Nitroprusside, cyanide poisoning

Cyanide poisoning (e.g., nitroprusside), methanol, ethanol, and ethylene glycol... 

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... 

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... 

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. 

Diagnosis Cyanide poisoning from toxic dose of nitroprusside. 

Cyanide forms a stable complex with the ferric ion of cytochrome oxidase enzymes, inhibiting cellular respiration. What is the connection between the management of cyanide poisoning and the drugs amyl nitrite and nitroprusside The Skill Keeper Answer appears at the end of the chapter. 

Posner MA, Rodkey FL, Tobey RE. Nitroprusside-induced cyanide poisoning Antidotal effect of hydroxocobalamin. Anesthesiology. 1976 44 330-335. 

C. Acute cyanide poisoning is relatively rare with nitroprusside infusion (at normal infusion rates) or after ingestion of amygdalin-containing seeds (unless they have been pulverized). 

B. Prophylaxis against cyanide poisoning during nitroprusside infusion. 

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. 

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. 

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-. 

The drug must be administered as a controlled continuous infusion, and the patient must be closely observed. Most hypertensive patients respond to an infusion of 0.25-1.5 flg/kg/min. Higher infusion rates are needed to produce controlled hypotension in normotensive patients under surgical anesthesia. Infusion of nitroprusside at rates >5 flg/kg/min over a prolonged period can cause cyanide and/or thiocyanate poisoning. Patients receiving other antihypertensive medications usually require less nitroprusside to lower blood pressure. If infusion rates of 10 pg/kg/min do not produce adequate reduction of blood pressure within 10 minutes, the rate of administration of nitroprusside should be reduced to minimize potential toxicity. 

The released CN is transformed into SCN" by a hepatic and renal enzyme, rhodanese [43—45], this sulfuryl transferase being discovered in 1933 [46]. The enzymatic reaction proceeds slowly unless sulfur is supplied and is stimulated by thiosulfate, which is therefore a powerful antidote for CN poisoning. Another antidote is vitamin B12, and results indicate that as plasma cyanide increases the vitamin Bj2 level decreases suggesting that the vitamin may be a cofactor of rhodanese. Vitamin Bj2 will be in the aqua (not hydroxo) form at physiological pH [47], and cyanocobalamin formation is believed to be responsible for the antidotal properties [48—50]. Side effects have also been noted, however, in this connection [43, 51], and low plasma B12 levels may complicate treatment. The direct interaction between nitroprusside and vitamin B12 has been examined by NMR and 1 1 and 1 2 adducts have been observed [47],... 

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