雙異丙吡胺磷酸鹽
**雙異丙吡胺磷酸鹽 (Disopyramide phosphate)** 是一種 Ia 類（膜穩定）抗心律不整藥物，結構上與奎尼丁 (quinidine) 和普魯卡因胺 (procainamide) 不同，但藥理作用相似。 * **臨床應用**：在獸醫學中極少使用（主要被視為犬的二線或三線藥物），因為其半衰期短且具有強烈的負性肌力作用。 * **主要特徵**：它能降低心肌興奮性和傳導速度。值得注意的是，它具有顯著的抗膽鹼（迷走神經抑制）活性（150 mg 的雙異丙吡胺約等於 0.09 mg 的阿托品），這極大地影響了其副作用和禁忌症。 * **心血管影響**：雖然它通常對靜息心率或血壓影響極小，但可使全身外周阻力增加高達 20%，並顯著抑制心肌收縮力。
作用機制: * Blocks **fast inward sodium (Na⁺) channels** → decreases the rate of phase 0 depolarization → slows conduction velocity through the atria and ventricles. * Inhibits **potassium (K⁺) channels** → prolongs the action potential duration and increases atrial and ventricular refractory times. * Decreases automaticity of ectopic atrial or ventricular pacemakers and shortens sinus node recovery time. * Exerts a direct **negative inotropic effect** on the myocardium, reducing cardiac contractility. * Possesses significant **anticholinergic (vagolytic) activity**, which can alter autonomic tone to the heart.
各物種劑量
- Antiarrhythmic (almost never used) · 7-30 mg/kg PO q4h · PO · q4h · Considered a 2nd or 3rd line agent.
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
給藥途徑
禁忌症
- Hypersensitivity to the drug
- 2nd or 3rd degree AV block (unless a pacemaker is inserted)
- Cardiogenic shock
- Severe uncompensated or poorly compensated cardiac failure
- Hypotension
- Glaucoma (closed-angle)
- Urinary retention
- Myasthenia gravis
不良反應
- Dry mouth, eyes, or nose
- Constipation
- Urinary hesitancy or retention
- Urinary frequency and urgency
- Edema
- Hypotension
- Dyspnea
- Syncope
- Conduction disturbances (e.g., AV block)
- Vomiting and diarrhea
- Intrahepatic cholestasis
- Hypoglycemia
- Fatigue and headache
- Muscle weakness and pain
- Prolonged QT interval (at 15 mg/kg q8h in dogs)
- Widened QRS complex (at doses >30 mg/kg in dogs)
藥物相互作用
- Anticholinergic drugs (atropine, glycopyrrolate) · Additive anticholinergic effects may be encountered.
- Cisapride · Additional prolongation of the QT interval.
- Macrolide antibiotics (erythromycin, clarithromycin) · Increased disopyramide levels; prolongation of QT interval may occur.
- Phenobarbital · May increase disopyramide's metabolism and reduce serum levels.
- Procainamide, Lidocaine · May be used concurrently, but widening of QRS and prolongation of QT interval may occur.
- Quinidine · May increase disopyramide levels; disopyramide may decrease quinidine levels.
- Rifampin · May increase disopyramide's metabolism and reduce serum levels.
- Verapamil · Because of additional negative inotropic effects, use of disopyramide within 48 hours of using verapamil is not recommended.
- Propranolol · May cause additive negative inotropic effects.
監測
- ECG (monitor for QT prolongation and QRS widening)
- Blood pressure
- Clinical signs of adverse effects (anticholinergic and cardiovascular)
- Liver function tests (if on chronic therapy)
- Serum drug levels (Therapeutic: 2-7 mcg/mL; Toxic: >9 mcg/mL)
過量
**Clinical signs of toxicity**: Anticholinergic effects, apnea, loss of consciousness, hypotension, cardiac conduction disturbances and arrhythmias, widening of the QRS complex and QT interval, bradycardia, congestive heart failure, seizures, asystole, and death. **Treatment**: * Initially consists of prompt gastric emptying, activated charcoal, and cathartics. * Follow with vigorous symptomatic therapy using cardiac glycosides, vasopressors, sympathomimetics, diuretics, mechanically assisted respiration, and endocardial pacing if necessary. * Disopyramide can be removed with hemodialysis.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。