What is the mechanism of action (MOA) of nitroprusside (sodium nitroprusside)?

From the Guidelines

Sodium nitroprusside works by releasing nitric oxide (NO) in vascular smooth muscle cells, leading to vasodilation in both arterial and venous vessels, which reduces both preload and afterload. This mechanism of action is crucial in understanding its use in clinical practice, particularly in the management of heart failure and hypertensive emergencies. The most recent guideline from 2022 1 supports the use of sodium nitroprusside in specific scenarios, such as severely congested patients with hypertension or severe mitral valve regurgitation complicating left ventricular dysfunction. Key points to consider when using sodium nitroprusside include:

• It is a potent vasodilator that requires careful titration due to its rapid onset of action
• It should be used in an intensive care setting with invasive hemodynamic blood pressure monitoring
• Prolonged use can lead to thiocyanate and cyanide toxicity, particularly in patients with renal insufficiency and significant hepatic disease
• Typical dosing begins at 0.3-0.5 mcg/kg/min and can be titrated up to 10 mcg/kg/min, with doses above 2 mcg/kg/min increasing the risk of cyanide toxicity The use of sodium nitroprusside is limited to the relief of dyspnea in hospitalized heart failure patients with intact or high blood pressure, as there are no data suggesting it improves outcomes in these patients 1. Overall, the decision to use sodium nitroprusside should be made with caution, considering the potential benefits and risks, and should be guided by the most recent clinical guidelines and evidence-based practice.

From the FDA Drug Label

The principal pharmacological action of sodium nitroprusside is relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins. Sodium nitroprusside is more active on veins than on arteries, but this selectivity is much less marked than that of nitroglycerin. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end diastolic pressure and pulmonary capillary wedge pressure (preload) Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload).

The mechanism of action (MOA) of nitroprusside is through the relaxation of vascular smooth muscle, leading to dilatation of peripheral arteries and veins. This results in:

• Decreased preload due to peripheral pooling of blood and reduced venous return to the heart
• Decreased afterload due to arteriolar relaxation, reducing systemic vascular resistance and mean arterial pressure 2

From the Research

Mechanism of Action of Nitroprusside

• Nitroprusside is a balanced arterial and venous vasodilator that improves hemodynamic and clinical status by reducing systemic vascular resistance, left ventricular filling pressure, and increasing cardiac output 3.
• It releases nitric oxide (NO) in situ, which causes rapid vasodilation and acutely lowers blood pressure 4, 5.
• The release of NO from nitroprusside is pH-dependent and increases with pH, with the maximum release occurring at around pH 7 5.
• The endothelium plays a role in potentiating the vasorelaxation induced by nitroprusside, and this effect is mediated by the release of endogenous NO from constitutive nitric oxide synthase (cNOS) 6.

Clinical Use of Nitroprusside

• Nitroprusside is used clinically in cardiac surgery, hypertensive crises, heart failure, vascular surgery, pediatric surgery, and other acute hemodynamic applications 4.
• It is an effective agent for reducing blood pressure and improving cardiac output in patients with advanced low-output heart failure 7.
• However, its use is associated with the risk of cyanide accumulation and toxicity, and agents to ameliorate this effect are limited 4.

Pharmacological Effects of Nitroprusside

• Nitroprusside causes vasodilation by releasing NO, which activates guanylyl cyclase and increases cyclic GMP levels in vascular smooth muscle cells 3, 6.
• It also reduces systemic vascular resistance and left ventricular filling pressure, which improves cardiac output and reduces the workload on the heart 7, 3.
• The pharmacological effects of nitroprusside are rapid and short-lived, making it a useful agent for acute hemodynamic applications 4.