Sodium nitroprusside

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.{{cite web|url=https://www.drugs.com/pregnancy/nitroprusside.html|title=Nitroprusside Pregnancy and Breastfeeding Warnings|date=2018|website=Drugs.com|archive-url=https://web.archive.org/web/20161221005738/https://www.drugs.com/pregnancy/nitroprusside.html|archive-date=21 December 2016|url-status=live|access-date=14 December 2016}} High doses are not recommended for more than ten minutes.{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free | page=283 }} It works by increasing nitric oxide levels in the blood, which increases cGMP levels in cells, and causes dilation of blood vessels.

Sodium nitroprusside was discovered as early as 1850 and found to be useful in medicine in 1928.{{cite journal | vauthors = Friederich JA, Butterworth JF | title = Sodium nitroprusside: twenty years and counting | journal = Anesthesia and Analgesia | volume = 81 | issue = 1 | pages = 152–162 | date = July 1995 | pmid = 7598246 | doi = 10.1213/00000539-199507000-00031 | publisher = Lippincott Williams & Wilkins | doi-access = free }}{{cite book|url=https://books.google.com/books?id=pEpgDAAAQBAJ&pg=PA192|title=Critical Heart Disease in Infants and Children| vauthors = Nichols DG, Greeley WJ, Lappe DG, Ungerleider RM, Cameron DE, Spevak PJ, Wetzel RC |date=2006|publisher=Elsevier Health Sciences|isbn=9780323070072|edition=2|page=192|language=en}} It is on the World Health Organization's List of Essential Medicines.{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free}} Sodium nitroprusside is light sensitive, so it needs to be shielded from light to prevent degradation.{{cite book| vauthors = Lip G |title=Comprehensive Hypertension|publisher=Mosby|year=2007|isbn=978-0-323-03961-1|pages=761–774|language=English|doi=10.1016/B978-0-323-03961-1.X5001-6}}

Sodium nitroprusside is intravenously infused in cases of acute hypertensive crises.{{cite book | isbn = 978-0-85711-084-8 | title = British National Formulary (BNF) | author = Joint Formulary Committee | year = 2013 | publisher = Pharmaceutical Press | location = London, UK | edition = 65th }} Its effects are usually seen within a few minutes.{{cite book|title=Goodman and Gilman's The Pharmacological Basis of Therapeutics| vauthors = Brunton L, Chabner B, Knollman B |publisher=McGraw-Hill Professional|year=2010|isbn=978-0-07-162442-8|edition=12th|location=New York|title-link=Goodman and Gilman's The Pharmacological Basis of Therapeutics}}

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).{{cite book|title=Australian Medicines Handbook|publisher=The Australian Medicines Handbook Unit Trust|year=2013|isbn=978-0-9805790-9-3| veditors = Rossi S |edition=2013 |place=Adelaide }}

