Equine veterinary journal2020; 53(2); 356-363; doi: 10.1111/evj.13323

Impact of concurrent treatment with omeprazole on phenylbutazone-induced equine gastric ulcer syndrome (EGUS).

Abstract: Phenylbutazone is commonly prescribed for treatment of various painful or inflammatory disorders in horses, but is associated with gastrointestinal (GI) adverse effects. Anecdotally, many practitioners prescribe omeprazole concurrently with phenylbutazone to reduce development of equine gastric ulcer syndrome (EGUS), but the efficacy and safety of this practice remains unknown. Objective: To evaluate the effect of omeprazole on phenylbutazone-induced equine glandular gastric disease (EGGD) and equine squamous gastric disease (ESGD). Methods: Randomised block experimental design. Methods: Twenty-two horses with EGGD and ESGD scores ≤2 were included. Horses were assigned to treatment groups: phenylbutazone (4.4 mg/kg PO q 12 h; PBZ), phenylbutazone plus omeprazole (4 mg/kg PO q. 24 h; PBZ/OME) or placebo (CON) in a randomised block design based upon initial EGGD score. Horses were treated for up to 14 days. Gastroscopy was performed weekly; CBC and biochemistry were performed at Day 0 and study end. Horses were monitored for signs of colic and/or diarrhoea. Results: EGGD score increased in PBZ (median change 1, inter-quartile range, [IQR], 0-2) compared to PBZ/OME (median change 0, IQR -1 to 0; P = .05). PBZ/OME (6/8) had more intestinal complications than CON (0/6; difference between proportions = 75%; 95% CI, 23%-93%; P = .03). Plasma protein concentrations decreased in PBZ, compared to CON (mean difference between groups, 14 g/L; 95% CI, 1.04-27; P = .03). Five horses were withdrawn from the study due to intestinal complications (n = 3 PBZ/OME and n = 2 PBZ); one horse (PBZ) was withdrawn due to severe grade 4 EGGD. Conclusions: Small sample size and changes in management for the 2-3 days prior to study initiation; variable treatment duration among groups due to development of complications. Conclusions: Administration of omeprazole ameliorated PBZ-induced EGGD, but was associated with an increase in intestinal complications. Caution should be exercised when co-prescribing NSAIDs and omeprazole in horses, particularly in association with change in management.
Publication Date: 2020-08-18 PubMed ID: 32697849DOI: 10.1111/evj.13323Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates the impact of combining omeprazole with phenylbutazone – often used for treating painful or inflammatory disorders in horses. The aim was to see whether the addition of omeprazole could counteract gastrointestinal side effects associated with phenylbutazone. The results revealed that while omeprazole did reduce gastric issues caused by phenylbutazone, it also led to an increase in intestinal complications.

Research Methodology and Design

  • The study involved a randomized block experimental design with 22 horses, all of which had equine glandular gastric disease (EGGD) and equine squamous gastric disease (ESGD) scores of 2 or less.
  • The horses were divided into three groups: one group was given phenylbutazone, another received a combination of phenylbutazone and omeprazole, and the last group was given a placebo.
  • All of the horses underwent treatment for up to two weeks. During this period, they were monitored for signs of colic and/or diarrhea, and weekly gastroscopy was conducted. Complete blood count (CBC) and biochemistry tests were carried out at the beginning and at the end of the study.

Study Findings

  • The study found that the EGGD score increased in the group given only phenylbutazone.
  • Contrastingly, the horses treated with a combination of phenylbutazone and omeprazole experienced no increase in EGGD scores.
  • However, the combined treatment group had more instances of intestinal complications than the placebo group.
  • Furthermore, plasma protein concentrations fell in the phenylbutazone-only group when compared to the placebo group.
  • Five horses underwent withdrawal from the study due to intestinal complications. Three of these horses were in the combined treatment group and two were in the phenylbutazone-only group. Another horse from the phenylbutazone-only group was also removed due to a severe case of EGGD.

