A. By uniting those substances which are calculated to produce the SAME ULTIMATE RESULTS, although by totally different modes of operation.

It has been already stated, (page 152), that we may frequently combine substances together whose modes of operation are dissimilar, with considerable advantage, provided they be not physiologically incompatible with each other. We may illustrate this subject by a reference to the operation of purgatives; a series of medicinal substances may be produced, each of which has the property of exciting catharsis, but by a very different mode of action; one for instance stimulates the muscular fibres of the intestines; a second acts upon the exhalant vessels, and mucous glands; and a third exerts its influence upon the neighbouring organs, so as to produce an increased flow of their secretions into the bowels; but since such modes of action are quite compatible with each other, they may be simultaneously established, not only without any loss of efficacy, but with the most decided advantage; suppose, for instance, we administer a substance which, either from its insolubility or peculiar nature, acts exclusively upon the muscular fibres of the alimentary canal, its peristaltic motions will be undoubtedly thus increased, and the contents of the bowels evacuated, but the operation will be slow, and probably accompanied with considerable tormina; now it is evident that if to such a remedy we add those which can produce an increased flow of serous fluids, the effect will be both quicker and easier. The infusion of Senna is thus quickened and corrected by Soluble Tartar. In the same manner various substances included in the class of diuretics, which, although different, still if they be not adverse in their operation, may be conjoined; Digitalis and Potass are not similar, nor are they incompatible, for while the alkali, through the medium of the circulation, stimulates the secreting organs of the kidneys, the foxglove may, by its sympathetic action, rouse the energy of the absorbents. In the administration of diaphoretics we shall frequently derive additional force, as well as certainty, by combining those which act by relaxing the cutaneous emunctories, with those which prove diaphoretic by imparting a general increase of momentum to the blood.

B. By combining Medicines which have entirely different powers, and which are required to obviate different symptoms, or to answer different indications.

Arrangements constructed upon this principle constitute some of the most valuable remedies with which we are acquainted; they are in general extemporaneous, because their value depends upon their being varied and modified according to the symptoms and circumstances of each particular case. The following general elucidation of the subject may serve to demonstrate the nature and importance of such combinations.

Purgatives with Antispasmodics. The practice suggested by Drs. Stoll and Warren, in the treatment of Cholica Pictonum, affords a striking example of the expediency of combinations of this nature. It is found in that disease, as well as in others attended with spasmodic constriction of the intestinal canal, that purgatives produce no effects unless the spasm be allayed by combining them with Opium, (see Form. 71, 75, 76,) it is from such a cause that the purgative so popular with tailors and shoemakers, and which consists of Aloes with Sagapenum or Galbanum, affords such prompt relief in the spasmodic cholic to which they are subject.

Purgatives with Tonics. In the exhibition of cathartics how frequently it occurs in practice that the patient’s strength will hardly allow the evacuation; in such a case the addition of steel as a roborant (Form. 72, 92, 93,) or even of æther, or ammonia, as a diffusible stimulant, is strongly indicated: the Cheltenham waters offer a natural combination of this character. So again in the cure of dropsy we have often two indications to fulfil—to evacuate the water, and to support the strength of the patient; hence the necessity of combining brisk and stimulating purges, such as Scammony, Jalap, &c. with active tonics, (83.) In the treatment of amenorrhæa the same medicinal arrangement is not unfrequently indicated.

Purgatives with Mercurial Alteratives. In habitual costiveness, where there appears to be a deficiency of bile, a combination of Pilula Hydrargyri, with certain Aloetic compounds, may prove serviceable; for while the latter remedy will, in the absence of bile, supply to the intestines a congenial stimulus, the former will tend to restore the bilious secretion by its influence upon the hepatic system. See Form. 79, 81.

Purgatives with Diaphoretics. This combination of effects is often useful in practice, but it is desirable that the latter should not be established until the operation of the purgative upon the bowels has subsided. This is accomplished by certain doses of Tartarized Antimony in conjunction with some purgative. The Pulvis Aloes Compositus of our Pharmacopœia produces a somewhat similar effect.

Diaphoretics with Tonics. How frequently is the practitioner desirous of determining to the skin, and at the same time of supporting the strength of the general system? in the progress of a continued fever we are repeatedly called upon to fulfil such indications. Dr. Bree^[260] also observes that “in the exhibition of Diaphoretics the addition of a bitter infusion, or tincture, is frequently proper; for the stomach should be gently excited and strengthened during the use of a diaphoretic draught.” On the other hand, Tonics not unfrequently require the aid of a diaphoretic; for instance, in the cure of Cynanche maligna, the use of bark is indicated; but if the skin be hot and dry, it should be accompanied with a diaphoretic. See Form. 126.

