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

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exposure to arsenical vapor in aniline works, by Dr. G. de Mussy (Lancet,
i., 1876). Dr. Leroy (d'Etiolles), who has written specially on the subject,
describes a case of paraplegia succeeding to acute arsenical symptoms after
the application of a caustic paste to a cancerous breast, and another ag-
gravated case of paraplegia, weakness and anaesthesia of arms with diar-
rhoea, and ultimately death from marasmus (Gazette Ilebdom., 1857).

Christison has remarked that arsenical palsy resembles that of lead in
its character, and Gubler and Duchenne have found it sometimes indenti-
cal. Leroy, however, points out that it not so invariably affects the ex-
tensors, and that it is more generalized.

The wasting of limbs is more general, and they may become semi-
flexed; when all are affected, the upper recover before the lower, a point
of difference from cerebral palsies. An average duration is from four to
ten months, and the prognosis is favorable under treatment.



ARSENIC. 33

Circulatory System. After administration of arsenic, analysis has de-
tected it in the clot i.e., united with globules, and not simply dissolved
in the serum. Claude Bernard taught that it acted on the corpuscles in
such manner as to diminish the activity of interchange of oxygen and
carbonic acid (Medical Times, ii., 1861). The experiments of Brodie had
already indicated undue fluidity of blood as an effect of arsenic, and mod-
ern observations refer this condition to a solvent action on haemoglobin:
thus, if arseniuretted hydrogen be passed into defibrinated blood, it be-
comes black, and gives with the spectroscope one large dark band instead
of the two normal ones; by degrees, the spectrum wholly disappears, the
haemoglobin is destroyed, and the liquid turns yellowish-green. It seems
probable that the same gas is developed to some extent from arseniates
absorbed into the living organism, and that it exerts a similar destructive
action on the globules; this would explain the anaemia, and the consequent
oedema and anasarca, met with after continued use of even medicinal
doses, as well as the icteric tint of skin, and the petechiae and hemor-
rhages in cases of poisoning. Though there is evidence that in certain
forms of anaemia the number of the corpuscles is increased under arsenic
(Gowers: Practitioner, July, 1878, and Bramwell), there can be no doubt,
that an opposite result follows both its long-continued use in disease, and
any appreciable quantity of it taken by healthy persons. Thus, Lemare-
Piquot (Honfleur), suffering from cerebral congestion, had himself bled
many times, and by careful observations of the proportion of clot to se-
rum showed that the continued use of arsenic could markedly lessen the
former. The normal maximnm proportion of clot he reckoned at 54 per
cent. ; with any amount above this, cerebral symptoms, such as giddiness
and oppression, appeared. In October, 1845, when suffering from such
a condition, he found, on being bled, that the proportion of clot was 68
per cent., the serum being at 32 per cent. only. During the next four
years he was bled more than twenty times with but partial and temporary
relief. In March, 1849, he began the use of arsenical solution in small
doses twice daily, at that time his proportion of clot being 69 per cent.
After one month's arsenical treatment he felt well, and the proportion
found on bleeding was reduced to 52 per cent. In succeeding years the
same result occurred several times; he illustrated it also in other cases,
and concluded, both from analyses and clinical results, that arsenic always
rendered the blood less plastic, and lessened the number of globules (Bul-
letin de Therapeutique, t. Ivii., 1859). More recently Cutler and Bradford
also found red and white corpuscles to 'be diminished in number under
arsenical medication, and Malcolm Morris reports diminution in some
cases of psoriasis when the general health was good e.g., F., aged twen-
ty-three, on August 14th, showed 58 corpuscles in each square (of Dr.
Gowers' instrument), was ordered Fowler's solution (TTt,v. ter die), and on
21st showed 48 only per square: continuing treatment, on September llth
VOL. II. 3



34 MATERIA MEDICA AND THERAPEUTICS.

there were only 37.3 the eruption was nearly gone {Practitioner, 1880).
The force and frequency of the heart's action and the activity of the
capillary circulation are usually increased by minute doses (Feltz, Har-
less) and especially in weakly persons (u. p. 35) : larger quantities induce
palpitation with quick, small, and irregular pulse ; the face is flushed,
while the extremities are cold.

