Cyanide and nitroprusside toxicity

Cyanide toxicity causes lactic acidosis by disabling the electron transport chain of oxidative phosphorylation.

Cyanide causes a rapid and complete blockade of cellular respiration by binding to cytochrome A3 of the  cytochrome oxidase system, a part of the oxygen transport chain. The result is a sudden and massive lactic acidosis, as all of your tissues become dependent on anaerobic metabolism. The presenting lactate in these people is usually the highest lactate you have ever seen – one study of a man who swallowed a potassium cyanide capsule reports a presenting lactate of 53.

Where the hell did he get it? Who knows. Certainly, these days one cannot simply walk into a pharmacy and purchase a packet of potassium cyanide capsules over the counter. An adult lethal dose is about 200mg of potassium cyanide. Although Grigori Rasputin reportedly survived a dose five times greater, he was lucky enough to be full of delicious chocolate cream cakes, which likely reduced the bioavailability of cyanide by binding irreversibly with the simple carbohydrates in his stomach. Hours afterwards he was in “vigorous health”, requiring further gunshot wounds, bludgeoning, and being submerged in the icy Neva river while rolled up in a carpet.

More frequently, one sees this overdose with careless laboratory staff, firemen who inhale the fumes of burning polyurethane, and patients in the ICU who are infused with sodium nitroprusside (each molecule of which contains five cyanide molecules). Seems like 5-10mcg/kg/minute of nitroprusside for 3-10 hours is enough to cause serious problems. A common household source of hydrogen cyanide gas is the products of combustion of synthetic rubber, and interestingly melamine (the coating used to reinforce cheap fibreboard furniture). Indeed, owing to the ubiquity of nitrile plastics and polyurethane, it seems about a third of household fire victims have clinically significant cyanide toxicity at presentation. Other more exciting exposures include drinking acetonitrile (a nail polish remover) and making dodgy low-quality homebrew PCP.

The cyanide ion (CN-) has a very high affinity for metal ligands in general, and it binds happily to the ferric ion on the haem moiety of the oxidised form of  cytochrome A3. All the other processes continue, of course; specifically glycolysis carries on but now the pyruvate can no longer be metabolised in Krebs Cycle and the only way to process it is by conversion into lactate.

Apart from being a nightmarish cytotoxin, cyanide also inhibits a number of other enzymes (superoxide dismutase, carbonic anhydrase,  and many others). Not only that, but in aqueous solution hydrogen cyanide is an acid (“Prussic acid”), although it is not an amazingly corrosive one.