cyanide presentation

USAMRICDUSAMRICDPROTECT, PROJECT, SUSTAIN

Cyanide

CYANIDECYANIDE

U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSEU.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE

CHEMICAL CASUALTY CARE DIVISIONCHEMICAL CASUALTY CARE DIVISION


Cyanide

M_Cyanide 2

Objectives

•• Distribution (occurrence) and historyDistribution (occurrence) and history

•• Physical and chemical propertiesPhysical and chemical properties

•• Mechanism of actionMechanism of action

•• Clinical presentationClinical presentation

•• TreatmentTreatment


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Distribution and History

•• Ubiquitous (in low concentrations)Ubiquitous (in low concentrations)•• Interstellar space and prebiotic earthInterstellar space and prebiotic earth•• Most living organismsMost living organisms

ww Man: < 0.20 Man: < 0.20 µµµµg / mL (8 g / mL (8 µµµµmol / L) in bloodmol / L) in blood

•• Poisonous in higher concentrationsPoisonous in higher concentrations•• Favorite of assassins and terroristsFavorite of assassins and terrorists•• CW agents: CW agents: ACAC and and CKCK

•• Do not confuse CNDo not confuse CN-- (cyanide ion) with (cyanide ion) with CN CN (chloroacetophenone)(chloroacetophenone), a riot control agent, a riot control agent


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History and Military Use

•• Ancient Egypt and RomeAncient Egypt and Rome

•• Scheele: Isolated Prussic acid (1782)Scheele: Isolated Prussic acid (1782)

•• Playfair: Advocated use during Crimean WarPlayfair: Advocated use during Crimean War

•• Napoleon III: Proposed use in FrancoNapoleon III: Proposed use in Franco--Prussian warPrussian war

•• WW I: French (Vincennite) and BritishWW I: French (Vincennite) and British

•• Nazi Germany: Zyklon BNazi Germany: Zyklon B

•• Middle East: Apparent use in Hama and HalabjaMiddle East: Apparent use in Hama and Halabja


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Cyanide off the Battlefield

•• TerroristsTerrorists

•• HomicidalHomicidal and and suicidalsuicidal useuse

•• Judicial Judicial executionsexecutions

•• CombustionCombustion (plastics, cigarettes, vehicle exhaust)(plastics, cigarettes, vehicle exhaust)

•• IndustryIndustry (ore processing, chemical syntheses)(ore processing, chemical syntheses)

•• Household products Household products (silver polish, acetonitriles)(silver polish, acetonitriles)

•• Illicit manufacture of PCPIllicit manufacture of PCP

•• Iatrogenic exposures: Iatrogenic exposures: Sodium nitroprussideSodium nitroprusside

•• Pseudomonas infectionsPseudomonas infections


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Cyanogenic Glycosides in Plants

•• AmygdalinAmygdalin (Laetrile(Laetrile®®; bitter almonds, apricot seeds); bitter almonds, apricot seeds)

•• PrunasinPrunasin (cherry laurel water;(cherry laurel water;also primary metabolite of amygdalin)also primary metabolite of amygdalin)

•• DhurrinDhurrin (sorghum, bamboo shoots, other grasses)(sorghum, bamboo shoots, other grasses)

•• LinamarinLinamarin (cassava [manioc], certain lima beans,(cassava [manioc], certain lima beans,linseed oil)linseed oil)

•• Hydrolysis by Hydrolysis by ββββ --glucosidase in emulsin yields HCNglucosidase in emulsin yields HCN


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Diseases Related to Cyanide Exposure•• Tropical ataxic neuropathyTropical ataxic neuropathy (TAN)(TAN)

•• KonzoKonzo (upper(upper--motormotor--neuron disease in Zaire)neuron disease in Zaire)

•• Subacute combined degenerationSubacute combined degeneration of the spinal cordof the spinal cord

•• Retrobulbar neuritisRetrobulbar neuritis in pernicious anemiain pernicious anemia

•• Dominantly and recessively inherited Dominantly and recessively inherited optic atrophiesoptic atrophies

•• Leber’s hereditary optic atrophyLeber’s hereditary optic atrophy (LOA)(LOA)

•• Tobacco amblyopiaTobacco amblyopia


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CN-: Chemistry and Biochemistry

