biochem.cyanide poisoning

7/27/2019 BIOCHEM.cyanide Poisoning.

1/8

What is oxidative phosphorylation?

Oxidative phosphorylation is defined as the culmination of energy yielding metabolism in aerobic organisms. Itis the final stage of respiration wherein the energy of oxidation drives the synthesis of ATP (Lehninger, ). Ineukaryotes, this process occurs in mitochondria. It involves the reduction of O 2 to H 2O with electrons donatedby NADH and FADH 2 (Granner et al., 2003) .

What is respiratory chain?The respiratory chain is the one responsible for collecting and transporting reducing equivalents directingthem to their final reaction with oxygen to form water that produce most of the reducing equivalents(Granner et al., 2003).

Where it all happens?

Image retrieved from: (Cox et al., 2003)


2/8

What is cyanide?

It is a term used to any compound that contains monovalent group CN - (cyano group), which consists of asingle carbon atom that is triple bonded to a nitrogen atom (URL1).

Cyanide is a reactive chemical that can pose different threats to health upon exposure to it. Sometimes, itssmell is occasionally described as bitter almond although it does not always give off a distinct odor. Cyanide

exists in nature in different forms. It could be a colorless liquid such that of hydrogen cyanide (HCN) orcolorless gas such as cyanogen chloride (CNCl), a crystal form such as sodium cyanide (NaCN) or potassiumcyanide (KCN) (URL2).

Hydrogen cyanide/ Prussic acid

It is a colorless liquid that is miscible in water and ethanol. It has a boiling point slightly abovethe normal room temperature at 26 C or 79F. It is weakly acidic with a pK a of 9.2. Moreover, it partiallyionizes in water to give off the cyanide anion, CN -. The mixture of water and hydrogen cyanide in a solution iscalled hydrocyanic acid whereas their salts are termed cyanides.

Cyanogen chloride/ Chlorcycan

It is an inorganic compound that exists as triatomic pseudohalogen that could easily becondensed as a colorless gas. It is a linear molecule where carbon and chlorine are linked by a single bondwhile carbon and nitrogen are linked by a triple bond. CNCl is produced by the oxidation of sodium cyanidewith chlorine,

NaCN + Cl2 ClCN + NaCl

Sodium cyanide

It is an inorganic compound that appears white or crystalline solid that is water soluble. It hashigh affinity for metals rendering its high toxicity. This compound is produced by the reaction betweenhydrogen cyanide and sodium hydroxide,

HCN + NaOH NaCN + H2O or,

Castner- Kellner process

NaNH2 + C NaCN + H2

Potassium cyanide

It is a colorless crystalline compound that resembles the appearance of a sugar. It is highlysoluble in water and has a high characteristic of being toxic. This compound can be produced by the reactionbetween hydrogen cyanide and potassium hydroxide,

HCN + KOH KCN + H2O or,

by reaction between formamide and potassium hydroxide,


3/8

HCONH2 + KOH KCN + 2H2O

Different forms of cyanide has different uses like in mining where it aids in dissolving metals like goldand silver in order to form a soluble derivatives. In addition to that, it also stabilizes metal ions in electrolytesolutions during the process of electroplating (URL 1).

In industrial organic chemistry, they are widely used in order to produce nylon. This is given by the

combination of hydrogen cyanide with alkenes and this reaction is catalysed by metal catalysts. Moreover,they are also used in textile and plastic industries (URL 2). Practical application of cyanide gas also includes theextermination of pests and vermin in ships and buildings.

In small doses, cyanide is usually metabolized into thiocyanate with the assistance of the hepaticenzyme, rhodanese, thus, resulting to excretion of thiocyanate in the urine. Rhodanese is a mitochondrialenzyme that detoxifies cyanide (CN -) into thiocyanate (SCN -) (URL 4) .

*maix may chemical reaction dito, en.m.wikipedia.org/wiki/Rhodanese

Mabagal kasi net ditto sa bahay. sorry

Another way of metabolizing it is through its conversion to carbon dioxide which then leaves the body throughexhalation. And lastly, cyanide can also react with hydroxycobalamin to form vitamin B 12 (URL1). The normalmetabolism of cyanide is limited by the availability of sulfane which is a substrate for the enzyme rhodanese(URL 3).

Cyanide Poisoning

Inhalation of hydrogen cyanide gas or ingestion of potassium cyanide causes a rapid and extensive inhibitionof the mitochondrial electron transport chain at the cytochrome oxidase step. Cyanide has been recognized as

one of the most potent and rapidly acting poisons. Unlike in haemoglobin, the iron in electron transport chainis in the ferric form, cyanide binds to the Fe3+ in the heme of the cytochrome a,a 3 component of the terminalstep in the electron transport chain. Thereby preventing oxygen (the final electron acceptor) from reactingwith cytochrome a,a 3 (Devlin, 1997).

