A SHORT STUDY ON CYANIDE POISONING

About Authors:
*S.Swain, S.K.Sahoo
University Department of Pharmaceutical Sciences,
Utkal University
*sabyasachi590@gmail.com

Introduction
Cyanides are the chemical compounds that contains cyano groups (-C≡N) or when dissolved in water produces a cyanide ion (CN⁻). This class of compounds are abundantly available around us. Due to the wide availability of compound the chance of misuse increases. The cyanide ion halts cellular respiration by inhibiting cytochrom oxidase a3, an enzyme in the mitochondria. In layman's language Cyanide generally reduces oxygen absorbing capacity of cell which may leads to cell death. Rapid action and wide availability makes it a poison of choice for suicide, homicide and terrorism.

REFERENCE ID: PHARMATUTOR-ART-1821

Sources of cyanides [1-23]
basically there are three sources of cyanide poisoning

1)Artificial sources

insecticide(Zyklon B)
photographic solution (Potassium ferricyanide, Potassium Dichromate)
metal polishing material
jewelry cleaner
acetonitrile
electro pleating material (Cuprous Cyanide,Sodium Copper Cyanide etc)
synthetic products(rayon, nylon, polyurethane fome, insulation, adhesive resins)

2)Natural sources
seeds, fruits and roots of

apple
cherry
apricot pill
Cassava roots
Lima beans
Almonds

3) Environmental sources
smoke inhaled in closed space fire

Name of certain cyanide compound commonly found in pharmacy laboratory . [25]
Hydrogen cyanide, cyanic acid, sodium salt of cyanogen, cyanidol, cyanogen halides, cyanoacetic acid, Cyanamid, cyanotrimeprazine, acylonitrite, Potassium cyanide, cuprous cyanides etc.

Signs and symptoms [25]
As the effects of cyanide ingestion are very similar to the effects of suffocation, Cyanide poisoning is difficult to detect. Because cyanide stops the cells of the body to be oxygenated.

The common symptoms of cyanide poisoning are general weakness, confusion, boring behavior, excessive drowsiness, coma, shortness of breath, headache, dizziness. Typically, a severe intake will immediately cause bradicardia. It may also instantaneously affect the CNS and cause a seizure or coma. The skin of a cyanide-poisoned person seems to be unusually pink or cherry-red because oxygen will remain in the blood and not get into the cells. The person may also have a very fast pulse rate .

Diagnosis [25]
Victim's condition determines the treatment procedure. Cyanide poisoning can be managed but most people die because of slow diagnosis, or lack of care from the beginning. As cyanide poisoning is rare, the treating doctor should be alert of the risk. Blood tests, X-rays, and other procedures should be carried out to determine cyanide poisoning, how bad the poisoning is, or if some other type of poisoning has occurred. The diagnostic test for cyanide takes long time to perform. Thus, the doctors will rely on a combination of what rescuer told them, how the victim looks like, and supporting laboratory data to decide the possibility of actual cyanide exposure.

Pathophysiology [2-23]
Cyanide is highly lethal because it penetrates into tissues and binds to target sites within seconds. Intravenous and pulmonary exposures produce more rapid signs and symptoms than oral ingestion because the first two routes provide faster diffusion and direct distribution to target organs via the bloodstream.

Metabolism of cyanide [2-23]
The enzyme rhodanese acts as a catalyst in conversion of cyanide to the nontoxic thiocyanate in the liver, and the thiocyanate is then excreted through the kidneys .

Excretion of Cyanide [2-23]
Cyanide is metabolized in liver to produce Thiocyanate. Rhodanese catalyzes the conversion of cyanide to thiocyanate, and excreted through the kidneys. This mechanism is moderated by high doses of cyanide in acute poisoning or in patients with impaired kidney function.

