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first consider intestinal purgatives, [then intestinal antiseptics]
and [finally] intestinal astringents.

Purgatives are divided into the following classes.

Laxatives. These are substances which slightly increase the
action of the bowels chiefly by stimulating their muscular coat.



They are

(1) Whole meal bread.

(2) Honey.

(3) Treacle.

(4) Most fruits, especially

(5) Tamarind,

(6) Fig,

(7) Prune, and



(8) Stewed apples.

(9) Manna.

(10) Cassia [Fistula].

(11) Sulphur.

(12) Magnesia.

(13) Olive oil.

(14) Castor oil (small doses).



These are all domestic remedies employed for slight cases of
constipation, especially in children ; some, as brown bread,
fruits, honey, form articles of diet with persons who are liable
to constipation. [Ergot, physostigma, nux vomica, belladonna,
hyoscyamus, and stramonium are also laxatives, but are not used
except under medical orders.] Nux vomica is most valuable ;
it is probably a direct stimulant to the muscular coat, hardly in-
fluencing secretion. It is largely used in cases of chronic con-
stipation, especially when occurring in anaemic persons, or in
those in whom, for any reason, it is likely that the intestinal
peristalsis is feeble.



92 PHARMACOLOGY AND THERAPEUTICS.

Belladonna in small doses increases peristaltic movements
because it paralyzes the inhibitory fibres of the splanchnics, but
in moderate doses it completely arrests peristaltic movements.
It is chiefly employed for this latter purpose, especially in com-
bination with opium. Hyoscyamus acts on the intestines in the
same way, and small doses of it are often given with other pur-
gatives to prevent griping, for it gives an orderly rhythm to the
irregular contractions which the stronger purgatives produce.

Ergot and physostigma are hardly ever used for their laxative
effect. [Ergot, however, so often produces diarrhoea that its
purgative action should be kept in mind.]

Simple purgatives. These are rather more powerful in their
action than laxatives. They stimulate peristalsis and also increase
secretion. Some of the laxatives, as castor oil and magnesia,
when given in large doses become simple purgatives.



The simple purgatives are

(1) Aloes.

(2) Rhubarb.

(3) Rhamnus Frangula.



(4) [Rhamnus Purshiana.]

(5) Senna.

(6) Pel Bovis.



These are all in common use. The indications for each will
be given under the individual drug.

Drastic purgatives, often called cathartics. These excite
greatly increased secretion and peristaltic movements, and if
given in large doses cause severe irritation of the intestine, with
much secretion of mucus, great vascular dilatation, and even
haemorrhage, severe abdominal pain and collapse, with profuse
diarrhoea. The peristaltic contractions are often irregular, and
hence there may be much griping pain ; therefore it is usual to
prescribe hyoscyamus with these drugs, which are in order of
efficiency



(1) Calomel.

(2) Podophyllum.

(3) [Leptandra.]

(4) Aloes.

(5) Jalap-

(6) Scammony.



(7) Gamboge.

(8) Oleum Terebinthinae.

(9) Colocynth.

(10) Elaterium.

(11) Croton oil.



DRUGS ACTING ON THE DIGESTIVE APPARATUS.



93



The most powerful are placed last. Some, as jalap, elaterium, scammony,
are often called hydragogue, because of the large amount of secretion they
excite.

Therapeutics. Drastic purgatives are employed in obsti-
nate constipation, and also to produce very watery evacuations
with the object of removing as much fluid from the body as pos-
sible. Hence the frequent use of jalap in Bright' s disease.

Saline purgatives. The action of these is obscure, but it
seems certain that they very greatly increase the secretion of
intestinal fluid, and hinder its reabsorption, so that a large
amount of it accumulates in the intestine. The distension due
to this accumulation excites gentle peristalsis, and consequently
an easy, painless evacuation of the bowels. Secretion goes on
till the fluid in the intestine has become a 5 or 6 per cent, solu-
tion of the drug, so that if a very concentrated solution is given,
much intestinal fluid is secreted. There is some doubt whether
osmosis plays any part in the process. The action is entirely
local, for no purgation follows if the salts are injected into the
blood. [Magnesium sulphate, administered hypodermatically,
purges. It is possible that other salines may act similarly.] The
saline purgatives are



(1) Potassium [and sodium]

tartrate.

