulceration compared with non selective NSAIDs
What can increase the ulcerogenic potential of an NSAID?
Concurrent corticosteroids
Dehydration
Hypovolaemic Shock
How does COX-2 inhibition effect the kidney?
COX-2 has physiological roles in the kidney so when renal perfusion is reduced, COX-1 and COX-2 maintain renal blood flow through vasodilatory actions hence why you cannot use NSAIDs in a dehydrated animal
Can we use Galliprant (the EP4 receptor antagonist) as an alternative to NSAIDs in patients with renal compromise?
NO- EP4 is expressed in the glomerulus and collecting duct & helps regulate glomerular tone and renin release
Why do NSAIDs carry the risk of Haematopoietic side effects?
COX-1 inhibitors also inhibit Thromboxane which is a vasoconstrictor and activates platelet aggregation- inhibition of this can lead to increased bleeding
Due to the risk of Nephrotoxicity with NSAIDs in patients with pre exisiting renal issues, can we use ACE inhibitors to reduce inflammation instead?
NO- ACE inhibitors decrease renal vascular resistance, therefore increasing blood flow which strains the renal system
What effect does alpha2 agonists have on NSAIDs?
Using alpha2 agonists as premedication before administering an NSAID may enhance the analgesic and anti-inflammatory effect of NSAIDs but also improve gatstrointestinal tolerability
Why should you avoid a high dose of Acepromazine as a pre medication before administering an NSAID?
Acepromazine interacts with NSAIDs- causes an increased risk of Hypertension
What is the result of using Diuretics and NSAIDs at the same time?
COX-2 inhibition reduces the effect of the diuretic
