Lecture 11 and 12 Flashcards
What are the two different is-forms of COX and which one is beneficial and which one has the potential to be detrimental?
COX-1 = good one has many house keeping roles involved in blood vessels, gastrointestinal mucosa and kidney (PGE2, PGI2) COX-2 = induced after an insult (trauma) to produce mediators of inflammation, pain and pyrexia
Name an NSAID that is highly selective for COX-2 inhibition over COX-1:
Firocoxib
Do NSAID’s have any effect on chronic inflammation?
No the NSAIDs only impact upon the acute inflammation state almost no impact upon the chronic proliferative phase. (the damage has already been done)
Explain the NSAID gastro-intestinal side effects related to the inhibition of COX-1:
The good prostaglandins (PGI2 and PGE) normally inhibit acid secretion, increase mucosal blood flow and increase mucus production. As a result the NSAID’s have potential for erosion, ulceration and haemorrhage.
Explain the NSAID side effects of altered platelet function related to the inhibition of COX-1:
Thromboxane (TXA2) is a pro-aggregator of platelets needed for thrombus formation and haemostasis. PGI2 from endothelial COX leads to the inhibition of platelet aggregation.
As a result there will be an irreversible decrease in platelet thromboxane and a temporary decrease in endothelial PGI2. As a result a net decrease in platelet aggregation will be seen.
Explain what the side effects of NSAID’s related to the kidney will be:
PGE2 (increases salt and water excretion), does partially via inhibition of ADH. Whereas, PGI2 also increases salt and water excretion and causes renal vasodilation which promotes blood flow to the kidney. Kidneys typically rely on approximately 25% of cardiac output (CO).
As a result the NSAID’s lead to water retention causing hypertension and decreased renal blood flow leading to interstitial papillary necrosis and nephritis. .
What is the maximum dose of aspirin for a cat?
1/10th of a 300mg tablet every 3-6 hours.
What are the implications for NSAID’s being highly protein bound?
Means that they will accumulate at sites of inflammation.
Outline some of the clinical applications of the NSAID’s:
Analgesia through anti-inflammation = decreasing PG concentrations which would otherwise amplify the pain sensitisation effects of histamine and other inflammatory mediators. The clinical uses include surgery and other medical problems.
Provide an 2 examples of the COX-2 selective NSAID’s (the coxibs) and state which species their use has been registered for:
Firocoxib: only registered for use in dogs
Robenacoxib: registered for dogs and cats - known to have impressive feline palatability
What is the longest acting NSAID available:
Mavacoxib: dose on day 1, two weeks later, monthly for five months
What is the most common NSAID that is used for horses?
Phenylbutazone
What is a common NSAID that can be used for colic horses?
Flunixin - very commonly used. An excellent analgesic for colic horses.
What is a potential problem with the use of phenylbutazone for use within production animals?
No established WHPs in production animals due to decreased and unpredictable drug clearance.
How do dietary fatty acids (not NSAID’s) alternative treatments work?
provide an alternative substrate for the phospholipase to target.
