II. The Adjuvans; that which assists and promotes its operation.
III. The Corrigens; that which corrects its operation.
IV. The Constituens; that which imparts an agreeable form.
These elements however are not all necessarily present in every scientific formula, for many medicines do not require any addition to promote their operation, and the mild and tractable nature of others renders the addition of any corrective unnecessary; whilst many again are in themselves sufficiently manageable, and do not therefore require the intermede of any vehicle or constituent. It also frequently occurs that one element is capable of fulfilling two or more of the objects required; the Adjuvans for instance, may at the same time act as the Corrigens, or Constituens; thus the addition of Soap to Aloes, or Extract of Jalap, mitigates their acrimony, and at the same time quickens their operation (80.) So again Neutral Salts both quicken and correct the griping which attends the operation of resinous purgatives. The disposition of the key letters placed opposite to the elements of the following Formulæ, will furnish the practitioner with a farther elucidation of these principles, viz. 70, 71, 76, 77, 101, 102, 105, 135, &c. This coincidence, if possible, should be always attained, for it simplifies the formula, and by decreasing the bulk of the remedy, renders it less nauseous and more elegant.[276]
This division also affords the best general rule for placing the ingredients of a formula in proper order, for the order should correspond with that of the arrangement; and those elements intended to act in unity should be marshalled together. The chemical and mechanical nature however of a medicinal substance will occasionally offer exceptions to any general rule; thus the volatile ingredients should be those last added, and the constituent or vehicle should be placed next the particular element to which it is intended to impart convenience or efficacy of form, or a capability of mixing with the other ingredients, as may be seen in Formulæ 69, 71, 127, 136, &c. This consideration induced the Committee, appointed to revise the late Pharmacopœia, to alter the order of the ingredients in the “Mistura Ferri composita,” and to place the “Spiritus Myristicæ” next in succession to the “Potassæ Sub-carbonas” and Myrrh. If any substance require decoction or infusion, a question then arises, determinable only by a knowledge of its chemical composition, whether the remaining ingredients should be added previous to, during, or subsequent to, that operation; Formula 40, which is recommended by Pringle as a remedy for Typhus fever, may serve to exemplify this principle. The preparation of the ingredients is resolved into three distinct stages, and it is easy to discover that by any other arrangement their several virtues could not be fully obtained, and secured from change. The Cinchona, for instance, yields its full powers only by decoction, a process which would necessarily impair those of Serpentaria, connected as they are with an essential oil; whilst the addition of the acid at any other stage of the process than that directed, would produce decompositions in the vegetable substances; and it is evident that were the Spirit of Cinnamon added previously, it would be entirely lost by vaporization. So in making the Compound Decoction of Sarsaparilla, the Sassafras should be added after the other ingredients have undergone boiling. The Decoctions of Lichen Islandicus and Sarsaparilla constitute a popular remedy on the Continent, in certain forms of Phthisis; now it is evident that as the former plant loses its virtues by long coction, and the latter requires a protracted ebullition for the extraction of its virtues, they ought not to be included under the same general directions; each decoction should be separately performed, and the results subsequently mixed.
Compound Medicines have been divided into two Classes, viz.
I. Officinal Preparations,
which are those ordered in the Pharmacopœias, and kept ready prepared in the shops. No uniform class of medicines however can answer the indications of every case, and hence the necessity of
II. Magistral or Extemporaneous Formulæ.
These are constructed by the practitioner at the moment, and may be either arrangements altogether new, or officinal preparations with additions, or modifications. Too much importance cannot be assigned to the Art which thus enables the physician to adopt and graduate a powerful remedy to each particular case by a prompt and accurate prescription; without this knowledge, the practitioner of the nineteenth century, with all the collateral aid of modern science, will be as helpless in the chamber of sickness as the physicians of ancient Egypt, who were obliged by the laws to follow with servile exactness the unvarying mandates of their medical code. Extemporaneous are also preferable to Officinal Formulæ, whenever the powers of the compound are less liable to deterioration from being long kept; for examples, see Mistura Ferri composita; Infusum Sennæ; Liquor Hydrargyri Oxymuriatis, &c.
The Chemical and Pharmaceutical Errors, which may be committed in the composition of Extemporaneous Formulæ, are referable to the following Sources.
1.—Substances are added together which are incapable of mixing, or, of forming Compounds of uniform and suitable consistence.
This may be termed an error in the Mechanism of the Prescription, and has been generally regarded as being more inconvenient than dangerous, more fatal to the credit of the Prescriber than to the case of the Patient: the observations however which are offered in this work, especially under the article Pilulæ, must satisfy the practitioner that this error is more mischievous in its effects than has been usually supposed; it is so palpable and self-evident in its nature, that it will be unnecessary to illustrate it by more than one or two examples. Calomel, for instance, has been ordered in an aqueous vehicle, and certain resinous tinctures have been directed in draughts, without the necessary intervention of mucilage; so again, an intermixture of substances has been formerly ordered in powder that possess the perverse property of becoming liquid by triture (see Pulveres), and bodies have been prescribed in the form of pills, whose consistence[277] renders it impossible that they should preserve the globular form; or else they have been so hard and insoluble, that they might be fired through a deal board.[278] In the London Pharmacopœia of 1809, an error of this kind unfortunately passed without correction with regard to the Formula for preparing the Syrup of Senna.
