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Non-steroidal anti-inflammatory treatment in the horse

by
01 June 2017, at 1:00am

ROSIE J. NAYLOR of Virbac looks at the various treatment options available and the body of research that backs them up

PAIN RELIEF IS COMMONLY ADMINISTERED TO HORSES either as short-term treatment following acute injury or as part of longer-term management of chronic disease, such as osteoarthritis. By far the most commonly used products in the management of equine pain are the non-steroidal anti-inflammatory drugs (NSAIDs). There are numerous NSAIDs licensed for use in the horse, with mechanism of action, analgesic and anti-inflammatory efficacy, formulation, palatability and dosing frequency varying between products. Treatment choice therefore requires vets to be aware of these differences and assess case requirements on an individual basis. NSAIDs act by inhibiting cyclooxygenase enzymes (COX). There are two isoforms: COX-1 is traditionally associated with many important housekeeping functions within the body, such as maintaining the integrity of the gastrointestinal mucosa or blood flow to the kidneys; COX-2 is induced when inflammation occurs, although some expression in healthy tissues has been reported. Reported side-effects of NSAID administration in the horse include gastric ulceration, right dorsal colitis and renal injury and these have been attributed to suppression of constitutively expressed COX. Traditional NSAIDs such as phenylbutazone are not COX-selective – they inhibit both enzymes to a similar extent. More recently, COX-2 selective NSAIDs have been developed, with the aim of limiting the side-effects associated with NSAID treatment. In the UK, meloxicam is the most commonly used COX-selective NSAID in the horse, although others such as fibrocoxib are also available. Clinical studies in horses have shown that oral meloxicam has fewer negative effects on the permeability of the gastric mucosa than phenylbutazone (D’Arcy-Moskwa et al, 2012) and that oral meloxicam was not associated with the same reduction in blood albumin concentration that was seen following 13 days’ administration of phenylbutazone (Noble et al, 2012). There are also differences in the antiinflammatory effects of the available NSAIDs, as demonstrated in recent studies of experimentally-induced acute synovitis in the horse. Oral administration of meloxicam significantly reduced inflammatory mediators such as substance P and matrix metalloproteinase activity within synovial fluid (de Grauw et al, 2009), while no reduction in these mediators was observed in horses treated with phenylbutazone (de Grauw et al, 2014). These studies also showed that meloxicam reduced inflammationinduced cartilage catabolism, which phenylbutazone did not. This suggests that meloxicam is a good choice for the treatment of acute inflammatory orthopaedic conditions. Few studies comparing the analgesic efficacy of the available NSAID products have been published. In a recent blinded study of 77 horses with chronic lameness, meloxicam was shown to have equivalent analgesic efficacy to phenylbutazone (Olsen et al, 2016). It also appears that analgesic efficacy may depend on the inciting cause of orthopaedic pain, with meloxicam demonstrating superior efficacy to phenylbutazone in a model of acute synovitis, but not in a model of mechanical lameness (Banse et al, 2017).

Practical considerations

In addition to clinical efficacy, there are practical considerations that contribute to choice of analgesic product. Ease of administration and patient compliance are important to guarantee effective treatment. Palatability has been an issue, particularly with traditional phenylbutazone preparations. However, some of the newer products are apple-flavoured and are more readily consumed. Drugs that require once-daily dosing such as meloxicam may be more convenient and better tolerated than others that
require dosing more frequently such as phenylbutazone or suxibuzone. Oral NSAIDs are available as pastes, oral suspensions or granules for the horse. Pastes are advantageous if the horse will not consume the product voluntarily; however, both pastes and oral suspensions are generally associated with greater expense than granule formulations. This often precludes their use long-term. There are now phenylbutazone, suxibuzone, flunixin and most recently meloxicam granules available in the UK for the horse. In competition horses, the detection time is often an important determinant in treatment selection. This varies considerably between different drugs and is significantly longer for phenylbutazone/suxibuzone than other active ingredients. Clinicians also need to be mindful of legal requirements for documenting the administration of phenylbutazone, as failure to ensure the declaration within the horse’s passport is signed at
the time of administration can result in prosecution by DEFRA/Food
Standards Agency and a significant fine. Using alternative NSAID products relieves this responsibility and may be preferable if the horse’s passport is not available. Over the past few years several new studies have been published, enhancing our knowledge of equine NSAID treatment options. With the availability of different products and new formulations, the clinician now has an armoury of therapeutic options which can be critically evaluated.

References

D’Arcy-Moskwa, E., Noble, G. K., Weston, L. A., Boston, R. and Raidal, S. L. (2012) Effects of meloxicam and phenylbutazone on equine gastric mucosa permeability. J Vet Intern Med 26 (6): 1,494-1,499.
Noble, G., Edwards, S., Lievaart, J., Pippia, J., Boston, R. and Raidal, S. L. (2012) Pharmacokinetics and safety of single and multiple oral doses of meloxicam in adult horses. J Vet Intern Med 26 (5): 1,192-1,201.
de Grauw, J. C., van de Lest, C. H., Brama, P. A., Rambags, B. P. and van Weeran, P. R. (2009) In vivo effects of meloxicam on inflammatory mediators, MMP activity and cartilage biomarkers
in equine joints with acute synovitis. Equine Vet J 41 (7): 693-699.
de Grauw, J. C., van Loon, J. P., van de Lest, C. H., Brunott, A. and van Weeran, P. R. (2014) In vivo effects of phenylbutazone on inflammation and cartilage-derived biomarkers in equine joints with acute synovitis. Vet J 201 (1): 51-56.
Olsen, M. E., Nagel, D., Custead, S., Wise, W., Penttila, K., Burwash, L., Ralston, B., Schatz, C. and Matheson- Bird, H. (2016) The palatability and comparative efficacy of meloxicam
oral suspension for the treatment of chronic musculoskeletal disease in horses. J Equine Vet Sci 44: 26-30. Banse, H. and Cribb, A. E. (2017) Comparative efficacy of oral meloxicam and phenylbutazone in 2 experimental pain models in the horse. UCVM Class of 2016. Can Vet J 58 (2): 157-167.