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The Action of Medicines in the System

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Title: The Action of Medicines in the System

Author: Frederick William Headland


        
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Language: English

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*** START OF THE PROJECT GUTENBERG EBOOK THE ACTION OF MEDICINES IN THE SYSTEM ***

THE

ACTION OF MEDICINES

IN

THE SYSTEM;

OR,

"ON THE MODE IN WHICH THERAPEUTIC AGENTS INTRODUCED
INTO THE STOMACH PRODUCE THEIR PECULIAR
EFFECTS ON THE ANIMAL ECONOMY."

Being the Prize Essay

TO WHICH THE MEDICAL SOCIETY OF LONDON AWARDED THE
FOTHERGILLIAN GOLD MEDAL FOR MDCCCLII.

BY

FREDERICK WILLIAM HEADLAND, B.A.,

M. R. C. S., ETC.

[Illustration]

PHILADELPHIA:
LINDSAY AND BLAKISTON.
1853.


WM. S. YOUNG PRINTER


TO

THE PRESIDENT, OFFICERS, AND FELLOWS

OF THE

MEDICAL SOCIETY OF LONDON,

This Essay

IS RESPECTFULLY INSCRIBED, BY THEIR VERY OBLIGED

FRIEND AND SERVANT,

THE AUTHOR.




   CONTENTS.

   CHAPTER I.
                                                                   PAGE

   INTRODUCTORY REMARKS                                              13

   CHAPTER II.

   ON SOME OF THE MORE IMPORTANT CLASSIFICATIONS OF
   MEDICINES, AND OPINIONS OF AUTHORS RESPECTING
   THEIR ACTIONS                                                     29

   CHAPTER III.

   ON THE GENERAL MODES OF ACTION OF THERAPEUTIC
   AGENTS INTRODUCED INTO THE STOMACH; TREATED OF IN
   TEN PROPOSITIONS                                                  60

   PROP. I.                                                          61

   That the great majority of medicines must obtain entry
   into the blood, or internal fluids of the body, before their
   action can be manifested.

   PROP. II.                                                         68

   That the great majority of medicines are capable of solution
   in the gastric or intestinal secretions, and pass without
   material change, by a process of absorption, through the
   coats of the stomach and intestines, to enter the capillaries
   of the Portal system of veins.

   PROP. III.                                                        87

   That those medicines which are completely insoluble in
   water, and in the gastric and intestinal juices, cannot gain
   entrance into the circulation.

   PROP. IV.                                                         90

   That some few remedial agents act locally on the mucous
   surface, either before absorption, or without being absorbed
   at all. That they are chiefly as follow:--

    _a._ Irritant Emetics.
    _b._ Stomach Anæsthetics,
    _c._ Irritant Cathartics.

   PROP. V.                                                          98

   That the medicine, when in the blood, must permeate the mass
   of the circulation, so far as may be required to reach the
   parts on which it tends to act.

   That there are two possible exceptions to this rule:--

    _a._ The production of sensation or pain at a distant point.
    _b._ The production of muscular contraction at a distant
         point.

   PROP. VI.                                                        103

   That while in the blood the medicine may undergo changes,
   which in some cases may, in others may not, affect its
   influence. That these changes may be--

   _a._ Of Combination.
   _b._ Of Reconstruction.
   _c._ Of Decomposition.

   PROP. VII.                                                       106

   That a first class of medicines, called Hæmatics, act while
   in the blood, which they influence. That their action is
   permanent.

     1. That of these some, called Restoratives, act by supplying,
        or causing to be supplied, a material wanting;
        and may remain in the blood.

     2. That others, called Catalytics, act so as to counteract
        a morbid material or process; and must pass out of
        the body.

   PROP. VIII.                                                      217

   That a second class of medicines, called Neurotics, act by
   passing from the blood to the nerves or nerve-centres, which
   they influence. That they are transitory in action.

     1. That of these some, called stimulants, act so as to
        exalt nervous force, in general or in particular.

     2. That others called Narcotics, act so as first to exalt
        nervous force, and then to depress it; and have also a
        special influence on the intellectual part of the brain.

     3. That others again, called Sedatives, act so as to depress
        nervous force, in general or in particular.

   PROP. IX.                                                        256

   That a third class of medicines, called Astringents, act by
   passing from the blood to muscular fibre, which they excite
   to contraction.

   PROP. X.                                                         268

   That a fourth class of medicines, called Eliminatives, act
   by passing out the blood through the glands, which they
   excite to the performance of their functions.

   CHAPTER IV.                                                      309

   ON THE ACTION OF SOME OF THE MORE IMPORTANT MEDICINES
   IN PARTICULAR




A

CLASSIFICATION OF MEDICINES

WHICH

ACT AFTER ENTERING INTO THE BLOOD, ACCORDING TO

THEIR SUPPOSED MODES OF OPERATION.

                  PAGE

   CLASS I. HÆMATICA 106


   DIV. I. RESTAURANTIA 113

   Ordo 1. Alimenta 115

   Ordo 2. Acida 120

   Ordo 3. Alkalia 126

   Ordo 4. Tonica 129

   Ordo 5. Chalybeata 145

   Ordo 6. Solventia 149


   DIV. II. CATALYTICA 157

   Ordo 1. Antiphlogistica 185

   Ordo 2. Antisyphilitica 188

   Ordo 3. Antiscrofulosa 191

   Ordo 4. Antiarthritica 194

   Ordo 5. Antiscorbutica 205

   Ordo 6. Antiperiodica 207

   Ordo 7. Anticonvulsiva 211

   Ordo 8. Antisquamosa 213


   CLASS II. NEUROTICA 217


   DIV. I. STIMULANTIA 226

   Ordo 1. Stimulantia Generalia 227

   Ordo 2. Stimulantia Specifica 232


   DIV. II. NARCOTICA 234

   Ordo 1. Inebriantia 237

   Ordo 2. Somnifera 238

   Ordo 3. Deliriantia 240


   DIV. III. SEDANTIA 242

   Ordo 1. Sedantia Generalia 244

   Ordo 2. Sedantia Specifica 249


   CLASS III. ASTRINGENTIA 256

   Ordo 1. Astringentia Mineralia 260

   Ordo 2. Astringentia Vegetabilia 265


   CLASS IV. ELIMINANTIA 268

   Ordo 1. Sialagoga 281

   Ordo 2. Expectorantia 283

   Ordo 3. Cathartica 286

   Ordo 4. Cholagoga 295

   Ordo 5. Diaphoretica 298

   Ordo 6. Diuretica 302




ON

THE ACTION OF MEDICINES

IN

THE SYSTEM.




CHAPTER I.

INTRODUCTORY REMARKS.


In commencing this Essay on the Action of Medicines, I must confess that
I feel at first a certain discomfort when I consider the magnitude of
the task before me. Many a volume has been written to elucidate the
operations of single medicines, and when the variety and complexity of
such an operation is considered, the space devoted to its consideration
will hardly seem too great. Thus it is not to be wondered at that, when
pausing on the threshold of my subject, I should be sensible of the many
difficulties with which such an inquiry is surrounded.

In this introductory chapter it will be my aim, in the first place, to
set forth briefly the great importance and extent of the subject,
showing that it is an essential requisite in the advance and perfection
of medical science. Next, I must insist on the advantage of correctness
and clearness of language and argument in the treatment of such topics
as this, and show in what manner I propose myself to attain to it. And
in the third place, I must shortly explain the scheme or arrangement
which will be followed in this Essay. If the preliminary remarks
contained in this chapter are not first considered and clearly
apprehended, I fear that I may be but imperfectly understood in what I
shall have to say hereafter.

There have been, more or less, in all ages, two systems or schools of
medical treatment, of which the one prevails among ignorant men, and in
rude states of society, but the other requires a higher degree of
enlightenment. These are the Empirical and the Rational systems. The
first is founded on simple induction. By accident or by experience it is
found that a certain medicine is of use in the treatment of a certain
disorder: it is henceforth administered in that disorder; and on a
number of such separate data an empirical system is constructed. It
naturally requires for its elaboration a comparatively small degree of
knowledge.

Now this observation of facts is indispensable as a beginning, but
something more is required. We must not be satisfied with taking them
separately, but we must proceed to compare together a large number of
facts, and draw inferences from this comparison. And our plan of
treatment will become rational, when on the one hand, from an accurate
knowledge of the symptoms of diseases, we are better enabled to meet
each by its appropriate remedy, and on the other hand, from some
acquaintance with the general action of a medicine, we are fitted to
wield it with more skill and effect, and to apply it even in cases where
it has not yet been proved beneficial. Thus, for the proper perfection
of medicine as a rational science, two things are in the main needed:
the first is a right understanding of the causes and symptoms of
disease; the second, a correct knowledge of the action of medicines.
Should our acquaintance with these two subjects be complete, we should
then be able to do all that man could by any possibility effect in the
alleviation of human suffering. This sublime problem is already being
unravelled at one end. Diagnosis and Nosology are making rapid strides;
and perhaps we shall soon know what we have to cure. But at the other
end our medical system is in a less satisfactory condition; and though
some impatient men have essayed, as it were, to cut the Gordian knot,
and have declared boldly on subjects of which they are ignorant, yet it
must be confessed, that in the understanding of the action of medicines,
and of their agency in the cure of diseases, we do not so much excel our
ancestors. While other sciences are moving, and other inquiries
progressing fast, this subject, so momentous in its applications, has,
in spite of the earnest labours of a few talented investigators, made
after all but small progress. Let but those who feel this want bestir
themselves to remove it, and it will soon be done. Those doubts and
difficulties, which are now slowly clearing away before the efforts of a
few, will then be finally dispelled by the united energies of all; and
instead of our present indecision and uncertainty on many points, we
shall find ourselves eminently qualified to wage the conflict with
disease, being skilled in that science whose name bespeaks its peculiar
importance, the science of _Therapeutics_.

The subject assigned to me as the text of this Essay concerns this
problem:--"On the mode in which Therapeutic Agents introduced into the
stomach produce their peculiar effects on the Animal Economy." It is
naturally a subject of very great extent; and one difficulty with which
I am beset is that I scarcely know how to compress what I have to say on
the action of medicines into the compass required. It will be granted
that it is an important subject; it is also a difficult one. This
difficulty depends mainly on the variety and complexity of the proof
required to establish any one point with absolute certainty.[1] A long
time ago, when men knew and understood less than they do now, it was
fancied that the action and choice of medicines was a thing of the
utmost simplicity; that it was comparatively an easy matter to fix at
once upon that remedy required most in any particular case.[2] But the
light of science, which in this day burns more brightly, at the same
time that it displays all objects with greater distinctness, discloses
to us also many dim vast tracts in the distance, of which nothing had
been seen or imagined before. In this, as in other things, the more we
know the more we discover our real ignorance. It is wrong, then, to
treat dogmatically of matters that we cannot comprehend; and when
perfectly in the dark as to the operation of a medicine, we should rest
content with declaring the result of that operation. This by itself will
be of great use to us.[3]

I am induced to lay stress on the difficulties surrounding an inquiry
into the _modus operandi_ of medicines, because it will be some excuse
for the manifest insufficiency of the sketch which I am about to draw.
For this, too, I may find a further apology in the fallacies and
mistakes, both of reasoning and statement, of which previous writers
have been guilty. These are best shown by their discrepancies. On no
question, perhaps, have scientific men differed more than on the theory
of the action of medicines. Either facts essentially opposed and
incompatible have been adduced by the disagreeing parties; or, which is
nearly as common, the same fact has received two distinct and opposite
interpretations. Many hypotheses, when tested, are seen to be grounded
on bare assertions, and to be destitute of logical proof; many others
are attempted to be established on ill-sustained analogies. Analogy, in
such a case as this, may be used to increase a probability already
evidenced; but by itself it is no proof, for we find often that
medicines are capable of producing the same result in very dissimilar
ways.

How then are we to arrive at the truth! The best and surest way is to be
extremely careful in the means which we employ in its discovery.

It is, I think, impossible to overrate the importance of _exact
precision of language and thought_ in scientific details, and in the
deduction of conclusions from them.[4] A subject so interesting as this
requires to be treated in a logical way. Facts, when ascertained, should
be ranged together and compared, and exact inferences made, without ever
straining a point. And when we are inclined to hazard a theory that is
barely supported, we should take care to state it as a theory, and not
to bring it forward as a truth. It has not been an uncommon habit among
scientific authors, who should be of all men the most careful and exact,
to confound assertion with fact--to mistake hypothesis for truth. In
such illogical and incorrect reasoning is to be found the true source of
a multitude of errors.

Being sensible of this danger, I have endeavoured to keep it in view in
the arrangement of this Essay. In order to obtain, if possible, this
clearness and precision, or at all events, to be better understood, I
have arranged the heads of my ideas on the action of medicines in a
number of distinct propositions, the scope of which will be presently
described. I shall attempt to prove each of them separately, as if it
were a theorem in geometry, sometimes dividing it first into a number of
minor propositions, which, taken together, imply the original one, and
which have to be severally discussed.

The great use of such an arrangement is its distinctness: so that it may
in any case be easily seen whether a proposition has been established,
or whether I have failed to prove it. These propositions are the
foundation of the Essay; and upon them has been erected a superstructure
of more or less logical consistency. In them has been stated about as
much of the general principles by which medicines operate as seems to me
to be capable of distinct proof: _i.e._ which may be regarded with that
kind of certainty which we generally expect to attain to in scientific
matters. So far, then, I have kept myself in a straight road, between
two walls, diverging neither to the right nor to the left to gratify my
inclination; it being, as I have said, a most obvious duty to guard
against stating that for fact which is at the best uncertain. But having
gone so far, I have in several instances indulged in speculations and
hypotheses on certain matters, taking care to state that such
explanations are only probable, and very far from determined. But it is
often our duty to inquire into uncertain things; and those who do so,
who officiate, in however humble a capacity, as the pioneers of
knowledge, have to hazard many conjectures before they arrive at the
truth. In striving after truth, we must investigate many an unknown
path, and try at many a door where we have not before entered. Thus,
when in some cases I have perceived before me a line of thought
stretching onwards, and seeming to lead somewhere in the direction of
truth, I have not, as it were, shunned it, or turned aside to tread only
in more certain paths, but I have thought it my duty to follow it up,
and to investigate it thoroughly, to see if by any means it might not
help me on my way to that desired haven. These theories are the weak
points of the Essay, but I must crave indulgence for them on the grounds
alleged above. It will be observed that the original propositions are so
stated, that the overthrow of any one of these extra hypotheses would
not shake them, or in any way invalidate their proof.

I will now sketch out the arrangement which I propose to follow in the
consideration of the topics which present themselves to me.

In the next chapter I shall take a brief review of the opinions of other
writers on the subject of the action of medicines; knowing, indeed, that
in so short a notice I shall be perfectly unable to do them justice, but
wishing, in some broad points, to draw the line between what is known
and what is unknown,--what is ascertained and what is debated,--what is
approved and what condemned. In some cases also I may venture to object
to opinions hitherto unquestioned. Now, as the best key to the main
opinions of authors on this subject, we have to consider the various
classifications of medicines which they have adopted. A classification
of remedies presupposes a set of theories concerning either their
primary action or their general results, and is, in fact, identical with
them. The formation of such an arrangement depends on the necessity of
considering medicines in groups, each possessed of some common
character, in order that their various properties may be simplified, and
admit of being compared.

In a classification we do not so much consider the peculiarities of
single remedies, as the points in which large numbers agree together.
These points of resemblance we gene rally find to be of the most
importance. I have to consider three sets of authors in the second
chapter. The first set treat of the general or ultimate effect of a
medicine on the system; and classify medicines accordingly. A second set
of writers have arranged therapeutical agents according to the organ or
part of the body to which their action is especially directed. Neither
of these deal with the mode in which medicines act as the basis of
classification. A third set of writers have attempted in various ways to
explain the modes of operation of medicines. They have laid down general
rules about these operations, and have constructed more or less
plausible theories on the subject. Some few have classified remedies on
this plan. Now, with these theories I am more particularly concerned, as
they trench immediately on the subject of this Essay. But they are not
many, and it will not take us long to review them.

It is easier to find fault than to teach. After pointing out the
shortcomings of some who have preceded me, I find myself necessitated in
the third chapter to state my own conclusions as to the _modus operandi_
of medicines.

Let us consider, as it were, the history of a remedy from the beginning
to the end of its course. It is already "introduced into the
stomach"--we must commence with it there. Now it does not remain there.
It cannot act from the surface of the stomach through the medium of the
nervous system.

In the _First Proposition_ it is affirmed that it must obtain entry into
the fluids of the body--pass, that is, from the intestinal canal into
the system at large--before its action can begin. There are four proofs
of this. It is shown that when introduced at another part of the body a
medicine acts in the same way as when placed in the stomach. It is found
by direct experiment that a poison will not act through the medium of
nerves only, but that its passage in the blood is required. Thirdly, the
course of the circulation is quick enough for the most rapid poison or
medicine to pass quite round the body from the veins of the stomach
before it begins to operate. The last and most conclusive argument to
show that medicines pass out of the stomach into the system, is that
they have actually been detected by chemists, not only in the blood, but
in the secretions formed from the blood. Remedies, then, pass from the
stomach into the blood and fluids. How do they do so?

In the _Second Proposition_ it is laid down that all those which are
soluble in water, or in the secretions of the stomach or intestines,
pass through the coats of these organs into the interior of the
capillary veins which surround them. It has already been shown that most
medicines pass through in some way; we shall now have to learn how they
pass, and what special arrangements are made for the passage of
substances differing in nature. By the physical process of absorption a
liquid may pass through the animal membranes, from the interior of the
stomach or intestine to the interior of the small vein which lies close
outside it. In examining the laws by which this process is conducted, we
shall find that all the requirements are present in these parts,
provided only that the substance to be absorbed shall be first in some
way dissolved, and reduced to the liquid state. In the stomach there is,
in contact with the substance just introduced, a thin watery secretion
containing acid and a matter called pepsin: this is the gastric juice. A
large number of medicines are soluble in water. They are dissolved in
this fluid. Some others are soluble in dilute acid. These too are
dissolved here. Albumen, and matters like it, are reduced to solution by
the aid of the pepsin, which is the principle of digestion. But there
are some few mineral bodies, and many vegetable substances, as fats and
resins, which cannot be thus dissolved by the juice of the stomach. They
are soluble, more or less, in a weak alkaline fluid; and such a fluid is
the bile, which is poured out into the first portion of the intestine.
They too are reduced to solution and absorbed. In this manner it is
shown that a very great majority of remedial agents are capable of being
reduced to solution, of being absorbed without material change, and of
passing thus into the circulation.[5] Very few are quite insoluble; but
some that are dissolved with difficulty may be left partly undissolved
in the intestinal canal. What becomes of these?

It is asserted in the _Third Proposition_ that substances which are thus
insoluble cannot pass into the circulation. Arguing from a physical law,
we should say at once that it was impossible; but the matter cannot be
so lightly dismissed, for a foreign professor has lately asserted that
insoluble matters may and do pass into the circulation. I have made
experiments to satisfy myself on the point, and have come to the
contrary conclusion.

In the _Fourth Proposition_ it is stated that some few substances may
act locally, by irritation or otherwise, on the mucous surface of the
stomach or intestines. These are not many; they act without being
absorbed; and they do not extend into the system at large. In some few
cases, these local actions may be succeeded by changes in distant parts,
on the principle of _Revulsion_.

Having just shown how medicinal substances are absorbed, we have now to
suppose that they are in the blood.

It is next maintained, in the _Fifth Proposition_, that the medicine,
being in the blood, must permeate the mass of the circulation as far as
to reach the part on which it tends to act. This it can easily do. The
circulating blood will conduct it any where, in a very short time.
Supposing a medicine has to act on the liver, or on the brain, or on the
kidney, it does not influence these organs at a distance, but it passes
directly to them in the blood, and then its operation is manifested.
This may be called the rule of _local access_. Its proof depends on two
things: on the impossibility of the medicinal influence reaching the
part in any other way, as shown in the first proposition; and on the
fact of medicinal agents having been actually detected in many cases in
the very organs over which they exert a special influence. But are there
any exceptions to this? Can a medicine ever produce an effect without
actually reaching the part? It seems that there may be two exceptions.
In some cases an impression of _pain_ may be transmitted along a nerve
from one part to another; and in some other few instances a muscle, when
caused to contract by the influence of a medicine, may cause other
muscles near it to contract by sympathy.

