Cyanide Poisoning

GROUP 4
CYANIDE POISONING
I.
II.
III.
IV.
V.
VI.
VII.
Define cyanide poisoning (acute and chronic exposure)

Identify the sources characteristics, purposes of cyanide.
Enumerate causes of cyanide poisoning.
Discuss the normal metabolism of cyanide in the body.
Illustrate how cyanide disrupts the electron transport chain
Explain the molecular basis of the different clinical manifestations observed in
cyanide poisoning.
Discuss the management and rationale for treatment of cyanide poisoning.
CYANIDE
- Cyanide is fast-acting, bitter-tasting and one of the deadliest known. Its
compound has famously been utilized in suicide pills over the years.
- Exists in gaseous, liquid, and solid forms. Hydrogen cyanide (HCN, also
known as prussic acid) is a volatile liquid that boils at 25.6 C (78.1 F).
Potassium and sodium cyanide salts are water soluble and gets
converted to HCN by stomach acid.
- Hydrogen cyanide is a colorless gas or liquid with a faint, bitter almond odor
(odor threshold of 0.58 parts per million)
- Sodium cyanide and potassium cyanide are both colorless solids that has
a slight odor of bitter almonds
- Uses:
o Historically, they were used as a chemical weapon in World War I and II.
o Used in pesticides and fumigants, plastics, electroplating,
photodeveloping and mining
o Also used by dye and drug companies [vasodilator nitroprusside
sodium, which may produce iatrogenic cyanide poisoning during
prolonged or high-dose intravenous (IV) therapy (>10 mcg/kg/min)]
- Sources:
o Combustion of rubber, plastic, wool, polyurethane, and silk produces
cyanide fumes
o Photography, chemical research, synthetic plastics, metal processing,
and electroplating industries
o Plant sources: apricot pits, cassava (104 mg CN/100g), almond (250
mg CN/100g), wild cherries (140-370 mg CN/ 100g), lima beans (100300 mg CN/ 100g) and sorghum (250 mg CN/100 g)
o Laetrile, a compound that contains amygdalin (a chemical found in the
pits of raw fruits, nuts, and plants) has been purported as a cancer
treatment worldwide
o Cigarette smoke (most common source of cyanide exposure)
CYANIDE POISONING
Rare form of poisoning, occurs relatively frequently in patients with smoke

inhalation from residential or industrial fires.
Results from inactivation of cytochrome oxidase (at cytochrome a3), thus
uncoupling mitochondrial oxidative phosphorylation and inhibiting cellular
respiration, even in the presence of adequate oxygen stores
Causes:
o Smoke inhalation during house or industrial fire: major source of
cyanide poisoning in USA (blood cyanide concentrations >40 mmol/L or
approx. 1 mg/L)
o Intentional poisoning: uncommon, but effective means of suicide
o Iatrogenic exposure: vasodilator sodium nitroprusside when used in
high doses or over a period of days can produce toxic blood
concentrations
o Industrial exposure: metal trades, mining, jewelry manufacturing,
dyeing, photography and agriculture, etc.
o Ingestion of cyanide-containing supplements or plants: rare (Amygdalin
or synthetic laetrile, also marketed as vitamin B-17 postulated to have
anticancer properties contains cyanide)
ACUTE CYANIDE POISONING

Short-term inhalation exposure to 100 milligrams per cubic meter or
more of hydrogen cyanide will cause death in humans (fatal dose in
humans of 1.5 mg/kg body weight)
At lower doses (6 to 49 mg/m3 ) will cause variety of effects in humans,
such as weakness, headache, confusion, nausea, increased rate or
respiration, and eye and skin irritation
May progress to deep coma and finally cardiac arrest
CHRONIC CYANIDE POISONING
Exposure to lower levels of cyanide over a long period results in
increased blood cyanide levels, which can result in weakness and a
variety of symptoms including permanent paralysis, nervous lesions,
hypothyroidism and miscarriages
Exposure to very small concentration daily of pesticides, tobacco smoke,
smoke, some foods like almonds, apricot kernel, cassava, etc
Non-carcinogenic even in chronic cyanide poisoning (classified by EPA as
Group D, not classifiable as to human carcinogenicity).
TOXIC DOSE
Hydrogen Cyanide
- Fatal: 150-200 ppm
- Air level: 50 ppm
- Permissible exposure limit: 10 ppm
Sodium Cyanide/Potassium Cyanide
Ingestion of Cyanide salts may be fatal with as little as 200 mg

Solutions of Cyanide Salts can be absorbed through intact skin or through the
conjunctiva of the eye
How is Cyanide normally metabolized in the body?

