Arthur Robertson Cushny.

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leucin crystals, which are not always present in the urine, however,
although they have been found in the blood in some quantity. Bau-
mann found an increase in the substances of th6 aromatic series in
the urine. The phosphates of the urine are often very considerably
augmented, but not because of the excretion of phosphorus as phos-
phates, for the quantity absorbed is too small to cause any appreciable
change. The increase in the phosphates is rather to be ascribed to an
augmented waste of the tissues, and the sulphates are also excreted
in larger quantity for the same reason.

When icterus is present, the urine may be dark in color from the
bile pigment excreted, and bile acids are also often contained in it.

Metobolism. — ^The carbonic acid excretion and oxygen absorption
by the lungs are generally found to undergo comparatively slight
changes in phosphorus poisoning, while all the evidence points to grave
derangement in the protein metabolism. Meyer found the alkalinity
of the blood reduced through the presence of lactic acid in excess in
the tissues, and this has the further effect of increasing the ammonia
of the urine; lactic acid is also found in the stomach along with hydro-
chloric acid. It is believed to arise from the glycogen of the liver,
which is much reduced in amount. The great similarity between the
results of normal autolysis and of phosphorus poisoning has led to
the view that the essential effect of phosphorus is an acceleration of
*See Ammonia, p. 557; Acids, p. 562.

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the autolytic process, and this is supported by the results obtained
in experiments in which the autolysis of the normal liver was com-
pared with that of the liver obtained from an animal poisoned with

Autolysis or destructive metabolism occurs in normal living cells,
but in phosphorus poisoning it is supposed to proceed more rapidly,
and many of its products are not so completely decomposed as not-
mally, so that intermediate products, such as leucin, tyrosin and other
amino-acids appear in large quantities in the organs and often in the
excretions ; lactic acid is similarly a product of autolysis, which fails
- to be oxidized to carbonic acid as in the normal body. This accel-
erated autolysis occurs not only in the liver but also in other organs,
although in a less marked degree.

It seems probable that the fatty degeneration is a secondary result
of the accelerated autolysis ; the cells are supposed to absorb fat from
the blood more rapidly than normally and to store it in their interior
in the form of globules, and as the fat of the blood is thus reduced the
normal fat deposits in the body are drawn upon to replace it and this
results in the transference of fats from the subcutaneous tissues to
such organs as the liver, kidney and heart. But these have lost to a
large extent their normal capacity of decomposing fats, which are
therefore deposited in the cells in the same forms as occur in the
normal adipose tissue.

In view of the curious eflFect of phosphorus on the tissue change of
the vertebrates, its action upon simpler forms possesses some interest.
It has been found, however, that yeast, infusoria and bacteria are very
little affected by the presence of this poison, and living microbes are
found in large numbers on solid pieces of phosphorus. The ferments
are also unaffected for the most part, pepsin and pancreatin acting in
the presence of phosphorus. The synthesis of hippuric acid in the
kidney is lessened if to the blood used to perfuse the organ some
phosphorus is added.

The Temperature is often low in the later stages of phosphorus
poisoning, but slight fever is also observed in some cases.

The Fate of phosphorus in the body is still obscure. It is possible
that some of it is oxidized to phosphoric acid, and some phosphorus is
said to be excreted by the lungs, although the statement that the breath
becomes phosphorescent seems to be extremely improbable. Jt is also
excreted in the urine in some organic combinations, of which nothing
is known, though they are said to be volatile. In pregnant animals
poisoned with phosphorus the foetus is found to undergo fatty degen-
eration, so that the poison would seem to pass through the placenta.
Phosphorus injected hypodermically acts much more slowly than
when swallowed.

Phosphuretted hydrogen (PHg) induces the same symptoms as
phosphorus, when it is given in repeated small quantities. Larger
doses are very rapidly fatal and the symptoms differ entirely from
those of phosphorus poisoning, consisting of marked dyspnoea, purga-

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PH08PH0BUS. 607

tion, weakness^ tremor, and finally violent convulsions and respiratory
failure. The oxygen compounds do not seem to have any such effects,
and for the most part are harmless except in very large doses.


Phosphorus (U. S. P., B. P.), a translucent, nearly colorless solid resembling
wax in lustre and consistency. It emits white fumes in the air, which are
luminous in the dark and takes fire spontaneously. The fumes have the odor
of garlic and in dilute solution phosphorus has a harsh, disagreeable taste.
It is very little soluble in water, more so in alcohol, and dissolves to about two
per cent, in fats and oils. J-1 mg. (tJtj-^V gr.) (B. P. tW-A gr.).

