Action of Nitroprusside

In bioinorganic terms, the mechanistic interest lies in the involvement, and necessity of the NO group. The biochemical explanations have evolved along with the more detailed understanding of the factors involved in muscle function. The presently held opinion on nitroprusside, and nitrites, is that activation of guanylate cyclase (cyclic GMP) [52] occurs which results in relaxation, perhaps by a chain of events eventually reflected as a lowering of Ca concentration and resulting in muscle contraction [53]. 

Structure—activity relationships have received scant attention. There is general agreement on the rapid breakdown of nitroprusside in vivo, yet all biological data indicate a nitrite (RN02)-type action. Nitroprusside must pass into the cell intact [54], but then the question is whether liberated 

NO or bound NO is responsible for the biological effects. Experiments in vitro showed that pe(CN)5L] L = H2O or NH3, and the Ru and Mo analogues of nitroprusside, relaxed smooth vascular muscle, albeit to a lesser extent than the parent iron complex [31, 32]. Further substitution of NO by NO2 and NOS also gave active iron-containing complexes [55]. In this latter study, [Mn(CN)5NO] was found to be inactive. The variation of charge, and perhaps also p(NO), in these complexes make any evaluation difficult. 

A recent fascinating mechanism has been proposed whereby compounds containing NO, released perhaps by thiols [56] and in the active form of nitrosothiols [57, 58], react with heme to give nitrosylheme, which is a potent activator of guanylate cyclase [59]. Guanylate cyclase is considered to be heme-dependent, and heme-enriched enzyme is markedly more activated than heme-deficient enzyme [59]. Activation may be similar to that shown by Fe(protoporphyrin IX) and there are similarities with respect to kinetic parameters [60]. Reference 59 details the argument. 

Miscellaneous biological effects of well-defined metal complexes include nitroprusside as vasodilator, neuromuscular blocking by large metal cations, and diuretic effects of mercury complexes. Their mechanisms of action all involve complicated inhibition of enzymes. 

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Sodium nitroprusside (SNP), which is also known as Nipruss or Nipride to medical practitioners, was the first iron nitrosyl complex, prepared as far back as 1850 by Playfair [40]. The hypotensive property of SNP was first demonstrated by Johnson [41] in 1929. It was shown that application of a moderate dose of SNP reduces the blood pressure of a severely hypertensive patient without any side effect [42]. Since that time considerable research has been carried out to understand the mode of action of nitroprusside and its metabolic fate. SNP is now regarded as a potent vasodilator that causes muscle relaxation by releasing NO which activates the cytosolic isozyme of guanylyl cyclase [43-46]. 

In the case of mercury-induced diuresis interference with ATPase and subsequent imbalance of the Na/K transport system may be involved. The large cations may also affect ATPases, in this case that responsible for Ca transport. The calcium blocking could increase the release of neurotransmitters such as acetylcholine. The mechanism of action of nitroprusside may involve a chain of events eventually leading to a lowering of calcium ion concentration and muscle contraction. 

Note cautiously the characteristic odour of acetaldehyde which this solution possesses. Then with the solution carry out the following general tests for aldehydes described on p. 341 Test No. I (SchiflF s reagent). No. 3 (Action of sodium hydroxide). No. 4 (Reduction of ammoniacal silver nitrate). Finally perform the two special tests for acetaldehyde given on p. 344 (Nitroprusside test and the Iodoform reaction). 

The action of 30% nitric acid on hexacyanoferrates(II) or (III) to produce penta-cyanonitrosylferrate(II) ( nitroprusside ) is violent. 

L A 50-year-old male ls seen in the emergency department (ED) with a blood pressure of 260/160 mmHg. Blurring optic discs with indistinct margins are seen on ophthalmologic examination. An intravenous drip of sodium nitroprusside is administered. What is the mechanism of action of sodium nitroprusside ... 

Nitroprusside has a rapid onset and a duration of action of less than 10 minutes, which necessitates use of continuous IV infusions. It should be initiated at a low dose (0.1 to 0.2 mcg/kg/min) to avoid excessive hypotension, and then increased by small increments (0.1 to 0.2 mcg/kg/min)... 

The therapeutic effects of sodium nitroprusside depend on release of nitric oxide which relaxes vascular muscle. Sodium nitroprusside is best formulated as a nitrosonium (NO+) complex. Its in vivo activation is probably achieved by reduction to [Fe(CN)5NO]3, which then releases cyanide to give [Fe(CN)4NO]2, which in turn releases nitric oxide and additional CN to yield aquated Fe(II) species and [Fe(CN)6]4 (502). There are problems associated with its use, namely reduced activity due to photolysis (501) and its oxidative breakdown due to the action of an activated immune system (503), both of which release cyanide from the low-spin d6 iron complex. 

