Clenbuterol toxicosis in three Quarter Horse racehorses after administration of a compounded product

Jessica A. Thompson Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

Search for other papers by Jessica A. Thompson in
Current site
Google Scholar
PubMed
Close
 DVM, MS
,
Mustajab H. Mirza Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

Search for other papers by Mustajab H. Mirza in
Current site
Google Scholar
PubMed
Close
 DVM, MS
,
Steven A. Barker Equine Medication Surveillance Laboratory and the Laboratory for Drug Residue Studies, Department of Comparative Biomedical Services, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

Search for other papers by Steven A. Barker in
Current site
Google Scholar
PubMed
Close
 PhD
,
Timothy W. Morgan Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

Search for other papers by Timothy W. Morgan in
Current site
Google Scholar
PubMed
Close
 DVM, PhD, DACVP
,
Rudy W. Bauer Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

Search for other papers by Rudy W. Bauer in
Current site
Google Scholar
PubMed
Close
 DVM, PhD, DACVP
, and
Rebecca S. McConnico Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

Search for other papers by Rebecca S. McConnico in
Current site
Google Scholar
PubMed
Close
 DVM, PhD, DACVIM

Abstract

Case Description—3 Quarter Horse racehorses were examined for suspected clenbuterol overdose 12 to 24 hours after administration by mouth of a compounded clenbuterol product.

Clinical Findings—All horses developed sinus tachycardia, muscle tremors, hyperhidrosis, and colic. Abnormalities on serum biochemical analysis included hyperglycemia, azotemia, and high creatine kinase activity. The presence of clenbuterol in the serum of all 3 horses and in the product administered was confirmed and quantified by use of liquid chromatography-electrospray tandem mass spectrometry.

Treatment and Outcome—Propranolol (0.01 mg/kg [0.005 mg/lb], IV) was administered to all 3 horses for antagonism of β-adrenergic effects and caused a transient decrease in heart rate in all patients. All horses also received crystalloid fluids IV and other supportive treatment measures. Two horses were euthanatized (2 and 4 days after admission) because of complications. One horse recovered and was discharged 4 days after admission to the hospital. In the 2 nonsurviving horses, skeletal and cardiac muscle necrosis was evident at necropsy, and tissue clenbuterol concentrations were highest in the liver.

Clinical Relevance—Clenbuterol is a β2-adrenergic receptor agonist licensed for veterinary use as a bronchodilator. At doses ≥ 10 2μg/kg (4.5 μg/lb), in excess of those normally prescribed, β-adrenergic stimulation by clenbuterol may cause sustained tachycardia, muscle tremors, hyperglycemia, and cardiac and skeletal muscle necrosis. Laminitis, acute renal failure, rhabdomyolysis, and cardiomyopathy were fatal complications associated with clenbuterol overdose in 2 horses in the present report. At the dose administered, propranolol was effective for short-term control of sinus tachycardia, but it did not alleviate all clinical signs in patients in the present report. These cases demonstrated the risks associated with the use of nonprescribed compounded medications for which the ingredients may be unknown.

Abstract

Case Description—3 Quarter Horse racehorses were examined for suspected clenbuterol overdose 12 to 24 hours after administration by mouth of a compounded clenbuterol product.

Clinical Findings—All horses developed sinus tachycardia, muscle tremors, hyperhidrosis, and colic. Abnormalities on serum biochemical analysis included hyperglycemia, azotemia, and high creatine kinase activity. The presence of clenbuterol in the serum of all 3 horses and in the product administered was confirmed and quantified by use of liquid chromatography-electrospray tandem mass spectrometry.

Treatment and Outcome—Propranolol (0.01 mg/kg [0.005 mg/lb], IV) was administered to all 3 horses for antagonism of β-adrenergic effects and caused a transient decrease in heart rate in all patients. All horses also received crystalloid fluids IV and other supportive treatment measures. Two horses were euthanatized (2 and 4 days after admission) because of complications. One horse recovered and was discharged 4 days after admission to the hospital. In the 2 nonsurviving horses, skeletal and cardiac muscle necrosis was evident at necropsy, and tissue clenbuterol concentrations were highest in the liver.

Clinical Relevance—Clenbuterol is a β2-adrenergic receptor agonist licensed for veterinary use as a bronchodilator. At doses ≥ 10 2μg/kg (4.5 μg/lb), in excess of those normally prescribed, β-adrenergic stimulation by clenbuterol may cause sustained tachycardia, muscle tremors, hyperglycemia, and cardiac and skeletal muscle necrosis. Laminitis, acute renal failure, rhabdomyolysis, and cardiomyopathy were fatal complications associated with clenbuterol overdose in 2 horses in the present report. At the dose administered, propranolol was effective for short-term control of sinus tachycardia, but it did not alleviate all clinical signs in patients in the present report. These cases demonstrated the risks associated with the use of nonprescribed compounded medications for which the ingredients may be unknown.

Contributor Notes

Dr. Morgan's present address is the Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, PO Box 6100, MS 39762.

The authors thank Drs. Tara Riddick and Alberto Rullan for assistance with patient management.

Address correspondence to Dr. McConnico (mcconnico@vetmed.lsu.edu).
  • 1.

