ベナゼプリル
ベナゼプリルは、犬および猫の心不全、全身性高血圧、慢性腎不全、および蛋白漏出性腎疾患の管理に獣医療で広く使用される**アンジオテンシン変換酵素（ACE）阻害薬**です。 **臨床上のポイント:** * ほぼ完全に腎臓から排泄されるエナラプリルとは異なり、ベナゼプリルの活性代謝物（ベナゼプリラト）は犬において**肝臓（55%）と腎臓（45%）の両方の経路**から排泄されます。この二重の排泄経路により、腎機能障害を併発している患者においてより適したACE阻害薬となります。 * 糸球体内の高血圧を低下させる効果があり、慢性腎臓病における蛋白尿の減少に特に有効です。 * （カプトプリルとは異なり）スルフヒドリル基を持たないため、免疫介在性の副作用を引き起こす傾向が低いです。
作用機序: Benazepril is a **prodrug** that is hydrolyzed in the liver to its active metabolite, **benazeprilat**. It competitively inhibits **Angiotensin-Converting Enzyme (ACE)**. * **Pathway:** Angiotensin I → (blocked by ACE) → **Angiotensin II** * **Hemodynamic Effects:** By preventing the formation of Angiotensin II (a potent vasoconstrictor), benazepril promotes vasodilation, reducing both preload and afterload in heart failure patients. * **Renal Effects:** It dilates the efferent arterioles of the glomerulus more than the afferent arterioles, reducing intraglomerular capillary pressure and subsequently decreasing proteinuria. * **Endocrine Effects:** Decreased Angiotensin II leads to reduced secretion of **aldosterone** from the adrenal cortex, minimizing sodium and water retention.
動物種別の用量
- Adjunctive treatment of heart failure · 0.25-0.5 mg/kg PO once daily · PO · q24h
- Adjunctive treatment of heart failure · 0.25-0.5 mg/kg PO once to twice daily · PO · q12-24h
- Adjunctive treatment of hypertension and/or proteinuria (first step) · 0.5 mg/kg q12h · PO · q12h · As a first step drug for systolic hypertension >160 mmHg, diastolic >120 mmHg
- Adjunctive treatment of hypertension and/or proteinuria · 0.25-0.5 mg/kg q12-24h · PO · q12-24h · Co-administration with a calcium channel antagonist may lower blood pressure when monotherapy is not sufficient.
- Hypertension associated with protein-losing renal disease · 0.5 mg/kg PO once daily (q24h) · PO · q24h
- Proteinuria, hypertension · 0.25-1 mg/kg PO q12-24h · PO · q12-24h · Potentially could worsen preexisting azotemia; lower dose and monitoring recommended.
- Heart failure · 0.25-0.5 mg/kg · PO · q24h · Long-term · Adjunctive treatment. Often used in conjunction with diuretics, pimobendan, spironolactone, or digoxin.
- Adjunctive treatment of hypertension/proteinuria · 0.25-0.5 mg/kg · PO · q12-24h · Long-term · May reduce blood pressure; more potent in dogs than cats.
- Adjunctive treatment of heart failure · 0.25-0.5 mg/kg PO once daily · PO · q24h
投与経路
禁忌
- Known hypersensitivity to ACE inhibitors
有害事象
- Anorexia
- Vomiting
- Diarrhea
- Hypotension
- Renal dysfunction (worsening azotemia)
- Hyperkalemia
薬物相互作用
- Aspirin · May potentially negate the decrease in systemic vascular resistance induced by ACE inhibitors (though low-dose aspirin may not significantly affect hemodynamics).
- Antidiabetic Agents (insulin, oral agents) · Possible increased risk for hypoglycemia; enhanced monitoring recommended.
- Diuretics (e.g., furosemide, hydrochlorothiazide) · Potential for increased hypotensive effects. Reducing furosemide doses by 25-50% is often recommended when initiating ACE inhibitors for heart failure.
- Potassium-Sparing Diuretics (e.g., spironolactone, triamterene) · Increased risk of hyperkalemia; enhanced monitoring of serum potassium is required.
- Lithium · Possible increased serum lithium levels; increased monitoring required.
- Potassium Supplements · Increased risk for hyperkalemia. · major
- Spironolactone · Potential for hyperkalemia due to additive potassium-sparing effects, though concurrent use is generally safe in practice. · moderate
- NSAIDs · Increased risk of nephrotoxicity and decreased clinical efficacy of benazepril. · major
- Diuretics (e.g., Furosemide) · Increased risk of hypotension and prerenal azotemia. · moderate
- Vasodilators (e.g., Amlodipine, Anesthetic agents) · Additive hypotensive effects. · moderate
- Beta-blockers · Increased risk of hypotension due to negative inotropic effects. · moderate
モニタリング
- Clinical signs of Congestive Heart Failure (CHF)
- Serum electrolytes (especially potassium)
- Renal panel (Creatinine, BUN)
- Urine protein (UPC ratio)
- Blood pressure (especially if treating hypertension or if signs of hypotension arise)
過量投与
In overdose situations, the primary concern is **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 massive overdoses should be managed using standard gut-emptying protocols (emesis, activated charcoal) as appropriate.
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