Nitroprusside, action

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)... 

Nitroprusside is the agent of choice for minute- to-minute control in most cases. It is usually given as a continuous IV infusion at a rate of 0.25 to 10 mcg/kg/min. Its onset of hypotensive action is immediate and disappears within 1 to 2 minutes of discontinuation. When the infusion must be continued longer than 72 hours, serum thiocyanate levels should be measured, and the infusion should be discontinued if the level exceeds 12 mg/dL. The risk of thiocyanate toxicity is increased in patients with impaired kidney function. Other adverse effects include nausea, vomiting, muscle twitching, and sweating. 

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]. 

Although its mode is uncertain, sodium nitroprusside (SNP) is one of the most valuable vasodilators. Its use in clinical practice is suspect as the cyano-ligands render cyanide poisoning a possibility. However for ex vivo experiments this consideration is less important but the possibility of some biological action due to these ions remains. The mechanism by which SNP acts as a vasodilator is not fully understood. With the discovery of a physiological role for NO there has been renewed interest in mechanistic studies of reactions involving SNP and a re-examination of studies of SNP undertaken before 1987. So far, only one simple reaction leading to the release... 

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. 

Nitric oxide coordinated to iron modifies, in a striking manner, the properties and reactivity of free NO (Sec. 6.2). Probably the most famous such coordinated entity is the nitroprusside ion, Fe(CN)5NO . An incisive review of its reactions particularly related to its hypertensive action (it reduces blood pressure of severely hypertensive patients) is available. Nitroprusside ion reacts with a variety of bases... 

The drugs of this class (hydralazine and sodium nitroprusside) lower arterial blood pressure primarily by direct spasmolytic action on smooth musculature of arterioles, which leads to a reduction of resistance of peripheral vessels by causing dilation. Diastolic pressure is usually lowered more than the systolic pressure. 

Sodium nitroprusside (SNP) is both a venous and an arterial vasodilator. An important part of its vasodilator action is caused by the release of nitric oxide (NO), similarly as for the organic nitrates. SNP can only be administered via the intravenous route. It is a rapidly and short acting vasodilator. It has been used in the treatment of hypertensive emergencies and in the management of myocardial ischaemia. In spite of its vasodilator action it hardly influences heart rate, in contrast to hydralazine and minoxidil. The dosage of SNP should not be higher than 3 pg/kg/min within 48 h, in order to avoid the rise of cyanide ions and thiocyanate in the blood. 

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. 

In contrast to hydralazine, minoxidil, and diazoxide, sodium nitroprusside relaxes venules as well as arterioles. Thus, it decreases both peripheral vascular resistance and venous return to the heart. This action limits the increase in cardiac output that normally follows vasodilator therapy. Sodium nitroprusside does not inhibit sympathetic reflexes, so heart rate may increase following its administration even though cardiac output is not... 

Close supervision is required when nitroprusside is used because of the drug s potency and short duration of action. 

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.

If a (3-adrenoceptor antagonist is administered prior to sufficient ol-radrenoceptor blockade, a hypertensive episode may be precipitated with cardiac failure and pulmonary oedema. Most intravenous anaesthetic agents have been used safely, but ketamine is contraindicated. Sodium nitroprusside can be used to achieve arteriolar dilation. Esmolol, a pi-selective antagonist with very short duration of action, is administered intravenously to prevent cardiac arrhythmias intra-operatively. After tumour removal, volume administration should be aggressive to maintain haemodynamic stability, and a noradrenaline infusion may be required. 

Sodium nitroprusside is a powerful parenterally administered vasodilator that is used in treating hypertensive emergencies as well as severe heart failure. Nitroprusside dilates both arterial and venous vessels, resulting in reduced peripheral vascular resistance and venous return. The action occurs as a result of activation of guanylyl cyclase, either via release of nitric oxide or by direct stimulation of the enzyme. The result is increased intracellular cGMP, which relaxes vascular smooth muscle (Figure 12-2). 

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. 

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