-
Cyanide is normally metabolized in the body through the enzyme rhodanese

(Thiosulfate cyanide sulfurtransferase). Rhodanese is an ubiquitous enzyme
that is known to be responsible for the biotransformation of cyanide to a less
toxic
thiocyanate.
cyanid
thiosulfat
thiocyana
sulfite
This mechanism involves binding of thiosulfate to a metal ion in the enzyme.

In this complex, there is election shift away from the planetary sulfur atom of
the thiosulfate with resultant stretching and weakening of the S S bond,
making it more susceptible to attack by a strong enzymic nucleophile which
affects the cleavage. The enzyme substrate complex, differing in reactivity
depending on the nature of sulfur donor substrate, is formed by discharging
sulfite ion from enzyme-thiosulfate complex. The acceptor substrate, cyanide
ion then combines with the E S intermediate to form the second product,
thiocyanate ion, thereby regenerating the free enzyme.
How does cyanide disrupts the electron transport chain?

- The primary effect of cyanide poisoning is the impairment of oxidative
phosphorylation a process whereby oxygen is utilized for the production of essential
cellular energy sources in the form of ATP (adenosine triphosphate). The cyanide ion
can rapidly combine with iron in cytochrome a3 (a component of the cytochrome
aa3 or cytochrome oxidase complex in mitochrondria) to inhibit this enzyme, thus
preventing intracellular oxygen utilization.
What is the molecular basis of the different clinical manifestations found

in cyanide poisoning? Why is a cyanide poisoned patient not cyanotic even
if he is gasping for breath?
Cyanide is known to bind and inactivate several enzymes, particularly those
containing iron in the ferric (Fe3+) state and cobalt. It is thought to exert its
ultimate lethal effect of histotoxic anoxia by binding to the active site of cytochrome
c oxidase, the terminal protein in the electron transport chain located within
mitochondrial membranes. By this means, cyanide prevents the transfer of
electrons to molecular oxygen. Thus, despite the presence of oxygen in the blood, it
cannot be utilized toward adenosine triphosphate (ATP) generation, thereby
stopping aerobic cell metabolism. Initially cells attempt to replenish the ATP energy
source through glycolysis, but the replenishment is short lived, particularly in the
metabolically active heart and brain. Binding to the cytochrome oxidase can occur
in minutes. A more rapid effect appears to occur on neuronal transmission. Cyanide
is known to inhibit carbonic anhydrase and this enzyme interaction may prove to be
an important contributor to the well-documented metabolic acidosis resulting from
clinically significant cyanide intoxication. Patients do not appear cyanotic because of
oxygenated venous blood.
Symptoms of Cyanide Poisoning
General weakness, confusion, bizarre behavior, excessive sleepiness, coma,

shortness of breath, headache, dizziness. An acute ingestion will have a
dramatic, rapid onset, immediately affecting the heart and causing sudden
collapse. It can also immediately affect the brain and cause a seizure or
coma. Chronic poisoning from ingestion or environmental poisoning will have
a more gradual onset. The skin of a cyanide-poisoned person can sometimes
be unusually pink or cherry-red because oxygen will stay in the blood and
not get into the cells. The person may also breathe very fast and have either
a very fast or very slow heartbeat. Person's breath can smell like bitter
almonds.
What is the rationale for treatment and management of cyanide
poisoning? What are the contents and mechanism of action of the Antidote
kit? Is oxygen administration useful?
The primary goal is to maintain cellular utilization of oxygen by interfering with
cyanide to prevent its interaction with cytochrome oxidase. Since cyanide poisoning
usually kills people in less than 15 minutes, immediate treatment is absolutely
essential. First induce vomiting if possible, or wash the stomach with a saline
solution. Then give amyl nitrite, sodium nitrite and sodium thiosulfate which are
contained in a cyanide antidote kit. And based on the case, Activated charcoal
suspension was administered because it acts as an adsorbent wherein it binds with
the poison in the stomach to decrease absorption of the poison into the body.
Contents of Antidote Kit
2 ampoules Sodium Nitrite Injection (300 mg in 10 ml of water/ a 3% solution)

