preceding, and shows what a protean aspect digitalin poisoning may
assume. A woman, twenty-three years old, took on June 26th, at 7 A.M.,
for the purpose of suicide, 16 granules of digitalin. Two hours later
there was shivering and giddiness, so that she was obliged to go to bed.
In the course of the day she had hallucinations. In the evening at 8
P.M., after eating a little food, she had a shivering fit so violent
that her teeth chattered; there was cold sweat, and difficulty in
breathing; she became gradually again warm, but could not sleep. At 1
A.M. the difficulty of breathing was so great that she dragged herself
to the window, and there remained until 3 A.M., when she again went back
to bed, slept until 7 A.M., and woke tolerably well. Since this attempt
of self-destruction had failed, she took 40 granules. After one hour she
became giddy, had hallucinations, chilliness, cold sweats, copious
vomiting, and colicky pains; there was great muscular weakness, but no
diarrhœa. Towards evening the vomiting became worse. There was no action
of the bowels, nor was any urine passed; she felt as if her eyes were
prominent and large. The sufferings described lasted during the whole
night until five o’clock the following day, when the vomiting ceased,
whilst the hallucinations, chilliness, and cold sweat continued; and the
thirst, sick feeling, and weakness increased. The next morning, a
physician found her motionless in bed, with pale face, notable double
exophthalmus, dilated pupils, and cold skin, covered with sweat; the
pulse was small and intermittent, sometimes scarcely to be felt (46 to
48 per minute); the epigastrium was painful on pressure. She passed this
second night without sleep, and in the morning the pulse had risen from
56 to 58 beats, but was not quite so intermittent. There was some action
of the bowels, but no urine was passed, nor had any been voided from the
commencement; the bladder was not distended. The following (third) day
some red-coloured, offensive urine was passed; the skin was warmer, and
the pulse from 60 to 64, still somewhat intermittent--from this time she
began to improve, and made a good recovery.[568]
[568] Related by Ducroix: _De l’Empoisonnement par la Digitale et la
Digitaline._ Paris, 1864.
§ 540. =Physiological Action of the Digitalins.=--Whatever other
physiological action this group may have, its effect on the heart’s
action is so prominent and decided, that the digitalins stand as a type
of _heart poisons_. The group of heart poisons has been much extended of
late years, and has been found to include the following:--Antiarin, an
arrow poison; helleborin, a glucoside contained in the hellebore family;
a glucoside found in the _Apocynaceæ_, _Thevatii neriifolia_, and
_Thevatia iccotli_; the poisonous principle of the _Nerium oleander_ and
_N. odorum_; the glucoside of _Tanghinia venenifera_; convallamarin,
derived from the species of _Convallaria_; scillotoxin, from the squill;
superbin, from the Indian lily; and the alkaloid erythrophlœin from the
_Erythrophlœum judiciale_ (see p. 432 _et seq._). This list is yearly
increasing.
§ 541. =Local Action.=--The digitalins have an exciting or stimulating
action if applied to mucous membranes--_e.g._, if laid upon the nasal
mucous surface, sneezing is excited; if applied to the eye, there is
redness of the conjunctivæ with smarting; if to the tongue, there is
much irritation and a bitter taste. The leaves, the extract, and the
tincture all have this directly irritating action, for they all redden
and inflame mucous membranes.
§ 542. =Action on the Heart.=--The earlier experimenters on the
influence of digitalis on the heart were Stannius and Traube.
Stannius[569] experimented on cats, and found strong irregularity, and,
lastly, cessation in diastole, in which state it responded no longer to
stimuli. Rabbits and birds--especially those birds which lived on
plants--were not so susceptible, nor were frogs.
[569] _Arch. f. Physiol._
Traube[570] made his researches on dogs, using an extract, and
administering doses which corresponded to from ·5 to 4·0 grms. He
divided the symptoms witnessed into four stages:--
[570] _Ann. d. Charité-Krankenhauses_, vol. ii. p. 785.
_1st Stage._--The pulse frequently diminishes, while the pressure of the
blood rises.
_2nd Stage._--Not seen when large doses are employed; pulse frequency,
as well as blood pressure, abnormally low.
_3rd Stage._--Pressure low, pulse beats above the normal frequency.
The slowing of the heart[571] is attributed to the stimulus of the
inhibitory nerves, but the later condition of frequency to their
paralysis. After the section of the vagi the slow pulse frequently
remains, and this is explained by the inhibitory action of the cardiac
centre. The vagus, in point of time, is paralysed earlier than the
muscular substance of the heart.
[571] Slowing of the pulse was mentioned first by Withering (_An Account
of the Foxglove_, Lond., 1785). Beddoes afterwards observed that
digitalis increased the force of the circulation, the slowing of the
pulse not being always observed; according to Ackermann, if the
inhibitory apparatus is affected by atropine, or if the patient is under
deep narcosis, the slowing is absent.
