Written by: Dr. Joan Norton

Horse Sport International’s resident vet Dr. John Norton discusses the latest changes to the FEI’s Equine Prohibited Substances List.

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Every year the FEI Bureau approves changes to the FEI Equine Prohibited Substances List according to recommendations made by ‘The List Group’. The Group consists of 12 experts, including veterinarians, pharmacologists, toxicologists and research scientists. The List revisions are made following extensive consultation by the Group in response to scientific advances and information available regarding the use of substances in horses. The List review process is continuous and results in the publication of an updated version which becomes effective each January 1st.

This year the FEI changed the status of one medication and added a few new names to the list.

Adrenocorticotropic hormone (ACTH)

ACTH is a corticotropic hormone that in nature is produced by the mammalian pituitary gland that sits within the skull just below the brain. ACTH travels through the bloodstream and acts directly on the adrenal glands (adjacent to the kidneys) to stimulate the production of natural steroids, most notably cortisol, in response to stress. This drug was previous considered a Banned Substance but has been moved to the Controlled Substance list because it is, ‘considered as having a therapeutic value in equine medicine.’

Synthetic ACTH can be produced and is used in a variety of diagnostic tests and for some treatments in human medicine. Diagnostically, ACTH can be injected into a patient in order to measure the adrenal glands’ response and categorize adrenal diseases such as Addison’s Disease and Cushing’s Disease in humans. ACTH was briefly investigated as a diagnostic test for Equine Cushing’s Disease (PPID). However, in horses it is the pituitary gland that is diseased, not the adrenal glands, and testing that investigates pituitary function are more sensitive.

Because ACTH stimulates the production of cortisol, an anti-inflammatory stress hormone, rheumatologists prescribe this medication to decrease inflammation and pain associated with a variety of syndromes. Unfortunately for those which benefit from this drug, it is prohibitively expensive and may not be as effective as advertised. This controversy was even covered by a New York Times story in 2012, exposing costs at upwards of $28,000 a vial.

In equine medicine, ACTH could be used as an anti-inflammatory, especially in cases of osteoarthritis. However, to my best knowledge, no controlled clinical trials have ever been published showing a beneficial effect of ACTH for any condition. Even if you could afford the cost, the risks outweigh the potential benefits because the chronic administration of exogenous ACTH could induce signs consistent with Cushing’s Disease. In Equine Cushing’s Disease, ACTH is overproduced by the body, leading to an excess of circulating cortisol. Excessive amounts of cortisol in the blood stream will lead to suppression of the immune system, poor wound healing and chronic illness. High levels of cortisol may also be connected to the high incidence of laminitis seen in PPID horses.

Ammonium Chloride

Ammonium chloride is one of the new additions to the Banned Substance list because of its ‘potential abuse as a nerve blocking agent.’ There are many compounds that when placed around a nerve will produce a numbing sensation. These local anesthetics certainly have their place in veterinary medicine as a part of our diagnostic lameness evaluations, to numb a surgical site or to briefly control pain.

There are several short-term local anesthetics such as lidocaine and mepivicaine (Carbocaine) that remain on the Controlled Substance list. These medications have quick onset of action and most importantly, a short duration (minutes to hours). In contrast, ammonium chloride delivers a much longer blockade of the nerve’s pathway. One study showed a decreased response to a painful stimuli for up to five days.

The danger in this type of long term numbing is that it can easily mask the development or worsening of an injury or disease. While the horse may look sound, whatever caused the pain in the first place has not been addressed and continuing to exercise or compete this animal could lead to catastrophic injury or permanent damage.

While your veterinarian may need to administer a nerve block to your horse for diagnostic or therapeutic reasons, there are many safe and legal options available and the loss of ammonium chloride as a nerve block agent should not affect our ability to properly care for our horses.

Gamma Hydroxybuterate (GHB) and Gamma-Butyrolactone (GBL)

GHB and GBL are previously unlisted drugs that have been added to the Banned Substance list because of a ‘high potential for abuse to improve athletic performance.’ GHB is the active compound and GBL is a prodrug that is metabolized into GHB after administration.

In humans it has been shown that GHB stimulates the production of growth hormone, up to five times baseline levels. This effect has been used and abused by bodybuilders to increase muscle gains and could have the same effect on our horses, though no studies have been performed to evaluate the safety of GHB in horses or whether it produces any anabolic effects.

