Charles D. F. (Charles Douglas Fergusson) Phillips.

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sels became dilated.

The coagulum formed in the living vessel by perchloride of iron is
soluble, to some extent, in the stream of alkaline blood, and especially so
if the astringent solution used be unduly weak; it is also soluble in
slightly acid liquids, but is rendered more consistent by combining the
iron with alkaline chlorides (Piazza: JSulletin de Therapetitique, 1868).
The blood-clot, with lactate of iron, is said to form more slowly, and to
be more permanent.

The antiseptic powers of astringent iron preparations are connected
with the coagulation of albumen, and strong solutions are fatal to the
lower forms of vegetable life. Ferreil ascertained that the neutral strong
solution of perchloride arrested decomposition in a blood-clot (when it
had commenced), and formed with fresh blood a coagulum that remained
unaltered for many months ( Union Medieale, 1859, p. 374). Similar ob-
servations have been repeated since, but the irritant, properties of the
strong iron chloride preparations make them less suitable for surgical
disinfectant purposes than they would otherwise be, and carbolates, sul-
phates, etc., have superseded them.

PHYSIOLOGICAL ACTION (INTERNAL). Circulatory System. Under
the ordinary use of neutral preparations of the drug, the pulse becomes
more full and forcible, and the color of face and mucous membranes more
florid. It is commonly said that if they be pressed beyond a certain
point, symptoms of plethora and of congestion set in, as shown by flushes



142 MATERIA MEDIC A AND THERAPEUTICS.

and giddiness, engorged viscera, and tendency to hemorrhage; but if the
patient have good air and exercise, and moderate food, such effects are
not likely to occur. The blood will not take up more than a certain
amount, and will protect itself by non-absorption, rather than by elimi-
nation. Hirtz even asserts that he has never seen congestive symptoms,
vertigo, etc., except from the excessive use of chalybeate waters contain-
ing carbonic acid, to which he attributed them (Nouveau Diet.).

According to Sasse and Pokrowsky, the use of iron salts increases the
heart-action, and Laschkewitsch proved increased blood-pressure in ani-
mals taking even small doses (Husemann). In illustration of the effect
of large doses (though complicated by alcohol), may be quoted the case
of a woman who swallowed 1 oz. of the tincture of perchloride, during an
excited condition; the pulse became quick and small, the eyes injected,
and the face flushed; convulsive attacks occurred, but were probably hys-
terical; she recovered after free vomiting (Warburton: Lancet, i., 1869).
In disease, on the other hand, there is evidence sometimes of a sedative,
effect on the circulation. Giacomini records a slow and feeble pulse,
pallor, etc., after 20 to 40 gr. of carbonate; and Pize found it lower the
pulse and quiet the circulation in purpura and chlorosis, when accompa-
nied with palpitation; in the former case, some gastric irritation was
probably caused; in the latter, good effects resulted probably from im-
proved blood-condition. I have known the acetate quiet the circulation
when the perchloride did not do so.

Action on JBlood. According to Nasse, there exists in 1,000 parts of
blood, 0.832 of iron oxide. Haemoglobin contains 0.42 per cent, as a con-
stant quantity; most of it is in direct organic union with the red corpus-
cles, in the proportion of about 1 part of iron to every 230 (Gorup Bes-
anez); when dried, they contain seven times as much as the fibrine, and
four times as much as the serum (Boussingault). Being required then
for the normal constitution of red blood, iron is essentially a food, but
since illness follows deficiency in the number or quantity of corpuscles,
and iron in substance will often remedy such illness, it equally comes
within our province as a medicine, and from its curative effects, we may,
inverting the general rule, deduce some part of its physiological action.
That it can increase the number of red corpuscles is shown by the obser-
vations, e.g., of Rabuteau, who counted them by Malassez's method, in a
case of chlorosis before and after twenty days' treatment by protochloride
of iron: he found the number in a cubic millimetre to be near-ly doubled
{Gazette des Hopitaux, January, 1875); and in a specimen analyzed by
Prof. Simon, the globulin and hasmatin were more than trebled (" Animal
Chemistry," Sydenham Society). I need not multiply examples of this
fact (though it has been denied), but there is something further to be
learnt from the recent and careful observations of Hayem, on the blood of
anaemic persons ( Comptes JRendus, 1876, p. 985). He found that in cases of



