compounds of the earths and metals--are absorbed in the stomach and
intestines. The conditions and the process of absorption have been
already stated. When solid they are first dissolved, when in a dense
solution diluted down by the gastric fluid before they are absorbed.
Thin watery liquids are quickly taken up. Motion on one side, and
pressure on the other, hasten the process. I am not inclined to make any
exception to this rule. This leads me to make some remarks on _the
Endosmotic theory of the action of saline purgatives_.
M. Poisseuille found that the serum of the blood would pass through an
animal membrane to a solution of Sulphate of Soda of greater specific
gravity. He thus concluded that an ordinary saline purgative of greater
specific gravity than serum (1.028) acted by causing the passage of this
serum outwards into the intestine, producing a watery evacuation. The
theory was taken up by Liebig and Matteucci, and by Laveran and Millon.
Dr. Pereira and Dr. Golding Bird have drawn some practical inferences
from it.
It is said that when a saline is absorbed it produces diuresis, and no
purging; that when it purges it is not absorbed; that when given to act
on the kidneys, the solution should be so diluted as to contain less
than five per cent. of the solid; and when administered as a purgative,
the specific gravity should be considerably above 1.028. Now I do not
deny that a weak solution is more likely to pass off by the kidneys, and
a dense one by the bowels; but I consider this due to the fact, that the
kidneys are the proper emunctories of water, and of such matters as are
soluble in it. But I believe that these solutions are equally absorbed,
both heavy and weak, and that the purging or diuretic effect depends
mainly on the quantity of the salt, as the kidneys will not eliminate
beyond a certain amount of it. I must allege, to support this view of
the question, firstly, some arguments _à priori_; and secondly, some
experiments which I have made to satisfy myself. To consider first the
former. Analogy is certainly against this theory. Other purgatives from
the vegetable kingdom produce their effect when injected into the blood,
and are yet often powerfully hydragogue. What effect on the process of
endosmosis can be exerted by Castor or Croton oils, or by calcined
Magnesia? On turning to what we know of the theory of digestive
endosmosis, we find that the solid parts of the food are diluted down so
as to be absorbed, and that the influence of pressure is to be taken
into calculation. It was laid down by the great Boerhaave that a
necessary requisite for the formation and absorption of chyle was the
contractile force of the viscera. (_Van Sweiten's Comment_, vol. i. p.
290.) This, in fact, would press the fluid into the absorbent vessels,
even if against the other endosmotic forces. Further, a fundamental
principle was insisted on by Dutrochet--that even when the liquids on
the two sides varied in density, they would both pass through to each
other, though in different proportions. The ultimate result of this
would be, that a heavy saline solution would be diluted down to the
specific gravity of the serum, and would then pass through. This point I
have illustrated in my first experiment. Thus it seems that my view is
favoured by these physical laws. But even if it were not so, I should
not be inclined to admit that all the endosmotic processes in the living
body were regulated by merely physical tendencies. This cannot be the
case with some of the secretions. The bile is of higher specific gravity
than the serum of blood. Urine in health is lower, but in diabetes often
much higher. The production of these secretions, differing in density
from the serum of blood, would be inconsistent with the first law of
endosmosis. Lastly, we find that in many known cases the theory which I
am contesting does not hold good. Seidlitz water and sea-water are both
known to be purgative. In both the specific gravity is _below_ that of
the serum of blood.
The first, according to Bergmann, has a density of 1.006. It contains in
each pint 192.8 grains of solid matter. Out of this, 180 grains consist
of Sulphate of Magnesia.
Sea-water has a specific gravity of 1.026, and its solid contents are
about 3.5 per cent. But Dr. G. Bird says that less than five per cent.
of saline matter constitutes a liquid diuretic.
These, then, are strong reasons against this idea considered merely as a
theory. But it can readily be put to the proof. With this purpose I have
made the following experiments. As far as they are concerned, they seem
to show that salines are in all cases absorbed, and that whether they
are subsequently excreted through the kidneys or by the bowels depends
more on the quantity administered than on the degree of dilution of the
dose.
EXP. 1.--A sufficient quantity of white sugar was dissolved in four
ounces of water to raise its specific gravity to 1.028, that of the
serum of the blood. Two drachms of sulphate of magnesia were
dissolved in another ounce of water, so that the solution measured
nine fluid drachms, and had a density of 1.060. This heavier
solution was introduced into an open wide tube, closed completely
below by a clean piece of bladder. It was introduced into a small
vessel containing the solution of sugar, and arranged so that the
height of the two liquids should correspond. After three days, the
inner solution measured two drachms more, and the specific gravity
had sunk to 1.050. The outer solution, after making up exactly the
loss by evaporation, was found to have risen in density to 1.040.
On adding a small quantity each of the solutions of phosphate of
soda and carbonate of ammonia, a copious precipitate took place,
indicating the presence of magnesia. Thus it appeared that the
fluids passed both ways, some of the heavy solution of magnesia
finding its way through to the lighter solution of sugar. The
tendency of this process was evidently to an equalization of their
densities, both by endosmose one way and by exosmose the other.
Thus, apparently, would it be with a saline purgative, and with the
serum of the blood.
EXP. 2.--Three drachms of Sulphate of Magnesia (a very mild
purgative dose) were dissolved in ten ounces of water, and thus
administered to a healthy young man. It produced, after some time,
slight purging, and some diuresis. The urine, when tested,
contained only a very little more than the usual quantity of
magnesia. The quantity in the dose was less than five per cent. of
the solution, and thus, according to the endosmotic theory, should
have produced no purging.
EXP. 3.--Six drachms of the same salt were given in eighteen ounces
of water to the same patient. After a few hours, it caused very
copious and long-continued watery purging. The urine did not seem
to be increased, and contained no excess of magnesia. It seemed,
that in spite of the dilution, the quantity of the salt was so
large, that it could not pass off by the kidneys, and so was
eliminated from the blood by the bowels, in the same way as other
purgative medicines. (_Vide_ Chap. IV.)
EXP. 4.--This trial was the reverse of the last. Two scruples of
Acetate of Potash were dissolved in three drachms of water, and
thus administered. The solution then contained about twenty per
cent. of the salt. According to the endosmotic theory, it should
have caused only slight purging, on account of its density. It did
not do so, but produced diuresis. The dose was so small, that after
absorption it was easily eliminated by the kidneys.
These experiments are in favour of my views, and seem, as far as they
go, to cast discredit on the theory of Poisseuille. It will be very easy
to multiply them, so as to place the fact beyond a doubt.[24]
This point being so far settled, and there being no physical reason why
any other soluble mineral substance should not be absorbed--it being,
moreover, proved, by repeated experiments, that they all pass into the
blood, we therefore proceed to the second class of bodies capable of
absorption.
2. Mineral substances soluble in acids.--It is apparent that if any
insoluble substance will admit of easy solution in the fluids of the
stomach and intestines, it may be brought to the condition of a soluble
one and thus absorbed. Now the gastric juice is acid. This secretion has
been variously ascribed to free hydrochloric, acetic, phosphoric, and
lactic acids; also to an acid phosphate or lactate of magnesia. There
seems to be most reason to conclude that it is lactic acid, which would
be easily formed out of the constituents of the food.[25]
But we have now only to regard the gastric juice as containing a free
acid. This would reduce to solution the carbonates and oxides of all the
metals; less perfectly when anhydrous, more easily when in the hydrated
form. In this manner are absorbed the oxides of Iron and Silver, the
carbonates of Lime and Magnesia, and other medicines of the same kind.
They would be slightly modified, being absorbed in combination with the
(lactic) acid of the stomach. In this they would differ somewhat from
the substances already soluble, which would probably be absorbed
unchanged, unless we except the alkalies and their carbonates, which
might be similarly decomposed. Even these, if given in solution, would
probably be absorbed faster than the gastric acid could be secreted to
neutralize them.
Other insoluble substances, such as calomel and metallic sulphurets,
would be more or less dissolved by the action of this acid. But as a
great part would necessarily escape its influence, being propelled
onwards by the muscular contraction of the stomach, it follows that
insoluble substances of this kind are much less active as medicines than
similar compounds introduced in a soluble state. It is also likely that
a certain quantity would be sufficient to exhaust for a time the acid
gastric secretion.
We now pass on to a third class of mineral products, which, though
insoluble both in water and in acid, yet, being soluble in alkalies,
appear to be in this way prepared by absorption.
3. Mineral bodies insoluble in water and in acid, but soluble in
alkalies.--These remain unaffected by the action of the gastric juice,
but on passing on as far as the centre of the duodenum, they meet with
two alkaline fluids. These are the bile and the pancreatic juice. We
know that some such insoluble bodies pass into the blood. It will be
shown in the proof of the next Proposition, that they cannot do so
without being first dissolved. Therefore, there must be in the
intestinal canal something capable of thus dissolving them. For this
purpose these two alkaline secretions are well adapted. As an example of
such mineral bodies, of which there are not many, I may adduce sulphur.
It unquestionably passes into the blood, and is found there in
combination with alkalies, as a sulphuret or sulphate. It has been
detected in the urine of those who were taking it, by Dr. Ronalds and
others. It is possible that iodine, bromine, and some of the hydrated
metallic oxides; may enter the blood in the same way.
4. Vegetable substances soluble in water.--These would be absorbed with
more or less readiness according to their degree of solubility. They
would probably be taken up in great part by the stomach. Some vegetable
matters--as Lignine, or woody fibre, and Resins--are insoluble in water.
Starch even is comparatively insoluble, and thus comes under another
division, being probably one of those vegetable substances which are
rendered soluble by the aid of the pepsin of the gastric juice.
These soluble vegetable matters are of several kinds. Cane-sugar and
grape-sugar are readily soluble. So also are the various vegetable
acids. There is another class of bodies which is highly important in a
medical point of view. These are the natural salts of the vegetable
alkaloids, of which are constituted so many of the active principles of
plants. In pharmaceutical operations we are enabled, by the judicious
employment of different menstrua, to extract from the crude and inert
mass these vegetable active principles, and thus to obtain in a
concentrated form the medicinal power for which each plant is esteemed.
This process is also performed in the stomach. By digestion and
concoction, with or without the aid of acid, it is enabled to dissolve
out these soluble and potent matters from the ligneous and bulky tissues
which surround them. For though the alkaloids themselves are in general
almost insoluble in water, yet their natural salts which occur in the
vegetable kingdom are mostly very soluble. The most important of these
salts are as follow. In Cinchona bark, the Kinates of Quina and
Cinchonia. In Opium, the Bimeconates of Morphia and Codeia. In Nux
Vomica, the Igasaurate of Strychnia. In Aconite, the Aconitate of
Aconitina. In Colchicum and Sabadilla, the Supergallates of Colchicia
and Veratria. There are some neutral soluble substances, not partaking
of the nature of Alkalies. Thus we find in Ipecacuanha and Ionidium,
Emetine; in Tea and Coffee, Caffeine; in Willow-bark, Salicine; and the
soluble active principles of Senna, Aloes, and Gentian, are probably of
the same nature. Many other alkaloids are known. Atropia in Belladonna,
Daturia in Stramonium, and Hyoscyamia in Hyoscyamus, occur in
combination with Malic acid. Conia in Hemlock, and Nicotia in Tobacco,
are peculiar volatile alkalies containing no Oxygen: thus in two
respects they resemble Ammonia. They too are soluble in water.
Alcoholic and Ethereal fluids may be enumerated here as soluble
products of the vegetable kingdom. Alcohol mixes with water to any
extent; and one part of Ether is soluble in ten parts of water. Nitric
Ether and Chloroform are also sufficiently soluble. So is Creosote, 1.25
parts of which dissolve in 100 of water. But this may be absorbed in
another way, as will be seen presently. Volatile Oils and Turpentine
come also under this head. They are all slightly soluble in water. The
former, when given in small doses, are probably absorbed in this way.