If this drug name sounds familiar to you in an ominous way it’s because it is more well known as ‘the date rape drug,’ due to its action as a narcotic sedative and ability to produce drowsiness, dizziness, loss of consciousness and even amnesia. None of these are effects that you would want to produce in your horses, no matter how great the athletic gain. In human medicine it is legally used to treat sleep related disorders such as narcolepsy by increasing slow-wave sleep but this use is closely regulated by the FDA through a patient registry. Not only is this medication illegal to use in FEI horses but in many US states it is a class I drug carrying fines up to $5 million and jail sentences as long as 20 years.

Metformin

Metformin is a new addition to the Controlled Substance list because of its ‘potential welfare risks.’ Metformin is a potent anti-diabetic drug that is widely used in human medicine. This drug works to lower blood sugar in hyperglycemic patients by increasing the uptake of glucose by the liver and muscle cells and decreasing the liver’s output of new glucose into the blood stream. In horses we have also recognized that metformin increases the intestinal cell’s utilization of carbohydrates, so that less sugar enters the blood stream after a meal. This medication is gaining popularity for the treatment of Equine Metabolic Syndrome and insulin resistance, especially in the presence of hyperglycemia or a higher carbohydrate diet.

This medication has great benefit for horses dealing with abnormally high blood glucose levels and syndromes that affect insulin sensitivity which can lead to laminitis, for example. However, while metformin will help lower high blood glucose back to normal, it will likewise decrease a normal glucose to a dangerously low level. Hypoglycemia in horses is characterized by weakness, collapse and seizures. By placing this medication on the Controlled Substance list the FEI is allowing veterinarians to treat horses that would truly benefit from this medication while protecting horses from competing while on a medication that could cause dangerous episodes of hypoglycemia.

Levothyroxine (Thyro-L)

Levothyroxine is another new addition to the Controlled Substance list because it ‘could enhance performance.’ Thyro-L is a commonly used and misused medication in equine medicine.

The labeled use for this drug is for the treatment of hypothyroidism. However, hypothyroidism in horses is extremely rare and often misdiagnosed based on simple baseline thyroid hormone levels. Thyroid hormone levels that are measured in the blood may not reveal true thyroid function and it is the function of the thyroid gland, and not the hormone levels, that are important for our horse’s health.

It is also known that certain medications (phenylbutazone and dexamethasone), strenuous exercise and diets high in energy, protein, zinc and copper, will falsely alter the levels of circulating hormones in the bloodstream. The only way to know about how the thyroid functions is to perform thyroid function tests, which are rarely done in the field because the medications needed to stimulate the thyroid (to prove that it is working) are not readily available.

Often times when horses that are showing the ‘classic’ signs of hypothyroidism (depression, weight gain, lethargy), and have low thyroid hormone levels are tested for true thyroid function, they are found to be normal. It is more likely that these horses are suffering from Equine Metabolic Syndrome and insulin resistance, leading to obesity and the other signs commonly associated with hypothyroidism.

The reason that Thyro-L has been so successful in treating these cases is because thyroid supplementation causes an increase in metabolism. By increasing the horse’s metabolism they are able to lose weight and correct their insulin resistance. It works so well that researchers are now recommending treating these types of horses with a much higher dose of thyroid supplementation, a “supraphysiologic dose.” Because of their increased metabolism these horses will consume more feed (if allowed) and have much higher energy levels as the body utilizes fat for fuel.

It is easy to see how this increase in metabolism and energy levels could improve performance as well. Equally, inappropriate use and long term administration of this hormone supplementation could be dangerous. Side effects of thyroid medications in humans include rapid and irregular heart rates as well as sweating and trembling. The long-term effects of chronic supplementation in horses has yet to be investigated. So, while Thyro-L does have its place in the treatment of obesity and obesity related diseases in horses, the use of this drug for performance enhancement could lead to unwanted and serious side effects.

These new changes to the FEI medications list are all designed to keep our horses safe and our competitions fair. The changes made will not adversely affect a veterinarian’s ability to keep athletes healthy. Make sure to discuss these changes with your own veterinarian to make sure that the medications your horses receive are not only FEI compliant but safe.