肼屈嗪
肼屈嗪（Hydralazine）是一種強效的**直接作用小動脈血管擴張劑**，主要用於治療全身性高血壓，以及作為小動物充血性心臟衰竭（CHF）的輔助治療（**降低後負荷**）。 * **臨床應用**：對於二尖瓣閉鎖不全、大型心室中膈缺損或嚴重主動脈瓣逆流的病例特別有益，因為降低心臟泵血的阻力（後負荷）至關重要。 * **難治性心臟衰竭**：當 ACE 抑制劑（如依那普利）無法有效改善二尖瓣閉鎖不全犬隻的臨床症狀時，常會使用此藥。 * **合併療法**：通常與利尿劑合併使用，以抵消其引起鈉水滯留的傾向；有時也與 β-受體阻斷劑併用，以減輕反射性心搏過速。 * **限制**：若原發性心肌疾病（如擴張性心肌病）是唯一問題且無明顯瓣膜逆流時，使用此藥治療心臟衰竭的效果不佳。
作用機制: 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.
各物種劑量
- 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.
給藥途徑
禁忌症
- Known hypersensitivity to hydralazine
- Coronary artery disease
- Hypovolemia
- Preexisting hypotension
- Hypovolaemia
- Hypotension
- Renal impairment
- Cerebral bleeding
不良反應
- 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)
藥物相互作用
- 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
監測
- 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
**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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