These drugs are an integral part of your veterinarian’s pain- and inflammation-fighting arsenal, but sometimes they do more harm than good
One of the most distressing things about horse ownership is seeing your beloved animal in pain. Whether it be colic- or lameness-related, your first instinct is to try to relieve the discomfort. Many horse owners have medications that their veterinarians have prescribed to manage their horses’ pain in these instances. But is administering these always the best decision? Could doing so cause more harm than good?
The most commonly administered medications for treating painful conditions in horses are phenylbutazone (Bute), flunixin meglumine (Banamine), ketoprofen (Ketofen), and firocoxib (Equioxx). These are classified as non-steroidal anti-inflammatory drugs, or NSAIDs.
“Non-steroidal anti-inflammatory drugs are used for their analgesic (pain-eliminating) and anti-inflammatory properties,” says Anthony Blikslager, DVM, PhD, Dipl. ACVS, professor of equine surgery and gastroenterology at North Carolina State University, in Raleigh.
Adds Lisa Fultz, DVM, Dipl. ACVIM, of Equine Medicine Specialists of South Florida, in Wellington, “NSAIDs are vital in our management of pain and inflammation in horses, from literally their eyes … to the tips of their toes.”
These drugs act by inhibiting the enzyme cyclooxygenase (COX), which has two major forms, or isoenzymes: COX-1 and COX-2. The first isoenzyme, COX-1, plays the role of “housekeeper” by regulating many of the body’s processes. Most notably, it acts on the stomach’s mucosal lining, protecting it by producing prostaglandins to maintain blood flow. (Prostaglandins are natural chemicals in the body responsible for regulating blood flow to many tissues.) The body produces the COX-2 isoenzyme chiefly in response to inflammation.
Two classes of NSAIDs are available to target these distinct enzymes: nonselective COX inhibitors and COX-2 inhibitors.
Nonselective COX inhibitors do not discriminate; they target both COX-1 and COX-2 and, so, decrease inflammation significantly, but at the cost of inhibiting COX-1’s protective mechanisms. These NSAIDs include phenylbutazone, flunixin meglumine, and ketoprofen.
Cyclooxygenase-2-selective inhibitors provide similar anti-inflammatory effects by targeting COX-2, but they affect COX-1 less. Therefore, these NSAIDs carry fewer systemic side effects associated with prolonged use. Equioxx is the only FDA-approved COX-2-selective NSAID for equine medicine.
NSAIDs Commonly Administered to Horses
|Drug||NSAID Class||Primary Uses||Possible Side Effects|
|Phenylbutazone (Bute)||nonselective COX inhibitor||Acute musculoskeletal pain, such as soft tissue tears, laminitis, and bone bruising||Jugular vein thrombus, gastric ulcers, right dorsal colitis, kidney damage|
|Flunixin Meglumine (Banamine)||nonselective COX inhibitor||Pain associated with smooth muscle, including colic and pneumonia; treating endotoxemia||Clostridial myositis if injected intramuscularly (TheHorse.com/129157), gastric ulcers, kidney damage, right dorsal colitis|
|Ketoprofen (Ketofen)||nonselective COX inhibitor||Same as above, with fewer side effects. Recommended for horses with sensitivity to Bute or Banamine||Gastric ulcers, kidney damage|
|Firocoxib (Equioxx)||COX-2 selective inhibitor||Small intestine colics, osteoarthritis, chronic laminitis, chronic bone injuries||Minimal, though right dorsal colitis cases have occurred|
The Side Effects
Veterinarians need NSAIDs to manage inflammatory and painful conditions such as colic, pneumonia, and orthopedic pain in horses. However, when used improperly, excessively, or without veterinary guidance, these drugs can cause unwanted and potentially serious side effects.
“It is vital to emphasize that NSAIDs are not vitamins or supplements, and although they have a margin of safety, they are medications and have many different effects throughout the body,” Fultz says.
For this reason, it’s important to always involve your veterinarian in decisions to medicate your horse. And knowing the common mistakes and side effects associated with NSAID administration can help prevent your good intentions from becoming dangerous.