(2) Potassium bitartrate.

(3) Potassium sulphate.

(4) Sodium sulphate.



(5) Sodium tartrate.

(6) Sodium citro-tartrate.

(7) Sodium phosphate.

(8) Magnesium sulphate and

other salts.



Therapeutics. These are very largely used as habitual pur-
gatives, especially for persons suffering from any form of gout.
They form the essential ingredient of most purgative mineral
waters, as Hunyadi Janos, [Apenta], Pullna, Friedrichshall,
^sculap, Rubinat, [Villacabras], etc. The best way of taking
them is to put the required dose of the salt, or the mineral
water, in a tumbler, add some [hot] water, and sip it slowly
while dressing in the morning.

Cholagogue purgatives will be described when speaking of the
liver.



94 PHARMACOLOGY AND THERAPEUTICS.

Enemata. Any fluid preparation, injected into the rectum,
is called an enema. When a purgative is liable to produce sick-
ness, or it is inadvisable, because of peritonitis, intestinal ob-
struction, ulceration, or other diseases, to give it by the mouth,
it may be given by the rectum. Castor oil, aloes, olive oil,
magnesium sulphate, soap, etc., may be administered in this
way. Enough of a vehicle must always be used to make a pur-
gative enema up to three-quarters of a pint or a pint [350. or 500.
c.c.], for distension of the rectum greatly aids purgation. A
teaspoonful [4 c.c.] of glycerin injected into the rectum, or the
same amount given as a suppository, often unlocks the bowels.

[Intestinal Antiseptics. These are believed to check fer-
mentation and putrefaction in the intestines and are



(1) Naphtol.

(2) Bismuth Naphtolate.

(3) Naphtalin.

(4) Bismuth Salicylate.

(5) Salol.

(6) Chlorine.



(7) Creosote.

(8) Corrosive Mercuric Chlo

ride.

(9) Oil of Turpentine.
(10) Silver Nitrate.









Naphtol has been shown to destroy micro-organism in situ.
Bismuth naphtolate has not the irritating properties of naphtol,
but appears to be equally effective. When pure, naphtalin is
not absorbed, it does not cause toxic symptoms, nor is there
any change in the urine. Salol, a combination of salicylic and
carbolic acids, decomposes only in an alkaline solution, and this
is useful for action in the small intestine. Chlorine water has
been used for the disinfection of the intestine in typhoid fever.
Creosote is valuable if administered in the form of enteric pills,
which are soluble only in the intestinal fluids. Corrosive mer-
curic chloride is too poisonous for use, save in exceptional cases.
The late George B. Wood, of Philadelphia, achieved brilliant
success with oil of turpentine in the treatment of typhoid fever.
Silver nitrate has a limited use as an antiseptic, in its local appli-
cation to dysenteric ulcerations within reach in the rectum and
sigmoid flexure. The intelligent use of the foregoing drugs has
greatly improved the success of the treatment of enteritis, diar-
rhoea, colitis, dysentery and typhoid fever.]



DRUGS ACTING ON THE DIGESTIVE APPARATUS.



95



Intestinal Astringents. These may be described under
the following heads :

Astringents acting on the vessels of the intestine. These are
the same as those acting on vessels generally. Those employed
for their action on the intestine are



(1) Lead salts.

(2) Dilute solutions of silver salts.



(3) Alum.

(4) Diluted sulphuric acid.



Astringents coagulating albuminous fluids and thus constricting
the vessels :



(1) Tannic acid, and all sub-

stances containing it, as

(2) Krameria,

(3) Kino,

(4) Haematoxylon,

(5) Cinnamon,

(6) Catechu, and



(7) Eucalyptus gum.

(8) Lead salts.

