A Shot in the Dark

Author's note: This article is intended to improve your understanding of drugs commonly used in equine veterinary care; it is not a "treatment guide" for the lay person. No medication or combination thereof should be given without veterinary consultation. Medications given in the wrong circumstance, via the wrong route, and/or in the wrong combination can hurt or kill. The administration of any medication to your horse should be taken very seriously.


All drugs can be toxic if used incorrectly. There are drugs that can be toxic at regular therapeutic doses if certain predisposing factors exist, and it is necessary to know what side effects can occur if there is an adverse reaction. This includes vaccines. Many people perform their own vaccinations to cut down on expenses; if you are going to take on this responsibility, you must also take on the responsibility of learning about what can happen if something goes wrong. It might only be 1 in 100,000 or so horses which have an anaphylactic reaction to a vaccination, but one thing is for certain--if your horse does have one and you don't know what to do, he will most likely die. If you are doing your own vaccinating and deworming, discuss this with your veterinarian and be prepared to recognize and deal with any complications that might occur.

Another potential concern when looking to cut costs is the quality of the drugs. Drugs aren't indestructible, and in addition to losing potency after their expiration date, the method of storage can affect their stability. When buying drugs, we are trusting that since leaving the pharmaceutical company, the drugs that required refrigeration were refrigerated at all times and other storage requirements were maintained. Remember that most of the time, prices too good to be true usually are. In general, you should only get pharmaceuticals from your veterinarian or from sources approved by him/her.

In the Beginning

All drugs start out as basic research ideas or observations showing therapeutic promise. Getting Food and Drug Administration (FDA) approval is a long, costly process, often taking eight to 12 years and costing $35-45 million (or more) from the day the idea is generated to the first lot being sold at the pharmacy. For better or worse, the pharmaceutical industry is very much profit-driven, which impacts medication prices and limits somewhat the development of drugs that would have low demand.

When a drug goes through the approval process, experimentation is typically limited to a relatively narrow usage. In other words, a drug will be evaluated at one specific dosage for a specific use in a specific species. Therefore, a particular drug might be licensed for use for treating a specific disease process in people at a specified dose. This does not mean that the drug would not be useful for treating a disease in the horse or other animal, but the necessary research to determine the best route of administration, dosage, frequency of administration, effectiveness, and side effects has not been done by the company making the drug.

With veterinary drugs, a pharmaceutical company usually won't spend the research and development (R&D) money to get a drug through the approval process unless it is for common usage and there is a good chance the company will make a return on its investment in the approval process during the period of patent protection. As a result of these limitations, a tremendous amount of additional research is required in order to determine if a new drug has the potential for "extra-label" use in the horse.

With an FDA ruling that went into effect in December of 1996, the administration of many commonly used drugs in horses technically was supported by the FDA. For example, most veterinary literature recommends using intramuscular penicillin at a dose approximately three times higher than the dose recommended on the human package label, and for certain diseases up to 10 times higher.

We continue to learn about a drug for a long time after it has been licensed. We often find that a different dose or method of administration works better in some situations and has little or no adverse effects, or that a drug has uses for other problems or disease processes. (Aspirin used prophylactically by humans for blood thinning against heart attacks is a good example.) This also works in reverse, where certain unacceptable side effects (or negative interactions with other drugs) are not discovered in a few thousand test subjects during the approval process, but are discovered after a million or so clinical cases are treated.

When a pharmaceutical company gets a drug approved by the FDA, an enormous body of scientific research data has been submitted to support both the effectiveness of the drug to work on the disease and the safety of the drug. Drugs are "licensed" for a specific purpose at a specific dose to be administered in a specific way to a specific species. If, as with penicillin, a drug is determined by the veterinary profession by experience and independent research to be more effective at treating a particular disease safely at double the dose, then that treatment methodology is generally adopted without breaking federal law.

The FDA ruling was extremely important for the veterinary profession and was supported by the American Veterinary Medical Association and the American Association of Equine Practitioners; it allows for better animal care and prevention/treatment of animal suffering.

