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Veterinary anaesthesia and analgesia2013; 41(1); 36-47; doi: 10.1111/vaa.12081

Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse.

Abstract: To describe the effects of alpha2 -adrenergic receptor antagonists on the pharmacodynamics of sublingual (SL) detomidine in the horse. Methods: Randomized crossover design. Methods: Nine healthy adult horses with an average age of 7.6 ± 6.5 years. Methods: Four treatment groups were studied: 1) 0.04 mg kg(-1) detomidine SL; 2) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.075 mg kg(-1) yohimbine intravenously (IV); 3) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 4 mg kg(-1) tolazoline IV; and 4) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.12 mg kg(-1) atipamezole IV. Each horse received all treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for yohimbine, atipamezole and tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume (PCV) and plasma proteins were monitored. Results: Chin-to-ground distance increased following administration of the antagonists, however, this effect was transient, with a return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia and increased incidence of atrioventricular blocks were either transiently or incompletely antagonized by all antagonists. PCV and glucose concentrations increased with tolazoline administration, and atipamezole subjectively increased urination frequency but not volume. Conclusions: At the doses administered in this study, the alpha2 -adrenergic antagonistic effects of tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited by SL administration of detomidine are transient and incomplete.
Publication Date: 2013-10-17 PubMed ID: 24134603DOI: 10.1111/vaa.12081Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial

Summary

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The study examined the effects of three alpha2-adrenergic receptor antagonists – yohimbine, tolazoline, and atipamezole – on the pharmacodynamics of detomidine, a drug commonly administered sublingually to horses, revealing that the antagonists have a temporary and incomplete effect on the impacts created by detomidine.

Study Design

  • The researchers utilized a randomized crossover design with four treatment groups and nine healthy adult horses.
  • The four treatment groups varied the combination of drugs administered to the horses – detomidine by itself, detomidine followed by yohimbine, detomidine followed by tolazoline, and detomidine followed by atipamezole.
  • Each horse underwent all treatments, with at least one week between each to curtail overlap effects.
  • A technique called liquid chromatography-mass spectrometry was used to analyze blood samples from the horses for the presence and concentration of yohimbine, atipamezole and tolazoline.
  • The researchers monitored the horses’ behavioral effects, heart rate, rhythm, and levels of glucose, packed cell volume, and plasma proteins during the treatment.

Findings

  • The distance from the horse’s chin to the ground increased after giving the antagonists, meaning the horse’s head was lifted. However, this effect was transient, as it returned to normal within an hour.
  • The administration of detomidine reduced the horses’ heart rates (bradycardia) and increased occurrence of irregular heartbeats (atrioventricular blocks). These heart complications were only temporarily or partially mitigated by the antagonists.
  • Administering tolazoline resulted in a surge in the horse’s packed cell volume and glucose concentrations. Atipamezole was subjectively observed to increase urination frequency (though not volume).

Conclusion

  • The study concluded that at the dosages used, the three alpha2-adrenergic antagonists resulted in temporary and incomplete effects on the cardiac and behavioral consequences brought about by detomidine.

Cite This Article

APA
Knych HK, Stanley SD. (2013). Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse. Vet Anaesth Analg, 41(1), 36-47. https://doi.org/10.1111/vaa.12081

Publication

ISSN: 1467-2995
NlmUniqueID: 100956422
Country: United States
Language: English
Volume: 41
Issue: 1
Pages: 36-47

Researcher Affiliations

Knych, Heather K
  • K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA; Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Stanley, Scott D

    MeSH Terms

    • Adrenergic alpha-Antagonists / administration & dosage
    • Adrenergic alpha-Antagonists / blood
    • Adrenergic alpha-Antagonists / pharmacokinetics
    • Adrenergic alpha-Antagonists / pharmacology
    • Animals
    • Cross-Over Studies
    • Drug Interactions
    • Female
    • Horses / blood
    • Imidazoles / administration & dosage
    • Imidazoles / blood
    • Imidazoles / pharmacokinetics
    • Imidazoles / pharmacology
    • Male
    • Tolazoline / administration & dosage
    • Tolazoline / blood
    • Tolazoline / pharmacokinetics
    • Tolazoline / pharmacology
    • Yohimbine / administration & dosage
    • Yohimbine / blood
    • Yohimbine / pharmacokinetics
    • Yohimbine / pharmacology

    Citations

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