When is hydralazine (apresoline) indicated for a patient with hypertension?

Hydralazine Use in Hypertension Management

Hydralazine should be used primarily as a secondary or third-line agent for resistant hypertension, in hypertensive emergencies, or in specific populations such as pregnant women with preeclampsia/eclampsia, always in combination with a beta-blocker and diuretic to counteract reflex tachycardia and fluid retention. 1, 2, 3

Appropriate Patient Populations for Hydralazine

Primary Indications

• Resistant hypertension: When BP remains uncontrolled despite optimal doses of three first-line agents (ACE inhibitor/ARB, calcium channel blocker, and thiazide diuretic) 4
• Hypertensive emergencies: As an IV agent when rapid BP reduction is needed 1, 5
• Pregnancy-induced hypertension: Particularly in preeclampsia and eclampsia 3, 5
• Heart failure with hypertension: When combined with isosorbide dinitrate (particularly beneficial in African American patients) 1

Positioning in Treatment Algorithm

1. Not a first-line agent: Hydralazine is classified as a secondary agent due to its side effect profile and the need for multiple daily dosing 1
2. Typical dosing: 100-200 mg/day divided into 2-3 doses 1
3. Always use in combination: Should be administered with a beta-blocker to prevent reflex tachycardia and a diuretic to prevent sodium retention 3, 6

Mechanism and Pharmacology

• Direct-acting vasodilator that primarily dilates resistance arterioles, reducing peripheral resistance 3
• Causes baroreflex-mediated venoconstriction and catecholamine-mediated cardiac stimulation 3
• Duration of action can be prolonged, with blood pressure effects persisting 30-140 hours after discontinuation 7

Precautions and Contraindications

Use with Caution in:

• Coronary artery disease: Can cause anginal attacks and ECG changes of myocardial ischemia 2
• Mitral valve disease: May increase pulmonary artery pressure 2
• Cerebrovascular disease: Use with caution in patients with cerebral vascular accidents 2
• Advanced renal disease: Though it may improve renal function in some patients, caution is advised 2

Monitoring Requirements:

• Complete blood counts and antinuclear antibody titers: Before and periodically during prolonged therapy 2
• Blood pressure: Check within 1 month of medication changes 4
• Symptoms of peripheral neuritis: Paresthesia, numbness, and tingling may indicate need for pyridoxine supplementation 2

Side Effects and Management

• Reflex tachycardia: Prevent with concomitant beta-blocker use 3, 6
• Fluid retention: Manage with diuretic therapy 3
• Headache: Common in early therapy, often prevented by beta-blocker use 3
• Lupus-like syndrome: Risk increases with high doses and long-term use, especially in slow acetylators 2, 6
• Blood dyscrasias: Including reduction in hemoglobin, leukopenia, agranulocytosis, and purpura 2

Special Considerations

• Unpredictable response: The response to hydralazine can be variable and its prolonged duration of action makes it less desirable as a first-line agent for acute treatment 1
• Acetylator status: Slow acetylators have better BP control but more side effects 6
• Drug interactions: Use caution with MAO inhibitors; profound hypotension may occur when combined with diazoxide 2
• Food interactions: Administration with food results in higher plasma levels 2

Practical Application

1. Start with 25-50 mg 2-3 times daily
2. Always initiate beta-blocker therapy before starting hydralazine to prevent reflex tachycardia 6
3. Add a diuretic to prevent sodium retention
4. Titrate dose based on BP response up to 200 mg/day maximum 1
5. Monitor for development of lupus-like syndrome with long-term use

In summary, hydralazine is not a first-line antihypertensive but remains valuable for specific situations such as resistant hypertension, hypertensive emergencies, pregnancy-related hypertension, and as part of combination therapy in heart failure. Its use requires careful monitoring and combination with other agents to mitigate predictable side effects.