II.—Substances are added together which mutually decompose each other, whence their original virtues are changed, or destroyed.
This is a more serious, but not a less frequent source of error; it has been already shewn in this Analysis (IV. B) that the judicious and scientific application of chemical science has furnished new and endless resources to the physician, by exalting the efficacy and correcting the acrimony of established remedies, or by combining inert substances so as to create new and powerful medicines. With equal truth and confidence it may be asserted, that the abuse of these means not only destroys the virtues of the most valuable articles in the Materia Medica, but that the mildest remedy may be thus converted into an instrument of torture, and even of death. In a lecture delivered at Apothecaries’ Hall, Mr. Brande stated that he had seen a prescription in which the blue, or mercurial pill, was ordered in conjunction with nitric acid, and that the patient was brought to “death’s door” from the formation of nitrate of mercury in his stomach! I have myself lately seen a Recipe, professing to afford a preparation similar to the “Black Drop,” and which directed a mixture of a Tincture of Opium, made with rectified spirit, with Nitric Acid; in this case, it may be very safely inferred that the author was not only ignorant of the chemical habitudes of these bodies, but that he never performed the experiment in question, or he would have learnt from dire experience, that in consequence of the rapid evolution of nitric ether, the contents of the phial will explode with violence, to the imminent hazard of the operator’s eye-sight. During the course of my professional practice I have witnessed more than an ordinary share of consumptive cases, and I can confidently state that in the treatment of Hæmopthysis, the styptic properties of Acetate of lead are entirely invalidated by combination with Alum,[279] or by its exhibition being accompanied with that of the acidulated infusion of roses, or with small doses of sulphate of magnesia; and yet, I would ask, whether this practice is not usual and general? The practitioner however cannot be too often reminded that he is not to reject a remedy whose value has been ascertained by experience, merely because it appears to be unchemical: the popular and certainly useful pill, consisting of calomel, rhubarb and soap, may be adduced as an example of this kind. Of the Mistura Ferri Composita, I will only say that it is a most valuable combination; and whether it be the product of accident, or the result of philosophical induction, it equally deserves a distinguished place in our list of tonic remedies: but it cannot be denied that many of our esteemed arrangements, which are in apparent contradiction to all the laws of composition, owe their efficacy to the operation of affinities altogether blind and fortuitous.
It has been observed that the practice of combining certain vegetable tonics with lime-water, although very common, is in cases where we are desirous to obtain their astringent effects, of very doubtful propriety; for the fact is, that Tannin forms with the alkalies and alkaline earths, compounds that are not soluble in water,[280] and which are therefore probably inefficacious. It may perhaps be said that such an argument cannot avail, because if the astringent matter be even introduced into the stomach in its purest form, it will immediately form an insoluble compound on its contact with gelatine.[281] We know so little of the laws of gastric chemistry, that it is difficult to learn what changes take place in the animal laboratory; but it would seem probable that the powers of the stomach rather consist in decomposing the ingesta into simple forms, than in complicating them by favoring new combinations; besides which, if such a compound were formed, it would be subsequently decomposed in transitu; for the experiments of Sir H. Davy shew that vegetable astringent matter passes through the body unchanged. (page 82.)
It is impossible to furnish any general rule that may enable the practitioner to avoid mixing together substances which are incompatible with each other; a knowledge of their chemical habitudes must in every case direct him, and these are enumerated in the second part of this work, under the history of each medicinal substance. The physician however will find it useful to retain in his remembrance the simple and beautiful law which has been so ably developed by the eminent author of the “Statique Chimique,” that whenever two salts in a state of solution are brought together, which contain, within themselves, elements capable of producing a soluble and insoluble salt, a decomposition must necessarily arise;[282] he illustrates this law by the example of Nitrate of Silver and Muriate of Potass, whose elements are capable of forming within themselves a soluble salt, Nitrate of Potass, and an insoluble salt, Muriate of Silver. It deserves also to be remembered, that a table of chemical affinity will not upon all occasions prove to the medical practitioner an unerring pilot; in those cases for instance, where a super or sub Salt is readily formed, a substance less weakly attracted by another than a third, will sometimes precipitate this third from its combination with the second, thus in the production of Nitric acid, we decompose the Nitrate of Potass by virtue of the superior affinity of the Sulphuric acid for its base, the nitric acid is accordingly disengaged, and a Sulphate of Potass remains in the retort; now, paradoxical as it may appear, if nitric acid be poured upon the Sulphate of Potass, a quantity of nitre will be reproduced, in consequence of the saturation of a portion of the base, in such a proportion as to enable the remaining atoms to form a Bi-Sulphate of Potass. In the same manner the Tartrate of Potass (Soluble Tartar) is, contrary to the usual affinities, decomposed by all sub-acid vegetables, which neutralize a portion of the base, and convert the salt into the Bi-tartrate of Potass (Cream of Tartar). The same effect is even produced by Carbonic acid.[283]
There are besides certain cases wherein Triple Salts are produced, which afford apparent exceptions to the usual affinities of the bodies involved in the combination; we have a very good illustration of this truth in the decomposition of the Liquor Ammoniæ Acetatis by Magnesia; if the practitioner refers to a table of affinities, he will perceive that Acetic acid has a greater attraction for Ammonia than for Magnesia; but if upon this assurance he were to administer these bodies together, he, or his patient, would soon discover that ammonia is developed with considerable pungency; now in this case the Magnesia forms a triple Acetate with one part of the ammonia, and consequently sets the remainder at liberty.
