MICHAEL WATTS – UNDER THE RADAR

OUT AND GONE

Back in the day when I was a student you could have bought a half ‘un and a beer chaser and still had change out of a pound note, and it was a pound note, not a coin. Snooker in the Mechanic’s Institute cost twenty pence an hour for your light which worked out dear enough if you made breaks like mine and frames could last well into the second hour. Alex Higgins’ title was safe in his hands.

Back in those days of petrol rationing, mass unemployment and rampant inflation there was basically one anti-inflammatory drug on the market if you did not want to use corticosteroids with all their side-effects and contraindications. Phenylbutazone came as an injectable solution, as a powder in wee sachets for horses and as shiny tablets like pearly grey Smarties for dogs. You gave the dogs 22mg/kg per day by mouth in divided doses with food. It worked pretty well for most dogs most of the time, which is about as much as you can ask of any drug in any era.

Reference to my well-thumbed copy of the 2018 Compendium of Data Sheets for Animal Medicines suggests that Phenylbutazone has gone the way of all flesh and is a thing of the past. There are however no fewer than twenty-one alternative oral non-steroidal anti-inflammatory products on the market for the treatment just of dogs. We are spoiled for choice, by the looks of things. One popular choice down the years has been Meloxicam, an anti-inflammatory drug widely used for “the alleviation of inflammation and pain in both acute and chronic musculo-skeletal disorders in dogs” as the manufacturer of one popular brand of the drug puts it. Other brands are available.

Popular in the poodle business it may still be, but back in April this year the Greyhound Board of Great Britain issued an alert to the trainers they licence sounding a note of caution regarding its use in race dogs. “A recent study looking at the administration of meloxicam to greyhounds” the Board advised “has raised issues as to its safety as a drug for treating greyhounds within a Drug-free Sport”. They go on to clarify this further, saying that “results from this research have demonstrated that meloxicam may persist in the greyhound for up to 25 days following a single dose”. The problem is an integrity issue. Treated dogs may potentially test positive for residues of the drug for a protracted period after treatment has ceased.

Dipping into Pharmacology #101 for a moment, in general terms when a drug enters the body of man or beast, any one of a number of things may happen to it. It might for example be active in the form in which it is administered or it might be metabolised into its active form within the body. The active form of the drug might not be metabolised at all but be excreted, usually in the urine or faeces, in its active form. Alternatively it might be inactivated by becoming gradually absorbed into a relatively inactive tissue such as fat. Then again the active form of the drug might be broken down in the body into a less active form, or into a completely inactive metabolite, which is subsequently excreted in the urine or faeces.

In dogs meloxicam follows the last of these routes. It is active in the form in which it is administered but with time it is extensively metabolised in the liver, where it is broken down into four metabolites or thereabout, but mostly to a one called 5’-carboxy meloxicam. None of these metabolites have any anti-inflammatory action, or any other action that we know of. They are simply markers which can be used to identify dogs previously treated with meloxicam. Theses end products of meloxicam metabolism are excreted in the faeces and urine in roughly equal amounts. The G.B.G.B currently recommends that trainers should not administer Meloxicam to any greyhound within 30 days of a race or trial. Clearly this puts an end to the use of meloxicam in the treatment of minor injuries where it is anticipated that the dog involved will make a rapid return to the racing strength. It might still be an option for those greyhounds unlucky enough to be on the easy list for the medium term.

I am not about to recommend that anybody should try to be their own vet.. Turkeys seldom vote for Christmas. However the information you need is widely available on the internet on your smartphone so I will save you the bother of googling it. (Other search engines are available). Meloxicam is available as a 5mg/ml injectable product which is licensed in the U.K. for the alleviation of inflammation and pain due to musculo-skeletal disorders in dogs and to reduce post-operative pain following orthopaedic and soft tissue surgery.

The recommended dose is 0.4ml//10kgs bodyweight, meaning that your average 30kg tracker would get a dose of 1.2ml. This should be given subcutaneously in cases of musculo-skeletal disorders but can be given intravenously in the treatment of post-operative pain. Trackside, when I am presented with an acutely injured dog in distress I know what rout I am going to use every time. One of the traditional responsibilities of the surgeon is to comfort always. You can also buy meloxicam as a 1.5mg/ml suspension. This is designed to be given by mouth at a dose rate of 0.2mg/kg bodyweight on the first day of treatment and 0.1mg / kg bodyweight subsequently. One brand of Meloxicam is available in tablet form, but these do not seen to be a big hit with my clients, although other may have had a different experience.

