Sodium nitroprusside ( SNP), sold under the brand name Nitropress among others, is a medication used to lower blood pressure.[ This may be done if the blood pressure is very high and resulting in symptoms, in certain types of heart failure, and during surgery to decrease bleeding.][ It is used by continuous injection into a vein.][ Onset is nearly immediate and effects last for up to ten minutes.]
It is available as a generic medication.
Side effects and mechanism
Common side effects include low blood pressure and cyanide toxicity.[ Other serious side effects include methemoglobinemia.][ It is not generally recommended during pregnancy due to concerns of side effects.][
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History
Sodium nitroprusside was discovered as early as 1850 and found to be useful in medicine in 1928.
Medical use
Sodium nitroprusside is intravenously infused in cases of acute hypertensive crises.
Nitric oxide reduces both total peripheral resistance and venous return, thus decreasing both preload and afterload. So, it can be used in severe congestive 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.[ It is sometimes also used to induce hypotension (to reduce bleeding) for surgical procedures (for which it is also FDA, TGA, and MHRA labelled).]
The medication is extremely beneficial for use in medical patients because the effects of the medication will directly stop the second that it stops being infused. This is due to the metabolism of the drug, and the rapid inactivation to thiocyanate once conversion of the drug stops.
This compound has also been used as a treatment for aortic valve stenosis,[ and Ergotism.]
Adverse effects
Adverse effects by incidence and severity[
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Common
Unknown frequency
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Nausea
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Retching
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Anxiety
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Chest discomfort
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Paraesthesial warmth
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Abdominal pain
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Orthostatic hypotension
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ECG changes
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Skin irritation
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Flushing
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Injection site erythema
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Injection site streaking
Serious
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Ileus
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Reduced platelet aggregation
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Haemorrhage
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Increased intracranial pressure
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Metabolic acidosis
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Methaemoglobinaemia
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Cyanide poisoning
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Thiocyanate toxicity
Contraindications
Sodium nitroprusside should not be used for compensatory hypertension (e.g. due to an arteriovenous stent or coarctation of the aorta).[ It should not be used in patients with inadequate cerebral circulation or in patients who are near death. It should not be used in patients with vitamin B12 deficiency, anaemia, severe renal disease, or hypovolaemia.][ Patients with conditions associated with a higher cyanide/thiocyanate ratio (e.g. congenital (Leber's) optic atrophy, tobacco amblyopia) should only be treated with sodium nitroprusside with great caution.][ Its use in patients with acute congestive heart failure associated with reduced peripheral resistance is also not recommended.][ Its use in hepatically impaired individuals is also not recommended, as is its use in cases of pre-existing hypothyroidism.][
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Its use in pregnant women is advised against, although the available evidence suggests it may be safe, provided maternal pH and cyanide levels are closely monitored.
Interactions
The only known drug interactions are pharmacodynamic in nature, that is it is possible for other antihypertensive drugs to reduce the threshold for dangerous hypotensive effects to be seen.[
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Overdose
Due to its cyanogenic nature, overdose may be particularly dangerous. Treatment of sodium nitroprusside overdose includes the following:
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Discontinuing sodium nitroprusside administration
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Buffering the cyanide by using sodium nitrite to convert haemoglobin to methaemoglobin as much as the patient can safely tolerate
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Infusing sodium thiosulfate to convert the cyanide to thiocyanate.
Haemodialysis is ineffective for removing cyanide from the body but it can be used to remove most of the thiocyanate produced from the above procedure.[
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Toxicology
The cyanide can be detoxified by reaction with a sulfur-donor such as thiosulfate, catalysed by the enzyme rhodanese.[ In the absence of sufficient thiosulfate, cyanide ions can quickly reach toxic levels.]
Mechanism of action
As a result of its breakdown to nitric oxide (NO), sodium nitroprusside has potent Vasodilation effects on arterioles and (arterial more than venous), whereas other nitrates exhibit more selectivity for veins (e.g. nitroglycerin).