A popular error exists with respect to the subject of chemical incompatibility, against which it may be here advisable to caution the inexperienced prescriber, viz. that no important change is produced, on the admixture of solutions, unless precipitation is occasioned. This however occurs only when the new compound produced is insoluble; thus Sulphuric acid may be added to Lime water, by which a Sulphate of Lime is formed, but as its proportion is not too large for the water to dissolve, no precipitate occurs; so again, a solution of Nitrate of Silver is not apparently disturbed by the addition of Ammonia, because the resulting Ammoniuret is a soluble compound. We should, nevertheless, commit a great error in supposing that, for such a reason, these bodies were not incompatible. On the other hand, the medicinal powers of a solution are not necessarily destroyed by the occurrence of a precipitate, although such a result should always be regarded with suspicion.
III.—The Methods directed for the preparation of the Ingredients are either inadequate to the accomplishment of the object, or they change and destroy the efficacy of the Substances.
The observations already offered upon Formula 40, will sufficiently explain the nature of the various errors comprehended under this head: so, again, if the virtues of a plant reside in essential oils, which are easily volatilized, or in extractive matter, which readily becomes oxidized, Decoction must necessarily destroy its efficacy; a striking example of this fact is presented us in the history of the Laurel and Bitter Almond: the poisonous influence of the essential oil and distilled water of these vegetable substances is well known, but their watery extracts are perfectly innocuous. A still more familiar example is to be found in the onion, or in garlic, which by simple coction is deprived of all its acrimonious qualities. On the other hand, an error equally injurious would be committed, by directing a simple infusion of a vegetable, whose medicinal properties depended upon resino-mucilaginous principles. Orfila found that an extract of Hemlock, prepared by boiling the dried powder in water and evaporating the decoction, was entirely destitute of activity. See Decocta, Infusa, Extracta.
An instance of the baneful effects which may arise from an erroneous method of preparation happened some time ago to fall under my immediate notice and care; it was in preparing an infusion of the root of the Veratrum with Opium, as directed by Mr. James Moore, when the dispenser ignorantly substituted a spirituous for a vinous menstruum.
A very common error may be here noticed, which is that of prescribing a substance in such a form, as not to be acted upon with any effect by the solvent; as an example it may be stated, that in preparing an infusion of Juniper Berries, unless pains be taken by strong contusion to break the seed, it will contain but little power as a medicine.
The unbruised seeds of Mustard were commended by Dr. Mead,[284] in Ascites, and by Bergius, in Intermittents; Dr. Cullen, however, has very properly observed that the seeds given in the above manner are never broken down or dissolved in the stomach, but pass away entire by stool, and cannot therefore occasion any beneficial result.
It is unnecessary to multiply examples in proof of the numerous errors into which a physician must unavoidably fall, who presumes to compose prescriptions without a knowledge of the chemical habitudes of the different substances which he combines. The file of every apothecary would furnish a volume of instances, where the ingredients of the prescription are fighting together in the dark, or at least are so adverse to each other, as to constitute a most incongruous and chaotic mass.
The Doses of Medicinal Substances are specific with respect to each, and can therefore be only learnt from experience; the young and eager practitioner, however, is too often betrayed into the error of supposing that the powers of a remedy always increase in an equal ratio with its dose, whereas The dose alone very often determines its specific action. “Medicines,” says Linnæus, “differ from poisons, not in their nature, but in their dose,” which is but a paraphrase of the well known aphorism of Pliny, “Ubi virus, ibi virtus.”[285]—So that food, remedies, and poisons, may be said to branch into each other by indefinable gradations;—Five grains of Camphor act as a mild sedative and slight diaphoretic, but twenty grains induce nausea, and act as a stimulant; so again, Opium, in too large doses, instead of promoting, prevents sleep, and rather stimulates the bowels than acts as a narcotic. Two ounces of any neutral salt are apt to be emetic, one ounce even of Alum to be cathartic, and two drachms to be refrigerant; in like manner the preparations of Antimony either vomit, purge, or sweat, according to the quantity exhibited.
Would it not appear that powerful doses rather produce a local than a general effect? Experience seems to prove in this respect, that the effect of an internal application is similar to that of an external impression; if violent, it affects the part only to which it is applied, as pinching does that of the skin, whereas titillation, which may be said to differ only from the former in degree, acts upon the whole system, and occasions itching and laughter, and if long continued, weakness, sickness, vomiting, and convulsions; in like manner Digitalis, if given in large doses, acts immediately upon the stomach or bowels, becoming emetic and cathartic, but in smaller proportions it produces a General effect, increasing all the excretions, especially that of urine; so, again, large doses of the Mercurial Pill act upon the bowels, and are eliminated from the body, whereas the same remedy in small doses affects the system generally, and excites a universal influence. I am well satisfied that the regulation of the dose of a medicine is even more important than it is usually supposed to be. Substances perfectly inert and useless in one dose may prove in another active and valuable. Hence may be explained the great efficacy of many mineral waters, whilst the ingredients which impart activity to them are found comparatively inert, when they become the elements of an artificial combination; and hence probably the failure of many alterative medicines, when no other rational cause can be assigned for it. We need not seek far for an example of the very different and opposite effects which the same substance can produce in different doses; the operation of Common Salt is familiar to us all; Sir John Pringle has shewn that in quantities such as we usually take with our food, its action is highly septic, softening and resolving all meat to which it is applied, whereas in large quantities it usually preserves such substances from putrefaction, and therefore, when so taken, instead of promoting, destroys digestion.