Antispasmodics with Tonics, or Narcotics. Under the history of Antispasmodics, (page 78) it is stated that there are certain bodies which seem to exert an absolute control over inordinate muscular action, from whatever general cause it may have arisen; in administering such remedies, however, the intelligent practitioner will not overlook the peculiar condition of the system in its relations to the disease; where debility is present, the Antispasmodic will be usefully combined with a Tonic; and, in certain morbid states of the nervous system, with a Narcotic.

Astringents with Diaphoretics. Dr. Fordyce has observed, that combinations of this kind are often indicated in cases of Diarrhœa, where it is necessary to astringe the vessels of the intestines, and at the same time to relax those of the skin; such an indication, he says, may be fulfilled by exhibiting Tormentil root, or any other vegetable astringent, with Ipecacuan.

Astringents with Narcotics, and Absorbents. It has been already observed, that in a Diarrhœa, depending upon the influx of acrid fluids into the intestines, there are three modes of treatment by which the malady may be obviated, viz. by a narcotic, diminishing the irritability of the intestines; by an astringent, restraining the serous excretion; and by an absorbent, neutralizing the acrid matter. As the modes of action are not incompatible with each other, they maybe simultaneously established with the greatest advantage. See Form. 52.

Astringents with Tonics. A combination of certain medicines belonging to these two classes is frequently indicated; in the treatment of passive hemorrhage, we have to astringe the bleeding vessels, and, at the same time, to cure the hemorrhagic diathesis by remedies which are capable of restoring the general tone of the system. In the treatment of the chronic and humid coughs of old persons, I have very frequently witnessed the beneficial union of the warm and stimulating influence of Myrrh with the astringent effects of Sulphate of Zinc. Form. 69 presents the combination which I have usually adopted with success on such occasions.

Diuretics with Tonics. As Dropsy is frequently associated with great debility, the practitioner should combine his diuretics with some tonic medicine; but in forming a judgment upon the case he must be guided by those precepts which have been laid down under the consideration of Diuretics at page 97. See Form. 114.

Diuretics with Aromatic Stimulants. Such a combination will be found advantageous in those cases where the powers of the system require to be excited by more prompt measures than those afforded by the agency of tonics. Ethereal preparations, with Squill and other stimulating diuretics, are well calculated upon such occasions to afford valuable assistance. Form. 101–116.

Tonics with Diffusible Stimulants. In the cure of dyspepsia, we frequently require a remedy, for the purpose of obviating debility, that is more sudden in its action, and prompt in its effects, than that of a bitter tonic, whose operation is almost imperceptible; while the case may at the same time stand in need of that permanent increase of tone, which the latter remedy can alone supply; such an indication therefore must be fulfilled by combination. Form. 40, 42.

Tonics with Purgatives. In the exhibition of tonic medicines it is frequently essential to accompany their operation with purgation; in intermittent fevers, for instance, when attended with a redundant secretion of bile, or any obstruction of the viscera, the bark must be given in combination with some laxative, for which purpose Boerhaave has recommended Muriate of Ammonia; Mead, Rhubarb; whilst in many cases, experience suggests the propriety of selecting some of the warmer cathartics, especially the Alöetic: and I shall take this opportunity to observe, that notwithstanding the opinion so strongly expressed by Sydenham, that “to add any thing to the bark argues either ignorance or craft,” the most respectable testimony may be adduced to demonstrate the great advantages which have arisen from the various combinations of this heroic remedy. Sir George Baker has said that “there is less of reason than of severity,” in the above remark of Sydenham; for that it was found in the cure of the intermittent fever, which he describes, that, according to circumstances, sometimes the Virginian snake root, and in other cases Myrrh, were added with propriety and advantage; and, according to the experience of several practitioners, a drachm of the rust of iron, and the same quantity of the powder of black pepper, added to each ounce of bark, were the means of subduing the most inveterate agues. Formula 44 presents a combination, which we learn from Dr. Petrie’s letter to Sir George Baker, constitutes a celebrated Dutch remedy for an ague, and which was tried with success in the hospital at Lincoln, in those obstinate intermittents which prevailed in the year 1781. Hillary speaks of an epidemic intermittent at Barbadoes, in which the bark was of no avail, unless combined with saline remedies, or some of the tonic bitters. Dr. Barton has stated that Bark combined with Mercury in a small proportion, is one of the best remedies for removing the swelling of the spleen after an intermittent.

Expectorants with Diffusible Stimulants. We have seen that expectorants may be usefully associated with tonics; it sometimes occurs that these remedies require the addition of some diffusible stimulant. In certain states of Peripneumonia notha, where the powers of life are ebbing, and the lungs become inundated with viscid mucus, I have experienced the value of a combination of some stimulating expectorant and ammonia.

