• A 31-year-old G1P0 woman presents to her obstetrician at 19 weeks gestation for a check-up. She feels well and has no complaints other than some minor back pain. At her last check-up 3 weeks ago, her blood pressure was 152/88 mmHg. Today, her blood pressure is 156/90 mmHg. She is diagnosed with chronic hypertension and started on oral hydralazine. 
  • 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
  • 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 coadministered 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) 
  • 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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