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DRUGS ACTING ON THE CARDIAC MECHANISM. 55

Veratrine applied to white corpuscles outside the body kills them.

Camphor, myrrh and other aromatics are said to increase their production
by increasing absorption from the intestine.

The following facts do not fall under any of the previous headings : Poi-
sonous doses of mercury increase the fluidity of the blood, impair its power
of coagulation, and diminish the solids in it. Cod-liver oil increases the solids
of the blood. Potassium iodide and calcium salts [especially the chloride] are
said to increase the power of coagulation ; other substances doing this will be
described under astringents.

DIVISION III. DRUGS ACTING ON THE CARDIAC MECHANISM.

The heart is capable of spontaneously originating impulses
which in health begin in the sinus venosus, and spread down-
wards over the auricle and the ventricle to the apex. It used to
be considered that these movements were due to spontaneous
impulses proceeding from the cardiac ganglia surrounding chiefly
the entrance of the superior and inferior venae cavae, the entrance
of the pulmonary veins, and the auriculo-ventricular groove ; but
we now know that there is no certain evidence that these ganglia
originate impulses, and most of the evidence goes to show that
the contraction of the muscular fibres is due to spontaneous im-
pulses arising in them. This contractile power of the muscular
fibres can be inhibited by the vagus, the fibres of which proceed
from the vagal nucleus in the medulla, and can be augmented by
the augmentor or accelerator nerve-fibres, which proceed down-
wards in the cervical spinal cord to the upper dorsal nerves, from
which they pass through the first thoracic ganglion to the sym-
pathetic, and so to the cardiac plexus, and thence to the heart.
We are ignorant of any function for the cardiac ganglia ; we
know that medullated nerve-fibres lose their medulla in them,
and that more fibres proceed from them than enter them. Possi-
bly they have a nutritive function. We have, therefore, only to
consider the action of drugs on the muscular substance of the
heart, on the vagal or inhibitory fibres, on the vagal centre, on
the augmentor, accelerator, or sympathetic fibres, and on the
accelerator centre. The centres are remarkably easily affected
by afferent impulses, proceeding from the heart itself or from
almost any part of the body. Our information concerning the



56 PHARMACOLOGY AND THERAPEUTICS.

action of drugs on the heart of man is necessarily rather inexact,
for many experiments are difficult to perform upon the mammalian
heart, consequently the cold-blooded animals have been largely
used ; and as some differences a^e observed among them for
example, between the ftog and the tortoise it is probable that
the deductions drawn from experiments upon the hearts of warm-
blooded animals are not wholly applicable to man. In the fol-
lowing account of drugs the action described is that of a moderate
dose ; the action of a large dose is generally the reverse of that
of a moderate dose.

A. Drugs acting upon the Heart directly. Our knowl-
edge of these has been gained by studying the action of drugs
upon excised hearts or pieces of the heart, and the action of
drugs locally applied to the heart, either by gently applying a
solution externally, or by means of a [transfusion] cannula. It is
difficult to decide whether a drug acts upon the muscular fibre
itself, or upon the fine nerves between these fibres, so that no
attempt will here be made to distinguish between these actions.
As the apex of the heart contains fewer nerves than the rest
of the organ, it has been concluded that if a drug acts upon the
apex, when it is cut off from the remainder of the heart, it acts
upon the muscle only ; but it would be difficult absolutely to
deny the existence of fine nerve-fibres in the apex. The vagus
or inhibitory nervous mechanism has been much more studied
than the accelerating. The effect of stimulating the muscle may
be either to increase the rate or the force of the beat, or to do
both ; that of stimulating the minute branches of the vagus or
its terminations in the heart will be either to diminish the rate
or the force of the beat, or both ; and the effect of stimulating
the accelerator fibres will be just the opposite ; and in each
of these cases the effect of paralyzing will be the reverse of stimu-
lating. The distinction between a stimulating effect on the ter-
minations of the vagus and a depressing effect on the termina-
tions of the accelerator nerves might be determined by observing
the effect of stimulation of each of these nerves before and after
the local application of the drug, provided that it has been
shown that the muscle itself is not affected by the drug ; but this



DRUGS ACTING ON THE CARDIAC MECHANISM.



