Pathophysiology of cyanide poisioning

[chbare]

Hi Kenny, the chief way cyanide antidotes work is not really centered around directly acting on cytochrome c oxidase, but rather haemoglobin; at least in the case of the traditional therapy (Nitrates + Methylene Blue). As I outlined in the video, the traditional therapy changes the oxidation state of the Iron atom in the porphyrin ring of the sub units of haemoglobin. Typically, the Iron will be in a default configuration of +2/Fe II/Ferrous. Nitrates and other substances can further oxidise the Iron into the +3/FeIII/Ferric state. For reasons that I cannot pull out of my head (I suspect it has to do with the fact that Fe III is a strong Lewis acid and would not be able to coordinate reversibly with the Oxygen molecule.) Fe III does not coordinate with the Oxygen molecule. It however does coordinate exceptionally well with cyanide.

This will create a situation where kinetics and thermodynamics favour cyanide coordination with the haemoglobin as opposed to the Iron in the cytochrome c oxidase enzyme. However, this also means the patient has methaemoblobin toxicity and could develop histotoxic hypoxia due to ineffective haemoglobin function. Hence, the need to administer agents that can reduce haemoglobin such as methylene blue. 

However, the other antidote modality in the United States works very differently. Hydroxocobalamin is a vitamin B12 precursor that contains a Cobalt atom configured in a way that allows it to have a high affinity for the cyanide molecule. The high affinity favours the coordination of cyanide with the Cobalt as opposed to the Iron in cytochrome c oxidase. Again, the exact details are complex, but chemical kinetics and thermodynamics favour Cobalt coordination in this case.  A relatively inert molecule known as cyanocobalamin is produced in a 1:1 manner (1 mole of hydroxocobalamin can coordinate with 1 mole of cyanide) that is easily eliminated in the urine.

Hopefully that helps out a bit.

No worries about being a student. Do not let anybody make you think humanity has developed a deep understand of these things. Much of the universe is a complete mystery to us and as you progress along your educational pathway, you will likely be disturbed from how inadequate and uncertain you feel at each step along the process. My experience has been that with every degree that I have obtained, I had the expectation that I would emerge with a more comprehensive understanding of the world. Every step left me lacking significantly. This was not due to lack of trying or failure of dedication, but a fundamental part of the uncertainty of being a human being attempting to understand a vast and complex universe.

Point being, I do not want you to be discouraged.

 

[Spock]

Cyanide poisoning is hypoxia at the cellular level.  Hydroxocobalamin is the best treatment since it is a precursor to vitamin B-12 and combines with cyanide to form B-12.  The other treatments try to eliminate cyanide by other mechanisms but less effectively.  

Hydroxocobalamin is expensive and not always readily available for prehospital services.  The Paris Fire Brigade did some of the early work on its use for patients with altered LOC after smoke inhalation and also with patients pulled from a fire scene in cardiac arrest.  The Advanced Hazmat Life Support text book is a fantastic reference for hazmat medicine although it is expensive.  

Hazmat medicine has moved into the Hot Zone and should not remain in the cold zone.  Early treatment is essential for survival and the attitude of my hazmat medical team is to enter the hot zone and apply airway, antidotes and tourniquets to the injured.  Airway is the King LTD (although we may switch to the i_Gel), antidotes are the Duo Dotes, and tourniquets are the CATS.  We have a process for transitioning the airway from the hot to the cold zone and have a variety of difficult airway devices available not to mention the appropriate drugs.  Our medical team also can serve as the RIT for the regular hazmat teams.  

Hazmat isn't for everybody and only those with specialized training should get into the mix.  My days as a fire fighter are long past and I wouldn't think of entering a burning building now but suiting up in level A hazmat is second nature.  To each his or her own.

Spock

May the tube be with you.

Sorry chbare, I didn't see your excellent post before I chimed in.  My humble apologies.

Spock

[Kenny0471]

Thank you guys appreciate the information.