Canis ISSN: 2398-2942

Spironolactone

Contributor(s): Fraser Broadfoot, Vetstream Ltd

Introduction

Name

  • Spironolactone.

Class of drug

  • Aldosterone antagonist.

Uses

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Indications

  • Licensed in dogs for the treatment of congestive heart failure Heart: congestive heart failure caused by mitral valve disease Heart: mitral valve degenerative disease.
  • A large scale double-blind placebo-controlled study has demonstrated that the addition of spironolactone to standard first-line therapy (ACE inhibitors ACE inhibitor: overview and furosemide Furosemide ) causes:
    • Statistically significant benefits in quality of life parameters, such as dyspnea, cough, syncope and mobility.
    • A 65% reduction in the risk of mortality from heart failure.
  • These results are similar to those demonstrated in human medicine, where the addition of spironolactone to ACE inhibitors and furosemide has been shown to cause a reduction in the risk of mortality from heart failure of 30%.
  • The survival benefits in people and dogs can be attributed to the cardioprotective effects of spironolactone. In man, the effect on reducing myocardial fibrosis has been shown to be particularly important. There is now evidence that dogs with heart failure also develop an increase in myocardial fibrosis and this is directly related to an increase in mortality.

Administration

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Precautions

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Interactions

with other drugs

  • In recent clinical and tolerance studies, spironolactone was co-administered with ACE inhibitors, pimobendan Pimobendan and furosemide Furosemide without evidence of associated adverse reactions.
  • Furosemide is known to stimulate aldosterone production in the dog. Adding spironolactone alongside furosemide therefore helps to counteract this potentially harmful effect.
  • In a recent clinical study, an increased incidence of hyperkalemia Hyperkalemia wasnotobserved when combining ACE inhibitors with spironolactone. However, in dogs with renal impairment regular monitoring of renal function and serum potasasium levels is recommended as there may be an increased risk of hyperkalemia in these cases.
  • The administration of either deoxycortisone or NSAIDs with spironolactone may lead to a moderate reduction in the diuretic effects of spironolactone.
  • Spironolactone may decrease digoxin Digoxin elimination and raise digoxin plasma concentration. It is therefore advisable to monitor closely dogs receiving both digoxin and spironolactone.
  • Spironolactone may cause both induction and inhibition of cytochrome P450 enzymes and affect the metabolism of other drugs utilizing these metabolic pathways.

Adverse Reactions

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Yang, Han, Zhou, Dong, Wang, Huo, Cao, Zhou, Xiu, Li (2008) Effects of spironolactone on electrical and structural remodelling of atrium in congestive heart failure dogs. Chinese Medical Journal 121(1), 38-42.
  • Falk T, Jonsson L, Olsen L H, Pedersen H D (2006) Arteriosclerotic changes in the myocardium, lung, and kidney in dogs with chronic congestive heart failure and myxomatous mitral valve disease. Cardiovasc Pathol 15, 185-193 PubMed.
  • Macdonald K A, Kittleson M D, Larson R F, Kass P, Klose T, Wisner E R (2006) The effect of ramipril on LV mass, myocardial fibrosis, diastolic function and plasma neurohormones in Main Coone cats with Familial Hypertrophic Cardiomyopathy without Heart Failure. JVIM 20, 1093-1106 PubMed.
  • Pederson H D, Schutt T, Sondergaard R, Qvortrup K, Olsen L.H., Kristensen A T (2003) Decreased Plasma Concentration of Nitric Oxide Metabolites in Dogs with Untreated Mitral Regurgitation. JVIM 17, 178-184 PubMed.
  • Suzuki G, Morita H, Mishami T, Sharov V G, Todor A, Tanhehco E J, Rudolph A E, McMahon E G, Goldstein S, Sabbad H N (2002) Effects of Long-Term Monotherapy With Eplerenone, a Novel Aldosterone Blocker, on Progression of Left Ventricular Dysfunction and Remodelling in Dogs with Heart Failure. Circulation 106, 2967-2972 PubMed.
  • Tidholm A, Haggstrom J, Hansson K (2001) Effects of dilated cardiomyopathy on the renin-angiotensin-aldosterone system, atrial natriuretic peptide activity, and thyroid hormone concentration in dogs. Am J Vet Res 62(6), 961-966 PubMed.
  • Zannad F, Alla F, Dousset B, Perez A, Pitt B (2000) Limitation of Excessive Extracellular Matrix Turnover May Contribute to Survival Benefit of Spironolactone Therapy in Patients With Congestive Heart Failure. Circulation 102, 2700-2706 PubMed.
  • Pitt B, Zannad F, Remme W J, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999) The Effect of Spironolactone on Morbidity and Mortality in Patients With Severe Heart Failure. The New England Journal of Medicine 341(10), 709-717 PubMed.
  • Haggstrom J, Hansson K, Karlberg B.E., Kvart C, Madej A, Olsson K (1996) Effects of long-term treatment with enalepril or hydralazine on the renin-angiotensin-aldosterone system and fluid balance in dogs with naturally acquired mitral valve regurgitation. Am J Vet Res 57(11), 1645-1652 PubMed.
  • Koch J et al(1995) Activation of the renin-angiotensin system in dogs with asymptomatic and symptomatic dilated cardiomyopathy. Res Vet Sci 59(2), 172-175 PubMed.
  • Pedersen H D et al(1995) Activation of the Renin-Angiotensin System in Dogs With Asymptomatic and Mildly Symptomatic Mitral Valvular Insufficiency. JVIM 9(5), 328-331
  • Wang W (1994) Chronic Administration of Aldosterone Depresses Baroreceptor Reflex Function in the Dog. Hypertension 24, 571-575 PubMed.
  • Knowlen G C, Kittleson M D, Nachreiner R F, Eyster G E (1983) Comparison of plasma aldosterone concentration among clinical status groups of dogs with chronic heart failure. JAVMA 183(9), 991-996 PubMed.

Other sources of information

  • BSAVA Small Animal Formulary. Ramsey I (2017) 9th edn. Cheltenham: BSAVA.
  • Elliott J, Guyonnet J, Kaltsatos V (2008) Experimental studies of the pharmacology of spironolactone in dogs.ECVIM congress, Ghent
  • EPAR. PRILACTONE® V-C-105, 2007, 18/23.
  • CEVA Statistical Report SAR_CLI/430B0/0704.
  • Falk, Jonsoon, Lisbeth, Olsen, Tarnow, Pedersen (2007) Correlation of cardiac pathology and clinical findings in dogs with naturally occurring congestive heart failure. ACVIM abstracts, 233, 636.

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