Before we inquire into the remedial action of the medicine in the blood,
we must consider whether that fluid may not first alter it in some way,
so as to hinder or affect its operation. To a certain extent this is
possible.

In the _Sixth Proposition_ it is asserted that while in the blood the
medicine may undergo change, which change may or may not affect its
influence. It will have to be shown that this change may be one of
_combination_, as of an acid with an alkali; of _reconstruction_, when
the elements of a body are arranged in a different way, without a
material change in its medical properties, as when benzoic is changed
into hippuric acid; or of _decomposition_, when a substance is
altogether altered or destroyed, as when the vegetable acids are
oxidized into carbonic acid.

Having considered these preliminary matters, we shall arrive at the
main point. The medicines are now in the blood. We must consider what
becomes of them; what they do next; where they go next; and how they
operate in the cure of diseases. I have made a classification in which
medicines are divided according to my views of their mode of operation.
The classes and their subdivisions will serve for references in
illustration of what I have to say. For it is not possible to speak of
the general operation of medicines without adducing particular
instances; nor will time and space always allow me, in doing so, to
refer to individual medicines.

There are four great groups of medicines, the action of each of which is
well marked and distinct. The first class acts in the blood; and as a
large number of diseases depends on a fault in that fluid, we may by
their means be enabled to remedy that fault. They are the most important
of all medicines. They are called Hæmatics, or blood-medicines. They are
used chiefly in chronic and constitutional disorders. But a second class
of remedies are temporary in their action. They influence the nervous
system, exciting it, depressing it, or otherwise altering its tone. They
are chiefly useful in the temporary emergencies of acute disorders. They
can seldom effect a permanent cure, unless when the contingency in which
they are administered is also of a temporary nature. They are called
Neurotics, or nerve-medicines. A third set of medicines, less extensive
and less important than the others, acts upon muscular fibre, which is
caused by them to contract. Involuntary muscular fibre exists in the
coats of small blood vessels, and in the ducts of glands. Thus
Astringents, as these agents are called, are able, by contracting
muscular fibre, and thus diminishing the calibre of these canals, to
arrest hemorrhage in one case (when a small vessel is ruptured,) and to
prevent the outpouring of a secretion in another case.

The fourth class is of considerable importance. Some medicines have the
power of increasing the secretions which are formed from the blood by
various glands at different parts of the body. By their aid we may be
enabled to eliminate from the blood a morbid material through the
glands; or we may do great good by restoring a secretion when
unnaturally suppressed. They are called Eliminatives. Like Hæmatics,
their influence is more or less permanent. That of Neurotics and
Astringents, particularly the former, is transient.

The general mode of action of these four classes of therapeutic agents
is laid down in the four remaining propositions, about as far as it
seems to me to be capable of a positive definition. Each proposition
concerns one of these classes of medicines. All I can do now is to
recapitulate the chief affirmations made; as to give any idea of their
proof would require me to enter into a number of details which had
better be postponed to the third chapter.

In the _Seventh Proposition_ it is stated of Hæmatic medicines that they
act while in the blood, over which fluid they exert an influence; and
that their effect, whatever it be, is of a more or less permanent
character. A line of distinction is drawn between two divisions of this
class of blood-medicines. Some of them are natural to the blood; they
resemble or coincide with certain substances that exist in that fluid;
so that, having entered it, they may remain there, and are not
necessarily excreted again. These are useful when the blood is wanting
in one or more of its natural constituents. This want causes a disease,
and may be supplied by the medicine, which in this way tends to cure the
disease. Medicines of this division are called Restoratives; for they
_restore_ what is wanting.

Some other blood-medicines, although they enter the blood, are not
natural constituents of the vital fluid, and cannot remain there, for
they are noxious and foreign to it. They must sooner or later be
excreted from it by the glands. They are of use when disease depends on
the presence and working in the blood of some morbid material or
agency, which material or action they tend to counteract or destroy.
They may be called _vital antidotes_; not strictly _specifics_, for they
are not always efficacious, on account of variations in the animal
poisons, or from the casual operation of disturbing causes. They are
applicable in those many disorders which depend, not on the absence of a
natural substance, but on the presence of an unnatural agent in the
blood. These medicines are called Catalytics, from a Greek word which
signifies _to break up_ or _to destroy_. Having performed this, their
function, they then pass out of the blood.

All this requires to be proved.

In the _Eighth Proposition_ it is stated of Neurotics, or
nerve-medicines, that they act by passing out of the blood to the
nerves, which they influence. This is only to insist on the rule of
_local access_, already laid down in Prop. V. It is further affirmed
that they are transitory in action. They appear to effect molecular
changes in nerve-fibre, similar to those by which the phenomena of the
senses are produced, and which are by nature transitory in their
results. And yet they may be very powerful, even so as to extinguish
vital force. Thus, short and unenduring as is the operation of these
agents, it may last long enough to cause death, and so a temporary
influence produce a permanent result. There are three divisions of
Neurotics. The first set are of use when there is a dangerous deficiency
of vital action. These are Stimulants. They exalt nervous force, either
of the whole nervous system, or only of a part of it. They vary very
much in power. A second set, called Narcotics, first exalt nervous
force, and then depress it. They have thus a double action; but they
have also a peculiar influence over the functions of the brain, which is
different from any possessed by other nerve-medicines. They control the
intellectual part of the brain, as distinguished from its organic
function; the powers of _mind_ more than those of _life_. Some
Narcotics tend to produce inebriation; others, sleep; others, again,
delirium. In the third place some Neurotics tend simply and primarily to
depress nervous force. They may act on the whole nervous system, or on a
part of it only. They are often very powerful; and they are of use when,
from any cause, some part of the nervous system is over-excited. They
are called Sedatives. Like other Neurotics, they are used in medicine as
temporary agents in temporary emergencies. If a permanent action be
required, the remedy must be constantly administered, that the effect
may be kept up by continual repetition.

In the _Ninth Proposition_ it is affirmed of Astringent medicines that
they act by passing out of the blood to muscular fibre, which by their
contact they excite to contraction. They do not so much influence the
voluntary fibre of the muscles, which is under the direct control of the
nervous system: but they chiefly manifest their action on the
involuntary or unstriped muscular fibre, which is not directly
controlled by the brain and nerve-centres, and for this reason more
under the operation of external or irritating agents. Meeting this in
the coats of the capillary vessels and of the ducts of glands, they are
enabled to act as styptics, and as checkers of secretion. The action of
Astringents appears to depend on a chemical cause; for we find that all
of them possess the power of coagulating albumen.

The _Tenth Proposition_ treats of Eliminatives. It is not said simply
that these increase the secretions of a gland; or that they stimulate
the glands while passing by them in the blood. But it is laid down as a
rule that they act by themselves passing out of the blood through the
glands, and that while so doing they excite them to the performance of
their natural function. They are substances which are unnatural to the
blood, and must therefore pass out of it. In so doing they tend to pass
by some glands rather than by others: in these secretions they may be
detected chemically; and it is on these glands that they have an
especial influence. Their uses in treatment are various and manifold.

In these classes are included all medicines that act after entry into
the blood. On referring to the classification which precedes this
chapter, it will be seen at a glance what groups of medicines are
arranged as orders under each class or division.[6] In the third chapter
I shall attempt at some length to prove the propositions which treat of
these four classes; and I shall also attempt to explain the nature and
mode of action of the orders, or small groups of remedies.

In the fourth chapter some of the more important medicines will be
considered separately, either as individually interesting, or as
illustrative of general modes of operation previously described.

I may point to some parts of the Essay as being more original than
others, although not perhaps for that reason more valuable. For this
purpose may be mentioned the treatment of the second proposition: the
distinction attempted to be drawn between the two divisions of
blood-medicines; the account given of Tonics in one of these divisions,
and of Anti-arthritics in the other; the theory of the action of
Eliminative medicines; and the experiments made on the action of
Aconitina.




CHAPTER II.

ON SOME OF THE MORE IMPORTANT CLASSIFICATIONS OF MEDICINES, AND OPINIONS
OF AUTHORS RESPECTING THEIR ACTIONS.


I have thought it necessary, before stating at length my own
conclusions, to refer to some of the more important statements of
authors concerning the subject of which I have to treat; because by so
doing I may to some extent indicate what points are to be regarded as
determined and proved, and what as still unsettled, and point out where
I can agree with other writers, and where I am disposed to differ from
them.

The opinions of authors on the general action of medicines are in most
cases best ascertained by observing the manner in which they have
arranged and classified them, grouping together those which they
consider to be alike in their mode of operation.

Differences of opinion respecting individual medicines will be best
considered afterwards, when we come to discuss those medicines. We are
now to make inquiry as to the action of classes and groups. So that, in
examining classifications as a key to the opinions of writers on this
matter, we are only concerned with those which are founded in some way
on the effects and operations of medicines.

Now there are three different points of view from which the action of a
medicine may be regarded. We may ask,--1. What is the ultimate effect of
its action on the system? 2. To what organ or tissue is its action
directed? 3. In what way does it operate?

In other words, we may speak of the _result of the action_ of a
medicine, of the _direction of the action_ of a medicine, or of the
_mode of operation_ of a medicine.

The first of these questions is the simplest, and may be answered from
experience. We know that one medicine is a purgative, because it opens
the bowels. We call another an alterative, because the manifestations of
vital action are somewhat different after its use from what they were
before. The last question is the most difficult to answer, because it
involves the exact mode in which a medicine first behaves itself, so as
to bring about its recognised operation.

Though the arrangements and theories of authors have generally taken
into account all three of these questions, yet they have usually given
greater prominence to one or other of them. And according to this their
predominant idea, I will take the liberty of grouping them into three
schools for the sake of convenience; considering, first, some theories
and therapeutical arrangements which are based upon the ultimate effect
of medicines; secondly, some that depend upon their local tendencies;
and thirdly, some others that concern their mode of operation.

Among those who have directed attention to their ultimate effect,
regarding that as generally sufficient for practical purposes, are
included the great majority of those who have classified medicines. Such
arrangements are practically useful, as by their means we are enabled
easily to select a medicine which shall produce a required result. A
classification founded upon local tendency is such as hardly to admit
of practical application, for it is too vague. It is said that the
action of mercury is directed to the blood; that of a tonic, to the
muscular system. It is not said how they operate, or how these parts are
affected. The terms employed are too wide and indefinite. Supposing the
word _Neurotic_ to signify a medicine acting on the nerves, we cannot
say that any known medicine may not at some time or in some way act on
the nervous system. The same term means a very different thing when
found in a classification based on the mode of operation of medicines,
for then it signifies a medicine acting on the nerves in a certain way
which is defined, and it conveys to us an amount of information
respecting that medicine and its applicability which we had not
otherwise acquired. A classification of this third kind, though
difficult of construction, would naturally be of great practical and
scientific utility. The precise mode in which groups of medicines
operate has first to be discovered and laid down, together with the
results of that operation; and it has then to be proved that each remedy
included in a class operates in the exact way predicated of that class.
None which do not do so can be consistently included in it. Such an
arrangement is precise; there may be a great deal of error, but there is
very little vagueness about it. Each name and term should contain in
itself and in its position an exact description of the general action of
the substances included under it. Such an arrangement I have attempted
to construct myself, as it is with the mode of operation of medicines
that I am particularly concerned. The chief and obvious objection to
such a classification consists in the insufficiency or insecurity of the
data which we have to guide us. Thus the best and safest way is to
select as the bases of primary subdivision those distinctions which
admit of being the most readily and firmly established, and not to rest
it on a number of uncertain or questionable hypotheses.


I. OPINIONS CONCERNING THE ULTIMATE EFFECT OF MEDICINES, AND
CLASSIFICATIONS FOUNDED ON THIS.

Most authors have grouped remedies together according to the broad
results of their action. They do not make inquiry as to the mode of
operation or behaviour of a medicine after passage into the system; nor
do they ask whether this action is especially directed to any organ or
tissue; but they judge by external evidence of its ultimate effect on
the body, and on the powers of life.

There is commonly a tendency to describe all medicines under two heads,
as either causing or diminishing vital activity. Dr. Murray indeed
confounds these two effects, and adopts an idea on this subject which
was originated by Mr. Brown. I shall now represent in an abridged form
the classifications adopted severally by Dr. Young, Dr. Duncan, and Dr.
Murray.

                DR. YOUNG.

    1. CHEMICAL AGENTS.
                 Caustics, etc.

    2. VITAL AGENTS.

       A. _Supporting strength._
                 Nutrients.

       B. _Causing action._
             (Partial and transitory.)
                 Stimulants, Irritants, Astringents,
                     Alteratives, Evacuants.
             (Permanent.)
                 Tonics.

       C. _Diminishing action or sensation._
             (Primarily.)
                 Narcotics, Nauseants, Sedatives,
                     Diaphoretics.
             (Secondarily.)
                     Exhaurients.

    3. INSENSIBLE AGENTS.
                     Specifics.

In the names of these three classes some reference is made to the _modus
operandi_ of medicines, but the distinctions thus attempted to be drawn
are of the slenderest possible description. Among _chemical_ agents are
included some that are applied externally, and act then on the tissues
in obedience to known chemical laws. But how can we affirm that some
medicines passing into the stomach may not operate chemically? The term
_vital_ signifies little; and the word _insensible_, applied to the
third class, is a confession of absolute ignorance. It does not attach
to a medicine any distinctive character to say that we know nothing of
its operation. Pursuing the subdivision further, we find that the
distinctions are not well maintained. Tonics support strength as well as
cause action; and it can hardly be said that the action of an
Alterative, such as mercury, is partial and transitory. It seems unwise
to have made a separate class of Specifics. They are especially
associated with Alteratives. Mercury, Iodine, and others, would fall
under both groups. Of Evacuants it may be observed, that they are also
Exhaurient, and thus included in two opposed classes; that their action
is not always partial and transitory, as, for example, Purgatives may
permanently remedy constipation; and that it seems wrong to have
separated Diaphoretics from them.

Thus neither the primary nor the secondary subdivisions of this
arrangement can be reasonably maintained in theory, and we must fall
back on the ultimate groups which are based upon common experience. From
this failure we may infer that the idea that medicines differ
prominently in causing or diminishing vital activity, upon which idea
this and many other arrangements are founded, is in fact an erroneous
one. There is no such universal distinction. A medicine which at one
time raises or excites the vital forces, may at another time depress
them; it may do one thing with a sick man, the other thing with a
healthy man; it may have the one effect when taken for a short time in
moderation, the other effect when taken for a long time or in excess. In
fine, the result of the operation of a medicine does not necessarily
depend upon this alternative. Although there are undoubtedly some
medicines which tend to stimulate the nervous forces, and others which
tend to depress them, yet as there are many remedies which may operate
well without doing either the one or the other, and whose operation does
not depend at all upon this, the distinction cannot be generally
applied.

The next arrangement, that of Dr. Duncan, appears, as far as it extends,
to be correct in theory. If some additions were made to it, it would be
a tolerably perfect classification of this kind. Assuming as a basis the
ultimate or practical effect of medicines, we may proceed to divide them
into groups in a natural way. Food and liquids are of use in the
nutrition of the tissues, and will form the first class. A second set of
substances act so as to expel from the body certain humours and
secretions. Another class exalt the tone of the nervous system, and
through it stimulate the system at large. A fourth set depress the same.
And a fifth group do none of these things; but their action results in
certain obvious changes in the chemical nature of the secretions.


                     DR. DUNCAN.

    ALIMENTA.
                       Diluentia, Demulcentia.
    EVACUANTIA.
                       Diaphoretica, Errhina, Expectorantia,
                         Cathartica, etc.
    STIMULANTIA.
                       Topica (irritants, etc.)
                       Generalia permanentia.
                       Generalia transitoria.
    DEPRIMENTIA.
                       Refrigerantia, Narcotica.
    CHEMICA.
                       Acida, Alkalina.

As far as it extends, this classification seems to be founded on correct
data. The smaller divisions are natural. Thus Evacuants are grouped
according to the part of the system at which the evacuation is made.
General Stimulants are divided into those which are transitory in
action, and those whose effect is permanent, as Tonics. Dr. Duncan is
concerned only with the ultimate effect, and enters into no theory
respecting the action of Tonics. I regard them as medicines acting
primarily in the blood, and, applying my terms with a view to the _modus
operandi_, I would restrict the term Stimulant to medicines acting on
the nerves, whose effect is transitory.

The great fault of this arrangement is the omission of the very
important class of Alteratives. We have medicines which increase
secretion; medicines which exalt or diminish the vital energy; but where
are the remedies which act in the blood? Where, for example, shall we
place such medicines as Mercury, Arsenic, and Iodine, which neither act
by eliminating, nor by stimulating, nor by depressing, but appear to
counteract in the blood the agency of certain morbid poisons? In an
arrangement founded on ultimate effect, they should be grouped in a
class as Alteratives, as medicines which result in _altering_ for the
better the condition of the system. Both Dr. Duncan and Dr. Murray seem
to have thought that no medicines could act in the fluids but such as
have a well known chemical effect upon them. It cannot be that medicines
should be able to affect the nerves, and to influence the glands, in
divers ways, but that none should exert any action upon the blood, a
most susceptible and changeable fluid, the medium of nutrition, the
source of all the tissues, the "_fons et origo_" of disease. It is only
very lately that authors have begun to recognise and include in their
arrangements the class of blood-medicines, which seem to me to be
considerably more important than any other.

Having shown thus what appear to me to be the correct bases upon which
an arrangement of this kind should be constructed, I shall quote as
another specimen the classification of Dr. John Murray, but mentioning
only its most prominent details.

              DR. MURRAY.

    GENERAL STIMULANTS.
                    _Diffusible_ {Narcotics.
                                      {Antispasmodics.
                    _Permanent_ {Tonics.
                                      {Astringents.
    LOCAL STIMULANTS.
                    Evacuants, Irritants.
    CHEMICAL AGENTS.
    MECHANICAL AGENTS.

We find in this division some reference made to the local tendencies of
medicines. Evacuants are classed as Stimulants which tend to act locally
on the glands. In the arrangement of Dr. A. T. Thomson, founded upon
this one, still further reference is made to the local tendencies of
different medicines. Dr. Paris also has adopted this arrangement, but in
a very much improved form. Both Dr. Thomson and Dr. Paris take exception
to the inclusion of Sedatives (under the head of Narcotics) among
general Stimulants. This is the great fault of Dr. Murray's
classification. The idea, as he states, was taken from Brown. It is
considered that both Stimulants and Narcotics act alike; that is, that
they both produce a primary stimulation followed by a secondary
depression; only that, in the case of Narcotics (under which head all
Sedatives are included) the stimulation is very brief, and rapidly
passes away, to be followed by a great depression. Now, even if this
were true, the most prominent action would be the depressing effect, and
it is on the most prominent action that denominations such as these are
usually based. But it is well urged by Dr. Thomson that in the case of
true sedatives there is no stimulant action whatever; and it is
manifestly unreasonable to suppose that the depressing effect follows as
a consequence on the primary stimulation, when the latter is so
inconspicuous. At any rate such an arrangement as that of Dr. Murray
can be of little practical utility in its original form. A man would be
considered to be indulging in the wildest and most dangerous fancies who
would run through the catalogue of Narcotics when he desired to produce
a general stimulant effect. To this system it might further be objected,
that Alteratives are again entirely omitted; and that the class of
Mechanical agents would seem to belong to the division of Irritants,
included among Local Stimulants. Dr. Murray classes Refrigerants among
Chemical remedies, for which, when I come to speak of Acids, I hope to
show that there are good reasons.


