Nitroprusside with erythrocytes

Individuals with high blood pressure might be considered a susceptible population. Schulz et al. (1982) reported on the infusion of 70 patients, ages 17 to 78, with nitroprusside solutions to lower blood pressure. Administration of nitroprusside with or without thiosulfate continued for several hours to several days, apparently without adverse symptoms. Schulz (1984) states that at 150 to 250 /.imol/L of erythrocyte concentrate headaches, palpitations, and hyperventilation occur. Unfortunately, blood cyanide levels were ex... 

This reaction normally represents hepatic detoxification of cyanide ions produced from nitroprusside in erythrocytes. The SCN- is 99% less toxic than CN-. NaSCN was also still official in the NF X (1960) as an antihypertensive drug. A nitroprusside mechanism on vascular smooth muscle by interference with the role of Ca2+ in the muscle contraction process has also been suggested. 

The exact nature of the NO-releasing reaction and the other products of reaction in mammalian tissue are still unclear. The matter has been discussed by a number of authors and a reductive mechanism in rat hepatocytes and human erythrocytes has been suggested in the presence of NADH and NADPH. Nitroprusside can pass through cell membranes and so there is no intrinsic difficulty with this suggestion. There is direct evidence from spin echo NMR studies to show the conversion, by nitroprusside, of glutathione into glutathione disulfide within erythrocytes [49]. 

The GSH level in erythrocytes is determined by a nitroprusside method (G20) slightly modified (B6). Another blood sample is incubated with acetylphenylhydrazine, and after this, another determination of GSH is carried out. Normal erythrocytes show no or little change of the GSH level after incubation with acetylphenylhydrazine, while those of unstable ones exhibit a decrease in the GSH level averaging... 

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. 

Sodium nitroprusside is not an active hypotensive drug until metabolized to its active metabolite, NO, the mechanism of action of which has been previously described (Fig. 29.1). Studies with sodium nitroprusside suggest that it releases NO by its interaction with glutathione or with sulfhydryl groups in the erythrocytes and tissues to form a S-nitrosothiol intermediate, which spontaneously produces NO, which in turn freely diffuses into the VSM, thereby increasing intracellular cGMP concentration (6,9). NO also activates K channels, which leads to hyperpolarization and relaxation. 

Hydroxycobalamin has been shown to be a potent antidote to cyanide in animal studies probably much of the cyanoco-balamin so formed is excreted, and it is relevant to note that in some investigations an inverse relationship between plasma B 12 and plasma cyanide levels was observed (149 ). In one patient a steady raise in total plasma B12 was apparent this may be due to mobilization of stored B12. A fall in plasma methylcobalamin after nitroprusside therapy, such as has been demonstrated, may possibly indicate an effect upon B12 distribution and metabolism. In one case treated with hydroxycobalamin, erythrocyte cyanide levels dropped sharply, despite continued nitroprusside administration (149 ). An adequate supply of thiosulphate to ensure sufficient endogenous formation of thiocyanate has been found useful (150 ). 

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