blood draw on a horse

Altered States – Equine Drugging Reaches Another Decade Mark

A decade on and no real changes in drug regulation: the western industries are worse now.

Reprinted from Barrel Horse News in November, 2012.

Some horses are bred to run long distances fast; some bloodlines are famous for the inherent burst of quick speed they pass on. Some horses are bred for their ability to bury their haunches in the ground and turn. Some are bred for their fluid movements. In an industry that has grown more specialized than ever before, one thing remains true of all horses — performance horses included, and that is all members of the equine species are in some way shape or form are born to run.

Ancient survival instinct drives them to move faster in response to fear and anxiety, and even activities that they enjoy can trigger the instinctive flight response.

The task of horsemen and women is to take these specially bred horses and train them to perform at their utmost abilities without pushing them beyond their mental and physical limits. Perhaps the late, great horseman and reined cowhorse legend Greg Ward summed up training great horses the best when he said, “You know how they say, ‘Genius borders on insanity?’ Well, that’s kind of where I put them, right there on the edge.”

To the edge
A dirty little secret in today’s performance horse industry, both Western and English, is the uncontrolled use of psychotropic drugs—sedatives and tranquilizers—that allow competitors to hold their horses at the edge without sending them over.

Most of the behavior-altering drugs used today in the horse industry came from human medicine. Acepromazine, chlorpromazine, fluphenazine and reserpine are antipsychotic drugs used to treat mental illnesses such as schizophrenia and bipolar disorder. Guanabenz is an antihypertensive used to control blood pressure.

In the barrel racing industry, these “calming agents” are generally used to take the edge off excitable and overly anxious horses to improve their focus and manageability, thus their performance. While some barrel racers use psychotropic drugs temporarily to help horses through stressful situations — like experiencing fireworks and Ferris wheels at rodeos to rehabilitating the minds of “blown-up” performers. Then, there are horses that never compete without some sort of chemical assistance.

While considered unethical by some, no rules to prevent their use currently exist in the barrel racing industry. The fractured nature of the governance of the industry has left it without a clear-cut leader or financial backing to research, establish and administer such policies.

Here, with a little help from world-renowned veterinary pharmacologist and toxicologist Dr. Thomas Tobin of the Gluck Equine Research Center at the University of Kentucky in Lexington, we take a look at the most commonly used behavior-modifying drugs. Tobin, author of the definitive work Drugs and the Performance Horse, is responsible for the development of many of the drug tests used today by the Thoroughbred racing industry.

The phenothiazines tranquilizers
bottle of Acepromazine a phenothiazine tranquilizer for horsesAcepromazine (“Ace”), chlorpromazine and fluphenazine are known as phenothiazine-type tranquilizers. Although they don’t contain phenothiazine, these drugs are classified as such because of their related molecular structure. Acepromazine is the most commonly used phenothiazine tranquilizer in the horse industry.

Actual Phenothiazine is an insecticide introduced to the United States in 1935 by DuPont In the 1940s, it was used as one of the first deworming drenches for sheep.

Phenothiazine tranquilizers act as potent adrenergic blocking agents, meaning they block the action of adrenaline, the so-called “flight or fight” hormone.

Ace is the most commonly used phenothiazine tranquilizer used in the horse industry. It’s been used to produce short-acting sedation for more than 40 years. Because it lowers a horse’s blood pressure, ace has also been used as a vasodilator in the treatment of laminitis and, reportedly, in some cases as a preventative treatment against Exercise-Induced Pulmonary Hemorrhage (EIPH or “bleeding”). Its sedative properties that facilitate muscle relaxation have led to it being used to treat exertional rhabdomyolysis, or “tying up,” as well as some episodes of colic.

An FDA-approved drug, Ace is not without its problems. It’s known to cause the penile retractor muscle to relax thus causing penile prolapse. While handy for sheath cleaning, in rare cases, speculated to be less than 1 in 10,000 cases, geldings and stallions develop paraphimosis, the inability to retract their penis into the sheath. Veterinarians have also speculated that the presence of circulating testosterone at the time of ace administration may increase the risk of paraphimosis for breeding stallions. In severe cases, penile paralysis may necessitate the amputation of the organ.

