Regarding cyanide poisoning, all of the following statements are true EXCEPT:

Explanation

## Mechanism of Cyanide Toxicity **Key Point:** Cyanide's lethality stems from its irreversible binding to cytochrome c oxidase (Complex IV), the terminal enzyme of the electron transport chain. ### Correct Statements (Options 0, 1, 2) **Option 0 — Binding to Cytochrome c Oxidase:** Cyanide binds with extremely high affinity to the ferric iron (Fe³⁺) of cytochrome c oxidase, forming a stable CN⁻–Fe³⁺ complex. This is the fundamental mechanism of toxicity. **Option 1 — Histotoxic Hypoxia:** The blockade of cytochrome c oxidase prevents the final step of aerobic respiration, halting ATP production. Tissues cannot utilize oxygen despite its availability — this is **histotoxic hypoxia** (also called cytotoxic hypoxia), distinct from hypoxemic or circulatory hypoxia. The brain and heart are most vulnerable due to high metabolic demand. **Option 2 — Rapid Absorption:** Cyanide salts (KCN, NaCN) and hydrogen cyanide gas are absorbed rapidly through: - Intact skin and mucous membranes - Respiratory tract (HCN gas) - Gastrointestinal tract This rapid absorption makes cyanide a potent poison. ### Incorrect Statement (Option 3) — **CORRECT ANSWER** **Option 3 — Mechanism of Sodium Thiosulfate:** Sodium thiosulfate does **NOT** displace cyanide from cytochrome c oxidase. Instead, it acts as a **sulfur donor** to the enzyme rhodanese (mitochondrial thiosulfate sulfurtransferase), which catalyzes the conversion of cyanide to thiocyanate: $$\text{CN}^- + \text{S}_2\text{O}_3^{2-} \xrightarrow{\text{rhodanese}} \text{SCN}^- + \text{SO}_3^{2-}$$ Thiocyanate is much less toxic and is readily excreted in urine. Sodium thiosulfate is a **substrate provider**, not a competitive antagonist. **High-Yield:** The three-pronged antidote regimen for cyanide poisoning: 1. **Sodium nitrite** — oxidizes hemoglobin to methemoglobin, which binds cyanide with higher affinity than cytochrome c oxidase (creates a "cyanide sink") 2. **Sodium thiosulfate** — provides sulfur for rhodanese-catalyzed conversion to thiocyanate 3. **Hydroxocobalamin** — binds cyanide directly to form cyanocobalamin (preferred in modern protocols, especially in Europe) **Clinical Pearl:** Hydroxocobalamin is increasingly preferred as first-line because it directly binds cyanide without the risk of methemoglobin-induced hypoxia that nitrites carry.