FA says induced methemoglobinemia (using nitrites, followed by thiosulfate) may be used to treat cyanide poisoning. Can we quickly go over the mech here? Many thanks!
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Nitrites (amyl or sodium ) cause oxidization of Fe2+ to Fe3+ (metHB) to release CN from ETC cytochrome Oxidase so we can make ATP. The MetHB binds well with CN (CN-metHB) and this displaces it from the Electron transport system.
Thiosulfate it donates its sulfur group to Liver Rhodanese(endogenous) this enzyme causes CN to thiocyanite(more water soluble for renal excretion )
Thiosulfate it donates its sulfur group to Liver Rhodanese(endogenous) this enzyme causes CN to thiocyanite(more water soluble for renal excretion )
Just for a quick review:
There are 3 antidotes:
Nitrates: Creation of a controlled state of,methemoglobinemia, that will compete for cyanide.
Combination and treatment choice is based on availability of drug and certainty of poisoning.
- Cyanide binds to Fe3+ → Blocks electron transport chain in mitochondria → Aerobic metabolism is stopped → Lactic acidosis (anion gap).
Note that cyanide poisoning is not cyanotic.
There are 3 antidotes:
Nitrates: Creation of a controlled state of,methemoglobinemia, that will compete for cyanide.
- Generate Fe3+ (methemoglobin) → binds cyanide (and gets it out from the mitochondria!)
- Precursor of VB12 binds cyanide → cyanocobalamin → excreted in urine
- Cyanide is transformed to thiocyanate → excreted in urine
Combination and treatment choice is based on availability of drug and certainty of poisoning.
- Thiosulfate + Hydroxocobalamin
- Thiosulfate + Nitrates (if hydroxocobalamin is not available and strong suspicion of cyanide poisoning)
- Thiosulfate alone (if CI to nitrates, or not certain cyanide poisoning)