Article by: Jeannine Miesle, M.A., M.Ed
There is some confusion among vets and bird-owners about the action of meloxicam and celecoxib. Many practitioners continue to prescribe meloxicam when celecoxib is far superior for pain and inflammation. The following information in quotes comes directly from Dr. Bob Dahlhausen’s 2018 lecture:
“Some dog and cat vets and even avian vets are not as familiar with the Cox-1 and Cox-2 inhibitors and choose to use Metacam (meloxicam). The oral form is not at all effective and even causes harm to birds. It’s designed for the digestive tract of dogs and cats. Birds’ digestive tracts are very acidic, so most of the meloxicam moves through and very little gets absorbed, so if you’re going to use it, you have to use high doses. Celebrex (celecoxib) is superior to meloxicam. It inhibits the normal inflammatory function in the bird. It doesn’t impact the GI function or platelet aggregation.”
“Meloxicam inhibits both Cox-1 and Cox-2 enzymes. Cox-1 is the good enzyme—you don’t want to inhibit that. Meloxicam alters the protective membrane or mucosal layers of the GI tract. Celebrex only inhibits the Cox-2 enzyme. We’ve since gone to Robenacoxib injections. It works really well. You only need to give it once a week. We’ll put a bird on it and in 4-6 weeks it really turns the bird around. (Oral Celebrex is still given for long-term pain and inflammation control.) A half a baby aspirin dissolved in water acts symbiotically with Celebrex and increases the pain control effect.”
Here is an explanation of the difference between the two drugs:
Cyclooxygenase (COX) is an enzyme produced by the body that is responsible for the formation of prostanoids, a group of fat-soluble compounds synthesized by nearly all the cells in the body. Prostanoids are essential to the proper functioning of the organs and are responsible for homeostasis, or maintaining the smooth, normal functioning of the body. Prostanoids are involved in the body’s inflammatory response. They are generated in response to inflammatory stimuli and play an important roles in normal physiology and disease. If the constant formation and release of prostanoids is interrupted, life-threatening conditions may develop. This can cause strokes, heart disease, and diabetes. Excessive production is linked to arthritis.
Prostanoids play pivotal roles in inflammation and pain. Cyclooxygenase (COX) inhibitors, the nonsteroidal anti-inflammatory drugs (NSAIDs), depress prostanoid formation and are widely used to treat inflammatory pain. However, their therapeutic benefit is sometimes be offset by serious side-effects, primarily gastrointestinal and cardiovascular complications.
Two Forms of Cyclooxygenase (COX)
In the 1990s, researchers discovered that two different COX enzymes existed, now known as COX-1 and COX-2. Cyclooxygenase-1 (COX-1) is known to be present in most tissues. In the gastrointestinal tract, COX-1 maintains the normal lining of the stomach. The enzyme is also involved in kidney and platelet function. Cyclooxygenase-2 (COX-2) is primarily present at sites of inflammation.
While both COX-1 and COX-2 convert arachidonic acid (a mechanism for controlling pain modulation and homeostasis, or balance, in the body) to prostaglandin, resulting in pain and inflammation, their other functions make inhibition of COX-1 undesirable while inhibition of COX-2 is considered desirable. (This is why veterinarians use COX-2 inhibitors, like Celebrex. JM)
NSAIDs Inhibit COX
Nonsteroidal anti-inflammatory drugs (NSAIDs), commonly prescribed to treat arthritis, work by inhibiting prostaglandins. Traditional NSAIDs (ibuprofen, naproxen), however, can cause gastrointestinal problems including ulcers. Traditional NSAIDs are considered “nonselective” because they inhibit both COX-1 and COX-2. The inhibition of COX-2 by traditional NSAIDs accounts for the anti-inflammatory effect of the drugs, while the inhibition of COX-1 can lead to NSAID toxicity and associated side effects (ulcers, prolonged bleeding time, kidney problems).
Some researchers believe, after finding low levels of COX-2 in some non-inflamed tissue, that COX-2 may also play a role in certain normal functions of the body other than inflammation. While NSAIDs and COX-2 inhibitors are considered significant treatment options for arthritis patients, the benefit and risks must be considered for each individual patient.
