K. K. Chen

Methylene Blue, Nitrites, and Sodium Thiosulphate against Cyanide Poisoning

Following the reports of Sahlin, 1 Eddy, 2 Brooks, 3 Geiger, 4 Hanzlik, 5 Hug, 6 and Wendel, 7 we investigated the comparative antidotal action of methylene blue and amyl nitrite in cyanide poisoning and found that methylene blue detoxified 2 M.L.D.s and amyl nitrite by inhalation 4 M.L.D.s of sodium cyanide. 8 Amyl nitrite is thus twice as effective as methylene blue. To date we have studied other nitrites and sodium thiosulphate. The last compound has been shown to have an antagonistic action against cyanide by several investigators.9-13 The results summarized in Table I were all obtained in dogs. It should be noted that nitroglycerine is ineffective as an antidote; while sodium thiosulphate detoxifies 3 M.L.D.s and sodium nitrite 4 M.L.D.s of sodium cyanide. A more striking antidotal effect is exhibited when amyl or sodium nitrite is supplemented with sodium thiosulphate. The combination of the nitrite and thio-sulphate does not only show synergistic action but surpasses the sum of their individual values. For example, the number of fatal doses detoxified by sodium nitrite and sodium thiosulphate is 13 instead of 7. It is a definite case of potentiation. Compared with methylene blue, the coupling of sodium nitrite and sodium thiosulphate is 6 1/2 times as effective. The following protocol is representative of the experiments: Dog, female, weighing 22 kg., received NaCN subcutaneously at 1:50 p. m., 78 mg. per kg. (13 M.L.D.s); 1:51 p. m., received intravenously NaNO2 22.5 mg. per kg. and Na2S2O3 2 gm. per kg.; 2:00-2:22 p. m. vomited 5 times; 2:23 p. m. drank water; 3:10 p. m. received intravenously NaNO2 10 mg. per kg. and Na2S2O3 0.5 gm. per kg.; 3:16 p. m. vomited; 4:53, 7:57, and 9:50 p. m. received intravenously NaN02 10 mg. per kg. and Na2S2O3 0.5 gm. per kg.; 8:15 a. m. of the next day, completely recovered. To test the crucial efficacy of the nitrite-thiosulphate therapy, dogs were given large amounts of cyanide, say 10 M.L.D.s, and allowed to develop the cardinal signs of cyanide poisoning such as convulsions, loss of corneal reflex, and failing respiration. As long as there was gasping, the intravenous administration of sodium nitrite and sodium thiosulphate enabled the animals to breath briskly at once, stand up within a few minutes, and recover completely in several hours.

Toxicity of 3,3-Methylenebis (4-hydroxycoumarin)

Summary (1) The median lethal doses of Dicumarol have been determined intravenously or by mouth in mice, rats, and guinea pigs. (2) Death uniformly occurs in rabbits with intravenous injection of daily doses of 1-2 mg per kg; in dogs with oral administration of daily doses of 5-50 mg per kg; and in mice and rats with the feeding of 0.01-1% Dicumarol in food. The majority of rabbits can tolerate daily doses of 0.1-0.5 mg per kg by vein for 6 weeks, and a few mice and rats can survive 30 days on a diet containing 0.005% Dicumarol. (3) Most animals dying from Dicumarol develop hemorrhage into various tissues and organs, and pulmonary edema. Central necrosis of the liver has been observed in about one-half of the rats examined, and occasionally in rabbits, mice, and dogs.

Potentiation of Antidotal Action of Sodium Tetrathionate and Sodium Nitrite in Cyanide Poisoning

In a previous communication we 1 reported the synergism and potentiation of the antidotal action of sodium or amyl nitrite and sodium thiosulphate against cyanide poisoning. The combination of sodium thiosulphate with sodium nitrite proves to be better than with amyl nitrite. It becomes interesting to ascertain whether or not sodium tetrathionate will similarly potentiate the detoxifying action of sodium nitrite, since the tetrathionate has been shown to reduce the toxicity of hydrocyanic acid by Foresti 2 and Draize. 3 In a series of experiments with dogs our results reveal exactly the same synergism and potentiation that occur with sodium thiosulphate. With the combination of sodium nitrite and sodium tetrathionate,∗ at least 3 dogs out of groups of 5 survived 13 or less M.L.D.s of sodium cyanide; whereas, with sodium nitrite alone only 4 M.L.Ds and with sodium tetrathionate alone 3 M.L.D.s of NaCN were detoxified. The antidotal effect of sodium nitrite and sodium tetrathionate given together thus exceeds the sum of those contributed individually by sodium nitrite and sodium tetrathionate. It is therefore another case of potentiation of action. The nitrite-tetrathionate combination is apparently efficacious in the late stages of cyanide poisoning. Dogs receiving large doses of NaCN have completely recovered at the point of respiratory failure. The following protocol can be taken as an example of our experiments: We have also studied the combination of methylene blue and sodium tetrathionate or thiosulphate in cyanide poisoning, and observed a synergistic action. The results are, however, much less striking.

Relative Susceptibility of Warm Blooded Animals to Ouabain, Cymarin, and Coumingine Hydrochloride

Summary 1. The acute toxicity of ouabain, cymarin, and coumingine hydrochloride has been compared by subcutaneous injection in cats, rabbits, guinea pigs, rats, and mice. 2. Both mice and rats are much more tolerant to ouabain and cymarin than cats in the ratios of 62:1 to 671:1. Regarding the alkaloid, coumingine HCI, which also has a digitalis-like action, their resistance is not so marked, being in the ratios of 13:1 to 29:1. 3. Guinea pigs and rabbits, like cats, are highly susceptible to ouabain, cymarin, and coumingine HCI.

Detoxification of Dendrobine by ‘Sodium Amytal’

Summary ‘Sodium Amytal’ detoxifies dendrobine. In rabbits it can antidote 5 minimal lethal doses of the alkaloid after definite signs of intoxication have been observed.

Potency of Cymarin and Coumingine Hydrochloride as Influenced by Environmental Temperature

Summary The susceptibility of the frogs heart to cymarin and coumingine hydrochloride increases with the rise of environmental temperature. Coumingine hydrochloride is approximately 5 times as potent at 33°C as at 13°C (bath temperature), and cymarin is more than twice as active at 33°C as at 13°C.

K-Strophanthin-β, K-Strophanthoside, Periplocymarin, and Periplocin

Summary K-Strophanthin-β is more potent than K-strophanthoside in frogs and cats, while periplocymarin is less potent than periplocin. The decrease in the number of sugar molecules of a cardiac glycoside, therefore, may or may not be accompanied by an increase in activity.