Sodium nitroprusside breaks down in circulation to release nitric oxide (NO).[ Myosin light chains are involved in smooth muscle contraction. The result is vascular smooth muscle relaxation, which allow vessels to dilate.]
A role for NO in various common psychiatric disorders including schizophrenia,[ Such a role is also supported by the findings of the recent SNP clinical trial.]
Structure and properties
Nitroprusside is an inorganic compound with the chemical formula Na2Fe(CN)5NO, usually encountered as the dihydrate, Na2Fe(CN)5NO·2H2O.
Nitroprusside is a complex anion that features an octahedral iron(II) centre surrounded by five tightly bound cyanide ligands and one linear nitric oxide ligand (Fe-N-O angle = 176.2°
Due to the linear Fe-N-O angle, the relatively short N-O distance of 113 pm[ and the relatively high stretching frequency of 1947 cm−1, the complex is formulated as containing an NO+ ligand.]
The chemical reactions of sodium nitroprusside are mainly associated with the NO ligand.
Preparation
Sodium nitroprusside can be synthesized by digesting a solution of potassium ferrocyanide in water with nitric acid, followed by neutralization with sodium carbonate:
Alternatively, the nitrosyl ligand can be introduced using nitrite:
Other uses
Sodium nitroprusside is often used as a reference compound for the calibration of Mössbauer spectrometers.
In physiology research, sodium nitroprusside is frequently used to test endothelium-independent vasodilation. Iontophoresis, for example, allows local administration of the drug, preventing the systemic effects listed above but still inducing local microvascular vasodilation. Sodium nitroprusside is also used in microbiology, where it has been linked with the dispersal of Pseudomonas aeruginosa by acting as a nitric oxide donor.
Analytical reagent
Sodium nitroprusside is also used as an analytical reagent under the name sodium nitroferricyanide for the detection of methyl , , and thiols. It is also used as a catalyst in the quantitative determination of ammonia in water samples via the phenate method.
Ketones
The nitroprusside reaction is used for the identification of ketones in urine testing.
In this test, known as Rothera's test, methyl ketones (CH3C(=O)-) under alkaline conditions give bright red coloration (see also iodoform test). Rothera's test was initially applied to detecting ketonuria (a symptom of diabetes) in urine samples. This reaction is now exploited in the form of urine test strips (e.g. "Ketostix").
Thiols and cysteine
The nitroprusside reaction is a chemical test used to detect the presence of thiol groups of cysteine in proteins. Proteins with the free thiol group give a red colour when added to a solution of sodium nitroprusside in aqueous ammonia. Some proteins test positive when denatured, indicating that thiol groups are liberated.
Sodium nitroprusside is used in a separate urinalysis test known as the cyanide nitroprusside test or Brand's test. In this test, sodium cyanide is added first to urine and let stand for about 10 minutes. In this time, will be broken by the released cyanide. The destruction of disulfide bonds liberates cysteine from cystine as well as homocysteine from homocystine. Next, sodium nitroprusside is added to the solution and it reacts with the newly freed sulfhydryl groups. The test will turn a red/purple colour if the test is positive, indicating significant amounts of amino acids were in the urine (aminoaciduria). Cysteine, cystine, homocysteine, and homocystine all react when present in the urine when this test is performed. This test can indicate inborn errors of amino acid transporters such as cystinuria, which results from pathology in the transport of dibasic amino acids.
Amines
Sodium nitroprusside is also used to detect , including those in illicit drugs. This compound is thus used as a stain to indicate amines in thin layer chromatography.
History
Sodium nitroprusside is primarily used as a vasodilator. It was first used in human medicine in 1928.[ By 1955, data on its safety during short-term use in people with severe hypertension had become available.][ Despite this, due to difficulties in its chemical preparation, it was not finally approved by the US FDA until 1974 for the treatment of severe hypertension.][ By 1993, its popularity had grown such that total sales in the US had totalled US$2 million.][
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