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(/) The stability of oxy hemoglobin is strengthened by qui-
nine, so that the blood does not yield up its oxygen as easily as
normally, consequently it cannot absorb oxygen readily. This
inability of haemoglobin to take up oxygen in the presence of
quinine is parallel with its action on other varieties of proto-
plasm. For example, fungi absorb oxygen slowly if quinine be
present, and thus fermentation may be prevented. Phosphores-
cent infusoria (the phosphorescence is due to rapid oxidation) lose
this property in the presence of quinine. The ozonizing power
of fresh vegetable juices is retarded by it. Quinine is, therefore,
very constant and very powerful in interfering with oxidation.

Circulation. Small doses of quinine probably increase the
activity of the heart reflexly because they stimulate the stomach ;
but large doses (larger than are given to man medicinally), either
applied to the excised heart or circulating through it, directly



47O ORGANIC MATERIA MEDICA.

paralyze the organ ; the pulse becomes slower and more feeble,
and the heart is finally arrested in diastole. Whether it acts on
the muscle or the ganglia is not known. I^rge doses lower the
blood-pressure considerably ; this is owing partly to the effect on
the heart, but it is probable that this fall of arterial pressure is
due in part also to the action of quinine on the blood-vessels.
If the spleen is enlarged as a result of malarial fever, the ad-
ministration of quinine, curing the fever, leads to a decrease in
the size of the spleen, but it has no direct effect on this organ,
as is often asserted.

Respiration. Although, as we have seen, quinine must, be-
cause of its retardation of oxidation, have a powerful influence
on internal respiration, diminishing the activity of metabolism,
it has but a moderate effect on respiratory movements. Small
doses slightly increase, large doses depress them.

Temperature. Quinine has very little power over the healthy
temperature, but that of fever is markedly reduced ; it is, there-
fore, an energetic antipyretic. Considering its direct capa-
bility of diminishing metabolism in the tissues, it seems fair to
assume that the drug diminishes heat production, and that
it does so by acting directly on the thermogenetic tissues ; but,
whether it decreases heat production by also influencing the cere-
bral thermogenetic centres is not known.

Cerebrum. Small doses are believed to stimulate cerebral
activity. The results of experiments upon the action of quinine
on the brain are so discordant as to be at present valueless. The
effects of a large dose in man will be described under Cin-
chonism.

Spinal cord and nerves. In frogs, quinine causes a lessening
of reflex excitability, which is removed by section below the
medulla; but in large doses it produces a permanent diminu-
tion of reflex excitability. In these animals quinine also first
excites and then paralyzes the sensory nerves or their peripheral
endings. The muscles are uninfluenced. These effects are not
seen in man.

Uterus. It has often been stated that quinine will lead to
abortion, that it will, when labor has commenced, aid the expul-



ANTI PERIODIC, ANTIPYRETIC, AND ANTISEPTIC DRUGS.

sion of the foetus, and that it will increase the menstrual flow if
that is scanty. It appears that the first statement is certainly
incorrect, and that the second and third are only correct for
some women.

Kidneys. After a full dose of quinine it is found in the
urine in half an hour, and is slowly excreted for several days,
but by far the greater part is eliminated within the first forty-
eight hours. The excretion of uric acid is greatly diminished,
and that of urea and other nitrogenous bodies in the urine is
also considerably lessened. This confirms the statement already
made that quinine retards considerably the metabolism of the
body, but it should be stated that very little alteration is observed
in the excretion of carbon [dioxide] by the lungs. It is said
that minute quantities of quinine are gotten rid of by all the
secretions, as it may be detected in milk, saliva, bile, tears, etc.,
and it may be found in dropsical fluids if the patient has been
taking it.

Cinchonism. In many persons a dose of ten grains ; [.60
gm.] or more of quinine produces a train of physiological symp-
toms, chiefly from its influence on the nervous system. The
patient soon complains of ringing in the ears, fullness in the
head, and slight deafness. With larger doses these symptoms
increase, disturbances of vision and giddiness are added, he
may stagger when he walks, and the headache may be very
intense.