Study Conclusions

  • The results suggested that while administering omeprazole can alleviate EGGD induced by phenylbutazone, it can also lead to an increase in intestinal complications.
  • The small sample size and certain variables (like changes in management for two to three days prior to the study) were identified as limitations.
  • Given these results, the researchers recommend caution when prescribing both non-steroidal anti-inflammatory drugs (NSAIDs) and omeprazole in horses, especially in tandem with changes in management.

Cite This Article

APA
Ricord M, Andrews FM, Yu00f1iguez FJM, Keowen M, Garza F, Paul L, Chapman A, Banse HE. (2020). Impact of concurrent treatment with omeprazole on phenylbutazone-induced equine gastric ulcer syndrome (EGUS). Equine Vet J, 53(2), 356-363. https://doi.org/10.1111/evj.13323

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 53
Issue: 2
Pages: 356-363

Researcher Affiliations

Ricord, Megan
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Andrews, Frank M
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Yu00f1iguez, Francisco J M
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Keowen, Michael
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Garza, Frank
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Paul, Linda
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Chapman, Ann
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Banse, Heidi E
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Horse Diseases / chemically induced
  • Horse Diseases / drug therapy
  • Horses
  • Omeprazole / adverse effects
  • Phenylbutazone / adverse effects
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / drug therapy
  • Stomach Ulcer / veterinary

