Cyanide poisoning

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Cyanide poisoning
Classification and external resources
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Cyanide poisoning
Classification and external resources

Cyanide poisoning occurs when a living organism is exposed to a compound that produces cyanide ions (CN) when dissolved in water. Common poisonous cyanide compounds include hydrogen cyanide gas and the crystalline solids potassium cyanide and sodium cyanide. The cyanide ion halts cellular respiration by inhibiting an enzyme in the mitochondria called cytochrome c oxidase.

Acute poisoning[edit]

Cyanide poisoning is a form of histotoxic hypoxia because the cells of an organism are unable to use oxygen, primarily through the inhibition of cytochrome c oxidase. Acute hydrogen cyanide poisoning can result from inhalation of fumes from burning polymer products that use Nitrile in their production, such as wool, silk, polyurethane, or vinyl.[1] If cyanide is inhaled it causes a coma with seizures, apnea, and cardiac arrest, with death following in a matter of seconds. At lower doses, loss of consciousness may be preceded by general weakness, giddiness, headaches, vertigo, confusion, and perceived difficulty in breathing. At the first stages of unconsciousness, breathing is often sufficient or even rapid, although the state of the victim progresses towards a deep coma, sometimes accompanied by pulmonary edema, and finally cardiac arrest. A cherry red skin color changes to dark may be present as the result of increased venous hemoglobin oxygen saturation. Cyanide does not directly cause cyanosis. A fatal dose for humans can be as low as 1.5 mg/kg body weight.[2]

Chronic exposure[edit]

In addition to its uses as a pesticide and insecticide, cyanide is contained in tobacco smoke and smoke from building fires, and is present in some foods such as almonds, apricot kernel, apple seeds, orange seeds, cassava (also known as yuca or manioc), and bamboo shoots. Vitamin B12, in the form of hydroxycobalamin, or hydroxocobalamin, may reduce the negative effects of chronic exposure, and a deficiency can lead to negative health effects following exposure.[3]

Exposure to lower levels of cyanide over a long period (e.g., after use of cassava roots as a primary food source in tropical Africa) results in increased blood cyanide levels, which can result in weakness and a variety of symptoms, including permanent paralysis, nervous lesions,[4][5][6] hypothyroidism,[5] and miscarriages.[7][8] Other effects include mild liver and kidney damage.[9][10]

Treatment of poisoning and antidotes[edit]

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.

NitritesThe 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.

ThiosulfateThe 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]
HydroxocobalaminHydroxocobalamin, 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-Dimethylaminophenol4-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 edetateCobalt 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]
GlucoseEvidence 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 prodrugsThe most widely studied cyanide-metabolizing pathway involves utilization of thiosulfate by the enzyme rhodanese, as stated above. In humans, however, rhodanese is concentrated in the kidneys (0.96 units/mg protein) and liver (0.15 u/mg), with concentrations in lung, brain, muscle and stomach not exceeding 0.03 U/ml.[17] In all these tissues, it is found in the mitochondrial matrix, a site of low accessibility for ionized, inorganic species, such as thiosulfate. This compartmentalizatiion of rhodanese in mammalian tissues leaves major targets of cyanide lethality, namely, the heart and central nervous system, unprotected. (Rhodanese is also found in red blood cells, but its relative importance has not been clarified.[18][19])

A different cyanide-metabolizing pathway, 3-mercaptopyruvate sulfur transferase (3-MPST, EC, which is more widely distributed in mammalian tissues than rhodanese, is being explored. 3-MPST converts cyanide to thiocyanate, using the cysteine catabolite, 3-mercaptopyruvate (3-MP). However, 3-MP is extremely unstable chemically. Therefore, a prodrug, sulfagene sodium (2, 5-dihydroxy-1,4-dithiane-2,5-dicarboxylic acid disodium salt), which hydrolyzes into 2 molecules of 3-MP after being administered orally or parenterally, is being evaluated in animal models.[20][21]

Oxygen therapyOxygen therapy is not a cure in its own right. However, the human liver is capable of metabolizing cyanide quickly in low doses (smokers breathe in hydrogen cyanide, but it is such a small amount and metabolized so fast that it does not accumulate).

The International Programme on Chemical Safety issued a survey (IPCS/CEC Evaluation of Antidotes Series) that lists the following antidotal agents and their effects: oxygen, sodium thiosulfate, amyl nitrite, sodium nitrite, 4-dimethylaminophenol, hydroxocobalamin, and dicobalt edetate ('Kelocyanor'), as well as several others.[22] Other commonly-recommended antidotes are 'solutions A and B' (a solution of ferrous sulfate in aqueous citric acid, and aqueous sodium carbonate, respectively) and amyl nitrite.

The UK Health and Safety Executive (HSE) has recommended against the use of solutions A and B because of their limited shelf life, potential to cause iron poisoning, and limited applicability (effective only in cases of cyanide ingestion, whereas the main modes of poisoning are inhalation and skin contact). The HSE has also questioned the usefulness of amyl nitrite due to storage/availability problems, risk of abuse, and lack of evidence of significant benefits. It also states that the availability of Kelocyanor at the workplace may mislead doctors into treating a patient for cyanide poisoning when this is an erroneous diagnosis. The HSE no longer recommends a particular cyanide antidote.[23] Qualified UK first aiders are now only permitted to apply oxygen therapy using a bag valve mask, providing they have been trained in its usage.

Historical cases[edit]


Gas chambers[edit]


Cyanides were stockpiled in chemical weapons arsenals in both the Soviet Union and the United States in the 1950s and 1960s.[citation needed] However, as a military agent, hydrogen cyanide was not considered very effective, since it is lighter than air and needs a significant dose to incapacitate or kill.

Although there have been no verified instances of its use as a weapon, hydrogen cyanide may have been employed by Iraq in the Halabja poison gas attack against the Kurds in the 1980s under Saddam Hussein.[27]


Cyanide salts are sometimes used as fast-acting suicide devices. Since cyanide works better with higher stomach acidity, it should, in theory, work best with an empty stomach.




In fiction[edit]




See also[edit]


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  17. ^ Aminlari, Mahmoud; Malekhusseini, Ali; Akrami, Fatemeh; Ebrahimnejad, Hadi (2006). "Cyanide-metabolizing enzyme rhodanese in human tissues: Comparison with domestic animals". Comparative Clinical Pathology 16: 47–51. doi:10.1007/s00580-006-0647-x. 
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