II. OPINIONS CONCERNING THE LOCAL TENDENCY OF MEDICINES, AND
CLASSIFICATIONS FOUNDED UPON THIS.

Here another step is made in the explanation of the action of medicines.
They are said to have particular tendencies towards certain parts of the
body, over which parts they exert a peculiar and special influence. It
is thought that we shall make an advance in our knowledge of the
subject, if we can discover what these tendencies are. An arrangement of
medicines may be made accordingly. It is certainly more scientific than
a merely empirical arrangement; and it will be so far of use that it
will enable us, when we wish to make an impression on a certain organ or
set of organs, to select those medicines which especially influence it
or them. There is no doubt whatever of the existence of these local
tendencies. There is no doubt that some medicines, such as Iodine,
Bromine, Mercury, and Iron, tend especially to affect the blood and the
blood-making organs, as the liver and spleen, rather than to act on the
nervous or glandular systems. That some tend particularly towards the
nerves, and prefer individually different parts of the nervous system,
as Opium acts on the brain, Aconite on the superficial sensory nerves,
Digitalis on the organic nerves of the heart, and Stramonium on those of
the lungs. Again, it is evident that some medicines tend to act on the
organs of secretion; and of these, particular sets select particular
glands, as Diuretics the kidneys, Diaphoretics the glands of the skin,
and Purgatives those of the bowels. There may be disagreements on minor
points, but there can be no dispute as to the fact of the existence of
these local partialities.[7]

But, though such statements are admitted to be correct in theory, it
remains still to be considered whether they form a fitting basis for a
classification of medicines. Now it will be observed that no theory of
action enters into such an arrangement, but merely the tendency of the
action of each medicine is considered; and as each medicine has
naturally many distinct tendencies, it comes therefore under many
different heads. But the chief practical use of a classification seems
to be, that we may quickly learn from it the general action or effect of
a medicine; so that, if it is stated to have many different tendencies,
and is ranged under no one particular head, we can gain from this no
very distinct practical information respecting it. In an arrangement of
the kind that we have last examined, the most important result is the
chief point considered. Thus it is rendered useful. And in one of the
third kind, where the mode of operation is the great thing taken into
account, as each remedy has only one primary operation, and according to
this is classified, we gain from its designation some useful information
respecting it. It may sometimes come under another head in its secondary
operation, but only according to the primary should it be classed, the
other term being supplementary. The designations founded on local
tendency are further of an indefinite character, because they do not
denote the kind of action exerted.

Of such a kind is the classification adopted by Dr. A. T. Thomson,
founded on that of Dr. Murray. He divides what he calls _Vital remedies_
into one division that acts on the nervous system, a second that affects
the secerning system, and a third that influences the muscular and
sanguiferous systems. This is certainly a step in the right direction.
Nerve-medicines seem to have no relation to those that act on the
glands, though connected with them as Stimulants by Dr. Murray. They are
thus separated. Tonics are also separated from Stimulants, and included
with those which act on the muscular and sanguiferous systems. This
seems to me to be a correct view of their action. I do not consider that
they act primarily on the nerves, but on the blood. Dr. Thomson places
Astringents beside them. Though alike in some points, as with regard to
their tendency to affect the condition of muscular fibre, yet there
appears to be very little agreement in the mode of operation of Tonics
and Astringents. There is not altogether much similarity between Quina
and Sulphuric acid.

I will now transcribe the chief divisions adopted in the classification
of Eberle, which seems to have been the prototype of that one since so
ably elaborated by Dr. Pereira.

             EBERLE'S CLASSES.

    A. Medicines acting on the intestinal canal, or its contents.
    B. Medicines acting on the muscular system.
    C. On the uterine system.
    D. On the nervous system.
    E. On the circulating system.
    F. On the organs of secretion.
    G. On the respiratory organs.

The subdivisions are founded on the kind of effect produced. As in Dr.
Thomson's arrangement, Tonics and Astringents are said to act on the
muscles; but no mention is made here of either of them acting on the
blood. While Narcotics are placed among nerve-medicines, Stimulants are
classed as acting on the circulating system. They no doubt act on the
nerves, and then through them on the vessels; but so also do Narcotics,
from which they are separated. If in class E are only included medicines
acting on the organic nerves of the heart and arteries, why were they
not placed in D, with Nerve-medicines? But if medicines acting on the
contents of the vessels are meant, why were not Blood-medicines, or
Alteratives, placed here? They are entirely omitted; which seems to be a
fault in this system.

Dr. Pereira seems to have adopted a more correct view of both of these
cases. He includes Stimulants with _Neurotics_, and places among
_"Hæmatics"_ those medicines which are commonly termed Alteratives. It
seems to me that when a medicine acts on the blood, this action ought
not to be thrown into the shade, but should rather be placed before all
its other operations, as being of more importance than any of them. Dr.
Pereira arranges in six classes those medicines which are given
internally, having previously made three classes of external or topical
agents, with which we are not now concerned. Some of the classes are
again divided into large groups, these and the other subdivisions being
either based on more particular local tendencies, or on the
_physiological action_ of the medicine on the part to which its
operation tends.

    DR. PEREIRA'S CLASSES.

    CLASS IV. Hæmatica.
                  1. _Spanæmica._
                  2. _Hæmatinica._

    CLASS V. Pneumatica.

    CLASS VI. Neurotica.
                 1. _Cerebro-spinalia._
                 2. _Ganglionica._

    CLASS VII. C[oe]liaca.

    CLASS VIII. Eccritica.

    CLASS IX. Genetica.

These groups, though differently placed, correspond to six of Eberle's
seven classes. The class acting on the muscular system is omitted. The
subdivision here is more accurate and scientific. _Hæmatics_ or
blood-medicines, are divided into two classes. _Spanæmics_ the first of
these, are named from their tendency to impoverish the blood.
_Hæmatinics_ including the compounds of Iron, tend to enrich it.
In the first division are included the medicines commonly termed
Alteratives, as well as Acids, Alkalies, the compounds of Lead, Silver,
Copper, etc. In the selection of the above name attention is paid to the
abstract physiological effect of these medicines, rather than to their
therapeutical applications. The impoverishing of the blood may be the
ultimate action of such a medicine as Potash or Mercury, but not exactly
the primary operation for which it is used in medicine. It is produced
by the remedy when taken in excess, and not when given in small doses.
_Neurotics_, or medicines which act on the nerves, are divided into
those which affect the brain and spinal system, and those which are
supposed to influence the ganglionic system, and through it the heart
and great vessels. (When we shall afterwards discuss the action of
nerve-medicines, it will be seen that it is very difficult, if not
impossible, to enforce this distinction.) The different kinds of
Narcotics form the first division, while the second includes Stimulants
and vascular Sedatives. The class of _Eccritics_ includes all medicines
acting on the glands, commonly called Evacuants.

The details of this arrangement, to which I shall at present venture to
object, are, first, the multiplicity of classes, and secondly, the
inclusion of certain medicines in the division of _Cerebro-spinals_.

Three of the classes seem to be superfluous, and only tend to confuse.
There is a class of _Pneumatics_, acting on the respiratory organs. But
Expectorants are found elsewhere among _Eccritics_; and those medicines
which influence the nerves of the lungs, among _Neurotics_. The same
with _C[oe]liacs_; for Cathartics, found among _Eccritics_, are the most
important medicines acting on the intestines. _Genetics_ contain
medicines which control the uterine and sexual systems, which may all be
reckoned among _Neurotics_. And yet this multiplicity of names is
consistently employed in carrying out the principle of this
classification, which is, to arrange according to the different parts of
the system all substances which have any tendency to act on those parts.

Dr. Pereira makes four orders of _Cerebro-spinals_; three include
different kinds of Narcotics, very minutely subdivided; another is
called _Cinetics_. They affect the muscular system; but it is altogether
an assumption to assert that these medicines, Astringents and Tonics, do
so by influencing the nerves. As to Astringents, it appears that they do
not affect the nerves in any way, for which reason I shall have to make
a separate class of them. For Tonics, there is great reason to suppose
that in the first place they act on the blood; so that I cannot agree
with Dr. Pereira, who ranks them among _Neurotics_. Emetics are classed
by him among _Eccritics_; but it seems to me that their action is either
external, and of an irritant nature, or when from the blood, that it is
exerted upon the nerves of the stomach. The stomach is not, like most
glandular organs, a simple emunctory, and it is affected by medicines in
a different way. Whereas gland-medicines increase secretion, the chief
action of Emetics is to cause an evacuation of the contents of the
stomach by contraction of itself and of other muscles. All substances
which touch the stomach cause the copious outpouring of a thin fluid by
mere contact; yet we cannot for this reason call them medicines which
tend to increase secretion. Emetics acting from the blood after
absorption, as Tartar emetic, which generally influence at the same time
either the lungs or the heart, parts supplied by the other branches of
the Vagus nerve, which is distributed to the stomach, seem to me to be
Specific Neurotics, probably acting on that nerve. So that in these
points, as well as in some others, I am disposed to differ from Dr.
Pereira.

It is apparent that in none of the classifications of this second kind
is any mention made of the primary action or _modus operandi_ of
medicines in the cure of disease, as a necessary basis of such
distinctions.


III. OPINIONS CONCERNING THE MODE OF OPERATION OF MEDICINES, AND
CLASSIFICATIONS FOUNDED ON THIS.

In this third division are included those writers who have attempted to
account for the mode in which medicines produce each their peculiar
effects after entering into the blood, and some who have classified them
according to their ideas on this point. It is with such theories as
these that I am more immediately concerned in this Essay. Such writers
have dived into a deeper subject than those who have directed attention
to the general effects or tendencies of medicines rather than to the
means by which such results are attained. Thus it is not to be wondered
at that they have sometimes failed. Those have erred most who have
allowed their imaginations to lead them astray from facts, or to guide
them in matters which are naturally incomprehensible, to which our
reason gives us no clue.

Attempts have been made to account for the _modus operandi_ of
therapeutic agents generally, in three different ways.

1. On mechanical principles.

2. On chemical principles.

3. On general or vital principles.

1. Mechanical theories of the action of medicines were greatly in vogue
during the seventeenth and eighteenth centuries. There is a tendency in
the human mind to explain every thing; and it was only natural for men
who knew little of chemistry or of physiology to resort to the science
of physics, which they could comprehend, in attempting the explanation
of observed phenomena.

John Locke, in his essay concerning the Human Understanding, published
in 1689, gave it as his opinion, that the shapes of the minute particles
of medicines were sufficient to account for their several operations.

"Did we know," said he, "the mechanical affections of the particles of
rhubarb, hemlock, opium, and a man, as a watchmaker does those of a
watch, whereby it performs its operations, and of a file, which, by
rubbing on them, will alter the figure of any of the wheels, we should
be able to tell beforehand that rhubarb will purge, hemlock kill, and
opium make a man sleep." This idea did not originate with the great
metaphysician. The first rudiments are to be found in the doctrines of
the _Methodic Sect_ among the Romans, a medical branch of the Epicurean
school. They held that diseases depended either on constriction or
relaxation of the tissues, and that medicines operated by mechanically
affecting these conditions.

The simple and philosophical statement of Locke was not improved by the
various applications which were subsequently made of it. At the early
part of the eighteenth century these ideas derived great support from
the principles inculcated by Dr. Herman Boerhaave, the learned physician
of Leyden. He likewise supposed that many diseases of the solid parts
were to be attributed to a weakness or laxity of the animal fibres, and
were to be cured by external or internal agents, which should act
mechanically on those fibres so as to increase their tenacity. Also,
that disorders of the fluids often depended on their being too viscid,
and that this condition might be improved by agents which should
attenuate this viscidity. Dr. Archibald Pitcairn, a Scotchman, the
immediate predecessor and contemporary of Boerhaave, was elected to the
Chair of Physic in Leyden in 1691, and was also an able exponent of the
mathematical theories. But he applied to physiology those ideas which
were employed by the other to throw light upon physic; if that may be
called _light_ which was at least an improvement on the ignorance which
preceded it.[8] He explained the digestive process by the mechanical
trituration to which the food was subjected in the stomach; and
accounted for secretion by supposing the existence in glands of vascular
pores of different sizes, which intercepted certain particles of the
blood; actually giving for the process a mathematical formula. He was a
vehement opponent of those who based their theories on the then youthful
science of chemistry, who, having scarce yet shaken off from them the
dust of alchemy, only substituting Acids, Alkalies, and Fermentations,
for _Salt_, _Sulphur_, and _Mercury_, fell easy victims to his satire.

Dr. Charles Perry, in 1741, propounded a mechanical view of the action
of Mercury and Arsenic. He thought that the particles of the former,
being round and heavy, were able, when shaken about in the vessels, to
break up and to annihilate those crude acrid humours which were the
causes of disease; and that Arsenic acted as an irritant by the sharp
and pointed nature of its atoms. He attributed the occasional poisonous
effects of Mercury to the presence of Arsenic or some such substance as
an impurity.[9]

Dr. Mead, in 1751, states that the administration of Mercury is
dangerous in cases where there is carious bone, as there is a fear that
its ponderous particles may break the weak lamellæ.[10] He was the Court
Physician in the reign of George II. He accounted for the poisonous
nature of the venom of serpents by asserting that it consisted of
pointed particles, which pierced and destroyed the globules of the
blood.

Dr. Perry conceived that some medicines, such as Steel and Antimony, did
not act by their mere bodily presence, but by certain subtle vapours
which emanated from them, and affected the vital spirits. This was a
very misty notion. He stated that he borrowed this idea from a great
philosopher of the German nation. This was probably Boerhaave, who
lectured at Leyden in 1707.

Among those who regarded with favour the mechanical hypothesis, were
Fourcroy and Hecquet in France, Van Swieten and Huygens in Holland, and
Bellini in Italy. Excepting perhaps the case of external irritants,
these explanations of the action of medicines have been universally
condemned by scientific men at the present day. Doubtless these old
authors were in the wrong, both in applying one hypothesis to the action
of all remedial agents alike, and still more, in carrying their theories
into such minute details, where it is impossible that they should be
verified. And yet we may go too far in our condemnation of all such
ideas. It does not seem to me to be so impossible, or even improbable,
that the operation of some medicinal agents, particularly those which
act on the nerves, may depend in some way on the shapes of the atoms of
these substances, as related to those of the tissues which they
influence. At least, there is no other possible explanation of the power
of such substances. We know that the nerves are very much under the
influence of mechanical impressions, upon which depend the phenomena of
two at least out of the five senses, those of hearing and touch, as
probably also of the other three, if we understood them better. We know
also that if we accept the Atomic theory, by which so many chemical
phenomena are cleared up and explained, we must admit a certain definite
and peculiar arrangement and shape to the ultimate particles of every
compound body. These considerations render it possible that the ultimate
particles of a stimulant medicine may be of such a nature as to
irritate, or to refuse to coincide with, the ultimate molecules of the
sensitive nerve with which they come in contact; and those of a sedative
may, on the other hand, be so shaped and arranged as to dove-tail with
those particles, and by extinguishing, as it were, their salient points,
to cloak their vital sensibility. This is obviously a mere conjecture,
and the only value which can attach to it is, that it appears in some
sort to explain a thing which without it is inexplicable.

Some modern writers have attempted to clear up the actions of certain
medicines by their supposed influence on the physical process of
endosmosis, as carried on through the coats of the stomach and
intestines. Poissenille and Matteucci have attempted to prove that the
action of saline liquids in causing purging, and that of a solution of
morphia in preventing the same, may be explained by the _endosmotic_
properties of these liquids, as ascertained by experiment. It does not
seem to me that these ideas can be successfully maintained. (_Vide_
Prop. II.)

2. Several attempts have been made to explain the general action of
medicines on chemical principles.

Perhaps the strange doctrine taught by Galen, which prevailed for so
many centuries afterwards, should be mentioned under this head as the
first approach to a chemical theory. He considered all medicines to be
_hot_, _cold_, _moist_, or _dry_. There were four degrees of each of
these properties. In the _Pharmacopæia Londinensis_ of 1702, translated
by Dr. Salmon, it is stated of every herb that it possesses in a
certain degree one or more of these qualities. It is amusing to find Dr.
Salmon in great doubt as to whether Opium were _hot_ or _cold_, as the
Ancients said one thing, and the Moderns another. Galen supposed that
diseases depended on similar qualities, and were to be counteracted by
medicines; that, for example, we were to meet a _hot_ disease by a
_cold_ remedy.

The next advance, if such it may be termed, was made by the Alchemists
of the middle ages, who frequently turned their attention towards the
healing art, and almost imagined that by their _Philosophers' stone_
they could purify and rekindle the perishable _base metal_ of the human
body. One of their dreams was, that from Gold, the most durable of
metals, or from Mercury, the most lively and volatile, they might by
their magical arts be enabled to prepare a medicine that should render
life perennial. A most impracticable formula for the preparation of this
_Elixir Vitæ_ was given, among others, by Carolus Musitanus. Basil
Valentine, who flourished in the fifteenth century, did good service by
adding to the Materia Medica the preparations of Antimony, as well as
the Mineral Acids. In the sixteenth lived Paracelsus and Von Helmont,
the latest and most enthusiastic of the medical Alchemists. They
considered the chemical principles of medicines, by virtue of which they
operated, to be three in number,--viz., _Salt_, _Sulphur_, and
_Mercury_. And though the seventeenth century was illumined by the
philosophy of Bacon, and the discoveries of Newton and Boyle, we find
that this strange doctrine survived in full vigour at the commencement
of the eighteenth. It is laid down as an axiom in Dr. Salmon's
Pharmacopæia in 1702.[11]

About the middle of this century there arose a new sect of chemical
philosophers, somewhat better informed than the last. They imagined that
most diseases depended on the predominance in the blood of _acid_ or
_alkalic humours_, and that each of these conditions should be
counteracted by a direct chemical antidote. They supposed also that the
various secretions were the products of _fermentations_ in the blood
which took place in the neighbourhood of the glandular organs. (_Vide_
Eliminatives.) In some of their ideas there was much that was
reasonable; but it must be confessed that they were rather imaginative
than argumentative, and, knowing really but little of the principles of
that science on which their system was ostensibly based, they were
ill-qualified to contend with their opponents of the mathematical
school, who at least understood their own position. Foremost among these
new chemical philosophers was Raymond Vieussens, who was severely
censured by Dr. Pitcairn for having asserted that he had found an acid
in human blood.[12] Vieussens was one of the earliest of the sect, which
afterwards numbered many followers.

There is very little that is tangible to be discovered in these old
chemical theories of the action of medicines; and it is not to be
wondered at that most of them have faded away before the advance of
science, and particularly before that wonderful development of the
science of chemistry, which has distinguished the end of the last, and
the first half of the present century.

We have seen that some of the early writers made great account of the
affinities of acids and alkalies. So also a chemical explanation of the
action of these remedies is generally adopted by writers at the present
day. It is known that they have powerful tendencies to combine with each
other, and it is supposed that these affinities are manifested even in
the living blood.

Schultz attempts a further chemical explanation of their action in some
diseases, particularly inflammations. He says that both affect the
condition of the blood; but that acids tend to dissolve and destroy the
corpuscles, wherefore he terms them _Hæmatolytica Physoda_; and alkalies
prevent the coagulation of the fibrine of the plasma, for which reason
he calls them _Hæmatolytica Plasmatoda_.

Some modern writers have tried to extend a chemical theory to the
operation of medicines in general. This is an error to which those who
have devoted themselves particularly to the study of chemical phenomena
are especially prone.

Müller thinks that the agency of many remedies may be explained by their
chemical affinities. He supposes that they may effect a change in the
nutritive fluids, or that they may so disturb the state of combination
in which the elements of an organ may be, that it becomes insensible to
the action of morbid stimuli. Some chemists have accounted for the
action of Alcohol by its chemical affinity for the brain substance.
Liebig considers that the similarity of their composition to that of the
brain may serve to explain the operation of such medicines as Quina and
Morphia. Such ideas as these are at the best purely hypothetical, and
even as theories they seem to me to be untenable,--for what reasons I
shall have to show when I consider these remedies. Liebig has hazarded
several other explanations of a similar kind, of which the following is
an example:--"The frightful effects of Sulphuretted Hydrogen and
Hydrocyanic Acid are explained by the well-known action of these
compounds on those of Iron, when Alkalies are present, and free Alkali
is never absent in the blood." (_Organic Chemistry_, p. 274.) Now in the
first place it is not proved that the complete abstraction of iron from
the blood would occasion sudden death, though doubtless it is a
necessary constituent of that fluid. Further, Prussic Acid acts on the
superficial nerves as an Anodyne when applied externally, which it can
hardly do by displacing iron. Besides, by parity of reasoning, Ammonia,
or Benzoic or Cinnamic Acid, should precipitate iron, if present in the
blood in the soluble state, and Sulphuric or Nitric Acid should dissolve
it, if in the state of peroxide; and yet none of these agents are
frightful poisons. It is not to be imagined that chemical solutions and
decompositions of every kind are allowed to take effect in the human
system in the same way as in the laboratory of the chemist, for there
are in the former many disturbing and controlling causes which suffice
to hold them in check.

