MudPhud20XX

5+ Year Member
Nov 26, 2013
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Medical Student
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!
 

RnaPolymerase2

2+ Year Member
May 17, 2015
29
10
Status
Medical Student
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 )
 
Jun 30, 2015
70
92
Zurich, Switzerland
Just for a quick review:
  • 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!)
Hydroxocobalamin (Cyanokit)
  • Precursor of VB12 binds cyanide → cyanocobalamin → excreted in urine
Thiosulfate
  • Cyanide is transformed to thiocyanate → excreted in urine

Combination and treatment choice is based on availability of drug and certainty of poisoning.
  1. Thiosulfate + Hydroxocobalamin
  2. Thiosulfate + Nitrates (if hydroxocobalamin is not available and strong suspicion of cyanide poisoning)
  3. Thiosulfate alone (if CI to nitrates, or not certain cyanide poisoning)