• 1. Westfall TC, Westfall DP. Adrenergic agonists and antagonists. In: Brunton L, Lazo JS, Parker KL, eds. Goodman and Gilman's pharmacologic basis of therapuetics. 11th ed. New York: McGraw-Hill, 2006;237296.

    • Search Google Scholar
    • Export Citation
  • 2. Bristow MR. Beta-adrenergic receptor blockade in chronic heart failure. Circulation 2000;101:558569.

  • 3. Cleland JG. Beta-blockers for heart failure: why, which, when, and where. Med Clin North Am 2003;87:339371.

  • 4. Eason BD, Fine DM, Leeder D, et al. Influence of beta blockers on survival in dogs with severe subaortic stenosis. J Vet Intern Med 2014;28:857862.

    • Search Google Scholar
    • Export Citation
  • 5. Monnet E, Orton EC, Gaynor JS, et al. Open resection for subvalvular aortic stenosis in dogs. J Am Vet Med Assoc 1996;209:12551261.

  • 6. Meurs KM, Spier AW, Wright NA, et al. Comparison of the effects of four antiarrhythmic treatments for familial ventricular arrhythmias in Boxers. J Am Vet Med Assoc 2002;221:522527.

    • Search Google Scholar
    • Export Citation
  • 7. Schober KE, Zientek J, Li X, et al. Effect of treatment with atenolol on 5-year survival in cats with preclinical (asymptomatic) hypertrophic cardiomyopathy. J Vet Cardiol 2013;15:93104.

    • Search Google Scholar
    • Export Citation
  • 8. Brown S, Atkins C, Bagley R, et al. Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med 2007;21:542558.

    • Search Google Scholar
    • Export Citation
  • 9. Abbott JA. Beta-blockade in the management of systolic dysfunction. Vet Clin North Am Small Anim Pract 2004;34:11571170.

  • 10. Papich MG. Saunders handbook of veterinary drugs: small and large animal. 3rd ed. St Louis: Elsevier Saunders, 2011;5456.

  • 11. McAinsh J, Holmes BF. Pharmacokinetic studies with atenolol in the dog. Biopharm Drug Dispos 1983;4:249261.

  • 12. Reeves PR, Barnfield DJ, Longshaw S, et al. Disposition and metabolism of atenolol in animals. Xenobiotica 1978;8:305311.

  • 13. Jürgens G, Graudal NA, Kampmann JP. Therapeutic drug monitoring of antiarrhythmic drugs. Clin Pharmacokinet 2003;42:647663.

  • 14. Talbert RL. Pharmacokinetics and pharmacodynamics of beta blockers in heart failure. Heart Fail Rev 2004;9:131137.

  • 15. Abbott JA, Broadstone RV, Ward DL, et al. Hemodynamic effects of orally administered carvedilol in healthy conscious dogs. Am J Vet Res 2005;66:637641.

    • Search Google Scholar
    • Export Citation
  • 16. Gordon SG, Arsenault WG, Longnecker M, et al. Pharmacodynamics of carvedilol in conscious, healthy dogs. J Vet Intern Med 2006;20:297304.

    • Search Google Scholar
    • Export Citation
  • 17. Uechi M, Sasaki T, Ueno K, et al. Cardiovascular and renal effects of carvedilol in dogs with heart failure. J Vet Med Sci 2002;64:469475.

    • Search Google Scholar
    • Export Citation
  • 18. Houston MC, Hodge R. Beta-adrenergic blocker withdrawal syndromes in hypertension and other cardiovascular diseases. Am Heart J 1988;116:515523.

    • Search Google Scholar
    • Export Citation
  • 19. Swedberg K, Hjalmarson A, Waagstein F, et al. Adverse effects of beta-blockade withdrawal in patients with congestive cardiomyopathy. Br Heart J 1980;44:134142.

    • Search Google Scholar
    • Export Citation
  • 20. Gilligan DM, Chan WL, Stewart R, et al. Adrenergic hypersensitivity after beta-blocker withdrawal in hypertrophic cardiomyopathy. Am J Cardiol 1991;68:766772.

    • Search Google Scholar
    • Export Citation
  • 21. Ross PJ, Lewis MJ, Sheridan DJ, et al. Adrenergic hypersensitivity after beta-blocker withdrawal. Br Heart J 1981;45:637642.

  • 22. Flannery G, Gehrig-Mills R, Billah B, et al. Analysis of randomized controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers. Am J Cardiol 2008;101:865869.

    • Search Google Scholar
    • Export Citation
  • 23. McAlister FA, Wiebe N, Ezekowitz JA, et al. Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med 2009;150:784794.

    • Search Google Scholar
    • Export Citation
  • 24. Meurs KM, Lehmkuhl LB, Bonagura JD. Survival times in dogs with severe subvalvular aortic stenosis treated with balloon valvuloplasty or atenolol. J Am Vet Med Assoc 2005;227:420424.