We may altogether conclude, that though the actions of many remedies may
be partly elucidated by chemical considerations, it is impossible to
account for the influence of all alike in this way. For at least the
actions of nerve-medicines and of gland-medicines cannot be reasonably
explained on any such hypothesis.

3. The most plausible explanations of the mode of operation of medicines
have been founded on _vital_ or _general_ principles. By _vital_ I mean
that these theories concern actions which could only take place in the
living body. They may be termed _general_ principles, because the
grounds on which they are based are neither mechanical nor chemical, but
something different from both. The term _dynamical_ has sometimes been
applied to an ill-understood vital action of this sort.

Many different ideas have been broached to account thus for the action
of medicines. Some, who have constructed very ingenious and plausible
systems, have explained in different ways the operations of different
groups of medicines. But when others have adopted a single inflexible
hypothesis to account for the action of all alike, this is found, as
might be supposed, to be of a very untenable character. I will now
consider very briefly several such ideas; first, for the sake of
clearness, dividing them into seven sections. I shall explain my meaning
as I proceed. Different writers have supposed that the general
operation of remedies in the cure of disease is conducted in these
various ways.

    _a._ By degrees of stimulation.
    _b._ By counter-stimulation.
    _c._ By opposition.
    _d._ By similar agencies.
    _e._ By elimination.
    _f._ By alterative actions.
    _g._ By various counteractions.

_a._ This idea has received the title of the "Brunonian Theory," from
the name of its founder. It was promulgated by the famous Dr. John Brown
at the close of the last century. He considered all diseases to arise
from excessive or diminished "excitement." He was of opinion that all
medicinal agents were stimulants, only that some acted so powerfully as
to produce "indirect debility." These latter were to be used in sthenic,
the others in asthenic disorders. But it is to be urged against this
idea, that many sedatives produce no appreciable degree of "primary
stimulation;" that alterative medicines are neither stimulant nor
depressent; and that the actions of different therapeutic agents,--as,
for example, of Opium, Mercury, and Rhubarb,--differ very much in
quality, and not simply in degree, as Dr. Brown supposed. The principle,
then, cannot be maintained.

_b._ Rasori and other Italians adopted a similar idea about the
commencement of this century, only that they supposed two contrary
agencies, instead of variations in the degree of the same action, like
the Brunonians. Giacomini classified medicines on this plan. The two
classes of medicines are termed "Hypersthenics," and "Hyposthenics,"--
_i.e._ Stimulants, and Contra-stimulants, or Sedatives.
These were to be used respectively in asthenic and in sthenic disorders.
But this idea did not originate with these physicians. It prevails among
the modern Hindoos, and seems to have been inculcated by certain
medical writers of that nation in very remote times. (_On the Hindoo
System of Medicine, by Dr. Wise_, 1845, p. 213.)

_c._ The last-mentioned idea supposes only one kind of opposition, and
therefore only two descriptions of diseased action. But a much more
plausible notion than that is, that each particular disease or symptom
is to be cured by administering a remedy which is capable of producing a
contrary state. By this contrary condition the disorder is to be
neutralized. This was the maxim of Hippocrates--[Greek: ta enantia tôn
enantiôn estin iêmata]--"contraries are the remedies of contraries." (De
Flatibus, par. iii.) On this principle we give purgatives in
constipation, opium in diarrh[oe]a, sedatives to relieve pain,
sudorifics to combat dryness of skin, etc. etc. But the rule becomes
inapplicable when the cause of disease is so complicated that we cannot
tell where to find a substance that shall directly oppose its agency.
Besides, it cannot in theory be universally applied, for it takes no
notice of treatment by evacuation or by revulsion.

_d._ I am brought now to an idea which is directly opposed to the last.
The rule of the disciples of Hahnemann is, "Similia similibus
curantur"--or, diseases are to be cured by remedies which shall produce
effects similar to them. Now if this were the case, the majority of
disorders would be hopelessly incurable. We know of no medicines that
are capable of producing such affections as ague, small-pox, or
phthisis; and when such remedies are known, their employment would
certainly be singularly objectionable. Who would administer Strychnia in
tetanus, Opium in congestion of the brain, or irritants in Gastrodynia?
The arguments alleged in support of the theory are of the most
fallacious kind. For example, it is said that diaphoretics cured the
sweating-sickness, and purgatives are given with advantage in
diarrh[oe]a, on the "Hom[oe]opathic" principle. But it should be
observed that the sweating in one case, and diarrh[oe]a in the other,
are the attempts of nature to get rid of the disease by eliminating a
poison; and that in seconding these attempts we are availing ourselves
of an agency which does not resemble the disease, but is like to the
natural mode of cure. Such treatment depends, in fact, upon the
principle which will have to be considered next in order.

The hom[oe]opathists would work a strange revolution in the Materia
Medica.[13] Charcoal, Silica, and other substances commonly supposed to
be inert, appear as remedies of wonderful efficacy. It is said that
Belladonna produces a state like scarlatina, and also a condition
resembling hydrophobia, and thus cures both of these disorders. Of these
three propositions it is almost needless to say that all are equally
erroneous. Further, an experimental trial of this principle was made by
Andral on a large number of patients at the Académie in Paris, with the
assistance of the hom[oe]opathists themselves. The medicines were
carefully and fairly administered, but in no one instance were they
successful. (_Medical Gazette_, vol. xv. p. 922.)

_e._ The idea that diseases are to be cured by assisting nature to
eliminate from the system the morbid material, is probably as old as
medicine. It was one of the doctrines of Hippocrates; but long even
before his time it appears to have been inculcated by a certain sect of
old medical writers among the Hindoos. These last were the very earliest
advocates of the humoral pathology. (_Dr. Wise_, _op. cit._ p. 212.) Dr.
Thomas Sydenham, born in 1624, the contemporary of Harvey, and the most
illustrious of the early English exponents of the humoral system, was
probably the first in this country who clearly elaborated this view of
the action of medicines by elimination; which has been more or less
approved, though not so universally applied, by all who have lived since
his time. Agreeing with Stahl in his view of the advantages of the
"expectant" treatment of diseases, he thought it better to rely on the
"vis medicatrix naturæ," than to make rash or violent attempts at a
cure. He maintained that what we call a _disease_ was in fact "no more
than a vigorous effort of nature to throw off the morbific matter, and
thus recover the patient."[14] He proposed, therefore, that our efforts
should be directed to assist nature to procure the evacuation of a
poison, promoting its elimination by acting on the various
secretions--as by purgatives, diaphoretics and such medicines. For he
had noticed that in fevers and febrile disorders the crisis or
turning-point was generally accompanied or preceded by an increase in
one or more of these secretions, and he regarded this as an indication
of the treatment to be pursued in all such cases. "That," said he,
"appears to be the best method of curing acute diseases, which, after
nature has pitched upon a certain kind of evacuation, assists her in
promoting it, and so necessarily contributes to cure the distemper."[15]
He further proposed, that in the treatment of chronic diseases, when
nature herself was slow in procuring this evacuation, we should seek for
_specific_ medicines, by which we might assist her in doing so, and thus
effectually expel the morbific matter. This theory was reasonable and
natural compared to those that followed it; but it was nearly
extinguished and forgotten amid the war of opinions which was
subsequently kindled by the _aphorisms_ of Boerhaave. About this time we
find Dr. Pitcairn mixing up this idea with his mechanical notions, in a
treatise "On the Cure of Fevers by Evacuation." Huxham also, in 1729,
maintained similar principles.


At the present day a more enlarged view is adopted. It is admitted that
we may often assist these attempts of nature at a cure, and do good by
the use, when thus needed, of evacuant medicines; but at the same time
we must allow that there are many other advantageous modes of
treatment,--that we may sometimes cut short a disease in the blood, or
relieve a disorder by controlling vascular or nervous excitement,
without resorting to elimination at all.

_f._ M. Broussais was one of the first who rightly maintained that many
medicines were of use by means of an _alterative_ or _revulsive_ action,
by producing a distinct effect which diverted the attention of the
system from the disease. His followers have classed remedies under three
heads,--as _Stimulants_, _Debilitants_, and _Revulsives_. He maintained
also some other peculiar ideas.

Blood-medicines are commonly termed _Alteratives_, from the notion that
they divert or alter the original disease by setting up in the system a
peculiar process of their own. The term _Revulsive_ is especially
applied to medicines which produce a powerful local effect, and are
supposed so to occupy the attention of the system as to tend to cure the
disease which formerly engaged it. Counter-irritants externally, and
emetics among internal medicines, are generally admitted as revulsives.

The idea of revulsion is a prominent feature in the arrangement of
medicines adopted by Dr. Schultz, of Berlin, who adds to the above,
Expectorants, Purgatives, Diuretics, and Sudorifics. He divides
medicines into _Biolytics_, tending to dissolve life and structure;
_Anabiotics_, which tend to stimulate the same; and _Agonistics_,
tending to produce a "defensive" process, and acting by revulsion. Each
class is again divided into those which affect the organs and nutrition
in general; those which act on the blood; and those which particularly
influence the nerves. I will give examples of each.


SCHULTZ'S CLASSIFICATION.

    A. BIOLYTICA. (_Depressents._)
              1. Plastilytica. (Mercury, Alteratives.)
              2. Hæmatolytica. (Acids, Alkalies.)
              3. Neurolytica. (Sedatives.)
    B. ANABIOTICA. (_Excitants._)
              1. Plastibiotica. (Astringents.)
              2. Hæmatobiotica. (Diffusible stimulants.)
              3. Neurobiotica. (Opium, Strychnia.)
    C. AGONISTICA. (_Revulsives._)
              1. Plastagonistica. (Purgatives, etc.)
              2. Hæmatagonistica. (Irritants.)
              3. Neuragonistica. (Emetics, Expectorants.)

These divisions are again subdivided with great minuteness, according to
their supposed operation. And yet it will be seen that, in spite of the
hard names, there is an admirable simplicity in this arrangement. So
many and so various are the statements made, and so plausible the
theories involved, that I cannot accord to it here a fair consideration.
I must object to it, however, that there is too much generalization,
and, what is more important, that many medicines may cure diseases
without necessarily causing either excitation or depression or acting
distinctly by revulsion. The only principles of action admitted here are
these three, the same which are adopted by the disciples of Broussais.
To suppose that medicines acting on the glands are only of use as
revulsives, that they have no influence on the blood, and are never
engaged in purging the system of peccant or morbid matter, is surely
incorrect in theory. Medicines of the first class, when given in proper
dose and in fit cases, are not engaged in _destroying_ organization, nor
is it invariably the case that such remedies as Mercury, Acids, and
Alkalies act even as depressents, when given in moderation.

Further, the lines of distinction are too arbitrary, and drawn with too
much precision. The variations in the actions of different medicines are
too many and too great to be thus easily accounted for, and we do not
know enough about many of them to be able to define their operation so
exactly. And there is no explanation at all given here of the special
tendencies of some remedies, by which we are enabled to cure a great
number of disorders.

_g._ The Hippocratic maxim was a step towards a correct solution of the
therapeutical operations of remedial agents. The humoral theory of
Sydenham, and the threefold action supposed by Broussais, were further
advances in the right direction. But these views were all too confined.
Correct as far as they extended, they did not embrace the whole range of
the subject; for it is impossible to explain by any one of them the
operations of all medicines.

Biassed by the satisfactory observation which he had made of the _modus
operandi_ of particular medicines, and misled by the insufficiency of
his knowledge, each of these writers was tempted to apply the view which
was applicable to a certain set to all remedies alike. Once persuaded of
its sufficiency, he easily found arguments by which to fortify both
himself and others against any subsequent objections.

The right course lies in a combination of these various theories,
embracing what is true and discarding what is erroneous in each of them,
and supplying what may seem to be wanting in the whole. None of these
ideas being by itself perfect, the sounder reasoners of the present day
are driven to suppose that there are _various_ different ways in which
medicines may _counteract_, and thus cure, different diseases. This
_counteraction_ is distinct from _contrary action_; it may be direct or
indirect; and it allows of any action in a medicine, tending to restore
health, except an effect similar to the disease. Such a view was adopted
by Dr. Cullen, the well known Nosologist, who lectured at Edinburgh
towards the close of the last century. He discarded all special and
confined views of the operation of medicines, believing that they acted
in many and various ways, all of which tended to the same end--to
counteract the influence of the disorder. This is well exemplified in
his admirable directions for the treatment of fever, in which he
enjoined the use of a number of different remedies, varied according to
the nature of the case, and progress of the symptoms.[16]

Dr. Pereira, the most learned and acute of living English writers on
this subject, appears, like many others, to prefer a wide explanation of
this description.

On such views my own statements are based. I suppose that a disease in
the blood is to be met by agents in the blood, which directly or
indirectly counteract it there; that disorders, generally temporary,
which depend on nervous derangement, are to be benefited by remedies
which affect the nerves; and in the same way that a laxity of muscular
fibre, or a failure in a secretion, should be treated by agents which
especially possess the property of restoring to a right condition such
parts or functions.

Concluding, then, that it is impossible to account clearly for the
actions of most medicines on _Mechanical_ or on _Chemical_ principles,
we are led to infer that their influence must for the most part be
_vital_ in its nature--that it must be such as could only be exerted in
the living body. Even then we are unable to fix upon any single rule or
formula which shall be capable of accounting for the actions of all at
once. So it seems that the only general explanation which we can offer
of the _modus operandi_ of medicines in the cure of diseases, is to say
that they operate by _various counteractions_.

This, then, introduces my Third Chapter.




CHAPTER III.

ON THE GENERAL MODES OF ACTION OF THERAPEUTIC AGENTS INTRODUCED INTO THE
STOMACH.


The principal affirmations which I have to make on this subject are
divisible into Ten Propositions, as seen in the Table of Contents.

The first four of these concern the general conduct of medicines after
their introduction into the stomach, and before their passage into the
blood. Some broad rules are laid down by which the course which they
take must be determined. The action of some few on the mucous membrane
is also defined.

The remaining six propositions treat of the subsequent behaviour of
those medicines which pass into the blood and fluids of the body. Of
these, the fifth specifies their general course. The sixth states that
they may undergo certain changes in the system. And the concluding four
treat of the various modes in which these agents may operate in the cure
of disease.

The first proposition lays down the great fundamental rule of the action
of medicines through the medium of the blood and fluids.

PROP. I.--_That the great majority of medicines must obtain entry into
the blood, or internal fluids of the body, before their action can be
manifested._

This is to say, that the mere contact of a medicine with the stomach is
not in general sufficient for the production of its peculiar action. It
will be seen that the only apparent exception to this rule consists of
agents having a mere local action on the mucous membrane, for which
simple contact is all that is required.

Even when acting on any part of the system removed from this mucous
surface, as when applied to the skin, it is necessary that the medicine
pass away from it to enter the blood or internal fluids. In the great
majority of instances it enters the blood directly. But we know that it
would be sufficient for its operation if it were to enter through the
chyle, or into the serous fluid which exists in the interstices of the
tissues throughout the body. For by these it might at length be
conducted to distant parts. This is what is meant by _internal fluids_.

We are not just now concerned with the way in which this passage into
the blood and fluids is obtained. It is by the process of absorption.
The question of passage by absorption is treated in the second and third
propositions. What we have now to decide is, whether a medicine acts by
mere contact with the stomach, its influence being propagated to distant
parts by means of the nerves; or by passage thence into the system,
acting through the medium of the blood and fluids. I affirm that it
operates in this latter way; and this is to be proved by four
considerations, which we will consider in succession.

_A medicine introduced into the system elsewhere acts in the same way as
when introduced into the stomach._

This proves at least that contact with the mucous surface is not an
essential requisite for the operation of a remedy. We may cause a
medicine to be absorbed by the skin, or inject it directly into an
opened vein. The result of this latter experiment proves not only that
entry into a distant part of the system is sufficient for the action of
a medicine, but that it will operate when introduced into the blood.
Numberless proofs of this affirmation may be adduced. Tartar Emetic
injected into the veins produces vomiting. Croton Oil rubbed on the
surface of the abdomen causes purging. Mercurial ointment applied by
friction to the skin will produce salivation. Extract of Belladonna
applied to the temples causes dilatation of the pupil of the eye; and
tincture of Opium dropped on the eyeball causes the pupil to contract.
Ammonia inhaled as gas into the lungs will relieve fainting in the same
way as when swallowed. The breathing of Prussic acid, causing its vapour
to be applied to the pulmonary surface, is sufficient to kill. Prussic
acid, dropped in a concentrated state into the eye of a dog, causes
speedy death. Solution of Aconitina, applied to the skin, will produce
numbness, and tingling of distant parts. Injection of Nux Vomica, or any
powerful poison, into the veins, is rapidly followed by symptoms of
poisoning, like those which would have followed its introduction into
the stomach.[17] Thus contact with the stomach is not necessary, but
introduction into the system any where is sufficient. But still, may not
the poison in either case act by influencing the nerves? Even when it
has entered the blood, it may not travel along in it, but act in a more
direct way. So in the second part of the proof we must show that a
remedy cannot act by an impression conducted from the surface of the
stomach by means of the nerves.

_The continuity of nerve is not necessary for the propagation of such
effects; but vascular connexion is necessary._

This alone, if established, would be sufficient to prove that a medicine
must be introduced into the circulation, in order to act on distant
parts. When confined to a surface, it can operate on the remote part
only by its contact with the superficial extremities of the nerves. For
vascular connexion to be established, it must first enter the vessels.
Many experiments have been made which demonstrate that the vessels are
the only channel by which medicinal effects can be propagated.

M. Magendie introduced some Woorara poison into the limb of a dog, which
was only connected with the trunk by means of quills uniting the divided
ends of the main vessels. It rapidly took effect. Having divided all the
nerves and lymphatics in the intestine of another dog, he introduced
into it some Nux Vomica, beyond the division. It quickly acted, and must
again have done so through the vessels. Sir B. Brodie cut all the nerves
of the anterior extremity of a rabbit, near the axilla, and then
introduced Woorara into the foot. It rapidly acted.[18] Thus we see that
vascular connexion is sufficient, and that nervous connexion is not
necessary. By other similar trials it is found that vascular connexion
is absolutely necessary, for when it is interrupted, the action cannot
be propagated along a nerve. If, on introducing poison into an
extremity, a cord be tightened round the limb above it so as to
intercept the flow of blood, no effect is produced. It takes effect
after the ligature is relaxed. Sir B. Brodie introduced Woorara into the
leg of a dog, which was connected with the trunk only by means of the
principal nerve, carefully dissected out. No effect followed. M. Ehbert
found that poison would not act when applied to an amputated limb
connected with the trunk by a nerve only. Thus vascular connexion is
necessary; whereas continuity of nerve is not necessary, neither is it
sufficient by itself.[19] Woorara poison is a substance which acts with
great rapidity on the nervous system; and if its action cannot be
propagated by means of the nerves, _à fortiori_ would it seem that
slower poisons must act through the circulation. But, granting that it
has been shown that introduction into the stomach is not necessary for
the action of a medicine, and that when in the stomach medicines do not
act by influencing the nerves, still it may be objected that the rule
cannot possibly be universal. It may be urged that some poisons and
medicines, as Hydrocyanic acid and Ammonia, act with such great
rapidity, that we can only suppose their influence to be transmitted
directly along a nerve-fibre to the nervous centre, because the process
of passage in the blood to this distant part would be far too slow. This
argument requires us to prove a third thing.

