Hydralazine

1. Drug Class

  • Direct-acting arterial vasodilator
  • Antihypertensive (non–RAAS, non–CCB)

2. Mechanism of Action (Clinical Perspective)

  • Causes direct relaxation of arteriolar smooth muscle
  • Likely via:
    • ↑ nitric oxide (NO) production
    • ↓ intracellular calcium in vascular smooth muscle
  • Minimal effect on venous capacitance vessels
    → ↓ afterload with little effect on preload

Clinical implication:

  • Reflex sympathetic activation → ↑ HR, ↑ renin release
  • Often combined with β-blocker ± diuretic to blunt reflex effects

3. Indications (Evidence-Based)

Indication Clinical Notes
Hypertension (2nd/3rd line) Useful when ACEi/ARB/CCB not tolerated
Hypertensive urgency/emergency (IV) Less predictable BP response vs labetalol
HFrEF (Black patients) In combination with isosorbide dinitrate (A-HeFT trial)
Pregnancy-related HTN Preferred agent in preeclampsia/eclampsia
Renal dysfunction Safe in CKD (not renally eliminated)

4. Dosing (Adult)

Oral (Chronic HTN / HF)

  • Start: 10 mg PO QID
  • Titrate every 3–7 days
  • Typical maintenance: 25–100 mg PO BID–QID
  • Max: 300 mg/day

IV (Acute BP Control)

  • 5–10 mg IV q20–30 min PRN
  • Onset: 10–20 min
  • Duration: 2–6 hours

Clinical Pearl:

  • IV hydralazine has unpredictable BP lowering, especially in elderly and CKD → avoid routine PRN use without clear parameters

5. Pharmacokinetics (High-Yield)

Parameter Notes
Bioavailability Variable (extensive first-pass metabolism)
Metabolism Hepatic acetylation
Acetylator status Slow acetylators → ↑ toxicity
Half-life 3–7 hours
Renal adjustment ❌ Not required

6. Adverse Effects (Clinically Important)

Common

  • Headache
  • Flushing
  • Palpitations
  • Reflex tachycardia
  • Edema

Serious / High-Yield

ADR Clinical Relevance
Drug-induced lupus (DIL) Dose- & duration-dependent
ANA positivity Up to 50% (not always symptomatic)
Pericarditis Rare but severe
Peripheral neuropathy Due to pyridoxine deficiency
Agranulocytosis (rare) Monitor CBC if symptomatic

7. Drug-Induced Lupus (DIL) – Key Points

  • Risk ↑ with:
    • Dose >200 mg/day
    • Therapy >6 months
    • Slow acetylators
  • Symptoms:
    • Arthralgia
    • Myalgia
    • Fever
    • Serositis
  • Management:
    • Discontinue hydralazine
    • Symptoms usually resolve in weeks–months

8. Monitoring Parameters

Parameter Frequency
BP / HR Baseline and ongoing
ANA Baseline + periodically (long-term therapy)
CBC If symptoms of infection or lupus
Renal function Routine (no adjustment required)
Signs of HF worsening Edema, weight gain

9. Drug Interactions (Practical)

  • β-blockers → beneficial (reduce tachycardia)
  • Diuretics → mitigate fluid retention
  • Other antihypertensives → additive hypotension
  • MAOIs → ↑ hypotensive risk (rare)

10. Special Populations

Population Consideration
Pregnancy Safe, widely used IV & PO
Elderly ↑ hypotension & reflex tachycardia
Heart failure Use with nitrates (mortality benefit)
CKD Preferred when RAAS blockade limited

11. Clinical Pearls for Pharmacists

  • Avoid PRN IV hydralazine without strict BP parameters
  • Always consider β-blocker + diuretic co-therapy
  • Monitor for lupus if dose >100–150 mg/day long-term
  • Useful alternative in ACEi/ARB intolerance
  • Unpredictable IV response → caution in stroke or ACS

12. Quick Summary

Hydralazine is a direct arterial vasodilator best used as a second-line agent, in pregnancy, or in combination therapy for HFrEF. Its major limitations are reflex tachycardia, fluid retention, and drug-induced lupus, making careful patient selection and monitoring essential.

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