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:—

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 ʒss, or even ʒj.) 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 diarrhœa, and is highly recommended by Dr. Theophilus Thompson in the diarrhœa 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 Homœopathic 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.

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 C₁₂H₁₂O₁₂. 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 (C₆H₅O₅, HO₇) 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.

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.

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.

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 (κινεω, 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.

Now is the primary action of Tonics distinguished by the above signs? Are they quick and sudden in action? Is their effect transitory? Is it evidenced in health as well as in disease? Do they act on the superficial nerves, when applied to them? In each case the answer must be a negative. In all of these particulars the operation of vegetable bitters differs from that of Neurotics, and coincides with that of Hæmatic medicines.

It appears that their action on the nervous and muscular systems is secondary. They could hardly in either case effect any permanent improvement without first acting on the blood, if we may argue from known analogies. For Neurotics and Astringents, which operate directly on these two systems, are alike transitory in the results of their action.

Another demonstration is required, before the presumption thus established can approach to a certainty.

We require proof to show that the disorders in which Tonics are used are blood-diseases. This does not seem to be difficult.

The condition of Debility, whatever its proximate cause, seems always to be traceable in the first place to a want in the blood, which interferes with the due exercise of their functions by the nerves and other organs, by impairing their nutrition. It follows fevers, and accompanies chronic diseases, in both of which cases the blood has been exhausted by continual waste and excretion, without the maintenance of a proper supply. In cancerous, scrofulous, scorbutic, and dyspeptic habits, the blood may be deteriorated by a fault in the assimilative processes. When in these instances there is marked Anæmia, iron may be of most service; but when the blood is poor without any apparent deficiency of red colouring matter, then are bitter Tonics needed to improve its condition, and form a valuable adjunct to the special remedies that the case may require. They ought not, as a general rule, to be administered in high fever, or when the pulse is hard, the tongue coated, or the stomach irritable. A loss of appetite, a nervous headache, a soft compressible pulse, a quivering tongue, a flabby condition of the muscles, with general inertia and indisposition to exertion, are indications for their employment. In some cases emetics and antimonials, in others mild purgatives, are of use in preparing the system for their reception.

It seems then that Debility is to be attributed generally to the state of the blood; and is to be cured by improving it. By so doing we may communicate tone to the muscular system, improve the appetite, and increase the nervous force.

Ague, or Intermittent fever, is also a blood-disease. If it were only from the analogy of other fevers, we might infer this. But there are more particular proofs. This disorder is caused by the exposure of the system to a certain peculiar poison or miasm, which is generated in the ground in certain places, and subject to known laws. The result of the influence of this miasm is a process in the blood which has been compared to fermentation, and which produces regularly recurring paroxysms of a peculiar kind. There is apparently some disturbance in the great calorifacient process, in which the blood is concerned, and not the nerves. Each fit commences with shivering; there is then a hot stage; and finally sweating. The attack then goes off, seemingly as if the poison that caused it were eliminated in the perspiration. But it is not all gone. After working in the blood for a definite period, most commonly two days, it again breaks out, and the same train of symptoms recurs. Thus this strange disorder, both in its origin and in its progress, appears to be seated in the blood. So also are its results evidenced there. Continual Ague deteriorates that fluid, causing general anæmia, and producing more or less enlargement of the spleen, which could only be brought about by some faulty condition of the circulation.

Against these proofs it has been urged that the nervous system has certainly an influence over this disorder, for that a sudden alarm has been known to arrest it. But this may occur also with other blood-diseases, and it does not prove that the nervous system is at all connected with their origin. It can hardly be supposed that Goitre or Scrofula is ever caused by a derangement of the nerves. And yet Baron Alibert relates an authentic case of a French lady who had a large goitre, which for a long time resisted all treatment, but which nevertheless disappeared entirely during the brief Reign of Terror in the French Revolution. In addition to these arguments it may be urged that Ague is often, if not always, connected with deranged hepatic functions, a fact that again points out that disease as a blood-disorder.

Seeing then that the medicines of this order of Tonics differ in each particular of their action from those remedies which influence the nerves directly, and that the diseases in which they act beneficially are essentially blood-diseases, there are sufficient grounds for concluding them to be Hæmatics, or blood-medicines.

We have now to consider the remaining minor propositions, which treat of their action as Restoratives; to ascertain whether they have been rightly allotted to this division.

Are there in healthy blood any substances which resemble them? This will appear to be a question of no small difficulty, when it is considered how little information we have actually obtained respecting the chemical composition of the vital fluid. It is nevertheless desirable that we should inquire into it to the best of our ability.