Understanding Medications

The basic study of how a drug is absorbed and distributed by the body is called pharmacokinetics, and the study of what a drug does and how well it does it is clinical pharmacology. The first step is to see how well a drug is absorbed via the chosen route of administration and determine what dose will need to be administered to achieve a therapeutic concentration of the drug in the various body systems.

The route of administration is determined by many factors. The oral route is the most convenient, but requires the drug to be absorbed from the gastrointestinal system well enough to provide therapeutic concentrations and at the same time not cause negative effects. Many of the antibiotics are absorbed well enough, but because of the very large population of bacteria in the horse's large intestine, they can cause very severe (sometimes fatal) diarrhea by killing off normal bacterial flora.

Many drugs are absorbed quite well by humans and other animals, but are not absorbed by the horse. Therefore, if a particular drug is not approved for oral use in the horse, its oral use will require some degree of independent research confirming the correct dose and frequency of administration to achieve therapeutic concentrations.

With some drugs, such as phenylbutazone (Bute), the route of administration might be confined to intravenous or oral use because of a severe local tissue reaction or poor absorption when injected into muscle tissue. Other drugs, such as the older injectable form of ivermectin (no longer available for use in the horse), greatly increase the risk of developing severe infections at the injection site when injected into muscle tissue.

If you're administering medications yourself, it's very important to follow directions from your veterinarian regarding route of administration as well as dose and frequency of administration, and to know that these guidelines were developed through a great deal of research. There are new articles on equine pharmacology and treatment almost monthly in a variety of medical journals that expand our knowledge in this rapidly growing area of research.

The math and terminology used in pharmacology can be confusing and misunderstanding--if you don't understand something in a medication's literature, ask your veterinarian about it before giving it to your horse. Not asking questions if you don't understand can lead to treatment failure at the very least, or cause fatal consequences in a worst-case scenario. If you have any questions or cannot read/understand the directions given with a drug prescribed for your horse, do not administer the drug until you know what is correct.

Terminology can be confusing. The terms "mL" and "cc" stand for "milliliter" and "cubic centimeter" and are the same volume of a liquid (1/1,000 of a liter). These terms are often confused for a concentration of drug, but 1 mL (cc) of a solution can contain 10 milligrams or 1,000 milligrams of the actual drug. The term "mg" stands for "milligram" and is a unit of weight measurement (1 milligram is 1/1,000 of a gram). Again, note that "mg" is quite different than "mL." A drug will contain an amount of drug per volume of what you are administering (milligrams per milliliter).

For example, the anti-inflammatory drug phenylbutazone has a concentration of 200 mg per mL (or cc), so 5 mL (or 5 cc) contains 1,000 mg (or 1 gram) of phenylbutazone. This would be the same for an oral solution/syrup.

Be very careful with paste products to understand how many milligrams of drug (concentration of drug) there are within the specified quantity of paste. The drug dose is calculated based on the drug concentration within the liquid, powder, or tablet. There is no standard--each drug is different, and the concentration of the active ingredient depends on its individual composition.

You also must be exact with the decimal points (is that 9.0 or 90?). Some drugs come in various strengths or concentrations, but are packaged and labeled similarly. Always double check the individual label and directions on every new bottle--read the label, check it, then double check it. I find it very helpful to have a focused conversation between myself and a client on dosage, in addition to providing clear written instructions. Remember, if you don't understand the instructions, ask questions.

Usually, the more people involved in the treatment of a horse, the greater the chances for an accident. Make sure that the necessary information gets passed along to the individuals who will be responsible for medicating the horse. In a large stable or boarding situation, it is sometimes helpful to designate one person to administer all of the medications and to have a chart to keep track of what, when, and how much is to be given (download an example chart here). Require the person to sign off on it just like in a hospital setting.

After a drug is given, it is either removed from the body via the kidneys (urine) and/or they are metabolized by the liver and excreted in the bile via the gastrointestinal system. The rate that an individual drug is metabolized and eliminated from the body varies greatly and will to some degree determine when the next dose will be needed.

The most common cause of treatment failure in both human and veterinary medicine is the failure to ensure that the dose is adequate and is given at the appropriate frequency for the appropriate duration of time. How many half-full prescription bottles are in your medicine cabinet? Once a course of therapy has been prescribed, it is important that the dose/frequency/duration be followed. There are important reasons why some drugs are given four times a day instead of three. If your individual situation (or your horse's) does not allow for frequent administration of a drug, be sure to point that out to your veterinarian. But keep in mind that you might be trading convenience for a less effective drug.

