Nitric oxide reduces both total peripheral resistance and venous return, thus decreasing bothpreload andafterload. So, it can be used in severecongestive heart failure where this combination of effects can act to increasecardiac output. In situations where cardiac output is normal, the effect is to reduceblood pressure.[13][15] It is sometimes also used to induce hypotension (to reduce bleeding) for surgical procedures (for which it is alsoFDA,TGA, andMHRA labelled).[13][14][16]
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.
Sodium nitroprusside should not be used for compensatory hypertension (e.g. due to an arteriovenous stent or coarctation of the aorta).[15] 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 withvitamin B12 deficiency, anaemia, severe renal disease, or hypovolaemia.[15] 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.[15] Its use in patients with acute congestive heart failure associated with reduced peripheral resistance is also not recommended.[15] Its use in hepatically impaired individuals is also not recommended, as is its use in cases of pre-existinghypothyroidism.[13]
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.[15][26] Some evidence suggests sodium nitroprusside use in critically ill children may be safe, even without monitoring ofcyanide level.[27]
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.[15]
The cyanide can be detoxified by reaction with asulfur-donor such asthiosulfate, catalysed by the enzymerhodanese.[30] In the absence of sufficient thiosulfate, cyanide ions can quickly reach toxic levels.[30]Hydroxocobalamin can be administered to reduce the risk of thiocyanate toxicity induced by nitroprusside.[31]
The only known drug interactions arepharmacodynamic in nature, that is it is possible for other antihypertensive drugs to reduce the threshold for dangerous hypotensive effects to be seen.[15]
Sodium nitroprusside breaks down in circulation to releasenitric oxide (NO).[7] It does this by binding to oxyhaemoglobin to release cyanide, methaemoglobin and nitric oxide.[7] NO activatesguanylate cyclase in vascular smooth muscle and increases intracellular production ofcGMP. cGMP activatesprotein kinase G which activates phosphatases which inactivate myosin light chains.[34]Myosin light chains are involved in smooth muscle contraction. The result is vascular smooth muscle relaxation, which allow vessels to dilate.[34] This mechanism is similar to that ofphosphodiesterase 5 (PDE5)inhibitors such assildenafil (Viagra) andtadalafil (Cialis), which elevate cGMP concentration by inhibiting its degradation by PDE5.[35]
A role for NO in various common psychiatric disorders includingschizophrenia,[36][37][38][39]bipolar disorder[40][41][42] andmajor depressive disorder[43][44][45] has been proposed and supported by several clinical findings. These findings may also implicate the potential of drugs that alter NO signalling such as SNP in their treatment.[38][44] Such a role is also supported by the findings of the recent SNP clinical trial.[46]
Structure of sodium nitroprusside in the solid state, obtained byneutron diffractionSpace filling model of sodium nitroprusside
Nitroprusside is aninorganic compound with thechemical formula Na2[Fe(CN)5NO], usually encountered as thedihydrate, Na2[Fe(CN)5NO]·2H2O.[47] This red-colored sodium salt dissolves in water or ethanol to give solutions containing the freecomplex dianion [Fe(CN)5NO]2−.
Nitroprusside is a complexanion that features anoctahedral iron(II) centre surrounded by five tightly boundcyanide ligands and one linearnitric oxide ligand (Fe-N-O angle = 176.2°[48]). The anion possesses idealizedC4vsymmetry.
Due to the linear Fe-N-O angle, the relatively short N-O distance of 113 pm[48] and the relatively high stretching frequency of 1947 cm−1, the complex is formulated as containing an NO+ ligand.[49] Consequently, iron is assigned an oxidation state of +2. The iron center has a diamagneticlow-spin d6 electron configuration, although a paramagnetic long-lived metastable state has been observed byEPR spectroscopy.[50]
The chemical reactions of sodium nitroprusside are mainly associated with the NO ligand.[51] For example, addition ofS2− ion to [Fe(CN)5(NO)]2− produces the violet colour [Fe(CN)5(NOS)]4− ion, which is the basis for a sensitive test for S2− ions. An analogous reaction also exists with OH− ions, giving [Fe(CN)5(NO2)]4−.[49]Roussin's red salt (K2[Fe2S2(NO)4]) andRoussin's black salt (NaFe4S3(NO)7) are related iron nitrosyl complexes. The former was first prepared by treating nitroprusside with sulfur.[52]
Sodium nitroprusside is primarily used as a vasodilator. It was first used in human medicine in 1928.[7] By 1955, data on its safety during short-term use in people with severehypertension had become available.[7] Despite this, due to difficulties in its chemical preparation, it was not finally approved by the USFDA until 1974 for the treatment of severe hypertension.[7] By 1993, its popularity had grown such that total sales in the US had totalledUS$2 million.[7]
Sodium nitroprusside spectrum is used to calibrate Mössbauer spectrometers
Sodium nitroprusside is often used as a reference compound for the calibration ofMössbauer spectrometers.[54] Sodium nitroprusside crystals are also of interest for optical storage. For this application, sodium nitroprusside can be reversibly promoted to a metastable excited state by blue-green light, and de-excited by heat or red light.[55]
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 ofPseudomonas aeruginosabiofilms by acting as a nitric oxide donor.[56][57]
Sodium nitroprusside is also used as an analytical reagent under the name sodium nitroferricyanide for the detection of methylketones,amines, and thiols. It is also used as a catalyst in the quantitative determination of ammonia in water samples via the phenate method.[58]
The nitroprusside reaction is used for the identification of ketones in urine testing.[59] Sodium nitroprusside was found to give a reaction with acetone or creatine under basic conditions in 1882. Rothera refined this method by the use of ammonia in place of sodium or potassium hydroxide. The reaction was now specific for methyl ketones. Addition of ammonium salts (e.g. ammonium sulfate) improved the sensitivity of the test, too.[60]
In this test, known as Rothera's test, methyl ketones (CH3C(=O)-) under alkaline conditions give bright red coloration (see alsoiodoform test). Rothera's test was initially applied to detectingketonuria (a symptom ofdiabetes) in urine samples. This reaction is now exploited in the form ofurine test strips (e.g. "Ketostix").[61]
Thenitroprusside reaction is achemical test used to detect the presence ofthiol groups ofcysteine in proteins. Proteins with the free thiol group give a red colour when added to a solution of sodium nitroprusside inaqueous ammonia. Some proteins test positive when denatured, indicating that thiol groups are liberated.[62][63][64]
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,disulfide bonds will be broken by the released cyanide. The destruction of disulfide bonds liberatescysteine fromcystine as well ashomocysteine fromhomocystine. Next, sodium nitroprusside is added to the solution and it reacts with the newly freedsulfhydryl 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 ascystinuria, which results from pathology in the transport of dibasic amino acids.[65]
Sodium nitroprusside is also used to detectamines, including those in illicit drugs. This compound is thus used as a stain to indicate amines inthin layer chromatography.[66] Sodium nitroprusside is similarly used as a presumptive test for the presence ofalkaloids (amine-containingnatural products) common in illicit substances.[67] The test, calledSimon's test, is performed by adding 1 volume of a solution of sodium nitroprusside andacetaldehyde indeionized water to a suspected drug, followed by the addition of 2 volumes of anaqueoussodium carbonate solution. The test turns blue for somesecondary amines. The most common secondary amines encountered in forensic chemistry include 3,4-methylenedioxymethamphetamine (MDMA, the main component in ecstasy) andphenethylamines such asmethamphetamine. Sodium nitroprusside is also useful in the identification themercaptans (thiol groups) in the nitroprusside reaction.
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