Consider human NSAIDs to nurse pain in horses

Treatment of painful conditions in horses has relied largely on nonsteroidal anti-inflammatory drugs (NSAIDs) for much of the last 25 years. For example, flunixin meglumine (Banamine®) and phenylbutazone (Butazolidin®) have dominated the market for treatment of colic and lameness respectively. However, it is becoming increasingly clear that these drugs also have some side effects, most notably gastrointestinal ulceration.

Photo 1: COX-2 inhibitors may be particularly useful for treatment of conditions such as acute synovitis, evident in the right knee of this horse.

To see how these beneficial and detrimental side effects can be resolved, veterinarians should take note of the human pharmaceutical market. In particular, the use of ibuprofen (Advil®) for treatment of arthritis is being replaced by a new group of NSAIDs called COX-2 inhibitors. Celecoxib (Celebrex®) and rofecoxib (Vioxx®), both of which are COX-2 inhibitors labeled for treatment of arthritis in people, are as effective as ibuprofen for reducing pain, but the incidence of gastric ulceration is greatly reduced.

As a result, the use of these drugs has taken off with record-breaking sales. Should equine practitioners be a part of this revolution in NSAID use? Some recent studies suggest we should.

Defining COX-2 inhibitors

NSAIDs work as analgesics by inhibiting the prostaglandin-producing enzyme cyclooxygenase (COX). However, the simplicity of this fact has recently been complicated by the discovery of two forms of COX: COX-1 and COX-2. For the most part, COX-1 is responsible for producing prostaglandins needed for normal daily function, including protection of the gastrointestinal mucosa.

Conversely, COX-2 lies dormant under normal circumstances, but is rapidly called into action during inflammation, producing excessive quantities of prostaglandins that exacerbate inflammation and hypersensitize nerves to pain (Figure 1, p. 4E).

Figure 1: Schematic role of the prostaglandin-producing cyclooxygenase (COX) enzymes in bodily functions.

Pharmaceutical companies have seized the opportunity provided by these findings to produce drugs capable of selectively inhibiting COX-2. Although these drugs have their limitations, diseases characterized by pain and inflammation such as arthritis appear to respond well to COX-2 inhibitors in both humans and dogs.

Are COX-2 inhibitors safe for horses?

The answer to this question depends on the perceived side effects of NSAIDs.

Since NSAIDs have a long track record of successful use in equine practice, it can be hard to consider changing to a new class of drugs. However, it is now widely recognized that NSAIDs can cause gastric ulcers, and, on occasion, more fatal conditions, such as colitis.

In addition, the horse-owning public is always on the lookout for new and improved methods of treatment, and many horse owners already know about NSAID side effects. Horse owner public opinion is often what drives changes in veterinary practice, so veterinarians should be knowledgeable about these new drugs as early in their development as possible.

In two recent studies reported at the 2002 American College of Veterinary Internal Medicine, COX-2 inhibitors were shown to work at least as well as phenylbutazone for treatment of synovitis or lameness in horses. One of the COX-2 inhibitors used in these studies is already on the market for treatment of arthritis in dogs (etodolac, Etogesic®), whereas the other is an experimental, more highly selective COX-2 inhibitor under study by Merck.

The equine dose of etodolac was determined to be 23 mg/kg twice daily by mouth.

We already know from previously published studies that etodolac is less damaging to the gut. Taken together with evidence of efficacy for treatment of synovitis, these studies suggest an alternative 'GI-safe' treatment for equine lameness. In addition, there is also evidence that COX-2 inhibitors may be helpful for treatment of colic.

Side effects reduced

Several points should be considered before instituting use of COX-2 inhibitors in practice. First, evidence from human studies shows that the COX-2 inhibitors have a lower incidence of gastrointestinal side effects than traditional NSAIDs, but side effects are not completely erased. This relates partly to the fact that even highly selective COX-2 inhibitors continue to inhibit COX-1 to some extent.

Secondly, since COX-2 inhibitors are still under patent, there are no generic COX-2 inhibitors, and they are therefore more expensive. It would be prohibitively expensive to use one of the human products on horses. It would also be more expensive to use a veterinary drug, such as Etogesic, although not prohibitive in a patient particularly in need of a drug with less gastrointestinal side effects. Probably the best example of the latter would be a horse with a chronic lameness condition such as laminitis that had already had some side effects on traditional NSAIDs.

Proceed with caution

Before COX-2 inhibitors become available on the equine market, practitioners should make sure that they use NSAIDs in the safest manner possible. This means using the correct dosages (maximal dose of flunixin 1.1 mg/kg twice daily, maximal dose of phenylbutazone 4.4 mg/kg twice daily), and reducing the dose of NSAIDs to as low a dose as possible as fast as possible.

Some things to avoid include use of these drugs at a higher frequency than intended (i.e., more than twice daily), and using maximal doses for prolonged periods of time, particularly in horses that have other systemic medical problems, most notably dehydration. In this way, NSAIDs can be used very successfully, to the point where some horses with chronic lameness receive phenylbutazone year-round (typically at a dose, such as 1g once daily). However, even in these horses, it is worth considering giving horses time off from treatment, such as by treating only before and after strenuous exercise on a restricted number of days per week.

Finally, veterinarians should be careful not to over-emphasize NSAID gastrointestinal side effects, but be on the lookout for new and improved drugs in the near future.

Suggested Reading

• Jones SL, Blikslager AT. The future of anti-inflammatory therapy. Vet Clin North Am Equine Pract 2001; 17: 245-262.

• McCann ME, Anderson DR, Brideau C, Black WC, Zhang DH, Hickey GJ. In vitro efficacy activity and in vivo efficacy of a novel COX-2 inhibitor in the horse. Proceedings, ACVIM Forum 2002, Dallas, TX, p. 789.

• Blikslager AT, Campbell NB. Alternative COX-2 inhibitors for treatment of pain in horses. Proceedings, ACVIM Forum 2002, Dallas TX, pp. 214-216.

• Campbell NB, Blikslager AT. The role of cyclooxygenase inhibitors in repair of ischemic-injured jejunal mucosa in the horse. Equine Vet J Suppl 2000;32:59-64.