How do Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) work?
What the drugs in this class have in common is that they inhibit cyclo-oxygenase (also known as COX), a key enzyme involved in the production of molecules (including prostaglandins) in the body in response to injury. This action gives them pain-relieving, fever-reducing (antipyretic) and anti-inflammatory effects.
Is there more than one type of cyclo-oxygenase in the body?
There are known to be at least two types of COX in the body: COX-1 and COX-2.
What is the difference between COX-1 and COX-2?
COX-1 is found in most, possibly all, cell types and is generally considered to be associated with normal body functions (e.g. producing protective prostaglandins in the gastrointestinal tract and kidney). COX-2 is formed at sites of inflammation, resulting in prostaglandins with inflammatory effects.
Do NSAIDs inhibit COX-1 and COX-2?
The pain-relieving and anti-inflammatory actions of NSAIDs were originally believed to depend mainly on their inhibition of COX-2, and the unwanted gastrointestinal and renal effects of NSAIDs on their inhibition of COX-1. It followed, in theory, that a drug that inhibits COX-2 at a lower concentration than is needed to inhibit COX-1 might be safer, and so NSAIDs that are more selective for COX-2 have been developed (these are referred to as COX-2 selective or preferential).
Is this all that NSAIDs do?
In the light of more recent research on COX, the concept of COX-1 as ‘good’ and COX-2 as ‘bad’ is now known to be an oversimplification. For instance, the effects of COX-2 are more complex than simply producing inflammatory prostaglandins, and there is now known to be a third type of COX – COX-3. More research into the effects of NSAIDs is also showing that they have effects other than COX inhibition that might also contribute to their actions.
What relevance does this have to treating canine osteoarthritis?
An NSAID is usually the first-line drug therapy for dogs with chronic pain with an inflammatory cause, as part of a multi-modal approach. However, there are seven different NSAIDs marketed in the UK for use in dogs. We reviewed the published evidence to find out whether there are any differences between the different NSAIDs in terms of efficacy or safety.
So is there any difference between the NSAIDs in how well they relieve pain in dogs with osteoarthritis?
An important point to make is that NSAIDs have been relatively well studied in dogs with osteoarthritis – there is more much evidence on NSAIDs than for any other drug treatment. That they have relieve pain and reduce inflammation is undisputed. For some reason, a dog may respond better to one NSAID than another (it’s the same for humans), so if one has no effect, it’s worth trying another. But overall, no one drug has been shown to be more effective than another.
So is there any difference between the NSAIDs in how likely they are to cause side effects?
Gastrointestinal reactions, including vomiting, diarrhoea and loss of appetite are the most commonly reported side effects of NSAIDs. There’s no evidence that any particular NSAID is less likely than another to cause these, or any other (including renal) side effects.
To help us understand more about adverse reactions, all adverse reactions seen with the use of NSAIDs (even older ones) should be reported to the Veterinary Medicines Directorate or the company that markets the drug. Anyone can report an adverse drug reaction.
See the full “Which NSAID?” module at https://www.veterinaryprescriber.org/subscribers/
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