Poisonous doses markedly depress the circulation, and ultimately ar-
rest heart-action (in diastole) in the lower animals, as found by Sklarek
in batrachia and in cats there was no previous stage of excitement
(Reichert's Archiv, 18G6). Although the frog lives on for ten minutes
after arrest of cardiac action, no stimulus will re-excite this, and yet ir-
ritability of cardiac muscular tissue persists, so that Sklarek concluded
that arsenic paralyzed the motor ganglia of the heart. Unterberger also
records a very pronounced fall in the blood-pressure and pulse-rate
(Archiv. filr Exper. JPathoL, Bd. ii.). There is clearly a direct depres-
sant effect on the heart in fact, this causes death in cold-blooded ani-
mals, though not usually in warm-blooded. Some palsy of vaso-motor
nerves is also indicated, and, according to several experiments, this is lim-
ited to the abdominal division of those nerves: the exact explanation,
however, requires further development. Though Lesser \erified Sklarek's
observations he did not come to the same conclusion that arsenic causes
death by paralysis of the heart, but denies it for the simple reason that
frogs survive excision of the heart for more than thirty minutes, while
arsenic kills them in ten minutes. Ringer and Murrell found (in frogs)
a varying effect upon the heart, it being sometimes completely arrested,
sometimes continuing to beat after complete general paralysis, but they
explained the difference by a variation in dose; a large one being quickly
absorbed and conveyed to the heart arrests it at once, leaving little for
the circulation to distribute, while a small dose paralyzes the central
nervous system before the heart (loc. cit.). In warm-blooded animals the
pulse-rate was increased at first by small and medium doses injected into
the veins, afterward it was diminished; by a large dose it was decreased
at once, and blood-pressure reduced. The increase of the pulse-rate was
traced to lessened influence of the vagus, and increased action of car-
diac ganglia, the decrease of pulse-rate to contrary conditions. Stimula-
tion of vaso-motor centres was not marked unless injections were made
directly into the carotid, and Lesser could not verify paralysis of those cen-
tres under any conditions (Virchow's Archiv, 1878). In the human sub-
ject, the pulse usually becomes weak, rapid, and gradually more irregular
till heart-action ceases : venous stasis naturally occurs, and there is pallor,
lividity, and finally cyanosis of the surface and of visible mucous mem-
branes.

Respiratory System. Lesser verified a markedly stimulant effect of
small doses, both on the respiratory centre and on the pulmonary ter-



ARSENIC. 35

minations of the vagi ; large quantities, on the other hand, extinguish
nerve-irritability in these parts. That the effect is directly on the centre
is clear from its occurrence even after section of the trunks of vagi, but
when these nerves are entire the effect is greater, so that they have some
share in it. Small doses taken under certain conditions as, for instance,
by the Styrian mountaineers render the respiration easier, less labored,
and less hurried under severe exertion. On the other hand, even medici-
nal doses, if long continued, will induce in some persons a dyspnoea,
allied to that of emphysema or even asthma, with dry cough or hawking
of .mucus. This I have verified several times in the subjects of eczema,
observing its cessation with the omission of the drug, and its return
under arsenical influence; there may be also hoarseness, coryza, tonsilli-
tis, or even, according to some observers, bronchitis (McCall Anderson),
probably from irritation excited in the bronchial mucous membrane by
the elimination of the drug; it has certainly some special determination
to the pulmonary tract. After large poisonous doses the dyspnoea is often
urgent, and the respiration stertorous.

Cutaneous System. In frogs, one effect of arsenic is to cause a ready
peeling or stripping of the whole cuticle some hours after hypodermic
injection (Ringer and Murrell). In man, small doses, continued for a
limited time, improve the skin-condition, and often (but not always) im-
part freshness and ruddiness to the complexion, while in animals they
render the hairy coat more glossy and bright. Kohler remarks that
since arsenic is eliminated by the sweat-gland -(especially when they are
acting vicariously for the kidneys), there is nothing remarkable in its
modifying the circulation and nutrition of the skin, and its effects are
explained by a capillary congestion and the presence of more blood in
the superficial vessels, and this again has been attributed to a vaso-motor
palsy allowing dilatation of such vessels.

Rabuteau thinks such a view cannot be accepted, because tempera-
ture is not raised as it is in experimental vaso-motor palsy i.e., after
sections of sympathetic. This, I think, is a question of degree the rise
might be more or less according to the amount of paralysis induced by a
drug it would not be so complete as after section. Moreover, Harless
reports a distinct rise, though recent experiments indicate a fall of tem-
perature as the more usual condition connected with arsenical action
(Lolliot). Rabuteau prefers to explain the florid color by an " altered
appearance of the globules."

