Direct-Acting Vasodilators

Snapshot

• 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. 

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 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) 

Minoxidil

• Mechanism of action
  • opens K+ channels → hyperpolarizes vascular smooth muscle → smooth muscle relaxation
• Clinical use
  • male-pattern baldness (androgenic alopecia)
• Toxicity
  • hypertrichosis