硝酸異山梨酯 / 單硝酸異山梨酯
硝酸異山梨酯 (ISDN) 和單硝酸異山梨酯 (ISMN) 是**有機硝酸鹽**，作為強效的**靜脈擴張劑**，主要用於降低心臟前負荷。雖然在人類醫學中廣泛用於心絞痛和充血性心力衰竭 (CHF)，但在小動物醫學中的臨床經驗和療效證據仍然有限。它們偶爾被用作難治性心力衰竭的輔助治療，或用於無法耐受 ACE 抑制劑的病患。與人類相比，犬隻似乎需要高得多的劑量才能達到治療性的血流動力學效果。持續使用可能導致**硝酸鹽耐受性**。
作用機制: Organic nitrates act as prodrugs that donate nitric oxide (NO) to vascular smooth muscle, leading to profound vasodilation (predominantly venous, with some arterial effects at higher doses). **Mechanism Pathway:** Organic Nitrate → converted to **free radical Nitric Oxide (NO)** → activates **soluble guanylate cyclase (sGC)** → increases intracellular **cyclic GMP (cGMP)** → activates **Protein Kinase G (PKG)** → decreases intracellular calcium and dephosphorylates **myosin light chain** → **Vascular Smooth Muscle Relaxation**. * **Hemodynamic Effects:** By dilating the venous capacitance vessels, nitrates significantly decrease venous return to the heart (**reduced preload**), which lowers ventricular filling pressures and helps alleviate pulmonary edema in CHF. * **Additional Effects:** Nitrates functionally antagonize acetylcholine, norepinephrine, and histamine. They also relax non-vascular smooth muscle, including biliary, bronchial, gastrointestinal, ureteral, and uterine tissues.
各物種劑量
- Adjunctive treatment of heart failure associated with thyroid storm · Isosorbide dinitrate at 0.5-2 mg/kg PO q8-12h · PO · q8-12h · Start at lowest level and titrate upward.
- Refractory heart failure or in combination with hydralazine or amlodipine in patients unable to tolerate ACE inhibitors · Isosorbide dinitrate at 0.5-2 mg/kg PO twice daily OR isosorbide mononitrate at 0.25-2 mg/kg PO twice daily · PO · twice daily · Efficacy is unknown.
- Refractory heart failure or in combination with hydralazine or amlodipine in patients unable to tolerate ACE inhibitors · Isosorbide dinitrate at 0.5-2 mg/kg PO twice daily OR isosorbide mononitrate at 0.25-2 mg/kg PO twice daily · PO · twice daily · Efficacy is unknown. It is unknown if nitrate-free periods are required to prevent nitrate tolerance.
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
- Cardiogenic or hypovolemic shock
- Severe hypotension
- Hypovolemia
- Use as a sole agent for treating heart failure
- Concurrent use with selective phosphodiesterase inhibitors (e.g., sildenafil)
不良反應
- Postural hypotension
- Reflex tachycardia
- Lethargy or weakness (secondary to hypotension)
- Gastrointestinal upset
- Restlessness
- Headache (well-documented in humans, difficult to assess in animals)
- Hypersensitivity reactions (rare)
藥物相互作用
- Antihypertensive Drugs (e.g., ACE inhibitors, amlodipine, beta-blockers) · Possible additive hypotensive effects; monitor blood pressure closely.
- Phenothiazines (e.g., acepromazine) · Possible additive hypotensive effects due to alpha-adrenergic blockade.
- Selective Phosphodiesterase Inhibitors (e.g., sildenafil, pimobendan) · Concurrent use with sildenafil can cause profound, life-threatening hypotension and is strictly contraindicated. Use with pimobendan (a PDE3 inhibitor) is common in vet med but requires monitoring for excessive vasodilation.
監測
- Clinical efficacy (improvement in respiratory rate/effort, resolution of pulmonary edema)
- Systemic blood pressure (monitor for hypotension)
- Heart rate (monitor for reflex tachycardia)
- Renal values and electrolytes (if used concurrently with diuretics and ACE inhibitors)
過量
**Toxicity Profile:** Isosorbide mononitrate caused significant lethality in rats and mice at massive dosages (2000 mg/kg and 3000 mg/kg, respectively). **Clinical Signs of Overdose:** * Profound venous pooling * Decreased cardiac output * Severe hypotension * Reflex tachycardia * Collapse or syncope **Treatment:** * Treatment is primarily **supportive**. * **Avoid Epinephrine:** Drug therapies with agents such as epinephrine are NOT recommended as they may exacerbate the cardiovascular collapse. * **Fluid Therapy:** Increasing central fluid volume may be useful to counteract venous pooling, but in patients with pre-existing congestive heart failure (CHF), IV fluids must be administered with **extreme caution** to avoid precipitating fulminant pulmonary edema.
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