Antacids with Tonics. In the cure of cardialgia we have obviously two indications; to neutralize the offending acid by some chemical agent, and to correct the morbid state of the digestive functions by some appropriate remedy. See Form. 152. The same observation will apply in the treatment of certain cases of chlorosis, where cardialgia is not unfrequently a very vexatious attendant, and solicits the union of emmenagogues with antacids, or absorbents, as in Form. 99.

Lithonthryptics with Narcotics. As a palliative in calculous irritation, the union of alkalies and opium proves a valuable resource. Henbane may likewise be advantageously combined with a Lithonthryptic; for, be it remembered, that few narcotics are more efficacious in allaying nephritic irritation. (Form. 156.) We have also frequently two important indications to fulfil in the treatment of urinary concretions; where the lithic acid diathesis prevails, it will be necessary to neutralize any acidity in the first passages, and at the same time to regulate the functions of the skin; we have moreover to give tone to the digestive organs; so that, in such cases, the art of medicinal combination is well calculated to extend our resources.

In the formation of these compounds we should rarely attempt to fulfil more than two indications, although cases may occur in which it will be eligible to assail the disease with an engine of triple powers, as exemplified by Form. 52 .

In constructing, however, such complex arrangements the practitioner must of course take care that he does not fall into the error of Contraindication, and combine substances which possess properties essentially different, and which are at variance with, or directly opposed to each other; it is an error of the most serious description, and unfortunately is one of too common occurrence in the lower walks of medical practice; “crimine ab uno disce omnes.” I lately met with a country practitioner who, upon being asked by a lady whom he attended, the intention of three different draughts which he had sent her, replied, that one would warm, the second cool her, and that the third was calculated to moderate the too violent effects of either; thus it is that discredit and contempt fall upon the use of medicines, which ought only to attach to the ignorant pretenders, or designing knaves who administer them.

Having, in the commencement of this inquiry, stated that all the principles of combination, capable of practical application in the construction of extemporaneous formulæ, are exemplified in the composition of the various productions of Nature, I shall conclude the present section by shewing, that many of our most valuable vegetables owe their useful properties to the joint operation of the several distinct and different ingredients which enter into their composition. How many substances does Nature produce in the vegetable kingdom, in which the permanent tonic quality of bitterness exerts its influence in union with the transient stimulating powers of an aromatic principle? indeed there is a series of vegetable remedies of this kind: commencing with those that are simply bitter, we gradually proceed through the different species, each blending as we advance an increasing proportion of aroma, until we arrive at those in which the aromatic quality greatly preponderates. Peruvian Bark may be said to combine within itself the properties of bitterness, astringency, and aroma; a fact which suggested the probability of our being able to produce an artificial compound that might emulate the effects of Cinchona, and to a certain extent the idea appears to have been realised; for we are told by Dr. Cullen, that he frequently succeeded in the cure of an intermittent by a combination of Oak Bark and Gentian, when neither bitters nor astringents, separately, produced the least impression; and I am informed by Dr. Harrison, that in the Horncastle Dispensary, of which he was for many years physician, he never employed any other remedy for curing the ague of Lincolnshire than equal parts of Bistorta (astringent) and Calamus Aromaticus (bitter and aromatic), neither of which plants, individually, ever produced the least benefit in such diseases. Berzelius attempted to produce a compound of this description by adding to the bark of the Ash some Tormentil root and Ginger; and he observes that it acted as an excellent tonic, and that according to the experiments of his friends it seemed to cure quartan agues.^[261] In the aromatic barks and woods, such as those of the Canella, Orange-peel, Sassafras, &c. the aromatic principle^[262] is combined with a bitter ingredient; a union which proves of singular service in the formidable bowel complaints so common in tropical climates.

The great superiority of the hop, as an ingredient in our malt liquors, depends upon the fact of its containing within itself several distinct and independent elements of activity, which the other bitter herbs that have at different times been employed as its substitute, do not possess. The philosophy of its operation may be adduced as a striking illustration of the present subject; first, then, it contains a bitter principle, which imparts to the beverage a tonic quality and an agreeable flavour; while at the same time an aromatic ingredient adds a warm and stimulant property and modifies the bitterness; the hop, moreover, contains an astringent ingredient (Tannin and Gallic Acid), the effects of which are to precipitate the vegetable mucilage, and thus to remove from the beer the active principle of its fermentation; every attempt therefore to substitute an ordinary bitter for that of the hop must necessarily fail, unless a compound can be so artfully constructed as to contain in due proportions, the principles of bitterness, astringency, and aroma. Quassia must therefore necessarily prove but a sorry substitute; it will impart bitterness enough, but it will not be modified by agreeable aroma; and as it contains no astringent principle, it will fail in precipitating the vegetable mucilage, or gluten; in consequence of which the beer so manufactured will be in a perpetual state of fermentation until it is entirely spoilt.^[263] Rhubarb is another medical plant which may be brought forward in elucidation of the analogies subsisting between natural and artificial combinations; in this case Nature has presented us with a singular and most important union of medicinal powers,—that of an astringent, with a cathartic property! virtues, which we might, without the light of experience, have pronounced to be incompatible with each other; and yet we find that in this instance the property of astringency never interferes with, or opposes the purgative force, since the former does not display itself unless the substance be administered in small doses; or, when given in larger ones, not until it has ceased to operate as a cathartic.