Non-Steroidal Anti-Inflammatories

Non-steroidal anti-inflammatory drugs (NSAIDs) are classified by their mechanism of action. There are more than a dozen available for use in people, but phenylbutazone, flunixin meglumine (Banamine), ketoprofen (Ketofen), and naproxen are the most common ones used in horses. These drugs relieve pain by reducing inflammation (anti-inflammatory) and are called analgesic agents (relief of pain).

These drugs function by blocking the production of an inflammatory chemical mediator called prostaglandin, thus they are also called "anti-prostaglandin" drugs. When the cells making up various body tissues are traumatized or damaged, a complex biochemical pathway is triggered, with one of the end results being the production of prostaglandins. The build-up of prostaglandins causes blood vessels to leak, causing edema (fluid swelling) within the affected tissues, the stimulation of pain receptors, and the dilation of blood vessels causing the primary and classic signs of inflammation--heat, pain, and swelling.

The NSAIDs block the production of prostaglandins. As with the NSAIDs in people, some horses and/or injuries respond better to one drug than the others. (For example, phenylbutazone is typically thought to be more beneficial in treating musculoskeletal inflammation and flunixin meglumine is thought to be more beneficial with gastrointestinal inflammation.)

The NSAIDs are known for their side effects on the gastrointestinal system; they can cause ulcer development in the stomach and large colon. This side effect is related to the fact that there are "protective" as well as "inflammatory" prostaglandins produced in the body. The protective prostaglandins help protect the stomach lining against damage from digestive acid and enzymes. Prostaglandins also protect parts of the colon and kidneys.

NSAIDs block all prostaglandins, both protective and inflammatory, to varied degrees depending on the individual drug. The ulcerative side effect is more commonly associated with higher doses and administration over time, but occasionally some horses show signs of gastric ulcers after only a few doses. This side effect is not entirely because the NSAIDs are "hard" on the stomach, as commonly thought. The side effect is mainly systemic, meaning that it is not caused by direct contact with the stomach. There is risk of toxicity with intravenously administered NSAIDs as with oral administration.

Care must be taken to minimize the dose and length of treatment, and if signs of ulcers develop (i.e., depression, not eating, teeth grinding, colic), the drug should be stopped immediately. Drugs more specific in blocking inflammatory prostaglandins are available for human use, but the available NSAIDs for horses aren't very specific in blocking the production of only inflammatory prostaglandins. Research on more specific NSAIDs for horses is needed.

Muscle Relaxant

Methocarbamol (Robaxin) is essentially the only muscle relaxant used in the horse. Its muscle relaxing action is not caused by a direct action on the muscle, but via effects on the central nervous system. This drug is most commonly used as part of the treatment of spasm/tightness of the long back muscles. In most cases, this condition involves some degree of inflammation of the muscles, requiring some degree of concurrent anti-inflammatory treatment.

Sometimes acepromazine, a tranquilizer, is used to relax a horse which is tying-up. It also improves muscle blood flow during tying-up.

Steroids

Steroids, very potent anti-inflammatory drugs, also interfere with the production of prostaglandins. Commonly used steroids in the horse are dexamethasone, methylprednisolone, betamethasone, triamcinolone, prednisone, and others. Steroids also block the biochemical pathways responsible for allergic reactions (NSAIDs do not have a significant effect with respect to allergic inflammation) and are often used for the treatment of hives, allergic airway disease, uveitis (moon blindness), and other immune-mediated diseases.

Since steroids (especially at higher doses or prolonged administration) suppress the immune system, they must be used with great care. Another potential side effect of steroids is the development of laminitis (founder); this is also typically with higher doses or long-term administration. A small number of horses appear hypersensitive and develop sore feet after only a relatively small dose. Triamcinolone is most often associated with these side effects due to its potency, but any steroid can cause problems if it isn't used with extreme caution. Care should be taken to monitor the feet for increased digital pulses, heat, or soreness in horses receiving steroids.