(9) Silver salts.

(10) Zinc salts.

(11) Bismuth salts.

(12) Copper salts, and especially

(13) Ferric salts.



Astringents diminishing the amount of intestinal fluid secreted :

(1) Opium. (3) Lead salts.

(2) [Goto.] (4) Calcium salts.

The precise action of these is obscure, but it is probable that they operate
in the way indicated.

Astringents diminishing the contractions of the muscular coat
of the intestines :



(1) Opium.

(2) Belladonna.

(3) Hyoscyamus.

(4) Stramonium.



(5) Lead salts.

(6) Lime.

(7) Bismuth salts.



Therapeutics. The first proceeding in every case of diar-
rhoea is to remove its cause ; if this can be done, it will probably
subside. Often the cause is some irritating, indigestible food,
and then it is advisable to give a mild purge, as castor oil, rhu-
barb, etc. , to get rid of it. The majority of cases of ordinary
diarrhoea are probably due to some slight enteritis, and then any
one of the astringents that have been named will be valuable, for



96 PHARMACOLOGY AND THERAPEUTICS.

it is desirable to constrict the dilated vessels, and to diminish the
secretion and the movements. Intestinal astringents are, there-
fore, often combined, and, when the diarrhoea is at all serious,
opium is of great service. If there is a persistent cause, as tuber-
culous ulceration, the hope of doing good is slight. But the treat-
ment by drugs is only a small part of the battle ; if the diarrhcea
is severe, absolute rest is necessary, food must be very simple
and given in small quantities at a time, not much fluid should
be drunk, and the patient must be kept warm.

E. Drugs acting on the Liver. The liver has several
distinct functions, viz. : (a) to secrete bile ; (/$) to form and
store up glycogen ; (V) to form urea ; (//) to excrete substances
absorbed from the intestine ; and (<?) to destroy poisonous sub-
stances absorbed from the intestine.

i. Drugs influencing the secretion of bile. It does not follow
because more bile appears in the faeces that more is secreted, for
it may be that the gall-bladder and ducts have been thoroughly
emptied, or that the bile which has been poured into the duode-
num has been swept along quickly before reabsorption, which is
ordinarily brisk, has had time to take place. Drugs which
increase the amount of bile actually secreted are called direct
cholagogues, or hepatic stimulants ; but this is a bad name,
as the liver has so many distinct -functions : those which simply
lead to a larger amount of bile being found in the faeces without
any extra secretion are called indirect cholagogues.

DIRECT CHOLAGOGUES. These have been studied in fasting,
curarized dogs. A cannula is inserted into the bile-duct, and is
brought out of the body, the drug to be experimented upon is
administered, and the amount of bile is secreted before and after
the administration is noted. No food must be given 'during the
experiment, as that alone causes a considerable increase in the
biliary flow.

Direct cholagogues (the most powerful being placed first) are



(1) Euonymus.

(2) Sodium benzoate.

(3) Sodium salicylate.

(4) Podophyllin.



(5) Iridin.

(6) [Leptandra.]

(7) [Corrosive] mercuric chlo-

ride.



DRUGS ACTING ON THE DIGESTIVE APPARATUS.



(8) Sodium sulphate.

(9) Sodium phosphate.

(10) Aloes.

(11) Ipecacuanha.

(12) Diluted nitric acid.

(13) Diluted nitrohydrochloric

acid.



(14) Colocynth.

(15) Colchicum.

(16) Potassium sulphate.

(17) Rhubarb.

(18) Ja>p.

(19) Scammony.

(20) Diluted arsenous acid.



There are individual differences among direct cholagogues. Some, as
sodium salicylate, make the flow very watery, others, as toluylendiamine,
which is not given to man, make it so thick that it flows through the duct with
the greatest difficulty. Euonymin, sodium benzoate, sodium salicylate, Harro-
gate old sulphur spring and Carlsbad water, all markedly increase both the
total quantity and the solids. Podophyllin and iridin, on the other hand,
increase the solids without affecting the quantity.