57



is often difficult to prove. It is easily seen that the complexity
of the problem is so great that it will be most convenient to
classify the drugs which act locally on the heart by the effect
they produce, without attempting to say whether they act on the
muscle or nerve terminations.



Drugs increasing the force of the contraction :

^(i) Digitalis. *Q- ^> (6) Convallaria Majaais.

(2) Strophanthus.g),. X. i ' j? (7) Caffeine.

(3) [Spa/teine.]
7 (4; Squill, f^

(5) Sapo'nin.



^ \-j I v*iiiciiic.

S (8) Veratrine.

(9) Erythrophlceum.
(10) Barium Salts.



In large doses these drugs in frogs always cause arrest of heart in systole ;
in mammals the final arrest may be in diastole with some, e.g., digitalis.
They all slow the pulse.



(13) Dilute solutions of zinc

double salts.

Dilute solutions of chloral. ;
Physostigfeine. t*
Camphor. <$. /t!^.^






>.






n Dilute solutions of salts
of the alkaline metals.
(12) Dilute solutions of copper
double salts.



These drugs have the same action without the final arrest in systole. The
rate of the pulse is not markedly altered.

Drugs the chief action of which is to decrease the force of the contraction,
usually with stoppage in diastole: .n, ' V~)V (JjL f, "H *tA?-

^ (I) Diluted acids. + * ^(7) Mu/carine. '.

-(8) Pilocarpine.
(9) Sapdnin (large doses).



(2) Strong solutions of salts of
the alkaline metals.



(4)
(5)
(6) Strong solutions of chloral.



. .

(3). " of barium salts. 'Xio) Apomorphine. ffxJ^i. k^

(11) Errfetine.



of copper double salts.

of zinc double salts. * ^(12) Salicylic acid (large doses).



Drugs an important action of which is to
beat:



(1) Atropine.

(2) Hyoscyamine.

(3) Daturine.



V



^ /iVW
'e the rate of the cardiat




(4) Duboisine

(5) Cocaine.

(6) Saponin.



PHARMACOLOGY AND THERAPEUTICS.



Drugs an important action of which is to slow the rate of the cardiac beat
(see also first list given above):

(i) Muscarine. | (2) Pilocarpine.

Drugs which increase both the force and the number of the beats :



(1) [Ammonium salts.]

(2) Alcohol.

(3) Ether.

(4) Chloroform.

(5) [Cactus.]



(6) Anaesthetics.
w (7) Arsenical salts.
' (8) Quinine.
(9) Strychnine.



Drugs which decrease both the force and the number of the beats :



(i) Antimony salts.
V (2) Aconite.

(3) Hydrocyanic acid.






(4) Ergot. t4#Jfa

(5) Veratrum Viride.

(6) [Cevadilla.]



B. Drugs acting on the Vagus Centre. If we observe
that the giving of a drug to an animal alters the beat of the heart,
but that this alteration can be done away with, either by cutting
the vagi or stimulating the peripheral end of the nerve, if one
only of them be cut, we may conclude that the drug acted on
the vagus centre in the medulla.



Drugs which stimulate the vagus
slowed, but this slowing disappears on

(1) Chloroform.

(2) Chloral hydrate.

(3) Butyl-chloral [hydrate.]

(4) Aconite.

(5) Veratrum Viride.

(6) Nicotine.

(7) Digitalis.

(8) [Sparteine.]

(9) Strophanthus.



centre : that is to say, the pulse is
section of the vagi :

(10) Squill.- tyl-

mi Convallaria Majalis.

(12) Hydrocyanic acid.

(13) Cocaine (large doses).

(14) Staphisagria (Delphinine.)

(15) Atropine. \ Only very

(16) Hyoscyamine. \ early in their

(17) Daturine. ) action.

(1 8) Increased blood-pressure.

(19) Venous blood.



Drugs which depress the vagus centre : Large doses of the drugs men-
tioned in the last list, and drugs which diminish the blood-pressure, such as
amyl nitrite [nitroglycerin, and the nitrites.]

