Thiosulfuric acid

Sodium thiosulfate doses of 20, 15 and 10 g/m² deliver sodium loads of 162, 121 and 81 mmol/m². One hour after infusion, the administration of sodium thiosulfate causes a transient increase in sodium of approximately 6 mmol/L; however, levels return to baseline 18 to 24 hours after infusion. The pharmacodynamics of sodium thiosulfate as an antidote for the treatment of acute cyanide poisoning were evaluated by measuring the rate of conversion of cyanide to thiocyanate. Pretreatment with sodium thiosulfate to achieve a steady state level of 2 µmol/mL increased the rate of conversion of cyanide to thiocyanate over 30-fold in dogs. The use of sodium thiosulfate may cause hypersensitivity reactions and lead to hypernatremia and hypokalemia. It may also lead to nausea and vomiting.

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.