Grant Funding

  • Charles V. Cusimano Equine Health Studies Program

References

This article includes 44 references
  1. Duz M, Marshall JF, Parkin TD. Proportion of nonsteroidal anti-inflammatory drug prescription in equine practice. Equine Vet J. 2019;51:147-53.
  2. Snow D, Douglas T, Thompson H, Parkins J, Holmes P. Phenylbutazone toxicosis in equidae: a biochemical and pathophysiological study. Am J Vet Res. 1981;42:1754-9.
  3. Monreal L, Sabate D, Segura D, Mayu00f3s I, Homedes J. Lower gastric ulcerogenic effect of suxibuzone compared to phenylbutazone when administered orally to horses. Res Vet Sci. 2004;76:145-9.
  4. Pedersen S, Cribb A, Read E, French D, Banse H. Phenylbutazone induces equine glandular gastric disease without decreasing prostaglandin E2 concentrations. J Vet Pharmacol Ther. 2018;41:239-45.
  5. MacAllister C, Morgan S, Borne A, Pollet R. Comparison of adverse effects of phenylbutazone, flunixin meglumine, and ketoprofen in horses. J Am Vet Med Assoc. 1993;202:71-7.
  6. Read WK. Renal medullary crest necrosis associated with phenylbutazone therapy in horses. Vet Pathol. 1983;20:662-9.
  7. MacKay R, French T, Nguyen H, Mayhew I. Effects of large doses of phenylbutazone administration to horses. Am J Vet Res. 1983;44:774-80.
  8. Collins L, Tyler D. Experimentally induced phenylbutazone toxicosis in ponies: description of the syndrome and its prevention with synthetic prostaglandin E2. Am J Vet Res. 1985;46:1605-15.
  9. Karcher LF, Dill SG, Anderson WI, King JM. Right dorsal colitis. J Vet Intern Med. 1990;4:247-53.
  10. Wallace JL, McKnight W, Reuter BK, Vergnolle N. NSAID-induced gastric damage in rats: requirement for inhibition of both cyclooxygenase 1 and 2. Gastroenterology. 2000;119:706-14.
  11. Wallace JL. NSAID gastroenteropathy: past, present and future. Can J Gastroenterol Hepatol. 1996;10:451-9.
  12. Watanabe T, Fujiwara Y, Chan FK. Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review. J Gastroenterol. 2020;55:481-95.
  13. Meschter CL, Gilbert M, Krook L, Maylin G, Corradino R. The effects of phenylbutazone on the intestinal mucosa of the horse: a morphological, ultrastructural and biochemical study. Equine Vet J. 1990;22:255-63.
  14. Meschter C, Gilbert M, Krook L, Maylin G, Corradino R. The effects of phenylbutazone on the morphology and prostaglandin concentrations of the pyloric mucosa of the equine stomach. Vet Pathol. 1990;27:244-53.
  15. McConnico RS, Morgan TW, Williams CC, Hubert JD, Moore RM. Pathophysiologic effects of phenylbutazone on the right dorsal colon in horses. Am J Vet Res. 2008;69:1496-505.
  16. Bjarnason I, Scarpignato C, Holmgren E, Olszewski M, Rainsford KD, Lanas A. Mechanisms of damage to the gastrointestinal tract from nonsteroidal anti-inflammatory drugs. Gastroenterology. 2018;154:500-14.
  17. Scheiman JM. The use of proton pump inhibitors in treating and preventing NSAID-induced mucosal damage. Arthritis Res Ther. 2013;15:S5.
  18. MacAllister C, Sifferman R, McClure S, White G, Vatistas N, Holste J et al Effects of omeprazole paste on healing of spontaneous gastric ulcers in horses and foals: a field trial. Equine Vet J. 1999;31:77-80.
  19. Andrews F, Sifferman R, Bernard W, Hughes F, Holste J, Daurio C et al Efficacy of omeprazole paste in the treatment and prevention of gastric ulcers in horses. Equine Vet J. 1999;31:81-6.
  20. Vatistas N, Snyder J, Nieto J, Thompson D, Pollmeier M, Holste J. Acceptability of a paste formulation and efficacy of high dose omeprazole in healing gastric ulcers in horses maintained in race training. Equine Vet J. 1999;31:71-6.
  21. Sykes B, Jokisalo J. Rethinking equine gastric ulcer syndrome: part 1-terminology, clinical signs and diagnosis. Equine Vet Educ. 2014;26:543-7.
  22. Sykes B, Hewetson M, Hepburn R, Luthersson N, Tamzali Y. European College of Equine Internal Medicine Consensus Statement-equine gastric ulcer syndrome in adult horses. J Vet Intern Med. 2015;29:1288-99.
  23. Sykes BW, Hewetson M, Hepburn RJ, Luthersson N, Tamzali Y. European College of Equine Internal Medicine Consensus Statement-equine gastric ulcer syndrome in adult horses. J Vet Intern Med. 2015;29:1288-99.
  24. Gwee KA, Goh V, Lima G, Setia S. Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits. J Pain Res. 2018;11:361.
  25. Wallace JL, Syer S, Denou E, de Palma G, Vong L, McKnight W et al Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology. 2011;141(4):1314-1322.e5.