C. Drugs acting on the Accelerating Centre. We do
not know anything of drugs which depress this. Probably some




DRUGS ACTING ON THE VESSELS. 59

stimulate it, for their administration renders the pulse still more
rapid after the vagi have been cut.



They are

(1) Ammonia.

(2) Caffeine.

(3) Picrotoxin.

(4) [Cactus.]



(5) Delphinine.

(6) Any drugs which make the

blood venous.



Therapeutics. The drugs most used for their action on the
heart are digitalis, strophanthus, [ammonium salts, sparteine],
squill, convallaria majalis, caffeine, alcohol, ether, chloroform,
[cactus] , strychnine, belladonna, aconite, antimony, and hydro-
cyanic acid. The therapeutic indication for each of these drugs
will be found given under the individual drug.

DIVISION IV. DRUGS ACTING ON THE VESSELS.

These are usually studied either by directly observing altera-
tions in the size of the vessels in some thin structure, such as the
ear of a rabbit, the mesentery, tongue, lung, web, or mylo-hyoid
[muscle] of a frog, or the wing of a bat ; or the rate of the flow
may be observed. This can be conveniently done by cutting
some part, as the toe of a frog, and noticing the rate at which
the blood flows from the cut vessels with and without the admin-
istration of the drug to the animal. It is often necessary that an
artificial circulation should be maintained ; for if not, it might
be difficult to prove that the alteration in the quantity of blood
flowing from the cut surface was not due to influences acting on
the cardiac mechanism. In order to determine if the changes
are due to local or central effects, it is necessary to destroy the
spinal cord, or to cut the nerves going to the part. When a drug
is applied locally, as to the mesentery, and the vessels alter, if the
nerves going to the part are not cut, it is difficult to say whether
this alteration is direct or reflex.

Drugs are applied to the interior of vessels by injecting them
into the circulation.

We know that each vessel is controlled by vaso-constrictor and
vaso-dilator nerves, and that these proceed by different paths



6o



PHARMACOLOGY AND THERAPEUTICS.



from the central nervous system, but we do not know by which
set of nerves drugs act ; probably some by the vaso -constrictor,
and some by the vaso-dilator. We can only classify the drugs
into those which dilate or contract the vessels by local action,
and those which produce these effects through their action on the
central nervous system. When a drug acts locally we cannot
tell whether it "acts on the muscle in the wall of the vessel, or
on the nerve terminations.

It of course follows that drugs acting on the heart, or on a
large area, will considerably modify the blood -pressure.

A. Drugs acting locally on Vessels.



Drugs which, when locally applied to

(1) Liquor Ammoniac.

(2) Silver nitrate

(3) Zinc chloride [ (strong).

(4) Copper sulphate J

(5) Mercuric nitrate.

(6) Arsenous acid.

(7) Antimony and potassium

tartrate.

(8) Iodine.

(9) Chlorine.

(10) Mineral acids (strong),
(n) Alcohol. ) If prevented

(12) Ether. [ from evaporat-

(13) Chloroform. J ing.

(14) Carbolic acid.

(15) Creosote.



vessels, dilate them :

(16) All volatile oils, as oils of

turpentine, and many sub-
stances containing them, as
mustard, [horse-radish] etc.

(17) Senega.

(18) Chrysarobinum.

(19) Ipecacuanha.

(20) Capsicum.

(21) Croton oil.

(22) Camphor.

(23) Cantharides.

(24) Phosphorus.

(25) Warmth, however applied,

but usually as a poultice.
[This is true if its evanes-
cent effect is desired. When
long applied it contracts
blood-vessels. ]



Irritants. All of the above, as they dilate
of as vascular irritants.



the vessels, are often spoken



Rubefacients are drugs which, when locally applied to the
skin, cause it to become red because of the vascular dilatation
induced. All the above drugs are rubefacients.

Vesicants. Many of these drugs are sufficiently powerful
irritants to cause inflammation. If this goes no further than the
exudation of plasma from the vessels, and this plasma collects



DRUGS ACTING ON THE VESSELS. 6 1

under the epidermis to form vesicles, the drug causing the pro-
duction of vesicles is said to be a vesicant ; e.g., cantharides.