•• High affinity for ions of transitional High affinity for ions of transitional metalsmetals•• CobaltCobalt•• Iron, especially ferric ion (FeIron, especially ferric ion (Fe3+3+))

ww Cytochromes (FeCytochromes (Fe2+2+ and Feand Fe3+3+))ww Heme in methemoglobin (metHb) (FeHeme in methemoglobin (metHb) (Fe3+3+))

•• Ability to react enzymatically with Ability to react enzymatically with sulfanessulfanes (S(S--SS--))

•• Other reactionsOther reactions(especially with carbonyl and sulfhydryl groups)(especially with carbonyl and sulfhydryl groups)


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CN-: Normal Metabolism

•• CNCN-- + Vitamin B+ Vitamin B12a 12a Cyanocobalamin (BCyanocobalamin (B1212))

•• CNCN-- + Sulfanes (S+ Sulfanes (S--SS--) Thiocyanates (SCN) Thiocyanates (SCN--))+ Sulfa+ Sulfates (SOtes (SO33

22--))•• Sulfane reaction Sulfane reaction catalyzedcatalyzed by rhodaneseby rhodanese

•• Sulfane reaction Sulfane reaction essentially irreversibleessentially irreversible

•• RateRate--limiting factor: Sulfanes (sulfur donors)limiting factor: Sulfanes (sulfur donors)

•• Reactions with carbonyl and sulfhydryl compoundsReactions with carbonyl and sulfhydryl compounds(directly [non(directly [non--enzymatically] and via enzymes such asenzymatically] and via enzymes such as33--mercaptopyruvate sulfur transferase [MPST])mercaptopyruvate sulfur transferase [MPST])


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AC: Hydrogen Cyanide

•• HCN HCN HH+ + + CN+ CN--

•• Highly water soluble, but only weakly acidic: Highly water soluble, but only weakly acidic: Hydrocyanic (Prussic) acidHydrocyanic (Prussic) acid

•• Very Very volatilevolatile; vapor and gas 94.1% as dense as air and ; vapor and gas 94.1% as dense as air and explosiveexplosive

•• Boiling point 25.6Boiling point 25.6°°°° C (78.1C (78.1°°°° F)F)


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AC: Hydrogen Cyanide

•• Faint Faint “musty”“musty” odor of odor of bitter almondsbitter almonds, , peach pitspeach pits, or , or burning ropeburning rope (ability to detect is genetically determined (ability to detect is genetically determined and is absent in up to 40and is absent in up to 40--50% of the population)50% of the population)

•• Onset time: Onset time: SecondsSeconds with high inhaled concentrationswith high inhaled concentrations

•• LCtLCt5050: 2500: 2500--5000 mg5000 mg--min / mmin / m33 (varies with concentration (varies with concentration of gas and duration of exposure)of gas and duration of exposure)


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CK: Cyanogen Chloride

•• CNClCNCl CNCN-- + Cl+ Cl22

•• Slightly water solubleSlightly water soluble

•• Very Very volatilevolatile; vapor and gas heavier than air; vapor and gas heavier than air

•• Boiling point 13.8Boiling point 13.8°°°° C (56.8 C (56.8 °°°° F)F)


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CK: Cyanogen Chloride

•• Pungent, biting odor masked by Pungent, biting odor masked by irritationirritation of eyes, of eyes, nose, and respiratory tractnose, and respiratory tract

•• Onset time: Onset time: SecondsSeconds with high inhaled with high inhaled concentrationsconcentrations

•• LCtLCt5050: 11,000 mg: 11,000 mg--min / mmin / m33 at physiological pHat physiological pH


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Comparative Toxicity of Cyanide

0

1000

2000

3000

4000

5000

6000

CL CG AC H GB VX BZ CS

AGENT (L) (L)(L)(L)(L) (E)(E)(L)

Ct50

(mg-min/m3)


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Cyanide: Toxicokinetics (ADBE)

•• AAbsorption: bsorption: InhalationInhalation > ingestion > percutaneous absorption> ingestion > percutaneous absorption

•• DDistribution: istribution: Wide distributionWide distribution to all tissues via bloodto all tissues via blood

•• BBiotransformation: iotransformation: Reactions with Reactions with ____________ and and ____________

•• EElimination:limination:ww Unchanged cyanideUnchanged cyanide in in breathbreath, , sweatsweat, and , and urineurineww ThiocyanateThiocyanate and and cyanocobalamincyanocobalamin in in urineurineww Iminothiocarboxylic acid (ITCA)Iminothiocarboxylic acid (ITCA)