Steroid treatment is standard for uveitis, but the use of ocular steroids predisposes horses to fungal infection (since the immune system is somewhat suppressed). It is necessary to carefully monitor an eye being treated with steroids. There are many ophthalmic antibiotic ointments that have steroids, so care must be taken not to inadvertently treat a corneal ulcer with an ointment containing steroids--again, read labels carefully.

Steroids are also useful for treating a variety of joint inflammations, but certain protocols must be followed. When used incorrectly, they can damage cartilage.

Steroids are powerful anti-inflammatory drugs, but they require careful, respectful use to avoid or minimize side effects.

Antibiotics

We are limited to a relatively small number of antibiotics for use in the horse compared to those available for humans and small animals, largely because many are cost-prohibitive when scaled up to horse doses. Some have severe side effects. One serious problem is the extremely rapid increase of antibiotic resistance. The emergence of bacteria that are highly resistant to antibiotics is frightening and in many cases related to poor judgment in antibiotic use.

If antibiotics are used, we have a high level of responsibility to ensure that:

  • The use of antibiotics is warranted;
  • An appropriate one is selected; and
  • They are administered by the appropriate route, at the appropriate dose, at the right frequency, and for the correct duration.

When an antibiotic is given, the choice of which one to use is at first an educated guess based on the knowledge of what the likely bacteria might be relative to the clinical nature of the infection (and frequently confirmed with laboratory testing). If an antibiotic is not a good "match" for the infection, or if the antibiotic is administered at the wrong dose based on body weight (and sometimes the type of bacteria involved), or if the daily frequency and total duration of treatment are not correct for the situation, there is a chance of promoting antibiotic resistance by allowing somewhat resistant strains to survive and reproduce.

As already mentioned, many antibiotics available to people and small animals are either cost-prohibitive or have severe side effects in horses. For these reasons, we should be very careful with respect to the serious rise in antibiotic resistance and guard against indiscriminate antibiotic use.

With some antibiotics, diarrhea can be a significant side effect due to a large portion of the horse's digestive system being dependent on a very specific population of bacteria within the colon. Although the development of diarrhea secondary to antibiotic use is more commonly associated with oral administration and a direct disturbance of the bacterial flora within the gastrointestinal system, diarrhea can occur with intravenous/intramuscular administration of certain antibiotics. Some antibiotics, such as terramycin, cannot be used in the horse at all due to the seriousness of gastrointestinal disturbance.

The antibiotic powders and liquids (terramycin, lincomycin, and others) intended for use in calves, poultry, and swine, or antibiotic injections intended for use in adult cattle that are available for sale at many feed and farm supply stores, should never be used in the horse due to the risk of them causing severe or even fatal diarrhea.

Another potential side effect of some antibiotics is kidney damage. For example, with prolonged gentamicin use in the horse, it is common to evaluate kidney function with blood analysis. Some of the more commonly used antibiotics in the horse are sulfadiazine-trimethoprim (TMS, or SMZ-TMS, sulfa-trimethoprim), penicillin, ampicillin, ceftiofur (Naxcel), gentamicin, oxytetracycline, and doxycycline.

Dimethyl Sulfoxide (DMSO)

This drug, used as an industrial degreasing agent 50 years ago, now has many pharmaceutical uses. These have been heavily researched; DMSO is mainly used as an anti-inflammatory medication based on its ability to neutralize "free radicals." Free radicals are chemicals produced by destroyed or damaged cell membranes. They are particularly destructive as they in turn destroy more cell membranes, creating more free radicals--it is a self-propagating biochemical chain reaction of tissue destruction.

DMSO can be administered orally and intravenously to treat a variety of neurologic and muscular disorders. One very special property of DMSO is its ability to pass through intact skin and penetrate deep into the tissue underneath and into the circulatory system within seconds.

Another special property of DMSO is its ability to carry deep into tissue a variety of substances that normally would not be absorbed. For that reason, DMSO can be used as a carrier agent for steroids, antibiotics, and antifungals. DMSO is often used to treat tendon, ligament, and muscular injuries (inflammation).