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,{{cite journal|vauthors=Ikram H, Low CJ, Crozier IG, Shirlaw T|date=February 1992|title=Hemodynamic effects of nitroprusside on valvular aortic stenosis|journal=Am. J. Cardiol.|volume=69|issue=4|pages=361–366|doi=10.1016/0002-9149(92)90234-P|pmid=1734649}} oesophageal varices,{{cite journal|vauthors=Sirinek KR, Adcock DK, Levine BA|date=January 1989|title=Simultaneous infusion of nitroglycerin and nitroprusside to offset adverse effects of vasopressin during portosystemic shunting|journal=Am. J. Surg.|volume=157|issue=1|pages=33–37|doi=10.1016/0002-9610(89)90416-9|pmid=2491934}} myocardial infarction,{{cite journal|vauthors=Yusuf S, Collins R, MacMahon S, Peto R|date=May 1988|title=Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomised trials|journal=Lancet|volume=331|issue=8594|pages=1088–92|doi=10.1016/S0140-6736(88)91906-X|pmid=2896919|s2cid=27098017}} pulmonary hypertension,{{cite journal|vauthors=Costard-Jäckle A, Fowler MB|date=January 1992|title=Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group|journal=J. Am. Coll. Cardiol.|volume=19|issue=1|pages=48–54|doi=10.1016/0735-1097(92)90050-W|pmid=1729345|doi-access=free}}{{cite journal|vauthors=Knapp E, Gmeiner R|date=February 1977|title=Reduction of pulmonary hypertension by nitroprusside|journal=International Journal of Clinical Pharmacology and Biopharmacy|volume=15|issue=2|pages=75–80|pmid=885667}}{{cite journal|display-authors=4|vauthors=Freitas AF Jr, Bacal F, Oliveira Júnior Jde L, Fiorelli AI, Santos RH, Moreira LF, Silva CP, Mangini S, Tsutsui JM, Bocchi EA|date=September 2012|title=Sildenafil vs. sodium before nitroprusside for the pulmonary hypertension reversibility test before cardiac transplantation|journal=Arquivos Brasileiros de Cardiologia|volume=99|issue=3|pages=848–56|doi=10.1590/S0066-782X2012005000076|pmid=22898992|doi-access=free}} respiratory distress syndrome in the newborn,{{cite journal|vauthors=Palhares DB, Figueiredo CS, Moura AJ|date=January 1998|title=Endotracheal inhalatory sodium nitroprusside in severely hypoxic newborns|journal=Journal of Perinatal Medicine|volume=26|issue=3|pages=219–224|doi=10.1515/jpme.1998.26.3.219|pmid=9773383|s2cid=31630912}}{{cite journal |vauthors=Benitz WE, Malachowski N, Cohen RS, Stevenson DK, Ariagno RL, Sunshine P |date=January 1985 |title=Use of sodium nitroprusside in neonates: efficacy and safety |url=https://www.jpeds.com/article/S0022-3476(85)80477-7/pdf |journal=J. Pediatr. |publisher=Elsevier Mosby |volume=106 |issue=1 |pages=102–110 |doi=10.1016/S0022-3476(85)80477-7 |pmid=3917495}} shock, and ergot toxicity.{{cite journal|vauthors=Merhoff GC, Porter JM|date=November 1974|title=Ergot intoxication: historical review and description of unusual clinical manifestations|journal=Ann. Surg.|volume=180|issue=5|pages=773–779|doi=10.1097/00000658-197411000-00011|pmc=1343691|pmid=4371616}}

Adverse effects by incidence and severity

Common

{{colbegin}}

• Bradyarrhythmia (low heart rate)
• Hypotension (low blood pressure)
• Palpitations
• Tachyarrhythmia (high heart rate)
• Apprehension
• Restlessness
• Confusion
• Dizziness
• Headache
• Somnolence
• Rash
• Sweating
• Thyroid suppression
• Muscle twitch
• Oliguria
• Renal azotemia

{{colend}}

Unknown frequency

{{colbegin}}

• Nausea
• Retching
• Anxiety
• Chest discomfort
• Paraesthesial warmth
• Abdominal pain
• Orthostatic hypotension
• ECG changes
• Skin irritation
• Flushing
• Injection site erythema
• Injection site streaking

{{colend}}

Serious

• Ileus
• Reduced platelet aggregation
• Haemorrhage
• Increased intracranial pressure
• Metabolic acidosis
• Methaemoglobinaemia
• Cyanide poisoning
• Thiocyanate toxicity

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.

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.{{cite journal|display-authors=4|vauthors=Sass N, Itamoto CH, Silva MP, Torloni MR, Atallah AN|date=March 2007|title=Does sodium nitroprusside kill babies? A systematic review|journal=Sao Paulo Medical Journal|volume=125|issue=2|pages=108–111|doi=10.1590/S1516-31802007000200008|pmid=17625709|doi-access=free|pmc=11014698 }} Some evidence suggests sodium nitroprusside use in critically ill children may be safe, even without monitoring of cyanide level.{{cite journal|vauthors=Thomas C, Svehla L, Moffett BS|date=September 2009|title=Sodium nitroprusside induced cyanide toxicity in pediatric patients|journal=Expert Opinion on Drug Safety|volume=8|issue=5|pages=599–602|doi=10.1517/14740330903081717|pmid=19645589|s2cid=5334690}}

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.

