USMLE Step 1




Cardiovascular Pharm



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Hydralazine causes direct arterial vasodilation which can be used to treat severe hypertension, especially in pregnant patients.  The arterial dilation leads to activation of the RAAS and fluid retention.  Additionally, reflex tachycardia is a common side effect and usually treated prophylactically using beta-blockers.  Don’t forget that hydralazine is also associated with a Lupus-like syndrome.

Key Points

  • Hydralazine
    • Mechanism
      • Direct arterial vasodilator
        • Thought to act via several mechanisms
          • Stimulates nitric oxide release from vascular endothelium →  ↑ cGMP → smooth muscle relaxation
          • Opens K+ channels → hyperpolarizes vascular smooth muscle → smooth muscle relaxation
          • Blocks IP3-dependent release of calcium from the smooth muscle sarcoplasmic reticulum → decreased calcium availability → impaired smooth muscle contraction
    • Physiological Effects
      • Arterial vasodilation
        • → decreased BP → decreased SVR / afterload → baroreceptor activation → reflex sympathetic activation
          • Increases catecholamine-mediated inotropy and chronotropy
          • RAAS activation → sodium and fluid retention
          • Increases venous return to the heart (via baroreceptor-mediated vasoconstriction)
    • Clinical Use
      • Hypertensive emergency in pre-eclampsia / eclampsia because it’s safe to use during pregnancy
      • Hypertensive emergency
        • Not first line because reflex sympathetic activation and short half-life
      • Heart failure
        • Hydralazine increases stroke volume and cardiac output
    • Adverse Effects
      • Reflex tachycardia
        • Contraindicated in angina / CAD
        • Often coadministered with a beta-blocker
      • Fluid retention / edema
        • Often coadministered with a diuretic
      • Drug-induced lupus
        • Causes lupus-like symptoms with +ANA and anti-histone abs
        • Increased risk in slow acetylators
          • Hydralazine is metabolized via phase II acetylation in the liver
      • Headache
      • Angina