Oleum Phosphoratum (B. P.) is a one per cent, solution in almond oil and
ether (1-5 mins.). Phosphorated oil ought to be freshly prepared and kept
in tightly stoppered bottles; solutions of one per cent, tend to lose their
strength by evaporation of the phosphorus and by oxidation, when the bottle
contains air. It is said to keep better in more dilute solution (one per mille).
It is probable that much of the oil dispensed is under one per cent, in strength.

PHuke Phoaphori (U. S. P.), each pill contains 0.6 mg. of phosphorus
(i>Sgr-). Dose, 1 pill.

PUula Phoaphori (B. P.), 2 per cent., 1-2 grs.

Therapeutic Uses. — Phosphorus has been recommended in various
diseases of the central nervous system and in neuralgia, but it is still
questionable whether it is of any real benefit in these. There is more
reason to believe in its virtues in bone disease, more especially in
rachitis and osteomalacia, for in a number of instances marked im-
provement has been observed in these diseases under its use. It is
generally given in solution in cod-liver oil, and the benefit may be due
in part to the menstruum, but not entirely, for Sternberg observed a
relapse in a case of osteomalacia when pure cod-liver oil was substi-
tuted for the phosphorated oil. In rickets a solution containing 0.01
G. in 100 C.C. of cod-liver oil is recommended; 2-4 teaspoonfuls to
be given each day.^ In osteomalacia a 1 per cent, solution may be
prescribed and 1-6 mg. phosphorus taken each day. A number of
observers have found that in cases of rickets and osteomalacia more
lime was retained under phosphorus treatment than usual, the propor-
tion of the lime of the food which was excreted falling rapidly.

Other bone diseases, such as caries and ununited fractures, have
also been treated with phosphorus occasionally, but the results have
not been recorded in suflScient numbers to allow of any statement as
to the eflBcacy of the treatment.

Treatment of Fhosphonis Poisoning. — Phosphorus is comparatively
slowly absorbed from the alimentary canal, so that in the early stages
an attempt ought to be made to remove it by emetics or the stomach
tube, and by purges. Fats and oils must be avoided, as they tend to
dissolve the poison and promote its absorption. Phosphorus has been
found in the stools three days after its ingestion, and a sharp purge
may therefore be of use up to this time.

* TUB would be eqtuTalent to 1-2 mg. of phosphorus daily, but as a matter of
fact the phosphorated oU from which the prescription is filled contains much less
than one per cent., so that the dose actuaUy taken probably seldom amounts to
more than one milligram daily.

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Another method of treatment is that aiming at the oxidation of the
phosphorus in the stomach, or at the formation of unabsorbable com-
pounds. Turpentine oil was formerly used with the object of oxidiz-
ing the phosphorus or of forming some c9mpound with it in the
stomach, but this treatment has proved quite valueless (Plavec).
Sulphate of copper is recommended in phosphorus poisoning, a large
dose being given first as an emetic, and afterwards smaller doses to
form an insoluble compound, copper phosphide. Permanganate of
potassium solution, one per mille, has been recently advised to oxidize
the phosphorus, while peroxide of hydrogen solution is of less value.
In the secondary stage alkalies are recommended in order to neutralize
the excess of sarcolactic acid formed in the tissues.

Phosphorus necrosis has to be treated surgically on the same prin-
ciples as other necroses of bone.


Wegner. Virchow's Arch., Iv., p. 11.

Kassowite, Ztschr. f . klin. Med., vii., p. 36. I

Sternberg, Ibid., xzii., p. 265.

Stuhenrauch, Arch. f. klin. Chir., lix., p. 144; IxL, p. 547. I

Jacohy. Zeitschr. f. physiol. Ghem., xtt., p. 174.

Forges and Pribram, Arch, f . ezp. Path. u. Pharm., lix, p. 20.

Bey, Deutach. med. Woch., 1895, p. 569. |

Stadelmann, Arch. f. exp. Path. u. Pharm., xxiv., p. 270.

Aufreoht. Deutsch. Arch. f. klin. Med., zziii., p. 331.

Ackermann, Virchow's Arch., cxv., p. 216. I

Siolnickaw. Arch. f. Anat. u. Phys., 1887. Sapplement, p. 1. |

Sehuliee. Virchow's Arch., cii., p. 299.

Meyer. Arch, f . exp. Path. a. Pharm., xiv., p. 313.