Due to its cyanogenic nature, overdose may be particularly dangerous. Treatment of sodium nitroprusside overdose includes the following:{{cite journal|vauthors=Rindone JP, Sloane EP|date=April 1992|title=Cyanide toxicity from sodium nitroprusside: Risks and management|journal=Ann. Pharmacother.|volume=26|issue=4|pages=515–519|doi=10.1177/106002809202600413|pmid=1533553|s2cid=35273460}}

• Discontinuing sodium nitroprusside administration
• Buffering the cyanide by using sodium nitrite to convert haemoglobin to methaemoglobin as much as the patient can safely tolerate
• 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.

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.{{cite web|url=http://www.rxlist.com/nitropress-drug/clinical-pharmacology.htm|title=Nitropress (Nitroprusside Sodium) Drug Information: Clinical Pharmacology – Prescribing Information|date=4 July 2009|work=RxList|publisher=RxList Inc.|archive-url=https://web.archive.org/web/20140421234044/http://www.rxlist.com/nitropress-drug/clinical-pharmacology.htm|archive-date=21 April 2014|url-status=live|access-date=21 November 2013}} Hydroxocobalamin can be administered to reduce the risk of thiocyanate toxicity induced by nitroprusside.{{cite journal | vauthors = Zerbe NF, Wagner BK | title = Use of vitamin B12 in the treatment and prevention of nitroprusside-induced cyanide toxicity | journal = Critical Care Medicine | volume = 21 | issue = 3 | pages = 465–467 | date = March 1993 | pmid = 8440119 | doi = 10.1097/00003246-199303000-00027 | s2cid = 43866386 }}

As a result of its breakdown to nitric oxide (NO), sodium nitroprusside has potent vasodilating effects on arterioles and venules (arterial more than venous), whereas other nitrates exhibit more selectivity for veins (e.g. nitroglycerin).{{cite web|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6a44bcac-a0e1-4069-5691-db7b83dbb4b7|title=NITROPRESS (sodium nitroprusside) injection, solution, concentrate|date=January 2011|work=DailyMed|publisher=Hospira|archive-url=https://web.archive.org/web/20131203013703/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6a44bcac-a0e1-4069-5691-db7b83dbb4b7|archive-date=3 December 2013|url-status=dead|access-date=20 November 2013}}{{cite web|title=DBL® SODIUM NITROPRUSSIDE FOR INJECTION BP|work=TGA eBusiness Services|publisher=Hospira Australia Pty Ltd.|date=22 April 2010|access-date=20 November 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-04026-3|format=PDF|url-status=live|archive-url=https://web.archive.org/web/20170910175429/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-04026-3|archive-date=10 September 2017}}{{cite web|url=http://reference.medscape.com/drug/nipride-nitropress-nitroprusside-sodium-342312|title=Nipride RTU, Nitropress (nitroprusside sodium) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|archive-url=https://web.archive.org/web/20131203001417/http://reference.medscape.com/drug/nipride-nitropress-nitroprusside-sodium-342312|archive-date=3 December 2013|url-status=live|access-date=20 November 2013}}{{cite web|url=http://labeling.pfizer.com/ShowLabeling.aspx?id=4618|website=labeling.pfizer.com|access-date=1 August 2019|title=Nitropress- sodium nitroprusside injection, solution, concentrate }}

Sodium nitroprusside breaks down in circulation to release nitric oxide (NO). It does this by binding to oxyhaemoglobin to release cyanide, methaemoglobin and nitric oxide. NO activates guanylate cyclase in vascular smooth muscle and increases intracellular production of cGMP. cGMP activates protein kinase G which activates phosphatases which inactivate myosin light chains. Myosin light chains are involved in smooth muscle contraction. The result is vascular smooth muscle relaxation, which allow vessels to dilate.{{cite journal|vauthors=Murad F|date=July 1986|title=Cyclic Guanosine Monophosphate as a Mediator of Vasodilation|journal=J. Clin. Investig.|volume=78|issue=1|pages=1–5|doi=10.1172/JCI112536|pmc=329522|pmid=2873150}} This mechanism is similar to that of phosphodiesterase 5 (PDE5) inhibitors such as sildenafil (Viagra) and tadalafil (Cialis), which elevate cGMP concentration by inhibiting its degradation by PDE5.{{cite journal|vauthors=Kukreja RC, Salloum FN, Das A|date=May 2012|title=Cyclic Guanosine Monophosphate Signaling and Phosphodiesterase-5 Inhibitors in Cardioprotection|journal=Journal of the American College of Cardiology|volume=59|issue=22|pages=1921–1927|doi=10.1016/j.jacc.2011.09.086|pmc=4230443|pmid=22624832}}