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Mechanism of Action

•• A “blood agent”? (compare CO)A “blood agent”? (compare CO)

•• Reaction with FeReaction with Fe2+2+ in HbOin HbO22 to form HbCNto form HbCN(quantitatively unimportant)(quantitatively unimportant)

•• Elevation of blood levels of ammonia and of neutral and Elevation of blood levels of ammonia and of neutral and aromatic amino acids (probably a secondary event)aromatic amino acids (probably a secondary event)

•• Lactic acidosis (predominantly a secondary event)Lactic acidosis (predominantly a secondary event)


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Mechanism of Action: The Classical Explanation

•• Primary site of action: Primary site of action: CellsCells rather than bloodrather than blood

•• Interruption of cellular respiration in mitochondriaInterruption of cellular respiration in mitochondria

•• Result: Histotoxic anoxiaResult: Histotoxic anoxia


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Classical Mechanism of Action

•• Binding of CNBinding of CN-- to cyt ato cyt a33 in mitochondriain mitochondria

•• Stable but not irreversible bindingStable but not irreversible binding

•• CNCN-- has higher affinity for the Fehas higher affinity for the Fe3+3+ in methemoglobin in methemoglobin (metHb)(metHb)

•• Interruption of oxidative phosphorylationInterruption of oxidative phosphorylation


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Oxidative Phosphorylation Chain (Terminal End)

cyt c cyt a cyt a3 Cu

O2 and H+

H2OCytochrome c oxidase(cytochrome aa3)

ADP ATP


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Oxidative Phosphorylation Chain (Terminal End) with CN-

cyt c cyt a cyt a3 Cu

O2 and H+

H2OCytochrome c oxidase(cytochrome aa3)

ADP ATP

CN -


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Effects on Cells and Blood

•• No generation of ATPNo generation of ATP;;cessation of all processescessation of all processesdependent upon ATPdependent upon ATP

•• No extraction of ONo extraction of O22 from bloodfrom blood;;decreased AV Odecreased AV O22 differencedifference

•• Pasteur shift to anaerobic glycolysisPasteur shift to anaerobic glycolysis;;lactic acidosis and high anion gaplactic acidosis and high anion gap


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Effects at Organ Level•• Carotid and aortic chemoreceptorsCarotid and aortic chemoreceptors

•• Intense stimulationIntense stimulation from lack of usable oxygenfrom lack of usable oxygenww Results in neural stimulation of respiratory center and adrenal Results in neural stimulation of respiratory center and adrenal medullamedulla

•• CNSCNS (nerve more sensitive than muscle)(nerve more sensitive than muscle)•• Variation of sensitivity and effects within CNSVariation of sensitivity and effects within CNS

•• RespiratoryRespiratory--center failurecenter failure (central apnea):(central apnea):USUAL MECHANISM OF DEATHUSUAL MECHANISM OF DEATH

•• HeartHeart•• Accumulation in left ventricleAccumulation in left ventricle

•• Increased demand (from released catecholamines)Increased demand (from released catecholamines)in the face of reduced energy supplyin the face of reduced energy supply

•• Cardiac dysrhythmias and heart failureCardiac dysrhythmias and heart failure


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Clinical Presentation with High Doses

•• Rapid onsetRapid onset when CNwhen CN-- inhaled in high concentrations inhaled in high concentrations

•• With massive doses, collapse and death may be With massive doses, collapse and death may be nearly nearly instantaneousinstantaneous (apoplectic form)(apoplectic form)

•• OnsetOnset often in often in 1010--18 seconds18 seconds

•• DeathDeath often in often in 55--8 minutes8 minutes


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Progression of Symptoms and Signs

•• Transient Transient increase in rate and depth of respirationincrease in rate and depth of respiration (from (from hypoxia of carotid and aortic bodies)hypoxia of carotid and aortic bodies)

•• Initial Initial hypertensionhypertension and and tachycardiatachycardia(from hypoxia of aortic body)(from hypoxia of aortic body)

•• ConvulsionsConvulsions / rigidity / opisthotonus / trismus / decerebrate / rigidity / opisthotonus / trismus / decerebrate posturing (20 posturing (20 -- 30 seconds)30 seconds)

•• Respiratory depression and arrestRespiratory depression and arrest (1 (1 -- 2 minutes)2 minutes)

•• BradycardiaBradycardia, , hypotensionhypotension, and , and cardiac arrestcardiac arrest


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Clinical Presentation: Skin

•• Initial Initial flushingflushing and and diaphoresisdiaphoresis may occurmay occur

•• Skin and breath may smell of Skin and breath may smell of bitter almondsbitter almonds

•• AcrylonitrileAcrylonitrile--induced bullaeinduced bullae

•• Cyanide poisoning is NOT characterized by Cyanide poisoning is NOT characterized by cyanosis cyanosis early in its course!early in its course!