Plaveo. Arch. f. exp. Path. u. Pharm., xlviii.,p. 150; Pfliiger's Arch., civ., p. 1.

Miura. Virchow's Arch., xcvi., p. 54.

Schulteen v. Biess, Annalen der Gharite, xv., p. 1.

Fraenkel. Berl. klin. Woch., 1878, p. 265; Virchow's Arch., IxviL, p. 278.

Mumer, Deutsch. Arch, f . klin. Med., lii., p. 199.

Taussig. Arch, f . exp. Path. u. Pharm., xxx., p. 161.

Hauser. Ibid., xxxvi., p. 165.

Pileecker. Ztsch. f. physiol. Chem., xli., p. 157.

Corin u. Ansiaux. Vierteljahr. f . ger. Med., 1894, i., pp. 80, 212.

Aihanasiu. Pfluger's Arch., Ixxiv., p. 511.

Taylor, Journ. of Exp. Med., iv., p. 399; Jonrn. of Med. Research, ix.

Stockman and Charteris, Journ. of Path, and Bact., 1903, p. 205.

Thayer and Wolf. Journ. of Med. Research, ix., pp. 191, 216.

Santesson, Skand. Arch. f. Phys., xv., pp. 259, 420.

Jokote. Arch. f. Hygiene, xlix., p. 275.

Bosenfeld. Cong. f. inn. Med., xv., p. 427.

Lindemann. Arch, f . exp. Path. u. Pharm., xli., p. 191. Ztschr. f . Biol., xxxix.

Steinhaus. Ziegler's Beitrage z. path. Anatomic, xxii., p. 466.

Monti, Slick, Frankel, Zweifel, KassowitB. Wiener klin. Woch., 1901.


Some of the less active preparations of arsenic, such as the sul-
phides, Realgar (AsgSa) and Orpiment (AsgSg), have been known in
therapeutics since the beginning of the Christian era, but this metal
was brought into especial prominence in later times through the fre-
quent use of the more dangerous oxides in criminal poisoning. Thus

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the notorious Aqua Tof ana of the sixteenth and seventeenth centuries
owed its activity to the presence of arsenic, and various arsenical com-
pounds have been used .up to the last few years more largely than
almost any other poison in suicide and homicide. This is to be ex-
plained by their having been widely employed in the arts, and thus
being readily accessible to all, and by the genjeral recognition of their
poisonous nature. Of late years intentional arsenic poisoning has be-
come somewhat less common, though on the other hand, accidental
poisoning is still met with not infrequently, especially in the chronic
forms. Many of these chronic cases are extremely difficult to diag-
nose, and probably often pass unrecognized by the attending phy-
sician. In view of this fact it seems desirable that more stringent
measures should be taken to reduce the use of arsenic in the arts, and
especially to prevent its being brought in contact with food. The
danger of the use of the green arsenical dyes, such as Scheele's Green
(arsenite of copper), and Schweinfurt's Green, or Paris Green
(arsenite and acetate of copper), is now generally recognized, but
arsenic is still used in the preparation of other colors, and these may
give ris^e to poisoning from the imperfect removal of the metal. It
has also been used in dilute solution to preserve food, and a solution
is often sprayed upon grape vines and other plants to preserve them
from the attacks of insects. Poisoning has occurred from these sources
and is difficult to diagnose, as it is in some cases impossible to find the
means by which the arsenic enters the system. A widespread epi-
demic of poisoning in England in 1900 drew attention to a source of
arsenic which had not up to that time received the attention it
merited. Several thousands of persons suffered from arsenic being
contained in cheap beers made from glucose, in the manufacture of
which sulphuric acid had been employed. The sulphuric acid was
formed from iron pyrites containing arsenic, and the poison was
carried from the sulphuric acid with the glucose into the beer. Sul-
phuric acid is used in the manufacture of so many drugs, foods and
other substances m, constant use, that this intimation that it may con-
vey arsenic into articles where its existence has not hitherto been
suspected, is of the gravest importance.