The increased blood pressure Traube attributed to increased energy of
the heart’s contraction, through the motor centre being stimulated
later; the commencing paralysis explains the abnormally low pressure.
There is, however, also an influence on vaso-motor nerves. What Dr.
Johnson has described as the “stop-cock” action of the small arteries
comes into play, the small arteries contract and attempt, as it were, to
limit the supply of poisoned blood. Ackermann,[572] indeed, witnessed
this phenomenon in a rabbit’s mesentery, distinctly seeing the arteries
contract, and the blood pressure rise after section of the spinal cord.
This observation, therefore, of Ackermann’s (together with experiments
of Böhm[573] and L. Brunton[574]) somewhat modifies Traube’s
explanation, and the views generally accepted respecting the cause of
the increased blood pressure may be stated thus:--The pressure is due to
prolongation of the systolic stroke of the cardiac pump, and to the
“stop-cock” action of the arteries; in other words, there is an increase
of force from behind (_vis a tergo_), and an increased resistance in
front (_vis a fronte_).
[572] _Deutsch. Arch. f. klin. Med._, vol. xix. p. 125.
[573] _Archiv f. d. Ges. Phys._, vol. v. p. 153.
[574] _On Digitalis, with Some Observations on the Urine_, Lond., 1868.
§ 543. =Action of the Digitalins on the Muco-Intestinal Tract and other
Organs.=--In addition to that on the heart, there are other actions of
the digitalins; for example, by whatever channel the poison is
introduced, vomiting has been observed. Even in frogs this, in a
rudimentary manner, occurs. The diuretic action which has been noticed
in man is wanting in animals, nor has a lessened diminution of urea been
confirmed.
Ackermann found the temperature during the period of increased blood
pressure raised superficially, but lowered internally. According to
Boeck[575] there is no increase in the decomposition of the albuminoids.
[575] _Intoxication_, p. 404.
§ 544. =The Action of Digitalin on the Common Blow-fly.=--The author
has studied the effects of digitalin, made up into a thin paste with
water, and applied to the head of the common blow-fly. There are at
once great signs of irritation, the sucker is extruded to its full
length, and the fly works its fore feet, attempting to brush or
remove the irritating agent. The next symptom is a difficulty in
walking up a perpendicular glass surface. This difficulty increases,
but it is distinctly observed that weakness and paralysis occur in
the legs before they are seen in the wings. Within an hour the wings
become paralysed also, and the fly, if jerked from its support,
falls like a stone. The insect becomes dull and motionless, and
ultimately dies in from ten to twenty-four hours. A dose, in itself
insufficient to destroy life, does so on repetition at intervals of
a couple of hours. The observation is not without interest, inasmuch
as it shows that the digitalins are toxic substances to the muscular
substance of even those life-forms which do not possess a heart.
§ 545. =Action of the Digitalins on the Frog’s Heart.=--The general
action of the digitalins is best studied on the heart of the frog. Drs.
Fagge and Stevenson have shown[576] that, under the influence of
digitalin, there is a peculiar form of irregularity in the beats of the
heart of the frog; the ventricle ultimately stops in the white
contracted state, the voluntary power being retained for fifteen to
twenty minutes afterwards; in very large doses there is, however, at
once paralysis. Lauder Brunton[577] considers the action on the heart to
essentially consist in the prolongation of the systole.
[576] _Guy’s Hospl. Reports_, 3rd ver., vol. xii. p. 37.
[577] _On Digitalis, with Some Observations on the Urine_, Lond., 1868.
Atropine or curare have no influence on the heart thus poisoned. If the
animal under the influence of digitalin be treated with muscarine, it
stops in diastole instead of systole. On the other hand, the heart
poisoned by muscarine is relieved by digitalin, and a similar influence
appears to be exercised by atropine. The systolic stillness of the
heart is also removed by substances which paralyse the heart, as
delphinin, saponin, and apomorphin.
Large doses of digitalin, thrown suddenly on the circulation by
intravenous injection, cause convulsions and sudden death, from quick
palsy of the heart. With frogs under these circumstances there are no
convulsions, but a reflex depression, which, according to Weil[578] and
Meihuizen,[579] disappears on decapitation. The central cerebral
symptoms are without doubt partly due to the disturbance of the
circulation, and there is good ground for attributing them also to a
toxic action on the nervous substance. The arteries are affected as well
as the heart, and are reduced in calibre; the blood pressure is also
increased.[580] This is essentially due to the firm, strong contraction
of the heart, and also to the “stop-cock” action of the small
arteries.[581]
[578] _Archiv f. Anat. u. Physiol._, 1871, p. 282.
[579] _Archiv f. d. Ges. Physiol._, vol. vii. p. 201.
[580] The following is a brief summary of observations on the blood
pressure; four stages may be noticed--(1) Rise of normal blood pressure,
not necessarily accompanied with a diminution of pulse frequency; (2)
continuation of heightened blood pressure, the pulse being raised beyond
the normal rate; (3) continued high pressure, with great irregularity of
the heart and intermittent pulse; (4) quick depression of pressure,
sudden stopping of the heart, and death.