The onset of the hypotensive action of sodium nitroprusside is rapid, within 30 seconds after intravenous administration. If a single dose is given, the action lasts for only a couple of minutes. Therefore, sodium nitroprusside must be administered by continuous intravenous infusion. After the infusion is stopped, blood pressure returns to predrug levels within 2 to 3 minutes. 

Figure 8.2 Proposed mode of action of the organic nitrates, nitroglycerin and nitroprusside. Note that nitroprusside acts as a direct donor of nitric oxide (NO), whereas the nitrates require the presence of nitrosothiols to produce NO.

Sodium nitroprusside was first prepared and investigated in the middle of the nineteenth century, and a comprehensive summary of the earlier chemical investigations has been published (17). Up to 1910-1930, the addition reactions of bases to NP were explored, involving the characterization of colored intermediates (e.g., with SH-, SR-, and SO3 ), useful for analytical purposes. The hypotensive action of NP was first demonstrated in 1929, and a considerable research effort has attempted to establish the mode of action of NP and its metabolic fate. Questions still arise on the mechanism of NO release from NP in the biological fluids, and we refer to them below. New accounts dealing with modern structural and reactivity issues associated with the coordination of nitrosyl in NP and other complexes have appeared (18-20). From the bioinorganic and environmental viewpoint, nitrosyl iron complexes have been studied with... 

Detection.—Sulphur in the free state is readily recognisable by its general appearance and characteristics, and especially by its combustion to sulphur dioxide. Both in mixtures and compounds the presence of the element can be demonstrated by heating with charcoal and an alkali carbonate,2 or even better, on a small scale, by heating with an equal bulk of sodium or potassium,3 or with powdered iron 4 in each case some of the sulphur is converted into sulphide, which may be detected by the action of an aqueous extract on mercury or silver, or on sodium nitroprusside the metals are blackened, whilst the nitro-prusside is very sensitive in giving a purple coloration (see p. 62). Alternatively, the solution of the alkali sulphide may be acidified and tests applied for hydrogen sulphide to the vapours evolved on warming. 

Even small amounts of alkali convert the nitroprusside ion to pentacyanonitroferrate (II) which, in turn, is changed to ferrocyanide by the action of cyanide. 

Nitroprusside [nye troe PRUSS ide] is administered intravenously, and causes prompt vasodilation, with reflex tachycardia. It is capable of reducing blood pressure in all patients, regardless of the cause of hypertension. The drug has little effect outside the vascular system, acting equally on arterial and venous smooth muscle. [Note Because nitroprusside also acts on the veins, it can reduce cardiac preload.] Nitroprusside is metabolized rapidly (t1/2 of minutes) and requires continuous infusion to maintain its hypotensive action. Sodium nitroprusside exerts few adverse effects except for those of hypotension caused by overdose. Nitroprusside metabolism results in cyanide ion production, although cyanide toxicity is rare and can be effectively treated with an infusion of sodium thiosulfate to produce thiocyanate, which is less toxic and is eliminated by the kidneys (Figure 19.14). [Note Nitroprusside is poisonous if given orally because of its hydrolysis to cyanide.]... 

Sodium nitroprusside (Na2[Fe(CN)s NO] 2H2O), possibly the best known of all nitrosyl complexes,107 is made either by the action of nitric acid (equation 8) or sodium nitrite (equations 9 and 10) on the hexacyanoferrate(II) anion. The equilibria (9) and (10) are driven to the right by the addition of barium chloride to the reaction mixture and by removing HCN in a stream of C02 passing through the hot solution. The overall process108 is shown in equation (11). 

Sulphide, (i) Dilute H2S04 on solid, and action of H2S on lead or cadmium acetate paper (IV.6, 1). (ii) Sodium nitroprusside test (IV.6, 6). 

The monohydrate has been obtained in crystalline form in several ways, such as, for example, by the action of concentrated potassium hydroxide solution upon potassium nitroprusside.2... 

Properties.—An aqueous solution of sodium nitroprusside deposits Prussian blue on exposure to light. In the presence of alkali sulphides— as, for example, ammonium sulphide—it yields a beautiful purple colour, which is very characteristic, and so sensitive that the presence of 0 0000018 gram of hydrogen sulphide in 0 004 c.c. can easily be detected.2 Ammonium hydroxide does not hinder the colour formation, but caustic alkalies destroy it. It gradually fades on standing, in consequence of oxidation of the sulphide to sulphite. The composition of the purple substance is uncertain, but Hofmann 3 suggests the formula Na3[Fe(CN)5(0 N.SNa)], since, by the action of thio-urea, CS(NH2)2, upon sodium nitroprusside, he obtained the complex derivative Na3[Fe(CN)5(0 N.SCNH.NH2)], as a carmine-red powder, closely similar to the substance under discussion.4... 

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