  26. Mu00e4kivuokko H, Tiihonen K, Tynkkynen S, Paulin L, Rautonen N. The effect of age and non-steroidal anti-inflammatory drugs on human intestinal microbiota composition. Br J Nutr. 2010;103:227-34.
  27. Freedberg DE, Toussaint NC, Chen SP, Ratner AJ, Whittier S, Wang TC et al Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome: a crossover trial. Gastroenterology. 2015;149(4):883-885.e9.
  28. Tyma JF, Epstein KL, Whitfield-Cargile CM, Cohen ND, Giguu00e8re S. Investigation of effects of omeprazole on the fecal and gastric microbiota of healthy adult horses. Am J Vet Res. 2019;80:79-86.
  29. Whitfield-Cargile CM, Chamoun-Emanuelli AM, Cohen ND, Richardson LM, Ajami NJ, Dockery HJ. Differential effects of selective and non-selective cyclooxygenase inhibitors on fecal microbiota in adult horses. PLoS One. 2018;13(8):e0202527.
  30. Van Hoogmoed L, Rakestraw P, Snyder J, Harmon F. In vitro effects of nonsteroidal anti-inflammatory agents and prostaglandins I2, E2, and F2alpha on contractility of taenia of the large colon of horses. Am J Vet Res. 1999;60:1004.
  31. Van Hoogmoed LM, Snyder JR, Harmon F. In vitro investigation of the effect of prostaglandins and nonsteroidal anti-inflammatory drugs on contractile activity of the equine smooth muscle of the dorsal colon, ventral colon, and pelvic flexure. Am J Vet Res. 2000;61:1259-66.
  32. Van Hoogmoed LM, Snyder JR, Harmon FA. In vitro investigation of the effects of cyclooxygenase-2 inhibitors on contractile activity of the equine dorsal and ventral colon. Am J Vet Res. 2002;63:1496-500.
  33. Roger T, Ruckebusch Y. Pharmacological modulation of postprandial colonic motor activity in the pony. J Vet Pharmacol Ther. 1987;10:273-82.
  34. Lowe J, Sellers A, Brondum J. Equine pelvic flexure impaction. A model used to evaluate motor events and compare drug response. Cornell Vet. 1980;70:401-12.
  35. Adams S, Lamar C, Masty J. Motility of the distal portion of the jejunum and pelvic flexure in ponies: effects of six drugs. Am J Vet Res. 1984;45:795-9.
  36. Noble G, Edwards S, Lievaart J, Pippia J, Boston R, Raidal S. Pharmacokinetics and safety of single and multiple oral doses of meloxicam in adult horses. J Vet Intern Med. 2012;26:1192-201.
  37. Lichtenberger LM, Bhattarai D, Phan TM, Dial EJ, Uray K. Suppression of contractile activity in the small intestine by indomethacin and omeprazole. Am J Physiol Gastrointest Liver Physiol. 2015;308:G785-93.
  38. Davis J. Nonsteroidal anti-inflammatory drug associated right dorsal colitis in the horse. Equine Vet Educ. 2017;29:104-13.
  39. Soma LR, Uboh CE, Maylin GM. The use of phenylbutazone in the horse. J Vet Pharmacol Ther. 2012;35:1-12.
  40. Toutain P, Autefage A, Legrand C, Alvinerie M. Plasma concentrations and therapeutic efficacy of phenylbutazone and flunixin meglumine in the horse: pharmacokinetic/pharmacodynamic modelling. J Vet Pharmacol Ther. 1994;17:459-69.
  41. Hu HH, MacAllister CG, Payton ME, Erkert RS. Evaluation of the analgesic effects of phenylbutazone administered at a high or low dosage in horses with chronic lameness. J Am Vet Med Assoc. 2005;226:414-7.
  42. Fernandes KA, Kittelmann S, Rogers CW, Gee EK, Bolwell CF, Bermingham EN et al Faecal microbiota of forage-fed horses in New Zealand and the population dynamics of microbial communities following dietary change. PloS one. 2014;9(11):e112846.
  43. Archer D, Proudman C. Epidemiological clues to preventing colic. Vet J. 2006;172:29-39.
  44. Christley R. Power and error: increased risk of false positive results in underpowered studies. Open Epidemiol J. 2010;3(1):16-9.

Citations

This article has been cited 4 times.
  1. Vokes J, Lovett A, Sykes B. Equine Gastric Ulcer Syndrome: An Update on Current Knowledge.. Animals (Basel) 2023 Apr 5;13(7).
    doi: 10.3390/ani13071261pubmed: 37048517google scholar: lookup
  2. Flood J, Stewart AJ. Non-Steroidal Anti-Inflammatory Drugs and Associated Toxicities in Horses.. Animals (Basel) 2022 Oct 26;12(21).
    doi: 10.3390/ani12212939pubmed: 36359062google scholar: lookup
  3. Jacobs CC, Schnabel LV, McIlwraith CW, Blikslager AT. Non-steroidal anti-inflammatory drugs in equine orthopaedics.. Equine Vet J 2022 Jan 25;54(4):636-48.
    doi: 10.1111/evj.13561pubmed: 35076950google scholar: lookup
  4. Hewetson M, Tallon R. Equine Squamous Gastric Disease: Prevalence, Impact and Management.. Vet Med (Auckl) 2021;12:381-399.
    doi: 10.2147/VMRR.S235258pubmed: 35004264google scholar: lookup