At the 2009 American Association of Equine Practitioners convention, Ann Wagner, DVM, MS, Diplomate of the American College of Veterinary Anesthesiologist and American College of Veterinary Practitioners, made the case against the use of Ace in colts and stallions after observing three cases of paraphimosis, or persistent penile prolapsed. Two of cases resulted in amputation of the penis, despite the fact that low doses of the drug were administered.

Given the devastating consequences for breeding stallions, Wagner recommended using alternative sedatives and tranquilizers that use some other mechanism of action rather than an adrenergic-blocking phenothiazine tranquilizer.

Longer acting than Ace, chlorpromazine is another phenothiazine tranquilizer that has also been used as a calming agent in performance horses. But it too has the same potential side effect when administered at large doses. Unfortunately, what exactly constitutes a large dose is highly variable and often horse and use dependent.

First used in 1950, chlorpromazine was the prototype for the phenothiazine class of drugs. Developed in France as a surgical pre-anesthetic, doctors discovered patients administered chlorpromazine reported feeling calm and relaxed while they were coming out of anesthesia. This development changed human psychiatric therapy. Known as the “chemical lobotomy,” chlorpromazine is considered one of the greatest advancements in human psychiatric care.

Chlorpromazine’s veterinary use is largely limited to small animal medicine. It’s commonly used to control vomiting in cats and dogs and is sometimes used as a sedative in cattle, swine, sheep and goats.

“Chlorpromazine is not FDA approved for use in the horse and there are no FDA approved veterinary formulations,” says Tobin. In Drugs and the Performance Horse, Tobin notes a study conducted by N.N. Booth, entitled “Psychotrophic drugs in veterinary medicine,” that detailed the undesirable side effects of chlorpromazine use in horses.

“According to Booth,” Tobin states, “after a few minutes of initial sedation following administration of the drug, the animal may become unsteady, sink backward on its hocks, and lunge forward in an uncoordinated manner. The horse may stumble and fall but then will stand up with continued lunging and rearing. This violent reaction reportedly alternates with periods of sedation.”

Anecdotal evidence suggests that horse owners who have used low doses of chlorpromazine to take the edge of nervous horses have also experienced such extremes.

Both Ace and chlorpromazine are relatively short acting with their pharmacological effect after a therapeutic dose ending within a number of hours.

“The advantage with a short-acting medication is that if you don’t like the response, you just wait,” says Tobin. “You either try a different dose next time, or you don’t.”

That isn’t the case with fluphenazine. A chemical cousin to ace and chlorpromazine, fluphenazine has some particularly nefarious side effects. A much more potent drug, approximately 50 to 70 times more potent than chlorpromazine, fluphenazine is available as a long-acting preparation that can be effective for several weeks, and if a horse is overly sensitive to it or is inappropriately dosed, it can be problematic.

A pharmacological cousin to acepromazine and chlorpromazine, fluphenazine is used in human medicine to treat schizophrenia and bipolar disorders. The long-acting form of the drug can be used to “take the edge off” a horse for several weeks, but the side effects can be particularly nasty.

bottle of fluphenazine is used in human medicine to treat schizophrenia and bipolar disorders.In humans, fluphenazine is used to treat schizophrenia and acute bipolar disorders. In veterinary medicine, it’s used for horses stall-bound due to injury and to take the edge off nervous horses. In some instances, it’s recommended for extremely excitable horses with chronic tying-up disorders.

The biggest drawbacks to fluphenazine are the extra-pyramidal effects, which refers to the parts of the brain that are affected by the drug. Extra-pyramidal effects leave the horse in a manic, excitatory state, where they are essentially uncontrollable. Horses suffering from fluphenazine toxicity also exhibit Parkinsonism — involuntary muscle moments, tremors, restlessness and agitation.

