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Have you ever wondered what the difference is between the brand name veterinary products your veterinarian sells and the products in catalogues and tack stores that claim to be exactly the same but cheaper and without a prescription? Most people think of these as generics, over the counter versions of these medications much like we have generic and OTC versions of our human products like allergy medications and painkillers. But this is may not be true and the distinction between prescription, generic and a compounded drug is very important to understand. A brand named prescription medication is one that is FDA approved and comes with all the bells and whistles of a newly developed product. Once this new product’s patent expires, other companies can produce the same drug, using the same formula, same dosage, same ingredients and same form, but usually at a lower cost. Generic medications go through the same rigorous FDA approval process to assure efficacy and safety before they are on allowed on the shelves.

To “compound” a medication is to mix drugs to create a product that is not commercially available (most common in vet med) or to change the delivery (pill to liquid) or flavor (most common in pediatric med). Compounding pharmacies are mostly self-regulated and have little to no external oversight, meaning no one is making sure their products contain what the label claims. This is different from a “generic” medication, which has FDA approval and regulations.

Prescribing generic forms of medications is completely legal because the FDA has approved these products. In veterinary medicine the FDA only allows for compounding of drugs that are not commercially available in an FDA approved form. Prescribing and using a compounded drug that is commercially available, besides being against the law, may not give you the results you are looking for, or worse, can be dangerous.

An FDA study showed that 34% of compounded drugs do not meet the potency standards compared to their approved counterparts, and most of these had less than 70% of the active ingredient the label claimed!!!  Another recent study presented at last year’s AAEP Convention compared compounded omeprazole products (lower cost versions of Gastrogard for the treatment of ulcers). The compounded forms had less than 63% of the label claim of omeprazole. Meaning, you’d have to give almost two tubes of compounded omeprazole to get the same effect as a single tube of Gastrogard! Additionally the materials used to make these medications do not always come from high quality sources or FDA approved manufacturers making their safety and stability questionable as well.

One of the most common examples of proper compounding in veterinary medicine is pergolide, the medication used to treat Cushing’s Disease in horses. Years ago there was an FDA approved human formulation of the drug that we were able to give to our horses. But more recently they had stopped making this medication for humans and we were forced to use a compounded form to continue treatment on these Cushing’s cases. Because these were not regulated formulations there was always a question as to whether or not there was the right amount of drug in the compound. Was the horse not responding because the diagnosis was wrong or the condition was worsening? Or was it just that we wanted to give 1mg of drug per day but the formulation only contained 0.5mg? Often times finding the right dose for each horse was a guessing game. Thankfully a new FDA-approved equine formulation of pergolide is on the market- Prascend® (Boehringer Ingelheim). Though many people have become used to using the compounded powder or suspension, veterinarians will be switching over to the approved product because we can be confident that it is efficacious and safe for our patients.

While we will always need to compound some drugs in order to have the full arsenal available to keep our animals healthy, when we do compound, we closely research the company and often employ outside labs to verify the concentration and purity.  So talk to your veterinarian about compounded medications and beware of online companies offering compounded versions of medications at reduced prices (especially if it is a prescription med and they do not ask for a script!) because you may not be getting what you need!

 
 
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This past Saturday night was the 35th Anniversary Gala for the Philadelphia Women’s Rugby Club, a team I was proudly a member of from 2002-2006 while living in Philly during vet school. Rugby is a rough sport (yes girls can play too, and yes we play by the same rules as the boys, no helmets, no pads, just knee socks and a mouth guard) and during my time with the Philly Women, in addition to making it to Nationals twice and being named to a few all-star teams, I also dislocated my right shoulder, broke my nose (for the 3rd and 4th time) and had more than one black eye that made my boyfriend afraid to be seen in public with me.  Ruggers know about pain, and pain management. And the one thing I was thinking about on Sunday morning, after a long night of reminiscing with old friends, dancing in 4” BCBG metallic blue stilettoes (a far cry from my old brown clogs) and one too many Yeungling lagers (you can’t get it in Indiana) was pain management.