It is moreover probable that medicinal, like nutritive substances, are more readily absorbed into the circulating system when presented in small quantities, than when applied in more considerable proportions. It is upon this principle that a large quantity of food, taken seldom, does not fatten so much as smaller quantities at shorter intervals, as is exemplified in the universal good condition of cooks and their attendants. It is not pressing the principle of analogy too far to suppose that the action of alteratives, which require to be absorbed, may be more effectually answered by similar management; that is, by exhibiting small doses at short intervals.
The operation of medicines is influenced by certain general circumstances, which should be also kept in mind when we apportion their dose; e.g. Age—Sex—Temperament—Strength of the Patient—Habit—Diet—Profession—Climate—Duration of the Disease—State of the Stomach—Idiosyncrasy—and The variable Activity of the Medicinal Substance.
Women generally require smaller doses than men. Habit, or the protracted use of a medicine, generally diminishes its power, although certain cathartics appear to offer an exception, for when long continued, their activity is proportionally increased, as is well known to every person who is familiar with the operation of the Cheltenham waters. Dr. Lamb has also stated with regard to the operation of Lead, “that the constitution, so far from being reconciled to it by habit, is rendered more and more sensible to its irritation by continuance.” Emetics also frequently become more powerful by repetition; Cullen informs us that he knew a person so accustomed to excite vomiting in himself that the one twentieth part of a grain of tartarized antimony was sufficient to excite a convulsive action of the stomach; in some cases such an effect may perhaps be referred to the operation of the mind; for after the frequent use of an emetic, the mere sight of it, or even conversation relative to it, has been found sufficient to excite nausea.
In apportioning the dose of a very active medicine, it is of the greatest moment to determine the relative degrees of power between the system and the remedy, and to know to what extent the latter is likely to be carried, consonantly with the powers of life to resist it; thus, after a patient has been exhausted by protracted and severe suffering and watching, a dose, different to one at the commencement of the disease is requisite. The importance of this precept is impressed upon my mind from having witnessed, in the course of my practice, several instances of the mischief which has arisen from a want of attention to it; that disease materially influences the condition of the body, and its susceptibility to remedial impressions, has been already demonstrated. Emetics act very readily in febrile affections, while in those of the Neuroses[286] they produce their effects with difficulty.
In the application of external remedies to diseased parts, it especially behoves the Surgeon to take into consideration the degree of vitality possessed by such parts, and to graduate their strength accordingly.
Mr. Henry Earle[287] has published a very interesting case in illustration of this principle. The arm of a person became paralytic, in consequence of an injury of the axillary plexus of nerves from a fracture of the collar bone; upon keeping the limb for nearly half an hour in a tub of warm grains, ‘which were previously ascertained by the other hand not to be too hot,’ the whole hand became blistered in a most alarming manner, and sloughs formed at the extremities of the fingers, and underneath the nails; a considerable degree of inflammation subsequently spread in the course of the absorbents, and matter formed in the axilla, which was soon absorbed, and the inflammation assuaged. Whence it follows, that a limb deprived of its usual supply of nervous energy cannot sustain, without injury, an elevation of temperature which would not be in the least prejudicial to a healthy member. Mr. Earle supports this conclusion by the relation of another case, in which the ulnar nerve had been divided, for the cure of a painful affection of the arm; the consequence of which operation was, that the patient was incapable of washing in water at a temperature that was quite harmless to every duly vitalized part, without suffering from vesication and sloughs.
Before we quit the subject of Dose, it may be necessary to observe, that there are many remedies that do not act with greater violence in a large dose than in one comparatively small; Ipecacuan, for instance, is more certain in its operation, but not more violent, when given in a large quantity; the same may be said of Aloes, and several other medicines.
The Variable Activity of a Medicine should also be appreciated, and perhaps the practitioner would act cautiously if he were to reduce the dose, should it be a very considerable one, whenever a fresh parcel of the medicine is commenced, especially of the powders of active vegetables liable to deterioration from being kept, as those of Digitalis, &c.
The Time of the Day at which remedies should be administered deserves likewise some attention. Evacuating Medicines ought to be exhibited late at night or early in the morning. It would seem that during sleep the bowels are not so irritable, and consequently not so easily acted upon, which allows time for the full solution of the substance; the same observation applies to Alterative and other medicines which are liable to suffer from a vexatious irritability of the bowels; it is on this account eligible to exhibit Guaiacum, Pilulæ Hydrargyri, &c. when they are not intended to purge, at bed time. On the other hand, where the effects of a remedy are likely to be lost by perspiration, as is the case with Diuretics, many of which are by external heat changed into Diaphoretics, it may become a question with the judicious practitioner whether he cannot select some more favourable period for their exhibition.
In fevers it is of importance to consult in all respects the quiet and comfort of the patient; Dr. Hamilton therefore, in his valuable work on Purgatives, very judiciously observes that, on this account, the exhibition of purgative medicines should be so timed, that their effects may be expected during the day.
