Product label: AMYL NITRITE inhalant Last revised: July 2010 Summary of clinical and non-clinical studiesĬyanide is a potent chemical that has been used as a poison for centuries, even before its isolation and identification (Gracia and Shepherd, 2004). This effect on vascular smooth muscle results in coronary vasodilation and decreased systemic vascular resistance and left ventricular preload and afterload. 1689-91Īmyl nitrite causes a non specific relaxation of smooth muscle with the most prominent actions occurring in vascular smooth muscle. 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 conversion to nitric oxide appears to occur only in tissues or blood with the lowest oxygen concentrations. Experimental evidence in organ damage induced by hypoxia or hypotension suggest that the benefits of nitrite may be related to its ability to be converted to nitric oxide, a potent vasodilator. It is possible that the benefits of nitrites given shortly after cyanide result from reversal of cyanide-induced circulatory effects rather than reversal of the effects of cyanide on cytochrome oxidase. Only the alpha-adrenergic antagonists and ganglionic blockers demonstrate antidotal activity, and only when administered with sodium thiosulfate. Reasoning that nitrite-induced vasodilation might be a part of the mechanism of action, investigators considered the antidotal actions of other vasodialators. The production of methemoglobin by nitrite is slow, but when methylene blue is administered to prevent methemoglobin formation, nitrite still is an effective antidote. Other faster methemoglobin induces, such as 4-dimethyaminophenol and hydroxylamine, also are affective as cyanide antidotes. Because nitrites are accepted antidotes for cyanide poisoning, for many years methemoglobin formation was assumed to be their sole antidotal mechanism of action. Nitrites oxidize the iron in hemoglobin to produce methemoglobin. Strom-free methemoglobin is effective against four minimum lethal doses of cyanide in rats. This drives the reaction toward cyanomethemoglobin and liberates cyanide from cytochrome oxidase.
The ferric iron in methemoglobin preferentially combines with cyanide, producing cyanomethemoglobin. Ĭyanide quickly and reversibly binds to the ferric iron in cytochrome oxidase, inhibiting effective energy production throughout the body. Nitrite-mediated antagonism of cyanide inhibition of cytochrome c oxidase in dopamine neurons. Leavesley HB, Li L, Mukhopadhyay S, Borowitz JL, Isom GE. In vivo antagonism of cyanide by NO(2)(-) appears to be due to both generation of mHb and direct displacement of cyanide from CcOX by NO. It was concluded that NaNO(2) antagonizes cyanide inhibition of CcOX by generating of NO, which then interacts directly with the binding of KCN x CcOX to reverse the toxicity. The NaNO(2) antagonism of cyanide was blocked by pretreatment with the NO scavenger PTIO. Pretreatment with NaNO(2) reversed KCN-mediated inhibition of both oxygen consumption and CcOX activity. Under similar conditions, KCN (20muM) inhibited cellular state-3 oxygen consumption and CcOX activity. PTIO reversed the NO-mediated inhibition, thus providing strong evidence that NO mediates the action of NaNO(2). NO generated from NaNO(2) decreased cellular oxygen consumption and inhibited CcOX activity. The NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxy 3-oxide (PTIO) reversed this increase in cellular and mitochondrial NO. NaNO(2) produced a time- and concentration-dependent increase in whole-cell and mitochondrial levels of NO. In this study, nitrite-mediated antagonism of cyanide inhibition of oxidative phosphorylation was examined in rat dopaminergic N27 cells.
On the other hand, NO(2)(-) can undergo biotransformation to generate nitric oxide (NO), which may then directly antagonize cyanide inhibition of CcOX. mHb generation is thought to be a primary mechanism by which the NO(2)(-) ion antagonizes cyanide. Amyl nitrite and sodium nitrite (NaNO(2)) antagonize cyanide toxicity in part by oxidizing hemoglobin to methemoglobin (mHb), which then scavenges cyanide. Summary StructureĬyanide inhibits aerobic metabolism by binding to the binuclear heme center of cytochrome c oxidase (CcOX). Evidence-based medicine for Chemical Defense - including efficacy and safety A. Chemical Defense therapeutic area(s) - including key possible usesĪmyl nitrite is typically used with other agents (sodium nitrite and sodium thiosulfate) as an antidote for acute cyanide poisoning. Name of Chemical Defense therapeutic agent/deviceĪmyl nitrite 2.
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