Effects of phenylbutazone, firocoxib, and dipyrone on the diuretic response to furosemide in horses.
Abstract: Treatment with phenylbutazone (nonselective COX inhibitor) decreases the diuretic and natriuretic effects of furosemide by nearly 30% but the effects of COX-2 specific inhibitors (firocoxib) and atypical NSAIDs (dipyrone) are unknown. Objective: Furosemide-induced diuresis after pretreatment with firocoxib or dipyrone is diminished to a lesser extent than after pretreatment with phenylbutazone. Methods: Eight healthy mares. Methods: Each mare received 4 treatments in a prospective experimental crossover study using a replicated 4 × 4 Latin Square design: furosemide alone (FU), furosemide and phenylbutazone (PB), furosemide and firocoxib (FX), and furosemide and dipyrone (DP). After 24 hours of NSAID treatment at recommended dosages, ureteral catheters were placed for continual urine collection. After a 30-minute baseline collection period, furosemide (1.0 mg/kg, IV) was administered, and urine and blood samples were collected for 4 hours. Data were assessed by repeated measures ANOVA. Results: Four-hour urine volume was (mean ± SD) ~25% less (P < .001) after pretreatment with all NSAIDs (PB 19.1 ± 2.1 mL/kg, FX 17.7 ± 3.5 mL/kg, DP 19.1 ± 3.9 mL/kg), as compared to FU (23.4 ± 5.1 mL/kg) (P < .001), but there were no differences between PB, FX, or DP. Interindividual variability in furosemide diuresis after pretreatment with different NSAIDs was observed. Conclusions: Though COX-2 selective NSAIDs and dipyrone might have less severe or fever gastrointestinal adverse effects in horses, our data suggest minimal differences in effects on furosemide-induced diuresis, and possibly, risk of nephrotoxicosis.
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2023-10-26 PubMed ID: 37882246PubMed Central: PMC10658499DOI: 10.1111/jvim.16914Google Scholar: Lookup
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Summary
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This research paper investigates the impact of various nonsteroidal anti-inflammatory drugs (NSAIDs) – phenylbutazone, firocoxib, and dipyrone – on the diuretic effects of furosemide in horses. The study finds that all three NSAIDs reduce the diuretic effect of furosemide, but there is little difference between the individual effects of these three drugs.
Objective and Methods
- The study aims to understand how firocoxib (a COX-2 specific inhibitor) and dipyrone (a variant of NSAID) diminish the diuretic effects of furosemide compared to phenylbutazone (a nonselective COX inhibitor).
- In a prospective experimental crossover study, the researchers employed a replicated 4×4 Latin Square design to test four different treatments on eight healthy mares.
- The four treatments include furosemide alone, furosemide and phenylbutazone, furosemide and firocoxib, and furosemide and dipyrone.
- After 24 hours of NSAID treatment at the standard dosages, tubes were placed in the mares’ ureters to continuously collect urine.
- Furosemide was then administered and urine and blood samples were collected for the following four hours.
- The data were analyzed using repeated measures ANOVA.
Results
- The urine volume of the mares over four hours was approximately 25% less after pretreatment with any of the NSAIDs compared to the administration of furosemide alone.
- However, there were no significant differences observed in the diuretic effects of the three NSAIDs used.
- The study also observed variability in the diuretic response to furosemide post NSAID pretreatment between individual horses.
Conclusion
- Despite the potential for COX-2 selective NSAIDs and dipyrone to have fewer or less severe gastrointestinal side effects in horses, this study’s data suggest that their impact on furosemide-induced diuresis (and by association, the risk of kidney damage) is largely similar.
- Therefore, using these NSAIDs in conjunction with furosemide does not significantly alter the diuretic response in horses compared to using phenylbutazone.
Cite This Article
APA
White JM, Colbath AC, Schott HC.
(2023).
Effects of phenylbutazone, firocoxib, and dipyrone on the diuretic response to furosemide in horses.
J Vet Intern Med, 37(6), 2544-2551.
https://doi.org/10.1111/jvim.16914 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
MeSH Terms
- Animals
- Horses
- Female
- Diuretics / pharmacology
- Furosemide / pharmacology
- Dipyrone / pharmacology
- Cross-Over Studies
- Cyclooxygenase 2
- Prospective Studies
- Phenylbutazone / pharmacology
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Grant Funding
- 25532 / American College of Veterinary Internal Medicine
- 6119824524 / Michigan State University College of Veterinary Medicine
Conflict of Interest Statement
Authors declare no conflict of interest.
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