A role for NO in various common psychiatric disorders including schizophrenia,{{cite journal|vauthors=Bernstein HG, Bogerts B, Keilhoff G|date=Oct 2005|title=The many faces of nitric oxide in schizophrenia. A review|journal=Schizophrenia Research|volume=78|issue=1|pages=69–86|doi=10.1016/j.schres.2005.05.019|pmid=16005189|s2cid=42764954}}{{cite journal|vauthors=Silberberg G, Ben-Shachar D, Navon R|date=October 2010|title=Genetic analysis of nitric oxide synthase 1 variants in schizophrenia and bipolar disorder|journal=Am. J. Med. Genet. B|volume=153B|issue=7|pages=1318–1328|doi=10.1002/ajmg.b.31112|pmid=20645313|s2cid=205325558}}{{cite journal|display-authors=4|vauthors=Bernstein HG, Keilhoff G, Steiner J, Dobrowolny H, Bogerts B|date=November 2011|title=Nitric oxide and schizophrenia: present knowledge and emerging concepts of therapy|journal=CNS & Neurological Disorders Drug Targets|volume=10|issue=7|pages=792–807|doi=10.2174/187152711798072392|pmid=21999729}}{{cite journal|vauthors=Coyle JT|date=July 2013|title=Nitric Oxide and Symptom Reduction in Schizophrenia|journal=JAMA Psychiatry|volume=70|issue=7|pages=664–665|doi=10.1001/jamapsychiatry.2013.210|pmid=23699799}} bipolar disorder{{cite journal|display-authors=4|vauthors=Yanik M, Vural H, Tutkun H, Zoroğlu SS, Savaş HA, Herken H, Koçyiğit A, Keleş H, Akyol O|date=February 2004|title=The role of the arginine-nitric oxide pathway in the pathogenesis of bipolar affective disorder|journal=European Archives of Psychiatry and Clinical Neuroscience|volume=254|issue=1|pages=43–47|doi=10.1007/s00406-004-0453-x|pmid=14991378|s2cid=24592011}}{{cite journal|display-authors=4|vauthors=Fontoura PC, Pinto VL, Matsuura C, Resende Ade C, de Bem GF, Ferraz MR, Cheniaux E, Brunini TM, Mendes-Ribeiro AC|date=October 2012|title=Defective Nitric Oxide–Cyclic Guanosine Monophosphate Signaling in Patients With Bipolar Disorder: A Potential Role for Platelet Dysfunction|journal=Psychosom. Med.|volume=74|issue=8|pages=873–877|doi=10.1097/PSY.0b013e3182689460|pmid=23023680|s2cid=37347633}}{{cite journal|display-authors=4|vauthors=Bielau H, Brisch R, Bernard-Mittelstaedt J, Dobrowolny H, Gos T, Baumann B, Mawrin C, Bernstein HG, Bogerts B, Steiner J|date=June 2012|title=Immunohistochemical evidence for impaired nitric oxide signaling of the locus coeruleus in bipolar disorder|journal=Brain Research|volume=1459|pages=91–99|doi=10.1016/j.brainres.2012.04.022|pmid=22560594|s2cid=25790297}} and major depressive disorder{{cite journal|vauthors=Gałecki P, Maes M, Florkowski A, Lewiński A, Gałecka E, Bieńkiewicz M, Szemraj J|date=March 2011|title=Association between inducible and neuronal nitric oxide synthase polymorphisms and recurrent depressive disorder|journal=Journal of Affective Disorders|volume=129|issue=1–3|pages=175–82|doi=10.1016/j.jad.2010.09.005|pmid=20888049}}{{cite journal|vauthors=Dhir A, Kulkarni SK|date=April 2011|title=Nitric oxide and major depression|journal=Nitric Oxide|volume=24|issue=3|pages=125–131|doi=10.1016/j.niox.2011.02.002|pmid=21335097}}{{cite journal|display-authors=4|vauthors=Savaş HA, Herken H, Yürekli M, Uz E, Tutkun H, Zoroğlu SS, Ozen ME, Cengiz B, Akyol O|year=2002|title=Possible role of nitric oxide and adrenomedullin in bipolar affective disorder|journal=Neuropsychobiology|volume=45|issue=2|pages=57–61|doi=10.1159/000048677|pmid=11893860|s2cid=7505572}} 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. Such a role is also supported by the findings of the recent SNP clinical trial.{{cite journal|display-authors=4|vauthors=Hallak JE, Maia-de-Oliveira JP, Abrao J, Evora PR, Zuardi AW, Crippa JA, Belmonte-de-Abreu P, Baker GB, Dursun SM|date=8 May 2013|title=Rapid improvement of acute schizophrenia symptoms after intravenous sodium nitroprusside: A randomized, double-blind, placebo-controlled trial|journal=JAMA Psychiatry|volume=70|issue=7|pages=E3–E5|doi=10.1001/jamapsychiatry.2013.1292|pmid=23699763|doi-access=free}}