In some cases the time of administering a remedy must be regulated by the stage of the disease; thus, in fevers, a dose of opium will either increase the heat of the body, augment thirst and restlessness, or occasion tranquillity and sleep, according to the temperature of the body at the time of its administration; for this reason Dr. Currie advises us not to give the evening dose of Opium in Typhoid fevers, till very late, or about one or two o’clock in the morning, when the heat is subsiding, and moisture is coming on. Emetics administered for the cure of the slighter cases of Pyrexia should be given in the evening, as their operation leaves a tendency to sleep and diaphoresis, which it is useful to promote. Remedies that require to be absorbed will probably be more efficient in the morning after sleep; the old custom of giving medicines on a morning fasting, is not quite so absurd as some modern practitioners have been led to suppose. Diaphoretics should be always given after the digestive process is ended, for during the performance of this function the emunctories of the skin are less disposed to action.
The Intervals between each Dose must be regulated by the nature of the remedy and that of the objects which it is intended to fulfil, and whether it be desirable or not that the latter dose should support the effects of the preceding one, or whether there be any fear of a reaction or collapse taking place after the effect of one dose has subsided, unless immediately repeated; thus the effects of diffusible stimulants, such as ammonia and æther, are very evanescent, they should therefore be repeated at short intervals; the same may be said of Diaphoretics, especially the lenient ones; we ought not to allow the period between the doses to be so remote as to occasion any striking abatement in the impression: so Opium, where its primary and stimulant operation is required, as in diseases of debility, such as fevers of the typhoid type, should be given in small doses at short intervals, so that it may enkindle and sustain a uniform and regular state of excitement: but where the object is to mitigate pain, allay irritation, and produce sleep, it ought to be exhibited in full doses, at distant intervals. There is a caution also which it is very necessary to impress upon the practitioner, respecting the power which some medicines possess of accumulating[288] in the system; this is notorious with regard to Lead and Mercury, and probably with the preparations of Arsenic, and some other metallic compounds. Dr. Withering has observed that the repetition of small doses of Digitalis, at short intervals, till it produces a sensible effect, is an unsafe practice, since a dangerous accumulation will frequently take place before any signals of forbearance present themselves. I have already alluded to the possibility of mercurial accumulation, and its developement at a remote period.
Constitutional Peculiarities, or Idiosyncrasies, will sometimes render the operation of the mildest medicine poisonous, “Virum novi,” says Gaubius, “qui cum fatuum lapidum cancrorum pulvisculum ingessit, vix mitius afficitur quam alii ab Arsenico.” I have seen a general Erysipelas follow the application of a blister, and tormina of the bowels, no less severe than those produced by the ingestion of Arsenic, attend the operation of purgatives composed of Senna! In some constitutions Antimony has been known to produce a ptyalism; Dr. James assured Sir George Baker that he knew six instances of it, although the patients thus affected had neither their teeth loosened, nor their breath made offensive. The peculiar susceptibility of certain individuals to the effects of particular plants is also very singular: Murray relates that unpleasant symptoms have been experienced by merely keeping Aconite for some time in the hand, or on the bosom. I am acquainted with two persons in whom the odour of Ipecacuan always produces a most distressing dyspnæa; Mr. Chevalier informs us, that he once knew a lady who could not take Powdered Rhubarb, without an erysipelatous efflorescence almost immediately shewing itself on the skin, and yet she could take it in the form of Infusion with perfect impunity. There are some idiosyncrasies so singular and incredible, that nothing but unimpeachable testimony could sanction our belief in their existence. Schenkius relates a case in which the general law of astringents and cathartics was always reversed. Donatus tells us of a boy whose jaws swelled, whose face broke out in spots, and whose lips frothed, whenever he eat an egg.
The late Pope Pius VII. had such an antipathy to musk, that on one occasion of presentation, an individual of the company having been scented with that perfume, his holiness was obliged to dismiss the party almost immediately.[289] Education, and early habits certainly establish very extraordinary peculiarities in different countries with respect to various objects of diet and luxury: what shall we say of the refinement of the Ancients who regarded the flavour of the Citron with disgust, while the odour of putrid fish was deemed by them so exquisite, that they carried it about in caskets of onyx as a favourite perfume! Custom makes the Greenlander relish his train oil; and Dr. Heberden tells us, that there is a town in North America, where the spring-water is brackish, and that, when the inhabitants visit any other province, they choose to put salt into their tea or punch, in order, as they say, “to make it taste as it should do.”[290]
Climate. Several observations have already been offered upon the influence of Climate in affecting the activity of our remedies.[291] With regard to its relations to Dose, I have only one remark to make to the English practitioner, and that by the way of caution, that he will not allow his own previous experience in hot climates, or the persuasions of other tropical practitioners to induce him to administer such doses of Mercury, in England, as may have been found salutary in India, or in other Colonies of similar temperature.
The popular scheme of Gaubius for graduating the doses of medicine to different ages, which was published in several of the former editions of this work, is now omitted, as being less easy of application than the following simple formula by Dr. Young.
RULE.
For children under twelve years, the doses of most Medicines must be diminished in the proportion of the Age, to the Age increased by 12.
| thus at two years to ⅐—viz. | ||
| 2 | 1 | |
| = | ||
| 2 + 12 | 7 | |
| At 21 the full dose may be given. | ||
Every general rule however respecting the doses of medicines will have exceptions. Thus children will bear larger doses of Calomel than even adults, and many medicines which do not affect adults, although exhibited in considerable quantities, prove injurious even in small doses to children.[292]
In concluding this part of the subject, it is proper to impress upon the practitioner the importance of writing his prescriptions in legible characters, and of avoiding all those abbreviations which are not generally understood, or which are capable of misconstruction.[293]
SOLID FORMS.