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Clinical Presentation: Other•• Exposure to low concentrationsExposure to low concentrations

•• Onset may be delayed and gradualOnset may be delayed and gradual•• Headache, anxiety, weakness, lightheadedness, vertigo, Headache, anxiety, weakness, lightheadedness, vertigo,

ataxia, nystagmus, muscle rigidityataxia, nystagmus, muscle rigidity

•• IngestionIngestion•• HypersalivationHypersalivation•• Acrid, burning, metallic, or constricting sensationsAcrid, burning, metallic, or constricting sensations•• Epigastric pain (with some plant ingestions)Epigastric pain (with some plant ingestions)•• Hyperthermia (with some plant ingestions)Hyperthermia (with some plant ingestions)•• Nausea and vomiting (central effect; may also be seen Nausea and vomiting (central effect; may also be seen

following inhalationfollowing inhalation


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Clinical Presentation: Classic Signs

•• Bright red venous blood, skin, and fundal vesselsBright red venous blood, skin, and fundal vessels

•• Profound metabolic acidosis with high anion gapProfound metabolic acidosis with high anion gap

•• Odor of bitter almondsOdor of bitter almonds

•• Tachypnea, hypertension, and bradycardiaTachypnea, hypertension, and bradycardiawithoutwithout cyanosiscyanosis

•• Respiratory depression Respiratory depression withoutwithout cyanosiscyanosis


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Cyanide and ASBESTOS

ww AAgent(s):gent(s): Type(s) and toxicity (including LDType(s) and toxicity (including LD5050))

ww SState(s):tate(s): Solid? Solid? LiquidLiquid? Gas? ? Gas? VaporVapor? Aerosol?? Aerosol?

ww BBody site(s):ody site(s): Where exposed / Route(s) of entry? [Where exposed / Route(s) of entry? [absorptionabsorption]]

ww EEffects:ffects: Local? Systemic? [Local? Systemic? [distributiondistribution]]

ww SSeverity:everity: Mild? Moderate? Severe?Mild? Moderate? Severe?

ww TTime course:ime course: Onset? Getting better/worse? Prognosis?Onset? Getting better/worse? Prognosis?

ww OOther diagnoses: Instead of? [ther diagnoses: Instead of? [DDxDDx] In addition to?] In addition to?

w Synergism: Combined effects of multiple exposures or insults?


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Treatment

•• Prerequisite: Prerequisite: Protect yourself!Protect yourself!

•• General supportive therapyGeneral supportive therapy

•• Specific antidotal therapySpecific antidotal therapy


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General Supportive Therapy•• Termination of exposureTermination of exposure

•• Removal of patient:Removal of patient:ww Physical removal, maskingPhysical removal, masking

•• Removal of agentRemoval of agentww Decontamination (soap and water)Decontamination (soap and water)ww Gastric lavage with activated charcoal, 5% sodium thiosulfate, 0Gastric lavage with activated charcoal, 5% sodium thiosulfate, 0.1% .1%

potassium permanganate, or 1.5% hydrogen peroxide (ingestion)potassium permanganate, or 1.5% hydrogen peroxide (ingestion)

•• AAirway, irway, BBreathing, and reathing, and CCirculationirculation(but beware unprotected mouth(but beware unprotected mouth--toto--mouth respiration)mouth respiration)

•• 100% 100% oxygenoxygen (normobaric vs. hyperbaric)(normobaric vs. hyperbaric)•• Correction of metabolic acidosisCorrection of metabolic acidosis•• ObservationObservation for at least 24 to 48 hoursfor at least 24 to 48 hours


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Goals of Specific Antidotal Therapy

•• Displacement of CNDisplacement of CN-- from cytochrome afrom cytochrome a33

•• Reaction of CNReaction of CN-- with metHb generated by with metHb generated by nitritesnitrites or or other metHb formersother metHb formers

