Hydroxocobalamin (Vitamin B12a)

Mechanism

Pharmacological Group and Molecular Target

Vitamin precursor metallocomplex coordinated with cobalt.

Detailed Mechanism of Action

The cyanide anion (CN^-) is an extremely fast mitochondrial toxicant that binds in a reversible and coordinated manner to the ferric iron atom (Fe³⁺) of the heme group of the mitochondrial cytochrome c oxidase (Complex IV). By blocking the final step of the electron transport chain, cellular aerobic oxidative phosphorylation is completely abolished. This forces the cell to carry out a massive and inefficient anaerobic metabolism, triggering an immediate lethal lactic acidosis with a high partial pressure of oxygen in venous blood due to the inability of tissue consumption.

Hydroxocobalamin has a corrin ring centrally coordinated with a trivalent cobalt atom attached to a hydroxyl ligand. Cobalt has a cyanide stability constant substantially higher than that of cytochrome oxidase iron. After IV administration, cellular and plasma cyanide coordinately binds to cobalt through the exchange of its hydroxyl ligand, forming the molecule cyanocobalamin (Vitamin B12), a stable non-toxic soluble complex that is passively excreted through the urine:

Pharmacokinetics

Pharmacokinetic and Toxicokinetic Profile

• Distribution: It is widely distributed in the intravascular and erythrocyte space. It does not bind significantly to plasma proteins.
• Excretion: Rapid renal in the form of free cyanocobalamin or hydroxocobalamin, giving an intense red-purple hue to the patient's urine, skin and body secretions.
• Elimination half-life: Between 24 and 30 hours.

Hydroxocobalamin (Cyanokit)

• Does not alter in any way the oxygen-carrying capacity of functional hemoglobin.
• Excellent security profile; indicated as first choice in complex prehospital environments.
• Neutralization by direct stoichiometric coupling of cyanide.
• Disadvantage: Causes red discoloration of the skin that temporarily interferes with colorimetric gas analyzers.

Taylor Antidote Kit (Sodium Nitrite)

• It exerts its action by deliberately inducing methemoglobinemia to capture cyanide.
• Contraindicated in poisoning by smoke from fires; The induction of methemoglobin in patients with previous carbon monoxide (COHb) critically decreases cellular oxygen transport, causing brain death.
• It causes severe systemic vasodilation with extreme refractory arterial hypotension.

Indicators and dose

Specific Clinical Indications

• Treatment of suspected or confirmed acute cyanide poisoning, typically associated with smoke inhalation in confined domestic fires (patients presenting with coma, hemodynamic instability and serum lactate greater than 8 mmol/L).

Dosage Scheme and Infusion Protocols

• Standard Dose (Adults): Administer 5 g of hydroxocobalamin intravenously (one bottle of Cyanokit) infused rapidly over a period of 15 minutes. In children, the dose is 70 mg/kg of body weight.
• Depending on the severity of lactic acidosis and rebound hemodynamic instability, a second dose of 5 g may be infused as a slow bolus over the course of the next 2 hours.