The mechanism of cyanide intoxication and its antagonism.
The mechanism of cyanide intoxication has been attributed to the inhibition of cytochrome oxidase, thereby decreasing the tissue utilization of oxygen. One mechanism of cyanide antagonism is by sequestering cyanide with methaemoglobin to form cyanmethaemoglobin and another mechanism is detoxifying with a sulphur donor to thiocyanate. Questions have been raised with regard to these classical mechanisms. Oxygen with nitrite-thiosulphate antagonizes the lethal effects of cyanide. Theoretically, increased oxygen should serve no useful purpose, as it is the tissue utilization of oxygen which is inhibited. In the nitrite-thiosulphate antidotal combination, the proposal is made that the predominate antidotal action of nitrite is a vasogenic action, rather than methaemoglobin formation, because when methaemoglobin formation is inhibited by methylene blue the protective action of sodium nitrite persists. This suggests that methaemoglobin formation plays only a small part, if any, in the therapeutic antagonism of the lethal effects of cyanide. The roles and implications of sodium thiosulphate and non-rhodanese substrates in the detoxification mechanism are compared. Lastly, a new approach to cyanide antagonism has been initiated which involves the erythrocyte encapsulation of thiosulphate and sulphurtransferase as an antidote and prophylaxis against cyanide.
Way
J L
JL
Department of Medical Pharmacology and Toxicology, Texas A & M University, College of Medicine, College Station 77843.
Leung
P
P
Cannon
E
E
Morgan
R
R
Tamulinas
C
C
Leong-Way
J
J
Baxter
L
L
Nagi
A
A
Chui
C
C
D000818:Animals; D000931:Antidotes; D001711:Biotransformation; D003035:Cobalt / Q000494:pharmacology; D003486:Cyanides / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D008706:Methemoglobin / Q000096:biosynthesis; D012977:Sodium Nitrite / Q000494:pharmacology; D013885:Thiosulfates / Q000494:pharmacology
D000931:Antidotes; D003486:Cyanides; D013885:Thiosulfates; D003035:Cobalt; D008706:Methemoglobin; C017717:sodium thiosulfate; D012977:Sodium Nitrite