While these adverse side effects are typically reported in horses that have received an overdose of fluphenazine, either at initial administration or following repeated dosing intervals, they can occur in horses that were given the same dose safely in the past. It’s highly dose, and horse, dependent.

Reserpine
Reserpine is one of the world’s oldest tranquilizers. Made from the climbing vine Rauwolfia serpentina native to India, it was known in ancient Hindu writings as the “insanity herb” and was used to treat high blood pressure, insomnia, and of course, insanity. Its ability to lower blood pressure made it valuable as a treatment for snakebites, and a particularly handy drug in a land populated by some of the world’s most deadly vipers. Mahatma Gandhi was said to have used reserpine as a tranquilizer, and ancient texts have Alexander the Great using it to treat his general Ptolemy, who had fallen in battle to a poison arrow.

The “Indian Snakeroot” made its way into modern medicine prior to World War II, when two Indian doctors first reported of its antipsychotic properties in a Western medical journal.

“Reserpine and acepromazine were introduced into Western medicine at about the same time,” notes Tobin, who did his PhD in pharmacology under the direction of Amar Sen, whose father was one of the introductory Indian doctors. “Reserpine was so long-lasting that they were overdosing patients. Its effects are relatively quite long lasting; the effect of a single dose can last up to maybe 30 days, but they would dose the drug daily. Psychiatrists then found that their patients were getting depressed and committing suicide, and they concluded that reserpine was unmasking latent suicidal tendencies, which was somewhat unlikely; much more likely was that it was simply an overdose situation.”

Today it’s rarely used as a human antipsychotic, but is still used to manage high blood pressure when other medicines have failed.

Although not FDA approved for use in horses, reserpine was once considered a possible treatment for fescue toxicity that causes gestational problems and abortion in mares, but its principal use in equine medicine today is to take the edge off excitable or difficult to manage horses.

“It’s a very subtle, long-acting tranquilizer,” says Tobin. “It’s a relatively potent drug. It’s also very difficult to detect. When we started this business [of drug detection] 30 years ago, we couldn’t detect a couple of milligrams of a substance like reserpine. On the other hand, one needs to keep in mind that testing is now about 1 million times more sensitive than when I started in this business 35 years ago, and nowadays virtually all drugs and medications are readily detectable, and some for quite long periods post-administration.”

Although highly detectable by today’s drug tests, a positive result can be complicated by the presence of trace amounts of similar substances from native plants, like periwinkles, that are found in some areas of the United States, particularly in the Southeast.

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Like other tranquilizers, reserpine is highly dose dependent.

“You can take the edge off a horse for up to two weeks with small doses of reserpine, if you’ve got the right horse and the right dose,” says Tobin. “The first day the horse may be a little depressed, have a little diarrhea or flatulence, but after two days or so, he’s normal to visual inspection, but if you know the behavior of the horse well, and especially if you know him to be excitable and difficult to manage, you will know he’s tranquilized.”

The use of reserpine in this manner is largely unstudied, but anecdotal evidence suggests that the drug may, in very rare instances, cause penile prolapse in male horses, thus making penile paralysis a possible side effect. Other possible side effects include violent colic, diarrhea and sweating over the back and hindquarters.

The reactions to reserpine can be variable among horses. Warns Tobin, “You need to know how to use it and it also helps to know your horse.”

Guanabenz
Guanabenz found its way into the horse industry over the past decade. It’s an anti-hypertensive drug used to treat high blood pressure in humans by decreasing heart rate and relaxing vessels for ease of blood flow.

Its ability to regulate blood pressure drew the interest of racetrack veterinarians who were looking for alternatives to the diuretic furosemide (Lasix®) to manage EIPH. Although its use in the management of EIPH has yet to be clinically proven, veterinarians noticed guanabenz was an effective calming agent.

Tobin was charged with the task of developing a post-race test to detect guanabenz.

