Cyanide ( hydrocyanic acid, prussic acid) is NOT a common poison.

Most cyanide ingestions occur from accidental exposure or intentional ingestion of a cyanide-containing compound.

Some fruit seeds contain TOXIC LEVELS of cyanide.

Amygdalin, which is hydrolyzed to hydrogen cyanide is present in the seeds of apple, peach, plum, apricot, cherry, and almond.

Usually exposure occurs in industry. Hydrocyanide and its derivatives are

used in electroplating, metallurgy, and extraction of gold and silver from ores, plastic manufacture, and many other industries.

It’s very important to know that intoxication does not happen only through ingestion, it also happens from inhalation or absorption through the skin.

In the presence of cyanide gas, a gas mask alone does not offer complete protection from intoxication.

Hydrogen cyanide is readily volatilized to hydrogen cyanide, with a characteristic odor of bitter almonds.

Cyanide salts are the most frequently encountered of all cyanide-containing compounds.

LD50 for these salts is 2 mg/kg, and the ingestion of 50-75 mg of these salts results in syncope and respiratory difficulty.

Cyanide produces histotoxic cellular Cyanide produces histotoxic cellular hypoxia by hypoxia by binding to ferric ( Febinding to ferric ( Fe3+3+ ) ion in ) ion in the electron transport system.the electron transport system.

Cyanide binds to the cytochrome oxidase Cyanide binds to the cytochrome oxidase system inhibiting electron transport , system inhibiting electron transport , consequently consequently no ATP can be generatedno ATP can be generated, , this results in reduced cellular utilization of this results in reduced cellular utilization of oxygen.oxygen.

As a summary, cyanide has the same As a summary, cyanide has the same pathophysiologic effect as a complete lack pathophysiologic effect as a complete lack of oxygen .of oxygen .

As a result, aerobic respiration ceases As a result, aerobic respiration ceases resulting in a decrease in pyruvate resulting in a decrease in pyruvate conversion in the Krebs cycle , therefore conversion in the Krebs cycle , therefore lactate increases resulting in metabolic lactate increases resulting in metabolic acidosis .acidosis .

cyanide is extremely rapid acting and capable of producing death within minutes.

the classic odor of bitter almond is not detected by everyone (genetically determined) .

Hydrogen cyanide vapors are the most rapidly acting. But when cyanide salts are ingested toxicity is delayed because they are slowly absorbed.

The severity of acute poisoning is determined by the dose and time since exposure.

Cyanide stimulates chemoreceptors in aortic and carotid bodies to signal respiratory center in the brain which results in increased respiration (hyperpnea, i.e. increased minute ventilation)

As cyanide levels increase (severe poisoning) respiration rate slows and gasping occurs, but still, with no or minimal cyanosis.

Severe CNS oxygen deprivation may cause hypoxic convulsions and death due to respiratory arrest.

Cardiovascular and central nervous system most affected body systems

Exposure is rapidly fatal unless antidote quickly administered

Depend on CN Levels in the body which are measured by the methemoglobin level:

Normally <1% of our Hb is methemoglobin

Pts remain Asx to a lvl up to 20% ,showing only skin discoloration

Sx start to appear at lvls >20% ,and manifest mainly as neurological toxicity ,tachypnea & tachycarida

1-3% - asymptomatic 3-15% - slight grayish-blue skin

discoloration 15-20% - asymptomatic, but

cyanotic So 25-50% - headache, dyspnea,

confusion, weakness, chest pain 50-70% - altered mental status,

delirium

Weakness Dizziness Headache Nausea and vomiting Tachycardia Flushing Those occur rapidly and non-

specific .

Stuporous but responsive to stimuli

Tachycardia Tachypnea

Comatose Unresponsive Hypotension Bradypnea & gasping Dilated pupils Cyanosis ( at high levels) Death unless treated immediately

The aim is to decrease the amount of cyanide available for cellular binding, and decrease its binding to cytochrome oxidase.

Treatment must be initiated immediately to be effective.

But because it acts so rapidly, intentional ingestion (suicide) almost always leads to death. In addition, diagnosis can be delayed, which also may result in death.

Luckily, specific antidotes are available.

1.Resuscitation :ABC2.Decontamination : If due to Inhalation :(remove

clothes ,flush with water ,removal of the individual from the source)

If due to Ingestion : (Administer activated Charcoal /gastric lavage)

3.Cyanide Antidote Package 4.Other CN Antidote kits :4-

methylaminophenol ,Hyperbaric oxygen

Cyanide (even at toxic concentrations) Cyanide (even at toxic concentrations) can dissociate from ferric ion binding can dissociate from ferric ion binding sites and be converted to thiocyanate sites and be converted to thiocyanate in the presence of thiosulfate and in the presence of thiosulfate and sulfur transferasesulfur transferase..

ThiocyanateThiocyanate is relatively is relatively nontoxicnontoxic and and is rapidly excreted by the kidneys.is rapidly excreted by the kidneys.

BUT, when this endogenous BUT, when this endogenous detoxification system becomes detoxification system becomes saturated, toxicity occurs, unless saturated, toxicity occurs, unless specific treat is initiated.specific treat is initiated.

The main principle of treatment is to The main principle of treatment is to produce methemoglobin because it produce methemoglobin because it contains ferric (Fecontains ferric (Fe3+3+ ) ion, and thus ) ion, and thus competes with cytochrome oxidase for competes with cytochrome oxidase for binding cyanide.binding cyanide.

Cyanide + methemoglobin Cyanide + methemoglobin cyanomethemoglobincyanomethemoglobin

Methemoglobin has a greater affinity for Methemoglobin has a greater affinity for cyanide than does cytochrome oxidasecyanide than does cytochrome oxidase. . Therefore, methemoglobin can bind to Therefore, methemoglobin can bind to free cyanide and also cause dissociation free cyanide and also cause dissociation of the cyanide-cytochrome oxidase of the cyanide-cytochrome oxidase complex, thus reactivating it.complex, thus reactivating it.

In summary, to treat cyanide poisoning In summary, to treat cyanide poisoning we have to produce methemoglobin in we have to produce methemoglobin in the blood!!!the blood!!!

How to produce methemoglobin?1. Methylene blue (in large doses)2. Amyl nitrite (inhalation) produces only

5%3. Sodium nitrite (IV)

Hemoglobin(Fe+2 ) + amyl nitrite &/or sodium nitrite methemoglobin (Fe+3 )

The desired percentage of methemoglobin is around 40%.

BUT, all the above reactions are REVERSIBLE and may shift in the opposite direction.

This is the reason that there is a 2nd phase of treatment.

The 2nd phase involves the binding of cyanomethemoglobin with thiosulfate in the presence of sulfur transferase to produce thiocyanate (which is excreted by the kidneys).

Cyanomethemoglobin + thiosulfate thiocyanate + sulfite + methemoglobin

BE CAREFUL, because too much methemoglobin can shift the oxygen dissociation curve to the left, thus decreasing the amount of oxygen available for the tissues. And because the tissue ability to utilize oxygen is already diminished by the presence of cyanide, too much methemoglobin can worsen tissue hypoxia.

However, this doesn’t happen unless methemoglobin concentration reaches 40-50%.

ALSO, nitrites can produce profound hypotension and cardiovascular collapse thus rendering the treatment completely ineffective.

Oxygen is NOT a specific antidote for cyanide poisoning. BUT, it is a necessary adjunct.

Mechanisms:1. Displace cyanide from cytochrome oxidase2. Nonenzymatically convert reduced

cytochrome to oxidized cytochrome enabling the electron transport system to function again

Unlike treating CO poisoning, oxygen administration does not produce significant benefits.