IRON. 143

moderate chlorosis, the number of corpuscles was not markedly less than
normal, but they were altered in shape and size, apparently in consist-
ence, but most markedly in color-power, so that a given quantity showed
a red tint not deeper than that of half the number of normal corpuscles.
Further, after a course of iron, the number of corpuscles in the same pa-
tient was not always increased, sometimes it was diminished, but then
the corpuscles individually had grown larger and of normal shape, and of
so good a color as to equal even a greater number of the ordinary kind;
he concludes then that iron acts by improving the internal nutrition of
the globules, " it solicits them " to take up more haematin, more coloring
matter. These observations confirm the older ones of Le Canu (These,
1847), that iron is the main constituent of haematin, is inseparable from
the coloring matter, and must be at least an important element in the
color itself. Hayem's conclusions are of still more importance as bearing
on the assertions of Denis and of C. Bernard, that there is no real defi-
ciency of iron in chlorotic blood, because they prove such a definite change
in its vital characters under the medicinal use of the drug. Granted that
there is no numerical, there is clearly a physical or a vital change pro-
duced by iron; and although it may be true that ordinary nutriment con-
tains as much iron as should be wanted (Bernard), yet it seems equally
true that we may sometimes have to give much that we may get a little
absorbed (Gubler), that we must therefore give it " en masse," as we do,
and (apart from all theory) Hayem furnishes us with a rational basis for
our therapeusis. That the proportion of iron can vary in blood is proved
by the analyses of Picard ( Comptes Itendus, November, 1874) ; in 100
c.c. taken from three dogs respectively young, adult, and weakened by
hemorrhage, he found that the amount of iron was .092, .065, and .041,
and he established also the fact of a definite and constant relation be-
tween the amount of iron in any specimen of blood, and the amount
of contained oxygen as liberated in vacuo from quantities of 100 c.c.

If it be asked how iron adds itself to the corpuscles and promotes
their growth, we must recognize that it is not by mechanical addition to
the formed corpuscle, or else the proportion in chlorotic blood could be
at once increased, and failure to cure would not occur, nor relapse be so
frequent. An observation by Quevenne throws some light upon the pro-
cess; he found in proteid solutions withdrawn from the stomach of dogs
more abundant precipitates of nutrient material if meat or wine, or iron
especially had formed part of a meal, and suggested that in the portal
vein a similar precipitate occurs (from the meeting of currents from
splenic and mesenteric vessels both laden with the results of digestion in
intimate contact with the added iron), that such precipitate is at least
precursory to the formation of globules, and that at this stage iron ex-
erts its blood-forming power (" M6moire," etc.). It would seem that
better corpuscles are formed when (the vital processes being fairly ac-



14:4 MATERIA MEDICA AND THERAPEUTICS.

live) one of their essential constituents is presented in unusual abun-
dance for absorption. It becomes then combined with them in some
organic, rather than chemical or mechanical union; and besides such di-
rect action in the formation of globules, iron exerts special stimulating
power over the blood-glands, which power, indeed, is by Trousseau and
others considered more important than the last-mentioned. Further,
when even a few new corpuscles have been formed, they add fresh nerve-
energy and improve digestion, and the blood-forming process becomes
still more actively assisted. Iron has been variously thought to be in
the corpuscles in its metallic state, as phosphorus exists in the brain (Le
Canu, Mulder), or as a free phosphate (Fourcroy), or as a peroxide (Denis,
Mialhe, and a majority of observers). A precise chemical theory was
elaborated by Liebig, who taught its presence as peroxide on account of
its reactions with sulphuric acid, and found that this hydrated peroxide,
in contact with moist organic membrane in partly closed vessels, could
change to a protocarbonate, and on free exposure to oxygen could change
back again, with evolution of carbonic acid: so that venous blood was
held to contain a protocarbonate, and recently aerated blood a peroxide.
It is difficult to accept so entirely chemical a theory, which implies that
the element is more loosely combined with the corpuscle more distinct
from its substance than it can be; other difficulties are stated in physi-
ological works, and Liebig's view, though highly ingenious, and contain-
ing no doubt a partial truth, can only be accepted as an hypothesis.

