In human fibroblasts incubated for 10 min with 500 microM of cyanide, the accumulation ratio was 25 at 37 degrees C (10.45 +/- 1.51 mM) and 11.9 at 4 degrees C. However, only few data are available on the influence of OHCbl on the intracellular cyanide pool. The rational for administering hydroxocobalamin (OHCbl) as an antidote to cyanide poisoning is based on the high affinity of CN ion for cobalt compounds. New York, NY: McGraw-Hill Medical, 2011 p. Goldfranks's Toxicologic Emergencies, 9 th Edition. Nelson LS, Lewin NA, Howland M, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. The same property potentially contributes to its beneficial effects by increasing systolic and diastolic blood pressure and improving the hemodynamic status of cyanide-poisoned patients. Hydroxocobalamin also binds nitric oxide, particularly in the absence of cyanide. In the setting of cyanide poisoning, hydroxocobalamin removes cyanide from the mitochondrial electron transport chain, allowing oxidative metabolism to proceed.
CODE OF FEDERAL REGULATIONS CYANIDE ANTIDOTE KIT SKIN
An ex vivo study using human skin fibroblasts demonstrates that hydroxocobaslamin penetrates intracellularly to form cyanocabalamin. Given the molecular weights of each, 52 g of hyroxocobalamin are needed to bind 1 g of cyanide.
One mole of hydroxocobalamin binds 1 mole of CN. The cobalt ion in hydroxocobalamin combines with cyanide to form the nontoxic cyanocobalamin. Product label: CYANOKIT (hydroxocobalamin) injection, powder, lyophilized, for solution Last revised: April 2011 Each hydroxocobalamin molecule can bind one cyanide ion by substituting it for the hydroxo ligand linked to the trivalent cobalt ion, to form cyanocobalamin, which is then excreted in the urine. The action of Cyanokit in the treatment of cyanide poisoning is based on its ability to bind cyanide ions. Signs and symptoms of acute systemic cyanide poisoning may develop rapidly within minutes, depending on the route and extent of cyanide exposure. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. In the absence of rapid and adequate treatment, exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Hydroxocobalamin Mechanism of actionĬyanide is an extremely toxic poison. Evidence-based medicine for Chemical Defense - including efficacy and safety A. Hydroxocobalamin is indicated as an antidote in patients with known or suspected cyanide poisoning.
Chemical Defense therapeutic area(s) - including key possible uses Name of Chemical Defense therapeutic agent/device
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