THE ACTION OF QUININE ON PROTEIN METABOLISM, RESPIRATORY EXCHANGE AND HEAT FUNCTION II. RESPIRATORY EXCHANGE AND HEAT FUNCTION

¹ Pharmacology Department, University of Edinburgh

1. A critical review of the previous important work is given. It is shown that a large part of it loses its value on account of the large and toxic doses used in experiments, while in some cases fundamentally unsound methods were used in investigation of the problem.

2. It is pointed out that a large number of those who found a fall in heat production and loss under quinine made their experiments on animals, giving the drug by subcutaneous or intravenous route, while many of those who obtained the opposite result experimented on human subjects who received the drug by the mouth—the existence of exceptions in each case is noted.

It is shown that a probable explanation of this difference lies in the different rate of absorption in the two cases, together with a difference in the susceptibility of the heat regulating mechanism.

3. The importance is pointed out of recognising drug action to be an event spread over an appreciable interval of time with its phases of development, maintainance and decline, and of giving due weight to such factors as dose, mode of administration etc.

4. My own experiments show that:

a. Doses of 15 or 20 mgm. per kilogram subcutaneously administered produce little change in the respiratory exchange of normal rabbits; but with higher doses up to 60 mgm. there occurs a definite fall in respiratory exchange and heat production, with a simultaneous but smaller fall in heat loss. This stage lasts only a short time, and at the end of three to three and a half hours there is a return to the original or a higher level. This constitutes the normal type of response in the rabbit.

The response of rabbits with coli fever is of the same type as that of the normal animal.

b. In the normal human subject with doses up to 2 grams by the mouth the prevailing tendency is towards a rise in the lung ventilation, respiratory exchange and heat production, with a higher rise in the heat loss.

The response of the febrile human subject to therapeutic doses given by mouth is not essentially different from that of the normal subject except that it is weaker so that the positive changes tend to be less pronounced and the negative more marked when present. But even when these last are considerable, there is a recovery to the initial or a higher level in about three hours or sometimes even earlier.

5. It is shown that the available evidence proves the antipyretic action of quinine to be central, and not a direct one on the tissues.