Enumerate mechanism of action of cyanides and the pharmacological effect of the antidotes.

Cyanides are highly toxic compounds that act by inhibiting cellular respiration, specifically by blocking the activity of cytochrome c oxidase, the terminal enzyme in the mitochondrial electron transport chain. This inhibition prevents cells from utilizing oxygen for energy production, leading to cellular hypoxia and metabolic dysfunction. Here are the mechanisms of action of cyanides and the pharmacological effects of their antidotes:

Mechanisms of Action of Cyanides:

1. Inhibition of Cytochrome c Oxidase: Cyanides bind to the ferric ion (Fe^3+) in the heme group of cytochrome c oxidase, preventing the enzyme from transferring electrons to molecular oxygen during cellular respiration. This blocks the electron transport chain, disrupting ATP synthesis and cellular energy production.
2. Formation of Cyanohemoglobin: Cyanides also bind to hemoglobin in red blood cells, forming cyanohemoglobin. This reduces the oxygen-carrying capacity of hemoglobin, further exacerbating tissue hypoxia.
3. Induction of Lactic Acidosis: Inhibition of cellular respiration by cyanides leads to anaerobic metabolism, resulting in the accumulation of lactate and metabolic acidosis.

Pharmacological Effects of Antidotes:

1. Sodium Thiosulfate: Sodium thiosulfate acts as a sulfur donor, facilitating the conversion of cyanide to thiocyanate by the enzyme rhodanese. Thiocyanate is less toxic and is excreted renally. By promoting the detoxification of cyanide, sodium thiosulfate helps restore cellular respiration and alleviates tissue hypoxia.
2. Hydroxocobalamin: Hydroxocobalamin, a form of vitamin B12, forms a stable complex with cyanide, effectively sequestering it and preventing its interaction with cytochrome c oxidase. This neutralizes the toxic effects of cyanide and allows cellular respiration to resume.
3. Sodium Nitrite and Sodium Thiosulfate (Nitrite-Thiosulfate): This combination therapy exploits the formation of methemoglobin by sodium nitrite, which has a high affinity for cyanide, forming cyanomethemoglobin. Sodium thiosulfate then facilitates the conversion of cyanomethemoglobin to thiocyanate, promoting cyanide detoxification.

In summary, cyanides exert their toxic effects by inhibiting cellular respiration, leading to tissue hypoxia and metabolic dysfunction. Antidotes such as sodium thiosulfate, hydroxocobalamin, and nitrite-thiosulfate combinations counteract cyanide poisoning by promoting the detoxification and elimination of cyanide, restoring cellular respiration, and alleviating tissue hypoxia.