Spironolactone
Spironolactone is a synthetic **aldosterone antagonist** and potassium-sparing diuretic. In veterinary medicine, it is primarily used as an adjunctive treatment for congestive heart failure (CHF), ascites, systemic hypertension, and primary hyperaldosteronism (especially in cats). **Clinical Pearls & Pharmacological Context:** * **Aldosterone Escape:** While its direct diuretic effect is relatively weak compared to loop diuretics like furosemide, spironolactone plays a crucial role in blocking the Renin-Angiotensin-Aldosterone System (RAAS). Even when patients are on ACE inhibitors, aldosterone levels can eventually rebound (a phenomenon known as "aldosterone escape"). Spironolactone mitigates this. * **Cardioprotection:** In human medicine, spironolactone is highly valued for its antifibrotic effects on the myocardium, helping to prevent detrimental cardiac remodeling. While the extent of this benefit in veterinary patients (like dogs with myxomatous mitral valve disease) has been debated, it is increasingly incorporated into standard multi-drug CHF protocols. * **Bioavailability:** Absorption is significantly enhanced when administered with food.
Mecanismo: Spironolactone acts as a competitive antagonist at the **mineralocorticoid receptor**. * **Mechanism:** It competitively inhibits **aldosterone** binding in the distal renal tubules and collecting ducts. * **Pathway:** Blockade of the receptor → prevents the synthesis of aldosterone-induced proteins (such as Na+/K+ ATPase and epithelial sodium channels) → **decreases sodium and chloride reabsorption** while **decreasing potassium, ammonium, and phosphate excretion**. * **Result:** Mild diuresis with potassium retention. It does not affect carbonic anhydrase or proximal renal transport mechanisms.
Dosificación por especie
- As a diuretic in CHF (when furosemide and ACE inhibitors alone do not control fluid accumulation) · 1-2 mg/kg PO q12h · PO · q12h · Refractory CHF
- As a diuretic in CHF (when serum potassium is low) · 1 mg/kg q12h PO · PO · q12h
- For adjunctive treatment of hypertension · 1-2 mg/kg PO q12h · PO · q12h
- For adjunctive treatment of hypertension (Step 3 drug) · 1-2 mg/kg twice daily · PO · q12h · When systolic BP >160 mmHg, diastolic >120 mmHg after amlodipine and ACE inhibitor.
- For adjunctive treatment of primary hyperaldosteronism · 1-2 mg/kg PO twice daily · PO · q12h · If potassium supplementation alone does not control clinical signs.
- Congestive heart failure, ascites, hyperaldosteronism · 2-4 mg/kg · PO · q24h · Continuous · Severe ulcerative facial dermatitis has been reported in Maine Coon cats.
- As a diuretic in CHF (when furosemide and ACE inhibitors alone do not control fluid accumulation) · 1-2 mg/kg PO q12h · PO · q12h · Refractory CHF
- As a diuretic in CHF (with other diuretics when hypokalemia is an issue) · 2-4 mg/kg PO once daily · PO · q24h
- As a diuretic in CHF (to allow further reduction of furosemide dose) · 0.5 mg/kg PO once daily to 2 mg/kg twice daily · PO · q24h to q12h · 0.5 mg/kg once daily for aldosterone blockage (weak diuretic effect); 2 mg/kg twice daily for stronger diuretic effect.
Vías de administración
Contraindicaciones
- Hyperkalemia
- Addison's disease (hypoadrenocorticism)
- Anuria
- Acute renal failure
- Significant renal impairment
- Hypoadrenocorticism
- Hyperkalaemia
- Hyponatraemia
- Concurrent use with NSAIDs in animals with renal insufficiency
- Pregnancy
- Lactation
- Animals intended for breeding
Efectos adversos
- Facial dermatitis (notably reported in Maine Coon cats)
- Hyperkalemia
- Hyponatremia
- Dehydration
- Increased BUN and mild acidosis (in patients with renal impairment)
- Gastrointestinal distress (vomiting, anorexia)
- CNS effects (lethargy, ataxia)
- Endocrine changes (anti-androgenic effects, e.g., gynecomastia in humans, feminization of male fetuses)
- Hyponatraemia
- Hyperkalaemia
- Reversible prostatic atrophy (in entire male dogs)
- Severe ulcerative facial dermatitis (in Maine Coon cats)
- Hepatotoxicity (reported in humans)
Interacciones farmacológicas
- Digoxin · Spironolactone may increase the half-life of digoxin; enhanced monitoring of digoxin serum levels is warranted. May also cause falsely elevated digoxin values if using a radioimmune assay (RIA). · moderate
- Mitotane · Spironolactone may mute the effects of mitotane if given concurrently; monitor carefully.
- Neuromuscular blockers, non-depolarizing · Possible increase in neuromuscular blockade effects.
- Potassium-sparing diuretics (e.g., triamterene) · Increased risk of hyperkalemia.
- Potassium supplements · Increased risk of hyperkalemia. · major
- Salicylates (e.g., Aspirin) · Spironolactone's diuretic effects may be decreased if administered concomitantly.
- Thiazide diuretics · Potentiates diuretic effects · moderate
- Loop diuretics · Potentiates diuretic effects · moderate
- ACE inhibitors · Increased risk of hyperkalaemia (though generally safe to use concurrently in practice; monitor potassium) · moderate
- NSAIDs · Increased risk of hyperkalaemia and nephrotoxicity · major
- Ciclosporin · Increased risk of hyperkalaemia · moderate
Monitorización
- Serum electrolytes (especially potassium and sodium)
- BUN and creatinine
- Hydration status
- Blood pressure (if indicated)
- Clinical signs of edema/ascites
- Patient weight
- Serum potassium
- Serum sodium
- Renal function (BUN, Creatinine)
- Digoxin levels (if used concurrently)
Sobredosis
Information on acute overdosage of spironolactone in veterinary patients is limited. * **Management:** Should an acute overdose occur, follow general guidelines for diuretic overdose (e.g., furosemide or chlorothiazide). * **Treatment:** Empty the stomach if ingestion was recent. Provide supportive care, monitor hydration status, and closely evaluate serum electrolytes (especially potassium and sodium). * Contact an animal poison control center for further guidance.
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