Methemoglobin cyanide binding

The purpose of sodium nitrite (or amyl nitrite in the absence of IV access) is to produce methemoglobin, which binds cyanide with greater affinity than mitochondrial cytochromes. In the presence of decreased oxygen carrying capacity, as in combined exposures to cyanide and carbon monoxide (e.g., some fires), sodium nitrite can be detrimental and should be avoided. 

Nitrites may be used as an antidote for cyanide poisoning if given rapidly. They convert hemoglobin to methemoglobin, which binds cyanide in the blood before reaching the tissues. Oxygen is also given if possible. 

Cyanide Sodium nitrate Forms methemoglobin, which binds cyanide, thus removing it from... 

Sodium nitrite or amyl nitrite can be used in cyanide poisoning. They promote formation of methemoglobin, which binds CN ions, forming cyanomethemogiobin. This prevents the inhibitory action of CN on complex IV of the electron transport chain. Cyanomethemogiobin is then reconverted to... 

A. Specific ieveis. Cyanide ieveis may be obtained but are not usually available rapidly enough to guide treatment when cyanide poisoning is suspected. Cyanide levels may not accurately reflect toxicity because of simultaneous production of methemoglobin, which binds some of the cyanide. Cyanide levels greater than 1 mg/L usually produce a demonstrable lactic acidosis. Thiocyanate levels higher than 50-100 mg/L may cause delirium and somnolence. 

Cyanide binds with metal ions that are biological constituents of several enzymes. Most important of these is the Fe in c5rtochrome oxidase. The ceU requires this enz)mie to utilize oxygen and cyanide will inhibit its function and ultimately result in cell death (Dixon and Webb 1958). It wfll also inhibit methemoglobin that competes with cytochrome oxidase for the cyanide ion. This competition is the basis for the first-aid procedures estabUshed for cyanide poisoning. 

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). 

In addition to binding to cytochrome c oxidase, cyanide inhibits catalase, peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, and succinic dehydrogenase activities. These reactions may make contributions to the signs of cyanide toxicity (Ardelt et al. 1989 Rieders 1971). Signs of cyanide intoxication include an initial hyperpnea followed by dyspnea and then convulsions (Rieders 1971 Way 1984). These effects are due to initial stimulation of carotid and aortic bodies and effects on the central nervous system. Death is caused by respiratory collapse resulting from central nervous system toxicity. 

The administration of sodium thiosulfate (12.5 grams a 25 percent solution administered intravenously at a flow rate of 2.5-5mL/min over a 10-minute period of time) will result in the conversion of the much more toxic cyanide to its less toxic thiocyanate form. This treatment of cyanide poisoning with sodium thiosulfate should follow the use of sodium nitrite. The administration of both the sodium nitrite and sodium thiosulfate is dependent upon the hemoglobin of the patient. The Fe2+ form of hemoglobin will also be oxidized by the sodium thiosulfate and sodium nitrite to the Fe3+ form (methemoglobin). This oxidized form binds cyanide readily to form a stable complex which can be metabolized. See ASIDEon CYANIDE. 

Cyanide has many sources natural (plant-Cassava), industrial (cyanide salts and nitriles), and accidental (fires). The target organ is the brain death is from respiratory arrest. Cyanide blocks cytochrome a-a3 (cytochrome oxidase) in mitochondria. The toxic level is 1 mg mL-1 in blood. Treatment involves giving dicobalt edetate (chelation). Alternatively, by giving NaNCb, levels of methemoglobin are increased, and this binds cyanide. Detoxication is catalyzed by the enzyme rhodanese, and this pathway may be increased by giving NaS207. 

Nitrite, which may be administered as sodium nitrite solution or inhaled as amyl nitrite, will oxidize hemoglobin to methemoglobin. This oxidized form of hemoglobin will bind cyanide more strongly than cytochrome a-a3 and therefore tend to remove the cyanide bound inside cells and sequester it in the blood from where it is more readily eliminated. 

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