Turpentine, when given in large doses, may perhaps, by undergoing a
change, come under the head of vegetable substances dissolved by
alkalies. Camphor may be included here: one part is soluble in 1000
parts of water.
The soluble gummy matters of plants, when added to the substances
enumerated above, constitute an aggregate which is called the _watery
extractive_ of a vegetable product: _i.e._ that part which is capable of
being dissolved out of it by pure water.
But there are other active parts of vegetables, such as oily and
resinous matters, and some neutral acrid principles, which, before they
can be dissolved by water, require the aid of an alkali. These will be
considered separately.
We now arrive at a fifth class of matters which are taken up by
absorption.
5. Animal and vegetable products dissolved by the gastric juice.--The
most important of these are the nitrogenous and nutritive constituents
of the flesh of animals and of the parts of vegetables. Albumen,
Glutine, Fibrine, and Caseine, are connected together as compounds of
Proteine. Animal Fibrine, and the analogous Glutine of vegetables, are
quite insoluble in water. Albumen and Caseine, though soluble, are
immediately precipitated by acids. This is known to be at first effected
by the gastric juice on their entry into the stomach. But the action of
the gastric juice which contains an acid, and a peculiar nitrogenous
material called Pepsin,--together with the temperature of the body,
which is about 100°,--causes at length the gradual solution of these
previously insoluble matters. This is found to take place out of the
body when the above conditions are imitated with an artificial gastric
fluid. The result of the process is a viscid fluid, which is then
absorbed. The hard Gelatine of gristle and bone is not soluble in water
at this temperature, but is readily soluble in the acid gastric juice.
The Pepsine seems to be an important agent in this process, for an acid
by itself is found to produce an imperfect solution. The nitrogenous
matters thus digested and absorbed constitute that portion of the food
which is of most use in the nutriment of the system; for the starchy
compounds cannot be appropriated to the more solid tissues, although in
some cases they may be converted into fat, as in herbivorous animals.
(Liebig's _Animal Chemistry_, p. 113.)
Starch itself is one of this class. Tiedemann and Gmelin found that by
the action of the gastric juice it was slowly converted into Dextrine,
which afterwards changed into grape sugar. Both of these are very
soluble. From the researches of Bouchardat and others, it appears that
other fluids, as the Saliva, the secretion of Brunner's glands, and the
Pancreatic juice, possess also this power of converting starch into a
more soluble compound. So that if any of it escape the action of the
stomach-secretion, it is probably reduced to solution and absorbed in
the small intestine.
This change of starch is the first of a series of transformations, now
ascertained, the ultimate result of which is its combustion and
resolution into carbonic acid. Thus the nitrogenous compounds are called
the _nutritive_, and the starchy materials the _calorifacient_ elements
of the food. Considered as medicines, these substances belong to the
division of Aliments.
6. We have already considered some few mineral substances which are
absorbed by the aid of the free alkali contained in the Biliary and
Pancreatic secretions.[26] The sixth kind of absorbed matters consists
of some vegetable and animal products which can only be rendered soluble
by a similar agency. Fats and oils, resinous matters, and some
principles resembling resins, come under this head. Fats and fixed oils
consist of acids, as Stearic, Margaric, and Oleic, insoluble in water,
in combination with a base, Glycerine, which, when isolated, is soluble.
With a free alkali such a fat forms a soluble salt, called a soap, and
the base Glycerine is set free.
In Man the Bile and Pancreatic juice are discharged together into the
middle of the Duodenum. The fatty matters of the food are not absorbed
before they meet with these secretions. But, after they have mixed with
them, a milky fluid, called chyle, is formed, which is then taken up by
the lacteal absorbents. It passes thence into the Thoracic duct, meeting
there with an albuminous lymph, and is discharged at length into the
general circulation at the junction of the left jugular and subclavian
veins.
M. Bernard, in some papers laid lately before the French Academy,
states, as the result of his experiments, that the function of the
Pancreatic juice is to reduce the fat to the condition of a white
emulsion. He states that no milky chyle is formed when the Pancreatic
ducts are tied in dogs. He considers it absolutely necessary that
saccharine and albuminous matters should be absorbed by the capillaries
of the Portal veins, and then pass through the liver; and believes that
the sole function of the lacteals is to take up fat thus emulsified. His
experiments and inferences have received the high sanction of M.
Magendie.
M. Frerichs has since affirmed that, whatever be the function of the
Pancreatic juice, the Bile, by virtue of the alkali which it contains,
is an indispensable agent in the absorption of fats. But M. Bernard has
also found that the Pancreatic juice is always alkaline in health.
Whatever be the particular function of the Bile, it may reasonably be
concluded that the alkali contained in one or both of these fluids is
engaged in the saponification and solution of the emulsified fats. If it
were not for this, this alkali would seem without an object; and
further, it is contrary to all we know of the process of absorption to
suppose that oil could pass through to a watery fluid without the
intervention of an alkali to reduce it to the soluble state.
Thus it would seem likely that by means of the Pancreatic juice, with or
without the aid of the Bile, fatty matters are first emulsified, in
order to undergo an increase of surface, and then again saponified
before they can be absorbed by the lacteal villi.
The principal fixed oils which are used in medicine are Castor, Olive,
Almond, Croton, and Cod oils. It is certainly to be regarded as a very
beautiful arrangement in the animal economy, that those substances which
are not acted upon by an acid fluid should be subsequently subjected to
the action of a free alkali, so that by the successive action of these
solvents, together with the peculiar process of stomach digestion, the
great majority of substances taken into the system are dissolved and
rendered fit for absorption.
There seem to be other vegetable substances which are rendered soluble
by means of alkali in the way already described. Resins form an
important class of remedial agents, in which are comprised many
Diuretics, Diaphoretics, and Purgatives. They consist chemically of
peculiar acids, which, though themselves insoluble in water, combine
with alkalies to form salts which are soluble. They are certainly in
most cases absorbed. They have been found in the blood, and detected
when passing out in the urine. From this last they may be precipitated
by an acid, indicating that they are held in solution by an alkali. In
large doses they may not be absorbed, but by irritating the surface of
the intestinal canal, may act externally as Cathartics, and be expelled
by the peristaltic action which they excite. But in small doses they
enter the circulation in solution, and affect remote organs. The only
way in which they can be dissolved is by means of the alkali of the two
intestinal fluids. Among resinous medicines I may mention Catechu, Kino,
Benzoin, Storax, Peru and Tolu, Copaiba, Guaiacum, the fetid resins,
etc. Many purgative drugs, as Jalap, Scammony, and Gamboge, owe their
efficacy to resin.
There are moreover certain neutral acrid principles, similar in their
nature to resins, which are soluble only in alkalies, and thus come
under this head. Such are Cantharidin, Piperin, Pyrethrin, Colocynthin,
Elaterin, and Capsicin, obtained from Cantharides, Pepper, Pyrethrum,
Colocynth, Elaterium, and Capsicum. But it should be observed that some
of these are soluble in Acetic acid; and if, as some have supposed, this
acid exist in the gastric juice, then they might be dissolved in the
stomach.
We may add here some medicines which were enumerated also in a former
division. Creosote, not very soluble in water, is easily dissolved in a
free alkali. This substance also, like the last, is soluble in Acetic
acid.
Some volatile oils, especially Turpentine, display a marked tendency to
oxidize into resins; and being themselves very sparingly soluble in
water, may perhaps be dissolved after having undergone this change. Thus
Turpentine changes into common Resin, which consists of two isomeric
acids, Pinic and Sylvic.
Turpentine = C_{20}H_{16}
Pinic Acid = C_{20}H_{15}O_{2}
and,
C_{20}H_{16} + 3O = C_{20}H_{15}O_{2} + HO.
or, Oil of Turpentine, with the addition of three atoms of Oxygen,
produces Pinic acid, _i.e._ Resin, and an atom of water.
Now Turpentine, when given in large quantities, irritates the surface of
the intestinal canal in man, and is not absorbed. But in the horse very
large doses are found to pass through the system into the urine. It is
not likely that a large quantity should enter in solution in water. It
seems more probable that it may first in some way become oxidized, and
then dissolved as a resin. The action of turpentine resembles that of
some other substances which contain resin, as Copaiba and Balsam of
Peru.
The resins thus dissolved would pass, like other solutions, through the
mucous membrane of the intestines into the Portal capillaries.
But of the fats and fixed oils it cannot be said to be _proved_ that
they are absorbed in a state of solution, although such a conclusion is
almost forced upon us by a consideration of the laws of endosmosis. They
do not pass into the veins, but are taken up by the lacteal absorbents.
They are _capable of solution_, and are thus not in that sense an
exception to the rule of Prop. II. But in another sense they are an
exception to it; for they do not pass directly into the veins, but
through the lacteal system. It seems that the sole purpose of these
lacteal vessels is to absorb fats. Thus it appears that all soluble
substances, whether in the food or given as medicine, and in whatever
manner rendered soluble, whether by acid, by alkali, or by stomach
digestion, are absorbed in the stomach and intestines. All of them, with
the exception of fatty matters, pass directly into the blood, traversing
the mesenteric and Portal veins, to reach the liver. From this organ
they pass on into the heart through the Vena cava inferior. I have shown
also that they are mostly absorbed without material change. Supposing
the stomach acid to be lactic, it would be too weak to displace mineral
acids. It would, however, decompose a few insoluble matters, and
combine with alkalies and their carbonates, forming salts which in the
blood would again change into carbonates. (_Vide_ Prop. VI.)
PROP. III.--_That those medicines which are completely insoluble in
water, and in the gastric and intestinal juices, cannot gain entrance
into the circulation._
It may at first sight be objected to this proposition, that fatty
matters may probably enter the lacteals in an undissolved state. But
this is not proved; and besides, whether dissolved or not, we know that
they are soluble in one at least of the intestinal juices--viz. the
Bile. So that they do not come under the above definition.
We have just seen that many medicines which are given in the insoluble
form are capable of being dissolved in the fluids of the intestinal
canal. This so much reduces the list of perfectly insoluble medicines,
that it is difficult to find any that come under such a definition. But
Charcoal, the simple metals, woody fibre, and Nitrate of Bismuth, will
serve as examples.
Sulphate of Lead is often quoted as perfectly insoluble; but this is not
the case. It is soluble in a solution of acetate of ammonia. This salt
is contained in the perspiration. Thus the sulphate, when substituted
for the carbonate in some lead works at Paris, proved fatal to the
foreman, who died of colic. M. Flandin found that it poisoned a dog when
rubbed into the skin as ointment. Even some metals may possibly be
brought within the influence of weak acids when in a fine state of
subdivision, as Mercury in blue-pill. Gold in a very fine powder has
been used successfully in syphilis.
Thus the list of insoluble substances is still further reduced. But
there is no doubt that many substances which are slightly soluble in the
intestinal fluids may in great part escape this solution, and pass out
with the fæces just as they went in.
To assert that the particles of an insoluble substance cannot pass
through the homogeneous wall of the capillary or absorbent vessels, is
merely to state what follows from an absolute physical law, and is
generally admitted by physiologists. But even this fundamental datum has
been lately attacked.
Professor [OE]sterlen of Dorpat has been induced to affirm the
possibility of the absorption of insoluble substances, from some
experiments which he has made. Finely-powdered charcoal was administered
to rabbits for some days. They were then killed, and globules of
charcoal, measuring from 1/6000 to 1/3000 of an inch, were found in the
blood of the Portal circulation. (_Zeitschrift für Rationelle Medizin_,
1847.) To obtain these results the microscope was used, a far less
certain test in such matters than chemical analysis. [OE]sterlen
reasonably concludes that, if charcoal can so pass, so also can any
other insoluble substance. The necessity of solution could then at once
be done away with, and the blood continually liable to admixture with
all kinds of heterogeneous and crude materials. [OE]sterlen asserts
further that he has found minute globules of mercury under the skin
after rubbing in mercurial ointment. (_Journal für Praktische Chem._,
No. IX. 1850.) Now, if these things were true, there could be no need to
suppose the solution of insoluble active medicines, for they would be
enabled without difficulty to pass through in an undissolved state.
