The United States standard cyanide antidote kit first uses a small inhaled dose of

amyl nitrite, followed by intravenous sodium nitrite, followed by intravenous

sodium thiosulfate.[11] Hydroxocobalamin is newly approved in the US and is
available in Cyanokit antidote kits.[12] Sulfanegen TEA, which could be delivered
to the body through an intra-muscular (IM) injection, detoxifies cyanide and
converts the cyanide into thiocyanate, a less toxic substance.[13] Alternative
methods of treating cyanide intoxication are used in other countries.

Agent Description
Nitrites The nitrites oxidize some of the hemoglobin's iron from the ferrous
state to the ferric state, converting the hemoglobin into methemoglobin.
Cyanide binds avidly to methemoglobin, forming cyanmethemoglobin, thus releasing
cyanide from cytochrome oxidase.[14] Treatment with nitrites is not innocuous as
methemoglobin cannot carry oxygen, and methemoglobinemia needs to be treated in
turn with methylene blue.

Thiosulfate The evidence for sodium thiosulfate's use is based on animal studies
and case reports: the small quantities of cyanide present in dietary sources and in
cigarette smoke are normally metabolized to relatively harmless thiocyanate by the
mitochondrial enzyme rhodanese (thiosulfate cyanide sulfurtransferase), which uses
thiosulfate as a substrate. However, this reaction occurs too slowly in the body
for thiosulfate to be adequate by itself in acute cyanide poisoning. Thiosulfate
must therefore be used in combination with nitrites.[14]
Hydroxocobalamin Hydroxocobalamin, a form (or vitamer) of vitamin B12 made by
bacteria, and sometimes denoted vitamin B12a, is used to bind cyanide to form the
harmless cyanocobalamin form of vitamin B12.
4-Dimethylaminophenol 4-Dimethylaminophenol (4-DMAP) has been proposed[by whom?]
in Germany as a more rapid antidote than nitrites with (reportedly) lower toxicity.
4-DMAP is used currently by the German military and by the civilian population. In
humans, intravenous injection of 3 mg/kg of 4-DMAP produces 35 percent
methemoglobin levels within 1 minute. Reportedly, 4-DMAP is part of the US
Cyanokit, while it is not part of the German Cyanokit due to side effects (e. g.
hemolysis).
Dicobalt edetate Cobalt ions, being chemically similar to iron ions, can also bind
cyanide. One current cobalt-based antidote available in Europe is dicobalt edetate
or dicobalt-EDTA, sold as Kelocyanor. This agent chelates cyanide as the
cobalticyanide. This drug provides an antidote effect more quickly than formation
of methemoglobin, but a clear superiority to methemoglobin formation has not been
demonstrated. Cobalt complexes are quite toxic, and there have been accidents
reported in the UK where patients have been given dicobalt-EDTA by mistake based on
a false diagnosis of cyanide poisoning. Because of its side effects, it should be
reserved only for patients with the most severe degree of exposure to cyanide;
otherwise, nitrite/thiosulfate is preferred.[15]
Glucose Evidence from animal experiments suggests that coadministration of
glucose protects against cobalt toxicity associated with the antidote agent
dicobalt edetate. For this reason, glucose is often administered alongside this
agent (e.g. in the formulation 'Kelocyanor').
It has also been anecdotally suggested that glucose is itself an effective
counteragent to cyanide, reacting with it to form less toxic compounds that can be
eliminated by the body. One theory on the apparent immunity of Grigory Rasputin to
cyanide was that his killers put the poison in sweet pastries and madeira wine,
both of which are rich in sugar; thus, Rasputin would have been administered the
poison together with massive quantities of antidote. One study found a reduction in
cyanide toxicity in mice when the cyanide was first mixed with glucose.[16]
However, as yet glucose on its own is not an officially acknowledged antidote to
cyanide poisoning.
3-Mercaptopyruvate prodrugs The most widely studied cyanide-metabolizing pathway
involves utilization of thiosulfate by the enzyme rhodanese, as stated above. In
humans, however, rhodanese is