Quinine is hardly ever given as a poison, but if it should be,
all these symptoms of cinchonism will be very severe ; the
patient may be delirious and comatose, quite deaf and blind, and
if he die it will be from collapse due to cardiac and respiratory
failure. Great congestion of the middle ear and labyrinth is
found in animals poisoned by quinine. The mild degrees of
cinchonism pass off directly [after] the drug is discontinued.
Rarely quinine causes an erythematous rash, and it has been
known to give rise to epistaxis. Those who work among cin-
chona barks may have a rash on their skin from the mechanical
irritation of the powder. Both hydrobromic acid and ergotin
are said to diminish the liability to cinchonism.



47 2 ORGANIC MATERIA MEDIC A.

Relative Action of the Alkaloids. The other alkaloids
are quite similar in their action to quinine, but they are not so
powerful. Their relative antipyretic effect is quinine 100, quini-
dine 90, cinchonidine 70, cinchonine 40.

THERAPEUTICS OF CINCHONA AND ITS ALKALOIDS.

External. Quinine is too expensive for use as an antiseptic.

Internal. Gastro-intestinal tract. It is very largely used
on account of its stomachic properties, chiefly for that variety of
indigestion which is the outcome of general ill-health, want of
fresh air, anaemia, etc., and not often when the stomach is the
organ primarily at fault. The preparations of cinchona bark are
very useful for this variety of dyspepsia ; they contain quite
enough of the alkaloids. The compound tincture has the advan-
tage of containing other stomachics. Iron is very commonly
given at the same time to correct the general condition. Quinine
is frequently prescribed with the tincture of [ferric] chloride ;
there is always enough free acid in this to dissolve any prepara-
tion of quinine. Alkalies, especially sal volatile, are often pre-
scribed with solutions of quinine sulphate, but they precipitate
the quinine, and therefore mucilage must be used to suspend it.
The dose of quinine sulphate or hydrochlorate as a stomachic
bitter is ^ to 2 gr. [.03 to .12 gm.] The hydrochlorate is often
preferred, as it is the more soluble. [Cinchonidine salicylate
(not official) is generally preferable to the sulphate as a tonic
and an antiperiodic in dose of from 5 to 10 gr.; .30 to .60 gm.]

Antipyretic effect. Quinine was commonly used as an anti-
pyretic, but for the rare occasions on which antipyretic drugs are
required, k has now been replaced by more certain drugs, as
phenacetin, acetanilid, and [antipyrin]. It is, however, a very
fairly certain antipyretic. It is best given for this purpose in a
single dose of 20 to 40 gr. [1.20 to 2.40 gm.] for an adult.
Such large doses may be prescribed either in cachets, or as a
solution of the hydrochlorate, or as the sulphate suspended in
milk [and at the same time sodium or potassium bromide should
be administered to avoid the disagreeable tinnitus which is set
up. The diluted hybrobromic acid is an excellent solvent, and,



ANTIPERIODIC, ANTIPYRETIC, AND ANTISEPTIC DRUGS. 473

at the same time, will relieve the ringing in the ears] . About
one or two hours elapse before the temperature begins to fall.
Quinine is more efficacious in reducing a temperature just begin-
ning to fall than a rising one. Hence, if possible, it should be
administered two or three hours before the time at which pre-
vious experience of the particular case shows the temperature
will probably attain its maximum ; then the fall will be more
marked and last longer than if the drug had not been given.