_The circulation of the blood is sufficiently quick to account even for
the operation of those poisons which act most rapidly by influencing the
nerve-centres._

There is no poison whatever which acts so quickly on distant parts that
the circulation cannot previously have had time to conduct it to them.
By means of an instrument invented by M. Poisseuille, Dr. Blake found
that a chemical substance traversed the whole circulation of a dog in
nine seconds, and of a horse in twenty seconds.[20] The results of
Hering were similar. M. Volkmann, in the tenth chapter of his work on
Hæmadynamics, states, as the result of several experiments, that the
whole circulation in an adult man occupies exactly 65.76 seconds.

Now a poison that operated by nervous connexion would probably operate
directly when it touched the stomach. This is not the case even with
Hydrocyanic acid. This, the most sudden of all poisons, before it takes
effect, allows sufficient time to elapse for the blood to conduct it to
the brain. Blake made an interesting experiment upon it. He placed some
on the tongue of a dog, having first fitted a tube into the larynx, so
as to prevent the vapour from passing into the lungs. The effect did not
commence until sixteen seconds had elapsed, and forty-five were required
for its completion. This allowed of time for absorption.

Thus it is proved that poisons act when introduced into the system at
any point; that vascular connexion is required for this action; and that
the rapidity of the circulation is in all cases quick enough to account
for it.

But this last is only a proof of _possibility_, and does not by itself
show that a substance may not nevertheless act through the nerves. And
to the experiments on nervous connexion some may object that no
conclusions on this point can be drawn from trials made on isolated and
exposed nerves. So we may imagine a person to be still incredulous as to
the truth of the Proposition, that medicines must pass into the blood
before they can act. But a fourth consideration will suffice to bring
this probability as close as possible to a certainty.

_The great majority of medicines have been detected in the blood, and
found in the secretions formed out of it._

Having tried to prove that they must pass into the blood, if we find
that they actually do so, we shall establish a stronger case. Isolated
observations on this subject have been frequently made. Thus in 1847 Mr.
Allen detected Daturia in the urine of a man poisoned by Stramonium. In
1824 M. Runge had discovered in the same way the principles of Henbane
and Belladonna. M. Ragsky has lately detected Chloroform in the blood.
(_Journal für Prakt. Chem. 1849._) Dr. Golding Bird observes that
Indigo, when given for Epilepsy, has turned the urine blue; that
Logwood also passes into it, and causes it to give a dark precipitate
with solutions containing iron; and that during a course of Copaiba or
Cubebs, a resin may be precipitated from it on the addition of Nitric
Acid. If a medicine cannot be proved to pass into the blood or
secretions, we cannot so certainly affirm that it does not act through
the nerves. But the experiments of Tiedemann and Gmelin, and since then
of Wöhler, have definitively settled this point. The former two have
found the great majority of mineral, and many vegetable substances, in
the blood of animals to which they had been administered.

Thus, from these four considerations, we are strictly justified in
concluding that a medicine must pass from the stomach into the blood
before its action can be manifested. This action cannot then be
conducted from the surface of the stomach through the agency of the
nerves. Some experiments made by Dr. Garrod and others on the action of
animal charcoal as an antidote, furnish again an additional confirmation
of this fact. He finds that if a sufficient quantity of this absorbing
agent be introduced into the stomach before time has been allowed for
the passage of a medicine through the mucous membrane, then even such
powerful nerve-medicines as Morphia and Strychnia, in very large doses,
are prevented from taking effect. Yet before the contact of the charcoal
they would have had time to act through the nerves, had they been
capable of any such action.

In the fifth Proposition the rule here laid down will have to be further
extended. It will be shown that medicines, having already passed into
the blood, must travel along in it so far as to reach the part of the
system on which they act.

Before concluding this question, a few remarks must be made on a subject
which will be again referred to in the discussion of the Fourth
Proposition.

The proper and peculiar action of a medicine, by which I mean that
action on the system which is immediately recognised as distinct from
that of any other agent, cannot be exerted on distant parts from the
stomach-surface, but requires the passage of the medicine into the
circulation. But can any other action on distant parts be produced by
the remedy while in the stomach? This is a different question, and must
be answered in the affirmative. Suppose a Cantharides plaster be applied
to the surface of the chest in a case of Pericarditis, so as to redden
or blister the skin, absorption of the fluid in the pericardium may
follow this application. But any other irritant would have done this. It
is not the proper or peculiar action of Cantharides, but an operation of
the nervous system which follows the local change. Such agents are said
to act by _Counter-irritation_ or _Revulsion_, because it appears that,
as a consequence of their action, the attention of the nervous system
may be drawn off from a morbid process going on at some other part of
the body. But it is only a consequence, and not a direct operation. Such
an effect is no more the action of Cantharides than the healthy
functions following recovery from sickness can be ascribed to the remedy
which has cured the latter.

Now some few medicines have a marked local action on the mucous surface
of the stomach and intestines. (_Vide_ Prop. IV.) These, and these only,
may, without passing into the blood, produce on distant parts an action
of this kind by counter-irritation. Thus the operation of an irritant
emetic may be followed by the arrest of some incipient inflammation,
_e.g._ Ophthalmia. This revulsive action, when carried to an extreme, so
powerfully impresses the nervous system, that it puts a stop to all
other actions, and produces Syncope or Death. This extreme action is
called _Shock_. Powerful corrosive poisons may effect this by a sudden
destruction of the mucous surface, operating like a surgical injury. But
such actions, not being the proper and characteristic operations of
medicines, but rather attributable to a change in the relations of the
nervous system, following a local impression, are not to be considered
as exceptions to the above rule, that medicines cannot from the surface
of the stomach or intestines propagate their influence to remote parts.


PROP. II.--_That the great majority of medicines are capable of solution
in the gastric or intestinal secretions, and pass without material
change, by a process of absorption, through the coats of the stomach and
intestines, to enter the capillaries of the Portal system of veins._

It has already been shown of medicines in general, that it is necessary
for them to pass away from the mucous surface into the circulation.
Mention has been made of their discovery in the blood by chemical means;
and as we proceed it will be shown more particularly of different sets
of medicines that each of them has been found in that fluid. Now, to
gain entrance there, the medicine must first pass through the soft
mucous membrane lining the stomach and intestine. This passage is
performed by a process to which the names of _Absorption_ and
_Endosmosis_ have been applied. Immediately outside this membrane, and
between the tubes and cells which are formed by its involution, is a
close net-work of very small veins, having thin and delicate walls. Now
the same forces, whatever they be, which conduct the medicinal solution
through the mucous membrane, cause it to pass on through the fine walls
of these vessels. The two membranes, lying in such juxtaposition, are to
all intents the same as one. Thus the medicine passes into the blood,
and this is the only direct way by which it can gain entrance into it.
These small veins, or capillaries, lead at length to the Mesenteric
veins, which pour into the Portal vein, by which the blood proceeding
from them is conducted into the Liver. The process of Absorption is the
only mode by which remedies can thus enter the blood; we have now to
consider what it is, and to show in what manner and by what agents
different medicines are fitted to undergo it.

The subject of this Proposition divides itself naturally into three
parts. We shall have to consider--1. What is the nature, and what the
function, of the gastric and intestinal secretions. 2. The laws of this
process of Endosmotic absorption, and how they are fulfilled in this
case; and, 3. The mode in which the great majority of medicines are
reduced to a state of solution, which is necessary before they can be
absorbed.

The process of stomach-digestion has been cleared up of late years by
the decisive experiments of Spallanzani and Réaumur, of Tiedemann and
Gmelin, and of Dr. Beaumont of Canada.

Immediately that a substance touches the mucous surface of the stomach
it causes the copious outpouring of a thin fluid, which is secreted by a
glandular apparatus. This gastric juice is highly acid, and contains
besides a peculiar nitrogenous substance called Pepsin. Dr. Prout
thought that the reaction was due to free Hydrochloric acid. But it
seems more likely that it is due to Lactic acid. Such at least is the
opinion entertained both by Liebig and Lehmann. Now the result of the
action of this fluid is to dissolve down the solid materials of the
food, or other substances presented to it, reducing them to a thin
watery pulp. This pulp is then mainly absorbed; and that which is not
taken up through the coat of the stomach is absorbed in the earlier
portion of the intestinal canal. I shall have to treat of Aliments as
one of the orders of Restorative Hæmatics.

We are now concerned with medicines in general. The same juice is poured
out to receive them. Such as are dissolved by it are immediately
absorbed. Some other matters may be rendered soluble by the agency of
the Bile and Pancreatic juice which are poured out into the middle of
the Duodenum. The former is an alkaline fluid, containing carbonate of
Soda. The Pancreatic juice is also said to be alkaline. That the
stomach is absorbent may be proved by the experiment of placing a
ligature round the intestine of a dog, just below the pylorus. It is
then found that soluble substances placed in the stomach pass rapidly
from it into the circulation. It is probable that all substances which
are easily dissolved pass through the coats of the stomach. That the
surface of the intestines is absorbent may be proved by the
disappearance of enemata thrown into them. Liebig states that a solution
of common salt, in the proportion of one part to eighty of water,
disappeared so completely in the rectum that an evacuation one hour
afterwards was found to contain no more than the usual proportion of
salt. (_Animal Chemistry_, _p._ 77.)

On the mucous surface of the small intestines are a number of small
projections, called Villi. Within these are the origins of the Lacteals,
a peculiar set of Lymphatic vessels, which are engaged in the absorption
of chyle. This chyle is a thick fluid which is formed by the meeting of
the Bile and Pancreatic juice with that part of the digested food which
passes into the Duodenum. It is generally white, from the presence of
fat. Now these lacteal vessels are no doubt absorbent, but are they ever
engaged in the absorption of medicinal solutions? It seems that they are
not in ordinary cases at all concerned in this; for three chief reasons.
In the first place it appears from the researches of Bernard and others
that the lacteal system is a special arrangement for the absorption of
fatty substances, and that other matters, such as albuminous compounds,
pass generally into the veins, and thence to the liver. Besides, it
seems that these lacteal absorbents are only in action during the
digestion of food, when the epithelium on the surface of each villus
becomes loosened, in order to allow to the chyle an easier access to the
lacteal within it.[21] So that it is likely that a small portion of a
fluid or soluble substance would be insufficient to rouse them to
action. And, inthe third place, direct experiments of a decisive kind
have been made on this point. Magendie has found that the ligature of
the lacteal trunks does not prevent the occurrence of poisoning from
agents introduced into the bowels. And Tiedemann and Gmelin have
carefully sought in the chyle for a number of different medicines
administered to animals in their food, and have been unable to detect
any of them there. So that, with the exception perhaps of fats and fixed
oils, we may reasonably conclude that no medicinal substances pass into
the system through the lacteals, but that all are absorbed by the veins
or capillary vessels.[22]

It seems probable that the Bile and Pancreatic juice may be engaged in
reducing to a soluble state certain medicines that are insoluble in the
Gastric secretion, and may thus procure the absorption of these
substances by the veins of the intestinal canal.

Having briefly considered the secretions which meet the medicine on its
first entrance into the system, we are next to inquire into the manner
in which this medicine gains admission into the blood. In the first
place, it must be in a fluid state, or it cannot be absorbed at all. It
will be most convenient to consider afterwards how different remedies
are to be reduced to this condition.

Now the force or process by which fluids are enabled to pass and repass
through an animal membrane, has been named by Dutrochet _Endosmose_ and
_Exosmose_, according as the current tends inwards or outwards.

There are fluids on both sides of the membrane. The circumstances which
determine their passage are mainly five. 1. _The densities of the
liquids:_ other things being equal, the lighter of the two tends to pass
through to the heavier, more than the heavier to the lighter. 2. _Their
attraction for the intervening membrane._--That one passes through most
which has the greatest affinity for the membrane. 3. _The affinity of
the fluids for each other._--A fluid passes through more rapidly when it
is readily taken up and dissolved by that on the opposite side. By
virtue of the last two laws, but contrary to the first, water passes
through to alcohol more rapidly than alcohol to water. 4. _The motion of
the fluid on one side_ promotes the passage through of that on the
other, because it is carried off as fast as it permeates the membrane.
This also will cause endosmosis in defiance of the first law. This may
be proved by a simple experiment. Let a large vein, cleanly dissected,
be attached at one end to the stopcock of a vessel containing pure
water. Let it then pass through a basin containing a strong solution of
Ferrocyanide of Potassium, and let the other end hang over a jar filled
with a solution of the Sesquichloride of Iron. If the cock be now
turned, and water be allowed to pass through the vein into the vessel
beyond, the solution of Iron will quickly acquire the tint of Prussian
blue; for the heavy solution in the central vessel has passed through to
the simple water of the vein, mainly by virtue of the motion of the
latter. It will be seen directly that this is a matter of considerable
importance. 5. The last law is, that _any pressure on the fluid on one
side of the membrane_ has a powerful influence in determining the
passage of the current from that side. (_Vide Liebig's Animal
Chemistry_, p. 72; _Liebig on the Motion of the Juices_; and the
_Lectures of Professor Matteucci of Pisa_.)

The mucous membrane and the coat of the capillary vessel beyond it are
probably subject to about the same physical conditions of absorption as
those which are thus found by experiment to regulate the passage of
fluids through dead animal membranes.

As to the first condition, it is probable that the aliment or medicine
which is digested, however solid and dense, may be diluted down by the
gastric juice until the solution is of less specific gravity than the
serum of the blood. With the second law we are not so much concerned, as
the medicine after solution has generally no repulsion for the animal
membrane. So also with the third, as the serum of the blood mixes
readily with all watery fluids. The fourth, viz. the condition of
motion, is of great importance; for by it the motion of the contents of
the capillary vessels will tend powerfully to determine the passage
through of the liquid on the other side. Fifthly, the influence of
pressure on endosmosis is one which is certainly exerted in the case of
the stomach and intestines, which are muscular, and during the process
of digestion contract on their contents with considerable force. This
contraction, together with the circulation of the blood in the
capillaries, would doubtless be sufficient to determine the passage of
the digested matters inwards, even in opposition to the first law.[23]

Under the first proposition I have shown that the majority of medicines
are absorbed into the system. It is now seen where and how they are
absorbed. But it still remains to be seen what particular substances or
classes of medicaments are thus taken into the blood, and whether while
so passing they undergo any modifications.

The following, then, are the chief classes which I believe to undergo
solution and absorption in the intestinal canal. They comprise the great
majority of all substances used either as food or medicine:--

    1. Mineral substances soluble in water.
    2. Mineral substances soluble in acids.
    3. Mineral substances soluble in alkalies.
    4. Vegetable products soluble in water.
    5. Animal and vegetable substances rendered soluble by
       the gastric juice.
    6. Fatty and resinous substances soluble in alkali.

1. All soluble mineral substances--acids, alkalies, salts, and soluble
compounds of the earths and metals--are absorbed in the stomach and
intestines. The conditions and the process of absorption have been
already stated. When solid they are first dissolved, when in a dense
solution diluted down by the gastric fluid before they are absorbed.
Thin watery liquids are quickly taken up. Motion on one side, and
pressure on the other, hasten the process. I am not inclined to make any
exception to this rule. This leads me to make some remarks on _the
Endosmotic theory of the action of saline purgatives_.

M. Poisseuille found that the serum of the blood would pass through an
animal membrane to a solution of Sulphate of Soda of greater specific
gravity. He thus concluded that an ordinary saline purgative of greater
specific gravity than serum (1.028) acted by causing the passage of this
serum outwards into the intestine, producing a watery evacuation. The
theory was taken up by Liebig and Matteucci, and by Laveran and Millon.
Dr. Pereira and Dr. Golding Bird have drawn some practical inferences
from it.

It is said that when a saline is absorbed it produces diuresis, and no
purging; that when it purges it is not absorbed; that when given to act
on the kidneys, the solution should be so diluted as to contain less
than five per cent. of the solid; and when administered as a purgative,
the specific gravity should be considerably above 1.028. Now I do not
deny that a weak solution is more likely to pass off by the kidneys, and
a dense one by the bowels; but I consider this due to the fact, that the
kidneys are the proper emunctories of water, and of such matters as are
soluble in it. But I believe that these solutions are equally absorbed,
both heavy and weak, and that the purging or diuretic effect depends
mainly on the quantity of the salt, as the kidneys will not eliminate
beyond a certain amount of it. I must allege, to support this view of
the question, firstly, some arguments _à priori_; and secondly, some
experiments which I have made to satisfy myself. To consider first the
former. Analogy is certainly against this theory. Other purgatives from
the vegetable kingdom produce their effect when injected into the blood,
and are yet often powerfully hydragogue. What effect on the process of
endosmosis can be exerted by Castor or Croton oils, or by calcined
Magnesia? On turning to what we know of the theory of digestive
endosmosis, we find that the solid parts of the food are diluted down so
as to be absorbed, and that the influence of pressure is to be taken
into calculation. It was laid down by the great Boerhaave that a
necessary requisite for the formation and absorption of chyle was the
contractile force of the viscera. (_Van Sweiten's Comment_, vol. i. p.
290.) This, in fact, would press the fluid into the absorbent vessels,
even if against the other endosmotic forces. Further, a fundamental
principle was insisted on by Dutrochet--that even when the liquids on
the two sides varied in density, they would both pass through to each
other, though in different proportions. The ultimate result of this
would be, that a heavy saline solution would be diluted down to the
specific gravity of the serum, and would then pass through. This point I
have illustrated in my first experiment. Thus it seems that my view is
favoured by these physical laws. But even if it were not so, I should
not be inclined to admit that all the endosmotic processes in the living
body were regulated by merely physical tendencies. This cannot be the
case with some of the secretions. The bile is of higher specific gravity
than the serum of blood. Urine in health is lower, but in diabetes often
much higher. The production of these secretions, differing in density
from the serum of blood, would be inconsistent with the first law of
endosmosis. Lastly, we find that in many known cases the theory which I
am contesting does not hold good. Seidlitz water and sea-water are both
known to be purgative. In both the specific gravity is _below_ that of
the serum of blood.

The first, according to Bergmann, has a density of 1.006. It contains in
each pint 192.8 grains of solid matter. Out of this, 180 grains consist
of Sulphate of Magnesia.

Sea-water has a specific gravity of 1.026, and its solid contents are
about 3.5 per cent. But Dr. G. Bird says that less than five per cent.
of saline matter constitutes a liquid diuretic.

These, then, are strong reasons against this idea considered merely as a
theory. But it can readily be put to the proof. With this purpose I have
made the following experiments. As far as they are concerned, they seem
to show that salines are in all cases absorbed, and that whether they
are subsequently excreted through the kidneys or by the bowels depends
more on the quantity administered than on the degree of dilution of the
dose.

     EXP. 1.--A sufficient quantity of white sugar was dissolved in four
     ounces of water to raise its specific gravity to 1.028, that of the
     serum of the blood. Two drachms of sulphate of magnesia were
     dissolved in another ounce of water, so that the solution measured
     nine fluid drachms, and had a density of 1.060. This heavier
     solution was introduced into an open wide tube, closed completely
     below by a clean piece of bladder. It was introduced into a small
     vessel containing the solution of sugar, and arranged so that the
     height of the two liquids should correspond. After three days, the
     inner solution measured two drachms more, and the specific gravity
     had sunk to 1.050. The outer solution, after making up exactly the
     loss by evaporation, was found to have risen in density to 1.040.
     On adding a small quantity each of the solutions of phosphate of
     soda and carbonate of ammonia, a copious precipitate took place,
     indicating the presence of magnesia. Thus it appeared that the
     fluids passed both ways, some of the heavy solution of magnesia
     finding its way through to the lighter solution of sugar. The
     tendency of this process was evidently to an equalization of their
     densities, both by endosmose one way and by exosmose the other.
     Thus, apparently, would it be with a saline purgative, and with the
     serum of the blood.

     EXP. 2.--Three drachms of Sulphate of Magnesia (a very mild
     purgative dose) were dissolved in ten ounces of water, and thus
     administered to a healthy young man. It produced, after some time,
     slight purging, and some diuresis. The urine, when tested,
     contained only a very little more than the usual quantity of
     magnesia. The quantity in the dose was less than five per cent. of
     the solution, and thus, according to the endosmotic theory, should
     have produced no purging.

