Nitrous acid (Nithiodote)

概览

Nitrous acid is an iron binder used to reverse life-threatening acute cyanide poisoning.

作用机制

Cyanide has a high affinity for the oxidized form of iron (Fe3+) such as that found in cytochrome oxidase a3 . Cyanide binds to and inhibits cytochrome oxidase a3, preventing oxidative phophorylation from occuring. The resultant lack of ATP cannot support normal cellular processes, particularly in the brain. Compensatory increases in anaerobic respiration result in rising levels of lactic acid and subsequent acidosis. Nitrite primarily acts by oxidizing hemoglobin to methemoglobin . The now oxidized Fe3+ in methemoglobin also binds cyanide with high affinity and accepts cyanide from cytochrome a3. This leaves cytochrome a3 free to resume its function in oxidative phosphorylation. The slow dissociation of cyanide from methemoglobin allows hepatic enzymes such as rhodanese to detoxify the compound without further systemic toxicity occuring. Methemoglobin is reduced back to hemoglobin by methemoglobin reductase allowing the affected blood cells to resume normal functioning. The reduction of nitrite by hemoglobin results in the formation of nitric oxide . Nitric oxide acts as a powerful vasodilator, producing vascular smooth muscle relaxation through activation of soluble guanylate cyclase and the subsequent cyclic guanylyl triphosphate mediated signalling cascade .

适应症

For sequential use with sodium thiosulfate for the treatment of acute cyanide poisoning that is judged to be life-threatening .

• Cyanide Poisoning