Oxidizing Power. To the metallic element in the corpuscles has been
somewhat fancifully attributed an electrical and a polarizing action, and
even a power of increasing heat by mechanical friction ! There is a gen-
eral and better-founded opinion that it greatly aids in the conveyance of
oxygen and in oxidation (a main function of the corpuscles), and some
modern researches support this opinion thus, Schonbein, quoted by Dr.
A. Sasse, proved that animals without blood-corpuscles were suffocated in
oxygen as much as others in nitrogen; that the gas must become changed
into ozone and antozone in order to be fully efficient, and that iron, or
corpuscles, will effect this change. Iodized paper is turned blue both by
ferric solutions and by diluted blood, and peroxide of iron can change into
protoxide and ozone. As an illustration, he quotes the spread of rust on
steel, or " iron mould " on linen, the stain extending by formation of
ozone, which corrodes the adjacent particles of the steel, while the re-
duced oxide attracts fresh oxygen from the air. Similarly, it is argued,
the iron in the corpuscle continues alternately to attract and to give up
oxygen, and to become a proto- or a per-salt until finally excreted
(Schmidt's Jahrb., v., 1865).

If iron, when taken into the system, does aid oxidation it should raise
the temperature and increase tissue-change, but the amount of scientific
evidence on the subject is unfortunately small. The observations of W.



IKON. 145

Pokrowsky, though valuable and often quoted, were made on patients
seriously ill and recently removed to hospitals, and seem scarcely sufficient
for the conclusions drawn from them. In five out of six cases the tem-
perature was slightly raised ; in one (a case of phthisis with haemoptysis,
taking small doses of tinctura ferri) it was lowered; the pulse was either
changed or slightly increased, the elimination of urea was augmented,
and weight was gained. In one case the rise of temperature followed
within five hours of the dose, and it occurred equally in the cases where
temperature was previously normal. It should be noted that the syrup
of iodide of iron was chiefly used, and the iodine must be allowed for as
influencing tissue-change; also that Pokrowsky himself, while recording
improved nutrition, traces it only to " improved tone of capillary vessels,"
not to increased oxidation (Virchow's ArcJdv, Bd. xxii., v. 6); he states
that he acted as a student under Dr. Botkin. I find no reference to other
observations by the latter upon healthy men, as mentioned by Sasse.

Some recent analyses by Rabuteau would seem to support the sup-
position of increased oxidation, but they refer only to the renal secretion;
comparing the results of five days when taking daily 12 ctgr. of perchlo-
ride of iron with the same period, on the same diet, but without the iron,
he concluded that it did not affect the quantity of his urine, but aug-
mented its acidity and its solid constituents and urea (10 per cent.).
Phosphoric acid was lessened, as it usually is, under cod-liver oil and
other restoratives.

The researches of Picard (v. p. 143) proving a definite ratio between
the amount of iron and of oxygen contained in the blood, are of impor-
tance in this connection, and it is an axiom that iron preparations exert
their best curative effect when the supply of oxygen is ample; but the
conclusion of Sasse that iron can supply the place of red corpuscles as
an ozonizing agent in the body can scarcely be correct; were it so, the
cure of anaamia and chlorosis would be more certain than it is. We can
but consider iron as an adjuvant, and as being, when in the corpuscles,
subject to other than merely chemical laws.

Different Action of Proto- and Per-salts. The important experiments
of Blake, so far as they can be practically applied, would point to a
marked difference between the action of proto- and per-salts on the blood
and the circulation. Injecting 10 gr. of protosulphate (in solution) into
the jugular vein of a dog, there occurred a quick but temporary depression
of the heart-action and blood-pressure; with 28 gr. heart-action stopped,
and pressure fell to zero; 70 gr., in divided doses, caused a gradual gen-
eral dulness, and death from asthenia the right cavities of the heart
were distended with dark blood, the left contained 1 oz. of brighter color,
but the coagulating power was lost.

When 2 gr. of persulphate, dissolved in 2 oz. of water, were injected
into the same vessel, pressure was diminished for a brief time, but quickly
VOL. II. 10



146 MATEEIA MEDIC A AND THERAPEUTICS.

rose again when 3 gr. more were given; death soon followed; the left
heart-cavities were empty and contracted, the right distended, the blood
coagulated at once when exposed; the lungs were bright scarlet and con-
tracted, and Dr. Blake attributed death to contraction of their capillaries
preventing the supply of arterial blood to the left heart. Five grains
thrown into the axillary artery raised the blood-pressure at once from 6
to 12 degrees (by the haemadynamometer) ; death followed, and both
sides of the heart contained dark blood, implying that the lung-contrac-
tion was overcome in this instance, but only by an extreme degree of
pressure. The obstruction of the lung-capillaries might be caused by a
physical change in the blood, rather than by contraction of the vessels,
but the quantity seems too small for the former effect, and an analogous
contraction of vessels is produced by digitalis, which proves its possibil-
ity.

