Hans Molitor

Oral and Parenteral Toxicity of Vitamin K1, Phthiocol and 2 Methyl 1, 4, Naphthoquinone

Summary The acute and chronic toxicity of Phthiocol, 2-methyl-1,4-naphthoquinone and vitamin K1 was studied in mice, rats, and chicks. The oral L.D. 50 in mice was found to be approximately 0.2 g per kg for Phthiocol and 0.5 g per kg for 2-methyl-1,4-naphtho-quinone; no lethal effect could be produced by doses up to 25 g per kg of vitamin K1. In the chronic experiments in rats, daily feeding over a period of 30 consecutive days of 0.35 g per kg of Phthiocol, and 0.5 g per kg of 2-methyl-1,4-naphthoquinone was toxic; doses of 0.1 g per kg of Phthiocol and 0.35 g per kg of 2-methyl-1,4-naphthoquinone produced a marked fall of the erythrocyte count and hemoglobin. No such effects were observed following vitamin K1 administration. In the abdominal cavity of animals sacrificed 10 days after an intraperitoneal injection of vitamin K1 considerable amounts of an oily suspension could be observed, indicating an extremely slow rate of absorption of vitamin K1.

Antimicrobial Action of Pyocyanine, Hemipyocyanine, Pyocyanase, and Tyrothricin

Summary The inhibition of growth of bacteria, yeasts and pathogenic fungi by natural and synthetic pyocyanine, synthetic hemipyocyanine, and natural pyocyanase and tyrothricin has been investigated. Natural and synthetic pyocyanine have equal activities which surpass those of pyocyanase. Tyrothricin is particularly inhibitory for Gram positive bacteria, especially streptococci. The considerable fungistatic potency of tyrothricin and hemipyocyanine suggests that these substances may be of value in the treatment of fungus infections.

THE PHARMACOLOGY OF STREPTOTHRICIN AND STREPTOMYCIN

Although streptothricinl and streptomycin2 possess rather similar chemotherapeutic properties, they differ considerably in their toxicity and pharmacodynamic effects. Furthermore, since neither of them has, as yet, been synthesized, nor is available in absolutely pure form, all studies, to date, have been performed with preparations containing varying amounts of impurities. Many of the pharmacological properties observed may be due, therefore, to these, rather than to the active principles, a factor which obviously complicates the pharmacological and clinical evaluation. It may seem inappropriate to open a discussion of the pharmacology of streptothricin and streptomycin by placing emphasis on impurities ; yet, the longer one studies these drugs, the less can one escape the conviction that the pharmacology of streptomycin and streptothricin, in the form in which we know them today, is, to a very large degree, due to one of their “standard” impurities. I shall use this term, in the following discussion, to designate contaminants which, unless specifically removed, may be expected to be constantly present in preparations of the average type, varying only quantitatively, but not qualitatively, as long as the parent strains of Aspergillus lavendulae and Aspergillus griseus, the composition of the nutrient media, and the processes of extraction, concentration, and finishing, remain the same. In contrast to these “standard” impurities, which are as much a part of the average streptomycin and streptothricin preparation as the active principle itself (but which vary widely with preparations of different origin), there may be found non-specific impurities, resulting from the use of impure ingredients, accidental contamination, errors in manufacturing, improperly cleaned equipment or containers, etc. We shall not concern ourselves with this type of non-specific impurity, which is rare and should never be encountered in a preparation that has been released for clinical use, provided, of course, that a rigid system of control is maintained. The existence of “standard” impurities, in practically every preparation of streptothricin and streptomycin, needs to be stressed, hecause some statements, though based on valid experimental evidence, may later have to be modified or completely discarded, once the experiments

Vitamins as Pharmacologic Agents

Publisher Summary This chapter describes the role of fat soluble and water soluble vitamin as pharmacologic agents. Any vitamin may be expected to restore to normal, functional changes which result from the deficiency of that vitamin. It is not easy to determine whether therapeutic results obtained by administration of a vitamin in diseases not following the pattern of a typical deficiency are ascribable to properties other than those necessary for the function as a vitamin. The pure toxic effects of vitamins are those of pyridoxine, which in excessive doses produces clonic-tonic convulsions or of riboflavin. Riboflavin, on repeated intravenous injection of large doses, is precipitated in the glomeruli, thus mechanically interfering with urinary excretion. Certain effects of vitamins cannot be observed by simple inspection or application of the commonly used pharmacologic technics. The pharmacologic effects of vitamins which constitute a restoration to normal of a typical vitamin deficiency are discussed in the chapter. The diagnostic value of vitamin administration is the response to B complex vitamins in cases of “subclinical” deficiency diseases is illustrated. The high specificity of vitamins is demonstrated in experimentally produced pathologic conditions, which resemble those observed in vitamin deficiencies.

Effect of Pyridoxine on Activity of Quinine and Atabrine Against Plasmodium lophurce Infections

Summary Pyridoxine when administered in doses several thousand times greater than required for the nutrition of the host will inhibit the activity of minimal effective doses of quinine and of atabrine against P. lophuræ infections in Pekin ducklings.

Toxic Manifestations After Oral Administration of Sodium Sulfapyridine

Summary Oral administration of sodium sulfapyridine produces marked gastric irritation and results in rats, rabbits and monkeys in the formation of urinary concretions. The minimal doses necessary to produce these phenomena vary from 0.25 g per kg in monkeys to 2 g per kg in rats, administered daily for 10 days. Larger doses (3 to 4.5 g per kg) may cause urolithiasis even after a single administration.

Elevated Plasma Fibrinogen Levels and Liver Necrosis in Rats Receiving Atabrine.

Summary The increase in plasma fibrinogen levels in rats receiving atabrine has been correlated with the presence and degree of necrosis in the liver. The maintenance of a blood level of about 5 γ per cc in 120 g rats was sufficient to induce gross liver damage after 5 weeks, irrespective of the number of doses given. When dosed on a mg per kg basis, older rats appeared to have a decreased tolerance to atabrine poisoning. Evidence has been presented to show that the decrease in the ratio of liver weight to body weight with age may account for the earlier onset of liver damage in older rats.