To test for myself the accuracy of such statements, I have made some
experiments, the object of which is to discover if some of the most
insoluble of our known remedies, which are yet known to obtain entry
somehow into the blood, could do so while yet in the insoluble state.
They are as follow:--
EXP. 1.--Ten grains of calomel were given to a large dog. It was
killed after three hours, allowing this time for digestion. A
considerable quantity of blood was collected from the Portal vein,
and submitted to analysis to determine whether it contained any
compound of Mercury in an insoluble form. The blood was dried and
pulverized. The result was boiled for some time in water, and the
insoluble part collected. It was dissolved in a small quantity of
aqua regia, and the clear acid solution placed in a test tube. A
slip of zinc foil was folded round a narrow plate made of gold
foil, and introduced into the solution. A galvanic current being
thus set up, the minutest quantity of mercury, if present, would
have been deposited on the gold, so as to tarnish it. But this did
not take place, and when at last the zinc was completely dissolved,
the gold remained as bright as before. Thus there was _no_ Calomel,
or compound of mercury, present in the insoluble form.
EXP. 2.--Ten grains of strong mercurial ointment (containing half
its weight of metallic mercury, with some oxide) were given to
another dog. He was killed after the same time, and the Portal
blood analyzed carefully in the same way, but here also _no_
mercurial compound was present in the insoluble form.
EXP. 3.--To a third dog five grains of Oxide of Silver were
administered. After three hours he was killed. The Portal blood was
dried in a water-bath, and reduced to powder. This was boiled for
some time in water, which was separated by filtration. Aqua regia
was then boiled on the insoluble part. This would convert any
silver into chloride. The acid was evaporated off as much as
possible, and the solid remainder heated in a small porcelain
crucible to dull redness. The result was powdered, and digested in
liquor ammoniæ. It was filtered, and excess of nitric acid was
added. There was not any precipitate. Had chloride of silver been
present, it would have been dissolved by the ammonia, and
precipitated by the acid. Thus no insoluble silver compound was
contained in the blood analyzed.
EXP. 4.--Ten grains of sulphur were administered in the same way to
a fourth dog. On killing it and opening the body, the thoracic duct
was found to be full. A considerable quantity of chyle was
collected from it. Now, as it is asserted by some, that fat passes
undissolved into the chyle, and as I believe that sulphur is
digested in the neighbourhood of the bile duct, this chyle was
chosen for analysis in preference to blood, as more likely to
contain any insoluble sulphur. Besides, the blood would be less
satisfactory, on account of the large quantity of albumen and
fibrine contained in it, both of them also containing sulphur. The
insoluble part of the chyle was obtained in the same manner as with
the blood. It was then boiled in a small quantity of a weak
solution of caustic potash. By this any free sulphur would be
converted into a soluble sulphate of Potassium. The solution was
filtered, and a few drops of a solution of the Nitro-prusside of
Potassium added. (This is a salt lately discovered by Dr. Playfair.
It is a delicate test for soluble sulphurets, with which it strikes
a deep purple colour.) No change was produced. Therefore no
insoluble sulphur was present in the chyle.
The results of these experiments are thus in direct opposition to those
of M. [OE]sterlen, and support a view of the question which seems even
_à priori_ more philosophical and reasonable than that which he has
adopted. I believe that no insoluble medicine can in any way gain entry
into the blood without first undergoing solution in some way or another.
PROP. IV.--_That some few remedial agents act locally on the mucous
surface, either before absorption, or without being absorbed at all.
That they are chiefly as follow:_--
_A. Irritant Emetics._
_B. Stomach Anæsthetics._
_C. Irritant Cathartics._
It has already been shown, during the consideration of the first
proposition, that medicines which act on distant parts of the body must
be, and are, absorbed before they can so act. This necessity for
absorption has been shown to extend even to medicines which act most
rapidly on the nervous system. If any medicines could produce a distant
effect by a mere contact with the coats of the stomach, such a power
would be ascribed to those stimulants and sedatives which, from the
suddenness of their action, are called diffusible. Such are Hydrocyanic
Acid and Ammonia. Their rapidity of action is to be ascribed to their
volatility, whereby they spread over a large surface, and are almost
_suddenly_ absorbed and transmitted through the blood. But Hydrocyanic
Acid may be absorbed from any surface. It is poisonous when inhaled into
the lungs. It rapidly causes death when dropped into the eye of an
animal. So also the results of the inhalation of ammoniacal gas are the
same as of the ingestion of its solution. I believe that the latter, on
account of its diffusibility and rapid absorption, escapes
neutralization by the stomach acid, and passes into the blood as free
Ammonia.
In the consideration of the first Proposition, I endeavoured to point
out that though the proper action of a medicine could in no case be
conducted, without absorption, from the mucous surface to a distant part
of the system, yet that a remote action of another kind might occur as
the result of a change in the nervous system produced by a powerful
local impression. I stated that the term _Counter-irritation_ was
employed to express this action, the nature of it being but ill
understood. A powerful impression on any surface of the body, external
or internal, seems to be capable of arresting and diverting, as it were,
the attention of the system, and thus, for a time, of checking a morbid
process.
Frictions and Sinapisms act on the skin externally on this principle. So
do Blisters and Issues; but they are not simply counter-irritants, for
they also drain away the serum of the blood. It is not now within my
province to consider such an action on the skin, any further than for
the purpose of stating that similar local impressions on the mucous
surface of the stomach and intestines are capable of operating on the
same principle.
We have then to consider what are the local actions that medicines are
capable of producing on these surfaces.
And first, it must be laid down as a rule, that all medicines, when
given in excess, act as irritants on the stomach and intestines. This is
more especially the case with mineral salts, with the bitter and
astringent principles of vegetables, and with acrid and resinous
matters. By irritating the stomach locally, they cause vomiting; by
causing peristaltic action of the bowels, purging. Some of them are
actually employed to produce these effects, and will be presently
specified.
The corrosive and narcotico-acrid poisons may produce by this local
action a degree of irritation sufficient to cause death. In the case of
the first, some erosion of the mucous surface may occur. By both kinds
violent vomiting and purging is apt to be produced, and succeeded by
symptoms of collapse. These last, however, are not _therapeutic_
agents, when in such doses.
Antidotes, employed to counteract these poisons, are remedies which are
given to act locally in extraordinary cases. There are three chief kinds
of them; Demulcents, to sheath the irritated surface, and protect it
from further injury; Emetics and Purgatives, to get rid of the poison;
and chemical antidotes, to neutralize it or render it insoluble while in
the stomach. With this last object, acids are given in alkaline, and
alkalies in acid poisoning. The soluble salts of Lead may be
precipitated and rendered insoluble by sulphuric acid or sulphates.
Those of Mercury, Copper, and Zinc, by albumen. Tannic acid precipitates
the vegetable alkaloids. There are some other special antidotes of the
same kind.
Let us now consider the three kinds of remedial agents in ordinary use,
which are employed for the purpose of producing a local effect on the
mucous surfaces, before absorption, or without absorption.
_a. Irritant emetics._--Two kinds of medicines are employed to produce
Vomiting,--specific emetics, and irritant emetics. The former act from
the blood; the latter, by local irritation. In the same way that
irritation of the external surface of the body will sometimes cause at
the same time the _direct_ contraction of a neighbouring muscle, and the
_reflex_ contraction of others at a distance, so does local irritation
operate on the surface of the stomach. On the one hand the muscle of the
stomach itself is caused to contract, so that, the pylorus being at the
same time forcibly closed, it tends to expel its contents in the wrong
direction. On the other hand, a large set of distant muscles is thrown
into sudden action. First, a quick deep breath is taken by means of the
inspiratory muscles. Then the aperture of the glottis is spasmodically
closed, so that, the lungs being full, the diaphragm cannot be pushed
upwards. Then immediately the abdominal muscles contract, and being
unable to act on the diaphragm, they press on the stomach, emptying it
forcibly of its contents.
All this is by reflex action, and follows sympathetically the
contractions of the stomach, co-operating with it, and resulting, like
it, from irritation of the sensitive mucous surface.[27] Such is the
action of an irritant emetic.
Now, Tartar Emetic and Ipecacuanha do not act in this way. When injected
into the blood elsewhere, in sufficient quantity, they are found to
produce vomiting. They have also special actions on the heart and lungs,
which are not possessed by merely irritant emetics. They seem to me to
act specifically on the Vagus Nerve, which is supplied to these organs
as well as to the stomach, and to cause vomiting by deranging its
functions. By this action on the Vagus while in the blood, they excite,
in a special way, the same reflex contractions which are produced, in
the case of an irritant emetic, by irritation of the extremity of that
nerve in the mucous membrane. They are thus Neurotics, or
nerve-medicines. They are not gland-medicines; or, at least, there is no
proof that they are excreted by the stomach, and thus they do not come
under my definition of Eliminatives. All substances which touch the
surface of the stomach cause it to pour out its secretion.
Specific emetics cause nausea, even without vomiting, depressing the
action of the heart by their influence over the Vagus nerve. Irritant
emetics scarcely cause nausea, producing only a feeling of discomfort,
arising from the inverted action of the stomach.
The Sulphates of Zinc and of Copper; common Salt, and among vegetables,
Mustard and Horse-radish, are used as irritant emetics. They cause, by
contact and irritation, a large quantity of the gastric juice to be
poured out. This, together with the emetic, and any contents of the
stomach, is rejected. The process is not followed by much inconvenience.
Such emetics are chiefly used when we wish to unload the stomach of any
irritating or poisonous matters; but not when our object is to cause
nausea, depression of the heart's action, or relaxation of the muscles.
The violent action which they produce may possibly act on remote parts
on the principle of counter-irritation. Thus emetics of various kinds
are often administered in the early stages of inflammatory disorders,
and have been known sometimes to cut them short. But such an effect is
much more likely to be produced by a specific emetic, which adds to this
counter-irritant action the production of nausea, by which the force of
the heart is powerfully depressed, and the pulse reduced. Tartar Emetic,
the most powerful of these specific agents, must doubtless be absorbed
to a certain extent before it can produce its effect. Thus the important
difference between the modes of operation of irritant and specific
emetics is, that the former do not produce vomiting when injected into
the blood, but act locally; whereas the latter act from the blood on the
nerves. (_Vide Prop. VIII., Specific Sedatives._)
_b. Stomach-Anæsthetics._--There is a class of medicines used in
Gastrodynia which seem to act locally on the sentient nerves of the
stomach, in the same way that Aconite acts on the superficial nerves of
the skin. Although the majority of them are subsequently absorbed, yet,
in order to exert this particular action, it is not necessary that they
should pass beyond the substance of the stomach itself. They do not seem
to have any special or peculiar tendencies towards the stomach nerves.
But if introduced into the blood elsewhere, they would not pass the
nerves of the stomach in so concentrated a form as when coming directly
from the mouth, and thus would not be so useful as stomach-anæsthetics.
Thus this action depends upon local contact, and is so far a local
action.
Hydrocyanic acid, Creosote, and Nitrate (also called Tris-Nitrate) of
Bismuth, are the most useful of these medicines. The first two are
subsequently absorbed, and pass into the blood. The third is a very
insoluble salt. It acts also as an astringent on the mucous surface
of the intestine, and is probably the only astringent which is not
absorbed. Being insoluble, its action is quite confined to the mucous
surface. It may be given safely in very large doses, (as [dram]ss,
or even [dram]j.) and it is likely that its anæsthetic action may be
in some part mechanical in nature, and depend upon its affording a
mechanical sheath to the irritable and painful surface of the stomach.
