ジゴキシン
ジゴキシンは、主に陽性変力作用（心筋収縮力の増加）および陰性変時作用（心拍数の低下）を目的として使用される強心配糖体です。獣医学では、うっ血性心不全（CHF）や心房細動・粗動などの上室性頻脈性不整脈の治療に利用されます。 **臨床上のポイント：** * **治療域が狭い：** 治療量と中毒量の差が非常に小さいため、慎重な投与と薬物治療モニタリング（TDM）が不可欠です。 * **治療パラダイムの変化：** 歴史的にはCHF管理の要でしたが、ピモベンダンのようなより安全で効果的な強心血管拡張薬の登場により、現在では犬や猫の心不全の第一選択薬とは見なされていません。現在は主に心房細動のレートコントロールとして、ジルチアゼムと併用されることが多いです。 * **投与量の基準：** ジゴキシンは脂肪や腹水にはほとんど分布しないため、投与量は**除脂肪体重**に基づいて計算する必要があります。 * **動物種による感受性：** 猫は犬に比べてジゴキシンの毒性に対して非常に敏感です。
作用機序: Digoxin exerts its effects through the reversible inhibition of the **Na⁺/K⁺-ATPase** pump in the myocardial cell membrane. * **Positive Inotropy (Contractility):** Inhibition of **Na⁺/K⁺-ATPase** → Increased intracellular Na⁺ → Decreased driving force for the **Na⁺/Ca²⁺ exchanger (NCX)** → Decreased Ca²⁺ extrusion → Increased intracellular Ca²⁺ → Increased Ca²⁺ uptake into the sarcoplasmic reticulum. Upon the next action potential, more Ca²⁺ is released, leading to increased myocardial contractility. * **Negative Chronotropy/Dromotropy (Heart Rate/Conduction):** Digoxin increases vagal (parasympathetic) tone → Decreased conduction velocity through the **AV node** and prolonged effective refractory period (ERP) → Slowed ventricular response rate in supraventricular arrhythmias. * **Neurohormonal Effects:** At low doses, digoxin restores baroreceptor sensitivity, which decreases sympathetic outflow and reduces the neurohormonal activation seen in heart failure.
動物種別の用量
- Dilated cardiomyopathy or advanced atrioventricular valve insufficiency · 0.007 mg/kg PO every other day · PO · q48h · Use lean body weight. Measure serum level 10+ days later, 8-10 hours after dosing. Therapeutic level: 1-2 ng/mL.
- Starting dose for normal cats weighing less than 3 kg · 1/4th of a 0.125 mg tablet administered every other day · PO · q48h · Tablets are better tolerated than the alcohol-based elixir.
- Starting dose for normal cats weighing 3 to 6 kg · 1/4th of a tablet every day · PO · q24h · Using 0.125 mg tablet.
- Starting dose for normal cats weighing more than 6 kg · 1/4th of a tablet every day to q12h · PO · q12h-q24h · Using 0.125 mg tablet.
- Management of supraventricular tachyarrhythmias · 10 μg/kg (equating to 1/4 of a 125 μg tablet). Start at lower dose range and titrate up. · PO · q24-48h · Long-term · Cats are highly sensitive to toxicity.
- Management of supraventricular tachyarrhythmias (Emergency/Rare) · 1-1.6 μg/kg · IV · q12h · As needed · Only use IV if essentially indicated. Administer very slowly.
- Dilated cardiomyopathy · 0.01 mg/kg PO once daily initially · PO · q24h · Use oral liquid. May increase to twice daily if necessary.
- Maintenance · 0.005-0.01 mg/kg PO once to twice daily · PO · q12h-q24h · Using the elixir; monitor blood levels if possible.
- Dilated cardiomyopathy long-term maintenance · 0.01 mg/kg q24h · PO · q24h · Long-term · Used with furosemide (2 mg/kg q12h) and enalapril (0.5 mg/kg q48h).
投与経路
禁忌
- Ventricular fibrillation
- Digitalis intoxication
- Hypertrophic cardiomyopathy in cats (relative contraindication, may increase myocardial oxygen demand and dynamic outflow obstruction)
- Frequent ventricular arrhythmias
- Atrioventricular (AV) block
- Feline hypertrophic cardiomyopathy
- Hypokalaemia
有害事象
- Cardiac arrhythmias (complete or incomplete heart block, bigeminy, ST segment changes, paroxysmal ventricular or atrial tachycardias, multifocal VPCs)
- Mild GI upset
- Anorexia
- Weight loss
- Diarrhea
- Vomiting (especially associated with IV injections)
- Vomiting
- Diarrhoea
- Depression
- Arrhythmias (AV block, bigeminy, paroxysmal ventricular or atrial tachycardias with block, multiform VPCs)
- Vasoconstriction (with IV administration)
薬物相互作用
- Aminosalicylic Acid · May reduce digoxin serum levels
- Antacids · May reduce digoxin serum levels · moderate
- Chloramphenicol · May reduce digoxin serum levels in dogs
- Cholestyramine · May reduce digoxin serum levels
- Cimetidine · May reduce digoxin serum levels · moderate
- Metoclopramide · May reduce digoxin serum levels · moderate
- Neomycin (Oral) · May reduce digoxin serum levels
- Phenobarbital · May reduce digoxin serum levels
- St John's Wort · May reduce digoxin serum levels
- Sucralfate · May reduce digoxin serum levels
- Sulfasalazine · May reduce digoxin serum levels
- Amiodarone · May increase serum levels, decrease elimination rate, or enhance toxic effects · major
- Anticholinergics · May increase serum levels, decrease elimination rate, or enhance toxic effects
- Captopril (or other ACEIs) · May increase serum levels, decrease elimination rate, or enhance toxic effects
モニタリング
- Serum digoxin levels (Trough levels recommended: Dogs 0.8-1.2 ng/mL; Cats 0.9-2 ng/mL; Other species 0.5-2 ng/mL. Wait at least 6 days after starting therapy to reach steady-state)
- Appetite and body weight
- Cardiac rate and ECG changes
- Serum electrolytes (especially potassium)
- Renal function tests
- Clinical efficacy for CHF (improved perfusion, decreased edema)
- Serum digoxin levels (check after 7-10 days, sample taken 6-8 hours post-pill. Ideal trough therapeutic level: 0.6-1.2 ng/ml)
- ECG (monitor for AV block and ventricular arrhythmias)
- Serum potassium levels (hypokalaemia increases toxicity risk)
- Renal function (BUN, Creatinine)
過量投与
**Acute Toxicity:** In dogs, the acute toxic dose after IV administration is reported to be 0.177 mg/kg. **Treatment of Toxicity:** * **Chronic Toxicity:** Often resolves by temporarily stopping the drug and reevaluating the dosage regimen. * **Acute Ingestion:** If recent and no cardiotoxic/neurologic signs are present, empty the stomach followed by activated charcoal. Repeated charcoal administration may be beneficial due to enterohepatic recirculation. Anion-exchange resins (colestipol, cholestyramine) can reduce absorption but are rarely available. * **Supportive Care:** Continuous ECG monitoring, correct acid-base/hypoxia/fluid/electrolyte imbalances. *Note: Potassium use in normokalemic patients is controversial and requires expertise.* * **Antiarrhythmics:** Lidocaine and phenytoin are commonly used for life-threatening digitalis-induced arrhythmias. Atropine may treat sinus bradycardia, SA arrest, or AV block. * **Antidote:** **Digoxin immune Fab** (ovine antibodies) binds directly to the drug, inactivating it. It is highly effective but very expensive, and veterinary experience is limited.
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