Pustulants are such of the above drugs as are sufficiently
powerful irritants to cause the inflammatory process to proceed to
the passage of leucocytes through the- walls of the capillaries.
They collect in the vesicles, which consequently become pus-
tules ; e.g. , croton oil.

Escharotics or caustics are the most powerful of all the
above drugs. Their local application destroys the vitality of the
part to which they are immediately applied, and sets up vascular
dilatation of the surrounding area ; e.g., strong nitric acid, zinc
chloride, silver nitrate, and arsenous acid.

Counter-irritants. It has been shown by experiments on
animals that when the vessels of the skin are dilated by the appli-
cation of an irritant, those of the subjacent viscera are often
reflexly altered in size. The same is probably true of man. An
irritant is called a counter-irritant when it is applied to the skin
with the object of altering the size of the vessels of the subjacent
viscera. It is particularly to be remembered that the action is a
reflex nervous one, and is in no way due to the withdrawal of
blood into the dilated vessels of the skin.

The following, when inhaled, dilate peripheral vessels by acting locally on
them :



(1) Amyl nitrite.

(2) [Nitroglycerin.]

(3) Sodium nitrite.



(4) Ethyl nitrite.

(5) Spiritus aetheris nitrosi.

(6) Erythrol tetranitrate.



Drugs which, taken by the mouth, dilate arterioles by acting locally on
them :



(1) Caffeine.

(2) Amyl nitrite.

(3) [Nitroglycerin.]

(4) Sodium nitrite.



(5) Ethyl nitrite.

(6) Spiritus aetheris nitrosi.

(7) Erythrol tetranitrate.

(8) Nicotine.



Drugs which, taken by the mouth, contract arterioles by acting locally on
them :



(1) Ergot.

(2) Caffeine (early in its action).



(3) Digitalis.

(4) Physostigmine.



The following have been shown by experiments in the laboratory to cause
contraction of small arteries through which they circulate : copper, zinc, tin,



62



PHARMACOLOGY AND THERAPEUTICS.



platinum salts all cause powerful contraction. Lithium, calcium, strontium,
magnesium, cadmium, nickel, cobalt and iron salts cause slight contraction.

Drugs which, when locally applied to vessels, contract them :

These may act in two ways, either by contracting the muscular
coat of the vessels, or by coagulating the albuminous fluids
around them, the coagulum by its contraction constricting the
vessels.

Those which act on the muscular coat of the -vessels :



(1) Cold, however produced ; hence

rapidly volatilizing substances
as ether. [This effect is but
temporary. If cold is long
continued it dilates blood-ves-
sels.

(2) Cocaine.]

(3) Lead salts.



(4) Dilute solutions of silver salts.

(5) Diluted sulphuric acid.

(6) Alum.

(7) Hamamelis.

(8) [Ergot.

(9) Hydrastis.]

(10) Acetanilid.

(11) [Antipyrin.]



Those which coagulate the albuminous fluids around the vessels :



(1) Tannic acid and all sub-
stances containing it : e.g.,
[nutgall,] krameria,kino,h3em-
atoxylon, hamamelis, cinna-
mon, eucalyptus gum, and
catechu.

(2) Lead salts.



(3) Silver salts.

(4) Zinc salts.

(5) Copper salts.

(6) Alum.

(7) Ferric salts.

(8) Bismuth salts to a slight ex-
tent.



B. Drugs which act on the Vaso-motor Centres.

Drugs which, by their action on the vaso-motor centres, dilate the vessels .



(1) Belladonna.

(2) Stramonium.

(3) Hyoscyamus.

(4) Alcohol.

(5) Ether.

(6) Chloroform.

(7) Chloral hydrate.

(8) [Antimony and Potassium

Tartrate.]



(9) Aconite.

(10) Ipecacuanha.

(11) Lobelia.

(12) Tobacco.

(13) Veratrine.

(14) Hydrocyanic acid.

(15) Opium.