IV.
TO OBTAIN A NEW AND ACTIVE REMEDY NOT AFFORDED BY ANY SINGLE SUBSTANCE.

A. By combining medicines which excite different actions in the Stomach and System, in consequence of which New, or modified results, are produced.

This constitutes by far the most obscure part of the subject of medicinal combination, and must ever continue so until we become better acquainted with the laws which govern the action of medicinal substances upon the living system. That the most valuable effects, however, are really produced by such arrangements, we have the testimony of long experience, and examples are furnished in the valuable and well-known operation of many officinal preparations; thus the “Pulvis Ipecacuanhæ compositus” contains as its active elements, Opium and Ipecacuanha; and yet, in well regulated doses, it neither possesses the narcotic operation of the former, nor the nauseating effects of the latter; they appear to be mutually lost, and converted into a powerful diaphoretic: so again, the emetic operation of Sulphuret of Antimony, and the specific influence of Calomel, are changed by combination with each other, giving rise to a remedy eminently distinguished for its powers as an alterative. Dr. Bree observes that Tincture of Squills combined with Extract of Henbane, and the Nitric Acid, have been proved by much experience to be expectorant and sedative in a paroxysm of asthma, although each article, uncombined, had been given without success. See Form. 139. The efficacy of Hemlock, in quieting Pulmonary irritation, has been frequently adverted to in the course of this work; I have to state, in this place, that its value, on such occasions, is generally enhanced by combination with Ipecacuanha.

It is probable that many of our natural remedies owe their efficacy to the results of a similar species of combination. In the fourth edition of this work it was stated that, according to the assertion of Dr. Chapman, “Kino, when administered in union with Calumba, constituted a pretty certain, and powerful purgative;” since the publication of this fact, I have investigated what, if true, would appear to be a most extraordinary anomaly in the philosophy of medicinal combination, and I find that the statement of Dr. Chapman^[264] is not borne out by experiment. That we might arrive at a just conclusion upon this subject, I requested the assistance of my friend Dr. John Davy, whose character for experimental accuracy, and whose situation as Superintendant of the Medical Division of the General Military Hospital at Chatham, seemed to point him out as a person peculiarly adapted for such an inquiry; the result of his trials does not establish that of the experiments of Dr. Chapman, but on the contrary it seems to prove, that neither Kino nor Calumba, when taken separately, has a constipating effect, and that in the form of powder (especially the Calumba) each has an aperient quality, which is not increased by exhibiting the two medicines together in a state of mixture. The trials from which these inferences are drawn were made on different individuals in tolerable health, and they were repeated more than once; in some cases they were given separately, and in others, mixed together, in doses varying from a scruple to a drachm of each.

B. By combining Substances which have the property of acting chemically upon each other; the result of which is the formation of new Compounds, or the decomposition of the original Ingredients, and the developement of their more active Elements.

A. The Formation of New Compounds.

It is not necessary to extend our researches beyond the range of the Pharmacopœiæ,^[265] to collect a variety of interesting and important examples, in illustration of this division of our subject; if we require a striking example of the agency of chemical combination in destroying the identity of the original constituents, and of giving origin to a compound of new powers, it may be exemplified by the well known instance of Sulphate of Potass, a substance possessing but a weak affinity for water, and exerting but little energy upon the animal œconomy; whereas the two ingredients of which it consists are distinguished for the extreme eagerness with which they unite with water, and for the caustic activity which they display in their action upon animal matter.

Under this head the class of metals will also present itself to our consideration, all the individuals of which, with the exception perhaps of iron, are perfectly inert and harmless; even arsenic, lead, copper, and mercury, which in certain states of combination constitute some of the most virulent of known substances, exert no action upon the living system, unless they be in union with some other body; but when so united, how valuable do they become, and what various medicinal effects may they not be made to produce.

