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Updated: Dec 17 2021

Direct-Acting Vasodilators

  • Snapshot
    • A 29-year-old G2P1 woman presents to her obstetrician at 18 weeks gestation for a check-up. Aside from mild nausea earlier in her pregnancy, she feels well overall and has no major complaints. At her last checkup 3 weeks ago, her blood pressure was 150/86 mmHg. Today, her blood pressure is 152/88 mmHg. She is started on oral hydralazine for confirmed chronic hypertension.
  • Introduction
    • Direct-acting vasodilators function by dilating arterial vessels without any direct activity on venous circulation
    • Drugs
      • hydralazine
        • oral or parenteral agent used to treat hypertensive diseases
      • minoxidil
        • topical agent used to treat male pattern baldness
  • Hydralazine
    • Mechanism of action
      • the exact mechanism is unclear
      • appears to act via multiple simultaneous 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
    • Physiologic effects
      • decreases peripheral resistance
      • activates baroreflex-mediated vasoconstriction
        • increases venous return to the heart
        • increases catecholamine-mediated inotropy and chronotropy
          • often co-administered with a sympathetic inhibitor (e.g., β-blocker) to inhibit this compensatory response
    • Clinical use
      • hypertensive crisis
      • congestive heart failure
        • ↓ afterload →  ↑ stroke volume and ↑ ejection fraction
      • hypertensive diseases of pregnancy
        • chronic hypertension
        • gestational hypertension
      • moderate to severe hypertension
        • not first-line due to short half-life and precipitation of reflex sympathetic activation
    • Toxicity
      • contraindicated in patients with coronary artery disease
        • can ↑ cardiac demand due to baroreflex-mediated sympathetic activation
      • fluid retention
      • headache
      • lupus-like syndrome (especially for slow acetylators) 
  • Minoxidil
    • Mechanism of action
      • opens K+ channels → hyperpolarizes vascular smooth muscle → smooth muscle relaxation
    • Clinical use
      • male pattern baldness (androgenic alopecia)
    • Toxicity
      • hypertrichosis
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