File:Sodium-nitroprusside-xtal-3D-balls-A.png]]

File:Nitroprusside-anion-from-xtal-3D-vdW.png

Nitroprusside is an inorganic compound with the chemical formula Na₂[Fe(CN)₅NO], usually encountered as the dihydrate, Na₂[Fe(CN)₅NO]·2H₂O.{{cite journal|vauthors=Butler AR, Megson IL|year=2002|title=Non-Heme Iron Nitrosyls in Biology|journal=Chem. Rev.|volume=102|issue=4|pages=1155–1165|doi=10.1021/cr000076d|pmid=11942790}} This red-colored sodium salt dissolves in water or ethanol to give solutions containing the free complex dianion [Fe(CN)₅NO]²⁻.

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°{{cite journal|vauthors=Navaza A, Chevrier G, Alzari PM, Aymonino PJ|year=1989|title=Single-crystal neutron diffraction structure of sodium pentacyanonitrosylferrate(2-) (sodium nitroprusside) dihydrate|journal=Acta Crystallogr. C|volume=45|issue=6|pages=839–841|doi=10.1107/S0108270188013691|bibcode=1989AcCrC..45..839N }}). The anion possesses idealized C_4vsymmetry.

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. Consequently, iron is assigned an oxidation state of +2. The iron center has a diamagnetic low-spin d⁶ electron configuration, although a paramagnetic long-lived metastable state has been observed by EPR spectroscopy.{{cite journal|vauthors=Tritt-Goc J, Piślewski N, Hoffmann SK|year=1997|title=EPR evidence of the paramagnetism of a long-living metastable excited state of a sodium nitroprusside single crystal|journal=Chemical Physics Letters|volume=268|issue=5–6|pages=471–474|bibcode=1997CPL...268..471T|doi=10.1016/S0009-2614(97)00217-0}}

The chemical reactions of sodium nitroprusside are mainly associated with the NO ligand.{{cite journal|vauthors=Coppens P, Novozhilova I, Kovalevsky A|year=2002|title=Photoinduced Linkage Isomers of Transition-Metal Nitrosyl Compounds and Related Complexes|journal=Chemical Reviews|volume=102|issue=4|pages=861–883|doi=10.1021/cr000031c|pmid=11942781}} For example, addition of S²⁻ 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⁻. Roussin's red salt (K₂[Fe₂S₂(NO)₄]) and Roussin's black salt (NaFe₄S₃(NO)₇) are related iron nitrosyl complexes. The former was first prepared by treating nitroprusside with sulfur.{{cite journal|vauthors=Reihlen H, von Friedolsheim A|year=1927|title=Über komplexe Stickoxydverbindungen und das sogenannte einwertige Eisen|journal=Justus Liebigs Annalen der Chemie|volume=457|pages=71–82|doi=10.1002/jlac.19274570103}}

