Enalapril
Enalapril is a widely used **Angiotensin-Converting Enzyme (ACE) inhibitor** in veterinary medicine. It acts as a balanced vasodilator, reducing both preload and afterload, making it a cornerstone in the management of congestive heart failure (CHF) in dogs and cats, often used alongside pimobendan and furosemide. Beyond its cardiovascular applications, enalapril is highly valued for its **renoprotective properties**. By decreasing efferent glomerular arteriolar resistance, it effectively reduces intraglomerular pressure and proteinuria, making it a standard adjunctive treatment for chronic kidney disease (CKD) and protein-losing nephropathies (PLN). > **Clinical Pearl:** Enalapril is a **prodrug** that requires hepatic biotransformation into its active metabolite, **enalaprilat**. In patients with severe hepatic dysfunction, conversion may be impaired, and alternative therapies might be considered. Because it is primarily excreted by the kidneys, dosage adjustments are often necessary in patients with significant renal impairment.
Mecanismo: Enalapril is a prodrug converted in the liver to the active compound **enalaprilat**. Enalaprilat competitively binds to and inhibits **Angiotensin-Converting Enzyme (ACE)**. * **RAAS Inhibition:** Prevents the conversion of inactive **Angiotensin-I** → active **Angiotensin-II** (a potent vasoconstrictor). * **Vasodilation:** Decreased Angiotensin-II leads to reduced total peripheral resistance, pulmonary vascular resistance, and blood pressure (↓ afterload and preload). * **Aldosterone Reduction:** Lower Angiotensin-II levels reduce the secretion of **aldosterone** from the adrenal cortex, leading to decreased sodium and water retention, while mildly increasing potassium retention. * **Renal Hemodynamics:** Preferentially dilates the **efferent arteriole** of the glomerulus. This reduces intraglomerular hydrostatic pressure, thereby decreasing the filtration of proteins into the urine (anti-proteinuric effect) and slowing the progression of glomerular disease.
Dosificación por especie
- For adjunctive treatment of heart failure due to hypertrophic cardiomyopathy · 1.25-2.5 mg (total dose) PO once daily (q24h). · PO · q24h
- For adjunctive treatment of heart failure due to hypertrophic cardiomyopathy · 0.25-0.5 mg/kg (roughly 1.25-2.5 mg per cat) PO once a day (q24h) · PO · q24h
- For adjunctive treatment of heart failure due to hypertrophic cardiomyopathy · 0.5 mg/kg PO once daily, twice daily if necessary · PO · once to twice daily
- For proteinuria, hypertension in chronic kidney disease · 0.25 mg/kg PO once daily to 0.5 mg/kg PO twice daily; rarely higher · PO · once to twice daily
- For systemic hypertension · As a 2nd step drug when systolic BP >160 mmHg, diastolic >120 mmHg: 1) amlodipine (0.625 mg per cat q24h, if cat greater then 6 kg, 1.25 mg/cat q24h), add ACE inhibitor if proteinuric; 2) ACE inhibitor (benazepril/enalapril 0.5 mg/kg q12h); 3) spironolactone (1-2 mg/kg twice daily); 4) hydralazine 0.5 mg/kg PO twice daily. Each step added (except when increasing amlodipine dose) if after 1-2 weeks systolic BP > 160 mmHg. · PO · q12h · Stepwise therapy protocol.
- For adjunctive therapy for heart failure · 0.5 mg/kg PO once every other day (q48h) initially and may be increased to once a day if tolerated. · PO · q48h to q24h · Dissolve tablet(s) in distilled water and add a methylcellulose suspending agent (e.g., Ora-Plus) and cherry syrup for flavor.
- For dilative cardiomyopathy · 0.25-0.5 mg/kg PO once a day to every other day · PO · q24h to q48h
Vías de administración
Contraindicaciones
- Hypersensitivity to ACE inhibitors
- Pregnancy (Category C in first trimester, Category D in second/third trimesters due to fetal kidney developmental risks)
Efectos adversos
- Anorexia
- Vomiting
- Diarrhea
- Weakness
- Hypotension
- Renal dysfunction
- Hyperkalemia
- Lethargy (especially in cats)
- Inappetence
Interacciones farmacológicas
- Antidiabetic agents (insulin, oral agents) · Possible increased risk for hypoglycemia; enhanced monitoring recommended
- Diuretics (e.g., furosemide, hydrochlorothiazide) · Potential for increased hypotensive effects; furosemide doses may need reduction (by 25-50%) when adding enalapril
- Potassium-sparing diuretics (e.g., spironolactone, triamterene) · Increased hyperkalemic effects; enhanced monitoring of serum potassium recommended
- Hypotensive agents · Potential for increased hypotensive effect
- Lithium · Increased serum lithium levels possible; increased monitoring required
- NSAIDs · May reduce the anti-hypertensive or positive hemodynamic effects of enalapril; may increase risk for reduced renal function
- Potassium supplements · Increased risk for hyperkalemia
Monitorización
- Clinical signs of CHF (respiratory rate/effort, exercise tolerance)
- Serum electrolytes (especially potassium)
- Renal panel (creatinine, BUN)
- Urine protein (UPC ratio)
- CBC with differential (periodic)
- Blood pressure (especially if treating hypertension or if clinical signs of hypotension arise)
Sobredosis
In dogs, a dose of 200 mg/kg was lethal, but 100 mg/kg was not. * **Primary Concern:** Severe **hypotension**. * **Treatment:** Supportive treatment with volume expansion using normal saline is recommended to correct blood pressure. * **Monitoring:** Because of the drug's long duration of action, prolonged monitoring and treatment may be required. * **Decontamination:** Recent overdoses should be managed by using gut emptying protocols when warranted.
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