INDIRECT CHOLAGOGUES. These cause no increase in the
amount of bile secreted ; they act by stimulating the upper part
of the jejunum and the lower part of the duodenum, thus sweep-
ing the bile on before there is time for it to be re-absorbed.

They are (i) Mercury; (2) most Cathartic purgatives, especially
Calomel.

Therapeutics. Cholagogues are used for cases of dyspepsia
in which there is reason to believe that the liver is the organ
at fault, and certainly they often have a very markedly beneficial
effect. It is clearly an advantage to combine direct and indirect
cholagogues in order to insure that the bile shall be excreted.
As bile itself is a stimulant to the peristaltic movements of the
intestine, all cholagogues are purgatives, and form a distinct class
of purgatives. In cases of hepatic dyspepsia attention to diet is
of the greatest importance, and muscular movements, as riding,
rowing, etc., aid in the expulsion of bile from the gall-bladder
and ducts.

ANTI -CHOLAGOGUES. These are often called hepatic depres-
sants. They decrease the quantity of the bile secreted. Calomel,
castor oil, gamboge, magnesium sulphate, opium and lead acetate
have this effect, but it is not sufficiently marked to interfere with
their therapeutic use for other purposes, and they are never em-
ployed for this action.

7



98 PHARMACOLOGY AND THERAPEUTICS.

2. Drugs modifying the glycogenic ftmction oj the liver. [We
will here refer to those drugs which cause sugar to appear in the
urine, and to those drugs which diminish the glycogenic function
of the liver.

DRUGS CAUSING SUGAR TO APPEAR IN THE URINE. Until re-
cently it was assumed that all these drugs acted on the liver,
probably by increasing the amount of sugar made from the hepa-
tic store of glycogen ; but now we have reasons for thinking that
sometimes the pancreas may be the organ at fault in diabetes, for
its excision causes sugar to appear in the urine, and other symp-
toms of diabetes ; also it has been suggested that perhaps some
perversion of processes going on in muscles may cause diabetes,
therefore it is rash to assume that all drugs causing sugar to
appear in the urine (glycosuria) must act on the liver. What
little can be stated as to the mode of action of these drugs will
be given when each individual drug is considered.

The drugs stated to cause glycosuria have already been mentioned ( See
p. 70).]

DEPRESSANTS OF THE GLYCOGENIC FUNCTION. Phosphorus, arsenic,
and antimony diminish and' even stop the formation of glycogen by the liver ;
they also cause fatty degeneration of it. In certain forms of diabetes, opium,
morphine, and codeine have a most marked effect in diminishing the quan-
tity of sugar in the urine.

3. Drugs modifying the formation of urea by the liver. It is
believed that some of the nitrogenous substances, especially
leucin, arriving at the liver, are there converted into urea. The
quantity of urea excreted by the urine is increased by phosphorus,
arsenic, antimony, ammonium chloride, and iron. Phosphorus
may also lead to the appearance in the urine of leucin and tyro-
sin. There is some evidence that this drug causes an increase of
the urea through its action on the liver, for in phosphorus poison-
ing that organ undergoes extreme fatty degeneration, and jaun-
dice supervenes. Whether the other drugs act through the liver
is doubtful. Antimony and arsenic, if given in large doses for
some time, both produce general fatty degeneration. All these
substances must be administered in almost poisonous doses in



DRUGS ACTING ON NERVOUS AND MUSCULAR SYSTEMS. 99

order to increase the urea in the urine, and they are not employed
therapeutically for this purpose.

Opium, colchicum, alcohol, and quinine are said to increase
the quantity of urea excreted.

DIVISION X. DRUGS ACTING ON THE NERVOUS AND MUSCULAR

SYSTEMS.

A. Drugs acting on the Muscles. Pharmacologists have
devoted much attention to this class of drugs ; but as the facts
ascertained are not used in medicine, we need not stop to con-
sider them. Brunton gives the following classification, founded
on that of Kobert :

Class I. Irritability of muscle unaffected ; total amount of work it can
do diminished. The following produce this effect : Apomorphine, delphine,
saponin, copper, zinc, and cadmium, and in large doses, antimony, arsenic,
platinum, and iron.