     EXP. 3.--Six drachms of the same salt were given in eighteen ounces
     of water to the same patient. After a few hours, it caused very
     copious and long-continued watery purging. The urine did not seem
     to be increased, and contained no excess of magnesia. It seemed,
     that in spite of the dilution, the quantity of the salt was so
     large, that it could not pass off by the kidneys, and so was
     eliminated from the blood by the bowels, in the same way as other
     purgative medicines. (_Vide_ Chap. IV.)

     EXP. 4.--This trial was the reverse of the last. Two scruples of
     Acetate of Potash were dissolved in three drachms of water, and
     thus administered. The solution then contained about twenty per
     cent. of the salt. According to the endosmotic theory, it should
     have caused only slight purging, on account of its density. It did
     not do so, but produced diuresis. The dose was so small, that after
     absorption it was easily eliminated by the kidneys.

These experiments are in favour of my views, and seem, as far as they
go, to cast discredit on the theory of Poisseuille. It will be very easy
to multiply them, so as to place the fact beyond a doubt.[24]

This point being so far settled, and there being no physical reason why
any other soluble mineral substance should not be absorbed--it being,
moreover, proved, by repeated experiments, that they all pass into the
blood, we therefore proceed to the second class of bodies capable of
absorption.

2. Mineral substances soluble in acids.--It is apparent that if any
insoluble substance will admit of easy solution in the fluids of the
stomach and intestines, it may be brought to the condition of a soluble
one and thus absorbed. Now the gastric juice is acid. This secretion has
been variously ascribed to free hydrochloric, acetic, phosphoric, and
lactic acids; also to an acid phosphate or lactate of magnesia. There
seems to be most reason to conclude that it is lactic acid, which would
be easily formed out of the constituents of the food.[25]

But we have now only to regard the gastric juice as containing a free
acid. This would reduce to solution the carbonates and oxides of all the
metals; less perfectly when anhydrous, more easily when in the hydrated
form. In this manner are absorbed the oxides of Iron and Silver, the
carbonates of Lime and Magnesia, and other medicines of the same kind.
They would be slightly modified, being absorbed in combination with the
(lactic) acid of the stomach. In this they would differ somewhat from
the substances already soluble, which would probably be absorbed
unchanged, unless we except the alkalies and their carbonates, which
might be similarly decomposed. Even these, if given in solution, would
probably be absorbed faster than the gastric acid could be secreted to
neutralize them.

Other insoluble substances, such as calomel and metallic sulphurets,
would be more or less dissolved by the action of this acid. But as a
great part would necessarily escape its influence, being propelled
onwards by the muscular contraction of the stomach, it follows that
insoluble substances of this kind are much less active as medicines than
similar compounds introduced in a soluble state. It is also likely that
a certain quantity would be sufficient to exhaust for a time the acid
gastric secretion.

We now pass on to a third class of mineral products, which, though
insoluble both in water and in acid, yet, being soluble in alkalies,
appear to be in this way prepared by absorption.

3. Mineral bodies insoluble in water and in acid, but soluble in
alkalies.--These remain unaffected by the action of the gastric juice,
but on passing on as far as the centre of the duodenum, they meet with
two alkaline fluids. These are the bile and the pancreatic juice. We
know that some such insoluble bodies pass into the blood. It will be
shown in the proof of the next Proposition, that they cannot do so
without being first dissolved. Therefore, there must be in the
intestinal canal something capable of thus dissolving them. For this
purpose these two alkaline secretions are well adapted. As an example of
such mineral bodies, of which there are not many, I may adduce sulphur.
It unquestionably passes into the blood, and is found there in
combination with alkalies, as a sulphuret or sulphate. It has been
detected in the urine of those who were taking it, by Dr. Ronalds and
others. It is possible that iodine, bromine, and some of the hydrated
metallic oxides; may enter the blood in the same way.

4. Vegetable substances soluble in water.--These would be absorbed with
more or less readiness according to their degree of solubility. They
would probably be taken up in great part by the stomach. Some vegetable
matters--as Lignine, or woody fibre, and Resins--are insoluble in water.
Starch even is comparatively insoluble, and thus comes under another
division, being probably one of those vegetable substances which are
rendered soluble by the aid of the pepsin of the gastric juice.

These soluble vegetable matters are of several kinds. Cane-sugar and
grape-sugar are readily soluble. So also are the various vegetable
acids. There is another class of bodies which is highly important in a
medical point of view. These are the natural salts of the vegetable
alkaloids, of which are constituted so many of the active principles of
plants. In pharmaceutical operations we are enabled, by the judicious
employment of different menstrua, to extract from the crude and inert
mass these vegetable active principles, and thus to obtain in a
concentrated form the medicinal power for which each plant is esteemed.
This process is also performed in the stomach. By digestion and
concoction, with or without the aid of acid, it is enabled to dissolve
out these soluble and potent matters from the ligneous and bulky tissues
which surround them. For though the alkaloids themselves are in general
almost insoluble in water, yet their natural salts which occur in the
vegetable kingdom are mostly very soluble. The most important of these
salts are as follow. In Cinchona bark, the Kinates of Quina and
Cinchonia. In Opium, the Bimeconates of Morphia and Codeia. In Nux
Vomica, the Igasaurate of Strychnia. In Aconite, the Aconitate of
Aconitina. In Colchicum and Sabadilla, the Supergallates of Colchicia
and Veratria. There are some neutral soluble substances, not partaking
of the nature of Alkalies. Thus we find in Ipecacuanha and Ionidium,
Emetine; in Tea and Coffee, Caffeine; in Willow-bark, Salicine; and the
soluble active principles of Senna, Aloes, and Gentian, are probably of
the same nature. Many other alkaloids are known. Atropia in Belladonna,
Daturia in Stramonium, and Hyoscyamia in Hyoscyamus, occur in
combination with Malic acid. Conia in Hemlock, and Nicotia in Tobacco,
are peculiar volatile alkalies containing no Oxygen: thus in two
respects they resemble Ammonia. They too are soluble in water.

Alcoholic and Ethereal fluids may be enumerated here as soluble
products of the vegetable kingdom. Alcohol mixes with water to any
extent; and one part of Ether is soluble in ten parts of water. Nitric
Ether and Chloroform are also sufficiently soluble. So is Creosote, 1.25
parts of which dissolve in 100 of water. But this may be absorbed in
another way, as will be seen presently. Volatile Oils and Turpentine
come also under this head. They are all slightly soluble in water. The
former, when given in small doses, are probably absorbed in this way.
Turpentine, when given in large doses, may perhaps, by undergoing a
change, come under the head of vegetable substances dissolved by
alkalies. Camphor may be included here: one part is soluble in 1000
parts of water.

The soluble gummy matters of plants, when added to the substances
enumerated above, constitute an aggregate which is called the _watery
extractive_ of a vegetable product: _i.e._ that part which is capable of
being dissolved out of it by pure water.

But there are other active parts of vegetables, such as oily and
resinous matters, and some neutral acrid principles, which, before they
can be dissolved by water, require the aid of an alkali. These will be
considered separately.

We now arrive at a fifth class of matters which are taken up by
absorption.

5. Animal and vegetable products dissolved by the gastric juice.--The
most important of these are the nitrogenous and nutritive constituents
of the flesh of animals and of the parts of vegetables. Albumen,
Glutine, Fibrine, and Caseine, are connected together as compounds of
Proteine. Animal Fibrine, and the analogous Glutine of vegetables, are
quite insoluble in water. Albumen and Caseine, though soluble, are
immediately precipitated by acids. This is known to be at first effected
by the gastric juice on their entry into the stomach. But the action of
the gastric juice which contains an acid, and a peculiar nitrogenous
material called Pepsin,--together with the temperature of the body,
which is about 100°,--causes at length the gradual solution of these
previously insoluble matters. This is found to take place out of the
body when the above conditions are imitated with an artificial gastric
fluid. The result of the process is a viscid fluid, which is then
absorbed. The hard Gelatine of gristle and bone is not soluble in water
at this temperature, but is readily soluble in the acid gastric juice.
The Pepsine seems to be an important agent in this process, for an acid
by itself is found to produce an imperfect solution. The nitrogenous
matters thus digested and absorbed constitute that portion of the food
which is of most use in the nutriment of the system; for the starchy
compounds cannot be appropriated to the more solid tissues, although in
some cases they may be converted into fat, as in herbivorous animals.
(Liebig's _Animal Chemistry_, p. 113.)

Starch itself is one of this class. Tiedemann and Gmelin found that by
the action of the gastric juice it was slowly converted into Dextrine,
which afterwards changed into grape sugar. Both of these are very
soluble. From the researches of Bouchardat and others, it appears that
other fluids, as the Saliva, the secretion of Brunner's glands, and the
Pancreatic juice, possess also this power of converting starch into a
more soluble compound. So that if any of it escape the action of the
stomach-secretion, it is probably reduced to solution and absorbed in
the small intestine.

This change of starch is the first of a series of transformations, now
ascertained, the ultimate result of which is its combustion and
resolution into carbonic acid. Thus the nitrogenous compounds are called
the _nutritive_, and the starchy materials the _calorifacient_ elements
of the food. Considered as medicines, these substances belong to the
division of Aliments.

6. We have already considered some few mineral substances which are
absorbed by the aid of the free alkali contained in the Biliary and
Pancreatic secretions.[26] The sixth kind of absorbed matters consists
of some vegetable and animal products which can only be rendered soluble
by a similar agency. Fats and oils, resinous matters, and some
principles resembling resins, come under this head. Fats and fixed oils
consist of acids, as Stearic, Margaric, and Oleic, insoluble in water,
in combination with a base, Glycerine, which, when isolated, is soluble.
With a free alkali such a fat forms a soluble salt, called a soap, and
the base Glycerine is set free.

In Man the Bile and Pancreatic juice are discharged together into the
middle of the Duodenum. The fatty matters of the food are not absorbed
before they meet with these secretions. But, after they have mixed with
them, a milky fluid, called chyle, is formed, which is then taken up by
the lacteal absorbents. It passes thence into the Thoracic duct, meeting
there with an albuminous lymph, and is discharged at length into the
general circulation at the junction of the left jugular and subclavian
veins.

M. Bernard, in some papers laid lately before the French Academy,
states, as the result of his experiments, that the function of the
Pancreatic juice is to reduce the fat to the condition of a white
emulsion. He states that no milky chyle is formed when the Pancreatic
ducts are tied in dogs. He considers it absolutely necessary that
saccharine and albuminous matters should be absorbed by the capillaries
of the Portal veins, and then pass through the liver; and believes that
the sole function of the lacteals is to take up fat thus emulsified. His
experiments and inferences have received the high sanction of M.
Magendie.

M. Frerichs has since affirmed that, whatever be the function of the
Pancreatic juice, the Bile, by virtue of the alkali which it contains,
is an indispensable agent in the absorption of fats. But M. Bernard has
also found that the Pancreatic juice is always alkaline in health.

Whatever be the particular function of the Bile, it may reasonably be
concluded that the alkali contained in one or both of these fluids is
engaged in the saponification and solution of the emulsified fats. If it
were not for this, this alkali would seem without an object; and
further, it is contrary to all we know of the process of absorption to
suppose that oil could pass through to a watery fluid without the
intervention of an alkali to reduce it to the soluble state.

Thus it would seem likely that by means of the Pancreatic juice, with or
without the aid of the Bile, fatty matters are first emulsified, in
order to undergo an increase of surface, and then again saponified
before they can be absorbed by the lacteal villi.

The principal fixed oils which are used in medicine are Castor, Olive,
Almond, Croton, and Cod oils. It is certainly to be regarded as a very
beautiful arrangement in the animal economy, that those substances which
are not acted upon by an acid fluid should be subsequently subjected to
the action of a free alkali, so that by the successive action of these
solvents, together with the peculiar process of stomach digestion, the
great majority of substances taken into the system are dissolved and
rendered fit for absorption.

There seem to be other vegetable substances which are rendered soluble
by means of alkali in the way already described. Resins form an
important class of remedial agents, in which are comprised many
Diuretics, Diaphoretics, and Purgatives. They consist chemically of
peculiar acids, which, though themselves insoluble in water, combine
with alkalies to form salts which are soluble. They are certainly in
most cases absorbed. They have been found in the blood, and detected
when passing out in the urine. From this last they may be precipitated
by an acid, indicating that they are held in solution by an alkali. In
large doses they may not be absorbed, but by irritating the surface of
the intestinal canal, may act externally as Cathartics, and be expelled
by the peristaltic action which they excite. But in small doses they
enter the circulation in solution, and affect remote organs. The only
way in which they can be dissolved is by means of the alkali of the two
intestinal fluids. Among resinous medicines I may mention Catechu, Kino,
Benzoin, Storax, Peru and Tolu, Copaiba, Guaiacum, the fetid resins,
etc. Many purgative drugs, as Jalap, Scammony, and Gamboge, owe their
efficacy to resin.

There are moreover certain neutral acrid principles, similar in their
nature to resins, which are soluble only in alkalies, and thus come
under this head. Such are Cantharidin, Piperin, Pyrethrin, Colocynthin,
Elaterin, and Capsicin, obtained from Cantharides, Pepper, Pyrethrum,
Colocynth, Elaterium, and Capsicum. But it should be observed that some
of these are soluble in Acetic acid; and if, as some have supposed, this
acid exist in the gastric juice, then they might be dissolved in the
stomach.

We may add here some medicines which were enumerated also in a former
division. Creosote, not very soluble in water, is easily dissolved in a
free alkali. This substance also, like the last, is soluble in Acetic
acid.

Some volatile oils, especially Turpentine, display a marked tendency to
oxidize into resins; and being themselves very sparingly soluble in
water, may perhaps be dissolved after having undergone this change. Thus
Turpentine changes into common Resin, which consists of two isomeric
acids, Pinic and Sylvic.

    Turpentine = C_{20}H_{16}
    Pinic Acid = C_{20}H_{15}O_{2}

and,

    C_{20}H_{16} + 3O = C_{20}H_{15}O_{2} + HO.

or, Oil of Turpentine, with the addition of three atoms of Oxygen,
produces Pinic acid, _i.e._ Resin, and an atom of water.

Now Turpentine, when given in large quantities, irritates the surface of
the intestinal canal in man, and is not absorbed. But in the horse very
large doses are found to pass through the system into the urine. It is
not likely that a large quantity should enter in solution in water. It
seems more probable that it may first in some way become oxidized, and
then dissolved as a resin. The action of turpentine resembles that of
some other substances which contain resin, as Copaiba and Balsam of
Peru.

The resins thus dissolved would pass, like other solutions, through the
mucous membrane of the intestines into the Portal capillaries.

But of the fats and fixed oils it cannot be said to be _proved_ that
they are absorbed in a state of solution, although such a conclusion is
almost forced upon us by a consideration of the laws of endosmosis. They
do not pass into the veins, but are taken up by the lacteal absorbents.
They are _capable of solution_, and are thus not in that sense an
exception to the rule of Prop. II. But in another sense they are an
exception to it; for they do not pass directly into the veins, but
through the lacteal system. It seems that the sole purpose of these
lacteal vessels is to absorb fats. Thus it appears that all soluble
substances, whether in the food or given as medicine, and in whatever
manner rendered soluble, whether by acid, by alkali, or by stomach
digestion, are absorbed in the stomach and intestines. All of them, with
the exception of fatty matters, pass directly into the blood, traversing
the mesenteric and Portal veins, to reach the liver. From this organ
they pass on into the heart through the Vena cava inferior. I have shown
also that they are mostly absorbed without material change. Supposing
the stomach acid to be lactic, it would be too weak to displace mineral
acids. It would, however, decompose a few insoluble matters, and
combine with alkalies and their carbonates, forming salts which in the
blood would again change into carbonates. (_Vide_ Prop. VI.)


PROP. III.--_That those medicines which are completely insoluble in
water, and in the gastric and intestinal juices, cannot gain entrance
into the circulation._

It may at first sight be objected to this proposition, that fatty
matters may probably enter the lacteals in an undissolved state. But
this is not proved; and besides, whether dissolved or not, we know that
they are soluble in one at least of the intestinal juices--viz. the
Bile. So that they do not come under the above definition.

We have just seen that many medicines which are given in the insoluble
form are capable of being dissolved in the fluids of the intestinal
canal. This so much reduces the list of perfectly insoluble medicines,
that it is difficult to find any that come under such a definition. But
Charcoal, the simple metals, woody fibre, and Nitrate of Bismuth, will
serve as examples.

Sulphate of Lead is often quoted as perfectly insoluble; but this is not
the case. It is soluble in a solution of acetate of ammonia. This salt
is contained in the perspiration. Thus the sulphate, when substituted
for the carbonate in some lead works at Paris, proved fatal to the
foreman, who died of colic. M. Flandin found that it poisoned a dog when
rubbed into the skin as ointment. Even some metals may possibly be
brought within the influence of weak acids when in a fine state of
subdivision, as Mercury in blue-pill. Gold in a very fine powder has
been used successfully in syphilis.

Thus the list of insoluble substances is still further reduced. But
there is no doubt that many substances which are slightly soluble in the
intestinal fluids may in great part escape this solution, and pass out
with the fæces just as they went in.

To assert that the particles of an insoluble substance cannot pass
through the homogeneous wall of the capillary or absorbent vessels, is
merely to state what follows from an absolute physical law, and is
generally admitted by physiologists. But even this fundamental datum has
been lately attacked.

Professor [OE]sterlen of Dorpat has been induced to affirm the
possibility of the absorption of insoluble substances, from some
experiments which he has made. Finely-powdered charcoal was administered
to rabbits for some days. They were then killed, and globules of
charcoal, measuring from 1/6000 to 1/3000 of an inch, were found in the
blood of the Portal circulation. (_Zeitschrift für Rationelle Medizin_,
1847.) To obtain these results the microscope was used, a far less
certain test in such matters than chemical analysis. [OE]sterlen
reasonably concludes that, if charcoal can so pass, so also can any
other insoluble substance. The necessity of solution could then at once
be done away with, and the blood continually liable to admixture with
all kinds of heterogeneous and crude materials. [OE]sterlen asserts
further that he has found minute globules of mercury under the skin
after rubbing in mercurial ointment. (_Journal für Praktische Chem._,
No. IX. 1850.) Now, if these things were true, there could be no need to
suppose the solution of insoluble active medicines, for they would be
enabled without difficulty to pass through in an undissolved state.

To test for myself the accuracy of such statements, I have made some
experiments, the object of which is to discover if some of the most
insoluble of our known remedies, which are yet known to obtain entry
somehow into the blood, could do so while yet in the insoluble state.
They are as follow:--

     EXP. 1.--Ten grains of calomel were given to a large dog. It was
     killed after three hours, allowing this time for digestion. A
     considerable quantity of blood was collected from the Portal vein,
     and submitted to analysis to determine whether it contained any
     compound of Mercury in an insoluble form. The blood was dried and
     pulverized. The result was boiled for some time in water, and the
     insoluble part collected. It was dissolved in a small quantity of
     aqua regia, and the clear acid solution placed in a test tube. A
     slip of zinc foil was folded round a narrow plate made of gold
     foil, and introduced into the solution. A galvanic current being
     thus set up, the minutest quantity of mercury, if present, would
     have been deposited on the gold, so as to tarnish it. But this did
     not take place, and when at last the zinc was completely dissolved,
     the gold remained as bright as before. Thus there was _no_ Calomel,
     or compound of mercury, present in the insoluble form.

     EXP. 2.--Ten grains of strong mercurial ointment (containing half
     its weight of metallic mercury, with some oxide) were given to
     another dog. He was killed after the same time, and the Portal
     blood analyzed carefully in the same way, but here also _no_
     mercurial compound was present in the insoluble form.

