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<br />10 BIOLOGICAL IIEPORT 85(1.23)
<br />oxygen, methylene blue, 4-dimethylaminophenol,
<br />various aromatic amino- and nitro-compounds
<br />(such as aniline, p-aminopropiophenone, nitroben-
<br />zene), carbon:~l compounds, and sodium pyruvate
<br />(Egekeze and Oehme 1980; EPA 1980; Solomonson
<br />1981; Way 1981, 1984; Biehl 1984; Becker 1985;
<br />Ballantyne 1987b; Marrs 1987; Marrs and Ballan-
<br />tyne 1987; W ay et al. 1988). Different anti dotes are
<br />preferred in different countries: in the United
<br />States, a mixture of sodium nitrite and sodium
<br />thiosulfate; in France and the United Kingdom, co-
<br />balt edetate, also known as Kelocyanor; and in
<br />Germany, a mixture of 4-dimethylaminophenol
<br />and sodium thiosulfate.
<br />The classic nitrite-thiosulfate treatment of
<br />cyanide poisoning, developed almost 60 years ago,
<br />is one of the antidotal combinations still employed
<br />(Way 1981). Excess ox}'gen improves this antidotal
<br />combination by potentiating the effectiveness of
<br />the nitrite-thiosulfate combination, as confirmed
<br />by studies in sheep and rats (Way 1984), even
<br />though, theoretically, oxygen should serve no use-
<br />ful purpose (Way et al. 1988). This therapeutic
<br />regimen protected rats against 20 LD50 doses of
<br />cyanide (Towil] et al. 1978). Nitrite converts hemo-
<br />globin to methemoglobin, which has a high afl-inity
<br />for cyanide. The methemoglobin-HCN complex
<br />then slowly releases cyanide, which is converted to
<br />thiocyanate by way of rhodanese (Solomonson
<br />1981). Sodium nitrite, administered intrave-
<br />nously,is now considered one of the more rapid
<br />therapeutic methods (Way 1984). The injection of
<br />sodium thiosulfate provides sulfur for the enzyme
<br />rhodanese to mediate the biotransfonnation of
<br />cyanide to the much less toxic thiocyanate
<br />(Egekeze and Oehme 1980). Multiple injections of
<br />sodium thiosulfate protected mice against death
<br />b}' organic c}•anides and were more effective than
<br />sodium nitrite (Willhite and Smith 1981). The ni-
<br />trite-thiosulfate antidotal combination is one of
<br />the mosteflective treatments of cyanide poisoning,
<br />even though the specific mechanism of action of
<br />these two compounds is now being questioned, and
<br />concerns have been raised because of the toxicity' of
<br />nitrite (Way 1981, 1964}, One accepted therapy' is
<br />an intravenous combination of sodium nitrite (1
<br />mL of 20Sc solution) and sodium thiosulfate (3 mL
<br />of 20ib solution ),giving 4 mL of this mixture per 45
<br />kg of bad}' weight (Egekeze and Oehme 1980). For
<br />maxima] effectiveness in treating cyanide intoxi-
<br />cation in sheep, large doses of sodium thiosulfate
<br />(660 mg/kgB1~V1 are given in combination with con-
<br />ventional doses of sodium nitrite (6.6 mg/kg BVd;
<br />Egekeze and Oehme 1980). Livestock treatment in
<br />l- J
<br />cases ofsuspected cyanide intoxication consists of
<br />intravenous administration of sodium nitrite at
<br />10-20 mglkg BR' followed by sodium thiusulfate at
<br />30-40 mg/kg BW; however, a sodium thiosulfate
<br />dose of500 mg/kg B1>r', or more, maybe more effica-
<br />cious (Biehl 1984 ).Once clinical signs have abated,
<br />1 g of activated charcoal per kilogram BW may be
<br />administered as a drench by way of a stomach tube
<br />(Biehl 1984). A 30-kg female goat (Capra sp.) was
<br />successfully treated after eating tlhe ]eaves and
<br />fruit of the crab apple (Malus sytupstris), a plant
<br />that contains high levels of cyanog~nic glycosides
<br />in leaves and fruits (Shaw 1986). Treatment con-
<br />sisted ot[our hourly treatments of 7100 g of animal
<br />charcoal and bismuth subnitrate in water as a
<br />drench, followed by 300 mg sodium Nitrite as a 1°ro
<br />aqueous solution, then 25 g of sodium thiosulfate.
<br />Another goat died despite identical trc.itment
<br />(Shaw 1986).
<br />Cobalt compounds, such as hydroxocobalamin
<br />and its derivatives (i.e., cobalt higtidine, cobalt
<br />chlonde, dicobalt ethylenediamine tktracetic acid)
<br />have been used to treat cyanide poisoning for more
<br />than 100 years. Their efficacy was confirmed in pi-
<br />geons (Columba sp.) and rabbits(Oryctolagus sp.),
<br />but cobalt compounds did not receive wide support
<br />as cyanide antagonists because oftheinherenttox-
<br />icity of cobalt ion (R'sy 1981, 1984). Nevertheless,
<br />proponents of th a use of cobalt compounds (i.e., the
<br />United Kingdom, Scandinavia, much of Europe)
<br />stress the rapidity of action in forming a stable
<br />metal complex with cyanide, thereby preventing
<br />its toxic effect (Towill et al. 1978; Way 1984). One
<br />of the more frequently used cobalt compounds in
<br />cyanide treatment is hydroxocobalantin, which re-
<br />verses cyanide toxicity by combining with cyanide
<br />to form cyanocobalamin (~~tamin Bi4; EPA 1980;
<br />Solomonson 1981). Hydroxocobalamin has been
<br />used in guinea pigs and baboons (Papio anuliis) to
<br />lower blood cyanide levels, and in humans after in-
<br />halation or ingestion of cyanide compounds
<br />(Egekeze and Oehme 1980).
<br />Dimethylaminophenol (DMAP) forms met-
<br />hemoglobin by setting up a catalytic cycle inside
<br />the erythrocyte, in which oxygen gxidizes the
<br />DMAP to N-N-dimethylyuinoneimine, the latter
<br />oxidizing the hemoglunin to me{hemoglobin
<br />(Marrs 1987). Dogs poisoned with KCJQ and given
<br />DMAP intravenously had restored respiration and
<br />decreased plasma cyanide levels. 'P'he 4-dime-
<br />thylamino-phenol induced femhemgglobin pro-
<br />duction, which combined with the cyanide in the
<br />red cells to form ferrihemoglobin cyanide iChriste]
<br />et al. 1977).
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