Class II. Both the irritability and the capacity for work diminished.
The following produce this effect : Potassium, lithium, ammonium, quinine,
alcohol, chloral [hydrate], and chloroform.

Class III. Diminish the capacity for work, and make the excitability very
irregular. Lead, emetine, and cocaine.

Class IV. Alter the form of the muscle curve. Veratrine, barium, stron-
tium, and calcium salts, digitalis, and squill.

Class V. Increases the, excitability. Physostigmine.

Class VI. Increase the capacity for work. Caffeine and theobromine.

Small doses of strychnine and veratrine shorten the latent period ; large
doses lengthen it.

Dilute alkalies diminish the extensibility ; dilute acids increase it.

B. Drugs acting on the Peripheral Endings of Motor
Nerves. Of the drugs belonging to this group the action of
curare has been worked out most fully. If curare is given to an
animal, it is found that the muscles will respond to a mechanical
stimulus, although they will not contract when the motor nerve is
stimulated. If a single muscle be removed from the circulation
by ligature of its vessels before the administration of curare,
afterwards it will be the only one .that will respond to stimula-
tion of its motor nerve. As this was the only muscle of the body
that the drug could not reach, and it is the only one not poi-



IOO PHARMACOLOGY AND THERAPEUTICS.

soned, the poison clearly acts locally on the muscles ; but as the
curarized muscle will respond to mechanical stimulation, curare
must paralyze the motor nerves within the muscle, probably the
end plates.

Drugs paralyzing the termination of the motor nerves in muscle :



(1) Curare.

(2) Conium.

(3) Belladonna (atropine).

(4) Stramonium.
-=- (5) Hyoscyamus.

(6) Saponin.

(7) Sparteine.

^ (8) Amyl nitrite.
(9) Diluted hydrocyanic acid.

(10) Cocaine.

(11) Camphor.



(12) Lobeline.

(13) Nicotine.

(14) Methyl -brucine.

(15) Methyl-cinchonine.

(1 6) Methyl-codeine.

(17) Methyl-morphine.

(1 8) Methyl- quinine.

(19) Methyl-nicotine.

(20) Methyl-strychnine,

and many others.



Curare and conium are by far the most important. Therapeutically we
never desire to paralyze motor nerve endings.

Drugs stimulating the termination of motor nerves in muscle :



(1) Aconite.

(2) Nicotine.



(4) Pyridine.

(5) Strychnine (slightly).



(3) Pilocarpine.

Excepting that perhaps some of the beneficial action of strychnine in
certain cases may be due to its slight action on motor nerves, we do not em-
ploy these drugs for this action.

C. Drugs acting on the Peripheral Endings of
Sensory Nerves (other than those of special sense). Our
knowledge of these is derived almost entirely from observations
on man, for it is very difficult to experiment upon animals, as
they have such imperfect means of communicating their sensa-
tions to us.

Drugs which stimulate the termination of sensory nerves,
These, when applied locally, cause pain. They are the same as
the local vascular irritants which have already been enumerated
(p. 60) ; in fact, most of them give rise to pain by causing local
inflammation. There is no need to repeat the list.

Therapeutics. Local irritants are chiefly employed for



DRUGS ACTING ON NERVOUS AND MUSCULAR SYSTEMS. IOI

their action on the vessels, but as they are also counter-irritants,
their application to the skin, while causing some pain there, will
often relieve a deep-seated pain. Although pain is always referred
to the periphery, it is appreciated centrally, and therefore periph-
eral stimulation of nerves, which also reflexly excites the heart
and respiration, is used to rouse people from unconsciousness,
such as that of fainting, opium poisoning, etc. For these pur-
poses the stimulus must be prompt, hence the application of the
faradic current to the skin is a good means to employ.