    • Search Google Scholar
    • Export Citation
  • 25. Tsutsui H, Spinale FG, Nagatsu M, et al. Effects of chronic beta-adrenergic blockade on the left ventricular and cardiocyte abnormalities of chronic canine mitral regurgitation. J Clin Invest 1994;93:26392648.

    • Search Google Scholar
    • Export Citation
  • 26. Cavero I, Riggenbach H, Wall M, et al. Analysis of cardiac chronotropic responses to some autonomic blocking agents in conscious trained dogs. Eur J Pharmacol 1976;39:193202.

    • Search Google Scholar
    • Export Citation
  • 27. Meurs KM, Stern JA, Reina-Doreste Y, et al. Impact of the canine double-deletion beta1 adrenoreceptor polymorphisms on protein structure and heart rate response to atenolol, a beta1-selective beta-blocker. Pharmacogenet Genomics 2015;25:427431.

    • Search Google Scholar
    • Export Citation
  • 28. Ware WA, Lund DD, Subieta AR, et al. Sympathetic activation in dogs with congestive heart failure caused by chronic mitral valve disease and dilated cardiomyopathy. J Am Vet Med Assoc 1990;197:14751481.

    • Search Google Scholar
    • Export Citation
  • 29. Zucker IH, Wang W. Modulation of baroreflex and baroreceptor function in experimental heart failure. Basic Res Cardiol 1991;86(suppl 3):133148.

    • Search Google Scholar
    • Export Citation

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Duration of β-adrenoceptor blockade associated with once-daily oral administration of atenolol in healthy dogs

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  • 1 Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
  • | 2 Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
  • | 3 Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
  • | 4 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.

Abstract

OBJECTIVE To test the hypothesis that once-daily oral administration of atenolol would attenuate the heart rate response to isoproterenol for 24 hours.

ANIMALS 20 healthy dogs.

PROCEDURES A double-blind randomized placebo-controlled crossover study was conducted. Dogs were assigned to receive atenolol (1 mg/kg, PO, q 24 h) or a placebo for 5 to 7 days. After a washout period of 7 days, dogs then received the other treatment. Heart rate at rest (HRr) and heart rate induced by administration of isoproterenol (HRi) as a constant rate infusion (0.2 μg/kg/min for 5 to 7 minutes) were obtained by use of ECG 0, 0.25, 3, 6, 12, 18, and 24 hours after administration of the final dose of atenolol or the placebo. A mixed-model ANOVA was used to evaluate effects of treatment, time after drug or placebo administration, treatment-by-time interaction, period, and sequence on HRr and HRi.

RESULTS Effects of sequence or period were not detected. There was a significant effect of treatment and the treatment-by-time interaction on HRi. Atenolol significantly attenuated HRi for 24 hours but did so maximally at 3 hours (least squares mean ± SE, 146 ± 5 beats/min and 208 ± 5 beats/min for atenolol and placebo, respectively). The effect at 24 hours was small (193 ± 5 beats/min and 206 ± 5 beats/min for atenolol and placebo, respectively). Atenolol had a small but significant effect on HRr.

CONCLUSIONS AND CLINICAL RELEVANCE This study of healthy dogs receiving atenolol supported a recommendation for a dosing interval < 24 hours.

Abstract

OBJECTIVE To test the hypothesis that once-daily oral administration of atenolol would attenuate the heart rate response to isoproterenol for 24 hours.

ANIMALS 20 healthy dogs.

PROCEDURES A double-blind randomized placebo-controlled crossover study was conducted. Dogs were assigned to receive atenolol (1 mg/kg, PO, q 24 h) or a placebo for 5 to 7 days. After a washout period of 7 days, dogs then received the other treatment. Heart rate at rest (HRr) and heart rate induced by administration of isoproterenol (HRi) as a constant rate infusion (0.2 μg/kg/min for 5 to 7 minutes) were obtained by use of ECG 0, 0.25, 3, 6, 12, 18, and 24 hours after administration of the final dose of atenolol or the placebo. A mixed-model ANOVA was used to evaluate effects of treatment, time after drug or placebo administration, treatment-by-time interaction, period, and sequence on HRr and HRi.

RESULTS Effects of sequence or period were not detected. There was a significant effect of treatment and the treatment-by-time interaction on HRi. Atenolol significantly attenuated HRi for 24 hours but did so maximally at 3 hours (least squares mean ± SE, 146 ± 5 beats/min and 208 ± 5 beats/min for atenolol and placebo, respectively). The effect at 24 hours was small (193 ± 5 beats/min and 206 ± 5 beats/min for atenolol and placebo, respectively). Atenolol had a small but significant effect on HRr.

CONCLUSIONS AND CLINICAL RELEVANCE This study of healthy dogs receiving atenolol supported a recommendation for a dosing interval < 24 hours.

Contributor Notes

Dr. Waterman's present address is VCA Advanced Veterinary Care Center, 15926 Hawthorne Blvd, Lawndale, CA 90260.

Dr. Eriksson De Rezende's present address is Blue Pearl Paramus, 545 Rte 17 S, Paramus, NJ 07652.

Address correspondence to Dr. Abbott (abbottj@vt.edu).