Direct vasodilators

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Mechanisms & Hemodynamics - Pipe-Opening Principles

  • Primary Action: Directly relax arteriolar smooth muscle, leading to vasodilation.
  • Hemodynamic Effect: Marked ↓ in Systemic Vascular Resistance (SVR) and afterload.
    • Minimal effect on venous capacitance; preload is largely unaffected.
  • Compensatory Response: Baroreceptor-mediated stimulation of the sympathetic nervous system.
    • Results in reflex tachycardia, ↑ contractility, and ↑ renin release.

Exam Favorite: The profound reflex sympathetic activation often necessitates co-administration with a beta-blocker to manage the resulting tachycardia and increased myocardial oxygen demand.

Arterial Vasodilators - The 'Artery-Only' Agents

  • Hydralazine

    • Mechanism: ↑ cGMP → smooth muscle relaxation. Primarily dilates arterioles, reducing afterload.
    • Metabolism: Acetylation in the liver. Status (slow vs. fast acetylator) affects drug levels and risk of toxicity.
    • Use: Severe HTN, hypertensive emergencies (incl. pregnancy), co-administered with nitrates for heart failure.
    • Adverse Effects: Reflex tachycardia, fluid retention/edema, headache, angina. Drug-induced lupus-like syndrome.
  • Minoxidil

    • Mechanism: Opens ATP-sensitive K+ channels ($K_{ATP}$) in vascular smooth muscle → hyperpolarization & relaxation.
    • Use: Severe, treatment-refractory hypertension.
    • Adverse Effects: More potent than hydralazine. Causes significant reflex tachycardia and fluid retention. 📌 Hypertrichosis (hirsutism) - exploited for topical use (Rogaine) in alopecia.

High-Yield: Hydralazine-induced lupus is more common in patients who are slow acetylators and is associated with anti-histone antibodies.

Mixed Vasodilators - The Emergency Responders

  • Sodium Nitroprusside
    • MOA: Directly releases Nitric Oxide (NO) → ↑ cGMP → potent vasodilation of both arterioles and venules.
    • Hemodynamic Effects: ↓↓ Preload (venous pooling) & ↓↓ Afterload (reduced SVR).
      • Maintains stroke volume; ↑ heart rate (reflex tachycardia).
    • Use: Hypertensive emergencies (e.g., malignant hypertension, aortic dissection). Administered via continuous IV infusion.
    • Metabolism & Toxicity:
      • Metabolized to cyanide and NO.
      • ⚠️ Cyanide Toxicity: Risk ↑ with renal impairment or prolonged (>24-48 hrs) / high-dose infusions. Presents with altered mental status, seizures, lactic acidosis.
      • Antidotes: Sodium thiosulfate (provides sulfur groups), hydroxocobalamin (binds cyanide), sodium nitrite (induces methemoglobinemia).
    • 📌 Mnemonic: NitroPrusside → NO Provider.

Exam Favorite: Nitroprusside can cause coronary steal syndrome by dilating coronary arterioles, potentially shunting blood away from ischemic areas.

Sodium Nitroprusside: Mechanism & Cyanide Toxicity

High‑Yield Points - ⚡ Biggest Takeaways

  • Hydralazine and Minoxidil are primarily arteriolar vasodilators, causing a significant decrease in afterload.
  • The profound drop in blood pressure triggers reflex tachycardia and fluid retention, necessitating co-administration with β-blockers and diuretics.
  • Remember drug-induced lupus for Hydralazine and hypertrichosis for Minoxidil.
  • Sodium nitroprusside dilates both arteries and veins for hypertensive emergencies but carries a risk of cyanide toxicity.
  • Fenoldopam, a D1 agonist, uniquely increases renal blood flow, making it ideal for hypertensive crises with renal insufficiency.
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Practice Questions: Direct vasodilators

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A 72-year-old man comes to the emergency department because of blurry vision for the past 3 days. He has also had 4 episodes of right-sided headaches over the past month. He has no significant past medical history. His father died of coronary artery disease at the age of 62 years. His temperature is 37.2°C (99°F), pulse is 94/min, and blood pressure is 232/128 mm Hg. Fundoscopy shows right-sided optic disc blurring and retinal hemorrhages. A medication is given immediately. Five minutes later, his pulse is 75/min and blood pressure is 190/105 mm Hg. Which of the following drugs was most likely administered?

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Flashcards: Direct vasodilators

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Dihydropyridine CCBs may cause reflex _____ (HR)

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Dihydropyridine CCBs may cause reflex _____ (HR)

tachycardia

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