260 
MALARIA 
of the organs—lungs, liver, kidneys, heart, 
and brain (Hatcher and Weiss 1926). A 
considerable amount, however, cannot be 
accounted for. Weiss and Hatcher (1927) 
believe that the liver destroys the greater 
part of an intravenous dose. Determina¬ 
tions of the quinine content of human blood 
after intravenous quinine therapy give re¬ 
sults consistent with the above mentioned 
experimental findings. Hatcher and Gold 
(1927), for example, found only traces of 
quinine in 60 ec of blood after the intra¬ 
venous administration of 650 mg of quinine 
hydrochloride. 
A detail of the pharmacology has to do 
with the effect of quinine or quinidine 
when given intravenously. Such a proce¬ 
dure is rarely necessary. According to 
Maxcy (1928) such a route of administra¬ 
tion has per se no superiority over the oral 
one, and should be reserved for occasions 
when oral administration is impossible. 
When quinine or quinidine is given intra¬ 
venously there always results a fall in blood 
pressure, due in part to a depression and 
weakening of the heart muscle, and in part 
to a dilatation of blood vessels. The degree 
of fall is in part dependent on the concen¬ 
tration of the solution and in part on the 
rapidity of injection. Such an injection 
should therefore be carried out very slowly, 
and should be of a well diluted solution. 
The statement is commonly made that in¬ 
jections of epinephrine may be used to 
counteract the circulatory depression. It 
does not seem to be widely known that one 
of the characteristic actions of quinine and 
quinidine is to antagonize the pressor effects 
of epinephrine, so that it is very much less 
effective under these circumstances than is 
normally the case (Nelson 1927b). 
Another point of practical concern in the 
pharmacology of quinine is its action upon 
the pregnant uterus. It is commonly be¬ 
lieved to be hazardous to administer 
quinine to a pregnant patient. Further, 
quinine is credited with being an effective 
oxytocic substance and is often used by 
obstetricians for its stimulating action upon 
the uterus. Whether such an action 
actually exists may be questioned. Re¬ 
cently Reed (1940) has reiterated the view, 
previously expressed by others, that the 
danger from miscarriage in untreated 
malaria is greater than the likelihood of 
stimulation of the uterus to evacuation by 
the use of quinine. This reviewer, speaking 
as a pharmacologist and not as a clinician, 
has long felt that the oxytocic action of 
quinine was very much overestimated. 
There still remains, however, the possibility 
of injury to the fetus in utero by the admin¬ 
istration of quinine. 
There are a number of preparations of 
quinine available differing chiefly in their 
solubility. This matter of solubility prob¬ 
ably modifies the taste more than it does 
the rate of absorption. The preparation 
that has had the most extensive use in the 
United States is the sulfate, which is a rela¬ 
tively insoluble form (1 gm in 810 cc water 
at 25° C). Clinical experience certainly 
indicates that it is absorbed fairly readily 
and promptly. Quinine, the base, is only 
half as soluble as the sulfate, and is con¬ 
siderably less bitter. The tannate and 
ethyl-carbonate are still less soluble and 
practically tasteless. They make a satisfac¬ 
tory dosage form for administration to chil¬ 
dren. For intravenous administration 
there are three soluble preparations avail¬ 
able, quinine dihydrochloride, quinine and 
urea hydrochloride, and the N.F. ampule 
of quinine hydrochloride and urethane. 
Since the size and frequency of dosage and 
the duration of treatment are taken up else¬ 
where in this volume, they will not be con¬ 
sidered here. 
Cinchona and its alkaloids have long 
played a most important role in the attack 
upon malaria. While the drug does not 
meet every requirement of modern medi¬ 
cine, it still remains one of the most power¬ 
ful weapons in the physician’s armamen¬ 
tarium, and certainly is not to be discarded 
until more effective substances are avail¬ 
able. 