Specific action. Quinine, and to a less extent the other cin-
chona alkaloids, have the remarkable property of arresting the
paroxysms of malaria fever, [because it prevents the entrance
of spores into the red blood-corpuscles where only their cycle
of development occurs.] If 15 to 30 gr. [i. to 2. gm.] be
taken about one or two hours before the attack is due, it will
not take place, or it will be very mild. [If a more prompt effect
is desired, quinine carbamide (not official), which is very soluble,
can be administered hypodermatically ; a smaller dose, 5 to 8 gr.;
.30 to .50 gm., in an hour or two, is almost invariably successful
in preventing the next immediate chill.] The same effect [may]
be produced if smaller doses, about 5 gr. [.30 gm.] have been
taken four or five times a day during the period between the
attacks. Not only is it thus prophylactic, but the continued use
of it is curative. It is also preventive, even if the persons to
whom it has been given have never had ague. For this purpose
it is administered to soldiers and sailors who have to enter mala-
rious regions, and it is then found that few of them get ague.
If the disease is very severe it is best to give single large doses.
[Clark's powder consists of quinine, 10 ; powdered capsicum,
4 ; powdered opium, i part. This is given in 15 gr. ; i.oo gm.,
doses, and is said to be more efficacious in the treatment of ague
than larger doses of quinine when given alone.]

If a person has once had ague, illnesses that -he subsequently
suffers from are liable to assume a malarial type. This is espe-
cially the case with neuralgia, which is then peculiarly paroxys-
mal. It is often on the forehead, when it is called brow-ague.
In such cases the effect of quinine is frequently very well-marked,
and a cure speedily takes place. Sometimes neuralgia which is



474 ORGANIC MATERIA MEDICA.,

not malarial is temporarily benefited. Quinine cures ague by
acting, while circulating in the blood, as a direct poison to
the haematozoa (protozoa), the [plasmodium malariae,]
which infests the blood and is the cause of ague. It has been
given for a host of diseases, especially septicaemia, but there is
not any evidence that it does good to any except those men-
tioned. The preparations of the bark contain so little quinine
that they cannot be used as antipyretics or antiperiodics.

Lately it has been stated that quinine causes black -water fever ;
this is a pernicious error, as it will cure this form of malaria.

Quinine should, if possible, be avoided in (i) persons suffer-
ing from acute or subacute disease of the middle ear ; ( 2 ) those
suffering from gastro-intestinal irritation, which it may increase ;
(3) those people, occasionally met with, in whom quite small
doses produce very severe symptoms of cinchonism ; (4) [Men-
ingitis and (5) Inflammation of genito-urinary tract.]

Warburg s tincture is a medicine which has a very high reputation in
India for malaria. It has been called Tinctura Antiperiodica. The published
formula states that it is a proof-spirit tincture, containing Quinine Sulphate, 80 ;
Socatrine Aloes, loo ; Opium, I ; Rhubarb, 32 ; Camphor, 8 ; with Angelica,
Elecampane, Saffron, Fennel, Gentian, Zedoary, Cubeb, Myrrh, and Agaric,
as aromatics, with menstruum to 4000. [This contains about 9^ gr. ; .60
gm., to the ounce ; 30. c.c. , of menstruum.] Dose, I to 4 fl. dr. [4. to 15.
c.c.j It is often prescribed to be made without the Aloes.

SALICINUM.

SALICIN. C, S H, 8 O 7 [=285.33. A neutral principle (glucoside) ob-
tained from several species of Salix and Populus (nat. ord. Salicaceae). Syn-
onym. Willow. Habitat. Europe, naturalized in North America ; culti-
vated.

SOURCE. (l) Make a strong decoction of willow bark. (2) Remove the
tannic acid by wanning and agitating the decoction with Lead Oxide. (3)
Evaporate the solution. Salicin crystallizes out, and is purified by repeated
solution, and crystallization.

CHARACTERS. Colorless, or white, silky, shining crystalline needles, or
a crystalline powder, odorless, and having a very bitter taste. Permanent in
the air. Solubility. In 28 parts of water, and in 30 parts of Alcohol ; almost
insoluble in Ether or Chloroform. ]

Dose, 5 to 30 gr. ; [.30 to 2.00 gm.]



ANTIPERIODIC, ANTIPYRETIC, AND ANTISEPTIC DRUGS. 475



ACIDUM SALICYLICUM.

SALICYLIC ACID. HC 7 H 5 O 3 [=I37.67. An organic acid, existing
naturally, in combination, in various plants, see Oleum Gaultherise and Oleum
Betulse Volatile ; but most largely prepared synthetically from Carbolic
Acid.]