PULVERES. Powders.
The form of powder is in many cases the most efficient and eligible mode in which a medicinal substance can be exhibited, more especially under the following circumstances.
1. Simple Powders.
1. Whenever a remedy requires the combination of all, or most of its principles, to ensure its full effects, as Bark, Ipecacuan, Jalap, &c.
2. Where medicinal bodies are insoluble, and indisposed to undergo those essential changes, in transitu, which render them operative; for it must be remembered that by minute division, every particle is presented to the stomach in a state of activity, being more immediately exposed to the solvent or decomposing powers of that organ.
3. Where the mechanical condition of the substance is such as to occasion irritation[294] of the stomach, as the Sulphuretum Antimonii, or in external applications to produce an improper effect upon the skin, as Hydrargyri nitrico-oxydum.
The degree of fineness to which substances should be reduced by pulverization, in order to obtain their utmost efficacy, is a very important question. The impalpable form appears to be extremely injurious to some bodies, as to cinchona, rhubarb, guaiacum, and to certain aromatics, in consequence, probably, of an essential part of their substance being dissipated, or chemically changed by the operation. Fabbroni, for instance, found by experiment that cinchona yielded a much larger proportion of soluble extractive, when only coarsely powdered. I think it may be laid down as a general rule, that extreme pulverization assists the operation of all substances whose active principles are not easily soluble, and of compound powders whose ingredients require, for their activity, an intermixture; whilst it certainly injures, if it does not destroy, the virtues of such as contain as their active constituent, a volatile principle which is easily dissipated, or extractive matter which is readily oxidized.
2. Compound Powders.
The disintegration of a substance is much accelerated and extended by the addition of other materials; hence the pharmaceutical aphorism of Gaubius, “Celerior atque facilior succedat composita, quam simplex pulverisatio.” Thus several refractory vegetable bodies, as myrrh, gamboge, &c. are easily reduced by triturating them with sugar or a hard gum; and some gum resins, as assafœtida or scammony, by the addition of a few drops of almond oil. Upon the same principle the Pharmacopœia directs the trituration of aloes with clean white sand, in the process for preparing Vinum Aloes, to facilitate the pulverization and to prevent the particles of aloes, when moistened by the liquid, from running together into masses; some dispensers very judiciously adopt the same mechanical expedient in making a tincture of myrrh; so again, in ordering a watery infusion of opium, it will be judicious to advise the previous trituration of the opium with some hard and insoluble substance, as directed in the Pulvis Cornu Usti cum Opio, otherwise its particles will adhere with tenacity, and the water be accordingly unable to exert a solvent operation upon its substance.[295] It is equally evident that in the construction of compound medicinal powders, the addition of an inert ingredient, which the mere chemist might condemn and discard as useless, not unfrequently acts a very important part in the combination, owing to its effects in dividing and comminuting the mere active constituents: the sulphate of potass in Dover’s powder acts merely in dividing and mixing more intimately the particles of opium and ipecacuan: the phosphate of lime appears to act in the same mechanical manner in the Antimonial Powder; so again, in the Pulvis Contrajervæ compositus, the prepared oyster shells may be a necessary ingredient: in the Pulvis Jalapæ compositus of the Edinburgh College, the cream of tartar greatly increases the activity of the jalap, by breaking down its substance and dividing its particles; and Van Swieten observes that the operation of this resinous purgative is improved by bruising it with sugar, and adding some aromatic. The old combination of Pulvis Helvetii consisted of alum and dragon’s blood, and there can be no doubt but that the effect of this latter ingredient, which has been often ridiculed, was to retard the solution of alum in the stomach, in consequence of which the preparation was likely to produce less inconvenience, and could therefore be administered in larger doses; the Edinburgh college has substituted gum Kino in their Pulvis Aluminis compositus, which may have the same effect in modifying the solubility of the alum.
In rubbing together different substances, it is necessary to remember that there are many saline bodies, which in the dry state become moist and even liquid, by triture with each other, and that, under such circumstances, they are susceptible of mutual decomposition. This change is effected by the action of water, derived from the following sources.
1. From the water of crystallization. This always operates when the proportion contained in the original ingredients is greater than that which the products can dispose of; that is to say, whenever the capacity of the new compound for water is less than that of the original ingredients. By previously driving off this water by heat, we shall of course avoid such a source of solution, and no liquefaction can ensue. Thus, if recently burnt quick-lime be triturated with calomel, the resulting mixture will be white, shewing that no decomposition can have arisen, but add a few drops of water, and it instantly assumes a dark aspect. If crystallized sulphate of copper be triturated with Acetate of lead, the resulting mixture will assume a fine green colour, but if the sulphate of copper be previously heated, and its water of crystallization driven off, no change of colour will be produced; if, for Acetate of lead, we substitute muriate of lime, and the sulphate of copper be crystallized, we shall obtain a result of a yellow colour, but if the sulphate of copper be anhydrous, the product will be colourless, becoming however instantly yellow, like the former, on the addition of a drop of water; and on a further addition of this fluid, the yellow product in both instances will be rendered blue; which proves that a chemical decomposition has taken place, and a muriate of copper resulted; for this salt is rendered yellow by a small, and blue by a larger proportion of water. The Cuprum Ammoniatum presents another illustration, for the ingredients, when rubbed together, become extremely moist, and undergo a chemical decomposition. Certain resinous bodies also, as myrrh, become liquid by triture with alkaline salts, in which case the resin and alkali form a soluble compound, which the water of crystallization, thus set at liberty, instantly dissolves.