The general results of the experiments go to demonstrate that proto-
salts lower cardiac irritability, and in toxic doses arrest heart-action, cause
slow respiration, sedation of nerve-system, and death by depression: per-
salts, on the other hand, have no direct action on the heart, certainly do not
lessen its irritability; they cause symptoms of pressure on the nerve-cen-
tres, and death through interference with the pulmonary circulation, cut-
ting off the supply to the left heart. Collaterally, it is argued that proto-
salts cannot be readily oxidized in the blood, or else some " peroxide-ef-
fects " would be developed from 70 gr. of a proto-salt; and that per-salts
are not readily reduced, or the effects of such small quantities would not
be so persistent (Journal of Anatomy and Physiology, 1869), but re-
. viewing all the experiments and conclusions, we must doubt whether the
mechanical forcing of substances into the blood-current can be held to
compare with natural absorption and assimilation. The difference, how-
ever, exerted by the two classes of salts upon coagulation, has an impor-
tant bearing upon their use for local injections, on the formation and solu-
tion of clot, on embolism, etc.

Digestive System. Most of the soluble salts of iron have an inky as-
tringent taste, and by continued use, stain the teeth and mouth of a dark
color (tannate of iron). Compounds with a mineral acid exert a local
astringent action on the mouth and stomach, and if the dose be small and.
diluted, may improve the tone and the functional power of the gastric
membrane: but these, or any other preparation, if given in undue quan-
tity, may irritate, and cause indigestion (from lessened secretion), with
sense of weight, nausea, or diarrhoea.

Quevenne experimented with gastric fluid withdrawn through a fistula
from the stomach of dogs, and judged of the effects of iron on digestion
by the precipitates of peptones obtained from the fluid at certain periods
after a meal. There was less precipitate when the juice was acid than
when partly neutralized, but he concluded that various forms of iron, given



147

with food, improved the character and amount of the precipitate: they
did not increase the proportion of pepsine, nor alter the duration of the
digestive process, but were quite readily absorbed, and the dogs thrived
and gained flesh under their use. On the other hand, when given with-
out food, and especially in the metallic form, iron did not stimulate the
formation of sufficient secretion to dissolve itself, but acted as a foreign
body, and impaired digestion: 10 to 20 gr. of reduced iron would cause
diarrhoea, hence a reason for the ordinary rule of ordering iron prepara-
tions at the time of a meal, and in small doses (2 to 3 gr.). The sulphate
and chloride of iron have sometimes, by mistake or for criminal purposes,
been taken in large quantities (1 oz. and upward), and have caused vio-
lent pain and vomiting, with other symptoms of irritant poisoning, and
gastro-enteritis, but have rarely proved fatal (Taylor).

Secretion. Astringent preparations will usually lessen the secretions,
especially those of the gastro-intestinal tract. Upon the kidney, in health,
the effect as to quantity of secretion is not much, but some irritation of
the bladder and the urinary tract may lead to increased frequency of mic-
turition. In some persons, however, and in some diseases, iron prepara-
tions, especially the tincture of the chloride, the citrate, and the tartrate,
have proved good diuretics, directly or indirectly: the tincture, in fact, is
termed by Simpson a "renal purgative" when recommending it in "sur-
gical fever" (Medical Times, i., 1859, p. 517). The secretion of milk has
diminished or ceased in cows drinking a ferruginous water, and in some
suckling women taking a course of iron (Martin) ; Bistrow records a sim-
ilar result in a goat under the use of lactate of iron : on the other hand,
there is clinical evidence that non-astringent preparations taken by anse-
mic women during lactation will improve the secretion as well as the gen-
eral health (Routh: Medical Times, i., 1859). The effect is clearly that
of a restorative, and as we find so often in the use of iron, it will vary
with the preparation and the patient taking it.