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When you look at the Pain Relief aisle of your local Walgreens or CVS, for pills containing the anti-inflammatory drug ibuprofen there are a million and one choices: joint & muscle pain, back pain, childrens’ pain, arthritis pain, menstrual pain, migraine pain and oral pain. And I’ve always wondered; How do the drugs in this ibuprofen pill treat just my back pain? What makes that ibuprofen pill just go to my headache? But when you read the fine print on the label, many of these pill contain the same concentration of the same drug, no magic road map to your pain, its just that they are marketed for certain ailments (and usually the arthritis pills have an easy to open cap and the childrens’ pills have a child-saftey cap).  And while we tend to use them interchangeably, most of us understand that ibuprofen is not the same as aspirin, which is not the same as naproxen (Aleve®), making the choice even more confusing. Luckily in the horse world we don’t have so many choice. Pretty much just two dominate the field: phenylbutazone (Bute) and flunixin meglumine (Banamine®).

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Their innovative marketing techniques aside, the most misleading part of the previous paragraph is how the section in the pharmacy is labeled: Pain Relief. I think that it is very important to understand how these drugs work and why we prescribe them. Yes, they do relieve pain, but that is a secondary benefit of their main focus: control of inflammation. This is why we call them Non-Steroidal Anti-Inflammatory drugs, or NSAIDs, which include phenylbuazone, flunixin meglumine, firocoxib (Equioxx®), ketoprofen and carprofen (Rimadyl® for our dogs). They are “non-steroidal” because this group does not contain corticosteroids (dexamethasone) which also stop inflammation but also affect the immune system. They are anti-inflammatory because they stop the affects of inflammation by blocking the production of prostaglandins, one of the final products of the inflammatory pathway. Prostaglandins are produced by many tissues in the body as part of normal functions like blood flow to the stomach and colon lining and the kidneys (remember this point, it’ll come up again later). 

So are Bute and Banamine® the same? Not exactly… Banamine® has been shown to be more effective in relieving gastrointestinal, soft tissue and systemic inflammation and pain. Think colic, eye pain, sepsis. Bute on the other hand is more commonly used for musculoskeletal inflammation and pain (muscle pain, arthritis, tendon/ligament injury).

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So now that you have an idea of which drug to give when, the next questions are: How do I give it? How much? and How often? 

Both Bute and Banamine® are prescription medications and should be obtained from your veterinarian to treat a specific problem on a specific horse. That being said, we all know it lives in every medicine chest of every farm out there. Bute comes in an injectable solution that should only be given intravenously (IV) by an experienced person, namely your veterinarian. It is very irritating and if it gets outside of the vein or in the muscle it can cause severe inflammation, necrosis and sloughing of the tissue.

The safer formulations for laypeople to use are the oral forms, powder or paste. Make sure you read the label to know how many grams are in one scoop of powder or one turn of the dial on the paste tubes (its usually 1g). Banamine® also comes in injectable and oral formulations. The injectable form can be given IV (again make sure you have an experienced hand giving the injection) or intramuscularly (IM). I tend to discourage people from giving Banamine® IM because it has been closely associated with Clostridial myositis, a severe and often life threatening bacterial infection in the muscle. You can also give the injectable formulation orally! Yes, draw the same amount from the bottle that you would have giving IV or IM and squirt it in their mouth! It has similar oral bioavailability, which means its absorbed just as well. NB Injectable Banamine® is VERY bitter (trust me, I’ve accidentally gotten some sprayed in my face) and your horses will appreciate it if you mix it with applesauce or molasses before giving it orally. Banamine® also comes in a paste and granules to be given orally.