2. From aqueous vapour in the atmosphere. The water of the atmosphere does not act upon these occasions, unless it be first attracted and absorbed by one of the triturated bodies; e. g. if Acetate of lead and recently burnt alum be triturated together, no change will be produced; but, if the burnt alum be previously exposed for a short time to the atmosphere, these bodies will, in that case, become liquid.
The physician, without this chemical knowledge, will be often betrayed into the most ridiculous blunders, an instance of which very lately came to my knowledge in a prescription for the relief of cardialgia and constipation, in the case of dyspepsia; it directed sulphate of soda and carbonate of potass, in the form of a powder, but the fiat of the physician, upon this occasion, only served to excite the ridicule of the dispenser, who soon discovered that the ingredients in his mortar dissolved into liquid.
During the exhibition of powders containing insoluble matter, it is always important to maintain a regularity in the alvine excretions, or an accumulation may take place attended with very distressing symptoms. Dr. Fothergill relates a case of this kind which succeeded the use of powdered bark; and Mr. E. Brande has communicated a similar instance of mechanical obstruction, produced by the habitual use of magnesia. I could also add, if it were necessary, some striking facts of a similar tendency, which occurred from eating bread that had been adulterated with pulverized felspar. The precaution seems more particularly necessary in the case of children, whose bowels are very impatient of extraneous and insoluble contents.[296] The dose of a powder ought not to exceed ʒj; and, when taken, should be diffused in water, wine, or any other convenient liquid; resinous and metallic powders require a thick and consistent vehicle, as syrup or honey, since they subside from those which are more fluid.
PILULÆ. Pills.
These are masses of a consistence sufficient to preserve the globular form, and yet not so hard as to be of too difficult solution in the stomach. The subject offers some extremely interesting points of inquiry. The following general rules will enable the practitioner to select those substances to which the form of pill is adapted, and to reject those to which it is not suitable, as well as to direct, extemporaneously, the most efficient mode of preparation.
I. The Selection of Substances.
1. Suitable Substances are, 1, All remedies which operate in small doses, as Metallic Salts; and 2, Those which are designed to act slowly and gradually, as certain Alterative Medicines, or 3, which are too easily soluble when exhibited in other forms, as Gamboge, &c. 4, Substances which are not intended to act until they reach the larger intestines, as in pills for habitual costiveness; see Aloes. 5, Bodies whose specific gravities are too considerable to allow their suspension in aqueous vehicles. Efflorescent salts may also be exhibited in this form, but they ought to be first deprived of their water of crystallization, or the pills composed of them will crumble into powder as they dry.
2. Unsuitable Substances are, 1, Those which operate only in large doses. 2, Which deliquesce. 3, Whose consistence is such as to require a very large proportion of dry powders to afford them a suitable tenacity, as oils, balsams, &c. 4, Substances that are so extremely insoluble, that when exhibited in a solid form they pass through the canal unaltered, as certain extracts.
Many remedies which are incompatible with each other in solution, may be combined in pills, unless indeed their medicinal powers are adverse or inconsistent, or their divellent affinities sufficiently powerful to overcome their state of aggregation.
II. Their Formation into Masses.
This is a subject of far greater importance than is usually assigned to it, as will be more fully explained in the sequel.
1. Many substances, as vegetable extracts, may be formed into pills without any addition; others, as gum resins, become sufficiently soft by being beaten, or by the addition of a drop or two of spirit, or liquor potassæ. Some dry substances react upon each other, and produce, without the addition of any foreign matter, soft and appropriate masses. The Pilulæ Ferri Compositæ, of our Pharmacopœia afford a very striking example of this peculiar change of consistence, which the mutual reaction of the ingredients produces by simple triture. The Pilulæ Aloes Compositæ offer another instance; for the extract of gentian, upon being triturated with aloes, produces a very soft mass, so that the addition of a syrup, as directed by the Pharmacopœia, is quite unnecessary. See Form: 12.