COX-2 Selective NSAIDs
NSAIDS are considered preferable to opioids for controlling pain and inflammation because of the side effects and potential addictive qualities of opioids. In the late 1990s, the first COX-2 selective NSAID (Celebrex) was developed, and others soon followed. Over the years, many have been produced, tested, and even prescribed, but were discontinued because of their side effects.
While many NSAID’s are considered to have equivalent efficacy, there is now no doubt that NSAID’s have different side-effect profiles The explosion of knowledge about the different cyclooxygenase enzymes has given us a more fundamental understanding of the actions and side effects of these drugs.
Both COX-1 and COX-2 have the same affinity to convert arachidonic acid to prostaglandin. Because COX-1 is associated with the gastrointestinal tract, it maintains normal gastric mucosa and influences kidney function. The inhibition of COX-1 is therefore undesirable. On the other hand, because COX-2 is involved with pain and inflammation, the inhibition of COX-2, is a desirable effect.
Truly specific COX-2 inhibitors are celecoxib (Celebrex®, Pfizer Corporation) and robenacoxib (Onsior®, Elanco corporation)
Celecoxib (Celebrex®), the first of the new class of drugs, was passed by the FDA for use in rheumatoid and osteoarthritis. Celecoxib (Celebrex®) for example, is 375-fold more selective for COX-2 compared to COX-1. It does not inhibit COX-1 at therapeutic doses in contrast to standard NSAID’s currently available. Studies show effective benefit with no gastrointestinal adverse effects compared to placebo.
Meloxicam is one of several so called “preferential” COX 2 inhibitors which have been developed. Meloxicam has been shown to be less selective than Celebrex for pain and inflammation. Meloxicam is only 3 times more selective for COX-2, compared with Celecoxib (Celebrex), which is 325 times more selective. In fact, analysis of the therapeutic plasma levels of Meloxicam show these to be greater than the amounts required for inhibition of COX-1. Thus inhibition of COX-1 will occur, and side effects are therefore possible. Meloxicam is therefore NOT a specific COX 2 inhibitor, and thus is not as effective as Celecoxib. The injectable form (robenacoxib) can be used if there is poor GI transit.
The oral form of meloxicam is formulated for the GI tract of the dog and cat. The stomach of the bird has a much higher pH. Clinically, the oral form is not as effective in birds.
Plasma levels of Celecoxib however, at therapeutic doses, do not exceed the levels required for COX-1 inhibition while inhibiting COX-2 effectively. Studies on Celecoxib confirm gastrointestinal side effects to be similar to a placebo. The drug, therefore, is the first specific COX-2 inhibitor and is the first to be so recommended by the FDA. This proves that Meloxicam is not as efficient in the reduction of pain and inflammation as is Celebrex.
The overall effect would appear to be that the specific COX-2 drugs relate to good gastrointestinal and renal side-effect profiles. They are major clinical advances in the management of pain and arthritis.
Truly selective COX-2 inhibitors have been shown to have no effect on gastric mucosal prostaglandin synthesis, to cause no acute injury, and no chronic ulceration compared to placebo.
Conclusion:
The enzyme, cyclooxygenase, is produced by mammalian and avian bodies and are important in maintaining homeostasis and promote inflammation and pain through prostanoids. There are two types: COX-1 and COX-2. COX-1 is present mostly in the gastrointestinal tract, and COX-2 is present at the site of pain and inflammation. Since COX-2 promotes pain and inflammation at the site of an injury, it is important to use a medication that will control and reduce these effects. These medications are called, “inhibitors.” The best inhibitors are NSAIDS, which work to reduce the discomfort without the use of opioids. Because the inhibitors that work best against pain and inflammation are directed toward COX-2, Celebrex is considered the most valuable of the inhibitors available.
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Miesle J. Notes from Dr. Bob Dahlhausen’s 2018 lecture on geriatrics. (This contains information on the Cox-1 and Cox-2 inhibitors. In the files of “The Science of Avian Health.”)