Drugs which depress the terminations of sensory nerves. Of
these there are two kinds : those which only relieve pain, or
local anodynes ; and those which diminish sensibility, or
local anaesthetics.

Local Anodynes. These have no action unless pain be present. They
are



(1) Aconite.

(2) Carbolic acid.

(3) Menthol.

(4) Diluted hydrocyanic acid.

(5) Vera trine.

(6) Ether. -v These must be

(7) Alcohol. tallowed to eva-

(8) Chloroform. J porate.



(9) Chloral [hydrate.]

(10) Belladonna.

(11) Stramonium.

(12) Hyoscyamus.

(13) Opium.

(14) Sodium bicarbonate.

(15) Zinc oxide.



In the above list the most powerful are placed first. Many other sub-
stances are said to be local anodynes, but their claim to the title is doubtful.
Cold is a powerful depressant of sensibility, and therefore it is an excellent
local anodyne ; so also is warmth, for heat primarily dilates the vessels, and
thus relieves tension, which is a very powerful factor in causing pain.

Therapeutics. It is clear that the scope for the employ-
ment of local anodynes is very wide. If possible, the first thing
is to remove the cause of the pain, but often, as in neuralgia and
many forms of pruritus, we cannot do this.

Local Anaesthetics. These are [ethyl chloride, rhigolene], cocaine,
[eucaine], carbolic acid, and extreme cold, whether produced by ice or
the ether spray. This spray was formerly employed to produce local anaes-
thesia before doing small operations, but it has [the disadvantage of stiffening
the parts so that it is only useful for single incision as for opening furuncles.



IO2 PHARMACOLOGY AND THERAPEUTICS.

Upon a damp day it is ineffectual. Ethyl chloride sprayed from tubes by the
heat of the hand is the best method and the one most frequently employed at
present. Eucaine and] cocaine, which produce a high degree of local insen-
sibility, [are largely employed].

D. Drugs acting on the trunks of Nerves. These are
of greater pathological than pharmacological interest. If taken
for a long time they produce chronic inflammation of the nerves,
which is shown by the great increase of the fibrous tissue between
the nerve-fibres and the fatty degeneration of the fibres them-
selves. During the earlier stages the irritation of the nerves
causes much pain and tingling ; later, as they lose their function,
numbness, with loss of sensation, and paralysis set in, often ac-
companied by trophic lesions. For further details books on
medicine must be consulted.

The drugs producing peripheral neuritis are

(1) Lead. I (3) Arsenic.

(2) Mercury. (4) Alcohol.

E. Drugs acting on the Spinal Cord. The difficulties
of experiment are so great that we know nothing of the action
of drugs on the sensory portions of the cord. We are also
ignorant of the action of drugs on the motor fibres. The follow-
ing method is adopted to discover whether a drug acts on the
cells of the anterior cornua. Suppose we are studying a drug
which stimulates them. After the drug has been given, a slight
peripheral stimulus will produce such marked reflex action that
convulsions will ensue upon the stimulation. If the cord is cut
across and the convulsions follow the stimulus as before, it is
clear that these cannot be of cerebral origin, for in that case
they would not take place below the point of section. Again,
if before injection of the drug into the circulation, the vessels of
the cord are ligatured, and then the drug causes no convulsion,
it is clear that it acts on the cord, and not on the muscles Oi
nerves. These results are confirmed, if, when the drug is in-
jected into vessels by which it reaches the cord quickly, convul-
sions occur sooner than when it is thrown into other vessels ;
also if convulsions do not take place when the cord is destroyed ;



DRUGS ACTING ON NERVOUS AND MUSCULAR SYSTEMS. 1 03



and lastly if, when the destruction is gradually caused by pushing
a wire down the vertebral canal, the convulsions cease from
above downwards as the cord is destroyed.

The drugs increasing the irritability of the anterior cornua are



(1) Strychnine.

(2) Brucine.

(3) Ammonia.

(4) Thebaine.



(5) Chloroform.

(6) Ether.

(7) Ergot.

(8) Opium.



(The last four only slightly, and early in their action.)



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