•• Enzymatic conversion of CNEnzymatic conversion of CN-- to thiocyanateto thiocyanate•• Administration of a sulfane (e.g., Administration of a sulfane (e.g., sodium thiosulfatesodium thiosulfate) )

as a sulfur donoras a sulfur donor


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Cyanide and Cytochrome a3

O2Lungs

Tissues

Hb

(Fe2+)

HbO2

(Fe2+)

CN-

cyt a3

(Fe2+ and Fe3+)cyt a3 - CN

O2


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O2Lungs

Tissues

Hb(Fe2+)

HbO2(Fe2+)

CN-

cyt a3


NO2-

metHb(Fe3+)

CNmetHb

Displacement of CN- from cyt a3

O2


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O2Lungs

Tissues

Hb(Fe2+)

HbO2(Fe2+)

CN-

cyt a3


NO2-

metHb(Fe3+)

CNmetHb


O2


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Amyl Nitrite: (C5H11NO2)•• Therapeutic effect noted as early as 1888Therapeutic effect noted as early as 1888

•• One of three components of the commercially One of three components of the commercially available cyanide antidote kitavailable cyanide antidote kit

•• Given by Given by inhalationinhalation by crushing vialsby crushing vials

•• Converts Hb (FeConverts Hb (Fe2+2+) to metHb (Fe) to metHb (Fe3+3+), but ), but inhalation leads to variable metHb levelsinhalation leads to variable metHb levels


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Sodium Nitrite (NaNO2)

•• Converts HbOConverts HbO22 (Fe(Fe2+2+) to metHb (Fe) to metHb (Fe3+3+))

•• Therapeutic effect seen before metHb generatedTherapeutic effect seen before metHb generated

•• Vasodilatory mechanism of action?Vasodilatory mechanism of action?

•• Adverse effectsAdverse effects•• Methemoglobinemia (maintain <40% metHb)Methemoglobinemia (maintain <40% metHb)•• HypotensionHypotension


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Sodium Nitrite: Administration

•• 10 mL IV of a 3% soln (30 mg / mL) = 300 mg10 mL IV of a 3% soln (30 mg / mL) = 300 mg

•• Administer over at least a 3Administer over at least a 3--minute periodminute period

•• Give half original dose if signs recurGive half original dose if signs recur


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O2Lungs

Tissues

Hb(Fe2+)

HbO2(Fe2+)

CN-

cyt a3


NO2-

metHb(Fe3+)

CNmetHb

O2


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Conversion of CN- to Thiocyanate

O2Lungs

Tissues

Hb(Fe2+)

HbO2(Fe2+)

CN-

cyt a3


NO2-

metHb(Fe3+)

CNmetHb

+ Na2S2O3SCN- + SO32-

(urine)

rhodanese

O2


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O2Lungs

Tissues

Hb(Fe2+)

HbO2(Fe2+)

CN-

cyt a3


NO2-

metHb(Fe3+)

CNmetHb

O2


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Conversion of CN- to Thiocyanate

O2Lungs

Tissues

Hb(Fe2+)

HbO2(Fe2+)

CN-

cyt a3


NO2-

metHb(Fe3+)

CNmetHb

+ Na2S2O3SCN- + SO3

2-

(urine)

rhodanese

O2


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Sodium Thiosulfate (Na2S2O3)

•• Enzymatically reacts with CNEnzymatically reacts with CN-- to form thiocyanate (SCNto form thiocyanate (SCN--) ) and sulfite (SOand sulfite (SO33

22--))

•• Irreversible reaction; thiocyanate excreted by kidneyIrreversible reaction; thiocyanate excreted by kidney

•• Adverse effects few and usually not seriousAdverse effects few and usually not serious

•• Nausea, vomiting, arthralgias, psychosis only with Nausea, vomiting, arthralgias, psychosis only with levels > 10 mg /dLlevels > 10 mg /dL


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Sodium Thiosulfate: Administration

•• 50 mL IV of a 25% soln (250 mg / mL) = 12.5 g50 mL IV of a 25% soln (250 mg / mL) = 12.5 g

•• Administer over a 10Administer over a 10--minute period beginning minute period beginning immediately after nitrite administrationimmediately after nitrite administration