Hydrocyanic acid and Creosote,--general sedatives,--act locally as
anodynes to the nerves of the stomach.
_c. Irritant Cathartics._--As there are two kinds of emetics, differing
in their mode of operation, so also do there seem to be two kinds of
Cathartics. But the distinction between them is not exactly the same. As
with the Emetics, one kind seem to act by topical irritation, exciting
an outpouring of the intestinal secretions, and causing an expulsion of
the contents by exciting peristaltic contraction. But Specific Emetics,
which act from the blood, seem to produce their effect by influencing
the nerve of the stomach; so that they are Neurotic medicines. Specific
Cathartics act differently. They are truly Eliminatives. They exert no
influence over nerves, but they operate by passing out of the blood
through the intestinal glands. Like Specific Emetics, they must be first
absorbed. I will not now enter into the theory of Elimination, which I
shall have to consider afterwards, but I wish merely to distinguish
between local action on a surface, and specific action on a gland,
exerted from the blood. Many substances used as purgatives are capable
of absorption, and are absorbed. But it seems that they are not fit to
remain in the blood; and after passing round in the circulation, they
are expelled by the depurative force at a point near to that at which
they previously entered by the laws of absorption, namely, the mucous
surface of the bowels. They are most commonly expelled by the glands of
this surface somewhere in the lower or fæcal portion of the intestinal
canal, which is more engaged in secretion, but less active in
absorption, than the upper part. The increased secretion which they
excite causes peristaltic action, which expels both it and them, so that
they cannot again be absorbed.
Such a specific Cathartic would be capable of acting thus if introduced
into the system at any point. Castor Oil and Croton Oil, whether
received into the stomach, or injected into the veins, or introduced
into the system at any part, equally produce purging. So also do
Rhubarb, Aloes, and Senna. The principles of these medicines have been
detected in the blood by Tiedemann, Gmelin, and others. Colocynth and
Elaterium have also been proved to act specifically.[28]
It is to be inferred from analogy that other resinous Cathartics, as
Jalap, Scammony, and Gamboge, must also act from the blood. It has also
been shown that both from actual experiment, and from a consideration of
the laws of the process of absorption, we must conclude that saline
Cathartics are absorbed into the blood before they cause purging.
But we have now to do with Cathartics that act by topical irritation.
Which are they? I believe that the same resinous Cathartics which have
the power of acting specifically, may have, especially when in large
doses, a double action. It has been shown that resins are difficult of
absorption; and whether they be absorbed or not, we know that they must
irritate the intestinal surface, from the violent griping which often
attends their operation. Thus Scammony does not act so well, and does
not gripe, when the bowels are lined with mucus. Gamboge and Euphorbium
are irritant in an extreme degree, and are therefore too dangerous for
general use. The powder of Euphorbium resin has been used as an Errhine,
for, by irritating the mucous membrane of the nose, it increases its
secretion. This illustrates the operation of irritant Cathartics. A
great part of the fæces is secreted by the mucous membrane of the bowel.
This secretion a Cathartic may increase by mere contact and irritation;
or, being also a specific agent, by absorption and elimination
likewise.[29]
Some Cathartics employed as Vermifuges, as the hairs of _Mucuna
pruriens_, metallic Mercury, and Tin powder, cannot be absorbed at all,
and must act solely and altogether by irritation.
These Vermifuges, or Anthelmintics, are employed for a strictly local
purpose--that of killing and expelling intestinal worms. Any powerful
Cathartic may be used to expel them. But such an agent should generally
be conjoined with a medicine that tends directly to kill the parasite;
for after that it will be more easily dislodged. For this purpose the
root of Male Fern, Kousso, and the bark of the root of Pomegranate, have
been used with advantage in the case of tape-worm. Ascarides are
situated low down in the intestine, and may be dislodged by the use of
an enema, as of Salt.
Turpentine is often very efficacious in cases of this kind, being at
once a poison to the worms and a powerful irritant cathartic.
I have already alluded to Nitrate of Bismuth, as seeming to be an
astringent to the mucous surface of the intestine, although apparently
incapable of absorption. It has been used with advantage in diarrh[oe]a,
and is highly recommended by Dr. Theophilus Thompson in the diarrh[oe]a
of Phthisis.
But all other astringents are absorbed; and when they act on the mucous
glands of the intestines, it is probably from the blood.
It has been supposed by M. Poisseuille and others that the action of
Opium in confining the bowels is to be attributed to a power of checking
the process of endosmosis, said to be possessed by a solution of
Morphia. I shall afterwards state my reasons for discrediting this
explanation. (_Vide Chap. IV., Art. Opium._)
Thus we have concluded the list of substances which seem to act locally
on the mucous surface, without passing into the blood.
Having previously endeavoured to explain the various modes in which
medicines are absorbed and pass into the blood, and having now defined
the action of some few before absorption, the greater part of our
investigation remains still to be accomplished. The actions of medicines
in the blood, and their various and complicated operations in the cure
of diseases, have to be traced out, and, if possible, accounted for.
The remaining six Propositions concern the behaviour of medicines after
their passage into the blood. The first two of them are comparatively
unimportant. The Fifth is merely an extension of the First
Proposition,--in which the same rule is applied to the blood which was
there proved of a surface,--and indeed follows in part from the latter.
The Sixth Proposition defines three kinds of changes which certain
medicines are liable to undergo during their stay in the system.
PROP. V.--_That the medicine, when in the blood, must permeate the mass
of the circulation, so far as may be required to reach the parts on
which it tends to act._
_That there are two possible exceptions to this rule:_
_a. The production of sensation or pain at a distant point._
_b. The production of muscular contraction at a distant point._
We might already have concluded that, as a general rule, it is
impossible for medicines to exert their primary action on a remote part
by nervous or any other agency, but that they must actually reach the
part which they affect by means of the circulation. The experiments,
already quoted, of Magendie, Blake, Ehbert, and others, show that even
those medicines and poisons which tend most powerfully to influence the
nervous centres, cannot act by nervous connexion, or without being
allowed to pass on in the blood. They must actually reach the brain,
before they can act upon it. The circulation of the blood is
sufficiently quick to allow of this.
The action of nerve-medicines when applied to a part, being similar to
that which follows their absorption, would alone render it highly
probable that in the latter case they reached the part in the blood.
Thus Morphia, Hydrocyanic Acid, Chloroform, and Aconite, benumb the
superficial nerves: Belladonna dilates the pupil; and Strychnia augments
muscular irritability; whether locally applied, or administered through
the stomach.
Neurotic medicines have even been detected after death in the parts and
organs which they influence. Thus Alcohol has been found in the brain,
and Lead in the spinal cord and muscles.
From these various facts we may conclude that however near these
remedies may be brought to that part of the nervous system over which
their power extends, whether it be centre or periphery, they do not in
general affect it, unless they are allowed to reach it.
And what is proved of nerve-medicines holds good still more obviously
with medicines that act on the blood, and on blood disorders. Nearly all
of these have been found to exist in the blood, and to pervade the whole
mass of the circulation, wherever at first introduced.
The glands of the body form a third case in which we require proof of
actual local access. This matter will be discussed when we have to
consider the subject of Eliminative medicines, when I shall attempt to
show that the majority of those medicines actually pass through and are
excreted by the glands which they affect. When Mercury is chemically
detected in the secretions of the liver and bowels; Sulphur in that of
the skin; Turpentine and Copaiba in that of the kidneys; it is evident
that these substances must have reached bodily the glandular organs to
which their action is directed.
Astringents are medicines which from the very nature of their
action--apparently a chemical one--cannot operate at all without
touching the muscular fibre, which they cause to become contracted.
But in laying down this rule of the necessity of local access for the
production of the primary[30] effect of a medicine, we must be careful
that we do not make it too absolute. In saying that no action at all can
be propagated by the agency of the nervous system, we do not make proper
allowance for the vital properties of nerve-fibre. The vital nature of
common nerve-fibre is such that two actions can be conducted along
it;--an impulse producing sensation, or an impulse producing muscular
action, at a distant point. It is known that an impression on the
terminal extremity of a sensory nerve is capable of producing either
sensation or motion at a distance, by what is called _reflex nervous
action_. Though this impression must pass through the brain or spinal
cord, yet these centres are not appreciably affected by it. Now it is
possible, though it does not often happen, that the action of a medicine
on the extremity of a nerve may cause this distant action, without
reaching the part at which it is manifested. It may be positively
affirmed that in no other case can the direct action of a medicine be
conducted along a nerve.
Having made allowance for the physiological characters of nerve, we must
also take notice of the vital properties of muscular fibre. We sometimes
find, especially in the case of unstriped muscle, that when one part of
a muscular organ is caused to contract, a wave of contraction is
propagated along the fibres; and this action may even be extended to a
neighbouring muscle, either by contact or sympathy. In one or two cases
it seems that muscular contraction may occur in this way as the result
of the action of a medicine.
We will now consider separately the two exceptional cases.
_a._ _A medicine may occasionally produce pain or sensation at a distant
part, without reaching that part._ We often find that a morbid action at
one part of the body is capable of producing pain or uneasiness at
another distant part by a reflex nervous action. We are familiar with
instances of this among the symptoms of disease. The pain in the knee
which occurs in disease of the hip-joint; in the left arm, in some cases
of heart disease; and in the right shoulder, in disorders of the liver;
are examples. Certain impressions on the surface of the stomach may
cause such a reflex pain. Swallowing a piece of ice will sometimes
produce pain over the brow; and it is likely that the headache which
follows over-eating, or a large dose of a tonic medicine, may result in
a similar way from mere irritation of the stomach. Any irritant, as a
solution of Iron, Arsenic, or Zinc, will do the same. The action of a
violent purgative will cause headache while it lasts. Although we cannot
deny the possibility of other actions of the same kind, yet there are so
few medicines which, in ordinary and safe doses, are capable of
producing pain in any way, that it becomes difficult or impossible to
adduce a satisfactory example of an agent which operates on distant
parts in this manner when in the blood.
_b._ _A medicine may occasionally produce muscular contraction at a
distant part, without reaching that part._ This may be done in two ways;
either by a reflex nervous action, or by a propagation of the
contraction from one muscle to another in its neighbourhood. The first
of these never results from the action of a medicine while in the blood;
but it may follow an impression on a surface. Thus we have already seen
that the irritation of the mucous membrane of the stomach, and probably
of the filaments of the Vagus nerve distributed in it, which precedes
the act of vomiting, may cause the contraction of the muscles of the
abdomen.
The propagation of contraction from one muscular organ to another
appears to take place in the case of violent purgatives, particularly
some, as Aloes and Savine, which act on the lowest portion of the large
intestine, exciting it to a peristaltic contraction,--whose action may
thus be extended to the contiguous Uterus in the female, causing it also
to contract. This renders the employment of such medicines dangerous in
cases of pregnancy, as tending to produce abortion. In other cases these
agents may be useful; for by the irritation and congestion which follows
this action on the Uterus, they may cause the appearance of the
menstrual secretion when deficient or retained. This also is the result
of an action on a surface.
Now, though in such cases the action of a medicine seems to be continued
from the part where it is situated to a distant point, there are
certainly no authenticated examples of such an action by a remedy in the
blood. Yet it would not be reasonable to deny the bare possibility of
such a thing. But such instances are at all events rare, and, being
cases of the manifestation of their vital properties by nerve and
muscle, rather than of the proper action of a medicine, must not be
considered to invalidate the above proposition, which, as a general
rule, is of considerable importance.
PROP. VI.--_That while in the blood, the medicine may undergo change,
which in some cases may, in others may not, affect its influence. That
these changes may be--_
_a._ _Of Combination._
_b._ _Of Reconstruction._
_c._ _Of Decomposition._
Before advancing to the consideration of the modes in which medicines
operate in the cure of disease, it is of importance to mention that some
of them are liable to undergo changes in the animal organism, because in
particular cases these changes may materially affect their action, and
in all cases they have some bearing upon it. With a view to this point I
have divided these changes, somewhat arbitrarily, into three kinds,--of
which the first does not hinder the effect of a medicine--the second may
alter it slightly--and the third entirely changes or neutralizes it.