Sodium nitroprusside can be synthesized by digesting a solution of potassium ferrocyanide in water with nitric acid, followed by neutralization with sodium carbonate:{{cite book|title=Handbook of Preparative Inorganic Chemistry|publisher=Academic Press|year=1963| veditors = Brauer G |edition=2nd|volume=2|location=New York|pages=1768|chapter=Sodium Nitrosyl Cyanoferrate|lccn=63014307 |chapter-url=https://archive.org/details/Handbook_of_Preparative_Inorganic_Chemistry_1_2_Brauer/page/n1813}}

:{{chem2 | K4[Fe(CN)6] + 6 HNO3 -> H2[Fe(CN)5(NO)] + CO2 + NH4NO3 + 4 KNO3 }}

:{{chem2 | H2[Fe(CN)5NO] + Na2CO3 -> Na2[Fe(CN)5(NO)] + CO2 + H2O }}

Alternatively, the nitrosyl ligand can be introduced using nitrite:{{cite book|title=Inorganic Chemistry| vauthors = Housecroft CE, Sharpe AG |publisher=Pearson|year=2008|isbn=978-0-13-175553-6|edition=3rd|page=721|chapter=Chapter 22: d-Block metal chemistry: the first row metals }}

:{{chem2 | [Fe(CN)6](4-) + H2O + NO2- -> [Fe(CN)5(NO)](2-) + CN- + 2 HO- }}

File:Sodium nitroprusside Mössbauer spectrum.svg

Sodium nitroprusside is often used as a reference compound for the calibration of Mössbauer spectrometers.{{cite book|url=https://www.nist.gov/srm/upload/SP260-13-2.PDF|title=NBS Misc. Publ. 260-13: Mossbauer Spectroscopy Standard for the Chemical Shift of Iron Compounds| vauthors = Spijkerman JJ, Snediker DK, Ruegg FC, DeVoe JR |publisher=National Institute of Standards and Technology|archive-url=https://web.archive.org/web/20160304073048/http://www.nist.gov/srm/upload/SP260-13-2.PDF|archive-date=4 March 2016|url-status=live}} 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.{{cite journal|vauthors=Woike T, Krasser W, Bechthold PS, Haussühl S|year=1984|title=Extremely Long-Living Metastable State of Na₂[Fe(CN)₅NO]·2H₂O Single Crystals: Optical|journal=Physical Review Letters|volume=53|issue=18 |pages=1767–1770|bibcode=1984PhRvL..53.1767W|doi=10.1103/PhysRevLett.53.1767}}

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 biofilms by acting as a nitric oxide donor.{{cite journal|display-authors=4|vauthors=Barraud N, Hassett DJ, Hwang SH, Rice SA, Kjelleberg S, Webb JS|year=2006|title=Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa|journal=Journal of Bacteriology|volume=188|issue=21|pages=7344–53|doi=10.1128/JB.00779-06|pmc=1636254|pmid=17050922}}{{cite journal|display-authors=4|vauthors=Chua SL, Liu Y, ((Yam JKH)), Tolker-Nielsen T, Kjelleberg S, Givskov M, Yang L|year=2014|title=Dispersed cells represent a distinct stage in the transition from bacterial biofilm to planktonic lifestyles|journal=Nature Communications|volume=5|pages=4462|doi=10.1038/ncomms5462|pmid=25042103|bibcode=2014NatCo...5.4462C|doi-access=free}}

Sodium nitroprusside is also used as an analytical reagent under the name sodium nitroferricyanide for the detection of methyl ketones, amines, and thiols. It is also used as a catalyst in the quantitative determination of ammonia in water samples via the phenate method.{{cite book|title=Standard Methods for the Examination of Water and Wastewater|year=2017|isbn=978-0-87553-287-5|pages=4500-NH3 F., 4–114| veditors = Rice EW, Bridgewater L, Easton AD | publisher = American Public Health Association }}

