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Clonidine interaction in amitriptyline poisoning.

K Knudsen1, S E Ricksten, A Heath

  • 1Department of Anesthesia and Intensive Care, University of Gothenburg, Sahlgren's Hospital, Sweden.

Journal of Toxicology. Clinical Toxicology
|January 1, 1988
PubMed
Summary
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Clonidine did not reverse amitriptyline-induced cardiotoxicity in rats. This alpha-2 agonist may worsen outcomes in tricyclic antidepressant poisoning by increasing afterload.

Area of Science:

  • Cardiology
  • Pharmacology
  • Toxicology

Background:

  • Tricyclic antidepressants (TCAs) like amitriptyline can cause life-threatening cardiotoxicity.
  • Alpha-2 adrenergic agonists, such as clonidine, are sometimes considered for managing TCA overdose, but their efficacy is debated.

Purpose of the Study:

  • To investigate the effects of clonidine on amitriptyline-induced cardiotoxicity in an experimental rat model.
  • To determine if clonidine administration alters the cardiovascular effects or mortality associated with amitriptyline toxicity.

Main Methods:

  • Rats received a continuous infusion of amitriptyline (30 mg/kg/h) until death.
  • Clonidine (50 micrograms/kg) was administered intravenously 15 minutes after initiating the amitriptyline infusion.
  • Hemodynamic parameters including blood pressure, left ventricular end-diastolic pressure, cardiac contractility, and heart rate were monitored.

Related Experiment Videos

  • Electrocardiograms (ECGs) were analyzed for signs of sympathetic outflow changes.

    • Main Results:

    • Clonidine administration resulted in increased blood pressure and left ventricular end-diastolic pressure.
    • Heart rate decreased, and cardiac contractility remained unchanged.
    • These hemodynamic changes were attributed to peripheral vasoconstriction and increased afterload, not central sympathetic inhibition.
    • No improvement in amitriptyline-induced cardiovascular toxicity or mortality was observed.

    Conclusions:

    • Clonidine did not mitigate amitriptyline-induced cardiotoxicity in this rat model.
    • The peripheral vasoconstrictive effects of clonidine may exacerbate cardiac strain and potentially increase mortality.
    • Clonidine may be harmful if used in the treatment of tricyclic antidepressant poisoning due to increased afterload.