SOURCE. [Made by combining Sodium Carbolate with Carbon Dioxide
Gas. Thus, dry Carbon Dioxide is passed through Sodium Carbolate heated
to 428 F. ; 220 C.]. 2NaC 6 H 5 O-f-CO 2 =Na !1 C 7 H 4 O 3 (Sodium Salicylate),
-fC 6 H 6 O (Phenol). This is treated with Hydrochloric Acid. Na.,C 7 H 4 O 3
-f2HCl=2NaCl+HC 7 H 5 O 3 (Salicylic Acid).

CHARACTERS. [Light, fine, white, prismatic needles, or a light, white,
crystalline powder ; odorless, having a sweetish, afterwards acrid taste, and
permanent in the air. Solubility. In about 450 parts of Water, and in 2.4
parts of Alcohol ; also soluble in 2 parts of Ether, 2 parts of Absolute Alcohol,
and 80 parts of Chloroform.] Resembling Artificial Salicylic Acid. Strych-
nine, but the crystals of Strychnine are larger, colorless, non-irritating, less
soluble, and the solution is very bitter.

INCOMPATIBLE. Spirit of Nitrous Ether.

IMPURITIES. Orthocreosotic, metacreosotic, and paracreosotic acids, only
in artificial salicylic acid. In the best specimens they are absent.

Dose, 5 to 60 gr. ; [.30 to 4.00 gm.]

SODII SALICYLAS. Sodium Salicylate. NaC 7 H 5 O 3 [=i59.67].

SOURCE. Obtained by acting on Sodium Carbonate with Salicylic Acid.
[2HC 7 H 5 O 3 + Na 2 CO 3 =2NaC 7 H 5 O 3 +H. i O-t-CO 2 . The solution may be
strained through muslin and heated to expel the Carbon Dioxide.]

CHARACTERS. [A white, amorphous powder, odorless, and having a
sweetish, saline taste. Permanent in cool air. Solubility. In 0.9 part of
Water, and in 6 parts of Alcohol ; also soluble in Glycerin.]

INCOMPATIBLE. Hydrobromic acid, for sodium bromide is formed and
salicylic acid is precipitated.

IMPURITIES. Orthocreosotic, metacreosotic, and paracreosotic acids.

Dose, 5 to 60 gr. ; .30 to 4.00 gm.

[LITHII SALICYLAS. Lithium Salicylate. (LiC 7 H 5 O s =i43.68.)

SOURCE. Obtained by heating Salicylic Acid, Lithium Carbonate, and
Water, until the effervescence ceases, filtering and evaporating. Li^CO,
-f2HC 7 H 5 O 3 =2LiC 7 H 5 O 3 +H 2 O+CO )1 .

CHARACTERS. A white', or grayish-white powder, odorless, and having a
sweetish taste ; deliquescent on exposure to air. Solubility. Very soluble in
Water and in Alcohol.

Dose, i to 15 gr. ; .06 to i.oo gm.]

For Bismuth Salicylas see p. 183, and for Salol see p. 481.



476 ORGANIC MATERIA MEDICA.

ACTION OF SALICIN, SALICYLIC ACID AND OF SODIUM [AND
LITHIUM] SALICYLATES.

External. Salicin and salicylic acid are antiseptics rather
more powerful than carbolic acid. They are stimulant and mildly
irritant to the skin. Locally applied, they check sweating.
The salts of salicylic acid are not [strongly] antiseptic.
Salicylic acid softens and removes epithelium.

Internal. Alimentary tract. When inhaled or applied to
the throat, salicylic acid is irritating, causing sneezing and
cough. In the stomach also it is irritant, giving rise to pain,
nausea, and vomiting unless well diluted. The sodium [and
lithium] salts and salicin are much less irritating. The gluco-
side, salicin, is in the bowel converted into glucose and saligenin
(C 7 H 8 O 2 ), and this is further decomposed into salicylic acid,
salicyluric acid (HC 9 H 8 NO 4 ), and salicylous acid (HC,H 6 O 2 ).
Liver. The bile is rendered much less viscid ; [in fact salicylic
acid is probably the strongest cholagogue known]. Sodium
salicylate, like sodium benzoate, increases both the amount and
the solids t>f the bile.