“I was bringing up a test for it, and as we were dosing horses with various amounts, I noticed some very interesting pharmacology,” says Tobin. “It’s just like detomidine [Domosedan], except it’s longer-acting and has better analgesic responses, so I filed for a patent on its use in the horse.”

Detomidine, a widely used chemical restraint in the same family as xylazine (Rompun), is much stronger than the phenothazine tranqulizers. It’s known to cause hypertension shortly after administration followed by a period of bradycardia, a slowing of the heartbeat. Other side effects include muscle tremors, excess sweating and partial penile prolapse. Horses are extremely lethargic and often stand with their heads lowered between their legs.

Compared to detomidine, guanabenz is a long-acting and rapidly reversible sedative. While detomidine may last less than an hour, the effects of guanabenz at sedative levels can last for several hours.

Just how affective guanabenz is as a calming agent in performance horses was studied by researchers at the University of Florida. In their paper “The effect of adrenergic suppression induced by guanabenz administration on exercising Thoroughbred horses,” published in the August 2006 Equine Veterinary Journal Supplement, researchers concluded guanabenz did induce signs of adrenergic suppression.

During exercise, the treated horses had lower heart rates, lower levels of the stress hormone cortisol and adrenaline in their bloodstreams when compared to the untreated horses. The results suggested that guanabenz administration “may enhance endurance” but further research was needed.

Anecdotal evidence
The use of antipsychotic and antihypertensive drugs to calm horses is largely anecdotal. Veterinarians aren’t taught how to use them in vet school. While studies exist on their use as calmatives, even fewer exist on their performance enhancing effects.

Speaking off the record, trainers and competitors said they favored the drugs over “wet saddle blankets” and “loping down” because it saved their horses legs from exhaustion-related injuries. It was also cheap insurance on “a $100,000 investment.”

Barrel horse trainers were less concerned about the psychotropic drugs because of the fine line between taking the edge off and taking away the run needed to win. They were more concerned with the “hops,” the stimulant drugs used to make a horse run through pain and beyond their physical endurance. Sadly, in the barrel racing industry psychotropic drugs have been used to make horses under the influence of stimulant drugs and anabolic steroids more manageable.

person giving a horse medicine through it's mouthWhat remains unknown is the long-term effects on a horse’s physical and mental wellbeing afterwards, and just how much of a competitive edge they provide.

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Some veterinarians and horseman have hypothesized that the use of tranquilizers and sedatives, such as Ace that facilitates muscle relaxation, and may make horses more prone to soft tissue injuries. The theory being that ligaments take up some of the weight-bearing duties for overly relaxed muscles, making them more susceptible to injury. Others wonder if the overuse of psychotropic drugs is responsible for the large number of horses that are expressing neurological disorders such as Equine Protozoal Myleoencphelitis.

For all the theories of what these drugs may and may not do, their use in this manner has yet to be studied.

 

 

 

 

 

 

Taking a stand
When it comes to any type of illegal medical enhancement of performance and racehorses, the United States leads the way. In Europe, equestrian sports like three-day eventing, jumping, dressage and endurance racing, as well as the Western sports that have become popular there like reining and barrel racing, must comply with the Olympic-level standards of the FEI.

In the 1970s when veterinary pharmacologists such as Tobin developed tests to detect subtle levels of the earlier tranquilizers and sedatives, they were banned from FEI-sanctioned events. Subsequently, their banning trickled down to FEI affiliates and other horse sporting organizations that look to the FEI as the supreme governing body of all things equestrian.

Tobin’s understanding is that their use as shortcuts in the training process prompted the bans.

“They were reportedly being used as shortcuts to getting a desired effect that a skilled horseman may have to take a long time and a lot of effort to get,” he says. “You could potentially produce similar effects with the use of a tranquilizer within a relatively short period, so they were seen as an unfair and inappropriate advantage.”

