スピロノラクトン
スピロノラクトンは合成**アルドステロン拮抗薬**およびカリウム保持性利尿薬です。獣医療では主に、うっ血性心不全（CHF）、腹水、全身性高血圧、および原発性アルドステロン症（特に猫）の補助治療として使用されます。 **臨床のポイントと薬理学的背景:** * **アルドステロン・ブレイクスルー:** フロセミドなどのループ利尿薬に比べて直接的な利尿効果は弱いものの、レニン・アンジオテンシン・アルドステロン系（RAAS）の阻害において重要な役割を果たします。ACE阻害薬を服用していても、最終的にアルドステロン値が再び上昇する現象（アルドステロン・ブレイクスルー）を防ぐ効果があります。 * **心筋保護作用:** 人医療では、心筋の線維化を防ぎ、有害な心臓リモデリングを予防する効果が高く評価されています。獣医療（粘液腫様僧帽弁疾患の犬など）におけるこの効果の程度については議論がありますが、標準的なCHFの多剤併用プロトコルに組み込まれることが増えています。 * **バイオアベイラビリティ:** 食事と一緒に投与することで吸収が大幅に向上します。
作用機序: 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.
動物種別の用量
- 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.
投与経路
禁忌
- 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
有害事象
- 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)
薬物相互作用
- 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
モニタリング
- 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)
過量投与
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.
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。