NSAIDs - Donkey

The inflammatory response

The inflammatory response is a complex process that occurs following cellular injury. Cell membrane damage releases phospholipids, which are converted rapidly, mainly by phospholipase A2 to arachidonic acid. The cyclo-oxygenase enzymes (predominantly COX2) convert arachidonic acid into prostaglandins and thromboxanes, crucial mediators in the development of inflammation, pain and fever. Prostaglandins and thromboxanes are also produced constitutively (COX1) and serve numerous homeostatic roles, including protection of the gastric mucosa and kidneys.

Inhibition of COX

It is thought that inhibition of constitutive COX1 is responsible for many of the adverse effects of NSAIDs, e.g. gastric ulceration, impairment of renal function and inhibition of platelet aggregation. Both the gastric and renal effects are dose-related: the higher the dose the increased likelihood those side effects will develop. Even at normal therapeutic doses, renal effects are more likely in animals that are volume depleted, hypotensive or have pre-existing renal disease.

Aspirin induces irreversible inactivation of platelet COX1, making it an effective antithrombotic agent in horses. The effect of other commonly used NSAIDs on coagulation in horses is less clear; most are reversible inhibitors of COX1 and COX2.

Reduction of side effects

In an attempt to decrease NSAID side effects, new compounds that selectively inhibit the COX2 isoform have been developed, although only a few of these compounds have been studied in animals. It appears that enzyme selectivity is very species dependent, so a COX2 selective agent in one species may not be selective in another. Currently no NSAID has been shown to be a selective COX2 inhibitor in the horse.

Use in donkeys

In donkeys, NSAIDs are used most commonly in the management of pain and inflammation (analgesia), including laminitis, and hyperlipaemia. This large group of structurally diverse compounds shares a number of common features, e.g. relatively short plasma half-lives but a long duration of effect, with small Vds (due in part to a high degree of plasma protein-binding).

Side effects

Nearly all NSAIDs also potentially induce hepatic injury and this should be considered, particularly when these agents are administered concomitantly with other potentially hepatotoxic agents, such as the potentiated sulphonamides. NSAIDs should be used with particular care in aged animals, particularly with pre-existing renal, cardiac or hepatic disease, and in cases that are dehydrated, in shock or undergoing concurrent therapy with nephrotoxic drugs. Particular care is also required when NSAIDs are administered concurrently with other compounds that are also highly protein-bound, e.g. the sulphonamides.

References

• Horspool, L. (2008) Clinical pharmacology In Svendsen, E.D., Duncan, J. and Hadrill, D. (2008) The Professional Handbook of the Donkey, 4th edition, Whittet Books, Chapter 12

PHARMACOLOGY - DONKEY

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