Sodium nitroprusside, cyanide

Used in cyanide (including from sodium nitroprusside) intoxication... 

Sodium nitroprusside 0.25-10 mcg/kg/minute as IV infusion11 Immediate 1-2 minutes Nausea, vomiting, muscle twitching, sweating, thiocyanate and cyanide intoxication Most hypertensive emergencies use with caution with high intracranial pressure or azotemia... 

Cyanide compounds have been prescribed by physicians for treatment of hypertension and cancer (Sprine et al. 1982). Sodium nitroprusside (Na2Fe(CN)5NO 2H20) was widely used for more than 30 years to treat severe hypertension and to minimize bleeding during surgery (Solomon-son 1981 Vesey 1987). Laetrile, an extract of ground apricot kernels, has been used for cancer chemotherapy and, in deliberate high intakes, as an attempted suicide vehicle (Gee 1987). 

Elzubeir, E.A. and R.H. Davis. 1988a. Effect of dietary sodium nitroprusside as a source of cyanide on the selenium status of chicks given diets of varying selenium concentration. Brit. Poult. Sci. 29 769-777. 

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... 

Hydrogen cyanide (HCN) is a colorless, rapidly acting, highly poisonous gas or liquid that has an odor of bitter almonds. Most HCN is used as an intermediate at the site of production. Major uses include the manufacture of nylons, plastics, and fumigants. Exposures to HCN may occur in industrial situations as well as from cigarette smoke, combustion products, and naturally occurring cyanide compounds in foods. Sodium nitroprusside (Na2[Fe(CN)5 N0]-2H20), which has been used as an antihypertensive in humans, breaks down into nonionized HCN. 

HCN in the blood is almost completely contained in the red blood cells where it is bound to methemoglobin. Immediately after infusion of sodium nitroprusside into patients, 98.4% of the blood cyanide was found in the red blood cells (Vesey et al. 1976). At normal physiological levels of body methemoglobin (0.25% to 1% of the hemoglobin), a human adult can bind about 10 mg of HCN (Schulz 1984). 

HCN is detoxified to thiocyanate (SCN ) by the mitochondrial enzyme rhodanese rhodanese catalyzes the transfer of sulfur from thiosulfate to cyanide to yield thiocyanate, which is relatively nontoxic (Smith 1996). The rate of detoxification of HCN in humans is about 1 pg/kg/min (Schulz 1984) or 4.2 mg/h, which, the author states, is considerably slower than in small rodents. This information resulted from reports of the therapeutic use of sodium nitroprusside to control hypertension. Rhodanese is present in the liver and skeletal muscle of mammalian species as well as in the nasal epithelium. The mitochondria of the nasal and olfactory mucosa of the rat contain nearly seven times as much rhodanese as the liver (Dahl 1989). The enzyme rhodanese is present to a large excess in the human body relative to its substrates (Schulz 1984). This enzyme demonstrates zero-order kinetics, and the limiting factor in the detoxification of HCN is thiosulphate. However, other sulfur-containing substrates, such as cystine and cysteine, can also serve as sulfur donors. Other enzymes, such as 3-mercapto-pyruvate sulfur transferase, can convert... 

Thiocyanate in blood 40 (rg/l 00 mL in control nonsmokers 100 (rg/l00 mL in control smokers 420 (ig/100 mL in cyanide-exposed nonsmokers 480 pg/100 mL in cyanide-exposed smokers Maehly and Swensson (1970) Found no relationship between exposure and blood cyanide levels Blood CN—of control nonsmokers ranged from 3.5-10.1 pg/100 mL Blood CN—of control smokers ranged from 2.0-13.0 pg/100 mL Blood CN—of control and cyanide-exposed workers combined ranged from 2.0-15 pg/100 mL (Separate data were not provided for cyanide workers) Aitken et al. (1977) Male and female patients, ages 13-66, presurgery mean 2.7 pg/100 mL Following infusion of sodium nitroprusside 13-205 pg/100 mL Metabolic acidosis at >90 pg/100 mL Nitroprusside doses 12-783 pg/kg (0.8-9.8 pg/kg/min over durations of 15 to 86 min) ... 

Schulz, V., R.Gross, T.Pasch, J.Busse, and G.Loeschcke. 1982. Cyanide toxicity of sodium nitroprusside in therapeutic use with and without sodium thiosulphate. Klin. Wochensch. 60 1393-1400. 

Vesey, C.J., P.V.Cole, P.J.Simpson. 1976. Cyanide and thiocyanate concentrations following sodium nitroprusside infusion in man. Br. J. Anaes. 48 651-660. 

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. 

Sodium nitroprusside contains a nitroso (-NO) group, but is not an ester. It dilates venous and arterial beds equally. It is administered by infusion to achieve controlled hypotension under continuous close monitoring. Cyanide ions liberated from nitroprusside can be inactivated with sodium thiosulfate (Na2S203)(p.304). 