Image retrieved from: (Lipincotts, )


4/8

Mitochondrial respiration and energy production cease, and cell death occurs rapidly. Death due to cyanidepoisoning occurs from tissue asphyxia, most notably of the central nervous system. If cyanide poisoning isdiagnosed very rapidly, a patient who has been exposed to cyanide is given various nitrites that convertoxyhemoglobin to methemoglobin, which merely involves converting the Fe2+ of hemoglobin to Fe3+ inmethemoglobin. Methemoglobin (Fe3+) competes with cytochrome a,a 3 (Fe3+) for cyanide, forming amethemoglobincyanide complex. Administration of thiosulfate causes the cyanide to react with the enzymerhodanese, forming the nontoxic compound thiocyanate (Devlin, 1997).

The general clinical manifestations of cyanide poisoning include general weakness, confusion, unusual orbizarre behaviour, excessive drowsiness, coma, shortness of breath, headache, dizziness, seizure. Moreover,the skin of a cyanide poisoned patient can sometimes appear as cherry red because oxygen will stay in theblood and will not be transported into tissues/ cells (problem with extraction and utilization of O 2 on a cellularlevel).

The clinical manifestations of cyanide poisoning are largely a reflection of intracellular hypoxia (Table 1).

Table 1. Clinical manifestations of cyanides toxic effects

System ManifestationsCentral Nervous Early (due to hypoxia)

AnxietyHeadacheGiddinessDizzinessConfusionMydriasisBright retinal veins (elevated venous PO 2)

Late Decreased consciousnessSeizuresParalysisComatose

Respiratory Early Hyperventilation and tachypnea (due to hypoxic

stimulation of peripheral and centralchemoreceptors)

Late

Absence of cyanosis (caused by an increase inoxygen content in venous blood)HypoventilationApnea (cells cannot take up oxygen)

Cardiovascular Early Tachycardia

LateHypotensionSupraventricular tachycardia


5/8

Atrioventricular blocksVentricularr fibrillationAsystole

*Based on data from DesLauriers et al., Hall et al., and Nelson

Management:

Initial management of patients with acute cyanide poisoning requires rapid assessment and identification of the most likely route of exposure to determine proper decontamination. Patients with suspected inhalationexposure should first undergo decontamination by being evacuated from the contaminated area and havingaffected clothing removed.

For patients with oral ingestion, decontamination is also a crucial process. The decontamination process mayinclude the use of face mask, eye shield, and double gloving with frequent change or use of butyl rubbergloves. Emesis should not be induced in patients with suspected ingestion. Because cyanide causes a decreasein oxygen utilization, the administration of 100% oxygen by nonrebreather mask or endotracheal tube is

indicated in acute poisoning. Although 100% oxygen will not correct the problem, it may enhance theeffectiveness of antidotal therapy by competing with cyanide for cytochrome oxidase binding sites.

Table 2. The cyanide antidote kit and hydroxocobalamin

Medications Dosing Mechanism of ActionAmyl nitrite Crushed 0.3 mL ampule inhaled

for 15 sec; may repeat 3-5 minsuntil intravenous accessestablished*Amyl nitrite should be

discontinued once intravenousaccess is obtained and sodiumnitrite infusion is started

Induces methemoglobinemia viaoxidation to bind cyanide

Sodium nitrite 300 mg (10 ml in a 3% solution) or10 mg/kg given intravenously for3-5 mins

Induces methemoglobinemia viaoxidation to bind cyanide

Sodium thiosulfate 1 ampule, or 12.5 g in 50 ml, givenintravenously for 30 mins in adults*for children the dosage is 7g/m 2 ,not to exceed 12.5 g

Combines with unbound cyanideto form renally excretedthiocyanate

HydroxocobalaminHydroxocobalamin 5 g for adults, administered

intravenously for 15 mins, repeata half dose if needed; 70 mg/kg inchildren

Combines with unbound to formcyanocobalamin.

*Based on data from Koschel.


6/8

The use of hydroxocobalamin was approved by Food and Drug Administration in December 2006. Thisapproval is significant because of its low incidence of adverse events, hence, it is a potentially acceptablechoice in prehospital settings.

The Cyanide antidote kit

An understanding on both availability of antidotes and their respective benefits, contraindications, side

effects, and monitoring requirements is essential to the proper care and management of patients with acutecyanide poisoning.

This kit consists of 3 medications given together for their synergistic effect: amyl nitrite, sodium nitrite, sodiumthiosulfate. Amyl nitrite is administered via inhalation over 15-30 seconds while intravenous access isestablished. Sodium nitrite is then administered intravenously over 3 to 5 minutes, and then intravenoussodium thiosulfate over 30 minutes (Hamel, 2011).

The 2 nitrites are administered to form methemoglobin and bind cyanide. This is given by the action of nitritein oxidizing the iron in haemoglobin to form cyanmethemoglobin.