When the drug is omitted after continuous use, an opposite condition
one of pallor and anaemia is said to follow (Medical Times, ii., 1854).
Certainly arsenic, if long continued, leads to an unhealthy, dry, and
somewhat scaly condition of skin, which has been called by some pity-
riasis, and by others even psoriasis, though I have never seen anything
like a true case of the latter malady thus caused. Rabuteau observes,



36 MATERIA MEDICA AND THERAPEUTICS.

" We never see squamous affections from arsenic, contrary to the asser-
tions of homoeopaths " (" Elements," p. 200).

Perhaps the extreme and most characteristic cutaneous result of ar-
senical saturation is a brown color of the face and various parts of the
body (Kirchgasser: Centralblatt fur Med,, 1868). It is not common, but
has been sometimes seen in such a form as to resemble argyria. Prof.
Wilson gives the following illustration: A lady had taken for fifteen
months comparatively large doses of arsenic for gutta rosacea, and two
months after commencing the medicine, a change of color had been no-
ticed in the skin, first over the abdomen, then or* the breast, neck, face,
and hands. When seen by Prof. Wilson the face was yellowish-brown,
the eyeball dark, the whole body colored more or less; chronic erythema
affected the palms, there were hard dry points at the sweat-glands, the
eyelids and the extremities were cedematous (Journal of Cutaneous Medi-
cine^ vol. i., p. 354). In some of Mr. Hogg's cases, children got a " dusky
skin-eruption in patches " from arsenical wall-papers (British Medical
Journal, i., 1879). Such a condition depends not on chemical combina-
tion (as with silver) but on abnormal pigmentation (Gubler).

Cold clammy perspirations have also been connected with arsenical
action, and pustules and ulcerations have sometimes followed it. In
acute cases, either of poisoning or of unusual susceptibility to the action
of the drug, patches of erythema or of urticaria (local congestions of
skin) and even acute general lichen may occur. Macnab recorded an
eruption like measles produced by 3-min. doses of Fowler's solution daily
for three weeks (Medical Times, i., 1868), and Wyss says that he traced
to it a case of alopecia areata from affection of the trophic nerves of
hair-follicles (Archiv der Heilk., 1870, Hft. i.).

Among rarer consequences, erysipelas with bulke has been credited
to arsenic, herpes has been traced to it by Mr. Hutchinson, and an obsti-
nate eczema by Dr. Balfour (Edinburgh Medical Journal, 1860). Dr.
Imbert Gourbeyre has specially written on arsenical eruptions, and, in
cases of acute poisoning when the patient survived several days, has
seen them petechial, papular, vesicular, and pustular.

A degree of cutaneous swelling, characteristic enough to have re-
ceived the name " oedema arsenicalis" usually occurs first about the eye-
lids and suborbital tissues, and is one of the earliest symptoms of consti-
tutional action. In severe cases it may affect the extremities and even
the trunk, and amount to general anasarca, as recorded so early as 1819,
(Edinburgh Medical Journal, v., 15). In Dr. Feltz's cases already re-
ferred to, there occurred, on the second or third day, swelling of the eye-
lids and conjunctivas in some instances of the whole face, with a rash
like scarlatina or urticaria. In most of them there was itching of the sur-
face, and scratching gave rise to an urticarial rash; in one man the same
eruption, together with herpes, appeared on the scrotum.



ARSENIC. 37

Mucous Membranes. We have already noted characteristic arseni-
cal effects upon the membrane of the mouth and intestinal canal. The
lips, the nose, especially at its orifice, the anus, and the vulva often be-
come similarly irritated and inflamed, and urethritis has been traced to
medicinal doses of arsenic (Medical Record, 1878). On the mucous mem-
brane of the eye the effect of the drug is often very early seen, so that it
becomes a useful index of the degree of physiological action. Itching
about the lids is first complained of, and a rough sensation as of dust in
the eye; the conjunctiva is seen to be congested, and purulent secretion
may be formed. Conjunctivitis is a frequent symptom in arsenical poi-
soning, and Dr. Taylor describes " tumid, everted lids and painful vision "
in patients affected by arsenical papers, etc. ( Ophthalmic Hospital Report,
1859, and British Medical Journal, ii., 1871).

Glandular System. Under small doses of arsenic the secretions are
increased, especially of those glands by which the drug is eliminated. In-
crease of quantity of the saliva is exceptional in acute poisoning, but oc-
curs when absorption takes place slowly and gradually. The bile, the
intestinal secretions, and, generally speaking, the urine are augmented
under its use; and if there be no diuresis the perspiration is commonly
stimulated, and arsenic can be detected in it (Kohler: Ilandbuch, p.
724). Hoffmann, Glauber, Agricola, and Pott have even recommended
arsenic for a diaphoretic effect, and I have myself sometimes observed
this from it.

