What is the initial dose of hydralazine (direct vasodilator) to add to a patient on lisinopril (angiotensin-converting enzyme inhibitor) who remains hypertensive?

Hydralazine Dosing for Persistent Hypertension on Lisinopril

For a patient on lisinopril with persistent hypertension, hydralazine should NOT be used as a one-time dose for acute blood pressure control due to its unpredictable response and prolonged duration of action. 1, 2

Why Hydralazine is Inappropriate for Acute Use

• Hydralazine has an unpredictable response and prolonged duration of action (2-4 hours), making it unsuitable as a first-line agent for acute blood pressure treatment in most patients 1, 2
• The ACC/AHA guidelines explicitly state that hydralazine "is not a desirable first-line agent for acute treatment" due to these pharmacokinetic properties 2, 3
• Effects begin within 10-30 minutes but last 2-4 hours, creating risk of prolonged hypotension if the response is excessive 2, 4

Appropriate Use of Hydralazine in Resistant Hypertension

If you are considering adding hydralazine as a scheduled medication for resistant hypertension, the starting dose is 25 mg three times daily, with upward titration to a maximum of 100-200 mg daily. 1

Stepwise Approach Before Adding Hydralazine

Before initiating hydralazine, the AHA resistant hypertension algorithm requires completion of these steps: 1

1. Optimize the 3-drug regimen: Ensure the patient is on maximally tolerated doses of an ACE inhibitor (lisinopril), calcium channel blocker, and appropriate diuretic 1

2. Substitute thiazide-like diuretic: Switch to chlorthalidone or indapamide if not already using these agents 1

3. Add mineralocorticoid receptor antagonist: Spironolactone or eplerenone should be added before hydralazine 1

4. Add beta-blocker or alternative: Unless heart rate is <70 bpm, add metoprolol succinate, bisoprolol, labetalol, or carvedilol 1

5. Only then add hydralazine: Start at 25 mg three times daily and titrate upward to maximum dose 1

Critical Dosing Details

• Starting dose: 25 mg three times daily (not as a single one-time dose) 1
• Maximum dose: 100-200 mg daily in divided doses 1
• Frequency: 2-3 times daily due to duration of action 1
• Special consideration: In patients with heart failure with reduced ejection fraction, hydralazine should be administered with isosorbide mononitrate 30 mg daily (max 90 mg daily) 1

Important Adverse Effects and Monitoring

• Reflex tachycardia and sodium/water retention: Hydralazine causes compensatory tachycardia and fluid retention, which is why it requires concomitant use of a beta-blocker and diuretic 1, 4
• Drug-induced lupus: Risk increases at higher doses 1
• Blood pressure monitoring: Check BP at 10-30 minutes, 1 hour, and 2-4 hours after each dose when initiating therapy 4

Alternative Approach for Acute Blood Pressure Control

If you need acute blood pressure reduction in a patient already on lisinopril:

• For hypertensive emergency (with end-organ damage): Use IV nicardipine (initial 5 mg/h, increasing every 5 min by 2.5 mg/h to maximum 15 mg/h) or clevidipine (initial 1-2 mg/h) 3
• For hypertensive urgency (no end-organ damage): Optimize existing oral regimen rather than using one-time doses of unpredictable agents 1, 2