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but it is banned by the Food and Drug Administration for use in the United States. It is the
purified form of the natural cyanide compound,
amygdalin. Amygdalin is a cyanogenic glucoside,
a sugar compound with cyanide attached. When
laetrile is given intravenously, it is mostly excreted
unchanged in the urine, and cyanide toxicity is
not a significant concern. However, when these
products are ingested, the enzyme b-glucosidase
in the gastrointestinal tract metabolizes amygdalin
into hydrogen cyanide, resulting in toxicity.
Many published case reports describe deaths after
use of illegally acquired laetrile.2729
Amygdalin can be found in food, although it
rarely poses a risk of acute toxicity due to its very
low concentrations. The most well-known food
source of cyanide is the amygdalin in seeds and
fruit pits from the Prunus species (e.g., apple
seeds, chokecherries, bitter almonds, apricot
pits).30, 31 Of note, apricot pits and bitter almonds
have the highest concentrations of amygdalin.
Other relevant food sources include dietary
staples such as lima beans and cassava.32 Acute
cyanide toxicity can occur from exposure to the
wastewater from factories that process these
foods.33, 34
Toxic Dose and Onset of Toxicity
Cyanide is well known for its high degree of
lethality. It is estimated that the lethal dose in
adults is 50200 mg. This potency is a product
of cyanides rapid diffusion into tissues and
irreversible binding to target sites. It is the rapidity
of action rather than the minuteness of a dose
that makes cyanide lethal. In fact, the lethal dose
of cyanide is actually relatively high when compared
with other potential chemical weapons, such as
botulinum toxin, ricin, and sarin. The form of
cyanide significantly influences the toxic dose.35
Intravenous and inhalational exposures to cyanide
produce the most rapid onset of symptoms. Death
can occur within seconds to minutes. Apparent
toxicity from ingestion may be delayed for
several minutes until significant concentrations
have accumulated in the bloodstream. It may
take several hours before manifestations are seen
after a dermal exposure to intact skin. Significant
delay in clinical presentation of toxicity from
cyanogenic compounds that require metabolic
activation, such as the nitriles and amygdalin,
has been noted to occur.
Mechanism of Toxicity
The purported mechanisms of toxicity are
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ATP
(2)
Oxyhemoglobin
++
Cytochrome a3
NO2
(3)
Methemoglobin
(1)
Fe3+
Cytochrome a3+++
O2 + 2H2O
Cyanide
Cyanomethemoglobin
Cyanide + methemoglobin
(4)
Thiocyanate
(5)
Oxyhemoglobin
Figure 1. Binding of the cytochrome oxidase within the mitochondria, resulting in abrupt cessation of cellular respiration. (1)
Step 1 shows cyanide bindings to the ferric ion (Fe3+) in the cytochrome a3+ complex. (2) Step 2 illustrates that the electron
transport chain is inhibited, resulting in loss of aerobic metabolism and generation of adenosine triphosphate (ATP). (3) In
step 3, nitrites (NO2) react with oxyhemoglobin to form methemoglobin, which draws cyanide out of mitochrondria and forms
cyanomethemoglobin. (4) In step 4, the enzyme rhodanase combines thiosulfate with cyanomethemoglobin to form the less
toxic thiocyanate, which is excreted by the kidneys. (5) Finally, in step 5, methemoglobin is converted back to oxyhemoglobin
by the enzyme methemoglobin reductase.
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Concerns
Large dose required,
short half-life,
light sensitive,
tachyphylaxis
4-Dimethylaminophenol8486
Induces
methemoglobinemia
Antidote,
adjunct therapy
Documented
efficacy,
i.m. injection
Necrosis at injection
site, excessive
methemoglobinemia
Stroma-free
methemoglobin
Binds to cyanide
Investigational
Uncompromised
oxygen-carrying
capacity
Investigational
Dicobalt edetate88
Chelates cyanide
to cobalticyanide
Antidote
Conflicting reports
on efficacy
Extreme toxicity
a-Ketoglutarate
and related
cyanohydrinforming drugs8991
Prophylaxis,
adjunct therapy,
acute and chronic
exposures
Investigational
Dihydroxycetone92
Antidote,
adjunct therapy
Short duration of
action, investigational
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