Pimobendan
Pimobendan is a highly effective cardiovascular drug classified as an **inodilator**, meaning it possesses both positive inotropic (increases heart contractility) and vasodilatory properties. **Key Clinical Uses:** * **Dogs:** Primarily used to treat congestive heart failure (CHF) secondary to **dilated cardiomyopathy (DCM)** or **myxomatous/degenerative mitral valve disease (MMVD)**. It significantly improves survival times and quality of life compared to traditional ACE inhibitor/furosemide therapy alone. It is considered a first-line therapy for DCM in Doberman Pinschers and is a cornerstone of ACVIM Stage C and D heart failure management. * **Cats:** Used off-label for restrictive and dilated cardiomyopathy. It is generally contraindicated in hypertrophic cardiomyopathy (HCM) due to its positive inotropic effects. > **Clinical Pearl:** While the monograph notes ongoing studies for preclinical use, the landmark EPIC study has since established pimobendan as the standard of care for delaying the onset of heart failure in dogs with preclinical (ACVIM Stage B2) MMVD.
Mecanismo: Pimobendan exerts its dual **inodilator** effects through two distinct mechanisms: 1. **Positive Inotropy (Calcium Sensitization):** It increases the sensitivity of the cardiac myofilament **Troponin C** to intracellular calcium → enhances cardiac contractility. Unlike older inotropes (e.g., digoxin), it achieves this *without* increasing intracellular calcium levels → **no increase in myocardial oxygen consumption**. 2. **Vasodilation (PDE-III Inhibition):** It inhibits the enzyme **phosphodiesterase III (PDE-III)** in vascular smooth muscle → prevents the breakdown of cAMP → ↑ intracellular cAMP → smooth muscle relaxation → **mixed arterial and venous dilation**. This reduces both cardiac preload and afterload. Additionally, pimobendan possesses mild antithrombotic activity.
Dosificación por especie
- Management of myocardial failure (DCM), especially if not associated with taurine deficiency · 1.25-1.5 mg/cat PO q12hrs · PO · q12h · Off-label use. Little information about clinical efficacy due to rarity of condition.
- Heart failure associated with systolic dysfunction (Off-label) · 0.1-0.3 mg/kg · PO · q12h · Lifelong · Not authorized (off-label). Pharmacokinetics may differ from dogs. Administer 1 hour before food.
- Management of the signs of mild, moderate or severe congestive heart failure due to AV valve insufficiency or dilated cardiomyopathy · 0.5 mg/kg total daily dose. Divide daily dose into two portions that are not necessarily equal (using whole and half tablets) and administer approximately 12 hours apart. · PO · Divided q12h
- Treatment of congestive heart failure secondary to myxomatous mitral valve disease (MMVD) · 0.4-0.6 mg/kg PO divided twice daily · PO · Divided twice daily
- Treatment of heart failure secondary to dilated cardiomyopathy or chronic mitral valve insufficiency · 0.25 mg/kg PO twice daily · PO · Twice daily
- General dosing · 0.2-0.6 mg/kg PO divided q12h · PO · Divided q12h
- Adjunctive drug for the emergency treatment of CHF (if not overtly critical and a strong positive oral inotrope is needed) · 0.1-0.3 mg/kg PO q12h · PO · q12h
- Adjunctive treatment of acute or chronic stage D heart failure (refractory to standard treatment) · 0.3 mg/kg PO to three times daily · PO · Up to TID · Outside of FDA-approved labeling; requires client consent.
Vías de administración
Contraindicaciones
- Hypersensitivity to pimobendan
- Hypertrophic cardiomyopathy (HCM)
- Aortic stenosis
- Any condition where augmentation of cardiac output is inappropriate for functional or anatomic reasons
- Any condition where augmentation of cardiac output via increased contractility is not possible anatomically or functionally
Efectos adversos
- Poor appetite
- Lethargy
- Diarrhea
- Dyspnea
- Azotemia
- Weakness and ataxia
- Pleural effusion
- Syncope
- Cough
- Ascites
- Heart murmur
- Arrhythmias (atrial fibrillation, increased ventricular ectopic beats)
- Worsening mitral valve lesions (acute hemorrhages, endocardial papilloform hyperplasia) with chronic use
- Moderate positive chronotropic effect (tachycardia)
- Vomiting (dose-dependent)
- Reduced appetite or lethargy (rare)
Interacciones farmacológicas
- Verapamil · Calcium antagonist; attenuates pimobendan-induced increases in cardiac contractility.
- Propranolol · Beta-antagonist; attenuates pimobendan-induced increases in cardiac contractility.
- Diltiazem · Calcium channel blocker; assumed to potentially attenuate positive inotropic effects.
- Atenolol · Beta-blocker; assumed to potentially attenuate positive inotropic effects.
- Beta-blockers (e.g., atenolol, propranolol) · Attenuates the positive inotropic effects of pimobendan · moderate
- Calcium-channel blockers (e.g., verapamil, diltiazem) · Attenuates the positive inotropic effects of pimobendan · moderate
Monitorización
- ECG (rate and rhythm)
- Blood pressure
- Echocardiography (cardiac function and valve lesions)
- Clinical signs of heart failure (coughing, exercise intolerance)
- Resting respiratory rate (RRR) at home
- Heart rate and rhythm
- Respiratory rate and effort (Resting Respiratory Rate - RRR)
- Echocardiographic parameters (fractional shortening, left atrial/ventricular dimensions)
- Clinical signs of congestive heart failure
Sobredosis
Overdoses primarily manifest as cardiovascular signs. **Clinical Signs:** * Tachycardia (dose-dependent increases in heart rate) * Mild, non-clinical heart murmurs * Hypotension **Treatment:** * **Decontamination:** Induce emesis and administer activated charcoal if exposure was recent. * **Monitoring:** Continuously monitor heart rate, blood pressure, and ECG. * **Supportive Care:** Control hypotension with IV fluids and dopamine if necessary.
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