Pain Part III: NSAIDs

March 19, 2014

There are many options for managing pain in our pets which can be used alone or in combination with one another. This week we will discuss Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), one of the cornerstones of treating pain in both human and veterinary medicine. Veterinary NSAIDs are effective, widely available, and safe for the vast majority of patients at recommended doses, but the potential for adverse side effects ranging from mild to serious make it important to use them appropriately.

NSAIDs primarily work by inhibiting an enzyme called cyclooxygenase 2 (COX2). COX2 is released by injured tissues, activating inflammation.  Because inflammation is one of the major underlying mechanisms for activating the pain pathways and causing pain, NSAIDs are therefore a very important tool in pain management. They may also have a minor role in inhibiting perception of pain by the brain, but this effect is not well understood.  Individual response to NSAIDs as a whole and to specific NSAIDs varies greatly between patients; that is, some patients respond better than others to these drugs and/or one particular drug may work better than another for an individual patient. Some examples of veterinary drugs in this class include Rimadyl (carprofen), Metacam (meloxicam), Previcox (firocoxib), Deramaxx (deracoxib), and Onsior (robenacoxib).

Unfortunately, the same mechanism that inhibits inflammation can also cause adverse side effects. COX2, along with a closely-related enzyme called COX1, is active in the production of substances called protective prostaglandins that protect tissues such as the lining of the stomach and a section of the kidneys called the renal tubules.  This means that gastrointestinal erosions/ulcers or nephrotoxicity (damage to the kidneys) are possible adverse side effects when using these drugs. Fortunately, at normal prescribed doses these effects are very rare (fewer than 2% of patients are affected). There is also a very rare (less than 0.05% of patients) type of liver damage that can occur as an idiosyncratic reaction, separately from NSAIDs’ mechanism of action; this is a highly individual event.  While some individual NSAIDs have a reputation for being more likely to cause particular effects, all drugs in this class share the potential for the same side effects and no individual drug can be considered the “safest.” Risks do not necessarily increase with time, making these drugs appropriate for management of both acute and chronic pain conditions.

There is accumulating evidence in both human and veterinary medicine that suggests that improper use (increasing doses, accidental overdoses) and individual/idiosyncratic sensitivity to this class of drugs are the most likely factors contributing to adverse side effects. However, the risks can be minimized in all patients by taking a few simple precautions:

1. Realize that side effects are more common in patients with one or more risk factors that include things like dehydration, low blood pressure, or pre-existing or concurrent kidney, liver, heart, or GI disease. Avoiding use of NSAIDs in these higher risk patients and performing baseline and follow-up bloodwork in all patients to track liver and kidney values are important. Be sure to keep your veterinarian informed of any problems with vomiting or other unusual symptoms at home.
2. Always give NSAIDS as prescribed. “More is better” does not apply to these drugs and giving more than prescribed (or accidental overdoses) greatly increases the risk of adverse side effects.
3. Certain medications given together with NSAIDs can increase the risk of adverse effects, including other NSAIDs (especially aspirin), steroids, and some drugs used for heart or kidney disease. In addition, some over the counter products labeled as supplements may contain aspirin, or herbs or other ingredients that mimic the effects of NSAIDs and may increase the risk of adverse effects. Always keep your veterinarian informed of other drugs and supplements your dog is taking, read their labels carefully, and never give human NSAIDs or other human medications to your pet without consulting with your veterinarian.
4. Be alert for early signs of adverse side effects. Usually, a loss of appetite is the earliest sign of GI problems in dogs and cats. Vomiting may also occur. Also be alert for any lethargy or changes in water consumption. Usually adverse events will occur in the first 2-4 weeks of starting these medications, but can happen at any time.
5. Combining NSAIDS with other treatment options can help reduce the dose of NSAIDs needed for an individual, which can reduce the risk of adverse side effects. These options will be more thoroughly discussed in future blog posts but include other classes of drugs that work differently, joint supplements, antioxidants, fish oil, physical therapy, acupuncture, or chiropractic. In addition, trial and error can help reduce the dose of an NSAID to the lowest effective dose for any particular individual.
6. Some NSAIDs are “COX selective,” meaning that they do not affect COX2 and COX 1 equally. These NSAIDS are less likely to cause GI problems but still have the potential for kidney damage.
7. Particular care must be used when using NSAIDs in cats as their metabolism of a wide variety of drugs is unique and many drugs are not safe to use at all. There is a new NSAID that has been approved for use specifically in cats, but you should never give an NSAID prescribed for a dog or any human medication to a cat without specific instructions from a veterinarian.

As always, if you have any questions for our veterinarians please feel free to call the clinic to speak with one of our doctors.