The Acetic Acid and Ammonia become neutralized by combination with each other, affording a compound of new virtues. Sulphate of Zinc, and Acetate of Lead, when mixed together in solution, decompose each other, and the Acetate of Zinc which is formed, affords a more valuable remedy than either of the former salts, as an application in ophthalmia. The “Mistura Ferri Composita” of our Pharmacopœia offers another example of the same chemical resource. I also beg the reader to refer to the construction of Formula 82, which presents an instance of a purgative draught being produced by combination, in which the original properties of every element are entirely changed. See also Formula 87, the chemical actions of which are more complicated, but no less instructive than the preceding one; the ingredients of the formula are the Carbonates of Soda and Magnesia,—Sulphate of Iron,—Diluted Sulphuric Acid, and Water—and when mixed together, the following decompositions would appear to take place; the free Sulphuric Acid, together with that which exists in the Sulphate of Iron, being just sufficient to decompose the Carbonates of Soda and Magnesia, forms two neutral Sulphates (viz. Sulphates of Soda and Magnesia,) and thereby disengages a volume of Carbonic Acid gas, which not only increases the purgative operation of the new saline compounds, but, by its excess, holds in solution the Carbonate of Iron, which is formed by the decomposition of the Sulphate, and which in that state displays an effect powerfully tonic.

Before we quit the consideration of medicinal compounds as the results of chemical action, it is expedient to remind the practitioner of the essential difference between Mixture and Combination, a difference which affects the medicinal virtues no less than the chemical characters of bodies; it is determined by ample experience, that substances will produce effects upon the living system when presented in a state of simple mechanical mixture, very different from those which the same medicines will occasion when they are combined by the agency of chemical affinity, as is well exemplified in the comparative effects of alcohol as existing in ardent spirits, and in wine (see Vinum); or in the relative powers of Mercury in the Unguentum Hydrargyri of the London College, and the Unguentum Oxidi Hydrargyri cinerei of the Pharmacopœia of Edinburgh, (see Unguent. Hydrargyri); the former of which is a true chemical compound, whereas the latter is a simple mixture of its ingredients.

The accomplishment of such an effect is in many instances the sole object of a pharmaceutical process. It is thus that we obtain pure Citric acid from the juice of the Lemon; Tartaric acid, from Cream of Tartar; Benzoic acid, from the resinous substance known by the name of Gum Benzoin; upon the same principle, the Muriatic and Nitric acids are elicited from the saline compounds in which they exist. Ammonia, in its pungent form, is developed from its inodorous Muriate; and the fixed alkalies are obtained in their caustic state, from the comparatively mild carbonates in which they naturally exist. But a more striking and instructive instance of the effect of chemical action, in developing an active, or useful principle, cannot perhaps be selected than that of the well known stimulant Plaister, composed of Muriate of Ammonia, Soap, and Lead Plaister, in which the alkali of soap enters into combination with the muriatic acid, when the Ammonia, upon which the virtues of the plaister solely depend, is slowly disengaged in the form of gas, producing a powerfully rubifacient and stimulant effect: the “Cataplasma Fermenti,” or “Yeast Poultice,” is indebted for its antiseptic properties to a similar agency, for they do not depend upon any virtue in the ingredients themselves, but upon their decomposition, and the consequent developement of an active element, which is Carbonic Acid. The practitioner unacquainted with the modus operandi of these combinations, would inevitably fall into an error by which their efficacy must be lost; he would hardly apply them as soon as they were formed, nor would he be aware of the necessity of repeating them at short intervals.

The decomposition of Calomel by lime water, forming the well known “black wash” and that of corrosive sublimate in the same fluid, constituting the “aqua phagadenica,” furnish remedies which derive all their peculiar efficacy from the developement of the mercury in different states of oxidation. The reader will find another, and a very striking illustration of the same principle in the history of “Alterative Drops,” under the article “Hydrargyri Oxy-murias.”

A substance separated by chemical precipitation is often a valuable remedy, being in a much more subtle and impalpable form than any body can be rendered by mechanical triture and levigation;^[266] for example, the Carbonate of Lead, (Cerussa), when diffused in water, is according to the experience of our best surgeons, far less active as a topical application than the same substance when produced at once by precipitation from the Sub-acetate of that metal. In some cases, also, the substance obtained by precipitation is in a different state of oxidation from that which is prepared by a different process, see Mist. Ferri Comp: It is a question well worthy of consideration whether a more active preparation of the Antimonial powder might not be formed by obtaining the oxide by the precipitation of Tartarized Antimony.

Many interesting and important illustrations have been lately afforded by an extended knowledge of vegetable chemistry, recent analyses having developed principles of extreme activity from several of our most esteemed plants; thus have Sertuerner and Robiquet succeeded in separating a narcotic element from Opium (Morphia); Majendie, and Pelletier, an emetic principle from Ipecacuan, (Emeta); and the last mentioned chemist, together with Caventou, a tonic one from Peruvian Bark, (Cinchonia), the properties and applications of which will be fully explained hereafter, under the history of the different substances which contain them.

