Hydralazine
Hydralazine is a potent, direct-acting **arteriolar vasodilator** used primarily for the management of systemic hypertension and as an **afterload reducer** in the adjunctive treatment of congestive heart failure (CHF) in small animals. * **Clinical Utility**: Particularly beneficial in cases of mitral valve insufficiency, large septal defects, or severe aortic regurgitation where reducing the resistance against which the heart pumps (afterload) is critical. * **Refractory CHF**: Often utilized when ACE inhibitors (like enalapril) are insufficient to achieve clinical improvement in dogs with mitral insufficiency. * **Combination Therapy**: Frequently combined with diuretics to counteract its tendency to cause sodium and water retention, and sometimes with beta-blockers to blunt reflex tachycardia. * **Limitations**: Not particularly useful in treating heart failure when primary myocardial disease (e.g., dilated cardiomyopathy) is the sole issue without significant valvular regurgitation.
Mechanism: Hydralazine acts as a **semicarbazide-sensitive amine oxidase (SSAO) inhibitor**, directly relaxing vascular smooth muscle. * **Mechanism**: Alters cellular calcium metabolism in smooth muscle โ interferes with calcium movements โ 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 โ 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)** โ leading to sodium and water retention.
Dosing by species
- Adjunctive therapy in treatment of heart failure ยท start titration at 2.5 mg (total dose) and if necessary, increase up to 10 mg ยท PO ยท q12h ยท Follow similar titration protocols as dogs.
- Treatment of systemic hypertension (Fourth step drug) ยท 0.5 mg/kg ยท PO ยท twice daily ยท Added if systolic BP > 160 mmHg after amlodipine, ACE inhibitor, and spironolactone.
- Systemic hypertension ยท 2.5-10 mg/cat ยท PO ยท q12h ยท Long-term ยท Start at low dose and titrate upwards cautiously. Monitor blood pressure regularly.
- Adjunctive therapy in treatment of heart failure (afterload reducer) ยท 0.5 mg/kg ยท IV ยท Once ยท ARCI UCGFS Class 3 Drug.
- Adjunctive therapy in treatment of heart failure (long-term therapy) ยท 0.5-1.5 mg/kg ยท PO ยท q12h ยท Long-term
- Adjunctive therapy in treatment of heart failure (not receiving ACE inhibitors) ยท 1 mg/kg (starting dose, titrate up to 3 mg/kg if needed) ยท PO ยท q12h ยท 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) ยท 2 mg/kg ยท PO ยท Once ยท Given along with IV furosemide. May cause hypotension, but benefits outweigh risks.
- Adjunctive therapy in treatment of heart failure (receiving ACE inhibitors) ยท 0.5 mg/kg (starting dose, increase in 0.5 mg/kg increments to max 3 mg/kg) ยท PO ยท q12h ยท Give with extreme caution as severe hypotension may occur. Blood pressure monitoring required.
Routes of administration
Contraindications
- Known hypersensitivity to hydralazine
- Coronary artery disease
- Hypovolemia
- Preexisting hypotension
- Hypovolaemia
- Hypotension
- Renal impairment
- Cerebral bleeding
Adverse effects
- 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)
Drug interactions
- ACE-INHIBITORS ยท May cause additive hypotensive effect; usually used for therapeutic advantage
- BETA-BLOCKERS ยท May cause additive hypotensive effect; usually used for therapeutic advantage
- DIAZOXIDE ยท Potentially could cause profound hypotension
- DIURETICS ยท May cause additive hypotensive effect; usually used for therapeutic advantage ยท moderate
- FUROSEMIDE ยท Hydralazine may increase furosemide's renal effects
- MAO INHIBITORS ยท May cause additive hypotensive effect
- SYMPATHOMIMETICS (e.g., epinephrine) ยท Hydralazine may cause decreased pressor effect and may cause additive tachycardia
- ACE inhibitors (e.g., enalapril, benazepril) ยท Enhanced hypotensive effects ยท major
- Anaesthetics ยท Enhanced hypotensive effects ยท moderate
- Beta-blockers (e.g., propranolol) ยท Enhanced hypotensive effects ยท moderate
- Calcium-channel blockers (e.g., diltiazem, verapamil) ยท Enhanced hypotensive effects ยท moderate
- Corticosteroids ยท Enhanced hypotensive effects ยท minor
- NSAIDs ยท Enhanced hypotensive effects ยท moderate
Monitoring
- 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)
Overdose
**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.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.