Osseous System. Struck by Wegner's observations on bone-changes
under phosphorus, and following up the paper of Maas, " On the Influence
of Arsenic in Bone-growth, and its Value in Surgical Therapeutics "
(1872), Th. Gies has recently published some careful and interesting ex-
periments which well illustrate such influence (Archiv fur Exper. Path.,
etc., Bd. viii., Hft. iii., December, 1877). Using at first young rabbits
badly nourished, he found that arsenic destroyed them without causing
bone-change; but having, by careful food, secured for fresh animals ap-
parently more resisting power, the same daily doses (0.005 to 0.002
gramme arsenious acid) continued for nineteen to thirty -four days, seemed
to improve their condition, as compared with rabbits from the same litter,
and fed in the same manner (but without arsenic): the former were
larger, heavier, with clearer skin, and healthier-looking than the latter,
and after death the respective bones could be at once distinguished. In
the long bones of the arsenic-eaters was a special thick layer (arsen-
schichte) of bone between the epiphysis and the shaft; the shaft also was
thicker, and in bones, such as the ribs and the vertebras, the structure
was much more dense, and harder to divide, than in normal animals; the
new structure was true bone, but the bone-corpuscles and Haversian
canals were smaller than the average. Comparative experiments were
made with many rabbits, .cocks, and pigs, and in such manner as to



38 MATERIA. MEDICA AND THERAPEUTICS.

leave no doubt whatever that increased growth and condensation of
bony tissue were traceable to the action of arsenic. In old animals,
where epiphyseal gHowth had ceased, increase of thickness of bones oc-
curred: on the other hand, if the doses were increased beyond a certain
point, resorption of bone occurred, and symptoms of poisoning set in.
Bones purposely fractured had not united under the treatment, for their
small size made it impossible to keep them in position, but a false joint
formed, and much callus was round the broken ends;' there was fatty de-
generation of all internal organs. Gies does not adopt Wegner's view of
increased stimulus given to bone-formation, but rather that of Cunze and
Lolliot, that arsenic diminishes tissue-change, especially as regards carbo-
hydrates, and hence follow increased deposit and insufficient removal of
organic particles.

Genital System. This system often shares in the general stimulation
and irritation induced by small doses of arsenic, as has been noticed in
the arsenic-eaters of Styria, and in experiments on animals. Gies espe-
cially remarked it in the cocks used for his observations on bone-growth
(loc. cit.). Clinically, Prof. Charcot was led in two cases to a contrary
conclusion, but Devergie showed that this could not be sustained, and
that stimulation to some extent was not unusual (Bulletin de Thtrapeu-
tique, 1864); this, however, is not such as to preclude the medicinal use
of the drug, and it finds its place in the treatment of amenorrhoea.

In arsenical poisoning, inflammation of the genitals has been said to
occur (Hunt), and certainly much irritation of them has been present,
especially in women; but it would seem to be connected rather with the
general irritation of mucous membrane than with these special organs.
'The young of animals subjected to an arsenical course were born dead,
but fully developed; their birth was delayed rather than premature (Th.
Gies, loc. cit.), and no markedly injurious effect can be traced on the
uterus. In many instances of arsenic being taken by pregnant women,
even when with fatal results, abortion has not occurred ( Guy's Reports,
vol. vii.).

Urinary System. The urine is commonly increased in quantity for a
time under small doses, but with their continuance renal irritation may be
induced, so that the secretion is lessened, and elimination of the drug im-
peded. Hence it is an important practical point to examine the urinary
condition during arsenical treatment, and to use, if necessary, alkaline
diuretics. Lolliot traced hfematuria and albuminuria to arsenic, and, in a
case of pythisis, carefully recorded by Dr. Weir Mitchell, albuminus urine
was induced by 4 to 12 min. of Fowler's solution given daily for a few
weeks; anasarca also set in, and these conditions ceased and then re-
curred concurrently with omitting and resuming the medicine (New York
Medical Journal, vol. i.). After poisonous doses the urine, though at
first it may be passed too often, soon becomes scanty, and its evacuation



ARSENIC. 39

causes scalding pain and tenesmus; it may contain blood, albumen, and
casts, and sooner or later becomes suppressed; urethritis has been already
mentioned.