Mechanism of cyanide poisoning [2-23]
The toxicity of cyanide is due to the termination of aerobic metabolism of cell. Cyanide binds to the cytochrome oxidase a3 within the mitochondria that leads to reversible intracellular hypoxia. Cytochrome oxidase a3 is essential for the reduction of oxygen to water in the oxidative phosphorylation. Oxidative phosphorylation is required to synthesize adenosine triphosphate (ATP) and to maintain cellular respiration. Due to deficiency in ATP mitochondria is unable to take oxygen . As a result, metabolism shifts to glycolysis through anaerobic metabolism and produces lactate due to which metabolic acidosis may occure. Increase in oxygen concentration of blood occurs due to Poor oxygen aspiration. Oxygen transport is blocked due to binding of cyanide to haemoglobine.

How we can protect our self from cyanide

Run away and stay away from source
as cyanide is effective in inhalation so avoid breathing and stay away from source.
remove the clothes, because it may contain cyanide.
Dispose the clothing in proper way
try to breath in fresh air
rinse eyes and face with fresh water & if possible take a bath.

Antidotes [2-23]
Currently, 2 antidotes for acute cyanide poisoning are available the cyanide antidote kit, and hydroxocobalamin. Hydroxocobalamin is more used because of its less adverse effect . Hydroxocobalamin also appears to be safer than the cyanide antidote kit in hypotension and pregnant patients. A proper knowledge of all the available antidotes, their characteristics, benefits, adverse effects will help the physician to choose proper medication.

cyanide antidote kit [2-23]
The cyanide antidote kit consists of three medications given together for their synergistic effect: amyl nitrite, sodium nitrite, and sodium thiosulfate. Amyl nitrite is inhaled over 15 to 30 seconds then Sodium nitrite is given intravenously over 3 to 5 minutes, followed by intravenous sodium thiosulfate over 30 minutes.

Mode of action:
The nitrites are administered to form methemoglobin and bind cyanide because cyanide appears to bind preferentially to the ferric ion of methemoglobin rather than to the ferric ion of the cytochrome oxidase in the mitochondria. Methemoglobin takes cyanide away from the mitochondria. This process frees the mitochondria for electron transport and return to aerobic cellular respiration.

Sodium thiosulfate is administered in combination with the nitrites to clear unbound cyanide in the form of renally excretable thiocyanate.

An important adverse effects of nitrites vasodilatation and hypotension. Sodium nitrite must be administered slowly, over at least 3 to 5 minutes, with continuous blood pressure monitoring system.

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT articles@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE

Hydroxocobalamin [2-23]
The Food and Drug Administration approved Hydroxocobalamin (Cyanokit) for the treatment of acute cyanide poisoning in December 2006.A Hydroxocobalamin kit contains two 250-mL glass vials, and each vial contains 2.5 g of freeze dried Hydroxocobalamin. The kit also contains 2 sterile transfer spikes and 1 sterile intravenous infusion set. The manufacturer recommends storing the powder form at room temperature, or approximately 25?C. Once it is reconstituted, the medication can be kept at room temperature, but it must be used within 6 hours. An initial starting dose for adults is 5 g (two 2.5-g vials) diluted in 0.9 % saline and administered over 15 minutes . A second 5-g dose can be given over 15 minutes to 2 h thereafter if signs and symptoms of cyanide poisoning reoccurs.

Moad of action
Hydroxocobalamin detoxifies cyanide by binding with it to form the renally excreted, nontoxic cyanocobalamin. Cyanocobalamin releases cyanide at a rate that is slow enough to allow the enzyme rhodanese to detoxify the cyanide in the liver. Cyanide has a greater affinity for hydroxocobalamin than for the cytochrome oxidase within the mitochondria and so frees the mitochondria for cellular respiration. This characteristic makes hydroxocobalamin an effective antidote against cyanide poisoning. Because it binds with cyanide without forming methemoglobin, hydroxocobalamin also can be used to treat patients with cyanide poisoning without compromising the oxygen-carrying capacity of hemoglobin. This property is especially important for patients who already have decreased concentration of useful hemoglobin because of exposure to carbon monoxide or who are pregnant.