The label dose of Banamine® is 1.1mg/kg BID which is a fancy way of saying that a 1000lbs horse should get ~500mg (10cc or a 1000bls dose of paste) no more than once, every 12 hours. Bute’s label dose is 4.4-8.8mg/kg BID. Translation: a 1000lbs horse should get between 2 and 4 grams no more than once every 12 hours. It is very important to note that these volumes are based on body weight and are for a ONE THOUSAND POUND horse!!! If your horse weighs more or less than 1,000lbs, then these doses are not right for you! Example, a 500lbs pony is half the weight of a 1,000lbs horse (get out your calculator and check if you don’t believe me, but my mother will tell you I did very well in math as a child), therefore a 500lbs pony should receive HALF the dose of a full sized horse. I know, I know “But human medicine gives every adult the same amount of pills whether you’re a 90lbs gymnast or a 300lbs sumo-wrestler.” This doesn’t make sense to me, and I hope someday an MD will give me a good explanation as to why. And notice how I say “no more than once every 12 hours?” I didn’t say “twice in a day” because to some people that means, once, and then if it doesn’t work, another dose 20min later. And giving your 1000lbs horse 10cc of Banamine® and then another 10cc an hour later is the same as giving them 20cc at once, and you have overdosed your horse.

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So why is it that I’m so crazed with appropriate dosing? Because, being an internist, I get to deal with the sickest, most critical cases and I hate seeing ones that could have been prevented. While Bute and Banamine® are wonderful drugs that help us keep our horses comfortable and inflammation free, they are not without side effects. Remember how I said that there were “normal” functions of prostaglandins and how that fact would be important later? Well the time is now. Prostaglandins regulate blood flow to the kidneys and to the lining of the stomach and colon (specifically the Right Dorsal Colon). When NSAIDs are given, they block all prostaglandins, both normal and inflammatory, so you get decreased heat, swelling and pain but you also get decreased blood flow to your kidneys and gut lining. Now in a well-hydrated horse that is getting an appropriate dose for a short period of time, this usually won’t be a problem. If your horse is dehydrated, getting excessive doses or even normal doses but for long periods of time, you will see the harmful side effects. Gastric ulcers, colonic ulcers and renal failure. These can lead to colic, diarrhea, excessive drinking/urination and many other signs associated with NSAID-toxicity. This is a treatable condition but it can become so severe that no amount of treatment can repair the damage.

It’s not that we should never use these medications; we just need to know the appropriate doses and dosing intervals to make their use as safe and effective as possible.

Believe me, Sunday will not be the last time I reach for the ibuprofen (only at the labeled dose and I’ll keep hydrated with plenty of water) but I do so cautiously (and swear to myself I will never run down Walnut St in 4” heels in freezing temperatures again!). And the safest, most cautious way to administer NSAIDs to your horses is to do so under the direction of your veterinarian. Only he or she knows the right type and the right dose of NSAID for your horse based on the specific problem at the time.

 
 
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Horses loaded up and ready for the long haul!
   We all know that air travel often leads to the common cold in people, but can the same thing happen to our horses in the trailer?

   Yesterday, as I boarded a plane in Indianapolis for a trip to the East Coast (part work, part play), I realized too late that I had not packed my Airborne. As the doors closed and the cabin pressurized I heard the sounds that give every traveler that sinking feeling; coughs, sniffles and sneezes. I knew that no amount of in-flight complimentary orange juice would help, I was going to get a cold. It happens countless times every day all over the world, passengers, tired and stressed from the airline experience, mixing germs in the ultimate petri dish, a crowed plane. 

   All this thought of impending illness reminded me of one of the reasons for my trip east. The data for the final research project that I performed during my residency was analyzed and all that was left was to write the paper. Yes, I know, 18-months is a very long time to wait, and yes, I had probably forgotten more about the project than I knew in the first place, but sometimes science is slow, or sometimes researchers get busy with other things (moving thousands of miles, new jobs, new companies, puppy raising, wedding planning) and that little project gets forgotten. We had waited too long and this trip home was a perfect opportunity for my co-author and I to lock ourselves in an office and just get it written. The project looked at tracheal mucociliary clearance, a very important factor in the development of transport-associated pleuropneumonia in horses, or “shipping fever.”