Urinary Excretion in Relation to Tissue-change. The estimation of
urea and other constituents of the urine furnishes important evidence as
to the influence of arsenic upon general nutrition and tissue-change, for
it is clear that if the principal urinary ingredients are increased under its
use, tissue-changes must be going on rapidly, and vice versa. There has
been some contradiction between observers on these points. Sabelin re-
corded increased excretion of urea under arsenic (from 12 to 28 gr.); also
marked increase in the chlorides and earthy phosphates, and proportionate
diminution of uric acid an incompletely oxidized product (hence G. See
argued that the drug favored oxidation and promoted metamorphosis
(" Nouv. Diet.," Art. Asthme) he has, however, himself since withdrawn
these views). Fokker published two analyses showing a slight increase of
urea after 0.01-gramme doses (Schmidt's Jahrb., Bd. clviii.), and Gaeth-
gens recorded the same in two dogs taking soda arseniate; also decidedly
increased tissue-change under toxic doses (Centralblatt fiir Med., 18*75,
No. 32, s. 529, and 1876, No. 47, s. 833). Binz and Schulz, relying upon
these observations, and noting also that hypodermic injection of arseni-
ous acid did not produce a local caustiff effect but inflammation in distant
organs e.g., the stomach have recently argued that " this substance, in
contact with living protoplasm, acts in the tissues as an oxidizing agent
or carrier from one albuminous molecule to another, being converted dur-
ing this process into arsenic acid, then reduced, again oxidized, and again
reduced " ( Centralblatt filr Med., ii., 1879; Medical Times, i., 1879). But I
think the evidence insufficient for the conclusion, and all observations upon
fasting animals are open to the fallacy that urea may be increased by the
fasting, and consequent absorption of fat (Forster: Zeitschrift fur Biol-
ogic, xi., s. 522). The dogs utilized by Gaethgens were kept many days
on "water only, and a careful examination of the whole question leads to
the conclusion that the " tissue-change of inanition " is almost surely the
explanation of what he attributed to arsenic (F. A. Falck: Archiv fur
Exper. Path., August, 1877, Bd. vii.). Von Bock attributed any change
he could observe to the effect of fasting (Zeitschrift f 'fir Biologic, vii., s.
418-432), and held that arsenic acid in ordinary doses exerted no essen-
tial influence on tissue-change.

Others have concluded positively that it lessens excretion and change.
Thus Lolliot, in a careful thesis, records many observations and analyses,
from which he makes evident a diminution of urea and carbonic acid
under arsenic; he asserts, also, that it lowers temperature, and is a " medi-
cament d'epargne " it lessens the activity both of nutrition and denutri-
tion (" 3tude Physiol. de 1' Arsenic," Paris, 1868). Kohler classes it with
tea, coffee, cocoa, as " sparmittel " diminishing oxidation processes



40 MATERIA MED10A AND THERAPEUTICS.

(Handbuch der PhysioL TJierapeutik, 1876). In recent experiments by
Dr. Tamassia (Pavia), toxic doses of white arsenic given to animals, pro-
gressively lowered temperature up to, and after death (Medical Record,
January, 1878). Animals accustomed to an arsenical ration became py-
rexial and emaciated on its withdrawal, implying that some moderating
power had been removed. There is still, however, a discrepancy in the
observations on temperature; Harless reported a slight rise from small
doses, and Billroth, gradually increasing the dose to 40 min. daily in a
case of asthma, reported a febrile access in the evenings up to 101 F.
( Wiener Woch., 1871, No. 44).

Schmidt and Brettschneider found the excretion of urea and of car-
bonic acid under arsenic diminished 20 to 40 per cent. ; phosphates also
diminished. Schmidt and Stiirzwage likewise report diminution of car-
bonic acid and urea in rabbits under minute doses (Schmidt's Jahrb.,
Bd. clviii., pp. 13-15), and Rabuteau states that the elimination of urea
in a dog was lessened for three weeks after a few doses of arsenious acid,
at one time as much as 60 per cent.; he attributes its effect in lessening
tissue-change to an action on the blood-corpuscles.

I conclude that although some contradiction exists on this point be-
tween good authorities, yet the balance of recent evidence points to
lessened excretion, and consequently to lessened tissue-change as an effect
of arsenic.

Acute and Chronic Poisoning. Although not here concerned with
cases of poisoning further than as they illustrate physiological action, we
may note that if death occurs from large doses of several drachms, and in
the course of a few hours, it is generally from cardiac palsy, and is pre-
ceded by excessive prostration and fainting. If 1 or 2 dr. have been
taken, and the patient survives two or three days, the symptoms will be



Online LibraryCharles D. F. (Charles Douglas Fergusson) PhillipsMateria medica and therapeutics, inorganic substances; (Volume 2) → online text (page 5 of 40)