It is only here necessary to caution the practitioner against those fallacies into which the captivating theories of the chemist may seduce him; and, if the views which I have offered upon the subject of combination be correct, it will follow as a corollary, that the concentration of an active element must in many cases abridge its powers as a remedy; for although the matter thus removed may individually be quite inert, yet, in combination, it may subdivide the particles of the essential constituent, or modify its solubility, and give impulse and steadiness to its operation; thus the vegetable alkali Quina, although it indisputably constitutes the active matter of bark, will be found inefficacious when separated from it, unless it be rendered soluble by the addition of sulphuric, or some other acid.

C. By combining substances, between which no other chemical change is induced, than a diminution, or an increase, in the Solubilities of the principles, which are the repositories of their medicinal virtues.

The degree of solubility possessed by a medicinal substance may perhaps be regarded by some practitioners as a circumstance of but little or no importance; it will however appear in many cases that it not only influences the activity of a remedy, but, like its dose, goes far to determine its specific operation; indeed, where a medicine is not, in itself, very soluble, the increase of its solubility by any chemical expedient, is tantamount to an increase of its dose.

It is probably owing to the diversity which exists in the solubility of the active elements of certain purgatives, that so great a diversity occurs in their operation; it is, for instance, easy to conceive that a medicine may act more immediately and specially on the stomach, small, or large intestines, according to the relative facility with which its principles of activity enter into solution; that those which are dissolved before they pass the pylorus are quick and violent in their effects, and liable to affect the stomach, as is exemplified by the action of Gamboge, &c. whilst some resinous purgatives, on the other hand, as they contain principles less soluble, seldom act until they have passed out of the stomach, and often not until they have reached the colon. Colocynth has a wider range of operation, since its principles of activity reside both in soluble and in insoluble elements. Aloes again, being still further insoluble, pass through the whole alimentary canal before they are sufficiently dissolved, and act therefore more particularly upon the rectum, by which they are liable to produce piles, tenesmus, and the various effects which so usually attend their operation. The characteristic effects of Rhubarb, Senna, Saline Cathartics, and indeed of all individual substances which compose the class of the purgative medicines, will also admit of a satisfactory explanation from the application of these views. It ought moreover to enable the practitioner, by changing the solubilities of these substances, to change their medicinal effects. Experience shews that this is the fact, and that it may be effected either by the intervention of substances that act Chemically; or, by the addition of Ingredients whose operation is entirely Mechanical; thus by combining Aloes with Soap or an Alkaline Salt, we quicken their operation, and remove their tendency to irritate the rectum; the Compound Decoction of Aloes affords a combination of this kind. Gamboge, whose too ready solubility it is an object to obviate, should be intimately incorporated with some insoluble purgative, as for instance Aloes; a formula of this nature was introduced by Dr. George Fordyce, and it has been since simplified and admitted into our Pharmacopœia, under the title of “Pilulæ Cambogiæ Compositæ.” Tartrate of Potash, which, on account of its comparative solubility, has gained the name of Soluble Tartar, acts with corresponding briskness upon the small intestines; but by increasing its proportion of Tartaric Acid, we convert it into a super-tartrate or “Cream of Tartar,” which is a substance characterized by a comparative degree of insolubility, and a correspondent change is produced in the medicinal activity of the salt; its purgative effects are considerably diminished, whilst its diuretic powers are rendered more considerable. We may even extend this experiment by adding to the Cream of Tartar, Boracic Acid, a substance capable of increasing to a certain extent its solubility, when we shall again find that its purgative properties are strengthened in an equal proportion.

It has been observed that a mixture of different saline cathartics is more efficient than an equivalent dose of any single one, a fact which is strikingly exemplified in the prompt and active operation of Cheltenham Salts, in comparatively small doses, as well as in that of sea water. I submit whether this may not in some degree depend upon increased solubility; for it is a law well known to the chemist, that when water has ceased to act upon a salt, in consequence of its having obtained the term of saturation, the solution may still take up another salt of a different kind. I apprehend that an advantageous application of this law might be frequently made in practice, and the energies of a remedy thereby considerably extended.^[267]

Where the active principle of a cathartic is not sufficiently soluble, it is apt to vex and irritate the bowels, producing tormina instead of exciting a free and copious excretion; hence the reason why the operation of resinous purgatives is so commonly attended with griping, and why relief may be obtained by combining them with neutral salts. Thus also Senna, whose virtues reside in extractive matter, is apt by decoction, or long exposure to the air, to act with griping, in consequence of the extractive matter becoming by oxidation, resinous and comparatively insoluble: this effect is best counteracted by the addition of soluble Tartar, that will quicken its action, or by an alkaline salt that will increase its solubility.

It appears then to be established as a pharmaceutical maxim, that the intensity and even specific action of a purgative medicine may be modified or completely changed, by changing the degree of solubility possessed by the principles in which its activity resides.

