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 Hydroxocobalamin is an antidote that seems to have many of the characteristics of the ideal cyanide antidote: rapid onset of action, neutralizes cyanide without interfering with cellular oxygen use, tolerability and safety profiles conducive to prehospital use, safe for use with smoke-inhalation victims, not harmful when administered to non-poisoned patients, easy to administer.1. Hydroxocobalamin differs from these antidotes in that it has not been associated with clinically significant toxicity in antidotal doses. The potential for serious toxicity limits or prevents the use of the Cyanide Antidote Kit, dicobalt edetate, and 4-dimethylaminophenol in prehospital empiric treatment of suspected cyanide poisoning. The data available to date do not suggest obvious differences in efficacy among antidotes, with the exception of a slower onset of action of sodium thiosulfate (administered alone) than of the other antidotes. Each of the antidotes shows evidence of efficacy in animal studies and clinical experience. This paper reviews preclinical and clinical data on available cyanide antidotes and considers the profiles of these antidotes relative to properties of a hypothetical ideal cyanide antidote. Critical assessment of cyanide antidotes is needed to aid in therapeutic and administrative decisions that will improve care for victims of cyanide poisoning (particularly poisoning from enclosed-space fire-smoke inhalation), and enhance readiness for cyanide toxic terrorism and other mass-casualty incidents. The international medical community lacks consensus about the antidote or antidotes with the best risk-benefit ratio. Cyanide has several antidotes, with differing mechanisms of action and diverse toxicological, clinical, and risk-benefit profiles.
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