“The risk of giving an NSAID injection improperly can be very disfiguring and painful,” Fultz says. “If Bute contacts tissue outside of the vein during attempted IV (intravenous) administration, it can cause skin and tissue to slough.”
This scenario can also cause a blood clot, called a thrombus, in the jugular vein, which impedes blood return from the head to the heart. This results in backflow of blood in the veins of the head and neck, causing these vessels to bulge prominently.
“The great thing about the most commonly used NSAIDs is that they all have excellent absorption and efficacy when given orally,” Fultz says. “Therefore, the skills and risks associated with injection can … be avoided.”
When administered as oral pastes or ground tablets, NSAIDs occasionally cause direct-contact ulcerations on the horse’s lips, oral cavity, and/or tongue. But the bigger, more prevalent issue is damage to the stomach lining.
Veterinarians recognize that gastric ulceration is a common side effect of NSAID administration. The complex equine stomach has two regions: the squamous mucosa portion and the glandular portion, separated by a distinct line of tissue called the margo plicatus. The glandular portion of the stomach produces the gastric acid and tends to be a little more resistant to it.
Remember that NSAIDs inhibit prostaglandins, which might lead to decreased mucous production and a lower gastric pH. So prolonged NSAID administration can lead to squamous or glandular ulcers, or both.
As a result, affected horses might show signs of colic, especially after eating, or go off their feed. If your horse needs to be on NSAIDs long-term, your veterinarian might suggest administering gastroprotectants simultaneously to prevent gastric ulceration.
Right dorsal colitis
Ulceration can also occur in the large colon (intestine) during NSAID use, specifically in the right dorsal (upper) portion. This is usually associated with long-term administration of high doses of phenylbutazone; however, it can occur at lower doses and with other drugs, especially in horses that appear to be sensitive to NSAIDs’ toxic effects.
“The key way to avoid NSAID-induced right dorsal colitis is to use NSAIDs at as low a dose as possible for as short a period of time as possible,” Blikslager says. “To reduce the risk of NSAID-induced right dorsal colitis, one consideration is the use of COX-2 inhibitors.”
Because colonic ulcers result in protein loss, veterinarians can monitor total blood protein to help detect them early. These ulcers can cause clinical signs such as colic with soft manure or diarrhea.
“The prognosis for a horse with right dorsal colitis is guarded at best, with survival rates below 50%,” warns Blikslager. “To rescue horses from NSAID-induced right dorsal colitis, we use a drug called misoprostol, which is prostaglandin E1,” to replenish the prostaglandin the NSAID has inhibited.
Horses that are dehydrated are at increased risk of kidney damage when on NSAIDs. Prostaglandins regulate blood flow to the kidneys similar to how they do to the stomach. And again, we know that NSAIDs reduce prostaglandin levels, which in this case pares down blood supply to the kidney and results in a lack of oxygen delivery to the tissue, called ischemia. When blood flow decreases significantly, renal papillary necrosis might develop—in other words, the kidney tissues die, which severely impairs their function. One sign of this condition is urinating more frequently than normal.
Horses that have received high-dose NSAID therapy or were treated while dehydrated (a common clinical sign in colicky horses), for instance, are most at risk for this complication.
This is yet another important reason to have your veterinarian manage NSAID treatment. He or she can monitor your horse’s renal enzymes and hydration status to ensure his kidneys are functioning properly while on these medications.
When to Use NSAIDs
So, when should we reach for these drugs? “Responsible, veterinary-directed use of NSAIDs can be very beneficial and play a huge role in saving a lot of horses’ lives,” says Fultz. So the first step in using NSAIDs is calling your vet.
Veterinarians often prescribe flunixin meglumine for pain associated with the internal organs, including colic and pneumonia. Flunixin meglumine also has anti-endotoxemic properties.
Endotoxemia, or bacterial-associated sepsis (infection in the bloodstream), is a condition that occurs when Gram-negative bacteria die in the body and release toxins that can gain access to the systemic circulation via damaged gut lining. This can occur with severe colic lesions, such as intestinal strangulation, as well as with colitis and septic peritonitis (bacterial infection of the abdominal lining). Bacterial sepsis causes release of potent inflammatory mediators and prostaglandins, which most notably results in fever, depression, dehydration, and a high heart rate.
