Hydroxocobalamin (Vitamin B12a)
Hydroxocobalamin is said to be one of the most promising antidotes
available. The advantage using hydroxocobalamin is the lack of adverse
effects seen with the nitrites such as methemoglobinemia and hypotension.
It works by exchanging the hydroxy group for cyanide to form the non-toxic
cyanocobalamin (vitamin B12). One molecule of vitamin B12a is needed to
detoxify one molecule of cyanide. This is equivalent to a dose of about
50 times by weight of the hydroxycobalamin for each weight of the cyanide.
Thus, about 1400mg hydroxocobalamin is required to detoxify 1 mmol of
cyanide (corresponding to 65mg of KCN). Currently, a dose of about 4gm
is employed in Europe. However, the formulation available in Malaysia
is in ampoules containing 1-2mg. This formulation is only useful for the
treatment of vitamin B12 deficiency. It is not suitable for the treatment
of cyanide poisoning because too many ampoules are required.
Hydroxocobalamine formulation that is used for this purpose contains 4mg
of hydroxocobalamin powder and is available in France. Prior to use, the
powder is reconstituted with 80ml of a 10% thiosulphate solution. This
will reduce the total amount of hydroxocobalamin. Most common side-effects
observed with the use of hydroxocobalamin include an orange/red
discoloration of the skin, mucous membranes and urine lasting about 12
hours. These however are not of much concern.
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Patient receiving nitroprusside is also at risk of developing cyanide
toxicity, particularly with long-term infusions. Cyanide is an intermediate
metabolite of nitroprusside metabolism, while the thiocyanate which is
approximately 100 times less toxic than cyanide is the final metabolite.
Once the thiocyanate is formed, it is slowly excreted by the kidney. When
nitroprusside is administered into the body, the normal tissue rhodanese
and endogenous thiosulfate irreversibly converts the cyanide ions to
thiocyanate. A state of malnutrition, surgery and diuretic administration
can lower the body stores of thiosulfate. Cyanide levels begin to rise
when stores of thiosulfate are depleted and, methemoglobin is saturated.
Free cyanide binds and inactivates the ferric containing enzyme, cytochrome
oxidase, found in the mitochondria of cells. This will lead to tissue
anoxia and anerobic metabolism.

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Cyanide is readily attracted to many enzymes that has a metallic component
such as the cytochrome oxidase, nitrate reductase, myoglobin, ribulose
diphosphate carboxylase, and the catalase. Binding to the cytochrome
oxidase, a mitochondrial enzyme responsible for cellular respiration will
result in the inhibition of aerobic metabolism and consequent histotoxic
anoxia state.