What are the mechanisms of cyanide poisoning?

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From the Guidelines

Cyanide poisoning occurs when a person is exposed to cyanide compounds through inhalation, ingestion, or skin absorption, commonly from sources such as industrial processes, structure fires, or certain foods and medications, as noted in the 2023 American Heart Association guidelines 1. Cyanide poisoning can happen through various routes of exposure, including:

  • Inhalation of hydrogen cyanide gas, which can be liberated by the incomplete combustion of nitrogen-containing products such as plastic, vinyl, wool, and silk in structure fires 1
  • Ingestion of cyanide salts or foods containing cyanogenic glycosides, such as bitter almonds and cassava
  • Skin absorption of cyanide compounds, which can occur in industrial settings
  • Exposure to certain medications, such as sodium nitroprusside, which can release cyanide as a byproduct Once in the body, cyanide binds to the enzyme cytochrome c oxidase in mitochondria, blocking cellular respiration and preventing cells from using oxygen, leading to rapid cellular hypoxia and lactate accumulation, particularly affecting oxygen-dependent organs like the heart and brain 1. Symptoms of cyanide poisoning develop quickly and include:
  • Headache
  • Dizziness
  • Rapid breathing
  • Nausea
  • Vomiting
  • Confusion
  • Seizures
  • Eventually, respiratory failure and cardiovascular collapse Treatment requires immediate administration of antidotes like hydroxocobalamin (Cyanokit, 5g IV for adults) or sodium thiosulfate combined with sodium nitrite, as recommended by the 2023 American Heart Association guidelines 1. Additionally, supportive care including oxygen therapy and management of metabolic acidosis is crucial in managing cyanide poisoning, with the administration of 100% oxygen being a reasonable approach 1.

From the FDA Drug Label

Exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis.

Cyanide poisoning occurs when cyanide binds to cytochrome a3 in the mitochondria, preventing the cell from using oxygen and forcing anaerobic metabolism. This can happen through exposure to a high dose of cyanide, which can be fatal within minutes. The exact mechanisms of cyanide poisoning may involve other enzyme systems as well, especially in cases of massive acute cyanide poisoning 2.

From the Research

Mechanism of Cyanide Poisoning

  • Cyanide causes intracellular hypoxia by reversibly binding to mitochondrial cytochrome oxidase a(3) 3, 4.
  • This binding prevents tissue utilization of oxygen, leading to cellular asphyxiation 4.

Routes of Exposure

  • Inhalation of cyanide can produce reactions within a few seconds and death within minutes 4.
  • Ingestion of cyanide can also lead to poisoning, with symptoms occurring within a few minutes 3, 5.
  • Cyanide toxicity can also occur through dietary origin, such as ingestion of cyanogenic compounds 4.

Signs and Symptoms

  • Early manifestations of cyanide poisoning include anxiety, headache, giddiness, inability to focus the eyes, and mydriasis 3.
  • As hypoxia progresses, progressively lower levels of consciousness, seizures, and coma can occur 3, 6.
  • Other signs and symptoms include headache, vertigo, agitation, confusion, convulsions, and death 6.

Treatment

  • The key treatment for cyanide poisoning is early administration of antidotes, such as hydroxocobalamin or the cyanide antidote kit 3, 7.
  • Hydroxocobalamin detoxifies cyanide by binding with it to form the renally excreted, non-toxic cyanocobalamin 3.
  • Other treatments include sodium nitrite, sodium thiosulfate, and methylene blue 4, 7.
  • Supportive therapy, such as 100% oxygen, assisted ventilation, decontamination, correction of acidosis, and blood pressure support, is also important 6, 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cyanides and their toxicity: a literature review.

Tijdschrift voor diergeneeskunde, 1980

Research

A Review on Ingested Cyanide: Risks, Clinical Presentation, Diagnostics, and Treatment Challenges.

Journal of medical toxicology : official journal of the American College of Medical Toxicology, 2019

Research

Acute cyanide poisoning: clinical spectrum, diagnosis, and treatment.

Arhiv za higijenu rada i toksikologiju, 1996

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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