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 lips 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. A large number of experimental data are given
showing that
(a) Doses of 15 or 20 mg. per kilo subcutaneously administered produce little
change in the respiratory exchange of
normal rabbits; but with higher
doses up to 60 mg. 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 3 to 3.5 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 2g. 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 bf 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. :hut even when these last are considerable,
there is a recovery to the initial or a higher level
in about 3 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.
The current view that quinine lowers the
nitrogenous tissue waste is untenable. It is not
possible through quinine therapy in non -malarial
febrile conditions to lessen materially the waste of
energy or destruction of body tissues. Its effectiveness in malaria is not questioned, but there it
acts primarily against the cause of the disease itself.
