Veterinary Medicine - November 2007 - (Page 738)

Pimobendan update O P E E R - R E V I E W E D potential triggering calcium release from the sarcoplasmic reticulum.5 Normal cardiac muscle is distinct from skeletal and smooth muscle in that it relies on both extracellular (L-type calcium channels) and intracellular (sarcoplasmic reticulum) calcium sources for muscle contraction. Myocardial failure, best typified by dilated cardiomyopathy, is characterized by alterations of myocyte in- scored, and the calculated dose should be given to the nearest halftablet increment. Advanced dilated cardiomyopathy Pimobendan’s strongest indication is to treat patients with advanced dilated cardiomyopathy because they have poor left ventricular systolic function and reduced ejection fraction. They are subject to increased afterload as a result We have not encountered arterial hypotension in dogs in which pimobendan was added to ACE inhibitor therapy. tegrity and severely disturbed intracellular calcium handling. 6 Cytosolic calcium ion concentrations are adequate, but the sensitivity of troponin-C to calcium ions is impaired.6,7 of dilation of the left ventricle with inadequate wall hypertrophy and arteriolar constriction (caused by activation of the renin-angiotensin-aldosterone system and increased plasma norepinephrine concentrations). This increased afterload negatively affects stroke volume and ejection fraction. Through phosphodiesterase III and V inhibition, pimobendan promotes both arteriolar and venous dilation, reducing afterload and preload, respectively. We administer pimobendan in dogs with cardiomyopathy in the face of overt or impending congestive heart failure. Clinical findings consistent with impending congestive heart failure include a gallop heart sound, atrial fibrillation, and nocturnal dyspnea. Pulmonary or hepatic vein distention on radiographic and ultrasonographic examination is also consistent with impending congestive heart failure. seem to be of little value. However, the vasodilator action may contribute to preload and afterload reduction. For dogs with degenerative mitral valve disease, we add pimobendan when overt or impending congestive heart failure occurs in the face of ACE inhibitor, spironolactone, and amlodipine treatment. According to owners, most dogs with overt signs of advanced heart disease feel better and have improved activity tolerance within a few days of adding pimobendan to existing treatment. The clinical improvement may not correlate with hemodynamic improvement. In these cases, pimobendan may have a central nervous system effect that promotes a feeling of physical and mental well-being in dogs as demonstrated by other phosphodiesterase inhibitors (i.e. propentofylline). PHARMACOLOGY OF PIMOBENDAN Pimobendan’s principal inotropic mechanism is troponin-C calcium sensitization, and this positive inotropic effect is accomplished with only a small increase in myocardial energy consumption. Pimobendan also causes peripheral arteriolar dilation, coronary artery dilation, pulmonary artery dilation, and peripheral venodilation by inhibiting phosphodiesterases III and V in vascular smooth muscle.1-4,8 USE IN DOGS Pimobendan treatment is initiated in symptomatic dogs with congestive heart failure that may benefit from positive inotropic action. The total dose is 0.5 mg/kg daily, which is divided into two doses (not necessarily equal) given 12 hours apart. 9 The Vetmedin chewable tablet sizes are 1.25, 2.5, and 5 mg. The tablets are Degenerative mitral valve disease Patients with degenerative mitral valve disease have good contractility as assessed by echocardiography, even when the left heart is severely dilated. Thus, the inotropic action of pimobendan would DRUG INTERACTIONS Pimobendan can be administered safely with diuretics, ACE inhibitors, and digoxin.3 The modest vasodilator action of pimobendan is additive to that produced by ACE inhibitors. However, we have not encountered arterial hypotension or a drop in measured systolic blood pressure in any dog in which pimobendan was added to ACE inhibitor monotherapy. Additive vasodilator action should be expected with nitrates (isosorbide dinitrate or nitroglycerin), amlodipine (Norvasc— Pfizer), or carvedilol (Coreg—GlaxoSmithKline). We have encountered mild clinically evident systemic hypotension in only one dog with advanced degenerative mitral valve disease when pimobendan was added to a combination therapy of an ACE inhibitor and amlodipine. We have not observed overt adverse effects with the combination of pimobendan, an ACE inhibitor (enalapril or benazepril), and spironolactone or furosemide treatment in dogs with congestive heart failure. In fact, improved heart function resulting from pimobendan treatment may permit a small reduction of the furosemide dosage. 738 November 2007 VETERINARY MEDICINE

Table of Contents Feed for the Digital Edition of Veterinary Medicine - November 2007

Veterinary Medicine - November 2007 Contents Leading Off The Veterinary Medicine Interview: Dr. Lila Miller Clinical Exposures Idea Exchange A Challenging Case: Uveitis and Secondary Glaucoma in a Cat Is it Immune-Mediated Neutropenia? Pimobendan Treatment in Dogs with Congestive Heart Failure CE Form Product Preview Advertiser Index Marketplace/Classifieds Mind Over Miller Special Supplement by Lilly: Flea Bite Facts Q&A

Veterinary Medicine - November 2007

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