Generative System. From an early period iron has had the repute
of specially stimulating this system. A classical cure of impotence by
iron-rust among the Argonauts is commonly quoted, and we may rescue
from oblivion the curious marriage-contract said to be common at one
time among the burghers of Frankfort, to the effect that their wives
should not visit the iron springs of Schwalbach more than twice in their
lives, for fear of being too fruitful (Dr. Jacques, These, Paris, 1843).
There is clinical evidence of its value in sexual debility, and in derange-
ment or suppression of the ovarian function, but it seems more explicable
by a general tonic and heematinic power than by a special local action,
though Trousseau attributes to iron aphrodisiac power. The tincture of
the chloride is in somewhat common use as a supposed abortifacient.
Taylor regards it as a dangerous drug for pregnant women, but his ex-
amples scarcely corroborate this, and the clinical evidence and experience



148 MATERIA MEDIC A AND THERAPEUTICS.

as to medicinal doses mentioned later on (v. p. 173) tend to an opposite
conclusion. We may recognize, however, that very large doses of as-
tringent preparations are not safe they may injure by general irritation
or local congestion, as shown in some cases reported in Medical Times,
ii., 1860, p. 81

SYNERGISTS. Manganese, and most tonics and acids: as astringent,
ergot, turpentine, etc.

ANTAGONISTS INCOMPATIBLES. Weakening and fluidifying agents
such as alkalies and mercurials: the former are also, together with sul-
phur and tannin, chemically incompatible with most iron preparations..
Gubler mentions nicotine as antagonistic.

THEBAPEUTICAL ACTION (EXTERNAL AND INTERNAL). In this in-
stance I find it undesirable to separate the external from the internal ap-
plication of the remedy, for they are very closely connected, and if one
set of observers prefer the one in any particular form of disease, parallel
observations will be found in favor of the other; thus it is as regards
hemorrhage, diphtheria, erysipelas, and even varix.

Iron in the metallic form was in early use as an astringent and robo-
rant, though we note the absence of any mention of it in Hippocrates. In
extraordinary demand at the early part of the last century, as a secret
remedy, and under the name of " Elixir d'Or," " Gouttes d'Or," " Tein-
ture de Bestuchef," etc., the perchloride solution with ether was priced
at a golden louis per \ oz., procured pensions and promotions for its
makers, and served as a present for sovereigns; but when its last paten-
tee revealed the secret, "for fear his death should lose it to the world,"
and when Catherine of Russia purchased the precious recipe for many
thousand rubles, and presenting it to the St. Petersburg College of
Medicine allowed it to be published (1780), this remedy which had been
held to cure "gout and epilepsy, cramps and paralysis, rheumatism and
hypochondriasis," sank into an obscurity as little deserved as was its pre-
vious reputation. Bayle, whose treatise is an excellent epitome of the
therapeutical knowledge of his time, mentions only the metal and the
carbonate as remedies in neuralgia and chlorosis (Biblio. de Therap., iv.,
1837), and the use of soluble ferric compounds a use so frequent and
so valuable in modern practice that we may wonder how our predecessors
fared without it dates really from about 1850.

Hemorrhage. The astringent compounds of iron with a mineral acid
are excellent local styptics in all forms of capillary hemorrhage, such as
from leech-bites, wounded gums, hemorrhoids, bleeding from the nose,
etc. The part should be thoroughly cleansed from clot, and then a plug
or compress moistened with the solution should be firmly pressed upon it,
or in cavities an injection (diluted) may suffice. Sir James Simpson
strongly commended a solution of the perchloride in glycerin, used it
freely for all forms of hemorrhage, and with special success in some se-



IRON. 149

vere cases of bleeding from the vagina and uterus (Medical Times, i.,
1858, p. 79). Demarquay, Lallemand, and Deleau were using the same
haemostatic with great advantage in France about the same time (Ga-
zette des Hopitaux, 1858-59).

The liquor ferri perchloridi fortior (British Pharmacopoeia) is quite
serviceable for the purpose, but is more acid, and proves often more irri-
tating than need be, and may be well diluted with an equal part of water
or glycerin. The liquor ferri sulphatis is preferred by many surgeons,
and by others the liquor ferri subsulphatis, or Monsel's solution l of the
U. S. Pharmacopoeia; this is made with sulphate of iron, sulphuric and
nitric acids, and is much less caustic and irritant than our solution; it is
used in rectal hemorrhage 1 part to 4 of water (Allingham: Lancet, i.,
1874) and the "haemostatic cotton" used by Marion Sims is prepared
with it. The so-called " iron alum " is probably an equally effective
preparation.

Tonsillar Hemorrhage Wounds. Wetherby, of New York, records
a very severe case of bleeding from the tonsil (cases which are specially
anxious ones, on account of the proximity of the carotid) completely con-
trolled by the application of Monsel's solution (Ranking, ii., 1866); and



Online LibraryCharles D. F. (Charles Douglas Fergusson) PhillipsMateria medica and therapeutics, inorganic substances; (Volume 2) → online text (page 18 of 40)