硝酸イソソルビド / 一硝酸イソソルビド
硝酸イソソルビド（ISDN）および一硝酸イソソルビド（ISMN）は、主に心臓の前負荷を軽減するために使用される強力な**静脈拡張薬**である**有機硝酸エステル**です。ヒト医療では狭心症やうっ血性心不全（CHF）に広く使用されていますが、小動物医療における臨床経験や有効性の証明は限られています。難治性心不全の補助療法や、ACE阻害薬に不耐容の患者に時折使用されます。犬はヒトと比較して、治療的な血行動態効果を得るためにかなり高用量を必要とするようです。継続的な使用は**硝酸エステル耐性**を引き起こす可能性があります。
作用機序: 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.
動物種別の用量
- 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.
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- 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)
有害事象
- 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)
薬物相互作用
- 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.
モニタリング
- 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)
過量投与
**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.
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。