Flunixin meglumine has been shown to reduce the adverse cardiovascular effects of these toxins more effectively than other NSAIDs. This so-called anti-endotoxic effect occurs at a lower total dose than the pain-relieving dose. Due to the potential for horses to suffer from sepsis-associated problems when they show signs of colic, veterinarians most commonly use flunixin meglumine to treat gastrointestinal pain.
Remember, however, that flunixin meglumine is a nonspecific COX inhibitor that impedes both COX-1 gut protection and COX-2 associated with inflammation. “We presently use Equioxx on small intestinal colic cases and have shown good pain control (as good as Banamine) and reduced markers of sepsis,” says Blikslager. “The ideal scenario would be to have Equioxx used in the field for a referral suspect, as it takes 24 to 48 hours to lose inhibition of COX-1 in horses that have had Banamine, and we believe that reduces gut repair.”
Flunixin meglumine’s counterpart, phenylbutazone, is more potent than the COX-2-selective inhibitors and, therefore, better for treating acute musculoskeletal pain. This includes injuries such as tendon or ligament tears, laminitis, bone bruising, or other orthopedic conditions.
“For laminitis, in particular, it is typically required to shut down the COX pathways to have any effect on pain,” says Blikslager. “The worst dilemma is a horse with laminitis and colitis. With these horses, it is best to start with NSAIDs but back off as soon as possible and hope other pain meds are helpful.”
For long-term anti-inflammatory use for osteoarthritis, chronic laminitis, or chronic stages of bone injuries, veterinarians typically reach for Equioxx. It might not be potent enough to provide relief during the acute stages of pain, but as a COX-2-selective inhibitor it limits the risk of side effects and is safer long-term.
Fultz emphasizes the importance of maintaining communication with your veterinarian while giving your horses prescribed NSAIDs. He or she can help monitor for complications and manage any side effects as soon as possible.
When Not to Use NSAIDs
“It is best to avoid NSAIDs when there is any evidence of complications or in dehydrated patients prior to rehydration,” says Blikslager.
Fultz agrees, adding, “Toxicity with NSAIDs is increased in animals off-feed, dehydrated, critically ill, or with pre-existing gastrointestinal disease, so veterinarians know to use caution in these cases.”
Due to the threats of renal papillary necrosis, gastric ulceration, and right dorsal colitis, it is essential to rehydrate horses that will be receiving NSAIDs.
“I recommend baseline bloodwork prior to starting a treatment plan involving NSAIDs,” says Fultz. Otherwise, “once anything out-of-character is noted, the horses may be more (adversely) affected than if caught early with bloodwork monitoring.”
In older horses veterinarians have historically used nonspecific COX inhibitors to treat chronic conditions such as osteoarthritis. “The ‘old school’ way of maintaining these horses is with Bute daily,” says Blikslager. “However, over time, that puts them at increased risk of GI and renal complications due to the length of time they are treated. This can be avoided by using a COX-2 inhibitor.”
Fultz recognizes that COX-2-selective NSAIDs have been shown to cause fewer side effects, particularly on intestinal tissues, in various studies, but points out an important detail: “Despite studying effects on numerous body systems up to three months, the manufacturer does not endorse Equioxx to be used for such long periods. If it will used for a prolonged period (beyond the recommended labeled duration) it is key to have a veterinarian be involved to help with monitoring beneficial outcomes and risks.”
Report any signs of the above complications in horses receiving NSAIDs to your veterinarian immediately. He or she might tell you to discontinue NSAID use and provide an alternative treatment.
Non-steroidal anti-inflammatory drugs serve an important role in managing equine pain and inflammation. These medications allow veterinarians and owners to provide sick or injured horses an improved quality of life. Each horse responds to NSAIDs differently, however, and because of their inherent risks, these drugs should always be used with a veterinarian’s advice. Knowing the signs associated with complications can help you recognize side effects early and address them properly. As with most medications, NSAIDs are best used in moderation.