Other Detoxifying agents [26-72]
4-Dimethylaminophenol
Intravenous injection of 3 mg/kg of 4-Dimethylaminophenol produces 35 percent methemoglobin levels within 1 minute.Methemoglobin (British English: methaemoglobin) (pronounced "met-hemoglobin") is a form of the oxygen-carrying metaloglobine, in which the iron in the heme group is in the Fe³⁺ (ferric) state, not the Fe²⁺ (ferous) of normal hemoglobin. Methemoglobin cannot bind oxygen. So this is not widely accepted.

Dicobalt edetate
Cobalt ions are similar to iron ions so it can 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.

Glucose
It has also been 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 study found a reduction in cyanide toxicity in mice when the cyanide was first mixed with glucose. However, yet glucose is not an officially acknowledged antidote to cyanide poisoning.

3-Mercaptopyruvate prodrugs
3-mercaptopyruvate(3-MP) converts cyanide to thiocyanate, using the cysteine.As because chemically 3-mercaptopyruvate is extremely unstable, a prodrug, sulfagene sodium (2, 5-dihydroxy-1,4-dithiane-2,5-dicarboxylic acid disodium salt)is used.On hydrolysis 2 molecules of 3-MP are found.

Oxygen therapy
Oxygen therapy has no effect on cyanide poisoning but it is useful as life support system for patient.

Summary [2-23]
Cyanide poisoning is rare but harmful to mankind. So everybody should be aware of every aspect of cyanide poisoning. We have 2 antidotes available with us to fight against cyanide. Out of these 2 antidotes hydroxylamine should be proffered because of its better efficacy and less adverse effect. Antidotes should be selected by knowing the patient history such as pre-existing hypertension and pregnancy. The physician must be aware of current option, adverse effects, contraindication, monitoring requirements for each antidotes ,proper care and management of patient with acute cyanide poisoning.

