Canis ISSN: 2398-2942

Spironolactone

Contributor(s): Fraser Broadfoot

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 fromPubMed.
  • 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 Journal121(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 Pathol15, 185-193PubMed.
  • 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.JVIM20, 1093-1106PubMed.
  • 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.JVIM17, 178-184PubMed.
  • 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.Circulation106, 2967-2972PubMed.
  • 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 Res62(6), 961-966PubMed.
  • 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.Circulation102, 2700-2706PubMed.
  • 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 Medicine341(10), 709-717PubMed.
  • 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 Res57(11), 1645-1652PubMed.
  • Koch Jet al(1995)Activation of the renin-angiotensin system in dogs with asymptomatic and symptomatic dilated cardiomyopathy.Res Vet Sci59(2), 172-175PubMed.
  • Pedersen H Det al(1995)Activation of the Renin-Angiotensin System in Dogs With Asymptomatic and Mildly Symptomatic Mitral Valvular Insufficiency.JVIM9(5), 328-331
  • Wang W (1994)Chronic Administration of Aldosterone Depresses Baroreceptor Reflex Function in the Dog.Hypertension24, 571-575PubMed.
  • 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.JAVMA183(9), 991-996PubMed.

Other sources of information

  • 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.
  • Based onSmall Animal Formulary.Tennant, Bryn (1999) 3rd edn. Cheltenham: BSAVA.

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