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.