NSAIDs have a higher incidence of toxicity in neonates because kidney function is not fully developed. When indicated in neonates, they should be administered at the lowest possible doses. NSAIDs should be administered very cautiously to dehydrated animals. As they predominately distribute in extracellular water, plasma concentrations will be greater than normal in the dehydrated animal and more likely to cause toxicity. As the cat is deficient in the glucuronidation enzyme system, drugs like aspirin and acetaminophen that are eliminated by this route have prolonged elimination half-lives and high potential for toxicity.
NSAIDs such as ketoprofen that are cleared by alternate pathways can be safely used in cats. Glucuronidation also results in significant enterohepatic recirculation. This tends to be greater in dogs than in other species, such as humans. GI prostaglandins are natural inhibitors of gastric acid secretion and support mucosal blood flow. NSAID inhibition of prostaglandin biosynthesis results in increased acidity and decreases mucosal blood flow and mucous production, leading to ulcer formation.
NSAIDs should not be used in conjunction with glucocorticoids as they potentiate gastrointestinal toxicity. Misoprostol, an orally administered synthetic prostaglandin E, may be beneficial in patients at risk for ulceration.
Hematological Toxicity: NSAIDs especially aspirin, ketoprofen, and tolfenamic acid should not be used in animals with concurrent hematological disorders or potential bleeding disorders, including thrombocytopenias and von Willebrand's disease. Their use should be avoided during or near surgeries where hemorrhage may be a problem. NSAIDs typically have little effect on renal function in normal animals. However, they decrease renal blood flow and glomerular filtration rate in patients with congestive heart failure, hypotension, or hypovolemia especially during anesthesia and surgery , or chronic renal disease.
Under these circumstances, acute renal failure may be precipitated as NSAIDs block the ability of renal prostaglandins to mitigate the vasoconstrictive effects of norepinephrine and angiotensin II on the glomerular afferent arterioles.
Currently, it is thought that COX-1 is responsible for renal prostaglandin production, so COX-2 selective drugs may avoid this problem. Although attributed to impaired renal blood flow, other mechanisms such as direct nephrotoxicity of the drug or its metabolites may also be involved. Recent reports of carprofen-induced hepatotoxicity in dogs may reflect an idiosyncratic reaction with this drug. In dogs and cats overdosed with acetaminophen, hepatic necrosis may occur if they survive the primary hematological toxicity.
All NSAIDs have the potential to be hepatotoxic however and should be used with caution in animals with underlying liver disease. By inhibiting prostaglandin synthesis, non-steroidal anti-inflammatory drugs NSAIDs cause mucosal damage, ulceration and ulcer complication throughout the gastrointestinal tract. The recognition that there are two cyclo-oxygenase enzymes, one predominating at sites of inflammation COX-2 and one constitutively expressed in the gastrointestinal tract COX-1 , has led to the important therapeutic development of COX-2 inhibitors.
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Difference in Functions: COX-1 play important role in housekeeping such as it protects gastric mucosa, regulate gastric acid and maintain normal functions of the kidney by stimulating prostaglainds. Difference in Usefulness: COX-1 enzymes are protective in nature and therefore are useful for the body. Difference in Inhibition: There are different types of drugs that are used to inhibit COX-2 enzyme including Celecoxib. Note: According to some studies COX-2 enzyme has also role in angiogenesis.
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