Some of these change have to be considered more at length in the
progress of the Essay, so that here I will only give an outline of them.
_Changes of Combination._--The chief, and indeed almost the only way of
detecting changes in medicines, is by taking notice of their effect upon
the composition of the secretions.
Now in the blood we have a slight excess of alkali; in the urine, an
excess of acid. Acids and alkalies are often given as medicines; and as
it is not right that there should be much excess of either in the blood,
both are generally soon neutralized in the system, and reduced to salts.
This may sometimes occur before absorption, but perhaps more often after
it. Now, it may seem strange for me to say that this neutralization does
not destroy their influence. But it evidently does not; for in being
neutralized they diminish in the blood, and in the system generally, the
quantity of basic or of acid matter, and thus tend to alter the reaction
of the secretions. Though an acid may combine in the blood with Soda, or
with salts of Soda, yet by so doing it causes an excess of some other
acid, probably an animal acid, which, being set free, acts on the
secretion of urine much in the same way that the first acid would have
done. It is easier to render the urine alkaline than to make it acid,
for two reasons; first, as I shall show hereafter, an acid may pass out
through other glands besides the kidneys; and secondly, an alkali is not
so easily neutralized, either before or after absorption, the blood
being already more or less alkaline.
A large quantity of acid would easily overcome the feeble reaction of
the blood, and thus, by remaining free, Sulphuric and other acids are
enabled to act as astringents on certain of the glands.
Other changes of combination have already been shown to take place
during the process of absorption. Alkalies and their carbonates are more
or less neutralized by the stomach acid. Substances soluble in alkalies
are probably absorbed in such solution. Calomel, Chalk, Magnesia, and
metallic oxides, as well as other insoluble medicines, are taken up in
the soluble form, in which only they are capable of acting. But we are
now concerned with medicines in the blood. And here I must protest
against the idea that all chemical affinities have free play in that
liquid. If it were so, many of our most valuable medicines would be
decomposed and rendered insoluble there. All the mineral salts would be
precipitated by the free Soda in that fluid. Acetate of lead would be
immediately decomposed by sulphates, and Nitrate of Silver precipitated
by chlorides. It is probable that the vital forces, as well as the
viscidity of the plasma, exert a retarding or controlling power over
such chemical tendencies.
Some substances are decomposed while passing out of the body.
Decomposing matters in the intestines and in the saliva, cause the
formation of Sulphuret of Iron, while chaly-beates are taken, which
blackens the fæces; and of Sulphuret of Lead, when lead is taken for
some time, producing the well known blue line on the gums.
_Changes of Reconstruction._--The elements of a body may be disturbed in
the system, and combined together anew, without any material or apparent
alteration of its properties. Probably many changes of this kind occur,
but only some isolated instances have been verified. Thus Tannic acid,
acquiring Oxygen, changes into Gallic. Benzoic and Cinnamic acids are
converted into Hippuric acid, which passes out in the urine. Turpentine
changes into a volatile oil, which communicates to the urine an odour of
violets. Ferridcyanide of Potassium changes in the system into
Ferrocyanide. Some of these changes will be afterwards considered more
at length.
_Changes of decomposition._--By this I mean such a disarrangement of
elements as shall neutralize or reverse the action of a medicine.
There is free Oxygen in the blood, and the most important change to
which all organic substances are liable there is _oxidation_.
This probably occurs in many cases. It always takes place with the
starchy elements of the food, and with those parts of the nitrogenous
tissues that have done their work, and are preparing to be excreted from
the body.
By this oxidation Wöhler has proved that the alkaline salts with
vegetable acids are changed in the blood into alkaline carbonates. From
being first neutral, they become now alkaline in their reaction, and
affect the urine in the same way as free alkalies.
(_Vide Hæmatics, ord. Acida, Alkalia, Tonica, Solventia._)
We have now to treat of the actions of medicines in the blood. These are
recited in the four remaining Propositions.
The seventh treats of Hæmatics, acting primarily in the blood.
The eighth treats of Neurotics, passing from the blood to the nerves.
The ninth of Astringents, passing to muscular fibre.
The tenth and last treats of Eliminatives, which pass out of the body
through the glands.
PROP. VII.--_That a first class of medicines, called_ HÆMATICS, _act
while in the blood, which they influence. That their action is
permanent._
1. _That of these, some, called_ RESTORATIVES, _act by supplying, or
causing to be supplied, a material wanting, and may remain in the
blood._
2. _That others, called_ CATALYTICS, _act so as to counteract a morbid
material or process, and must pass out of the body._
Supposing that a medicine has fairly passed into the blood, and
circulates round with it, there are now two ways in which it may behave
itself.
In the first place, it may have a tendency towards some tissues or parts
of the body, on which to exert its powers, as the nerves, or the glands,
or muscular fibre, and may use the blood only as a vehicle by which most
readily and easily to attain to these. Such are Neurotics, Astringents,
and Eliminatives. They may not affect the blood, but they must pass
through it.
But there is another and still more important class of medicines, whose
action is particularly directed towards the blood itself. The blood,
after their action, is different from what it was before. It may be a
change for the better or for the worse; but there certainly is a change.
Medical authors, with few exceptions, have been very backward to
acknowledge the existence of medicines of this description. But even
those who would fain have classed all medicines as stimulants or
sedatives, differing only in the kind or degree of their action on the
nervous system, have in many cases been obliged to confess that there is
a set of remedies which they call "Alteratives," whose action, though
slower, is more certain and more durable than that of the former. It is
allowed that they alter the condition of the blood. To suppose that they
do so by first influencing the nerves, is to adopt a circuitous and
uncalled-for explanation. It is proved that they pass into the blood. It
is known that when actually applied to nerves, they do not affect them.
From these considerations merely, without further evidence, it would
seem tolerably clear that they act by influencing the blood itself,
simply and solely. But this it will be my business to prove more at
length directly.
Such medicines, then, I have designated Hæmatics, a simple and
expressive term which has been used by others before me.
It is obviously necessary that a medicine of this class should be
absorbed.
Now some of them tend in the end to act on the nerves or on the glands,
not merely indirectly, but by bodily contact. But, whatever their
subsequent action, they exert a primary and apparent influence on the
blood itself. A little reflection will convince us that these remedies
are more efficient than any others that can be selected out of the
armory of physic.
It is easy, and satisfactory for the time, to allay nervous excitement
by employing a sedative, or by using a stimulant to communicate to the
system a temporary strength. It is easy to knock down an inflammation,
or to evacuate morbid humours, by stirring up the glands with a powerful
eliminative. But these are all at the best but temporary measures.
Unless the exigency be also of a temporary character, the disorder may
soon return with unabated violence; again is the patient bowed down by
its strong hand; again is the fatal termination seen looming in the
distance but too distinctly. Then has the physician to call to his aid
more potent means, remedies of more permanent and certain efficacy. The
disease is in the blood--ever circulating, breeding, and destroying. It
is there that it must be met; let the physician strike boldly and warily
there, if he would effect a cure.
These medicines, then, act in the blood. How they do so, and in what way
they prove of use in the cure of disease, I shall next have to show,
while attempting to prove the proposition in which I have briefly stated
this mode of operation.
Hæmatics are very numerous, and very important: I shall thus devote some
space to their consideration. But I must first lay down a broad
distinction between the two divisions of Hæmatic medicines. The diseases
in which they are used appear all to originate in the blood, however
they may manifest themselves.
Now some of these diseases originate in a want of some principle or
constituent of the blood, which want causes an aberration of the vital
functions.
Thus, in anæmia, there is a deficiency of the Hæmatosin of the blood
corpuscles. In simple debility a want of a similar nature probably
exists. In rheumatic fever and other disorders an excess of acid is
formed and eliminated, possibly from a want of the alkali by which it
should be neutralized. In common inflammatory fever there is an abnormal
oxidation of the Proteinaceous compounds, possibly arising, as we shall
see hereafter, from a failure of some principles which are the proper
food of the oxygen. In diseases causing urinary deposits there is a want
of those principles which should naturally retain them in solution. In
typhoid fever there is said to be an excess of basic matter, and a
deficiency of acid, in the blood. In pulmonary phthisis there is a
deficiency of fat in the system. In the latter stage of malignant
cholera there is an absence of watery particles in the blood. Some
suppose that in scurvy there is a want of the salts of Potash in the
blood.
These diseases, then, in some of which the want is proved, in others
partly hypothetical, may be treated by medicines which supply the
deficient matter, and thus restore a right state of things. They may
supply it to the blood directly, or else cause it to be generated there.
The former of these modes of restoration seems to be the most frequent,
and may possibly, when we shall know more of such matters, be found to
occur in all cases. This division of Hæmatics I have named Restoratives
(Restaurantia.) Their action, as we shall see, is in some cases
apparent, in others more obscure. They restore the blood directly to its
proper condition, if there is only a deficiency, but they do not in
general seem to have the power of counteracting any morbid or active
material that may exist in the blood. Nor do they, except in large
doses, exert themselves any peculiar action on that fluid. In these
respects they differ from the other division of Hæmatics. They also
differ in another important character. Each Restorative has in healthy
blood a substance analogous to, or identical with itself: it replaces
this when deficient.
Not so with other Hæmatics. There is in general nothing in the blood
corresponding to them--or if there be in some cases, they are not
introduced with the intention of supplying its wants. Thus Restoratives
may remain in the system, and are intended so to do; but these may not
remain. They must pass out. In so doing they come under the head of
Eliminatives, or that of Astringents. This is their secondary action,
distinct from their primary and most important operation. What then is
the curative action of these remedies?
A large class of diseases depends on the presence in the blood of a
morbid material, or, what amounts to the same thing, on the constant
working of a morbid process in that fluid. Some of these, as the
eruptive fevers, will run a certain course, and then come to an end.
These we cannot generally stop, but can only alleviate. But others, more
in number, and more commonly met with, tend naturally to run on for an
indefinite period, unless by any means we can arrest their progress.
Some depend on a contagious virus, communicable from one person to
another, as Syphilis. Some, as Ague, are dependent on atmospheric or
terrestrial influences. Others are due to some derangement of the
secondary assimilative processes, as Scrofula, Scurvy, Gout, and
Rheumatism. Others again, to causes that are ill understood, as
convulsive disorders and skin diseases. Lastly, some may be caused in
many different ways, as common inflammatory fever.
Now the object in the treatment of such diseases is to obtain in each
case some remedy, that shall be able to counteract this process,
something that shall destroy the morbid influence at work, and thus
restore health. Medicines that are used with this intention form the
second division of Hæmatics, which I have named Catalytics (Catalytica,)
from a Greek verb signifying to destroy or to unbind.
Now though I have a probable hypothesis to advance as to the action of
some of these, I would not have this considered as more than
hypothetical. I would not speak positively of the action of any one of
them, any more than to say that each of them tends to neutralize one or
more particular morbid poisons.
Some have tried to give a general explanation of their action, and have
talked of it as if it were easily understood by their known properties.
I am not of their opinion; and when I speak of Catalytics, I shall give
my reasons for disagreeing with them. Now each Catalytic has
peculiarities and affinities that distinguish it from all others. I have
not thought that I could arrange them more truthfully than by
subdividing them according to diseases which they tend to counteract.
How inadequately is the action of Mercury and of Iodine expressed by
calling them special stimulants, alteratives, or absorbents! Is it not
better and more correct to say at once that Mercury is useful in
checking inflammation in general, and in counteracting the poison of
Syphilis in particular? and that Iodine is effective in secondary forms
of the latter disorder, as well as in Scrofula?