References
1. en.wikipedia.org/wiki/cyanide
2. ccn.aacnjournals.org. A review of Acute cyanide poisoning with a treatment updates by Jillian Hamel.
3.Fortin JL, Giocanti JP, Ruttimann M, Kowalski JJ. Prehospital administration of hydroxocobalamin for smoke-inhalation associated cyanide poisoning: 8 years of experience in the Paris Fire Brigade. Clin Toxicol (Phila). 2006;44(suppl 1):37–44. CrossRef Medline
4.Borron SW, Baud FJ, Mégarbane B, Bismuth C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg Med. 2007;25(5):551–558. CrossRef Medline
5.Thompson RL, Manders WW, Cowan RW. Postmortem findings of the victims of the Jonestown tragedy. J Forensic Sci. 1987;32(2): 433–443. Medline
6.DesLauriers CA, Burda AM, Wahl M. Hydroxocobalamin as a cyanide antidote. Am J Ther. 2006;13(2):161–165. CrossRef Medline
7.Hall AH, Dart R, Bogdan G. Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning? Ann Emerg Med. 2007;49(6):806–813. CrossRef Medline
8.Bronstein AC, Spyker DA, Cantilena LR Jr., et al.; American Association of Poison Control Centers. 2007 Annual report of the American Association of Poison Control Centers’ National Poison Data System NPDS: 25th annual report. Clin Toxicol (Phila). 2008;46(10):927–1057.CrossRef Medline
9.Borron SW. Recognition and treatment of acute cyanide poisoning. J Emerg Nurs. 2006; 32(4 suppl):S11-S18. Search Google Scholar
10.Schnepp R. Cyanide: sources, perceptions and risks. J Emerg Nurs. 2006;32(4 suppl):S3-S7. CrossRef Medline
11.Shepherd G, Velez L. Role of hydroxocobalamin in acute cyanide poisoning. Ann Pharmacother. 2008;42(5):661–669. Abstract/FREE Full Text
12.Barillo DJ. Diagnosis and treatment of cyanide toxicity. J Burn Care Res. 2009;30(1):148–152. Medline
13.Smith D, Cairns B, Ramadan F, et al. Effect of inhalation injury, burn size, and age on mortality: a study of 1447 consecutive burn patients. J Trauma. 1994;37:655–659. Medline
14.Benowitz NL. Antihyptertensive agents. In: Katzung BG, ed. Basic and Clinical Pharmacology. 10th ed. New York, NY: McGraw-Hill Co Inc; 2007:173–174. Search Google Scholar
15.Nelson L. Acute cyanide toxicity: mechanisms and manifestations. J Emerg Nurs. 2006; 32(4 suppl):S8-S11. CrossRef Medline
16.Koschel MJ. Management of the cyanide-poisoned patient. J Emerg Nurs. 2006;32(4 suppl):S19-S26. CrossRef Medline
17.Chen KK, Rose CL. Nitrite and thiosulfate therapy in cyanide poisoning. JAMA. 1952; 149:113–115. CrossRef Medline
18.US Food and Drug Administration. FDA news: FDA approves drug to treat cyanide poisoning. US Food and Drug Administration Web site. fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108807.htm. Published December 15, 2006. Updated June 18, 2009. Accessed October 29, 2010.
19.Cyanokit [package insert]. Columbia, MD: Meridian Medical Technologies Inc. cyanokit.com/pdf/cyanokit_pi.pdf. Accessed October 29, 2010.
20.Uhl W, Nolting A, Golor G, Rost KL, Kovar A. Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study. Clin Toxicol (Phila). 2006;44(suppl 1): 17–28. CrossRef Medline
21.Dart RC. Hydroxocobalamin for acute cyanide poisoning: new data from preclinical and clinical studies; new results from the prehospital emergency setting. Clin Toxicol (Phila). 2006;44(suppl 1):1–3. Medline
22.Borron SW, Baud FJ, Barriot P, Imbert M, Bismuth C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2007; 49(6):794–801. CrossRef Medline
23.Lee J, Mukai D, Kreuter K, Mahon S, Tromberg B, Brenner M. Potential interference by hydroxocobalamin on cooximetry hemoglobin measurements during cyanide and smoke inhalation treatments. Ann Emerg Med. 2007;49(6):802–805
24. bt.cdc.gov/agent/cyanide/basics/facts.asp Centers for Disease Control and Prevention 1600 Clifton Rd. Atlanta, GA 30333, USA