     EXP. 3.--To a third dog five grains of Oxide of Silver were
     administered. After three hours he was killed. The Portal blood was
     dried in a water-bath, and reduced to powder. This was boiled for
     some time in water, which was separated by filtration. Aqua regia
     was then boiled on the insoluble part. This would convert any
     silver into chloride. The acid was evaporated off as much as
     possible, and the solid remainder heated in a small porcelain
     crucible to dull redness. The result was powdered, and digested in
     liquor ammoniæ. It was filtered, and excess of nitric acid was
     added. There was not any precipitate. Had chloride of silver been
     present, it would have been dissolved by the ammonia, and
     precipitated by the acid. Thus no insoluble silver compound was
     contained in the blood analyzed.

     EXP. 4.--Ten grains of sulphur were administered in the same way to
     a fourth dog. On killing it and opening the body, the thoracic duct
     was found to be full. A considerable quantity of chyle was
     collected from it. Now, as it is asserted by some, that fat passes
     undissolved into the chyle, and as I believe that sulphur is
     digested in the neighbourhood of the bile duct, this chyle was
     chosen for analysis in preference to blood, as more likely to
     contain any insoluble sulphur. Besides, the blood would be less
     satisfactory, on account of the large quantity of albumen and
     fibrine contained in it, both of them also containing sulphur. The
     insoluble part of the chyle was obtained in the same manner as with
     the blood. It was then boiled in a small quantity of a weak
     solution of caustic potash. By this any free sulphur would be
     converted into a soluble sulphate of Potassium. The solution was
     filtered, and a few drops of a solution of the Nitro-prusside of
     Potassium added. (This is a salt lately discovered by Dr. Playfair.
     It is a delicate test for soluble sulphurets, with which it strikes
     a deep purple colour.) No change was produced. Therefore no
     insoluble sulphur was present in the chyle.

The results of these experiments are thus in direct opposition to those
of M. [OE]sterlen, and support a view of the question which seems even
_à priori_ more philosophical and reasonable than that which he has
adopted. I believe that no insoluble medicine can in any way gain entry
into the blood without first undergoing solution in some way or another.


PROP. IV.--_That some few remedial agents act locally on the mucous
surface, either before absorption, or without being absorbed at all.
That they are chiefly as follow:_--

    _A. Irritant Emetics._
    _B. Stomach Anæsthetics._
    _C. Irritant Cathartics._

It has already been shown, during the consideration of the first
proposition, that medicines which act on distant parts of the body must
be, and are, absorbed before they can so act. This necessity for
absorption has been shown to extend even to medicines which act most
rapidly on the nervous system. If any medicines could produce a distant
effect by a mere contact with the coats of the stomach, such a power
would be ascribed to those stimulants and sedatives which, from the
suddenness of their action, are called diffusible. Such are Hydrocyanic
Acid and Ammonia. Their rapidity of action is to be ascribed to their
volatility, whereby they spread over a large surface, and are almost
_suddenly_ absorbed and transmitted through the blood. But Hydrocyanic
Acid may be absorbed from any surface. It is poisonous when inhaled into
the lungs. It rapidly causes death when dropped into the eye of an
animal. So also the results of the inhalation of ammoniacal gas are the
same as of the ingestion of its solution. I believe that the latter, on
account of its diffusibility and rapid absorption, escapes
neutralization by the stomach acid, and passes into the blood as free
Ammonia.

In the consideration of the first Proposition, I endeavoured to point
out that though the proper action of a medicine could in no case be
conducted, without absorption, from the mucous surface to a distant part
of the system, yet that a remote action of another kind might occur as
the result of a change in the nervous system produced by a powerful
local impression. I stated that the term _Counter-irritation_ was
employed to express this action, the nature of it being but ill
understood. A powerful impression on any surface of the body, external
or internal, seems to be capable of arresting and diverting, as it were,
the attention of the system, and thus, for a time, of checking a morbid
process.

Frictions and Sinapisms act on the skin externally on this principle. So
do Blisters and Issues; but they are not simply counter-irritants, for
they also drain away the serum of the blood. It is not now within my
province to consider such an action on the skin, any further than for
the purpose of stating that similar local impressions on the mucous
surface of the stomach and intestines are capable of operating on the
same principle.

We have then to consider what are the local actions that medicines are
capable of producing on these surfaces.

And first, it must be laid down as a rule, that all medicines, when
given in excess, act as irritants on the stomach and intestines. This is
more especially the case with mineral salts, with the bitter and
astringent principles of vegetables, and with acrid and resinous
matters. By irritating the stomach locally, they cause vomiting; by
causing peristaltic action of the bowels, purging. Some of them are
actually employed to produce these effects, and will be presently
specified.

The corrosive and narcotico-acrid poisons may produce by this local
action a degree of irritation sufficient to cause death. In the case of
the first, some erosion of the mucous surface may occur. By both kinds
violent vomiting and purging is apt to be produced, and succeeded by
symptoms of collapse. These last, however, are not _therapeutic_
agents, when in such doses.

Antidotes, employed to counteract these poisons, are remedies which are
given to act locally in extraordinary cases. There are three chief kinds
of them; Demulcents, to sheath the irritated surface, and protect it
from further injury; Emetics and Purgatives, to get rid of the poison;
and chemical antidotes, to neutralize it or render it insoluble while in
the stomach. With this last object, acids are given in alkaline, and
alkalies in acid poisoning. The soluble salts of Lead may be
precipitated and rendered insoluble by sulphuric acid or sulphates.
Those of Mercury, Copper, and Zinc, by albumen. Tannic acid precipitates
the vegetable alkaloids. There are some other special antidotes of the
same kind.

Let us now consider the three kinds of remedial agents in ordinary use,
which are employed for the purpose of producing a local effect on the
mucous surfaces, before absorption, or without absorption.

_a. Irritant emetics._--Two kinds of medicines are employed to produce
Vomiting,--specific emetics, and irritant emetics. The former act from
the blood; the latter, by local irritation. In the same way that
irritation of the external surface of the body will sometimes cause at
the same time the _direct_ contraction of a neighbouring muscle, and the
_reflex_ contraction of others at a distance, so does local irritation
operate on the surface of the stomach. On the one hand the muscle of the
stomach itself is caused to contract, so that, the pylorus being at the
same time forcibly closed, it tends to expel its contents in the wrong
direction. On the other hand, a large set of distant muscles is thrown
into sudden action. First, a quick deep breath is taken by means of the
inspiratory muscles. Then the aperture of the glottis is spasmodically
closed, so that, the lungs being full, the diaphragm cannot be pushed
upwards. Then immediately the abdominal muscles contract, and being
unable to act on the diaphragm, they press on the stomach, emptying it
forcibly of its contents.

All this is by reflex action, and follows sympathetically the
contractions of the stomach, co-operating with it, and resulting, like
it, from irritation of the sensitive mucous surface.[27] Such is the
action of an irritant emetic.

Now, Tartar Emetic and Ipecacuanha do not act in this way. When injected
into the blood elsewhere, in sufficient quantity, they are found to
produce vomiting. They have also special actions on the heart and lungs,
which are not possessed by merely irritant emetics. They seem to me to
act specifically on the Vagus Nerve, which is supplied to these organs
as well as to the stomach, and to cause vomiting by deranging its
functions. By this action on the Vagus while in the blood, they excite,
in a special way, the same reflex contractions which are produced, in
the case of an irritant emetic, by irritation of the extremity of that
nerve in the mucous membrane. They are thus Neurotics, or
nerve-medicines. They are not gland-medicines; or, at least, there is no
proof that they are excreted by the stomach, and thus they do not come
under my definition of Eliminatives. All substances which touch the
surface of the stomach cause it to pour out its secretion.

Specific emetics cause nausea, even without vomiting, depressing the
action of the heart by their influence over the Vagus nerve. Irritant
emetics scarcely cause nausea, producing only a feeling of discomfort,
arising from the inverted action of the stomach.

The Sulphates of Zinc and of Copper; common Salt, and among vegetables,
Mustard and Horse-radish, are used as irritant emetics. They cause, by
contact and irritation, a large quantity of the gastric juice to be
poured out. This, together with the emetic, and any contents of the
stomach, is rejected. The process is not followed by much inconvenience.

Such emetics are chiefly used when we wish to unload the stomach of any
irritating or poisonous matters; but not when our object is to cause
nausea, depression of the heart's action, or relaxation of the muscles.
The violent action which they produce may possibly act on remote parts
on the principle of counter-irritation. Thus emetics of various kinds
are often administered in the early stages of inflammatory disorders,
and have been known sometimes to cut them short. But such an effect is
much more likely to be produced by a specific emetic, which adds to this
counter-irritant action the production of nausea, by which the force of
the heart is powerfully depressed, and the pulse reduced. Tartar Emetic,
the most powerful of these specific agents, must doubtless be absorbed
to a certain extent before it can produce its effect. Thus the important
difference between the modes of operation of irritant and specific
emetics is, that the former do not produce vomiting when injected into
the blood, but act locally; whereas the latter act from the blood on the
nerves. (_Vide Prop. VIII., Specific Sedatives._)

_b. Stomach-Anæsthetics._--There is a class of medicines used in
Gastrodynia which seem to act locally on the sentient nerves of the
stomach, in the same way that Aconite acts on the superficial nerves of
the skin. Although the majority of them are subsequently absorbed, yet,
in order to exert this particular action, it is not necessary that they
should pass beyond the substance of the stomach itself. They do not seem
to have any special or peculiar tendencies towards the stomach nerves.
But if introduced into the blood elsewhere, they would not pass the
nerves of the stomach in so concentrated a form as when coming directly
from the mouth, and thus would not be so useful as stomach-anæsthetics.
Thus this action depends upon local contact, and is so far a local
action.

Hydrocyanic acid, Creosote, and Nitrate (also called Tris-Nitrate) of
Bismuth, are the most useful of these medicines. The first two are
subsequently absorbed, and pass into the blood. The third is a very
insoluble salt. It acts also as an astringent on the mucous surface
of the intestine, and is probably the only astringent which is not
absorbed. Being insoluble, its action is quite confined to the mucous
surface. It may be given safely in very large doses, (as [dram]ss,
or even [dram]j.) and it is likely that its anæsthetic action may be
in some part mechanical in nature, and depend upon its affording a
mechanical sheath to the irritable and painful surface of the stomach.
Hydrocyanic acid and Creosote,--general sedatives,--act locally as
anodynes to the nerves of the stomach.

_c. Irritant Cathartics._--As there are two kinds of emetics, differing
in their mode of operation, so also do there seem to be two kinds of
Cathartics. But the distinction between them is not exactly the same. As
with the Emetics, one kind seem to act by topical irritation, exciting
an outpouring of the intestinal secretions, and causing an expulsion of
the contents by exciting peristaltic contraction. But Specific Emetics,
which act from the blood, seem to produce their effect by influencing
the nerve of the stomach; so that they are Neurotic medicines. Specific
Cathartics act differently. They are truly Eliminatives. They exert no
influence over nerves, but they operate by passing out of the blood
through the intestinal glands. Like Specific Emetics, they must be first
absorbed. I will not now enter into the theory of Elimination, which I
shall have to consider afterwards, but I wish merely to distinguish
between local action on a surface, and specific action on a gland,
exerted from the blood. Many substances used as purgatives are capable
of absorption, and are absorbed. But it seems that they are not fit to
remain in the blood; and after passing round in the circulation, they
are expelled by the depurative force at a point near to that at which
they previously entered by the laws of absorption, namely, the mucous
surface of the bowels. They are most commonly expelled by the glands of
this surface somewhere in the lower or fæcal portion of the intestinal
canal, which is more engaged in secretion, but less active in
absorption, than the upper part. The increased secretion which they
excite causes peristaltic action, which expels both it and them, so that
they cannot again be absorbed.

Such a specific Cathartic would be capable of acting thus if introduced
into the system at any point. Castor Oil and Croton Oil, whether
received into the stomach, or injected into the veins, or introduced
into the system at any part, equally produce purging. So also do
Rhubarb, Aloes, and Senna. The principles of these medicines have been
detected in the blood by Tiedemann, Gmelin, and others. Colocynth and
Elaterium have also been proved to act specifically.[28]

It is to be inferred from analogy that other resinous Cathartics, as
Jalap, Scammony, and Gamboge, must also act from the blood. It has also
been shown that both from actual experiment, and from a consideration of
the laws of the process of absorption, we must conclude that saline
Cathartics are absorbed into the blood before they cause purging.

But we have now to do with Cathartics that act by topical irritation.
Which are they? I believe that the same resinous Cathartics which have
the power of acting specifically, may have, especially when in large
doses, a double action. It has been shown that resins are difficult of
absorption; and whether they be absorbed or not, we know that they must
irritate the intestinal surface, from the violent griping which often
attends their operation. Thus Scammony does not act so well, and does
not gripe, when the bowels are lined with mucus. Gamboge and Euphorbium
are irritant in an extreme degree, and are therefore too dangerous for
general use. The powder of Euphorbium resin has been used as an Errhine,
for, by irritating the mucous membrane of the nose, it increases its
secretion. This illustrates the operation of irritant Cathartics. A
great part of the fæces is secreted by the mucous membrane of the bowel.
This secretion a Cathartic may increase by mere contact and irritation;
or, being also a specific agent, by absorption and elimination
likewise.[29]

Some Cathartics employed as Vermifuges, as the hairs of _Mucuna
pruriens_, metallic Mercury, and Tin powder, cannot be absorbed at all,
and must act solely and altogether by irritation.

These Vermifuges, or Anthelmintics, are employed for a strictly local
purpose--that of killing and expelling intestinal worms. Any powerful
Cathartic may be used to expel them. But such an agent should generally
be conjoined with a medicine that tends directly to kill the parasite;
for after that it will be more easily dislodged. For this purpose the
root of Male Fern, Kousso, and the bark of the root of Pomegranate, have
been used with advantage in the case of tape-worm. Ascarides are
situated low down in the intestine, and may be dislodged by the use of
an enema, as of Salt.

Turpentine is often very efficacious in cases of this kind, being at
once a poison to the worms and a powerful irritant cathartic.

I have already alluded to Nitrate of Bismuth, as seeming to be an
astringent to the mucous surface of the intestine, although apparently
incapable of absorption. It has been used with advantage in diarrh[oe]a,
and is highly recommended by Dr. Theophilus Thompson in the diarrh[oe]a
of Phthisis.

But all other astringents are absorbed; and when they act on the mucous
glands of the intestines, it is probably from the blood.

It has been supposed by M. Poisseuille and others that the action of
Opium in confining the bowels is to be attributed to a power of checking
the process of endosmosis, said to be possessed by a solution of
Morphia. I shall afterwards state my reasons for discrediting this
explanation. (_Vide Chap. IV., Art. Opium._)

Thus we have concluded the list of substances which seem to act locally
on the mucous surface, without passing into the blood.

Having previously endeavoured to explain the various modes in which
medicines are absorbed and pass into the blood, and having now defined
the action of some few before absorption, the greater part of our
investigation remains still to be accomplished. The actions of medicines
in the blood, and their various and complicated operations in the cure
of diseases, have to be traced out, and, if possible, accounted for.

The remaining six Propositions concern the behaviour of medicines after
their passage into the blood. The first two of them are comparatively
unimportant. The Fifth is merely an extension of the First
Proposition,--in which the same rule is applied to the blood which was
there proved of a surface,--and indeed follows in part from the latter.
The Sixth Proposition defines three kinds of changes which certain
medicines are liable to undergo during their stay in the system.


PROP. V.--_That the medicine, when in the blood, must permeate the mass
of the circulation, so far as may be required to reach the parts on
which it tends to act._

_That there are two possible exceptions to this rule:_

_a. The production of sensation or pain at a distant point._

_b. The production of muscular contraction at a distant point._

We might already have concluded that, as a general rule, it is
impossible for medicines to exert their primary action on a remote part
by nervous or any other agency, but that they must actually reach the
part which they affect by means of the circulation. The experiments,
already quoted, of Magendie, Blake, Ehbert, and others, show that even
those medicines and poisons which tend most powerfully to influence the
nervous centres, cannot act by nervous connexion, or without being
allowed to pass on in the blood. They must actually reach the brain,
before they can act upon it. The circulation of the blood is
sufficiently quick to allow of this.

The action of nerve-medicines when applied to a part, being similar to
that which follows their absorption, would alone render it highly
probable that in the latter case they reached the part in the blood.
Thus Morphia, Hydrocyanic Acid, Chloroform, and Aconite, benumb the
superficial nerves: Belladonna dilates the pupil; and Strychnia augments
muscular irritability; whether locally applied, or administered through
the stomach.

Neurotic medicines have even been detected after death in the parts and
organs which they influence. Thus Alcohol has been found in the brain,
and Lead in the spinal cord and muscles.

From these various facts we may conclude that however near these
remedies may be brought to that part of the nervous system over which
their power extends, whether it be centre or periphery, they do not in
general affect it, unless they are allowed to reach it.

And what is proved of nerve-medicines holds good still more obviously
with medicines that act on the blood, and on blood disorders. Nearly all
of these have been found to exist in the blood, and to pervade the whole
mass of the circulation, wherever at first introduced.

The glands of the body form a third case in which we require proof of
actual local access. This matter will be discussed when we have to
consider the subject of Eliminative medicines, when I shall attempt to
show that the majority of those medicines actually pass through and are
excreted by the glands which they affect. When Mercury is chemically
detected in the secretions of the liver and bowels; Sulphur in that of
the skin; Turpentine and Copaiba in that of the kidneys; it is evident
that these substances must have reached bodily the glandular organs to
which their action is directed.

Astringents are medicines which from the very nature of their
action--apparently a chemical one--cannot operate at all without
touching the muscular fibre, which they cause to become contracted.

But in laying down this rule of the necessity of local access for the
production of the primary[30] effect of a medicine, we must be careful
that we do not make it too absolute. In saying that no action at all can
be propagated by the agency of the nervous system, we do not make proper
allowance for the vital properties of nerve-fibre. The vital nature of
common nerve-fibre is such that two actions can be conducted along
it;--an impulse producing sensation, or an impulse producing muscular
action, at a distant point. It is known that an impression on the
terminal extremity of a sensory nerve is capable of producing either
sensation or motion at a distance, by what is called _reflex nervous
action_. Though this impression must pass through the brain or spinal
cord, yet these centres are not appreciably affected by it. Now it is
possible, though it does not often happen, that the action of a medicine
on the extremity of a nerve may cause this distant action, without
reaching the part at which it is manifested. It may be positively
affirmed that in no other case can the direct action of a medicine be
conducted along a nerve.

Having made allowance for the physiological characters of nerve, we must
also take notice of the vital properties of muscular fibre. We sometimes
find, especially in the case of unstriped muscle, that when one part of
a muscular organ is caused to contract, a wave of contraction is
propagated along the fibres; and this action may even be extended to a
neighbouring muscle, either by contact or sympathy. In one or two cases
it seems that muscular contraction may occur in this way as the result
of the action of a medicine.

We will now consider separately the two exceptional cases.

_a._ _A medicine may occasionally produce pain or sensation at a distant
part, without reaching that part._ We often find that a morbid action at
one part of the body is capable of producing pain or uneasiness at
another distant part by a reflex nervous action. We are familiar with
instances of this among the symptoms of disease. The pain in the knee
which occurs in disease of the hip-joint; in the left arm, in some cases
of heart disease; and in the right shoulder, in disorders of the liver;
are examples. Certain impressions on the surface of the stomach may
cause such a reflex pain. Swallowing a piece of ice will sometimes
produce pain over the brow; and it is likely that the headache which
follows over-eating, or a large dose of a tonic medicine, may result in
a similar way from mere irritation of the stomach. Any irritant, as a
solution of Iron, Arsenic, or Zinc, will do the same. The action of a
violent purgative will cause headache while it lasts. Although we cannot
deny the possibility of other actions of the same kind, yet there are so
few medicines which, in ordinary and safe doses, are capable of
producing pain in any way, that it becomes difficult or impossible to
adduce a satisfactory example of an agent which operates on distant
parts in this manner when in the blood.