Some of the substances, which in small doses contract the vessels by cen-
tral action, in large doses dilate them ; viz., digitalis and squill.



DRUGS ACTING ON THE VESSELS. 63

Drugs which, by their action on vaso-motor centres, cause contraction of
vessels :



(1) Ergot.

(2) Digitalis.

(3) Strophanthus.

(4) [Sparteine.]

(5) Squill.

(6) Physostigmine.



(7) Cocaine.

(8) Hydrastis.

(9) Hamamelis.
(ID) Strychnine.
(n) Lead salts
(12) Ammonia



| (slightly.)



Also, for a very short early period of their action, some substances whose
main action is to dilate the vessels by their central action ; viz., belladonna,
stramonium, hyoscyamus, alcohol, ether, chloroform, hydrocyanic acid and
veratrine.

Astringents are drugs which diminish the size of the vessels,
and thus decrease the amount of exudation from them.

Styptics, or Haemostatics, are drugs which stop bleeding.
They comprehend all astringents, especially cold, lead and
copper salts, hamamelis, ergot, [hydrastis], tannic acid, and,
above all, ferric salts, for they coagulate the blood which is
flowing from the vessel, and the clot prevents further bleeding.
Matico leaves, because of the numerous hairs on their under sur-
face, favor coagulation of blood when locally applied to a bleed-
ing surface. Cobwebs act in the same way.

Therapeutics. Drugs which locally dilate vessels are [fre-
quently] applied to stimulate sores to heal, and to promote ab-
sorption of inflammatory products, as seen in the application
of iodine over joints in certain forms of joint disease; and as
counter-irritants in many forms of disease of deep-seated organs,
as in the application of a blister in pleurisy. Drugs whffch by
their central action cause dilatation of all the vessels of the body
are used in certain forms of heart disease, as in the use of amyl
nitrite in angina pectoris ; and some suppose that the good they
do is brought about by dilating the vessels, and so rendering the
work of the heart easier. Amyl nitrite and nitroglycerin are
much used for this purpose. Drugs causing general vascular
dilatation are also employed to cause dilatation of the vessels
of the skin with the object of thereby leading to an increase
of perspiration and an increased radiation of heat. Alcohol,



64 PHARMACOLOGY AND THERAPEUTICS.

Spiritus ^theris Nitrosi, and Ipecacuanha, amongst others, are
used in this way.

The most important use of astringents is as styptics ; they are
ilso used to check excessive discharges of all sorts, as in diarrhoea,
leucorrhcea, etc., and in relaxed conditions of vessels, such as are
i)ften seen in pharyngitis.

There is perhaps no better opportunity than this of mention-
ing emollients and demulcents.

Emollients are substances which soften and protect parts.
The word is usually employed for substances applied to the skin.

Common emollients are substances soaked in warm water, as hot fomenta-
Sons and poultices, fats of various sorts, as lard and lanolin (hydrous wool fat),
non-irritating oils, as olive oil, spermaceti, [petrolatum,] vaseline, etc.

Demulcents are substances which protect and soothe parts.
They are generally applied to mucous membranes, especially
when unduly dry, and thus they are often used for the mouth.

Instances of them are gelatin, isinglass, glycerin, gum, honey, flaxseed,
starch, and white of egg.

DIVISION V. DRUGS ACTING ON THE SKIN.

All those described in the last section act on the cutaneous
vessels, but in addition we have

A. Diaphoretics, or drugs which increase the amount of
perspiration. These may do so either by stimulating the sweat
centres in the spinal cord, the nerves proceeding from the centres
to the*glands, the terminations of the nerves in the gland, or the
glandular cells themselves ; or dilatation of the cutaneous vessels
may, by the increase in the amount of blood and the greater
warmth, stimulate the glands and lead to an increase of sweat.
It is difficult to tell whether drugs acting on the vessels do not
also act on the other parts of the mechanism ; and it is also diffi-
cult to decide whether a drug acts on the gland-cells or the ter-
mination of the nerves, so we will consider diaphoretics under
two headings, those which act centrally and those which act pe-
ripherally. These are differentiated by observing whether the



DRUGS ACTING ON THE SKIN. 65

drug acts after the spinal cord is destroyed, [or] on a part of the
skin after the nerves going to it are cut.

