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Thiosulfuric acid is a sulfur donor used sequentially with sodium nitrite for the reversal of life-threatening acute cyanide poisoning. Also used to reduce the risk of ototoxicity associated with cisplatin.
Thiosulfuric acid is a sulfur donor used sequentially with sodium nitrite for the reversal of life-threatening acute cyanide poisoning. Also used to reduce the risk of ototoxicity associated with cisplatin.
When administered with sodium nitrate, sodium thiosulfate acts as an antidote for the treatment of acute cyanide poisoning. Cyanide has a high affinity for cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. By binding and inhibiting cytochrome a3, cyanide prevents cells from using oxygen and forces anaerobic metabolism, inhibiting cellular respiration and resulting in lactic acidosis and cytotoxic hypoxia. Sodium nitrite reacts with hemoglobin to form methemoglobin, which competes with cytochrome a3 for the cyanide ion. Cyanide binds to methemoglobin to form cyanmethemoglobin, a nontoxic compound, and restore cytochrome oxidase activity. When cyanide dissociates from methemoglobin, sodium thiosulfate acts as a sulfur donor for the endogenous sulfur transferase enzyme and facilitates its conversion to thiocyanate, a less toxic ion. Sodium thiosulfate can also reduce the risk of ototoxicity associated with cisplatin. Pediatric patients treated with cisplatin have a high risk of developing ototoxicity, possibly due to a combination of reactive oxygen species (ROS) production and direct alkylation of DNA that leads to cell death. Sodium thiosulfate interacts with cisplatin to form inactive platinum species. It can also enter cells via the sodium sulfate cotransporter 2 to increase antioxidant glutathione levels and inhibit intracellular oxidative stress. Although a mechanism of action has not been fully elucidated, both activities are thought to reduce the risk of ototoxicity.
Thiosulfuric acid (as sodium thiosulfate) is indicated for sequential intravenous use with sodium nitrite for the treatment of acute cyanide poisoning that is judged to be life-threatening. Sodium thiosulfate is also indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors in the US. In Europe, it is indicated for the same prevention of ototoxicity for patients 1 month of age to < 18 years old.
