SOME TOXICOLOGICAL AND PHARMACOLOGICAL PROPERTIES OF STREPTOMYCIN

1. The pharmacological and toxicological properties of streptormycin were found to be greatly influenced by the presence of traces of impurities and varied considerably in different animal species. One such impurity has histaminelike properties and can be inactivated by histaminase.

2. The signs observed after administration of large doses of streptomycin consist, in order of appearance, of restlessness, respiratory distress, loss of consciousness, coma and respiratory failure. The latter is apparently the cause of death, since the heart continues to beat for several minutes after cessation of the respiration.

3. The acute intravenous toxicity of streptomycin increases greatly with the speed of injection. This factor is less influential with the intramuscular and subcutaneous administration. The rate of absorption varies with different lots and influences and outcome of subcutaneous and intramuscular toxicity experiments.

4. No pathologic changes were found in the organs and tissues of animals killed in acute toxicity experiments.

5. The signs and symptoms produced by repeated daily administration of streptomycin over periods of 5-80 days vary greatly with the animal species. Weanling rats show a slight retardation of growth and develop a pronounced nervous hyperexcitability. No such changes were noted in adult rats or in mice. Monkeys exhibit a slight impairment of hepatic and renal function and show upon autopsy a fatty infiltration of the liver and, to a lesser degree, of the kidney. These changes are reversible. Dogs develop a mild to severe impairment of renal function, and show upon autopsy lipoid deposits in the kidney and liver. In addition, they exhibit signs of cerebellar or labyrinthine disturbance.

6. The injection or topical application of streptomycin usually does not produce marked local effects.

7. Intravenous injection of streptomycin concentrates is often followed by a sharp drop of arterial blood pressure due to a histamine-like impurity. Pure streptomycin is free from this effect, but produces in large doses a gradual and prolonged depression of the blood pressure.

8. Injection of a large dose of streptomycin concentrate may cause a marked temporary inhibition of water diuresis. No such effect is found with pure streptomycin.

9. Streptomycin causes a relaxation of the isolated intestine.

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