(a) Diaphoretics acting peripherally : Pilocarpine greatly increases the
amount of sweat, acting in all probability on the nerve terminations in the
gland-cells, but certainly not on the vessels. Nicotine also acts peripherally.
Local applications of warmth, and alcohol taken internally perhaps act in
the same way in addition to their vascular action.



(b) Diaphoretics acting centrally :

(1) Antimony salts.

(2) Ammonium acetate.

(3) Ammonium citrate.



(4) Ipecacuanha.

(5) Opium.

(6) Camphor.



(f) Diaphoretics whose mode of action is doubtful : Senega, cubeb, col-
chicum, salicin, lobelia, arnica, aconite, potassium citrate and acetate. All
these, except the last two, are very feeble.

When a diaphoretic acts very powerfully it is called a Sudorific.

B. Anhidrotics, or Antihidrotics, drugs which diminish
the amount of perspiration. The part on which these act is de-
termined in the same way as in the case of diaphoretics.

(a) Anhidrotics acting peripherally : Atropine is very powerful ; it acts
on the terminations of the nerves in the glands ; and hyoscyamus and
stramonium probably act in the same way. The local application of cold
has a similar action.

(6) Anhidrotics the mode of action of which is doubtful :



(1) Acids.

(2) Muscarine.

(3) Nux vomica.

(4) Quinine.



(5) Picrotoxin.

(6) Zinc salts.

(7) Salicylic acid.
[(8) Camphoric acid.]



Therapeutics. Diaphoretics are used for three purposes:
either to increase the amount of sweat because that of the urine is
failing, and for this purpose pilocarpine is largely used ; or in the
hope that poisons may be excreted by the sweat, hence the use
of pilocarpine in uraemia ; or as mild antipyretics, in order to
increase the loss of heat by increased evaporation ; for this pur-
pose alcohol, ipecacuanha, ammonium acetate, and opium were
formerly much employed, but of late years much more efficient
antipyretics have been discovered.

5



66



PHARMACOLOGY AND THERAPEUTICS.



Anhidrotics are used either for general conditions, as phthisis,
or for local conditions, as sweating of the feet ; but they are not
of great use in medicine.

We do not know of any drugs which will alter the composi-
tion of the sweat, except in so far as that certain drugs may be
excreted in the sweat when taken internally ; such are iodine,
potassium iodide, succinic, tartaric, and benzoic acids, the last
in the form of hippuric acid.

We have no knowledge of the effects of drugs on the seba-
ceous secretion.

Certain drugs, when taken internally in large doses, pro-
duce a rash on the skin, possibly because in the course of their
excretion through the skin they irritate it. Such are



(1) Copaiba.

(2) Cubeb.

(3) Bromides.

(4) Iodides.

(5) Turpentine.

(6) Belladonna.

(7) Chioral [hydrate.]

(8) Opium.

(9) Quinine.

(10) Salicylic acid.



n Arsenical Salts.

(12) Acetanilid.

(13) [Antipyrin.]

(14) Phenacetin.

(15) Chloralamide.
1. 1 6 Antitoxins.

(17) Serums. "^

(18) Silver salts may discolor

the skin.

(19) [Sulphonal.]



[The following quite rarely produce an eruption :



DIVI



(1) Iron.

(2) Strychnine.

(3) Creosote.

(4) Mercury.

(5) Veratrum.



(6) Digitalis.

(7) Sulphur.

(8) Antimony.
9 Santonin.

(10) Cod Liver Oil.]



SIGN VI. SUBSTANCES ACTING ON THE URINARY SYSTEM.

I. Drugs increasing the quantity of urine secreted. These are
called diuretics. The kidney is a double organ with two dis-
tinct varieties of epithelium ; it is particularly well supplied with
vessels and vaso-motor nerves, and is also profoundly under the
influence of variations in the quantity of blood flowing through
it ; hence it is, with our present state of knowledge, impossible
to say how many diuretics act, but the following table modified,



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