_b._ _A medicine may occasionally produce muscular contraction at a
distant part, without reaching that part._ This may be done in two ways;
either by a reflex nervous action, or by a propagation of the
contraction from one muscle to another in its neighbourhood. The first
of these never results from the action of a medicine while in the blood;
but it may follow an impression on a surface. Thus we have already seen
that the irritation of the mucous membrane of the stomach, and probably
of the filaments of the Vagus nerve distributed in it, which precedes
the act of vomiting, may cause the contraction of the muscles of the
abdomen.

The propagation of contraction from one muscular organ to another
appears to take place in the case of violent purgatives, particularly
some, as Aloes and Savine, which act on the lowest portion of the large
intestine, exciting it to a peristaltic contraction,--whose action may
thus be extended to the contiguous Uterus in the female, causing it also
to contract. This renders the employment of such medicines dangerous in
cases of pregnancy, as tending to produce abortion. In other cases these
agents may be useful; for by the irritation and congestion which follows
this action on the Uterus, they may cause the appearance of the
menstrual secretion when deficient or retained. This also is the result
of an action on a surface.

Now, though in such cases the action of a medicine seems to be continued
from the part where it is situated to a distant point, there are
certainly no authenticated examples of such an action by a remedy in the
blood. Yet it would not be reasonable to deny the bare possibility of
such a thing. But such instances are at all events rare, and, being
cases of the manifestation of their vital properties by nerve and
muscle, rather than of the proper action of a medicine, must not be
considered to invalidate the above proposition, which, as a general
rule, is of considerable importance.


PROP. VI.--_That while in the blood, the medicine may undergo change,
which in some cases may, in others may not, affect its influence. That
these changes may be--_

_a._ _Of Combination._

_b._ _Of Reconstruction._

_c._ _Of Decomposition._


Before advancing to the consideration of the modes in which medicines
operate in the cure of disease, it is of importance to mention that some
of them are liable to undergo changes in the animal organism, because in
particular cases these changes may materially affect their action, and
in all cases they have some bearing upon it. With a view to this point I
have divided these changes, somewhat arbitrarily, into three kinds,--of
which the first does not hinder the effect of a medicine--the second may
alter it slightly--and the third entirely changes or neutralizes it.
Some of these change have to be considered more at length in the
progress of the Essay, so that here I will only give an outline of them.

_Changes of Combination._--The chief, and indeed almost the only way of
detecting changes in medicines, is by taking notice of their effect upon
the composition of the secretions.

Now in the blood we have a slight excess of alkali; in the urine, an
excess of acid. Acids and alkalies are often given as medicines; and as
it is not right that there should be much excess of either in the blood,
both are generally soon neutralized in the system, and reduced to salts.
This may sometimes occur before absorption, but perhaps more often after
it. Now, it may seem strange for me to say that this neutralization does
not destroy their influence. But it evidently does not; for in being
neutralized they diminish in the blood, and in the system generally, the
quantity of basic or of acid matter, and thus tend to alter the reaction
of the secretions. Though an acid may combine in the blood with Soda, or
with salts of Soda, yet by so doing it causes an excess of some other
acid, probably an animal acid, which, being set free, acts on the
secretion of urine much in the same way that the first acid would have
done. It is easier to render the urine alkaline than to make it acid,
for two reasons; first, as I shall show hereafter, an acid may pass out
through other glands besides the kidneys; and secondly, an alkali is not
so easily neutralized, either before or after absorption, the blood
being already more or less alkaline.

A large quantity of acid would easily overcome the feeble reaction of
the blood, and thus, by remaining free, Sulphuric and other acids are
enabled to act as astringents on certain of the glands.

Other changes of combination have already been shown to take place
during the process of absorption. Alkalies and their carbonates are more
or less neutralized by the stomach acid. Substances soluble in alkalies
are probably absorbed in such solution. Calomel, Chalk, Magnesia, and
metallic oxides, as well as other insoluble medicines, are taken up in
the soluble form, in which only they are capable of acting. But we are
now concerned with medicines in the blood. And here I must protest
against the idea that all chemical affinities have free play in that
liquid. If it were so, many of our most valuable medicines would be
decomposed and rendered insoluble there. All the mineral salts would be
precipitated by the free Soda in that fluid. Acetate of lead would be
immediately decomposed by sulphates, and Nitrate of Silver precipitated
by chlorides. It is probable that the vital forces, as well as the
viscidity of the plasma, exert a retarding or controlling power over
such chemical tendencies.

Some substances are decomposed while passing out of the body.
Decomposing matters in the intestines and in the saliva, cause the
formation of Sulphuret of Iron, while chaly-beates are taken, which
blackens the fæces; and of Sulphuret of Lead, when lead is taken for
some time, producing the well known blue line on the gums.

_Changes of Reconstruction._--The elements of a body may be disturbed in
the system, and combined together anew, without any material or apparent
alteration of its properties. Probably many changes of this kind occur,
but only some isolated instances have been verified. Thus Tannic acid,
acquiring Oxygen, changes into Gallic. Benzoic and Cinnamic acids are
converted into Hippuric acid, which passes out in the urine. Turpentine
changes into a volatile oil, which communicates to the urine an odour of
violets. Ferridcyanide of Potassium changes in the system into
Ferrocyanide. Some of these changes will be afterwards considered more
at length.

_Changes of decomposition._--By this I mean such a disarrangement of
elements as shall neutralize or reverse the action of a medicine.

There is free Oxygen in the blood, and the most important change to
which all organic substances are liable there is _oxidation_.

This probably occurs in many cases. It always takes place with the
starchy elements of the food, and with those parts of the nitrogenous
tissues that have done their work, and are preparing to be excreted from
the body.

By this oxidation Wöhler has proved that the alkaline salts with
vegetable acids are changed in the blood into alkaline carbonates. From
being first neutral, they become now alkaline in their reaction, and
affect the urine in the same way as free alkalies.

(_Vide Hæmatics, ord. Acida, Alkalia, Tonica, Solventia._)

We have now to treat of the actions of medicines in the blood. These are
recited in the four remaining Propositions.

The seventh treats of Hæmatics, acting primarily in the blood.

The eighth treats of Neurotics, passing from the blood to the nerves.

The ninth of Astringents, passing to muscular fibre.

The tenth and last treats of Eliminatives, which pass out of the body
through the glands.


PROP. VII.--_That a first class of medicines, called_ HÆMATICS, _act
while in the blood, which they influence. That their action is
permanent._

1. _That of these, some, called_ RESTORATIVES, _act by supplying, or
causing to be supplied, a material wanting, and may remain in the
blood._

2. _That others, called_ CATALYTICS, _act so as to counteract a morbid
material or process, and must pass out of the body._

Supposing that a medicine has fairly passed into the blood, and
circulates round with it, there are now two ways in which it may behave
itself.

In the first place, it may have a tendency towards some tissues or parts
of the body, on which to exert its powers, as the nerves, or the glands,
or muscular fibre, and may use the blood only as a vehicle by which most
readily and easily to attain to these. Such are Neurotics, Astringents,
and Eliminatives. They may not affect the blood, but they must pass
through it.

But there is another and still more important class of medicines, whose
action is particularly directed towards the blood itself. The blood,
after their action, is different from what it was before. It may be a
change for the better or for the worse; but there certainly is a change.
Medical authors, with few exceptions, have been very backward to
acknowledge the existence of medicines of this description. But even
those who would fain have classed all medicines as stimulants or
sedatives, differing only in the kind or degree of their action on the
nervous system, have in many cases been obliged to confess that there is
a set of remedies which they call "Alteratives," whose action, though
slower, is more certain and more durable than that of the former. It is
allowed that they alter the condition of the blood. To suppose that they
do so by first influencing the nerves, is to adopt a circuitous and
uncalled-for explanation. It is proved that they pass into the blood. It
is known that when actually applied to nerves, they do not affect them.
From these considerations merely, without further evidence, it would
seem tolerably clear that they act by influencing the blood itself,
simply and solely. But this it will be my business to prove more at
length directly.

Such medicines, then, I have designated Hæmatics, a simple and
expressive term which has been used by others before me.

It is obviously necessary that a medicine of this class should be
absorbed.

Now some of them tend in the end to act on the nerves or on the glands,
not merely indirectly, but by bodily contact. But, whatever their
subsequent action, they exert a primary and apparent influence on the
blood itself. A little reflection will convince us that these remedies
are more efficient than any others that can be selected out of the
armory of physic.

It is easy, and satisfactory for the time, to allay nervous excitement
by employing a sedative, or by using a stimulant to communicate to the
system a temporary strength. It is easy to knock down an inflammation,
or to evacuate morbid humours, by stirring up the glands with a powerful
eliminative. But these are all at the best but temporary measures.
Unless the exigency be also of a temporary character, the disorder may
soon return with unabated violence; again is the patient bowed down by
its strong hand; again is the fatal termination seen looming in the
distance but too distinctly. Then has the physician to call to his aid
more potent means, remedies of more permanent and certain efficacy. The
disease is in the blood--ever circulating, breeding, and destroying. It
is there that it must be met; let the physician strike boldly and warily
there, if he would effect a cure.

These medicines, then, act in the blood. How they do so, and in what way
they prove of use in the cure of disease, I shall next have to show,
while attempting to prove the proposition in which I have briefly stated
this mode of operation.

Hæmatics are very numerous, and very important: I shall thus devote some
space to their consideration. But I must first lay down a broad
distinction between the two divisions of Hæmatic medicines. The diseases
in which they are used appear all to originate in the blood, however
they may manifest themselves.

Now some of these diseases originate in a want of some principle or
constituent of the blood, which want causes an aberration of the vital
functions.

Thus, in anæmia, there is a deficiency of the Hæmatosin of the blood
corpuscles. In simple debility a want of a similar nature probably
exists. In rheumatic fever and other disorders an excess of acid is
formed and eliminated, possibly from a want of the alkali by which it
should be neutralized. In common inflammatory fever there is an abnormal
oxidation of the Proteinaceous compounds, possibly arising, as we shall
see hereafter, from a failure of some principles which are the proper
food of the oxygen. In diseases causing urinary deposits there is a want
of those principles which should naturally retain them in solution. In
typhoid fever there is said to be an excess of basic matter, and a
deficiency of acid, in the blood. In pulmonary phthisis there is a
deficiency of fat in the system. In the latter stage of malignant
cholera there is an absence of watery particles in the blood. Some
suppose that in scurvy there is a want of the salts of Potash in the
blood.

These diseases, then, in some of which the want is proved, in others
partly hypothetical, may be treated by medicines which supply the
deficient matter, and thus restore a right state of things. They may
supply it to the blood directly, or else cause it to be generated there.
The former of these modes of restoration seems to be the most frequent,
and may possibly, when we shall know more of such matters, be found to
occur in all cases. This division of Hæmatics I have named Restoratives
(Restaurantia.) Their action, as we shall see, is in some cases
apparent, in others more obscure. They restore the blood directly to its
proper condition, if there is only a deficiency, but they do not in
general seem to have the power of counteracting any morbid or active
material that may exist in the blood. Nor do they, except in large
doses, exert themselves any peculiar action on that fluid. In these
respects they differ from the other division of Hæmatics. They also
differ in another important character. Each Restorative has in healthy
blood a substance analogous to, or identical with itself: it replaces
this when deficient.

Not so with other Hæmatics. There is in general nothing in the blood
corresponding to them--or if there be in some cases, they are not
introduced with the intention of supplying its wants. Thus Restoratives
may remain in the system, and are intended so to do; but these may not
remain. They must pass out. In so doing they come under the head of
Eliminatives, or that of Astringents. This is their secondary action,
distinct from their primary and most important operation. What then is
the curative action of these remedies?

A large class of diseases depends on the presence in the blood of a
morbid material, or, what amounts to the same thing, on the constant
working of a morbid process in that fluid. Some of these, as the
eruptive fevers, will run a certain course, and then come to an end.
These we cannot generally stop, but can only alleviate. But others, more
in number, and more commonly met with, tend naturally to run on for an
indefinite period, unless by any means we can arrest their progress.
Some depend on a contagious virus, communicable from one person to
another, as Syphilis. Some, as Ague, are dependent on atmospheric or
terrestrial influences. Others are due to some derangement of the
secondary assimilative processes, as Scrofula, Scurvy, Gout, and
Rheumatism. Others again, to causes that are ill understood, as
convulsive disorders and skin diseases. Lastly, some may be caused in
many different ways, as common inflammatory fever.

Now the object in the treatment of such diseases is to obtain in each
case some remedy, that shall be able to counteract this process,
something that shall destroy the morbid influence at work, and thus
restore health. Medicines that are used with this intention form the
second division of Hæmatics, which I have named Catalytics (Catalytica,)
from a Greek verb signifying to destroy or to unbind.

Now though I have a probable hypothesis to advance as to the action of
some of these, I would not have this considered as more than
hypothetical. I would not speak positively of the action of any one of
them, any more than to say that each of them tends to neutralize one or
more particular morbid poisons.

Some have tried to give a general explanation of their action, and have
talked of it as if it were easily understood by their known properties.
I am not of their opinion; and when I speak of Catalytics, I shall give
my reasons for disagreeing with them. Now each Catalytic has
peculiarities and affinities that distinguish it from all others. I have
not thought that I could arrange them more truthfully than by
subdividing them according to diseases which they tend to counteract.
How inadequately is the action of Mercury and of Iodine expressed by
calling them special stimulants, alteratives, or absorbents! Is it not
better and more correct to say at once that Mercury is useful in
checking inflammation in general, and in counteracting the poison of
Syphilis in particular? and that Iodine is effective in secondary forms
of the latter disorder, as well as in Scrofula?

These medicines, then, are specifics, in so far as they are particularly
useful in certain disorders, and in those excel other remedies; but they
are not, in the vulgar acceptation of that term, the only medicines
which can be employed in such a disease, nor is their use to be
restricted to it alone. I have already said that a Catalytic tends of
itself to work out a peculiar process in the blood. For this reason
their administration in health generally does harm. They have nothing in
the blood corresponding to them; or if so, they are not introduced to
supply its want. Thus they must eventually pass out of the body. Before
doing so, some may act on the nerves. While so passing out, they may, as
I have said, act either as Astringents or Eliminatives on the glands.
Under these heads their secondary action will be subsequently
considered.

Being thus foreign to the blood, Catalytics do not remain there to
supply a want; but just long enough to counteract a morbid action, and
are then excreted.

Such is the difference between Restorative and Catalytic medicines.
Although so far as this their action is sufficiently distinct, yet some
care is required in separating the remedies in one division from those
in the other. Sometimes both kinds are used in the same disorder. For
whenever the action of a morbid poison causes any derangement in the
proportion of the normal constituents of the blood, a Restorative may
become of use to supply this defect. Thus a cancerous or scrofulous
condition may cause a deficiency in the red colouring matter of the
blood, which may be supplied by Iron. When, as in Gout and Rheumatism,
there is an excess of acid in the system, partly due to an absence of
that basic matter which should be present to neutralize it, this may be
restored by an alkaline remedy. In both of these cases a Restorative may
be used in a disease which depends on a morbid agency. But other
remedies, Catalytic in their action, are of more direct use in such
disorders. They counteract the original poison, and striking at the root
of the evil, instead of correcting the consequences, they are more
likely to eradicate the disease.

Some medicines come under both heads, acting in different ways in
different cases. Thus Potash may be a Restorative in Rheumatism, but a
Catalytic in Scrofula.

The operation of some particular agents is rather obscure. I shall have
to show how it seems to me that the vegetable acids may act as
Restoratives in fevers; and also to explain why, of those medicines
which are used in Intermittents, I have placed Quina among Restoratives,
and Arsenic with Catalytics.

It may be remarked that the fact that Catalytic medicines produce of
themselves distinct actions in the blood has proved a stumbling-block to
the disciples of M. Hahnemann. For in some few cases their action may,
to a certain extent, simulate the disease which they tend to cure, and
has thus been confounded with it by this imaginative observer. This
partial resemblance is probably due to the fact that both disease and
remedy produce a series of changes in the same set of particles in the
blood. If it were not so, the remedy could not meet the disease. It
would be out of its province, as not acting at all in the same sphere.
But that the actions are essentially different is sufficiently proved by
the fact that they counteract each other. The remedy, moreover, is often
of equal efficacy in other different disorders. It has been shown in
Chapter II., that with regard to Eliminative medicines, the
Hom[oe]opathic theory is founded on a misapprehension of facts.

It must not be inferred, from what has been said on the importance of
blood-medicines, that I am disposed to agree with those who would
account for all diseases by some fault in the humours of the body. For
though we know that many cases of convulsive disorder, as of Hysteria,
Chorea, and Epilepsy, may be reasonably accounted for by supposing the
existence of a wrong in the blood, which has affected the nervous
system,--yet there are doubtless many nervous affections which are
primarily independent of the blood, which can only be treated by
Neurotic medicines, and even then often without benefit.

Thus far I have chiefly dealt in assertions on the subject of Hæmatic
medicines, but I am now about to attempt a thing which is more
difficult, that is, positive proof.

I shall treat separately of Restoratives and Catalytics; each division
will be divided into certain distinct orders of medicines; and of each
of these orders in turn I shall attempt to prove what is laid down
concisely in Proposition VII. To simplify this proof, that part of the
Proposition which relates to Restoratives will be divided first into a
number of minor propositions, which, taken together, imply the original
one. Each must be shortly proved applicable to each order of
Restoratives. The same will be subsequently done with Catalytics. Having
sustained the original proposition to my own satisfaction, I shall, in
some cases, venture to offer an additional hypothesis--only as
hypothetical--on the action of particular medicines.

Let us now proceed to the consideration of the first division of Hæmatic
medicines.


RESTORATIVES.

The general name given to the medicines in this division is founded upon
a fact relative to their action, which will be acknowledged of most that
I have here included--namely, that they restore to the blood certain
materials in which it is deficient.[31]

I will divide them into six orders, which are all distinct and
characteristic in their mode of action.


     RESTAURANTIA.

    Ord. 1. Alimenta.
    Ord. 2. Acida.
    Ord. 3. Alkalia.
    Ord. 4. Tonica.
    Ord. 5. Chalybeata.
    Ord. 6. Solventia.

On reverting to Proposition VII., which treats of the action of the
first class of medicines, it will be seen that what has been there
stated with respect to the action of Restoratives resolves itself into
the following simple affirmations or minor propositions.

    _m. p._ 1.--That they act in the blood, and that their effect is
                      permanent.

    _m. p._ 2.--That there are naturally in the blood substances
                      which resemble or coincide with them.

    _m. p._ 3.--That they are not of necessity excreted, but may
                      remain in the blood.

    _m. p._ 4.--That they are of use when a disease depends on
                      the want of one or more materials in the blood.

It will be seen that the first minor proposition affirms them to be
Hæmatic medicines, according to the definition given before. The second
is required; for if there were not a necessity in the blood for
substances like them, they could supply nothing. The third also is
necessary, for if they were excreted in all cases, it is evident that
their Restorative action could not be lasting. An exception must be made
in the case of those that are used to supply something which is
necessary in order that a secretion may be properly elaborated.
Medicines of the Sixth Order are particularly used with this intent; as
also some acids and alkalies. But these are not repugnant to the blood,
like Catalytics. In the fourth place it is affirmed that being thus
fitted for the blood, and allowed to remain in it, they tend to cure a
disease which depends on the want of a substance similar in nature to
themselves.

After giving a brief account of each of the orders of Restoratives, it
will be my object to prove that these affirmations are severally
applicable to each of them.


ORD. I. ALIMENTS.

An article of food is the simplest form, and in fact the type, of all
medicines of this division. Out of the materials of the food the whole
blood is constantly elaborated, and all the tissues are constructed.

Aliments were divided by Dr. Prout into four kinds:--(1) Aqueous; (2)
Albuminous; (3) Saccharine; (4) Oleaginous. These kinds differ much in
chemical conformation. The second kind alone contain Nitrogen. The last
two are both called _carbonaceous_; but those of the fourth kind contain
more Carbon than those of the third. The following will serve to
illustrate the differences in the chemical composition of these groups.

    1. Water = H O
    2. Proteine = C_{40}H_{31}N_{5}O_{12}
    3. Starch = C_{10}H_{10} O_{10}
    4. Stearic Acid = C_{68}H_

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