800-CDC-INFO (800-232-4636) TTY: (888) 232-6348
25. emedicinehealth.com/cyanide_poisoning, cyanide poisoning overview, by John p. Cunha ,DO, FACOE
26. en.wikipedia.org/wiki/cyanide poisoning
27."Cyanide [Technical document – Chemical/Physical Parameters]". Health Canada.
28.Crampton RF, Gaunt IF, Harris R, et al. (1979). "Effects of low cobalamin diet and chronic cyanide toxicity in baboons". Toxicology (National Library of Medicine) 12 (3): 221–34. doi:10.1016/0300-483X(79)90068-4. PMID 494304.
29.Soto-Blanco B, Maiorka PC, Gorniak SL. (2002). "Effects of long-term low-dose cyanide administration to rats". Ecotoxicology and Environmental Safety 53 (1): 37–41. doi:10.1006/eesa.2002.2189. PMID 12481854.
30.a b Soto-Blanco B, Stegelmeier BL, Pfister JA, et al. (2008). "Comparative effects of prolonged administration of cyanide, thiocyanate and chokecherry (Prunus virginiana) to goats". Journal of Applied Toxicology 28 (3): 356–63. doi:10.1002/jat.1286. PMID 17631662.
31.Soto-Blanco B, Maiorka PC, Gorniak SL. (2002). "Neuropathologic study of long term cyanide administration to goats". Food and Chemical Toxicology 40 (11): 1693–1698. doi:10.1016/S0278-6915(02)00151-5. PMID 12176095.
32.Soto-Blanco B, Gorniak SL. (2004). "Prenatal toxicity of cyanide in goats—a model for teratological studies in ruminants". Theriogenology 62 (6): 1012–26. doi:10.1016/j.theriogenology.2003.12.023. PMID 15289044.
33.Soto-Blanco B, Pereira, Verechia FT, et al. (2009). "Fetal and maternal lesions of cyanide dosing to pregnant goats". Small Ruminant Research 87 (1–3): 76–80. doi:10.1016/j.smallrumres.2009.09.029.
34.Sousa AB, Soto-Blanco B, Guerra JL, Kimura ET, Gorniak SL. (2002). "Does prolonged oral exposure to cyanide promote hepatotoxicity and nephrotoxicity?". Toxicology 174 (2): 87–95. doi:10.1016/S0300-483X(02)00041-0. PMID 11985886.
35.Manzano H, de Sousa AB, Soto-Blanco B, et al. (2007). "Effects of long-term cyanide ingestion by pigs". Veterinary Research Communications 31 (1): 93–104. doi:10.1007/s11259-006-3361-x. PMID 17180454.
36.Toxicity, Cyanide~overview at eMedicine
37.a b Toxicity, Cyanide~treatment at eMedicine
38. news.yahoo.com/antidote-cyanide-found-132827160.html[full citation needed]
39.a b Leybell, Inna. "Cyanide Toxicity". Medscape.
40.Hall, AH, Dart, R, Bogdan, G (2007). "Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning?". Annals of emergency medicine 49 (6): 806–13. doi:10.1016/j.annemergmed.2006.09.021. PMID 17098327.
41.Nagler, J, Provoost, RA, Parizel, G (1978). "Hydrogen cyanide poisoning: Treatment with cobalt EDTA". Journal of occupational medicine 20 (6): 414–6. PMID 209160.
42.Gerardo, I, Ilsen, R, Ernesto, I, Egar, S, Magaly, T, Marcelo, G (2005). "Valoración de la glucosa como antídoto ^ Crampton RF, Gaunt IF, Harris R, et al. (1979). "Effects of low cobalamin diet and chronic cyanide toxicity in baboons". Toxicology (National Library of Medicine) 12 (3): 221–34. doi:10.1016/0300-483X(79)90068-4. PMID 494304.
43.Soto-Blanco B, Maiorka PC, Gorniak SL. (2002). "Effects of long-term low-dose cyanide administration to rats". Ecotoxicology and Environmental Safety 53 (1): 37–41. doi:10.1006/eesa.2002.2189. PMID 12481854.
44.a b Soto-Blanco B, Stegelmeier BL, Pfister JA, et al. (2008). "Comparative effects of prolonged administration of cyanide, thiocyanate and chokecherry (Prunus virginiana) to goats". Journal of Applied Toxicology 28 (3): 356–63. doi:10.1002/jat.1286. PMID 17631662.
45.Soto-Blanco B, Maiorka PC, Gorniak SL. (2002). "Neuropathologic study of long term cyanide administration to goats". Food and Chemical Toxicology 40 (11): 1693–1698. doi:10.1016/S0278-6915(02)00151-5. PMID 12176095.