Currently, all the drugs previously mentioned in this article are banned drugs, meaning they cannot be found in any level in a horse’s system, under FEI rules. Ace is the only exception. FEI lists it as a control substance, meaning it must be used under certain guidelines.

The AQHA and United States Equestrian Federation, which governs mostly English horse sports, both have judicious-use guidelines. For instance, the AQHA has guidelines for the use of “therapeutic medications” such as phenylbutazone (“bute”), diclofenac (Surpass®), flunixin (“banamine”), ketoprofin,  Furosemide (Lasix®), Isoxsuprine and Dexamethasone, etc. However, in regards to other drugs, like tranquilizers, sedatives and performance enhancers, they are strictly forbidden as they “depress the cardiovascular, respiratory or central nervous system.”

The National Reined Cowhorse Association, National Reining Horse Association and National Cutting Horse Association all have similar policies in place.

Jerry Black, DVM, a breeder and owner of cutting horses who now serves as the Director of Equine Science Undergraduate Programs at Colorado State University in Fort Collins, was part of the NCHA committee that put forth the association’s drug testing initiative.

“The AAEP, American Horse Council, the USEF and AQHA have taken the stance that there is no place for psychotropic drugs, sedatives or tranquilizers in the performance industry,” said Black, who was one of the founders of Pioneer Equine Hospital in Oakdale, Calif. “I think when it gets right down to it, given the opportunity there will always be those looking for a competitive edge of some kind or to alter the way they need to train a horse. The sad thing is we’re so far into (the use of behavioral modifying drugs) that we’re crowning multiple champions that do not perform well without these types of drugs, and consequently, we’re breeding a horse that’s become dependent on them to show. There comes a point when we have to say the welfare of the horse is a priority.

“The worst thing is that we’ve allowed this to get completely out of hand. There are young trainers and some older trainers that don’t think they can compete without these medications. It’s become the new industry standard.”

With public outcry after the horrific breakdown of the gallant mare Eight Bells at the end of the 2008 Kentucky Derby and the tragic death of 21 polo ponies due to the administration of a performance-enhancing vitamin cocktail in 2009, the time for drawing a line the sand is now, said Black.

“Society won’t accept it now,” he said. “They won’t accept it in human athletes and they certainly won’t accept it in the performance horse world, nor should they really. This is a public issue, particularly after there was a Congressional hearing conducted after the Eight Belles incident, it’s obvious if we don’t take care of this ourselves, within the industry, it will be legislated.”

Changing the Tide
Changes of this nature are never easy, but they can be done.

“Changes comes along gradually,” says Jim Heird, PhD, executive professor and coordinator of the Equine Initiative at Texas A&M University in College Station. “We are making progress.”

Heird points to the drastic improvements in the Walking Horse industry. The fallout from the practice of “soring,” where caustic materials and devices are used to produced the “Big Lick” gaited steps, left the industry without a championship show because competitors feared federal (yes federal) inspectors from the United States Department of Agriculture.

Black says the use of psychotropic drugs often becomes a mindset—trainers think they have to use them to win.

“You always want to have a level playing field and the welfare of the horse in mind,” says Black. “Those are paramount for any horse event. We have to remember the horse is what got us here, and it’s our obligation to take care of them.

“It’s going to be difficult for some people to adjust, but what choice do we have?”

What will be difficult to overcome in the barrel racing industry is the lack of a unifying governing body.

“If you don’t have an association that governs what you’re doing, change is going to be difficult,” Heird says. “You have to have leadership and membership that wants to make a change. The membership has got to want to do and you have to have leadership with courage. If you don’t have enough people calling for change, the industry isn’t ready for it.”

When an industry can’t or won’t police itself, outsiders often step in, like the federal government did with the Walking horse industry. The important thing to realize is that what’s become acceptable to the industry, isn’t necessary acceptable to the general public.

Heird urges trainers and competitors to look at what they’re doing from an outsider’s perspective.

“I always ask people, ‘Could you defend this on 60 Minutes? If you can’t, you need to stop doing it.”