Canis ISSN: 2398-2942

Ibuprofen toxicity

Contributor(s): Lisa Moore

Introduction

  • Cause: ingestion of non-steroidal anti-inflammatory agent (NSAID).
  • Signs: polydipsia, vomiting, melena.
  • Diagnosis: history, clinical signs.
  • Treatment: symptomatic.
  • Prognosis: good.
  • No adverse clinical signs or abnormal laboratory parameters if serum ibuprofen concentrations <31 ug/ml.
    Print off the owner factsheet Ibuprofen and Naproxen toxicosis Ibuprofen and Naproxen toxicosis to give to your client.

Pathogenesis

Pathophysiology

  • Low safety margin in dogs as excreted slowly.
  • Absorbed from gut to give peak levels.
  • Toxic dose 50-125 mg/kg.
  • Competitive inhibition of cyclo-oxygenase step of prostaglandin synthesis. Such inhibition and subsequent reduction in concentrations of PG12 and PGE2 account for the major effects seen in poisoning cases.
  • PGs are concernced with control of gastric acid production, stimulation of secretion of mucous and bicarbonate by the gastric epithelium, and maintenance of mucosal blood flow. In the kidneys, prostaglandins are concerned with renal homeostasis; they maintain afferent arteriolar regulation of renal blood flow and glomerular filtration rate.

Low doses cause gastrointestinal effects

  • In the GI tract prostaglandins have a cytoprotective function as they control production of gastric acid, stimulate secretion of mucous and bicarbonate by the gastric epithelium and maintain mucosal blood flow by causing vasodilation. Deficiency results in increased gastric acid secretion and reduction in mucous production and mucosal blood flow. These effects and the acidic nature of the drug itself all increase risk of ulcer formation.

Higher doses cause renal effects

  • In the kidneys PGs maintain afferent arteriolar dilatation regulating renal blood flow and glomerular filtration rate also control renin release and maintenance of water balance. NSAID inhibition of prostaglandin synthesis will result in reduction of renal blood flow and disrupt normal renal function and homeostatic mechanisms. Constriction of renal arterioles may result in renal papillary necrosis. These effects may be more evident in animals that are dehydrated or volume depleted.

Timecourse

  • Signs develop within 2 hours of acute intoxication.
  • Chronic therapy may also cause signs.
  • Renal failure may develop within 24 hours of massive dose.
  • Can be delayed up to 3-5 days at lower dose.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Williamson K K, Willard M D, Payton M E, Davis M S (2010) Efficacy of omeprazole versus high-dose famotidine for prevention of exercise-induced gastritis in racing Alaskan sled dogs. J Vet Intern Med 24 (2), 285-288 PubMed.
  • Bersenas A M, Mathews K A, Allen D G, Conlon P D (2005) Effects of ranitidine, famotidine, pantoprazole, and omeprazole on intragastric pH in dogs. Am J Vet Res 66 (3), 425-431 PubMed.
  • Hata J, Kamada N, Manabe N, Kusunoki H, Kamino D, Nakao M, Fukumoto A, Yamaguchi T, Sato M, Haruma K (2005) Famotidine prevents canine gastric blood flow reduction by NSAIDs. Aliment Pharmacol Ther 21 (Suppl 2), 55-59 PubMed.
  • Dunayer E (2004) Ibuprofen toxicosis in dogs, cats and ferrets. Vet Med 99 (7), 580-586 ASPCA pro.
  • Richardson J A (2000) Management of acetaminophen and ibuprofen toxicoses in dogs and cats. J Vet Emerg Crit Care 10 (4), 285-291 Wiley Online Library.
  • Poortinga E W, Hungerford L L (1998) A case control study of acute ibuprofen toxicity in dogs. Prevent Vet Med 35 (2), 115-124 PubMed.
  • Villar D, Buck W B, Gonzalez J M (1998) Ibuprofen, aspirin and acetaminophen toxicosis and treatment in dogs and cats. Vet Hum Toxicol 40 (3), 156-162 PubMed.
  • Smith K J, Taylor D H (1993) Another case of gastric perforation associated with administration of ibuprofen in a dog. J Am Vet Med Assoc 202 (5), 706 PubMed.
  • Godshalk C P, Roush J K, Fingland R B, Sikkema D, Vorhies M W (1992) Gastric perforation associated with administration of ibuprofen in a dog. J Am Vet Med Assoc 201 (22), 1734-1736 PubMed.
  • Earl J A (1987) Flurbiprofen warning. Vet Rec 120 (14), 349 PubMed.
  • Scherkl R, Frey H H (1987) Pharmacokinetics of ibuprofen in the dog. J Vet Pharmacol Ther 10 (3), 261-265 PubMed.
  • Spyridakis L K, Baci J J, Barsanti J A, Brown S C (1986) Ibuprofen toxicosis in a dog. J Am Vet Med Assoc 189 (9), 918-919 PubMed.
  • Larsson H, Carlsson E, Junggren U, Olbe L, Sjöstrand SE, Skånberg I, Sundell G (1983) Inhibition of gastric acid secretion by omeprazole in the dog and rat. Gastroenterology 85 (4), 900-907 PubMed.
  • Adams S S, Bough R G, Cliffe E E, Lessel B, Mills R F (1969) Absorption, distribution and toxicity of ibuprofen. Toxicol Appl Pharm 15 (2), 310-330 PubMed.

Other sources of information

  • Poppenga R H, Gwaltney-Brant S M (2011) Small Animal Toxicology Essentials.Wiley-Blackwell, pp 236-238.
  • Osweiler G D, Hovda L R, Brutlag A G, Lee J A (2011) Blackwells Five-Minute Veterinary Consult: Clinical Companion Small Animal Toxicology.Wiley-Blackwell, pp 292-299.
  • Baxter K (ed) (2010) Stockleys Drug Interactions, 9th edition. London: Pharmaceutical Press.
  • Ramsey I (ed) (2010) BSAVA Small Animal Formulary,7th edition. BSAVA, Gloucestershire.
  • Boots plc. 1984 Personal Communication.

Organisation(s)


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