Sodium nitroprusside

Sodium nitroprusside is the chemical compound with the formula Na₂[Fe(CN)₅NO]·2H₂O. This salt serves as a source of nitric oxide, a potent peripheral vasodilator that affects both arterioles and venules (venules more than arterioles). Sodium nitroprusside is often administered intravenously to patients who are experiencing a hypertensive emergency.

Chemistry

"Nitroprusside" is an anion that is usually available as the dihydrated disodium salt, Na₂[Fe(CN)₅NO]·2H₂O. This red solid dissolves in water, and to a lesser extent in alcohol to give a solution containing the dianion [Fe(CN)₅NO]²⁻. This metal nitrosyl complex is the active agent. In this anion, the iron is octahedral, surrounded by five tightly bound cyanide ligands and one linear nitric oxide ligand. When the linear nitrosyl ligand is assigned a single positive charge, the iron is assigned an oxidation state of 2+. As such it has a low-spin d⁶ electron configuration, and is diaamagnetic. Its chemical reactions have been studied intensively.

Indications

It reduces both total peripheral resistance as well as venous return, thus decreasing both preload and afterload. For this reason, it can be used in severe cardiogenic heart failure where this combination of effects can act to increase cardiac output. In situations where cardiac output is normal, the effect is to reduce blood pressure.

Nitroprusside is light-sensitive, and breaks down in sunlight, producing cyanide.

Despite its toxicity, nitroprusside is still used because it remains an effective drug in certain clinical circumstances such as malignant hypertension or for rapid control of blood pressure during vascular surgery and neurosurgery.

Nitroprusside is contraindicated in patients with renal failure.

Mechanism of action

Its mechanism of action appears to be liberation of nitric oxide (NO), which causes relaxation of vascular smooth muscle. Nitroprusside also releases cyanide ions which are converted in the liver to thiocyanate by the enzyme rhodanase, a reaction which requires a sulfur donor such as thiosulfate. Alternatively, cyanide may react with methemoglobin to form cyanomethemoglobin. Thiocyanate is then excreted by the kidney. In the absence of sufficient thiosulfate, cyanide ions can quickly reach toxic levels. The half-life of nitroprusside is 1-2 minutes although thiocyanate has an excretion half life of several days. The duration of treatment should not exceed 72 hours and thiocyanate plasma concentrations should be monitored.

Role in research

Sodium nitroprusside (often abbreviated SNP) is frequently used in vascular research to test endothelium-independent vasodilation. One method of administering SNP is by iontophoresis. This allows local administration of the drug, preventing the systemic effects listed above but still causing local microvascular vasodilation. NO liberated from the SNP diffuses into the vascular smooth muscle causing relaxation and subsequent vasodilatation. This vasodilatation is quantified by various techniques. This role in the treatment of hypertension was first performed at the Cleveland Clinic.

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