The nitroprusside reaction is used for the identification of ketones in urine testing.{{cite book|url=https://books.google.com/books?id=spsD4WQbL0QC&pg=PA98|title=Clinical Biochemistry of Domestic Animals|publisher=Academic Press|year=2008|isbn=9780080568829|veditors=Kaneko JJ, Harvey JW, Bruss ML|edition=6th|pages=98}} 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.{{cite journal|vauthors=Rothera AC|year=1908|title=Note on the sodium nitro-prusside reaction for acetone|journal=J. Physiol. (Lond.)|volume=37|issue=5–6|pages=491–494|doi=10.1113/jphysiol.1908.sp001285|pmc=1533603|pmid=16992945}}

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").{{cite book|title=Clinical Methods: The History, Physical, and Laboratory Examinations|vauthors=Comstock JP, Garber AJ|publisher=Butterworths|year=1990|isbn=9780409900774|veditors=Walker HK, Hall WD, Hurst JW|edition=3rd|location=Boston|chapter=Chapter 140. Ketonuria|pmid=21250091|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK247/|via=NCBI Bookshelf}}

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.{{cite book|url=https://books.google.com/books?id=p6AEfAEACAAJ|title=Textbook of Biochemistry for Dental/Nursing/Pharmacy Students|vauthors=Chatterjea MN|date=1 January 2004|publisher=Jaypee Brothers Publishers|isbn=978-81-8061-204-6|location=India|page=51|oclc=1027921456}}{{cite book|url=https://books.google.com/books?id=QqXpWJHICUYC&pg=PA56|title=Biochemistry|vauthors=Das D|publisher=Academic Publishers|year=1980|isbn=978-93-80599-17-5|page=56}}{{cite book|url=https://books.google.com/books?id=Acf9BkEqJWYC&pg=PA64|title=Question Bank of Biochemistry|vauthors=Joshi RA|publisher=New Age International|year=2006|isbn=978-81-224-1736-4|page=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 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.{{cite journal|display-authors=4|vauthors=Finocchiaro R, D'Eufemia P, Celli M, Zaccagnini M, Viozzi L, Troiani P, Mannarino O, Giardini O|year=1998|title=Usefulness of cyanide-nitroprusside test in detecting incomplete recessive heterozygotes for cystinuria: a standardized dilution procedure|journal=Journal of Urology and Research|volume=26|issue=6|pages=401–5|doi=10.1007/s002400050076|pmid=9879820|s2cid=28323457}}

Sodium nitroprusside is also used to detect amines, including those in illicit drugs. This compound is thus used as a stain to indicate amines in thin layer chromatography.{{cite web|url=http://lcso.epfl.ch/files/content/sites/lcso/files/load/TLC_Stains.pdf|title=TLC Visualization Reagents|publisher=École Polytechnique Fédérale de Lausanne|archive-url=https://web.archive.org/web/20150513014330/http://lcso.epfl.ch/files/content/sites/lcso/files/load/TLC_Stains.pdf|archive-date=13 May 2015|url-status=dead|access-date=21 November 2013}} Sodium nitroprusside is similarly used as a presumptive test for the presence of alkaloids (amine-containing natural products) common in illicit substances.{{cite journal|vauthors=O'Neala CL, Croucha DJ, Fatahb AA|year=2000|title=Validation of twelve chemical spot tests for the detection of drugs of abuse|journal=Forensic Science International|volume=109|issue=3|pages=189–201|doi=10.1016/S0379-0738(99)00235-2|pmid=10725655}} The test, called Simon's test, is performed by adding 1 volume of a solution of sodium nitroprusside and acetaldehyde in deionized water to a suspected drug, followed by the addition of 2 volumes of an aqueous sodium carbonate solution. The test turns blue for some secondary amines. The most common secondary amines encountered in forensic chemistry include 3,4-methylenedioxymethamphetamine (MDMA, the main component in ecstasy) and phenethylamines such as methamphetamine. Sodium nitroprusside is also useful in the identification the mercaptans (thiol groups) in the nitroprusside reaction.

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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{{Nonsympatholytic vasodilatory antihypertensives}}

{{Nitric oxide signaling}}

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