Metallic arsenic is insoluble in water, and passes through the
alimentary canal for the most part unchanged and without action,
but it is possible that small quantities may be oxidized to arsenious
acid in the stomach and intestine under some conditions. Some
symptoms have been observed when it is rubbed on the skin in a state
of fijie division, and these are probably due to its absorption in the
form of an oxide. The characteristic " arsenic " action is induced by
the salts of arsenious acid (AsOgHg), and by its anhydride (AsgOg)
which is often known as arsenic, and which exists in the tissues as
arsenites. Arsenic action is therefore due, not to the element, but to
the ion of arsenious acid. The anhydride and salts of arsenic acid
(H3ASO4) cause similar symptoms, but are less poisonous and act

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more slowly than those of arsenious acid, and may probably owe their
effects to the formation of arsenites in the tissues. The action being
due to the ion and not to the element, it necessarily follows that com-
pounds from which the ion is not liberated do not induce the arsenic
action, or do so only when they are changed to bodies which can dis-
sociate the arsenious acid ion. Thus organic arsenic combinations in
which the metallic atom is directly attached to carbon are only feebly
poisonous, but in course of time seem to be changed to arsenious acid
in the tissues, and then cause typical poisoning.

Arsenious acid, which in the following pages will be taken as the
representative of " arsenic " action, has a somewhat sweetish taste,
and is therefore not so likely to be detected by the victim as many of
the other poisons.

SymptosiB. — In large quantities arsenic very often causes no symp-
toms for half an hour or more, but then the patient complains of a
feeling of constriction in the throat, of difficulty in swallowing, and
of discomfort in the stomach region. This soon increases to violent
pain, and is accompanied by vomiting, and later by watery diarrhoea.
The stools are at first of ordinary diarrhoeic appearance, but later re-
semble the " rice-water " stools of cholera, in that they consist almost
entirely of minute shreds of disintegrated mucous membrane sus-
pended in a serous fluid; sometimes, however, they are clear and
gelatinous in appearance. In some cases, blood appears in the
vomited matter and also in the stools, but this is not by any means
an invariable feature. The urine is diminished, or entirely sup-
pressed, from the great amount of fluid eliminated by the stomach and
bowel. These symptoms from the alimentary tract are accompanied
by giddiness, cramps in the muscles, headache, and soon by collapse,
with cold damp skin, pallor, feeble pulse and weak, sighing respira-
tion ; this later passes into coma, and death follows with or without
convulsions. In cases in which the dose is smaller than the fatal one,
or in which much of the poison is eliminated by vomiting, the patient
may recover without further symptoms than those already described.
Frequently, however, he recovers from the acute symptoms only io
develop those of chronic arsenical poisoning. In some instances it is
said that no symptoms are present except those of collapse and coma-
In acute poisoning death may occur within 24 hours, but more fre-
quently the patient lives for 2-4 days longer, and then succumbs to
exhaustion. The fatal dose is very uncertain, because arsenic is very
insoluble, and much of the poison may be thrown up by vomiting, or
pass out in the stools unabsorbed. Thus in some cases, recovery has
followed after very large quantities, while in others about 0.1 G.
(IJ grs.) has proved fatal.

Chronic Arsenic Poisoning may arise from a single large dose, the
effects persisting for weeks or months after the ingestion and new
symptoms arising as the earlier ones disappear; more frequently,
however, it is induced by the prolonged absorption of small quantities-
The milder symptoms may arise from its therapeutic use, but typical

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cases are generally due to the presence of arsenic in the form of dyes
in wall paper or clothes, or in stuffed animals in the rooms inhabited
by the victims, or to the constant handling of arsenical pigments and
other compounds in mines and manufactories. Widespread poisoning
has been observ,ed from the use of wines containing arsenic at Hyeres
in France, from milk diluted with arsenical water in London, and
from beer in the Manchester district. In these last cases the arsenic
was in solution, but it often seems to be inhaled in the form of fine
dust, which falls from the walls or other objects. It has been sug-
gested that the arsenic dyes are decomposed by microbes and the
volatile arseniuretted hydrogen (AsHg) inhaled, but there seems no
reason to suppose that this is the case, and the inhalation of fine
particles is a sufficient explanation.

The symptoms of chronic arsenic poisoning, which are often very
obscure, may be divided into three phases. In the first of these, the
patient complains of weakness and languor, loss of appetite, some
nausea and occasionally vomiting, with a sense of heaviness and dis-
comfort in the stomach. Diarrhoea may be present, but is often
absent, and in fact some constipation may occur.

