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Amyl and sodium nitrite are effective cyanide antidotes when they are administered in a timely fashion. Amyl nitrite is volatile and available in ampules that can be broken and administered by inhalation while sodium nitrite is being prepared to administer intravenously. Although the exact mechanism of action of the nitrites is unclear, the production of methemoglobin is both therapeutic in cyanide poisoning and potentially life threatening if nitrites are administered to a patient with impaired oxygen-carrying capacity, from smoke inhalation or elevated concentrations of carboxyhemoglobin or methemoglobin from any cause. In the latter cases, sodium thiosulfate and/or hydroxocobalamin can still be administered intravenously without causing harm.

Expanding on earlier work that demonstrated the limited role of methylene blue and the efficacy of sodium nitrite in cyanide-poisoned animals, inhaled amyl nitrite prevented and protected against cyanide-induced seizures and muscular rigidity in dogs.3 Amyl nitrite administered by inhalation protected dogs from up to four minimum lethal doses of sodium cyanide (a total of 24 mg/kg subcutaneously). In the regimen used, therapy started within 5 to 7 minutes of exposure and continued for several hours. The frequency of inhalations was based on clinical response. These experimental results led to the use of inhaled amyl nitrite for patients poisoned by cyanide. The same authors discovered that intravenous (IV) use of sodium thiosulfate alone protected against three minimum lethal doses of cyanide in dogs and that the combination of sodium thiosulfate with either inhaled amyl nitrite or IV sodium nitrite protected against 10 and 13 to 18 minimum lethal doses, respectively.2,4

The chemical formula for sodium nitrite is NaNO2 and for amyl nitrite is C5H11NO2. Sodium nitrite has a molecular weight of 69 daltons and amyl nitrite 117 Da. Amyl nitrite is volatile even at low temperatures, and is highly flammable.

Cyanide quickly and reversibly binds to the ferric iron in cytochrome oxidase, inhibiting effective energy production throughout the body. The ferric iron in methemoglobin preferentially combines with cyanide, producing cyanomethemoglobin. This drives the reaction toward cyanomethemoglobin and liberates cyanide from cytochrome oxidase. Stroma-free methemoglobin is effective against four minimum lethal doses of cyanide in rats.17 Nitrites oxidize the iron in hemoglobin to produce methemoglobin. Because nitrites are accepted antidotes for cyanide poisoning, for many years methemoglobin formation was assumed to be their sole antidotal mechanism of action.13,21 Other, faster methemoglobin inducers, such as 4-dimethyaminophenol and hydroxylamine, also are effective as cyanide antidotes.13,19 The production of methemoglobin by nitrite is slow, but when methylene blue is administered to prevent methemoglobin formation, nitrite still is an effective antidote.13,21 Reasoning that nitrite-induced vasodilation might be part of the mechanism of action, investigators considered the antidotal actions of other vasodilators. Only the α-adrenergic antagonists and ganglionic blockers demonstrate antidotal activity, and only when they are administered with sodium thiosulfate.21 It is possible that the benefits of nitrites given ...

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