The application of this principle is highly important in practice, directing us in the choice of the different purgatives, according to the objects which we may wish to fulfil by them, and pointing out safe and easy methods by which we may increase, diminish, retard, or accelerate their operation; it thus enables us to construct new and powerful combinations, by imparting to established remedies fresh activity, or by mitigating the acrimony and violence of arrangements in other respects efficacious and eligible.

In the exhibition of solid substances, their mechanical state of division may be capable of modifying their operation, from the influence which this condition must necessarily exert upon their solubilities, although I am by no means disposed to assign to it the importance which Gaubius has ventured to express, “Sunt quæ ruditer pulverata alvum, subtilius vero urinas, aut alios humores movent;” and Ray, speaking of the Asarum (Hist. p. 208) has the following remark—“Quo tenuius est tritum, eo magis urinas movere, minus autem alvum ducere creditur;” and Linnæus^[268] observes that this same plant, when exhibited in the state of very fine powder, uniformly acts as an emetic, but that when coarsely powdered it always passes the stomach, and becomes cathartic. M. Virey has made a similar observation with respect to Hellebore,—“L’Hellebore pulverisé fait vomiter; concassé il purge; et en decoction prolongée, il en devient sudorifique ou diuretique.” I have endeavoured under the article Pulveres to establish some useful precepts upon this subject, to which I beg to refer the reader.

The influence of solubility upon the medicinal energies and specific effects of remedies, may be farther illustrated by a comparative examination of the virtues of the Acetate and Sub-acetate (Goulard’s Extract) of Lead: the former preserves its solubility and integrity under any degree of dilution, while the latter, when slightly diluted with the purest water, in consequence of the carbonic acid diffused through it, gives out a copious precipitate; the acetate therefore is undoubtedly the more immediately active application as a preparation of lead, but it is nevertheless perhaps less adapted to remove inflammation and abate irritation than the turbid mixture of the sub-acetate, since the slow and gradual action which is ensured by the latter is more desirable than the instantaneous operation of the same remedy, applied in a more soluble form: the popular injection for gonorrhæa, consisting of a mixed solution of Sulphate of Zinc and Acetate of Lead, probably owes much of its value to the insoluble precipitate of Sulphate of lead which necessarily takes place, and which, from becoming entangled in the mucus of the urethra, produces a more permanent stimulus than what could have happened from a soluble salt: (Form. 62) thus again the Sulphuret of Antimony, and some other preparations of that metal, of slow solubility, establish a more permanent influence than Tartarized Antimony, and may be preferable to it in cases where immediate and active evacuations are not required.

To Sir Francis Milman the profession is highly indebted for hints concerning the importance of accompanying the exhibition of Diuretics with plentiful dilution,^[269] the arguments he adduces elucidate in a very satisfactory manner the view which has been just taken of the Influence of Solubility.

The influence of solubility^[270] in increasing the virulence of a poisonous substance, has already been illustrated very fully (page 135,) and it has also been shewn under what circumstance it may be admissible. When these active substances are administered as remedies, in small doses, the precept respecting their solubility is even more important, for in such cases the smallness of the quantity places their operation more immediately under the control of various incidental agents; destroy the solubility of a medicine, and you will probably divest it of those properties which render it useful. Nitrate of Silver, by coming in contact with a Muriatic Salt, is rendered quite inert, and may be discovered unaltered in the fæces of persons to whom it has been administered. See Argenti Nitras.

Under the article Plumbi Acetas the practitioner will also find that the conjunction of this substance with any sulphuric salt, at once deprives it of its valuable properties as a remedy in Hæmopthysis.

Some practitioners, whose opinions I always receive with respect, have considered these views respecting the influence of solubility as savouring too much of the refinement of theory, and instances have been suggested which would appear to invalidate their pretensions; upon examination, however, it will be found that such exceptions are but apparent, and depend upon the solvent action of the gastric fluid. Thus the Protoxide of Iron would appear to be soluble in the fluids of the stomach, and is consequently an active medicine, whereas the Peroxide of the same metal, being insoluble under such circumstances, requires to be combined with an acid, as in the Tinctura Ferri Muriatis, to render it efficacious. The same remark will probably apply to the oxides of antimony.