These medicines, then, are specifics, in so far as they are particularly
useful in certain disorders, and in those excel other remedies; but they
are not, in the vulgar acceptation of that term, the only medicines
which can be employed in such a disease, nor is their use to be
restricted to it alone. I have already said that a Catalytic tends of
itself to work out a peculiar process in the blood. For this reason
their administration in health generally does harm. They have nothing in
the blood corresponding to them; or if so, they are not introduced to
supply its want. Thus they must eventually pass out of the body. Before
doing so, some may act on the nerves. While so passing out, they may, as
I have said, act either as Astringents or Eliminatives on the glands.
Under these heads their secondary action will be subsequently
considered.
Being thus foreign to the blood, Catalytics do not remain there to
supply a want; but just long enough to counteract a morbid action, and
are then excreted.
Such is the difference between Restorative and Catalytic medicines.
Although so far as this their action is sufficiently distinct, yet some
care is required in separating the remedies in one division from those
in the other. Sometimes both kinds are used in the same disorder. For
whenever the action of a morbid poison causes any derangement in the
proportion of the normal constituents of the blood, a Restorative may
become of use to supply this defect. Thus a cancerous or scrofulous
condition may cause a deficiency in the red colouring matter of the
blood, which may be supplied by Iron. When, as in Gout and Rheumatism,
there is an excess of acid in the system, partly due to an absence of
that basic matter which should be present to neutralize it, this may be
restored by an alkaline remedy. In both of these cases a Restorative may
be used in a disease which depends on a morbid agency. But other
remedies, Catalytic in their action, are of more direct use in such
disorders. They counteract the original poison, and striking at the root
of the evil, instead of correcting the consequences, they are more
likely to eradicate the disease.
Some medicines come under both heads, acting in different ways in
different cases. Thus Potash may be a Restorative in Rheumatism, but a
Catalytic in Scrofula.
The operation of some particular agents is rather obscure. I shall have
to show how it seems to me that the vegetable acids may act as
Restoratives in fevers; and also to explain why, of those medicines
which are used in Intermittents, I have placed Quina among Restoratives,
and Arsenic with Catalytics.
It may be remarked that the fact that Catalytic medicines produce of
themselves distinct actions in the blood has proved a stumbling-block to
the disciples of M. Hahnemann. For in some few cases their action may,
to a certain extent, simulate the disease which they tend to cure, and
has thus been confounded with it by this imaginative observer. This
partial resemblance is probably due to the fact that both disease and
remedy produce a series of changes in the same set of particles in the
blood. If it were not so, the remedy could not meet the disease. It
would be out of its province, as not acting at all in the same sphere.
But that the actions are essentially different is sufficiently proved by
the fact that they counteract each other. The remedy, moreover, is often
of equal efficacy in other different disorders. It has been shown in
Chapter II., that with regard to Eliminative medicines, the
Hom[oe]opathic theory is founded on a misapprehension of facts.
It must not be inferred, from what has been said on the importance of
blood-medicines, that I am disposed to agree with those who would
account for all diseases by some fault in the humours of the body. For
though we know that many cases of convulsive disorder, as of Hysteria,
Chorea, and Epilepsy, may be reasonably accounted for by supposing the
existence of a wrong in the blood, which has affected the nervous
system,--yet there are doubtless many nervous affections which are
primarily independent of the blood, which can only be treated by
Neurotic medicines, and even then often without benefit.
Thus far I have chiefly dealt in assertions on the subject of Hæmatic
medicines, but I am now about to attempt a thing which is more
difficult, that is, positive proof.
I shall treat separately of Restoratives and Catalytics; each division
will be divided into certain distinct orders of medicines; and of each
of these orders in turn I shall attempt to prove what is laid down
concisely in Proposition VII. To simplify this proof, that part of the
Proposition which relates to Restoratives will be divided first into a
number of minor propositions, which, taken together, imply the original
one. Each must be shortly proved applicable to each order of
Restoratives. The same will be subsequently done with Catalytics. Having
sustained the original proposition to my own satisfaction, I shall, in
some cases, venture to offer an additional hypothesis--only as
hypothetical--on the action of particular medicines.
Let us now proceed to the consideration of the first division of Hæmatic
medicines.
RESTORATIVES.
The general name given to the medicines in this division is founded upon
a fact relative to their action, which will be acknowledged of most that
I have here included--namely, that they restore to the blood certain
materials in which it is deficient.[31]
I will divide them into six orders, which are all distinct and
characteristic in their mode of action.
RESTAURANTIA.
Ord. 1. Alimenta.
Ord. 2. Acida.
Ord. 3. Alkalia.
Ord. 4. Tonica.
Ord. 5. Chalybeata.
Ord. 6. Solventia.
On reverting to Proposition VII., which treats of the action of the
first class of medicines, it will be seen that what has been there
stated with respect to the action of Restoratives resolves itself into
the following simple affirmations or minor propositions.
_m. p._ 1.--That they act in the blood, and that their effect is
permanent.
_m. p._ 2.--That there are naturally in the blood substances
which resemble or coincide with them.
_m. p._ 3.--That they are not of necessity excreted, but may
remain in the blood.
_m. p._ 4.--That they are of use when a disease depends on
the want of one or more materials in the blood.
It will be seen that the first minor proposition affirms them to be
Hæmatic medicines, according to the definition given before. The second
is required; for if there were not a necessity in the blood for
substances like them, they could supply nothing. The third also is
necessary, for if they were excreted in all cases, it is evident that
their Restorative action could not be lasting. An exception must be made
in the case of those that are used to supply something which is
necessary in order that a secretion may be properly elaborated.
Medicines of the Sixth Order are particularly used with this intent; as
also some acids and alkalies. But these are not repugnant to the blood,
like Catalytics. In the fourth place it is affirmed that being thus
fitted for the blood, and allowed to remain in it, they tend to cure a
disease which depends on the want of a substance similar in nature to
themselves.
After giving a brief account of each of the orders of Restoratives, it
will be my object to prove that these affirmations are severally
applicable to each of them.
ORD. I. ALIMENTS.
An article of food is the simplest form, and in fact the type, of all
medicines of this division. Out of the materials of the food the whole
blood is constantly elaborated, and all the tissues are constructed.
Aliments were divided by Dr. Prout into four kinds:--(1) Aqueous; (2)
Albuminous; (3) Saccharine; (4) Oleaginous. These kinds differ much in
chemical conformation. The second kind alone contain Nitrogen. The last
two are both called _carbonaceous_; but those of the fourth kind contain
more Carbon than those of the third. The following will serve to
illustrate the differences in the chemical composition of these groups.
1. Water = H O
2. Proteine = C_{40}H_{31}N_{5}O_{12}
3. Starch = C_{10}H_{10} O_{10}
4. Stearic Acid = C_{68}H_{68}O_{7}
Water is useful in dissolving the other elements, and reducing them to a
state of solution which is fitted for the formation of blood, and of the
other fluids of the body. We have already seen in what way these various
matters are dissolved and absorbed in the _primæ viæ_, and how they pass
into the circulation; that Proteinaceous and Saccharine matters pass
into the capillaries of the Portal vein, and thence onwards through the
liver; and that fatty matters are reduced to a kind of emulsion by the
intestinal juices, and pass through the lacteals into the thoracic duct,
by which they are conducted into the circulation at large.
What then are the chief uses for which these matters are required in the
system, and what great functions do they fulfil?
The nitrogenous Aliments are needed particularly to supply the growth
and waste of the muscular and nervous tissues, which both contain
Nitrogen; as also do all the parts of the body, excepting Fat. This
waste is continually going on. It depends upon the fact that, after
having lasted a certain time, the particles of all these tissues are
gradually displaced, oxidized, and conveyed away out of the blood into
the urine and other secretions. In the urine these waste matters are
found as Urea, Uric acid, and Kreatine.
The starchy and saccharine parts of the food are destined to pass
through a series of changes, which ends also in their being burnt and
oxidized, maintaining the animal heat, and forming Carbonic acid. Starch
passes first into grape-sugar, by taking into itself two atoms of water,
becoming C_{12}H_{12}O_{12}. The Ptyaline of Saliva, Pepsin of the
gastric juice, and some similar principle in the Pancreatic fluid, are
all capable of causing this first transformation. This sugar is more
soluble than Starch. When in the blood, it undergoes a further change,
the nature of which is not so clear. It is supposed to be into Lactic
acid (C_{6}H_{5}O_{5}, HO_{7}) whose equivalent number is just half that
of anhydrous grape-sugar, so that one atom of the latter may become two
of the former. This important compound was found by Berzelius, in 1807,
to exist constantly in the juice of muscle, as well as in the urine and
sweat. (_Annuaire_, 1848, p. 347.) Liebig at first controverted this,
but in 1847 he assented to the statement of Berzelius, which had already
been further confirmed by the experiments of M. Pelouze. Many modern
chemists, among whom may be mentioned Dr. Bence Jones,[32] consider that
Lactic acid, or some compound nearly resembling it, is formed at this
step of the process of changes connected with the function of
respiration. The acid next combines with free Soda, existing in the
blood; and this salt is oxidized into Carbonate of Soda and water, just
as a Tartrate or a Citrate might be. (_Vide_ page 127.) This has been
ascertained by Magnus and Dumas.
Fatty matters are used in the production and renovation of the adipose
tissues; and may also, like the last, be burnt and oxidized to support
the animal heat.
As a general rule, the diet of a man in health should contain a due
proportion of all four kinds of food; for each one of them is essential,
and has its proper function in the system. The albuminous material
cannot be dispensed with; and is also the only food which will suffice
by itself to sustain life. The mode in which it can adapt itself to
perform the office of the other varieties of food was ill understood,
until explained by the researches of M. Bernard.
From some experiments detailed in a paper read before the Académie
Française in 1848, he concluded that the liver was capable of actually
producing sugar and fat out of Proteine compounds. For he found sugar to
exist in the substance of the liver when none was to be detected in the
blood of the Portal vein which proceeds to it. His results have been
mainly confirmed by M. Lehmann. M. Bernard states further, that the
action of the liver is in some way essential to the assimilation of
saccharine matters; for he has found that when sugar is injected into
the veins beyond the liver, it passes out unaltered in the urine.
Thus the process of assimilation, whether of albuminous or of saccharine
matters, is not so easy and so simple a thing as might at first be
imagined. The study of this process is of great importance; and it
appears to afford us a clue to the causation of certain disorders of the
blood, of which I shall have to speak hereafter.
Upon the regulation of diet, one of the most important of the duties
that devolve upon the medical man, it is not my purpose to make more
than a few observations.
All kinds of food are less required by the system in inflammatory and
febrile disorders; and should then be administered sparingly, or wholly
denied, according to the severity of the case. But in Typhus fever long
abstinence would be dangerous; the patient is in peril from extreme
weakness and inanition, and, being often totally unconscious of his
natural wants, requires to be carefully sustained by constant and small
increments of animal and farinaceous food.
Water may be given largely whenever we wish to increase the amount of
any of the fluid secretions; as the urine, to render less likely the
deposition of gravel; or the perspiration, when it is desirable to
promote it in fevers or other disorders.
Albuminous food is always necessary in health, and is contained not only
in the flesh of animals, but in vegetable substances in their natural
condition. It is recommended to restrict it in the management of gouty
or plethoric patients. On the other hand, animal is more easily digested
than vegetable food in many cases of dyspepsia.
In Diabetes mellitus, when a large quantity of sugar is excreted in the
urine, it is a common practice to confine the patient to a diet of meat
and gluten bread. This latter is a tough horny material, prepared from
flour from which the starch has been separated by washing. It is thought
that if no starch be given, no sugar can be formed; but it is found
that, though both the amount of urine and the quantity of sugar in it
are diminished by this plan, yet the latter does not wholly disappear.
This may be easily accounted for, if we admit that sugar may be formed
from albumen. Water should be given sparingly in this disease; for the
more a patient drinks, the more urine he passes, and all of the same
high specific gravity.