2. Many substances are, in themselves, so untractable, that the addition of some matter foreign to the active ingredients, is absolutely essential for imparting convenience of form. It is generally considered that very little skill and judgment is required in the selection of such a substance, provided it can fulfil the mechanical intention just alluded to—the fact however is, that the medicinal power of the pill may be materially controlled, modified, or even subverted, by the mode in which it is formed into a mass. Where the active element of a pill is likely to be improved by minute division, a gummy or resinous constituent may be usefully selected: under the history of Aloes, I have alluded to a popular pill, known by the name of the dinner-pill, in which case the mastiche divides the particles of the aloes, and modifies the solubility of the mass. The Pilulæ Opii of the former Pharmacopœia of London, consisted of equal proportions of opium and extract of liquorice, and the mass was so insoluble that its effects were extremely uncertain and precarious; in the present edition, soap has been very judiciously substituted; but in certain cases where we wish to protract the influence of opium, or that of any other active body, so as not to obtain its full effects at once, we may very advantageously modify its solubility by combining it with a gum resin or some substance which will have the effect of retarding its solution in the stomach. The Pilulæ Styrace of the Dublin college, presents itself as an efficient example of this species of pharmaceutical address; see also Form. 10, 11, 12. I am well acquainted with many formulæ whose utility has been sanctioned by experience, and I have no hesitation in believing that their salutary mode of operation would receive a plausible explanation from this simple law of combination. Dr. Young has very justly stated in his Medical Literature,[297] that the balsam of copaiba envelopes metallic salts, so as to lessen their activity; he says that the sub-carbonate of iron, made into pills with copaiba, was given for some weeks without any apparent effect; and that a few hours after the same quantity had been given, with gum only, the fæces were perfectly black. I do not know a more striking and instructive proof of the influence of a glutinous or viscid constituent, in wrapping up a metallic salt, and defending the stomach from its action, than is presented in the case published by the medical attendant Mr. Marshall, in consequence of the attempt of Eliz. Fenning to poison the family of Mr. Turner of Chancery-lane by arsenic, which she providentially administered in a heavy yeast dumpling. Soap is very frequently used for the formation of pill-masses, and it is an excellent constituent for substances likely to be injured by meeting with an acid in the primæ viæ; many resinous bodies may also be reduced to a proper consistence by soap, although in prescribing it, its levity should be attended to, or otherwise the pills will be too bulky; in general it will combine with an equal portion of any resinous powder, as Rhubarb, Jalap, &c.; it is of course ineligible where the substances are decomposed by alkalies, as Tartarized Antimony; this last precaution will also apply to aromatic confection as a vehicle, on account of the carbonate of lime contained in it. The Conserve of Roses has the advantage of retaining its consistency much longer than mucilage, but as it contains an uncombined acid, it is frequently inadmissible; it could not for instance be with propriety employed with the precipitated sulphuret of antimony. Pills made with mucilage, are apt to crumble when they are rolled out; this is the case with the Pilulæ Hydrargyri submuriatis; some extract therefore would be a more convenient constituent; in this particular case, however, the addition of a few drops of spirit would supersede the necessity of any constituent. Castor oil, in some cases, especially with some of the harder purgative extracts, will impart an eligible consistence.
Crumb of bread, furnishes a convenient vehicle for those salts which are ponderous, active in very small doses, or which are liable to be decomposed by other vehicles; but an objection is attached even to this, for it is liable to become so dry and hard when kept, that pills made with it will frequently pass undissolved. Swediaur mentions this fact with reference to Plenck’s mercurial pill, as well as to one of corrosive sublimate, and he proposes for this reason to substitute starch; the addition however of a small portion of sugar will prevent the bread from becoming thus indurated, and with such a precaution it may be very safely employed. For the purpose of forming active vegetable powders into pills, such as Digitalis, Conium, &c., I am informed by Mr. Hume of Long Acre, that in his experience melasses or treacle is the best constituent that can be selected, for it undergoes no decomposition by time, but maintains a proper consistency, and preserves the sensible qualities of the plant quite unimpaired for many years. I have deposited in the cabinet of the College, specimens of such pills, of hemlock and foxglove, which retain the characteristic odour of these vegetables, notwithstanding they have been now made for several years. Honey has likewise the property of preserving vegetable substances; seeds may be kept in it for any length of time, some of which, on being taken out, washed, and planted, will even vegetate. It has also been used for the preservation of animal matter; the bodies of the Spartan kings, who fell at a distance in battle, were thus preserved, in order that they might be carried home.[298]
Water will on some occasions be found a convenient expedient; powdered Rhubarb or Jalap may be thus made into masses without any increase of bulk, but the pills will be apt, if kept, to become mouldy.
3. In the formation of pills the ingredients should be hastily rubbed together, whenever they are liable to be injured by long exposure to the air; thus in the formation of Pilulæ Hydrargyri submuriatis compositæ, the compound is rendered less active by too long continued triture. See Pulveres.
4. In dividing pill-masses, it is usual to add to them, and envelope them in, magnesia; where calomel is present, I have satisfied myself by experiment that a muriate of magnesia is formed under such circumstances, and it is owing to this partial decomposition, that the surface of the pill exhibits a greenish hue; starch, powder of liquorice,[299] or orrice root, might perhaps under such circumstances be more judiciously preferred. In Germany, the powder of Lycopodium is generally used. Formerly, the pill was covered with gold leaf, which protected it from the influence of the stomach, and frequently rendered it unavailing.
It has been observed that many of the pill-masses directed in our Pharmacopœias, are liable to become so hard[300] and dry by being kept, that they are unfit for that division for which they were originally intended; indeed Dr. Powel considers it doubtful whether the greater number of articles had not better be kept in powder, and their application to the formation of pills left to extemporaneous direction; the necessity of this is farther apparent, when we learn that it is a common practice for the dispenser to soften these masses by the application of a hot spatula, or pestle, which sometimes carbonizes, and frequently decomposes them.
III. Their Form of Prescription.
In our extemporaneous directions, it is necessary to apportion with accuracy the quantity of active materials which we may wish each pill to contain, and since the proportion of the constituent can rarely be exactly defined, the equable division of the whole mass, into a given number of pills, will be safer than defining the weight of each pill.
A pill, the bulk of whose ingredient is vegetable matter, ought not to exceed five grains in weight, but where the substances which compose it are metallic and ponderous, it may without inconvenience weigh six or even eight grains.