•• Give half original dose if signs recurGive half original dose if signs recur


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Experience with Antidotes

•• “The combination of sodium nitrite and sodium thiosulfate is “The combination of sodium nitrite and sodium thiosulfate is

the best therapy against cyanide and hydrocyanic acid the best therapy against cyanide and hydrocyanic acid

poisoning. The 2 substances intravenously injected, one poisoning. The 2 substances intravenously injected, one

after the other, namely the nitrite followed by the thiosulfate,after the other, namely the nitrite followed by the thiosulfate,

are capable of detoxifying approximately 20 lethal doses of are capable of detoxifying approximately 20 lethal doses of

sodium cyanide in dogs and are effective even after sodium cyanide in dogs and are effective even after

respiration has stopped. respiration has stopped. As long as the heart is still beating, As long as the heart is still beating,

the chances of recovery by utilizing this method are very the chances of recovery by utilizing this method are very

good.good.” ” --Chen et al.Chen et al.


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Other Specific Antidotes

•• Other methemoglobin formersOther methemoglobin formers

•• Cobalt compoundsCobalt compounds

•• Miscellaneous compounds under investigationMiscellaneous compounds under investigation•• Carbonyl compounds (pyruvate, alphaCarbonyl compounds (pyruvate, alpha--ketoglutarate, ketoglutarate,

glyoxal trimer)glyoxal trimer)•• Sulfhydryl compounds (e.g., mercaptopyruvate)Sulfhydryl compounds (e.g., mercaptopyruvate)•• CalciumCalcium--channel blockers (e.g., diltiazem, verapamil)channel blockers (e.g., diltiazem, verapamil)•• ChlorpromazineChlorpromazine•• Naloxone, etomidate, etc.Naloxone, etomidate, etc.


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Other Methemoglobin Formers•• 44--Dimethylaminophenol (4Dimethylaminophenol (4--DMAP)DMAP)

•• Forms metHb more rapidly than do nitritesForms metHb more rapidly than do nitrites•• No hypotension, but metHb levels often too highNo hypotension, but metHb levels often too high•• Local necrosis may occur after IM injectionLocal necrosis may occur after IM injection

(give IV only)(give IV only)•• Used in GermanyUsed in Germany

•• ParaPara--aminoproplophenone (PAPP)aminoproplophenone (PAPP)•• ParaPara--aminooctanoylphenone (PAOP)aminooctanoylphenone (PAOP)•• Hydroxylamine (50 mg / kg IM effective in beagles)Hydroxylamine (50 mg / kg IM effective in beagles)•• Primaquine analogs (8Primaquine analogs (8--aminoquinolines)aminoquinolines)


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Cobalt Compounds

•• Dicobalt edetate (CoDicobalt edetate (Co22 EDTA, Kelocyanor)EDTA, Kelocyanor)

•• Chelates CNChelates CN--

•• Adverse effectsAdverse effects

ww Angina pectoris, ventricular dysrhythmias, periorbital Angina pectoris, ventricular dysrhythmias, periorbital and laryngeal edema, convulsionsand laryngeal edema, convulsions

•• Used in the U.K., France, and the NetherlandsUsed in the U.K., France, and the Netherlands


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Cobalt Compounds

•• Hydroxocobalamin (vitamin BHydroxocobalamin (vitamin B12a12a))

•• Reacts stoichiometrically with CNReacts stoichiometrically with CN-- to form to form cyanocobalamin (vitamin Bcyanocobalamin (vitamin B1212))

•• Difficult to administer adequate amountsDifficult to administer adequate amounts


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Summary

•• On the battlefield, usually a On the battlefield, usually a vaporvapor or a or a gasgas

•• Variable potency (LCtVariable potency (LCt5050)) because of limited metabolism,because of limited metabolism,but but rapidly actingrapidly acting in high concentrationsin high concentrations

•• NOT primarily a “NOT primarily a “bloodblood” agent;” agent;rather, probably a rather, probably a cellular poisoncellular poison

•• NitritesNitrites generate generate metHbmetHb, which “pulls” cyanide from cyt a, which “pulls” cyanide from cyt a33 andandcombines with the cyanide (reversible reaction;combines with the cyanide (reversible reaction;temporary reservoir for bound cyanide)temporary reservoir for bound cyanide)

•• ThiosulfateThiosulfate irreversibly reacts with cyanide to form thiocyanateirreversibly reacts with cyanide to form thiocyanate(excreted in urine)(excreted in urine)

cyanide presentation

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