Equis ISSN 2398-2977

Toxicity: zilpaterol hydrochloride

Contributor(s): Kate Hepworth-Warren, Graham Munroe

Introduction

  • Cause: rare intoxication due to eating cattle feed containing zilpaterol as an additive. Illegal use as doping agent in competitive horses.
  • Signs: acute onset of profuse sweating, muscle tremors and tachycardia.
  • Diagnosis: history of administration of feeding cattle feeds in association with clinical signs.
  • Treatment: removal of feed, nursing care, propranolol over a long period with gradually decreasing dose, laminitis prevention and management.
  • Prognosis: uncertain due to paucity of reports, but all reported cases have survived.

Pathogenesis

Etiology

  • Zilpaterol hydrochloride is a beta-2 adrenergic agonist which was used mainly in North America as a repartitioning agent and to increase feed efficiency in cattle. It is related to clenbuterol   Clenbuterol hydrochloride  , ractopamine and salbutamol   Salbutamol sulfate  . It was approved by the FDA in the USA for feeding to cattle to improve weight gain and lean muscle deposition in 2006, but was suspended from the market in 2013 due to reports of potential adverse effects on the wellbeing of animals to which the drug was administered.

Zilpaterol is not licensed anywhere in the world for use in horses.

  • The beta-2 adrenergic agonists increase blood flow in adipose tissue, increase lipolysis, and decrease lipogenesis. In muscle tissue they increase blood flow and protein accretion.
  • In large doses, beta-2 agonists lose their selectivity for beta-2 receptors and can also act on beta-1 receptors.
  • It has potent repartitioning and lipolytic effects and as such has been used illegally in humans and horses to enhance performance by increasing lipolysis and lean muscle production.
  • There have been numerous anecdotal reports of illicit administration in equine athletes and it has been specifically banned by the Association of Racing Commissioners in the USA, the FEI, and the British Horse Racing Authority in the UK.
  • The clinical signs of toxicity with zilpaterol are similar to those seen in clenbuterol toxicity, and are typical of beta-agonist toxicity.

Predisposing factors

General
  • Access to cattle feed containing this supplement.
  • Illegal doping of competitive horses.

Specific

  • In one study, oral administration of 0.17 mg/kg zilpaterol hydrochloride induced sweating within 20 min and severe tachycardia (HR >150 bpm) after 40 min.

Pathophysiology

  • The physiological effects of beta-2 adrenergic receptors when stimulated by endogenous catecholamines are: vasodilation, smooth muscle relaxation in the gastrointestinal tract, urinary bladder and uterus, bronchodilation, glycogenolysis, and burning of calories.
  • The sweat glands in the horse are also under beta-2 adrenergic control.
  • Cardiotoxicity is mediated via beta-1 activity which at higher doses can be stimulated by beta-2 agonists.

Timecourse

  • First clinical signs develop rapidly after administration; within 20-25 min of administration restlessness, muscle fasciculations and hperhidrosis have developed.
  • Tachycardia in one report was identified 40 min after ingestion, and without therapy lasted for 2 weeks. Muscle fasciculations continued for 7 days following ingestion of zilpaterol.
  • Recovery to clinical normality without treatment took 203 weeks.
  • In one case, initiation of propranolol   Propanolol   therapy lead to resolution of muscle fasciculations and sweating and a marked reduction in heart rate within 3 h.

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.
  • Bertone J (2014) Accidental zilpaterol toxicity, food for thought. Equine Vet Educ 26 (2) 86-87 WileyOnline.
  • Hepworth-Warren K L & Alcott C J (2014) Treatment and resolution of zilpaterol hydrochloride toxicity in a Quarter Horse gelding. Equine Vet Educ 26 (2), 81-85 VetMedResource.
  • Wagner S A et al (2008) Adverse effects of zilpaterol administration in horses: three cases. J Equine Vet Sci 28 (4), 238-243 VetMedResource.

Other sources of information


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