2 vials Sodium Thiosulfate Injection (12.5 g in 50 ml of water/ a 25% solution)
12 ampoules Amyl Nitrite Inhalants Contents
Also: 10 mL plastic disposable syringe with a 22 gauge needle
1 sterile 60 ml plastic disposable syringe
1 sterile 20 gauge needle
1 stomach tube
1 non-sterile 60 ml syringe
1 tourniquet
1 set of instructions
Amyl Nitrite and Sodium Nitrite
The mechanism of action of amyl nitrite and sodium nitrite as antidotes for cyanide
poisoning is to produce methemoglobinemia and vasodilation. Intravenous sodium
nitrite produces significant methemoglobinemia. The cyanide bound to cytochrome
oxidase is then preferentially bound to methemoglobin, forming
cyanomethemoglobin. Rhodanese, an endogenous enzyme, then facilitates the
formation of thiocyanate, a much less toxic metabolite, which is renally excreted.
In the context of cyanide poisoning, the differences between nitrites lie in the route
of administration and the degree of methemoglobinemia they produce. Amyl nitrite
is inhaled, produces a minimal amount of methemoglobin, and is designed to be
administered pending the establishment of i.v. access, as is often the case in the
prehospital setting. Sodium nitrite is administered intravenously and results in a
methemoglobin concentration of about 15% in healthy adults. In other scenarios of
cyanide toxicity, particularly the intentional ingestion of cyanide salts, amyl nitrite
can be given to adults as one ampul (0.3 mL) inhaled until i.v. access is obtained,
followed by 300 mg (10 mL of 3%) i.v. sodium nitrite over two to four minutes.
Children should receive 6 mg/kg (0.2 mL/kg of 3%) sodium nitrite up to the adult
dose, at the same rate.
Sodium Thiosulfate
Cyanide is metabolized by the enzyme rhodanese to a less toxic metabolite,

thiocyanate, which is renally eliminated. However, this metabolic pathway is
capacity limited. Thiosulfate enhances the activity of rhodanese by donating a sulfur
group, thereby increasing the amount of thiocyanate that rhodanese can produce.
Sodium thiosulfate is relatively well tolerated, but there is a potential for nausea
and vomiting, as well as rate-related hypotension.
Because of its relatively favorable adverse-effect profile, sodium thiosulfate should
be given to all patients with suspected cyanide toxicity, including those with smoke
inhalation. The recommended dosage of sodium thiosulfate for adults is 12.5 g i.v.
(50 mL of 25% solution); for pediatric patients, it is 0.5 g/kg i.v. (2 mL/kg of 25%
solution) up to the adult dose.

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GROUP 4

Define cyanide poisoning (acute and chronic exposure)

Rare form of poisoning, occurs relatively frequently in patients with smoke

ACUTE CYANIDE POISONING

Ingestion of Cyanide salts may be fatal with as little as 200 mg

How is Cyanide normally metabolized in the body?

Cyanide is normally metabolized in the body through the enzyme rhodanese

This mechanism involves binding of thiosulfate to a metal ion in the enzyme.

How does cyanide disrupts the electron transport chain?

What is the molecular basis of the different clinical manifestations found

General weakness, confusion, bizarre behavior, excessive sleepiness, coma,

2 ampoules Sodium Nitrite Injection (300 mg in 10 ml of water/ a 3% solution)

Amyl Nitrite and Sodium Nitrite

Cyanide is metabolized by the enzyme rhodanese to a less toxic metabolite,

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