Blood. Salicylic acid, whether taken directly or formed in
the bowel from the decomposition of salicin, is rapidly absorbed
in spite of its insolubility, and therefore it is probably taken up
as sodium salicylate ; [at least] , this is the form in which it cir-
culates in the blood, and consequently the following description
will apply whether salicin, salicylic acid, or sodium salicylate has
been taken. It has been thought also to exist in the blood as an
albuminate, but of this there is no evidence, nor for the theory
that when the sodium salicylate meets with carbon [dioxide],
salicylic acid is set free. Some of the salicylic acid of the sodium
salt unites with glycocoll, forming salicyluric acid, which appears
in the urine. Thus: HC 7 H 5 O 3 +C 2 H 5 NO 2 (glycocoll)=HC 9
H 8 NO 4 (salicyluric acid) +H 2 O. It will be noticed that this
change is precisely analogous to the conversion of benzoic into
hippuric acid by its union with glycocoll. Binz has suggested
that the specific beneficial effect of the salicylates in acute rheu-
matism is due to setting free of salicylic acid in the inflamed



ANTIPERIODIC, ANTIPYRETIC, AND ANTISEPTIC DRUGS. 477

part by the carbon [dioxide] in it. The beneficial effect of this
acid is also seen in a disease of bees known as foul brood, and
due to certain schizophytes, for feeding the creatures on syrup
containing salicylic acid cures them.

Heart. Salicin and salicylic acid are often stated to depress
the force of the heart and cause, a fall of blood -pressure. Care-
ful comparison shows that salicin is not nearly so depressant as
the acid in fact, it is probable that it has not this action at all,
unless given in toxic doses. Further, natural salicylic acid is
not so depressant as the artificial variety. For example, Char-
teris found that 30 gr. [2. gm.] of salicin, or 10 gr. [.60 gm.]
of natural salicylic acid, or 32 gr. [2.12 gm.] of natural sodium
salicylate had no injurious effect on a rabbit, but that much
smaller doses than these of the artificial acid or its salt killed the
animal. The artificial variety was found to contain orthocreo-
sotic and paracreosotic acids, and these are powerful cardiac
depressants. Thus it seems probable that the depressing ef-
fects commonly ascribed to salicylic acid are really due to the
impurities occasionally present in the artificial form.

Respiration. Moderate doses have very little effect on respi-
ration. Toxic doses strongly depress it.

Temperature. In medicinal doses salicin and salicylic acid
have no influence on the temperature of man, in toxic doses they
slightly lower it ; but they readily depress a febrile temperature,
and are therefore called antipyretics. They cause a slight
increase of perspiration, but this is not sufficient to explain the
fall.

Salicylic acid and salicin are antiperiodic.

Nervous system. We know little of the effect of salicylic
acid on the individual parts of the nervous system. The clinical
symptoms known as salicylism will be described presently.

Kidney. Salicylic acid escapes chiefly through the kidneys.
It, to a much less extent, also leaves the body by the sweat, the
saliva, the bronchial secretions, and the faeces. It appears in
the urine very soon after its ingestion (in from 10 to 30 minutes),
but the elimination goes on slowly. It is excreted as salicyluric
acid and sodium salicylate, which is split up by the phosphoric



478 ORGANIC MATERIA MEDICA.

acid in the urine, yielding salicylic acid. The dark greenish
color of the urine sometimes seen is due to small quantities of
either indican or pyrocatechin. Occasionally salicylic acid
causes haematuria, due to congestion of the kidneys. Large
doses increase the nitrogenous elimination, the uric acid being
especially increased. The sulphur also is increased. It renders
the urine aseptic, and the salicyluric acid in that fluid will re-
duce Fehling's Solution. The urine of patients taking it gives a
purple color with [ferric] chloride.

