NSAIDs: the Past, Present, and Future Resident Seminar - November 2017 Lisanne Gallant, DVM Large Animal Medicine Resident
Outline Physiology Review Use in Large Animals Adverse Effects Cases The Future
Physiology Review Ziegler et al. Update on the use of cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs in horses. JAVMA 2017;250:1271-1274.
Analgesia Prostanoids at inflammatory/trauma sites = pain! NSAIDs inhibit COX pathways = prostanoids
Antiendotoxic Effects Mostly due to COX inhibition However, some COX-independent mechanisms: Preventing nuclear factor-κb (NF-κB) Inhibitory effect on MMPs
NSAIDs & COX Selectivity Nonselective NSAIDs COX-2-selective COX-2-preferential Cook et al. The use of nonsteroidal anti-inflammatory drugs in critically ill horses. J Vet Emerg Crit Care 2015;25(1):76-88.
NSAID Use in Horses Nonselective NSAIDs: flunixin meglumine, phenylbutazone COX-2-selective (or COX-1-sparing): firocoxib COX-2-preferential: meloxicam Cook et al. The use of nonsteroidal anti-inflammatory drugs in critically ill horses. J Vet Emerg Crit Care 2015;25(1):76-88.
Firocoxib COX-2-selective Proven efficacy in controlling pain and inflammation associated with osteoarthritis (Orsini et al. 2012) Comparable to phenylbutazone in controlling pain associated with osteoarthritis (Doucet et al. 2008) Comparable to flunixin meglumine in controlling gastrointestinal pain in post-operative horses with surgically-induced small intestinal strangulating lesions (Cook et al. 2009)
Firocoxib Allows for more efficacious intestinal healing when compared to nonselective drugs (Cook et al. 2009, Davis et al. 2007) Anti-endotoxic effect?
Firocoxib Use the appropriate dose! Loading dose 0.3 mg/kg once Maintenance dose 0.09 mg/kg Q24 Prohibited by the United States Equestrian Federation to use firocoxib concurrently with other NSAIDs.
Adverse Effects
Gastric Ulcers Often associated with NSAID use - however association unclear Possible role for COX-2 in mucosal repair? Horses with gastric ulcers should avoid NSAIDs Hepburn, 2017
Right Dorsal Colitis Prostanoids play important protective role in the gut Unclear why right dorsal colon seems most affected Hepburn, 2017
Gastric vs. Colonic Ulcers
Gastric vs. Colonic Ulcers
Acute Kidney Injury Prostanoids locally produced in kidneys vital to renal blood flow and glomerular filtration rate in the face of hypovolemia
Foals Different pharmacodynamics than adults More likely to develop glandular ulcers, diarrhea, and demonstrate lower plasma protein levels when receiving flunixin meglumine (Traub-Dargatz, 1988) Meloxicam, firocoxib?
Case #1 - Black Magic 6 year-old Thoroughbred mare Chronic history of tarsal osteoarthritis Routinely treated with 2-4 mg/kg doses of phenylbutazone oncetwice daily for weeks at time while competing Presented to MSU VMC for 2-3 day history lethargy, anorexia, and weight loss.
Case #1 - Black Magic Presenting PE was fairly normal, except for a low BCS of 4/9. Packed Cell Volume: 54% Total Solids: 2.0 g/dl Abdominal ultrasound revealed severely thickened and irregular large colon wall. Barton. Understanding abdominal ultrasonography in horses: which way is up? Vetlearn 2011:E1-E7.
Case #1 - Black Magic
Right Dorsal Colitis Ulcerative inflammatory bowel disorder of the horse Thickened, irregular colon wall on ultrasound Hypoproteinaemia, hypoalbuminemia Tx: dietary management, colon resection
Case #2 - Evie 10 year-old Appaloosa mare 2-day history of severe diarrhea and anorexia Suspected PHF, treated with 2 doses of oxytetracycline, twice daily doses of flunixin meglumine (1.1 mg/kg) and phenylbutazone (2.2 mg/kg)
Case #2 - Evie Hypothermic, tachycardic, tachypneic PCV: 60% TS: 3.8 g/dl Electrolyte derangements; leukopenic with degenerative left shift, toxic changes BUN 55 mg/dl Creatinine 2.8 mg/dl
Case #2 - Evie Tx: IV fluid therapy, plasma transfusion, ice boots Attitude improved overnight, urinating normally, continued to produce diarrhea The next day, digital pulses increased in all 4 feet, acutely lame
Case #2 - Evie
Conclusions All NSAIDs (whether COX-2 selective or not) may have significant adverse effects, especially in critically ill horses. Firocoxib may be a safer alternative to use in horses for long-term therapy, when used appropriately.
Questions?