Great caution must be taken when working with DMSO because of its carrier property. There are several documented cases of horses developing fatal kidney failure after DMSO was applied to a leg that had been previously blistered with a mercury compound. When using DMSO, make sure the skin is very clean and completely dry to avoid scalding of the skin (DMSO reacts with water, producing a significant amount of heat). Also, keep the bottle tightly capped and don't contaminate it with anything.

Remember, virtually any drug or substance that is mixed with DMSO or is on the skin prior to application will enter the bloodstream, potentially causing a tissue reaction, illness, or positive drug test. Be careful and wear gloves--it will penetrate your skin just as easily.

Sedatives

Common sedatives used on horses include xylazine (Rompun), detomidine (Dormosedan), acepromazine, and butorphanol (Torbugesic). Xylazine, detomidine, and butorphanol are known as sedative/analgesics because they provide both sedation and pain relief.

The analgesic properties of xylazine, detomidine, and butorphanol are caused by alteration of the perception of pain by the brain, and unlike NSAIDs have no effect on the inflammation causing the pain. These sedatives are typically used as chemical restraint for relatively short procedures and for severely intense gastrointestinal pain. Their effect can last 20-60 minutes depending on the dose, the horse, and the situation.

Great care is used with these drugs because they can significantly decrease blood pressure and heart rate (detomidine is extremely potent), so this must considered if the horse is experiencing shock from blood loss or other disease processes, or an irregular heart rhythm. In addition, xylazine, detomidine, and butorphanol have a negative effect on gastrointestinal motility depending on the dose, combination, and frequency used. This should be taken into consideration especially when they are to be given to horses with colic. They provide great pain control, but in some cases such as impactions I prefer to minimize their use. In other cases, such as colic caused from gas distension, the relaxation of the gastrointestinal system (as well as the horse) caused by these drugs can be beneficial by encouraging the movement of gas.

Acepromazine is purely a sedative with no analgesic properties. It is typically used alone or in combination with the other drugs for chemical restraint or when general sedation is desired. Acepromazine also can have a profoundly negative effect on blood pressure, so care is used in situations where this is a concern. Another side effect of acepromazine is paralysis of the penis in stallions; the use of acepromazine in stallions is not advised. The sedation provided by acepromazine can last up to two to three hours depending on the horse and dose.

These sedatives have been used in horses for many years and have been proven safe and dependable in many situations for managing sedation and pain when used by or under the supervision of a veterinarian.

Take-Home Message

Medications are more easily available to lay people today than any time in our history of owning horses, bringing you greater responsibility for current use. Always consult with your veterinarian before giving any medication--your horse's life might depend on it.


"In the Nov. 7, 1996, Federal Register, FDA published a final rule to allow veterinarians to prescribe extra-label [for use or at a different dose than designated on the package label] uses of certain approved animal drugs and approved human drugs for animals under certain conditions. This action implements the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA). This regulation provides veterinarians with greater flexibility in the use of approved animal drugs. These regulations put AMDUCA into effect on Dec. 9, 1996.

"Prior to the enactment of AMDUCA, the Federal Food, Drug, and Cosmetic Act (the Act) required users of approved new animal drug products to follow the exact directions on the labeling of the drug. This extra-label use restriction precluded use of an approved drug in species or for indications (disease or other conditions) not listed in the labeling, use of an approved drug at dosage levels higher than those stated on the label, and other extra-label purposes. In addition, the Act did not provide for the use of human drugs for treating animals.

"Because of AMDUCA, the Federal Food, Drug, and Cosmetic Act will now permit veterinarians, like physicians, to prescribe extra-label uses of approved drugs for their patients."

--Published in FDA Update, Nov. 7, 1996

About the Author

Michael Ball, DVM

Michael A. Ball, DVM, completed an internship in medicine and surgery and an internship in anesthesia at the University of Georgia in 1994, a residency in internal medicine, and graduate work in pharmacology at Cornell University in 1997, and was on staff at Cornell before starting Early Winter Equine Medicine & Surgery located in Ithaca, N.Y. He is also an FEI veterinarian and works internationally with the United States Equestrian Team.

Ball authored Understanding The Equine Eye, Understanding Basic Horse Care, and Understanding Equine First Aid, published by Eclipse Press and available at www.exclusivelyequine.com or by calling 800/582-5604.

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