In the second phase the conjunctiva is often red and inflamed, and
symptoms of coryza appear, with sneezing, hoarseness and coughing,
from a catarrhal condition of the mucous membranes of the nose and
larynx. Some swelling of the liver and jaundice may occur, but these
are not generally well marked. Skin eruptions of various forms — ^
papular, vesicular, or erythematous — are generally noted ; very often
the epidermis falls off in fine brownish scales, or, in the hands and feet,
in large fiakes (keratosis) ; a curious pigmentation is very common,
the skin assuming a dark metallic color resembling in extreme forms
that produced by rubbing a lead pencil upon it (arsenic melanosis).
This pigmentation is much more marked in persons of dark com-
plexion than in fair people, in whom it may be indistinguishable from
ordinary freckles ; it generally disappears when the patient is removed
from the poisonous atmosphere, but has been permanent in some cases.
In prolonged poisoning the eruptions may simulate almost any form
of skin disease, and the hair and nails fall off. Herpes is not infre-
quently observed and points to nervous disturbances such as are
prominent features in the next phase.

These phases are not always distinct in cases of poisoning, and very
often some of the symptoms of the second phase may appear before
any marked disorder of the digestive tract. In the prolonged thera-
peutic use of arsenic, the first indications of commencing poisoning
are redness, suffusion and swelling of the conjunctiva and eyelids,
and dryness of the nose and throat, as in coryza. On the other hand,
in workmen exposed to arsenical dust, the first symptoms may arise
from the skin or from bronchial irritation.

The third phase is marked by disturbance of sensation and motion
in localized areas, generally in the hands and feet (peripheral neu-
ritis). It is often ushered in by intense persistent headache or by

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acute pain located around the knee, ankle or foot, less frequently in
the wrist and hand. The patient complains of formication in the
extremities, and of the discomfort caused by the pressure of the bed-
clothes on the feet and legs. The palms of the hands and the soles of
the feet are often red, swollen and extremely sensitive to touch (erv-
thromelalgia), and pressure on the muscles induces the most intense
pain. Later, sensory paralysis may set in, especially in the extrem-
ities, and the less acute sense of touch in the feet and hands induces
symptoms resembling those of locomotor ataxia. The sensitiveness to
heat and cold may be exaggerated or dulled, or soinetimes heat is not
appreciated, while cold causes intensfirpain. The sense of pain varies
in different cases, in some being abnormally acute, in others deadened.
These sensory disturbances are followed in severe poisoning by motor
paralysis, which generally appears in the extensor muscles of the toes,
later in the peronei muscles. More rarely the flexor muscles of the
leg and foot are involved, and in some cases the affection conmiences
in the extensors of the hand and fingers. As a general rule the
paralysis is confined to the extremities, but in some cases it has been
found to invade the trunk. It is generally, but not invariably, sym-
metrical, and the muscles affected atrophy rapidly, and contract
weakly to the galvanic shock, not at all to the faradic except in the
beginning of the affection. This lessened excitability of the muscle?
sometimes appears before the typical degeneration reaction is observed
but is then followed by it later. The muscles are abnormally excit-
able to mechanical stimulation, however, while the tendon reflexes are
generally entirely absent. There is sometimes some difficulty eJ^-
perienced in diagnosing arsenic from lead paralysis, but in the former
there is often a history of acute poisoning, while the latter is almost
invariably due to prolonged absorption. Disturbances of sensatioo
are much more common in arsenic than in lead palsy, and in the latter
the forearm muscles are generally affected first, in the former those
of the leg. In arsenic poisoning atrophy is said to occur much more
rapidly, and there is no line on the gums. Another condition which
presents still greater difficulties in diagnosis is alcoholic neuritis.
But in the latter skin eruptions are extremely rare, coryza is not
present, and there are generally more marked brain symptoms than
in arsenical cases. In doubtful cases the urine and the hair of the
patient should be tested for arsenic.

Arsenic paralysis may appear as early as three days after an acutf
intoxication, but is commonly observed later, and may occur only after
3-4 weeks. Some authors have asserted that in chronic arsenic poi-
soning there is a paralysis of the sexual powers (anaphrodisia), and
ascribe this to an action on the nerves of the sexual organs, similar to
that observed in the extremities, but this symptom is not by anj
means generally present, and, in fact, abnormal sexual excitement has
been noted in some cases.

In very prolonged arsenic poisoning the patient may sink into an
apathetic, semi-idiotic condition, or may become epileptic. In most

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AB8ENIC. 613

cases the symptoms slowly disappear when the poison is removed, but
even slight paralysis may last for many years before it is entirely
cured, and after complete degeneration of the muscles little improve-
ment is to be expected. The contractures which follow are generally
due to the unopposed action of the sound muscles, but sometimes arise
from the shortening of the paralyzed ones.

Arsenic poisoning generally occurs from the inhalation of particles

Online LibraryArthur Robertson CushnyA textbook of pharmacology and therapeutics, or, The action of drugs in ... → online text (page 78 of 95)