ヒドララジン
ヒドララジン（Hydralazine）は、強力な**直接作用型細動脈拡張薬**であり、主に全身性高血圧の管理や、小動物のうっ血性心不全（CHF）の補助治療における**後負荷軽減薬**として使用されます。 * **臨床的有用性**：僧帽弁閉鎖不全症、大きな心室中隔欠損、または重度の動脈弁逆流症の症例において、心臓が血液を送り出す際の抵抗（後負荷）を減らすことが重要であるため、特に有益です。 * **難治性心不全**：僧帽弁閉鎖不全症の犬において、ACE阻害薬（エナラプリルなど）で十分な臨床的改善が得られない場合によく使用されます。 * **併用療法**：ナトリウムおよび水分の貯留を引き起こす傾向を相殺するために利尿薬と頻繁に併用され、反射性頻脈を抑えるためにβ遮断薬と併用されることもあります。 * **制限事項**：有意な弁逆流を伴わず、原発性心筋疾患（拡張型心筋症など）のみが問題である場合、心不全の治療にはあまり有用ではありません。
作用機序: Hydralazine acts as a **semicarbazide-sensitive amine oxidase (SSAO) inhibitor**, directly relaxing vascular smooth muscle. * **Mechanism**: Alters cellular calcium metabolism in smooth muscle → interferes with calcium movements → prevents the initiation and maintenance of the contractile state. * **Vascular Selectivity**: Exerts a much greater effect on **arterioles** than on veins. This selective arterial dilation significantly decreases systemic vascular resistance (SVR) and blood pressure. * **Cardiac Effects**: In CHF patients, the reduction in afterload → significantly increases forward cardiac output. * **Compensatory Responses**: In non-CHF hypertensive patients, the sudden drop in blood pressure can trigger baroreceptor-mediated **reflex tachycardia** and activation of the **renin-angiotensin-aldosterone system (RAAS)** → leading to sodium and water retention.
動物種別の用量
- Adjunctive therapy in treatment of heart failure · start titration at 2.5 mg (total dose) and if necessary, increase up to 10 mg · PO · q12h · Follow similar titration protocols as dogs.
- Treatment of systemic hypertension (Fourth step drug) · 0.5 mg/kg · PO · twice daily · Added if systolic BP > 160 mmHg after amlodipine, ACE inhibitor, and spironolactone.
- Systemic hypertension · 2.5-10 mg/cat · PO · q12h · Long-term · Start at low dose and titrate upwards cautiously. Monitor blood pressure regularly.
- Adjunctive therapy in treatment of heart failure (afterload reducer) · 0.5 mg/kg · IV · Once · ARCI UCGFS Class 3 Drug.
- Adjunctive therapy in treatment of heart failure (long-term therapy) · 0.5-1.5 mg/kg · PO · q12h · Long-term
- Adjunctive therapy in treatment of heart failure (not receiving ACE inhibitors) · 1 mg/kg (starting dose, titrate up to 3 mg/kg if needed) · PO · q12h · Effective dose is 0.5-3 mg/kg PO q12h. Titrate upwards carefully. If BP monitored, can titrate more rapidly in 1-2 hour intervals.
- Acute, fulminant heart failure due to severe mitral regurgitation (not receiving ACE inhibitors) · 2 mg/kg · PO · Once · Given along with IV furosemide. May cause hypotension, but benefits outweigh risks.
- Adjunctive therapy in treatment of heart failure (receiving ACE inhibitors) · 0.5 mg/kg (starting dose, increase in 0.5 mg/kg increments to max 3 mg/kg) · PO · q12h · Give with extreme caution as severe hypotension may occur. Blood pressure monitoring required.
投与経路
禁忌
- Known hypersensitivity to hydralazine
- Coronary artery disease
- Hypovolemia
- Preexisting hypotension
- Hypovolaemia
- Hypotension
- Renal impairment
- Cerebral bleeding
有害事象
- Hypotension
- Weakness and lethargy
- Syncope (fainting)
- Reflex tachycardia
- Sodium and water retention
- GI distress (vomiting, diarrhea)
- Increased creatinine levels
- SLE-like syndrome (documented in humans, theoretical in animals)
- Lacrimation and conjunctivitis
- Peripheral neuritis
- Blood dyscrasias
- Urinary retention
- Constipation
- Severe hypotension
- Anorexia (especially in cats)
- Vomiting (especially in cats)
薬物相互作用
- ACE-INHIBITORS · May cause additive hypotensive effect; usually used for therapeutic advantage
- BETA-BLOCKERS · May cause additive hypotensive effect; usually used for therapeutic advantage
- DIAZOXIDE · Potentially could cause profound hypotension
- DIURETICS · May cause additive hypotensive effect; usually used for therapeutic advantage · moderate
- FUROSEMIDE · Hydralazine may increase furosemide's renal effects
- MAO INHIBITORS · May cause additive hypotensive effect
- SYMPATHOMIMETICS (e.g., epinephrine) · Hydralazine may cause decreased pressor effect and may cause additive tachycardia
- ACE inhibitors (e.g., enalapril, benazepril) · Enhanced hypotensive effects · major
- Anaesthetics · Enhanced hypotensive effects · moderate
- Beta-blockers (e.g., propranolol) · Enhanced hypotensive effects · moderate
- Calcium-channel blockers (e.g., diltiazem, verapamil) · Enhanced hypotensive effects · moderate
- Corticosteroids · Enhanced hypotensive effects · minor
- NSAIDs · Enhanced hypotensive effects · moderate
モニタリング
- Baseline thoracic radiographs
- Mucous membrane color and capillary refill time
- Serum electrolytes and creatinine
- Arterial blood pressure (Target MAP 60-80 mmHg for short-term CHF treatment)
- Venous PO2
- Occasional CBC (due to possibility of blood dyscrasias)
- Systemic blood pressure (frequent monitoring during initiation)
- Heart rate and rhythm
- Renal function (BUN, Creatinine)
- Hydration status and body weight (to monitor for fluid retention)
過量投与
**Clinical Signs**: Overdoses are characterized by severe hypotension, reflex tachycardia or other arrhythmias, skin flushing, and myocardial ischemia. **Treatment**: * **Decontamination**: Evacuate gastric contents and administer activated charcoal using standard precautions if ingestion was recent and cardiovascular status is stable. * **Cardiovascular Support**: Treat shock using volume expanders. Avoid pressor agents if possible. * **Pressor Agents**: If required to maintain blood pressure, use a minimally arrhythmogenic agent (e.g., phenylephrine or methoxamine). * **Additional Support**: Digitalis agents may be required. Diligently monitor blood pressure and renal function.
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