I shall conclude this section upon the influence of Solubility, by the relation of an anecdote which may tend to confirm the justness of the views I have offered, more satisfactorily perhaps than any additional arguments derived from a scientific examination of chemical and medicinal facts; in as much as it presents us with a practice, the utility of which has been discovered by unassisted experience, and must consequently be independent of theory. The American Indians, whenever they undertake a long journey, and are likely to be destitute of provisions, employ Tobacco for the purpose of counteracting the uneasy sensations of hunger, and in its preparation for such a purpose they adopt an expedient for modifying its powers, and protracting its effects, which affords an instructive illustration of the influence of solubility; it consists in combining the juice of Tobacco, with the pulverized shells of snails, cockles, and oysters;^[271] the mass is dried, and formed into pills, of a convenient size to be held between the gum and lip, which being gradually dissolved and swallowed, fulfil the intention required.^[272]

V.
TO AFFORD AN ELIGIBLE FORM.

A. By which the efficacy of the remedy is enhanced.

After the views which have been submitted in the progress of the present inquiry, it is evident, that the form in which a remedy is administered may exert some influence upon its medicinal effects; for additional proofs of this fact, and for more particular directions, see Decocta, Infusa, Tincturæ, Misturæ, Pilulæ, Pulveres, &c.

When a substance, or a combination of substances, requires the addition of some other one, for the purpose of imparting a convenient, agreeable, or efficacious form, a vehicle should always be selected, whose effects will be likely to correspond with the intention of the other ingredients. This precept may be exemplified by a reference to Form. 80, 134, and others, the key-letters of which announce the modus operandi of their respective vehicles.

B. By which its aspect or flavour is rendered more agreeable.

It should ever be the object of the practitioner to accommodate, as far as he is able, the form and flavour of his medicines to the taste and caprice of his patient, provided always that he does not compromise their efficacy, and which often appears to be nearly connected with those sensible qualities which render them disgusting and objectionable.

Some medicines are more grateful to the stomach, as well as more efficacious in their operation, when exhibited in the state of effervescence. To effect this we have only to introduce an alkaline carbonate into the formula, and to direct a portion of some vegetable acid to be added just before it is swallowed. We must, however, take care that the ingredients are of a nature not likely to be decomposed by the alkali, in the first instance, or by the neutral salt, which is formed, in the second. See Form. 27, 82, 86.

C. By which it is PRESERVED from the spontaneous decomposition to which it is liable.

It is sometimes adviseable to add an ingredient for the purpose of preventing the sudden decomposition of a medicine; thus is the Compound Tincture of Cardamoms added to the Compound Decoction of Aloes, in order that the latter may be preserved a longer period without change. The addition of sugar will prevent ointments from becoming rancid. Vegetable infusions, that are susceptible of mouldiness, are best preserved from such deterioration by some aromatic addition. For the knowledge of this fact we are indebted to Dr. Mac Culloch, who in a very interesting paper, lately published in the Edinburgh Philosophical Journal^[273] has observed, that perfumes, such as Essential Oils, &c. will prevent the production and growth of those minute cryptogamous vegetables, upon which the phenomenon of mouldiness depends.^[274]

Such are the objects which are to be attained by combining several substances in one Formula, and such the laws by which these compositions are to be regulated; but unless a physician can satisfactorily trace the operation of each element in his prescription to the accomplishment of one or more of the objects which I have enumerated, SIMPLICITY should be regarded by him as the greatest desideratum. I was once told by a practitioner in the country that the quantity, or rather complexity of the medicines which he gave his patients, for there never was any deficiency in the former, was always increased in a ratio with the obscurity of their cases; “if,” said he, “I fire a great profusion of shot, it is very extraordinary if some do not hit the mark.” Sir Gilbert Blane^[275] has given us a similar anecdote; “a practitioner being asked by his patient why he put so many ingredients into his prescription, is said to have answered more facetiously than philosophically, in order that the disease may take which it likes best.” A patient in the hands of such a practitioner has not a much better chance than the Chinese Mandarin who, upon being attacked with any disorder, calls in twelve or more physicians, and swallows in one mixture all the potions which each separately prescribes!

Let not the young practitioner however be so deceived; he should remember that unless he be well acquainted with the mutual actions which bodies exert upon each other, and upon the living system, it may be laid down as an axiom, that in proportion as he complicates a medicine, he does but multiply the chances of its failure. Superflua nunquam non nocent: let him cherish this maxim in his remembrance, and in forming compounds, always discard from them every element which has not its mode of action clearly defined, and as thoroughly understood.

The perfection of a Medicinal Prescription may be defined by three words; it should be Precise (in its directions,) Concise (in its construction,) Decisive (in its operation.) It should carry upon its very face an air of energy and decision, and speak intelligibly the indications which it is to fulfil. It may be laid down as a position which is not in much danger of being controverted, that where the intention of a medicinal compound is obscure, its operation will be imbecile.

A Medicinal Formula has been divided into four constituent parts, a division which will be found to admit of useful application to practice, in as much as it was evidently suggested with a view of accomplishing the more prominent objects which have been related in the preceding pages; or, in the language of Asclepiades, of enabling the Basis to operate “Cito,” “Tuto,” et “Jucunde.” Quickly, Safely, and Pleasantly—thus

I. The Basis, or Principal Medicine.