    FDA. NADA 140–973 Ventipulmin Syrup—original approval. Available at: www.fda.gov/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/FOIADrugSummaries/UCM054881. Accessed Jan 23, 2011.

    • Search Google Scholar
    • Export Citation
  • 2.

    Guan F, Uboh CE, Soma LR, et al. Quantification of clenbuterol in equine plasma, urine and tissue by liquid chromatography coupled on-line with quadrupole time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 2002; 16: 16421651.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Ramos F, Silveira IM, Silva J, et al. Proposed guidelines for clenbuterol food poisoning. Am J Med 2004; 117:362.

  • 4.

    Sporano V, Grasso L, Esposito M, et al. Clenbuterol residues in non-liver containing meat as a cause of collective food poisoning. Vet Hum Toxicol 1998; 40: 141143.

    • Search Google Scholar
    • Export Citation
  • 5.

    Chodorowski Z, Sein Anand J. Acute poisoning with clenbuterol—a case report. Przeglad Lek 1997; 54: 763764.

  • 6.

    Hoffman RJ, Hoffman RS, Freyberg CL, et al. Clenbuterol ingestion causing prolonged tachycardia, hypokalemia, and hypophosphatemia with confirmation by quantitative levels. J Toxicol Clin Toxicol 2001; 39: 339344.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Pulce C, Lamaison D, Keck G, et al. Collective human food poisonings by clenbuterol residues in veal liver. Vet Hum Toxicol 1991; 33: 480481.

    • Search Google Scholar
    • Export Citation
  • 8.

    Soma LR, Uboh CE, Guan F, et al. Pharmacokinetics and disposition of clenbuterol in the horse. J Vet Pharmacol Ther 2004; 27: 7177.

  • 9.

    Schultz K. Counterfeit clenbuterol found in treated horses. Available at: www.veterinarynews.dvm360.com/dvm/Veterinary+news/Counterfeit-clenbuterol-found-in-treated-horses/ArticleStandard/Article/detail/398284. Accessed Jan 23, 2011.

    • Search Google Scholar
    • Export Citation
  • 10.

    FDA. FDA warns horse owners and vets about deaths due to unapproved clenbuterol. Available at: www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm048170.htm. Accessed Jan 29, 2010.

    • Search Google Scholar
    • Export Citation
  • 11.

    Ryder E. Concentrated counterfeit clenbuterol having deadly effect. Available at: www.thehorse.com/ViewArticle.aspx?ID=8230. Accessed Jan 29, 2010.

    • Search Google Scholar
    • Export Citation
  • 12.

    US FDA. Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA). Available at: www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/ActsRulesRegulations/ucm085377.htm. Accessed Jan 22, 2011.

    • Search Google Scholar
    • Export Citation
  • 13.

    Daubert GP, Mabasa VH, Leung VW, et al. Acute clenbuterol overdose resulting in supraventricular tachycardia and atrial fibrillation. J Med Toxicol 2007; 3: 5660.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Brambilla G, Cenci T, Franconi F, et al. Clinical and pharmacological profile in a clenbuterol epidemic poisoning of contaminated beef meat in Italy. Toxicol Lett 2000; 114: 4753.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Robinson NE. Clenbuterol and the horse, in Proceedings. 46th Annu Meet Am Assoc Equine Pract 2000; 229233.

  • 16.

    Re G, Belloli C, Badino P, et al. Identification of β-adrenergic receptor subtypes mediating relaxation in isolated equine ileum. Am J Vet Res 1997; 58: 621625.

    • Search Google Scholar
    • Export Citation
  • 17.

    Burniston JG, Ng Y, Clark WA, et al. Myotoxic effects of clenbuterol in the rat heart and soleus muscle. J Appl Physiol 2002; 93: 18241832.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Tan LB, Burniston JG, Clark WA, et al. Characterization of adrenoceptor involvement in skeletal and cardiac myotoxicity induced by sympathomimetic agents: toward a new bioassay for β-blockers. J Cardiovasc Pharmacol 2003; 41: 518525.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Belloli C, Re G, Arioli F, et al. Differences between longitudinal and circular smooth muscle in β-adrenergic control of motility of isolated equine ileum. Am J Vet Res 1997; 58: 14221426.

    • Search Google Scholar
    • Export Citation
  • 20.

    Badino P, Odore R, Re G. Are so many adrenergic receptor subtypes really present in domestic animal tissues? A pharmacological perspective. Vet J 2005; 170: 163174.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Burniston JG Chester N, Clark WA, et al. Dose-dependent apoptotic and necrotic myocyte death induced by the β2-adrenergic receptor agonist, clenbuterol. Muscle Nerve 2005; 32: 767774.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Burniston JG, Clark WA, Tan L-B, et al. Dose-dependent separation of the hypertrophic and myotoxic effects of the β2-adrenergic receptor agonist clenbuterol in rat striated muscles. Muscle Nerve 2006; 33: 655663.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Maistro S, Chiesa E, Angeletti R, et al. Beta blockers to prevent clenbuterol poisoning (lett). Lancet 1995; 346:180.

  • 24.

    Fielding CL, Brumbaugh GW, Matthews NS, et al. Pharmacokinetics and clinical effects of a subanesthetic continuous rate infusion of ketamine in awake horses. Am J Vet Res 2006; 67: 14841490.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement