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.
“Obstabat aliis aliud: quia corpore in uno
Frigida pugnabant calidis, humentia siccis,
Mollia cum duris, sine pondere, habentia pondus.”
_Ovid. Metamorph._ lib. 1. 19.
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.