NSAID Toxicity

Todayโ€™s path rounds are on ๐๐’๐€๐ˆ๐ƒ ๐ญ๐จ๐ฑ๐ข๐œ๐ข๐ญ๐ฒ!

๐–๐ก๐š๐ญ ๐ข๐ฌ ๐ข๐ญ?
๐๐’๐€๐ˆ๐ƒ๐ฌ (non-steroidal anti-inflammatory drugs) are a common class of drug used as anti-inflammatories and pain control. Human examples you might know include aspirin, ibuprofen and naproxen. We commonly use other NSAIDs in our veterinary species as well!

๐–๐ก๐จ ๐ ๐ž๐ญ๐ฌ ๐ข๐ญ?
Any species can develop this toxicity!

๐–๐ก๐š๐ญ ๐œ๐š๐ฎ๐ฌ๐ž๐ฌ ๐ข๐ญ?
NSAID toxicity can develop in a few ways. The most obvious is exposure to a lot of NSAIDs all at once, for example a dog getting into the medicine cabinet. However, NSAID toxicity can also occur in cases where animals are given a prescribed NSAID for a long period of time. This ๐œ๐ก๐ซ๐จ๐ง๐ข๐œ (long-term) exposure is probably the most common cause of NSAID toxicity, particularly in species like horses.

๐–๐ก๐ฒ ๐ข๐ฌ ๐ญ๐ก๐ข๐ฌ ๐š ๐ฉ๐ซ๐จ๐›๐ฅ๐ž๐ฆ?
The way that NSAIDs work is that they block the production of ๐ฉ๐ซ๐จ๐ฌ๐ญ๐š๐ ๐ฅ๐š๐ง๐๐ข๐ง, a critical hormone in the inflammatory pathway. This occurs by inhibiting the enzyme ๐‚๐Ž๐—, which produces prostaglandin. There are actually two forms of COX: COX-1 is expressed by pretty much every tissue in the body to produce prostaglandin needed for normal bodily functions, and COX-2 is associated with inflammation.

Most NSAIDs inhibit ๐›๐จ๐ญ๐ก COX-1 and COX-2, meaning that they can also disrupt normal bodily functions. The most common use of COX-1 is protecting the digestive tract from damage, so these ๐ง๐จ๐ง๐ฌ๐ž๐ฅ๐ž๐œ๐ญ๐ข๐ฏ๐ž NSAIDs can lead to ๐ฎ๐ฅ๐œ๐ž๐ซ๐š๐ญ๐ข๐จ๐ง (damage to the mucosa) within the stomach and intestines. COX-2 also helps regulate the amount of blood flow to the kidney, so chronic NSAID exposure can decrease this blood flow. This leads to ๐ฉ๐š๐ฉ๐ข๐ฅ๐ฅ๐š๐ซ๐ฒ ๐ง๐ž๐œ๐ซ๐จ๐ฌ๐ข๐ฌ, or cell death in the most central tissues of the kidney.

๐‡๐จ๐ฐ ๐ข๐ฌ ๐ข๐ญ ๐๐ข๐š๐ ๐ง๐จ๐ฌ๐ž๐?
Diagnosis is usually based on a history of NSAID use, combined with clinical signs like abdominal pain, diarrhea, vomiting or signs of kidney failure. In some cases, ulcers within the esophagus and stomach can be seen on ๐ž๐ง๐๐จ๐ฌ๐œ๐จ๐ฉ๐ฒ, where a long camera is used to examine the digestive tract.

๐‡๐จ๐ฐ ๐ข๐ฌ ๐ข๐ญ ๐ญ๐ซ๐ž๐š๐ญ๐ž๐?
First and foremost, the animal must be taken off any NSAIDs. Treatment then involves fluid therapy, to increase blood flow to the kidneys, and use of medications that help replace the normal protective coating of the digestive tract to prevent further damage. An example of this type of medication is ๐ฌ๐ฎ๐œ๐ซ๐š๐ฅ๐Ÿ๐š๐ญ๐ž, which basically coats any ulcers and forms a protective barrier.

๐๐ก๐จ๐ญ๐จ๐ฌ
1) Ulcers on the tongue from NSAID toxicity.
2) Stomach ulcers in a horse.
3-4) Ulcers in the large intestine from NSAIDs.
5-7) Examples of papillary necrosis! One of the images has a large ๐ง๐ž๐ฉ๐ก๐ซ๐จ๐ฅ๐ข๐ญ๐ก (kidney stone) which can also occur due to reduced blood flow.

๐’๐จ๐ฎ๐ซ๐œ๐ž๐ฌ
Khan SA. Analgesics (Toxicity). Merck Veterinary Manual 2016.

Photos 1, 3-4, 6-7 ยฉ Noahโ€™s Arkive contributors Acland, Rosell, Panciera licensed under CC BY-SA 4.0.
Photos 2 and 5 ยฉ University of Calgary Diagnostic Services Unit.

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