46.Soto-Blanco B, Gorniak SL. (2004). "Prenatal toxicity of cyanide in goats—a model for teratological studies in ruminants". Theriogenology 62 (6): 1012–26. doi:10.1016/j.theriogenology.2003.12.023. PMID 15289044.
47.Soto-Blanco B, Pereira, Verechia FT, et al. (2009). "Fetal and maternal lesions of cyanide dosing to pregnant goats". Small Ruminant Research 87 (1–3): 76–80. doi:10.1016/j.smallrumres.2009.09.029.
48.Sousa AB, Soto-Blanco B, Guerra JL, Kimura ET, Gorniak SL. (2002). "Does prolonged oral exposure to cyanide promote hepatotoxicity and nephrotoxicity?". Toxicology 174 (2): 87–95. doi:10.1016/S0300-483X(02)00041-0. PMID 11985886.
49.Manzano H, de Sousa AB, Soto-Blanco B, et al. (2007). "Effects of long-term cyanide ingestion by pigs". Veterinary Research Communications 31 (1): 93–104. doi:10.1007/s11259-006-3361-x. PMID 17180454.
50.Toxicity, Cyanide~overview at eMedicine
51.a b Toxicity, Cyanide~treatment at eMedicine
52. news.yahoo.com/antidote-cyanide-found-132827160.html[full citation needed]
53.a b Leybell, Inna. "Cyanide Toxicity". Medscape.
54.Hall, AH, Dart, R, Bogdan, G (2007). "Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning?". Annals of emergency medicine 49 (6): 806–13. doi:10.1016/j.annemergmed.2006.09.021. PMID 17098327.
55.Nagler, J, Provoost, RA, Parizel, G (1978). "Hydrogen cyanide poisoning: Treatment with cobalt EDTA". Journal of occupational medicine 20 (6): 414–6. PMID 209160.
56.Gerardo, I, Ilsen, R, Ernesto, I, Egar, S, Magaly, T, Marcelo, G (2005). "Valoración de la glucosa como antídoto en la intoxicación por cianuro" [Rating glucose as an antidote in cyanide poisoning]. Retel (in Spanish) (7).
57.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.
58.Baskin SI, Horowitz AM, Nealley EW (April 1992). "The antidotal action of sodium nitrite and sodium thiosulfate against cyanide poisoning". J Clin Pharmacol 32 (4): 368–75. doi:10.1002/j.1552-4604.1992.tb03849.x. PMID 1569239.
59.Alexander K, Procell LR, Kirby SD, Baskin SI (1989). "The inactivation of rhodanese by nitrite and inhibition by other anions in vitro". J. Biochem. Toxicol. 4 (1): 29–33. doi:10.1002/jbt.2570040106. PMID 2769694.
60.Crankshaw DL, Goon DJ, Briggs JE, et al. (December 2007). "A novel paradigm for assessing efficacies of potential antidotes against neurotoxins in mice". Toxicol. Lett. 175 (1–3): 111–7. doi:10.1016/j.toxlet.2007.10.001. PMC 2171362. PMID 18024011.
61.Nagasawa HT, Goon DJ, Crankshaw DL, Vince R, Patterson SE (December 2007). "Novel, orally effective cyanide antidotes". J. Med. Chem. 50 (26): 6462–4. doi:10.1021/jm7011497. PMC 2274902. PMID 18038966.
62."Antidotes for Poisoning by Cyanide: 6. AMYL NITRITE". IPCS/CEC Evaluation of Antidotes Series; Volume 2.
63."Cyanide poisoning – New recommendations on first aid treatment". Health and Safety Executive.
64.Green, Richard J. "The Chemistry of Auschwitz: III. Zyklon B: A Pesticide and an Agent of Homicide". The Holocaust History Project. Archived from the original on 28 February 2009.
65."Gas Chamber Executions". About.com.
66."Nazi Deathcamps". The Holocaust FAQ. Retrieved 10 October 2010.
67."Facts About Cyanide". Centers for Disease Control and Prevention.
68."Michael Marin, former Wall Street trader, took cyanide after arson conviction, says autopsy". CBS News.
69.Randall, David (15 April 2012). "Briton in China mystery 'killed by drop of cyanide'". The Independent (London).
70."Cook County Medical Examiner Confirms USD 1 Million Lottery Winner Was Poisoned With Cyanide". ABC News. Retrieved 1 March 2013.
71."Chronology of Aum Shinrikyo's CBW Activities". Monterey Institute of International Studies. 2001.
72.Suskind, Ron (19 June 2006). "The Untold Story of al-Qaeda's Plot to Attack the Subway". Time magazine. Retrieved 20 January 2007.