Side effects also appear very quickly however, they last for a very short time because of their extremely short half-life. Sodium nitroprusside is biotransformed to cyanide and thiocyanate, which upon overdose can result in thiocyanate and cyanide intoxication. The presence of drugs such as diazoxide and sodium nitroprusside has significantly decreased the possibility of a sharp drop in arterial blood pressure and urgent situations which, however, should be used under the constant care of medical personnel. Synonyms of this drug are nipride, nipruton, and others. 

Sodium nitroprusside is the only clinically used metal complex of NO, so that its reactions provide an indication of the types of reactivity that metallonitrosyl complexes might be expected to have in physiological environments (see Fig. 1). The in vivo activation of nitroprusside depends on its reduction to [Fe(CN)5NO], which then releases cyanide to give [Fe(CN)4NO] which in turn releases NO and additional CN to yield Fejl,) and [Fe(CN)g] [75]. [Fe(CN)5(NO)] is paramagnetic (g, = 1.9993, g, = 1.9282, g = 2.008,... 

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. 

For the nitroprusside-cyanide reagent two solutions are prepared. For solution I, sodium nitroferricyanide (sodium nitroprusside, 1.5 g) is dissolved in 2M H2S04 (5mL) to which MeOH (95 mL) and NH4OH (10 mL) is added. A precipitate forms that is discarded. The clear, red solution is refrigerated. For solution II, sodium cyanide (2g) is dissolved in H20 (5 mL) and diluted with MeOH (95 mL), this is filtered if necessary. CAUTION Sodium cyanide can be absorbed through the skin and is extremely toxic. Appropriate safety precautions and first aid procedures should be adopted when handling sodium cyanide. 

The cyanide nitroprusside test determines the presence of free sulfhydryl or disulfide compounds in urine samples [1, 3,4]. During the first step of the assay, cyanide reduces any disulfides that are present to free sulfhydryl compounds. In the second step, a reddish color reaction results when the free sulfhydryl groups complex with nitroprusside. A positive result is most usually due to cystine in the urine. Familial cystinuria is among the most common aminoacidurias. Disulfides are also excreted in other metabolic disorders such as homo cystinuria and ji-m e reap lol ac la le - cy s lei ne disulfiduria. Both will also produce positive results according to the following reaction RSH + Na2Fe(CN)5NO (sodium nitroprusside) — chromophore + NO. 

These are formed much less commonly than electrophiles. An example is cyanide (CN-), which can be produced by metabolism of acrylonitrile, or of the drug sodium nitroprusside. Carbon monoxide is another example, which can be produced by metabolism of methylene chloride. 

Poisoning with cyanide may occur in a variety of ways accidental or intentional poisoning with cyanide salts, which are used in industry or in laboratories as a result of exposure to hydrogen cyanide in fires when polyurethane foam burns from sodium nitroprusside, which is used therapeutically as a muscle relaxant and produces cyanide as an intermediate product and from the natural product amygdalin, which is found in apricot stones, for example. 

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.]... 

Cyanide. In contrast to [Fe(CN)6]4 , the [Fe(CN)6]3 ion is quite poisonous for kinetic reasons the latter dissociates and reacts rapidly, whereas the former is not labile. There is a variety of substituted ions [Fe(CN)3X]" (X= H20, N02, etc.), of which the best known is the nitroprusside ion [Fe(CN)5NO]2. Crystalline sodium nitroprusside dihydrate exhibits extremely long-lived electronic excited states.47 A metastable state I and a metastable state II have lifetimes greater than 104 s at temperatures below 185 and 140 K, respectively. The nitroprusside anion is attacked by OH to give [Fe(CN)5N02]2-. 

Hydrochloric acid decomposes sodium nitroprusside, yielding hydrogen cyanide and ferric chloride. The ferric chloride then reacts with excess of the nitroprusside to form ferric nitroprusside.5... 

Blood-cyanide concentrations of up to 0.02 iLig/ml may be found in normal individuals who do not smoke smokers may have concentrations of up to about 0.05 LLg/ml. Acute toxicity is associated widi blood concentrations of 0.5 iLig/ml or more such concentrations may be encountered during sodium nitroprusside therapy for hypertension. Concentrations above 1 iLig/ml have been reported in fatalities. Cyanide is concentrated in the erythrocytes. 

An ethical drug that may also cause cyanide poisoning in overdose is the potent vascular smooth-muscle relaxant sodium nitroprusside. Although nitroprusside is related chemically to ferricyanide, unlike the latter it penetrates into erythrocytes and reacts with hemoglobin to release its cyanide (Smith and Kruszyna, 1974). Fortunately, the therapeutic margin for nitroprusside appears to be quite large. 

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