Salicylism. In some persons to whom salicylic acid or its
salt is given a train of symptoms is produced to which the above
name has been applied. They are very like those produced by
quinine. It is probable that the cause of at least some of them
is the impurities existing in artificial salicylic acid, but it is stated
that the natural acid may rarely give rise to them. Orthocreo-
sotic acid is certainly toxic, metacreosotic acid has no action, and
it is doubtful whether paracreosotic acid is toxic. The com-
monest is deafness, which is often accompanied by ringing in
the ears ; [these symptoms may be relieved by the administra-
tion of a small amount of alcoholic stimulant fifteen minutes be-
fore each dose.] Headache is also very frequent. The ad-
ministration of the drug is usually stopped when these symptoms
show themselves ; but if it is continued the patient becomes vio-
lently delirious, there is nausea and vomiting, the face is flushed,
and the other symptoms increase in severity. The pulse falls in
both frequency and force, it becomes irregular, epistaxis is com-
mon, and haemorrhages from other parts of the body have been
recorded, such as haematuria and retinal haemorrhages. Albu-
minuria without haematuria has been observed. One of the
rarest symptoms is erythema or urticaria. Very large doses may
cause the breathing to become weaker, and death may take place
either from cessation of the heart or the respiratory movements.

THERAPEUTICS OF SALICTN, SALICYLIC ACID AND OF SODIUM
[AND LITHIUM] SALICVLATES.

External. The ointment [official in B. P., i part of the
acid to 9 of hard, and 18 of soft paraffin] may be used when an



ANTIPERIODIC, ANTIPYRETIC, AND ANTISEPTIC DRUGS.

antiseptic stimulating ointment is required. A collodion com-
posed of salicylic acid, i ; flexible collodion, 8 ; or a glycerin
containing 10 per cent, of salicylic acid ; or a plaster, also 10
per cent., are good preparations. Strong applications of sali-
cylic acid are very useful for removing excess of epidermis,
warts, or corns [because it softens epithelium] . Salicylic acid,
ii ; extract of cannabis indica, 2 ; flexible collodion, 87 parts,
form an excellent remedy (commonly known as green solution)
for corns. Powdered salicylic acid mixed with starch or chalk
may be employed to check profuse perspiration of the feet and
axillae. The German Pharmacopoeia has for this purpose a Pulvis
Salicylicus cum Talco (salicylic acid, 3 ; wheaten starch, 10 ;
talc, in powder, 87). The sweats of phthisis may be treated in
the same way. A little salicylic acid is often added to Thomp-
son's fluid (see p. 275). [Salicylic acid is the principal ingre-
dient in Thiersch's solution. For this formula see p. 275.]

Internal. Salicylic acid is a specific for [many cases of]
rheumatic fever ; it lowers the temperature, lessens the swelling,
leads to a rapid cessation of pain, and [may] diminish the
liability to pericarditis and other complications. It must be
given well diluted to prevent dyspepsia. The sodium salt is
often preferred as being the most soluble, but in order to diminish
the risk of salicylism it should be prepared either from pure arti-
ficial or from natural salicylic acid. If the attack is severe, 20
gr. [1.20 gm.] every two or three hours should be given for the
first twelve or twenty-four hours ; then, if the patient is doing
well, the frequency of the dose may be gradually diminished, but
it should be continued thrice daily for ten days after the tem-
perature is normal and the pain has ceased. Salicin is not so
powerful as sodium salicylate, but it is said to be less depressant
than the synthetic acid.

These preparations are of no use for gout or severe osteo-
arthritis, but occasionally the pains of chronic rheumatism are
relieved.

Salicylic acid or salicin may produce a fall of temperature in
any fever, but, as we have more certain antipyretics, they are
not used except for rheumatic fever. Some writers have found



480 ORGANIC MATERIA MEDICA.

salicylic acid useful in migraine, sciatica, diabetes, and diph-
theria, but it is probably of little value for these disorders.
[The action of the salicylates in eliminating uric acid explains
their usefulness in migraine and sciatica which is incontestible in
some cases. So far as they limit intestinal fermentation they are
beneficial in the treatment of diabetes. For the glycosuria of
patients afflicted with gout or goutiness they are useful.] Sali-



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