硝酸イソソルビド / 一硝酸イソソルビド
Isosorbide Dinitrate / Isosorbide Mononitrate
1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate / 1,4:3,6-dianhydro-D-glucitol 5-nitrate
別名: Isordil · Ismo · Imdur · Isochron · Dilatrate-SR · Monoket · Titradose · ISDN · EV-151 · sorbide nitrate · AHR-4698 · BM-22145 · IS5-MN · isosorbide-5-mononitrate
VetSheet 獣医チームが監修更新日 2026年4月5日エビデンスに基づく獣医学リファレンス
用量は獣医専門家向けの臨床参考資料です。必ず最新の医薬品情報および個別症例に基づいて確認してください。
動物種別用量
🌎 NA — North America🌍 EU — Europe
犬
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| 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 | — | 🌎 NA |
- Refractory heart failure or in combination with hydralazine or amlodipine in patients unable to tolerate ACE inhibitors: Efficacy is unknown. It is unknown if nitrate-free periods are required to prevent nitrate tolerance.
猫
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| Adjunctive treatment of heart failure associated with thyroid storm | Isosorbide dinitrate at 0.5-2 mg/kg PO q8-12h | PO | q8-12h | — | 🌎 NA |
| 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 | — | 🌎 NA |
- Adjunctive treatment of heart failure associated with thyroid storm: Start at lowest level and titrate upward.
- Refractory heart failure or in combination with hydralazine or amlodipine in patients unable to tolerate ACE inhibitors: Efficacy is unknown.
用量は獣医専門家向けの臨床参考資料です。必ず最新の医薬品情報および個別症例に基づいて確認してください。
概要
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.
安全性・警告
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)
注意事項
Hemodynamic Warning: Use with extreme caution in patients with low blood pressure or uncorrected hypovolemia.
- Nitrate Tolerance: Continuous exposure may lead to tolerance. Consider dosing strategies that allow for a nitrate-free interval if chronic use is intended.
- Laboratory Interference: Serum cholesterol levels may be falsely decreased by nitrates when using the Zlatkis-Zak color reaction method.
- Pregnancy: FDA Category C. Use only if the potential benefit justifies the potential risk to the fetus.
医薬品相互作用
Possible additive hypotensive effects; monitor blood pressure closely.
Possible additive hypotensive effects due to alpha-adrenergic blockade.
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.
監視
- 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)
薬物動態
半減期
吸収
Dogs: Isosorbide mononitrate oral bioavailability is approximately 70%. Oral doses >2 mg/kg yield peak plasma levels >100 ng/mL (believed to be the minimum required for hemodynamic effects). Humans: Both ISDN and ISMN are well absorbed orally; food may delay the rate but not the extent of absorption.
分布
Widely distributed. Hemodynamic effects require minimum serum concentrations of approximately 100 ng/mL, though some canine studies showed no hemodynamic changes even at much higher peak levels.
代謝
Isosorbide dinitrate undergoes extensive first-pass hepatic metabolism primarily to isosorbide mononitrate. Isosorbide mononitrate is metabolized primarily in the liver but does not undergo first-pass metabolism.
消失
Metabolites do not appear to have pharmacologic activity and are principally excreted in the urine.
過剰投与
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.
製品
製剤
- Oral tablets
- Sublingual tablets
- Extended-release tablets
- Sustained-release capsules
ヒト用医薬品
- Isosorbide Dinitrate Oral Tablets: 5 mg, 10 mg, 20 mg, 30 mg, & 40 mg
- Isosorbide Dinitrate Sublingual Oral Tablets: 2.5 mg, & 5 mg
- Isosorbide Dinitrate Extended-Release Oral Tablets: 40 mg
- Isosorbide Dinitrate Sustained-Release Oral Capsules: 40 mg
- Isosorbide Mononitrate Tablets: 10 mg, & 20 mg
- Isosorbide Mononitrate Extended-Release Tablets: 30 mg, 60 mg, & 120 mg
規制ステータス
規制データなし: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
保管・安定性
Isosorbide dinitrate and standard isosorbide mononitrate tablets should be stored in well-closed/tight containers below 40°C (preferably between 15°-30°C). Isosorbide mononitrate extended-release tablets should be stored between 2°-30°C. Heat and moisture accelerate the loss of potency.
飼主向け情報
この薬の獣医療における使用経験は限られており、通常、進行した、または治療が困難な心疾患に限定して使用されます。食事の有無にかかわらず投与できます。体が薬に対する耐性を持つのを防ぐために特定のタイミングが必要になる場合があるため、獣医師の投与スケジュールに正確に従ってください。この薬は血圧を下げるため、ペットに脱力感、無気力、ふらつき、または失神の兆候がないか注意深く観察してください。これらの症状が現れた場合は、すぐに獣医師に連絡してください。薬の効力が失われるのを防ぐため、熱や湿気を避け、元の容器にしっかりと密閉して保管してください。
VetSheet医薬品リファレンスは獣医専門家の臨床意思決定支援を目的としており、専門的判断または製造業者の最新医薬品情報の代替にはなりません。