Antidotes for CN poisoning

Answer D. In addition to NO, metabolism of nitroprusside also releases small quantities of cyanide, a potent and potentially lethal inhibitor of cyt a/a (Complex IV). Thiosulfate is a common antidote for CN poisoning. 

Antidotes for CN Poisoning Bhattacharya et al (1995) and Cummings (2004) described the following approaches ... 

The released CN is transformed into SCN" by a hepatic and renal enzyme, rhodanese [43—45], this sulfuryl transferase being discovered in 1933 [46]. The enzymatic reaction proceeds slowly unless sulfur is supplied and is stimulated by thiosulfate, which is therefore a powerful antidote for CN poisoning. Another antidote is vitamin B12, and results indicate that as plasma cyanide increases the vitamin Bj2 level decreases suggesting that the vitamin may be a cofactor of rhodanese. Vitamin Bj2 will be in the aqua (not hydroxo) form at physiological pH [47], and cyanocobalamin formation is believed to be responsible for the antidotal properties [48—50]. Side effects have also been noted, however, in this connection [43, 51], and low plasma B12 levels may complicate treatment. The direct interaction between nitroprusside and vitamin B12 has been examined by NMR and 1 1 and 1 2 adducts have been observed [47],... 

Antidotes for cyanide poisoning (B). Cyanide ions (CN ) enter the organism in the form of hydrocyanic acid (HCN) the latter can be inhaled, released from cyanide salts in the acidic stomach juice, or enzymatically liberated from bitter almonds in the gastrointestinal tract. The lethal dose of HCN can be as low as 50 mg. CN binds with high af nity to trivalent iron and thereby arrests utilization of oxygen via mitochondrial cytochrome oxidases of the respiratory chain. Internal asphyxiation (histotoxic hypoxia) ensues while erythrocytes remain charged with 02 (venous blood colored bright red). 

Atropine Nonselective competitive antagonist at all muscarinic receptors in CNS and periphery Blocks muscarinic excess at exocrine glands, heart, smooth muscle Mandatory antidote for severe cholinesterase inhibitor poisoning Intravenous infusion until antimuscarinic signs appear continue as long as necessary Toxicity Insignificant as long as AChE inhibition continues... 

Pralidoxime Very high affinity for phosphorus atom but does not enter CNS Regenerates active AChE can relieve skeletal muscle end plate block Usual antidote for early-stage (48 h) cholinesterase inhibitor poisoning Intravenous every 4-6 h Toxicity Can cause muscle weakness in overdose... 

NIOSH REL (Nitriles) CL 6 mg/mVl5M SAFETY PROFILE Poison by ingestion, intraperitoneal, and intravenous routes. An experimental teratogen. A human skin irritant and allergen. In the preparation of sponge rubber, an azo compound is used that decomposes to form tetramethylsuccinonitrile or TMSN. Rats exposed to a concentration of 90 ppm exhibit their first convulsion after 1.5-2 hours or less. Rats exposed to concentration of 5.5 ppm exhibited their first convulsions in 27-31 hours and were dead in 31-46 hours. Absorbed by skin. The fatal dose in humans is thought to be about 25 mg/kg of body weight. TSN is slowly detoxified by the body. This nitrile is different from other nitriles in that thiosulfate is a poor antidote for intoxication. When heated to decomposition it emits toxic fumes of CN and NOx. See also NITRILES and CYANIDE. 

Other than for chelation therapy, in which the ligand is generally administered by slow, intravenous infusion, EDTA has been used in creams and ointments, pharmaceuticals, oils, soaps, bath preparations, cosmetics, and in hair dyes and permanent waving solutions. A novel application of an EDTA chelate is the use of the dicobalt chelate (dicobalt edetate) as an antidote in cyanide poisoning the CN ion forms a strong ionic complex with the Co ions in the chelate to form a relatively non-toxic and readily excretable species. 

We recommend that the treatment of choice based on efficacy and low therapeutic risk should be hydroxocobalamin, which may be used in combination with sodium thiosulfate. On a global basis and for emergency mass use, we stress the need for an international agreement on the management of CN poisoning, particularly with the antidote of choice for stockpiling. The criteria for choice of an anti-CN antidote have been given by Ballantyne et al. (2006). 

In respect of potential CN terrorism we believe that the following three critical items should be added to the CDC recommendations. First, before antidotes are stockpiled there should be international agreement on the most appropriate antidote (or combinations) for the treatment of acute CN poisoning. It is our opinion that hydroxocobalamin is the optimum choice. In the context of mass casualty situations with terrorist release of cyanides on the public, the chosen antidote should be readily available, effective, easy to administer (even by responders with limited training), nontoxic, and does not adversely interact with other antidotes (Thompson, 2004). Second, with respect to CN analyses, there is a requirement for a portable equipment that is specific and, at least semiquantitative, that can be used for on-site reliable bioidentification of CN intoxication. There is also a need for a reliable and sensitive environmental method for the instantaneous measurement of HCN concentrations, and ideally continuous monitoring with automatic warning devices for installation in sites with a potential for HCN attack. Third, educational materials should be made immediately available for distribution to the general population so that they can be prepared for what to expect in the event of a CN terrorism event. 

Hydrocyanic acid is a colorless liquid which boils at 26°, and when cooled forms crystals which melt at —14°. It has an odor which is similar to that of the oil of bitter almonds. It burns with a pale blue flame. Hydrocyanic acid is one of the most powerful poisons 0.05 gram is said to be a fatal dose. Hydrogen peroxide or the inhalation of air containing chlorine are said to be antidotes for hydrocyanic acid. The poisonous property of the acid is in some way associated with the CN ion. Substances from which this ion is produced are poisonous,whereas those, like potassium ferrocyanide, which do not give a simple CN ion are not poisonous. 

Atropine and praUdoxime are essential antidotes for the resuscitation and treatment of victims of nerve agent poisoning. Control of convulsions, if there is a significant central nervous system (CNS) involvement, must be achieved quickly with benzodiazepines. 

Cyanide poisoning poses some risk however, this is minimized both by the kinetic inertness of both Fe and Fe " cyano complexes and the high affinity of these ions for cyanide ([Fe"(CN)6] , fi6 10 [Fe "(CN)6] , Bg 10 [7, 35]. Small amounts of cyanide, which are released by photolysis and reduction products of nitroprusside, can usually be metabolized in the liver and kidneys by the enzyme rhodanase, which converts CN" to SCN [7, 36]. Cyanide can also be taken up by hydroxocobalamin to generate cy-anocobalamin (B12). As the conversion of cyanide to thiocyanate is dependent on the availability of sulfur, thiosulfate can be administered as an antidote [37]. Monitoring thiocyanate levels as an indicator of cyanide toxicity is no longer routine, but is done on patients with severe hepatic compromise who have been... 

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