Fat may be given in Diabetes, for it is not proved that it can be
converted into sugar; but as the contrary seems to be the case with
albumen, and it being impossible to withhold this, the cure of the
patient by mere dieting may be considered almost hopeless.
We have seen that Starchy and saccharine matters form an important
element of the food; and that, by combining in the blood with the Oxygen
absorbed in the respiratory process, they are of use in maintaining the
heat of the body. In some constitutions there is a peculiar tendency to
an abnormal oxidation of these materials into Oxalic acid. It appears
likely that Cane-sugar is more liable to this change than Grape-sugar,
although it may occur with the latter. Thus the patient is sometimes
benefited by an injunction to abstain entirely from this article of
food.
Fatty matters need not be given where there is organic disease of the
Pancreas; as in that case they are not rightly digested. This is a rare
case. They are sometimes repugnant to the stomach, from other causes.
The application of oily substances to the cure of Phthisis is a matter
of considerable importance. Of late years Cod-liver oil has been used
with more success than any other medicine, both as a prophylactic, and
as a curative agent in this disease. When this remedy is considered
separately in Chap. IV., mention will be made of several theories which
have been propounded to account for its mode of operation. Liebig's idea
that there is in Phthisis an excess of Oxygen in the system, would, if
sufficiently supported, serve to explain its action when considered
simply as oil. This Oxygen would consume the Carbon and Hydrogen in the
food, and prevent the accumulation of fat. (_Liebig's Animal Chemistry_,
part i. p. 126.) A supply of oil might then serve to restore this fat,
and afford a sufficient pabulum to the devouring element.
Thus an attention to diet is of great importance in the cure and
alleviation of different diseases; for by this means we are enabled,
within a certain limit, to regulate and control the composition of the
blood, and through it the nutrition of the body.
Thus are Aliments essentially Restorative, forming and supplying the
blood, and from it the several tissues, which are destined to work and
to endure, until, like all organic creations, their turn is come to die.
Then only are they excreted, and in a different form from that in which
they entered; at that time, developing into tissues of high
organization, they now decompose and retrograde into simpler bodies; at
first fitted for life, they are now shaping for destruction. The disease
which collectively they are intended to cure is Hunger; which is in fact
a call from the blood for the renovation of its failing constituents, a
demand for fresh supply from the body, which, because always changing,
is always requiring nutriment.
ORD. II. ACIDS.
(_Mineral:_--Sulphuric, Hydrochloric, Nitric, and Phosphoric Acids.
_Vegetable:_--Acetic, Citric, Tartaric, and Malic Acids.)
To this list may be added the super-salts of the alkalies, which have an
acid reaction.
Although the mineral differ from the vegetable acids in their ultimate
action, and are altogether more powerful than them, yet in their
proximate effects they are similar. They are all soluble in water, and,
when given as medicines, should be so diluted that they can exert no
corrosive action on the mucous coat of the stomach and intestines.
Dr. Pereira lays it down as an axiom that though they all act as acids
in the alimentary canal, yet that they enter the blood as salts. He
considers that they combine with free alkaline matters in the saliva,
bile, and Pancreatic juice. (_Materia Medica_, vol. i. p. 171.)
But this explanation seems to me to be calculated to communicate an
erroneous idea of their action. For supposing first that they did thus
combine with alkalies before entering the blood, yet as more alkaline
matter would then have to be secreted to supply that which they had
neutralized, they would thus immediately increase the amount of acid in
that fluid. The action of acids in the blood is very different from that
of their salts. Sulphuric acid does not act like the sulphates of Soda
and Magnesia, nor is the action of Hydrochloric acid the same as that of
common salt. Again, we must remember that the secretions mentioned are
either neutral or barely alkaline in their reaction, and that the acid
medicine, on passing into the stomach, would meet there with an active
absorbent surface, secreting an acid, and not an alkaline fluid. So that
it seems probable that the acid would enter the blood as such.
Now the presence of the acid is not unnatural to the blood. The mineral
acids exist there in combination, and the vegetable acids have an
analogue in lactic acid.
The blood is alkaline; which is due either to the presence of carbonate
of Soda, or (according to Liebig) of an alkaline phosphate of that base.
So that the acid, on entering into the blood, passes at once into
combination with this alkali, and the result of this is a general
diminution of the amount of basic matter in the system, and an increase
in that of acid. Thus a free acid may act as a Restorative in cases
where there is an excess of alkali in the blood. It may either remain in
the blood after entering into combination, or it may pass off by the
urine, supplying there the place of a natural acid, which it leaves
behind it in the system. It is on such a theory as this that the action
of mineral acids in typhoid and putrid fevers has been explained. I do
not mean to affirm positively that there is in these cases an excess of
alkali in the blood. Although likely, it is not proved. The explanation
is plausible.
Acids are used to correct a phosphatic deposit in the urine, caused by
an alkalinity of that secretion. The alkaline urine may be secreted so,
as has been observed in petechial fever by Dr. Graves and Dr. Golding
Bird, and in insanity by Dr. Sutherland, and may also occur in diseases
of the nervous centres; or it may be caused by a decomposition taking
place in the bladder, as in chronic inflammation, or in the case of
retention of urine from any cause. In the former case the acid may act
as a corrective to the fluids before secretion; in the latter case,
after it. But it is not always easy to cause acidity of the urine by any
medicines. Mineral acids may be excreted in other ways, and vegetable
acids are liable to decomposition in the system. (_Vide_ page 125.)
The use of mineral acids in assisting a weak digestion admits of a
simple explanation. For whatever notion we adopt as to the composition
of the gastric juice, it is certain that it contains an acid in excess.
Now an acid medicine would set free in the blood more of this acid which
it is the business of the stomach to furnish, and thus prove useful in
that kind of dyspepsia which depends on a failure of the gastric
secretion. Hydrochloric acid has been particularly recommended by those
who consider it to be the acid normally secreted by the stomach.
When not wanted in the system, it seems probable that acids pass in all
cases out of the blood in the same condition as they entered it. Thus
vegetable acids act as diuretics; and mineral, as astringents to the
glands generally. The latter, when given in excess, may prove hurtful by
causing a lithic deposit in the urine. The addition of a mineral acid to
healthy urine causes after some time a deposit of uric acid.
The action of acids on the urine is neither so constant nor so certain
as that of alkalies. In attempting to correct abnormal conditions of
that secretion, it must be remembered that its reaction is liable to
great variations in health. The whole amount passed during a day should
be examined together. Dr. Bence Jones states that the urine is most
alkaline just after meals, and most acid when a sufficient time has
elapsed for the completion of the digestive process. (_Animal
Chemistry_, p. 51.)
I shall have afterwards to consider the action of the mineral acids as
Astringents; and I must now add a few words on that use of the vegetable
acids which has gained for them the title of Refrigerants.
In febrile cases of all kinds it is often found that diluent drinks
containing the free vegetable acids, or solutions of their salts with
alkalies, act beneficially in lowering the pulse, and in moderating the
progress of the disorder. These should both be distinguished from
mineral saline drinks; for mineral salts, from their known effects on
the blood, would seem to belong simply to my division of Catalytics. But
the effect of these vegetable acids seems to be to restore the blood to
a more natural condition, and this independently of the action of the
diluent with which they are administered. Now of this effect there is no
certain explanation, but a theory, which may or may not be true, may be
ventured to account for it. Should it prove correct, it would seem that
in such cases the free vegetable acid acts as a Restorative; and that
the alkaline salt of this acid has at first the same action, but adds
to it afterwards a Catalytic operation. Let us then attempt to clear up
this matter.
It has long been considered probable, but may now be said to have been
proved by the researches of M. Becquerel, that in febrile disorders and
inflammations there is excreted in the urine an excess of Urea and of
Urate of Ammonia, substances which are formed by the oxidation of the
Nitrogenous tissues. This extra-oxidation probably arises from a
deficiency of that matter which is the proper food of oxygen in the
system. This, as we have seen, being the step between grape-sugar and
Carbonic acid, must either be Lactic acid, or something similar to it.
It must be remembered that no food is usually taken in fever; this would
at length quite cut off the usual source of this lactic acid, which is
the starch and sugar of the food, and render it necessary that the
animal tissues should continue to undergo oxidation, to maintain the
animal heat. Now if we compare the commonly received formula of Proteine
with those of Lactic acid and Tartaric acid, it will at once be seen, as
was pointed out some time ago by Dr. Murray, that the latter contain
more Oxygen, in proportion to their Carbon and Hydrogen, than is found
in Proteine, or Albumen.
Proteine = C_{40}H_{31}N_{5}O_{12}.
Lactic acid = C_{6}H_{6}O_{6}.
Tartaric acid = C_{8}H_{4}O_{10} + 2 HO.
Thus, while for 40 equivalents of Carbon, Proteine contains only 12 of
Oxygen; Lactic acid contains 40, and Tartaric 50, of that element. So it
seems that Albuminous matters, containing less Oxygen, would require
much more Oxygen for their combustion; this would produce more heat,
augment the number of respirations, and keep up the fever. And though it
has been proved by Wöhler that free vegetable acids pass out in the
urine without having undergone oxidation, yet the condition of fever
would probably be an exceptional case. Lactic acid, the natural fuel,
being deficient, the alkali with which it should combine must be present
in some excess; so it seems likely that a free vegetable acid would
combine at once with this alkali as the Lactic acid would have done, and
thus be burnt or oxidized instead of the latter. Its action would then
be simply Restorative. Requiring less Oxygen than the Proteine would
need to transform it into Carbonic acid, it would thus diminish the
number of the respirations, the frequency of the pulse, the temperature
of the body,--and in this way allay the fever. It would be strongly
confirmatory of this idea if it were proved that the amount of Urea and
Urates in the urine is actually diminished by the use of acid drinks and
fruits in febrile cases. This hypothesis can only be admitted on the
supposition that fever constitutes an exception to the general rule that
the vegetable acids pass through the blood without undergoing change.
Now, the salts of these acids, with alkalies, which are often
administered in the form of effervescing draughts, might exert the same
refrigerant action. But there would be this difference: the alkali of
the blood would not be required, the acid being already combined with an
alkali. M. Wöhler has found that these vegetable-acid salts always
undergo oxidation in the system, being converted into carbonates or
bicarbonates, and thus reacting on the secretions as alkalies. And so in
the same way it seems that the natural lactate of soda is formed into a
carbonate, the carbonic acid being afterwards freed from the base, to be
excreted by the lungs. But by this natural process the quantity of
alkali in the blood would not be increased, nor would it be augmented by
the action of a free vegetable acid. But the change undergone by a salt
of this acid would continually add to the alkaline matter already in the
system. Now, alkalies have a Catalytic action on the blood, which may
prove useful in some sthenic fevers; and therefore these salts have a
double action, and are not simply Restorative. (_Vide Alkalies_;
_Antiphlogistics_; _Antiscorbutics_.)
Rheumatism and Gout differ considerably from other fevers, both in their
nature, and in the remedies which they require. They are produced by
special morbid poisons or agencies, which we are enabled to counteract
by certain Catalytic medicines. There is in both of them an excess of
free acid formed in the system. Remedies which are apparently opposed in
nature have proved useful in these complaints. On the Restorative plan,
alkalies are the remedies required; for they neutralize the acid. But in
spite of this excess of acid, some of the free vegetable acids have been
used with advantage, particularly in rheumatic cases. We shall have
hereafter to consider how far this operation resembles the common
refrigerant action of these remedies just now considered. (_Vide
Antiarthritics._) Some obscurity rests upon the subject of the use of
Citric acid in scurvy; but as it seems to partake rather of the nature
of a Catalytic than of a Restorative action, I have placed
Antiscorbutics in the second division.
Now, though there are possibly some exceptions, yet in most cases Acids
act as simple Restoratives; but Alkalies certainly operate as Catalytics
in some disorders, and have thus to be included in both divisions of
Hæmatic medicines.
