Nitrite methemoglobin

Butyl nitrite is ineffective by ingestion because it is degraded in the gastrointestinal tract. A 44% uptake of butyl nitrite was observed when rats were atmospherically exposed for 5 min periods. It is very rapidly transformed in the body. The likely products of butyl nitrite in vivo might be butyl alcohol, methemoglobin, nitrite ion, nitrate ion, nitrosothiols, and possibly other nitroso compounds. Butyl nitrite... 

The oxides of nitrogen are somewhat sol in w, reacting with it in the presence of oxygen to form nitric and nitrous acids. This is the action that takes place deep in the respiratory system. The acids formed are irritants, causing congestion of the throat and bronchi, and edema of the lungs. The acids are neutralized by the alkalies present in the tissues, with the formation of nitrates and nitrites. The latter may cause some arterial dilation, fall in blood press, headache and dizziness, and there may be some formation of methemoglobin. However, the nitrite effect is of secondary importance... 

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. 

The primary function of the mammalian red blood cell is to maintain aerobic metabolism while the iron atom of the heme molecule is in the ferrous (Fe+2) oxidation state however, copper is necessary for this process to occur (USEPA 1980). Excess copper within the cell oxidizes the ferrous iron to the ferric (Fe+3) state. This molecule, known as methemoglobin, is unable to bind oxygen or carbon dioxide and is not dissociable (Langlois and Calabrese 1992). Simultaneous exposure of sheep to mixtures of cupric acetate, sodium chlorite, and sodium nitrite produced a dose-dependent increase in methemoglobin formation (Calabrese et al. 1992 Langlois and Calabrese 1992). 

Finally, the methemoglobin reduction test may be briefly mentioned. The test has been developed for the detection of primaquine sensitivity and depends on the function of the G-6-PDH system. Its principle consists in the oxidation of Hb to MHb by sodium nitrite and the subsequent enzymatic reduction to Hb in presence of methylene blue. The activity of this system can be followed easily by observation of alterations in color after an incubation period or by means of MHb determinations before and after this period (B18). 

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. 

Nitrites Methylene blue Reduces methemoglobin to hemoglobin... 

Since nitrite ions oxidize the iron atoms of hemoglobin and convert it to methemoglobin, there may be a loss in oxygen delivery to tissues. While methemoglobinemia does not follow therapeutic doses of organic nitrates, it can be observed after overdosage or accidental poisoning. 

The spontaneous reaction of nitric oxide with thiols is slow at physiological pH and the final product under anaerobic conditions is not a nitrosothiol (Pryor et al., 1982). The reaction is slow because it involves the conjugate base of the thiol (R—S"). At pH 7.0, the oxidation of cysteine by nitric oxide required 6 hr to reach completion and yields RSSR and N 2O as the products. The synthetic preparation of nitrosothiols usually involves the addition of nitrosonium ion from acidified nitrite to the thiol, or oxidation of the thiol with nitrogen dioxide under anaerobic conditions in organic solvents. Nitric oxide will form nitrosothiols by reaction with ferric heme groups, such as found in metmyoglobin or methemoglobin (Wade and Castro, 1990). It is also possible that nitrosyldioxyl radical also reacts with thiols to form a nitrosothiol. 

Gruetter, C. A., Gruetter, D. Y., Lyon, J. E., Kadowitz, P. J., and Ignarro, L. J. (1981). Relationship between cyclic guanosine 3 5 -monophosphate formation and relaxation of coronary arterial smooth muscle by glyceryl trinitrate, nitroprusside, nitrite and nitric oxide Effects of methylene blue and methemoglobin. J. Pharmacol. Exp. Ther. 219, 181-186. 

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. 

The importance of reaction (13) was also shown with stimulated human neutrophils, which generate OJ and are thus able to lyse erythrocytes. This hemolysis was inhibited by exogenous (Cu,Zn)-SOD in contrast with the heat-denatured enzyme and with catalase. When hemoglobin in the erythrocytes was converted into methemoglobin by a nitrite treatment, SOD became ineffective, but exogenous catalase protected. The erythrocyte became resistant to hemolysis when treated with carbon monoxide, whereby the formation of methemoglobin was blocked and reaction (13) avoided... 

Electron transfer. Charged species such as nitrite ions can oxidize the iron in hemoglobin. This is a potentially toxic effect as the methemoglobin produced will not carry oxygen. 

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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