Non-Steroidal Anti-inflammatory Drugs (NSAIDs) in Reptiles and Amphibians: A Review

Non-steroidal anti-inflammatory drugs are commonly used in veterinary medicine for managing acute and chronic pain and inflammation. Although they are used extensively in reptiles and amphibians, there are very few pharmacokinetic or pharmacodynamic studies of the use of these drugs in these species in the literature. This master class will review these drugs and their methods of action, and look at the safety, efficacy, toxicity, and recommended usage in reptiles and amphibians. Cyclooxygenase and Prostaglandins In 1971 it was discovered that aspirin inhibited the activity of a cyclooxygenase enzyme 1 (COX-1) that produced prostaglandins (PGs) involved in the pathogenesis of fever, pain, swelling, and inflammation.50,57 In the following 30 years, 2 more enzymes also would be discovered, COX-2 and COX-3. Cyclooxygenase oxidizes arachidonic acid to various eicosanoids, including prostaglandins. The initial prostanoid formed is prostaglandin hydroperoxide (PGG2), which is then converted to PGH2. PGH2 is then converted by prostaglandin E-synthetase to PGE2, by prostaglandin D-isomerase to PGD2, by prostaglandin F-reductase to PGF2, by prostacyclin synthetase to PGI2 (prostacyclin), and by thromboxane synthetase to thromboxane A2 and B2 (TXA2, TXB2). Arachidonic acid is also oxidized by 5-lipoxygenase (5-LOX) to form leukotrienes. Prostaglandins have a short half-life (4-6 min at 37o C), so they are subsequently synthesized constantly and not stored by the body. They tend to act locally at the site of production.50 The COX enzymes each have different roles. COX-1 produces prostaglandins that are involved in mucosal defense, such as secretion of mucus and bicarbonate, attenuation of constriction of mucosal blood vessels, and regeneration of mucosal epithelium. It generates TXA2, which is necessary for normal platelet function. It also has a cytoprotective function in some tissues, including the gastric mucosa, kidneys, reproductive tract, and central nervous system.50 COX-2 generates prostaglandins that exert anti-inflammatory effects by the inhibition of leukocyte adherence, prevent mucosal erosions and promote healing of these lesions, and play a role in the protection and maturation of the kidneys.50 COX-3 produces prostaglandins that initiate fever.50 Depending on the NSAID that is selected, expected effects can not only include decreased inflammation, but also alteration of platelet function, modulation of vascular tone in the gastric mucosa and kidneys, cytoprotective functions within the gastric mucosa, smooth muscle contraction, and alteration of body temperature.50 Prostaglandins are important local mediators of pain and inflammation. Of the prostaglandins, PGE2 and prostacyclin are the most potent mediators of pain and inflammation. They exert a hyperalgesic effect, and they enhance nociception produced by other factors, such as bradykinin. The COX-2 isoenzyme is upregulated in inflammatory states (up to 20 times its basal levels) and plays a key role in nociception, whereas COX-1 is produced constitutively and also plays an integral role in nociception.50 Prostaglandins are also known to lower activation thresholds to mechanical, thermal, and chemical stimulation. It has also been shown that NSAIDs produce much of their analgesic effects by inhibiting COX activity centrally.50