Of nitroprusside

Older adults are particularly sensitive to the hypotensive effects of nitroprusside. To minimize the hypotensve effects the drug is initially given in lower dosages Older adults require more frequent monitoring during the administration of nitroprusside. 

Hypotension is an important dose-limiting adverse effect of nitroprusside and other vasodilators. Therefore, nitroprusside is primarily used in patients who have a significantly elevated SVR and often requires invasive hemodynamic monitoring. 

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]. 

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... 

Sakurai, T. 1989. Toxic gas tests with several pure and mixed gases using mice. J. Fire Sci. 7 22-77. Schulz, V. 1984. Clinical pharmacokinetics of nitroprusside, cyanide, thiosulphate and thiocyanate. Clin. Pharmacokin. 9 239-251. 

A factor of 3 was applied to the supporting studies as no specific susceptible populations were identified in monitoring studies or during the clinical use of nitroprusside solutions to control hypertension. The detoxifying enzyme rhodanese is present in all individuals including newborns. Application of the uncertainty factor to the El Ghawabi et al. (1975 as adjusted by the NRC) and Grabois (1954) data results in a value close to the 8-h 1 ppm concentration in the Leeser et al. (1990) study. 

No specific susceptible populations were identified during monitoring studies or during the clinical use of nitroprusside solutions to control hypertension. The detoxifying enzyme rhodanese is present in all individuals, including newborns. 

An infusion of 50 mg of nitroprusside in 250 mL of D5W is to be provided to a patient weighing 132 pounds. What is the titration factor of this infusion between 0.5 to 1.5 mcg/kg/min to maintain mean blood pressure at 100 mmHg. 

Byproduct of nitroprusside (released slowly thiosulfate can be used to destroy the cyanide)... 

When nitroprusside is given in higher than usual doses, it may be accompanied by the administration of thiosulfate to reduce potential toxic side effects. Which complex associated with electron transport or oxidative phosphorylation is most sensitive to the toxic byproduct that may accumulate vvith high doses of nitroprusside ... 

Answer D. In addition to NO, metabolism of nitroprusside also releases small quantities of cyanide, a potent and potentially lethal inhibitor of cyt a/a (Complex IV). Thiosulfate is a common antidote for CN poisoning. 

The kinetics of formation of nitroprusside from [Fe VCN)5(H20)] indicate a mechanism of complex formation in which outer-sphere reduction to [Fe (CN)5(Fl20)] precedes substitution."" Reduction of the dimeric pentacyanoferrate(III) anion [Fe2(CI io]" by thiourea is a multi-stage process the first step is one-electron transfer to give [Fe2(CN)io], which dissociates to give [Fe(CN)5(tu)]2- and [Fe(CN)5(H20)] -.""... 

Cyanide poisoning poses some risk however, this is minimized both by the kinetic inertness of both Fe and Fe " cyano complexes and the high affinity of these ions for cyanide ([Fe"(CN)6] , fi6 10 [Fe "(CN)6] , Bg 10 [7, 35]. Small amounts of cyanide, which are released by photolysis and reduction products of nitroprusside, can usually be metabolized in the liver and kidneys by the enzyme rhodanase, which converts CN" to SCN [7, 36]. Cyanide can also be taken up by hydroxocobalamin to generate cy-anocobalamin (B12). As the conversion of cyanide to thiocyanate is dependent on the availability of sulfur, thiosulfate can be administered as an antidote [37]. Monitoring thiocyanate levels as an indicator of cyanide toxicity is no longer routine, but is done on patients with severe hepatic compromise who have been... 

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,... 

Nitrosyl complexes, in which Vno > 1886 cm or Fnq > 13.8 mdyn/A, usually react as electrophilic nitrosating agents so that the ligand can be considered NO [26]. Nucleophilic attack on the nitrosyl nitrogen is a common reaction encountered in the chemistry of nitroprusside and the rates and activation parameters for a number of different nucleophiles are listed in Table 3. Hydr-oxylamine adducts to nitroprusside via a rate law that is first order in the complex, the ligand and hydroxide (k = 4.5 x 10 M s ). 

This electron transfer pathway may partially explain the extraordinarily high efficacy of nitroprusside as it provides single electrons at a sufficiently negative potential to reduce both P450 (E° = — 0.17 to — 0.35 V) [148] and nitroprusside. Since NADPH/P450 reductase has been shown to be an efficient activator of this drug [43], NO may be evolved by NO-synthase reduction of nitroprusside at the same sites where NO is produced physiologically. 

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