   You see, humans aren’t the only ones who get sick after travel. Shipping fever is a well-described syndrome in horses, cattle and any other animals that are packed in trailers and sent around the country.  Shipping has been shown to increase stress markers, such as cortisol, in animals, which can lead to a decrease in immune function. In horses we recognize that tracheal clearance plays an important roll. The lining of the trachea is covered in microscopic finger-like projections called cilia (from the Latin word for eyelash). These cilia beat synchronously to move tiny particles of dust, debris and bacteria up the trachea, away from the lungs, where it can be coughed up. When we ship horses, we commonly tie them in some fashion so that their head is in an upwardly fixed position. Research done by Dr. Sharanne Raidal of the University of Sydney has shown that this prolonged upward fixation of the head and neck significantly decreases the rate at which particles move out of the trachea and that this leads to a significant increase in the number of bacteria and inflammatory cells found in the trachea and lungs. Combine this with decreased immunity, bits of hay and dust from the hay net being blown around in front of their face, not to mention the pollution of a diesel truck and its no wonder some horses develop pneumonia after shipping. The study I performed, the one I still had to write up, aimed to prove that pre-treatment with clenbuterol, a drug known to increase tracheal clearance, would prevent shipping fever…sadly it did not work as we hoped. It did increase the rate of clearance but this small increase was not enough to combat the barrage of insults that batter the respiratory system during transport.

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Millions of finger-like projections called cilia, beat in time to move debris and bacteria up the trachea and away from the lungs. These cilia can be easily damaged by viruses and the stresses of shipping, leading to pneumonia.
So what can be done to protect our equine travelers? Buckets full of OJ at each rest-stop? Giant sized Flinstone’s Vitamins? The solutions may be a bit simpler than that. First things first, don’t ship sick horses. Horses that are already compromised or are recovering from a recent illness are more likely to become sick after shipping. Upper respiratory tract viruses (like the Flu or Rhio virus) can blunt tracheal cilia. This damage can take weeks to a month to heal, leaving that horse even more susceptible. But once you have your healthy horses on the trailer, try to decrease the amount of particles their respiratory tract has to deal with. Ensure the trailer has good ventilation (especially in the winter when we tend to shut up all the windows, a few horses’ body heat in a small space will keep them warm).  Debris in the air can be controlled by soaking the hay for 5-10 minutes before hanging the hay nets (soaking any longer can leach out some of the sugars and decrease the nutrient values, which may not be a bad thing if your horse is an “easy keeper”), or ship them without hay at all. It may not be good for their attitude but it can save their lungs.  Next, let gravity lend a hand. Another study done by Dr. Raidal showed that the ill effects of the upwardly fixed head position can be negated by allowing the horse to lower its head to the ground several times throughout the trip. So when you stop for gas, remove the breast bar and let your horses have their heads, they may be able to empty out some of those bacteria that have been building up.

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    Unfortunately no matter how diligent we are, no matter how much OJ we guzzle at the airport, after a long trip some people and some horses will get sick. The best thing we can do for these cases, is recognize the illness and begin treatment as soon as possible. Taking your horses temperature several times a day and monitoring their attitude and appetite closely for the few days after a long trip can help you pick up on the early signs of illness. If you do have concerns about one of your travelers, contact your veterinarian. He or she can do a thorough assessment of your horse and may recommend blood work to look for signs of systemic inflammation. Many times, pneumonia in horses, if treated early, can be resolved quickly without too much time out of the saddle. However, left untreated, bacterial pneumonia can become very severe, require hospitalization and even be life threatening. In fact, studies out of Japan show that shipping fever is one of the leading causes of morbidity and mortality in racehorses.

    Don’t let your horse fall victim to this potentially terrible disease. Take precautions before, during and after shipping to keep your friends healthy and ready to go on your next adventure!

 

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