During the last few years, many propositions, intended to throw a light upon physiological science, have emanated from the fertile pen of M. Liebig of Giessen, who is rightly and universally ranked among the most illustrious of modern chemists. There are two which especially bear upon the present subject. In his first work on Organic Chemistry (p. 182,) he argued, that whereas the alkaloids Quina and Morphia resembled the brain substance in their chemical constitution, they were therefore enabled to exert a direct control over that organ by influencing its nutrition. But it is impossible to accept this explanation. The composition of the brain has been since more accurately investigated, and it has been shown to consist mainly of a mixture of albumen and fat. Now there is no reason why these substances should have a special affinity for albumen and fat in the brain, any more than for the same elements in other parts of the body. There is also no analogy at all between Quina and Morphia as medicines beyond their resemblance in chemical constitution. The theory seems to be altogether groundless.

Another, and a more important suggestion has been made by the same chemist. He has pointed out a chemical analogy between certain vegetable compounds and a substance which exists in the bile. He has shown that for the most part the elements of the bile re-enter the blood after passing into the intestine, scarcely more than the colouring matter being finally excreted with the fæces. He has found that if an enema of bile be injected into the rectum, it becomes absorbed there, and does not afterwards pass out into the urine.[33] (Animal Chemistry, p. 77.) What the exact function of the bile may be, is as yet undecided. Its most important constituents are, a non-saponifiable fat, Cholesterine; a neutral substance, Taurine; and an acid called Choleic, in combination with Soda,—which latter is present in excess. Bile is bitter to the taste; and ox-gall, or the bile of an ox, has been found, when administered as a medicine, to have an action which resembles that of Tonics. It appears that both the bitterness and the tonic action reside in the Taurine.

M. Liebig has pointed out an important chemical resemblance between this Taurine and the vegetable alkaloids. Of these he has singled out Caffeine, the peculiar principle of Tea and Coffee, as most analogous to the biliary product. From the analysis of these two substances he has deduced the following formulæ.

Then he shows that an atom of Caffeine, if added to 9 of water and 9 of oxygen, will form two atoms of Taurine. (Organic Chemistry, 1842, p. 180.)

It should be remarked that a different formula for Taurine has been arrived at by M. Lehmann and others, who assert that it contains Sulphur. Choleic acid, and other constituents of this complicated fluid, certainly contain sulphur. But even if Sulphur be combined with Taurine, it is not clear that it enters with it into the blood. And the above formula for Taurine has been confirmed by the analysis of M. Löwig.[34] It seems to be sufficiently correct for our purpose.

With the supposed function of Caffeine as a creator of bile, however probable or interesting, we are not now immediately concerned. We are engaged in inquiring whether there is naturally in the blood any substance which resembles the tonic alkaloids. Liebig has shown that this element of the bile is intended for re-absorption into the circulation. And without theorizing at all on the subject, it may readily be demonstrated that, with the existence in the blood of such a material as Taurine, we cannot say that we have not in that fluid an analogue to substances like Quina. Taurine is soluble in water, and crystallizable; is chemically analogous to the tonic bitter principles; and contains the same four elements as Quina. If necessary, this similarity could be exchanged for identity, and Quina could be formed into Taurine in the blood.

If there be one change in the blood to which, more than to any other, the substances which enter it are liable, it is certainly the process of oxidation. Free oxygen is continually entering the blood through the air-cells of the lungs.

The formula for Quina is C₂₀H₁₂NO₂. Adding to this 45 atoms of oxygen, we could make out of it one atom of Taurine, together with 16 of Carbonic acid, and 3 of water.

Thus it is conceivable that this and similar alkaloids may at the same time supply an important material to the blood, and serve as fuel to support the animal heat, by combining with oxygen and giving off Carbonic acid. I would not, of course, affirm that this actually does occur; but if it were to take place, we might gain, in this oxidation of Quina, some clue to the production of that quickening of the pulse and increase of the general temperature, which are affirmed by some to follow the ingestion of the alkaloid, even in small doses. But it is now sufficient for us if we have ascertained that there is naturally in the system, and in the blood, a substance which resembles Quina. We may be allowed to infer that the presence of the latter substance in that fluid would not be unnatural to it.

Having dismissed the second of the minor propositions which relate to Tonics as Restorative medicines, we pass on to the third. Are Quina and the vegetable bitters necessarily excreted from the blood?

It is not easy to answer this question with certainty, because it would be difficult to detect small quantities of this alkaloid in any of the secretions. But all that is known on the subject is in favour of a negative answer. A number of careful and elaborate experiments on the passage of medicines into the urine have been made by M. Wöhler, and in the long list of substances detected by him in that secretion, Quina is not mentioned. Neither has it been found in any other of the secretions. The same may be said of all the Tonic principles. There is no proof that they are necessarily excreted, but there is every reason to suppose that they may remain for a while in the blood.

Let us then consider the last question. Can Quina, or substances like it, improve the condition of the blood when deficient in any of its natural materials. We know that it is capable of curing simple debility, ague, and remittent fevers. It appears that it has also been successfully used of late by Dr. R. Dundas, in large doses, in the treatment of typhoid or continued fever. Supposing it to be proved that this agent operates in the blood, does it remedy a disease by supplying something wanting, or by counteracting something present in that fluid? In fine, is it a Restorative or a Catalytic medicine?