Nitrites + oxyhemoglobin methhemoglobin

+

Cyanide cyanmethemoglobin

Since cyanide appears to bind preferentially to ferric ion of methemoglobin rather than the ferric ion of cytochrome oxidase a 3 in the mitochondria, cyanmethemoglobin draws away from the mitochondria. Thisprocess frees the mitochondria for electron transport and return to aerobic cellular respiration. Hence, thecells are able to generate ATP and production of lactic acid ceases.

In addition to that, sodium thiosulfate is administered in combination with the nitrites to clear cyanide byacting as a sulfhydryl donor. That is, the unbound extracellular cyanide binds with sulphur of thiosulfate toform the renally excreted thiocyanate (Hamel, 2011).

Hydroxocobalamin

Hydroxocobalamin detoxifies cyanide by binding with it to form the renally excreted, nontoxic cyanocobalamin(Vit. B12). Cyanocobbalamin releases cyanide at a rate that is slow enough to allow the enzyme rhodanese toodetoxify 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 (Hamel, 2011).

It is considered to be the most effective antidote against acute cyanide poisoning because it binds withcyanide without forming methemoglobin. In addition to that, it can also be used to treat patients with cyanidepoisoning without compromising the oxygen- carrying capacity of haemoglobin, and this is crucial for pregnantpatients and those wo have decreased concentration of useful haemoglobin (Hamel, 2011).


7/8

Important considerations

Table 3. Nursing considerations for the cyanide antidote kit and hydroxocobalamin

Antidote Adverse Effects Other considerationsCyanide antidote kit Potent vasodilatation from the

nitriles which may lead tohypotension

Methemoglobin accumulationwhich may be harmful or lethal inpatients who already have adeficiency of oxygenated blood,such as those exposed to CO

Monitoring of methemoglobinlevels is indicated and should notexceed 20%

Contraindicated in smokeinhalation patients is notconsidered safe in pregnantpatients

Hydroxocobalamin May cause transient hypotension

Most common adverse effectsinclude reddening of the skin and

urine

Is safe for smoke- inhalationpatients

May be used in pregnant patients

May interfere with colorimetrictests because of its red color

Effect on blood pressure may bebeneficial in patients in shock

*Based on data from Shepherd, Velez, and Koschel.


8/8

Literatures Cited

URL 1: en.m.wikipedia.org/wiki/Cyanide. Date accessed: 30 August 2013

URL 2: www.bt.cdc.gov/agent/cyanide/basics/facts.asp . Date accessed: 30 August 2013

URL3: www.health.ny.gov..environmentat/emergency/chemical/terrorism/cyanide_ted.html Date

Accessed: 30 August 2013

URL 4: en.mwikipedia.org/wiki/Rhodanese. Date accessed: 30 August 2013

DesLauriers, CA., Burda, AM., Wahl, M., Hydroxocobalamin as a cyanide antidote. AM J Ther. 2006; 13(2)

:161-165

Devlin, T. (1997). Textbook of Biochemistry: With Clinical Correlations.4 th edition. US: John Wiley and Sons, Inc.

Granner, D., Mayes, P., Murray, R., and Rodwell, V., (2003). Harpers Illustrated Biochemistry. 26 th edition.

USA: McGraw- Hill Companies.

Cox, M., and Nelson, D., (2004) Lehningers Principles of Biochemistry. 4 th edition. USA: John Wiley and Sons,

Inc.

Hamel, J., A Review of Acute Cyanide Poisoning with a Treatment Update. American Association of Critical

Care Nurses . 2011. doi: 10.4037/ccn2011799.

Shepherd and Velez, L., Role of hydroxocobalaminin acute cyanide poisoning. Ann pharmacother . 2008;42 (5)

:661-669

Nelson, L., Acute cyanide toxicity: mechanisms and manifestations. J Emerg Nurs. 2006; 32(4suppl): S8-S11.

Koschel, MJ. Management of the cyanide poisoned patient. J Emerg Nurs . 2006; 32(4suppl): S19-S26.

US Food and Drug Administration. FDA news: FDA approves drug to treat cyanide poisoning. US Food and Drug

Administration website:

wwww.fda.gov/NewsEvents/NewsRoom/PressAnnouncements/2006/ucm108801.htm. Published

15 December 2006. Date accessed: 30 August 2013.
http://www.bt.cdc.gov/agent/cyanide/basics/facts.asphttp://www.bt.cdc.gov/agent/cyanide/basics/facts.asphttp://www.bt.cdc.gov/agent/cyanide/basics/facts.asphttp://www.health.ny.gov..environmentat/emergency/chemical/terrorism/cyanide_ted.htmlhttp://www.health.ny.gov..environmentat/emergency/chemical/terrorism/cyanide_ted.htmlhttp://www.health.ny.gov..environmentat/emergency/chemical/terrorism/cyanide_ted.htmlhttp://www.health.ny.gov..environmentat/emergency/chemical/terrorism/cyanide_ted.htmlhttp://www.bt.cdc.gov/agent/cyanide/basics/facts.asp

biochem.cyanide poisoning

Documents