Getting technical for a minute, Meloxicam is what is called a nonsteroidal anti-inflammatory drug [NSAID} of the oxi-cam class. It “acts by inhibiting prostaglandin synthesis, thereby exerting anti-inflammatory, analgesic, anti-exudative and antipyretic effects” which in plain English means something along the lines of it reduces inflammation, pain, and swelling of the tissues at the site of injury or surgery and helps bring down a high temperature.

Now you do not get anything for nothing in this life. As well as these beneficially anti-inflammatory and pain-reducing effects, the use of NSAID drugs notoriously may potentially have significant side-effects such as gastrointestinal ulceration, as many a fellow Ibuprofen junkie of the International Brotherhood of the Arthritic can testify. They can also have adverse effects on liver and kidney function. Studies have shown that both the desirable therapeutic effects of NSAIDs and their unwanted side-effects come about through one common mechanism, the inhibition of a group of enzymes called cyclooxygenases. Now you will have to near with me here, as biochemistry is not exactly my strong suit. Truth to tell, it was the only exam I failed at the first time of asking, causing me to spend much of the long hot summer of 1977 with my nose stuck in a book while others slaked their thirsts and cultivated their tans.

Traditionally biochemists divide these enzymes into two types. Cycloxygenase 1 [COX1] is always present and is involved in the manufacture of prostaglandins in tissues like the lining of the stomach and blood vessels, the platelet cells in the blood, the kidneys, pancreas and brain. In contrast Cycloxygenase 2 [COX 2] is what is called an induced enzyme, which is to say it is not normally present in the tissues in its active form but is manufactured in response to stimuli like pro-inflammatory agents, bacterial toxins and a variety of growth factors.

This is all a bit complicated and, I would be first to admit it, quite heavy going. It is important however because the sought-after good effects of NSAIDs tend to arise a result of inhibiting COX 2, while the unpleasant and potentially dangerous side-effects are generally the result of inhibition of COX1. In times past we gave sick and injured dogs phenylbutazone because it improved the quality of their lives. Undoubtedly it had its side effects but you used it because it was there, because it was a darned sight better than nothing, and because the alternative was nothing. Life was like that back in the day.

More modern NSAIDs are designed to be much more specifically COX 2 inhibitors, a point emphasised in the communique from the G.B.G.B It should not of course be forgotten that in the U.K. these drugs fall into a legal category called Prescription Only Medicines, which means they can only be supplied by a registered veterinary surgeon for animals under his or her care. Within this constraint, when seeking alternatives to Meloxicam, the G.B.G.B suggests the use of COX2 inhibitors such as Firocoxib.

This last is a fairly new product on the market, and as such there is to my knowledge only one brand currently licensed. As with any new drug, the manufacturers and patent-holders have a few years to recoup their research and development costs and generate a profit for their shareholders before other companies start manufacturing the same drug and the market price falls. This happened some time ago in the case of Meloxicam, which is marketed by a number of companies under the brand names Inflacam, Loxicom, Metacam and Rheumocam and maybe others.

The ending of a monopoly and the development of a competitive market in any drug is very much in the interests of the practicing veterinary surgeon, who can take advantage of the situation to source the drug at a keen price and pass that price on to their clients. In the case of Firocoxib that has yet to happen and in the cash strapped greyhound game it probably looks like a dear drug right now, although that situation may be subject to change before long. The G.B.G.B also suggests Carprofen as an alternative.

Networking in greyhound veterinary circles, I get the impression that many of the guys at the coalface prefer Carprofen to Meloxicam anyway, but as networking usually involves much liquid refreshment don’t quote me on that one. Like Meloxicam Carprofen has been around for a while and about half a dozen different Carprofen products are currently available. I am not going to mention any names here, as I am not in the pocket of any of the drug companies. Mind you every man has his price and I might be open to offers.

A range of comparable products competing in a free market helps to keep the price of drugs like Carprofen within reasonable bounds. It would be inappropriate for me to advocate choosing anti-inflammatory drugs purely on price but I do live in the real world. I appreciate that there is not a lot of spare cash floating about in the greyhound game right now and that veterinary services are not for nothing. Come to that I am not necessarily suggesting that you follow the advice of the G.B.G.B. slavishly either. What they are offering here is advice, albeit probably pretty sound advice.

The best person to decide which drug to use in an injured greyhound is the practicing veterinary surgeon into whose care said dog has been entrusted. But I would say that, wouldn’t I?

 

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