ORD. III. ALKALIES.
(Potash, Soda, Ammonia, Lime, Magnesia;--their Carbonates, and neutral
Acetates, Citrates, and Tartrates.)
We have to consider the alkalies now as Restoratives--treating of those
cases only in which they are used to restore a wanting material to the
blood or fluids of the body.
That they pass into the blood, is proved by their solubility, and their
appearance in the secretions; and that they are natural to it we know,
because they are all found in it.
Wöhler has demonstrated the curious fact that the neutral salts of the
alkalies with vegetable acids undergo oxidation in the blood, being
transformed into carbonates. (I have just said that it seems likely that
certain conditions of the system may determine this oxidation, even in
the case of the free acids.) Thus it may be easily shown how the neutral
(bibasic) tartrate of potash may, with the addition of ten atoms of
oxygen, produce two equivalents of bicarbonate of potash, together with
four of carbonic acid and four of water.
2 KO, C_{8}H_{4}O_{10} + 10 O=2 KO + 8 CO_{2} + 4 HO.
____________
=2(KO, 2 CO_{2}) + (4 CO_{2} + 4 HO.)
Again, one equivalent of the neutral acetate of potash, with eight of
Oxygen, will make one equivalent of the bicarbonate, two of free
carbonic acid, and three of water.
KO, C_{4}H_{3}O_{3} + 8 O=KO + 4 CO_{2} + 3 HO.
____________
=KO, 2 CO_{2} + (2 CO_{2} + 3 HO.)
This carbonate, easily decomposed by any acid, is equivalent to a free
alkali. Thus these salts fulfil a double function. They may supply the
respiratory process, as has already been explained. They also act on the
blood, and on the secretions, as alkalies.
Alkalies are used wherever there is an excess of acid in the system,
whatever that acid may be. Alkali should naturally be present to
neutralize it, for it is unnatural to have a large excess of acid in the
secretions, or any excess in the blood. We thus administer alkalies on
the restorative principle. They are not always excreted; but whether
excreted or not, they tend to render the secretions neutral and alkaline
by increasing the quantity of basic matter in the system. Alkalies being
more stable than acids, and being more invariably secreted by the
kidneys, it is more easy to render the urine alkaline than to make it
acid. Alkalies are thus of use in a tendency to lithic acid deposit. The
bicarbonates are probably the best for this purpose, for they may be
given in large doses, being less irritating. The celebrated Vichy water
contains bicarbonate of soda. Lime-water has been used as a solvent for
stone. These all act by first diminishing the acid of the blood, and
subsequently influencing the secretion of the urine, which secretion,
acting as a counterpoise to the condition of the blood, may be generally
taken as an index to it.
Dr. Pereira recommends alkalies in cases of dyspepsia and pyrosis, when
there is an excess of acid secreted by the stomach. He further thinks it
likely that they may aid in the digestion of fatty substances when there
is a deficiency of bile. This is quite hypothetical, and depends upon a
theory which has been shaken by M. Bernard. The same eminent authority
states that Ammonia invariably enters the blood as a salt, and thus can
exert no peculiar action beyond the coats of the stomach. I shall state
my reasons for doubting this when I consider Ammonia separately in
Chapter IV. Ammonia will be again enumerated as a stimulant--Potash as a
catalytic--and lastly, all the alkalies as diuretics.
The alkalies are useful in gout and rheumatism in diminishing the
acidity both of the blood and of the secretions. It is often
advantageous to apply an alkaline wash locally around an affected joint,
in the fluids about which the morbid process seems especially to have
fixed itself. If we may receive a certain theoretical explanation of
these two kindred diseases, still more light will be thrown on the
advantage attending the employment of alkaline restoratives. To this I
shall recur when I consider the Catalytics which are used to counteract
these same disorders, not, as here, by restoring a wanting material, but
apparently by determining the process in a different direction, and thus
checking it altogether.
The action of Catalytics is more obscure than that of Restoratives, but
there is generally a broad line between them. The most difficult case is
that of the medicines used in ague and other periodic diseases; of
these, for certain reasons that I shall state, I have grouped Quina and
tonics among Restoratives, placing Arsenic among Catalytic medicines.
It seems to me that Cinchona bears the same relation to Arsenic in the
treatment of ague, as Alkalies to Colchicum in gout; the former, in each
case, supplying a needful material, the latter neutralizing a morbid
process.
Thus, when air has been rendered impure by breathing, we may render it
again respirable by adding fresh oxygen; but still more certainly, by
neutralizing the carbonic acid.
ORD. IV. TONICS.
Under this term I intend to include only the bitter principles of
vegetables. The chief medicines of this order are as follow:
_Alkaloids and neutral principles._--Quina, Cinchonia, Bebeerine,
Narcotine, Salicine, etc.
_Bitter drugs._--Cinchona, Quassia, Cusparia, Gentian, Calumba,
Chiretta, Centaurium, Menyanthes, Rhubarb, Hops, Elm and Willow barks,
Tansy, Wormwood, Chamomile, Cascarilla.
The power by virtue of which these medicines are enabled to act as
Tonics, is due, in each case, to a vegetable alkaloid or neutral
principle, having a bitter taste. All of those mentioned above, with the
exception of Salicine, contain Nitrogen. The uses of Tonics are of a
twofold nature. Firstly, they are of use in simple debility and in
atonic dyspepsia. Here they give an appetite, increase the muscular
strength and powers of digestion, and improve the general health. In the
second place, they have all, more or less, a curative power in Ague and
other periodic disorders, caused by Marsh miasm. Many explanations have
been given of this curious and double action of vegetable bitters; and
some erroneous theories have been assumed, and false analogies
attempted, in the classification of these remedies. The subject is
certainly a difficult one, and there are, at starting, several
questions which require a distinct consideration and reply. Upon the
answers given to them it must depend whether they should rightly be
grouped with blood-medicines or with nerve-medicines; and, if the
former, with Restoratives or with Catalytics.
Do these medicines act primarily in the blood, or on the nerves? Is
their action of a permanent character? Are there any substances in the
blood which resemble them? May they remain in the blood, or are they
always excreted? If acting in the blood, are they wont to effect a cure
by supplying to it a material wanting, or by counteracting in it a
morbid process?
These questions require each a satisfactory reply, before it can be
proved that I have done rightly in classing Tonics among Restorative
medicines; for they coincide with the minor propositions in which I have
defined the action of such remedial agents.
Quina may be taken as the type of the whole order. It is the most
powerful; and the others all more or less resemble it. Perhaps Cusparia
bark comes nearest to the Cinchona alkaloids in its anti-periodic
action. It is worthy of remark, that some common bitters which owe their
efficacy, not to alkaloids, but to neutral principles, as Quassia,
Calumba, and Gentian, possess the least control over periodic
affections.
There can be no doubt that these active principles are all absorbed, and
pass into the blood. They may easily be dissolved out of the vegetable
which contains them, if not by simple water, at all events by such an
acid liquid as we find in the stomach. We possess positive proof of
absorption in the case of Quina, which has been detected by Tiedemann
and Gmelin in the blood of a patient to whom it was administered.
Having them now in the blood, we arrive at the first question. Do Quina
and other vegetable Tonics act on the blood or on the nerves? This has
been answered at once by many writers, as if it were a thing of great
simplicity. But it does not seem to be so. Tonics, as we know, have the
power of communicating health and strength in debility produced by
various causes, and also of arresting the progress of intermittent
fever. Do they effect these things by bettering the condition of the
blood, and, from it, that of the system at large, or do they at once,
and in the first place, influence the nervous system? This is an
important question, and it has been variously answered.
Dr. Pereira, in his classification of medicines, ranks them among
_Cinetics_ ([Greek: kineô], to move,) which are defined to be medicines
exerting a power over the motor system of nerves, and through them on
the muscles. But in a subsequent account of Quina, he states that its
action is quite inexplicable, and that its use in Ague must be ranked
with some other special and ill-understood actions, as that of Mercury
in Syphilis, or of Arsenic in Lepra.
Dr. Neligan, (in his work _On Medicines,_) lays it down that Tonics act
as stimulants when given to a healthy man. Dr. Pereira, on the contrary,
states what is more consonant with general experience, _i.e._ that a
moderate dose of a tonic has little or no effect on a man in perfect
health. Dr. Neligan admits that their action is permanent, and produced
slowly; he also declines any explanation of the action of Quina and
others in Ague, calling them specifics.
Some other authors have been still more decided in classing Tonics with
nerve-medicines. Dr. Guy, (in his edition of _Dr. Hooper's Physician's
Vade Mecum_,) considers that Stimulants and Tonics should rightly be
classed together, for that Stimulants act as Tonics to the weak, and
Tonics as Stimulants to the strong.
It should be observed, that the irritant action on the stomach of a
large dose of a bitter medicine appears to have been the chief
foundation of this frequent opinion of the stimulant action of tonics.
The irritable stomachs of nervous persons are more easily affected in
this way. Some too are met with who bear Tonics worse than others, on
account of an idiosyncrasy or peculiarity of constitution. But this
irritation, and the headache and febrile symptoms which succeed to it,
do not surely constitute the proper action of a tonic medicine, which is
found to operate most favourably when given in too small a dose to
produce any thing like a stimulant effect. Nor do I think it proved that
any true stimulants are capable of communicating a permanent tone to the
system, or to any part of it.
Dr. Ballard also, (in _Ballard and Garrod's Materia Medica_,) states
that Tonics acts first upon the nerves, and through them on the muscular
system. He opposes them to Sedatives, and ranks them with stimulants;
quoting Strychnia as an example of a stimulant which gives tone to the
muscular system. But, in the first place, this alkaloid is quite
exceptional among stimulants; and further, the comparison with Tonics
seems unnatural, inasmuch as the action of Strychnia is more or less
immediate, not slow and permanent, and it evidently influences the
spinal system of nerves in the first place.
The results of large doses of Quina, in producing determination of blood
to the head, ringing in the ears, and vomiting, seem to me to mark its
action as an irritant poison, and not to be characteristic of Tonic
medicines. (_Vide_ p. 91.)
The action of Tonics has been more correctly defined by another able
authority. "Tonics," says Dr. A. Billing, "are substances which neither
immediately nor sensibly call forth actions, like stimulants, nor
repress them, like sedatives, but give power to the nervous system to
generate or secrete the nervous influence by which the whole frame is
strengthened."
This definition I would accept in a modified sense, considering that no
permanent alteration in the nervous system can be produced without a
primary impression on the blood. Dr. Billing further considers, that the
supposed stimulant action of Tonics in some cases should either be
attributed to the operation of the disease, or of some other medicine
administered along with them; and that though in large doses they may
sometimes produce a quick pulse with headache, and in other instances
depression with nausea, yet that these effects should be ascribed merely
to their irritating action on the stomach.
On the whole, it seems to me that those authors who, in defining the
action of Tonics, have commenced by saying that they act on the nervous
system, have started with a mistaken notion; and I am more of the
opinion of Dr. A. T. Thomson, who classes them as medicines which act on
the muscular and sanguiferous systems.
I consider, then, that Quina is not in the first instance a Neurotic
medicine; and for the following reasons. The action of other
nerve-medicines is distinguished by the following signs. It is quick,
and very rapidly follows the administration of a substance. It is
transient, and does not endure. It requires no particular state, but
takes place in health: thus Alcohol stimulates and intoxicates both
healthy and sickly, and Digitalis would subdue a Hercules. Most
Neurotics are capable of acting without entry into the blood at large;
mere contact with the nerves, as when they are applied externally, being
sufficient for their action on those nerves. Again, Neurotics are
chiefly used in cases in which the nervous system is unusually excited
or depressed, and are of no permanent efficacy in diseases depending on
blood-disorder. The action of Hæmatics is of an opposite kind.