[581] According to Boehm (_Arch. f. d. Ges. Physiol._, Bd. v. S. 189)
and to Williams (_Arch. f. exper. Pathol._, Bd. xiii. S. 2), the rise of
pressure is due entirely to the heart, and not to the contractions of
the small arteries; but I fail to see how the small arteries can
contract, and yet not heighten the pressure.
§ 546. =Post-mortem Appearances.=--In the case of the recruit poisoned
by digitalis leaf (p. 425), the blood was found dark and fluid; the
right ventricle and auricle of the heart were filled with blood, the
left empty; the brain and its membranes were anæmic; the stomach and
mucous membrane of the intestines were in parts ecchymosed, and there
were patches of injection. In the case of the widow De Pauw, poisoned
with digitalin by the homœopath (Conty de la Pommerais), the only
abnormality discovered was a few hyperæmic points in the mucous membrane
of the stomach and small intestines. It is then certain that although
more or less redness of the lining membrane of the intestine track may
be present, yet, on the other hand, the active principle of the
digitalis may destroy life, and leave no appreciable sign.
§ 547. =Separation of the Digitalins from Animal Tissues, &c.=--It is
best to make an alcoholic extract after the method of Stas, the alcohol
being feebly acidulated by acetic acid, and all operations being carried
on at a temperature below 60°. The alcoholic extract is dissolved in
water feebly acidulated by acetic acid, and shaken up, first with
petroleum ether to remove impurities (the ether will not dissolve any of
the digitalins), then with benzene, and, lastly, with chloroform. The
benzene dissolves digitalein, and the chloroform, digitalin and
digitoxin. On allowing these solvents to evaporate spontaneously,
residues are obtained which will give the reactions already detailed.
Neither the bromine nor any other chemical test is sufficient to
identify the digitalins; it is absolutely necessary to have resource to
physiological experiment. The method used by Tardieu in the classical
Pommerais case may serve as a model, more especially the experiments on
frogs. Three frogs were properly secured, the hearts exposed, and the
beats counted. The number of beats was found to be fairly equal. Frog
No. 1 was placed under such conditions that the heart was constantly
moist. Frog No. 2 was poisoned by injecting into the pleura 6 drops of a
solution in which 10 mgrms. of digitalin were dissolved in 5 c.c. of
water. The third frog was poisoned by a solution of the suspected
extract. The number of beats per minute were now counted at definite
intervals of time as follows:--
TABLE SHOWING THE ACTION OF DIGITALIN ON THE FROG’S HEART.
+----------------------+--------------------+----------------------+
| Frog No. 1. | Frog No. 2. | Frog No. 3. |
| Unpoisoned. | Poisoned by a | Poisoned by the |
| | known quantity | suspected |
| | of digitalin. | extract. |
+----------------------+--------------------+----------------------+
| No. of beats | No. of beats | No. of beats |
| per minute. | per minute. | per minute. |
+----------------------+--------------------+----------------------+
| After 6 minutes, 42 | 20 | 26 |
| „ 10 „ 40 | 16 irregular. | 24 irregular. |
| „ 20 „ 40 | 15 | 20 „ |
| „ 28 „ 38 | 0 | 12 very irregular. |
| „ 31 „ 36 | 0 | 0 |
+----------------------+--------------------+----------------------+
In operating in this way--which is strictly comparative, and, with care,
has few sources of error--if the heart of the frog poisoned with the
unknown extract behaves in the number and irregularity of its
contractions similarly to that of the digitalin-poisoned heart, it is a
fair inference that, at all events, a “heart-poison” has been separated;
but it is, of course, open to question whether this is a digitalin or
one of the numerous groups of glucosides acting in the same way. If
sufficient quantity has been separated, chemical reactions, especially
the bromine test (Grandeau’s test), may decide, but with the larger
number (yearly increasing) of substances acting similarly on the heart,
great caution in giving an opinion will be necessary.
II.--Other Poisonous Glucosides Acting on the Heart.
§ 548. Several members of these glucosides have been studied by
Schmiedeberg,[582] and his convenient divisions will be followed here:--
[582] _Beiträge zur Kentniss der pharmakol. Gruppe des Digitalins._
1. CRYSTALLISABLE GLUCOSIDES.
=Antiarin= (C₁₄H₂₀O₅).--Antiarin is an arrow poison obtained from
the milky juice of the _Antiaris toxicaria_ growing in Java.
Antiarin is obtained in crystals, by first treating the inspissated
milky juice with petroleum ether to remove fatty and other matters,
and then dissolving the active principle out with absolute alcohol.
The alcoholic extract is taken up with water, precipitated with lead
acetate, filtered, and from the filtrate antiarin obtained by
freeing the solution from lead, and then evaporating. De Vry and
Ludwig obtained about 4 per cent. from the juice. Antiarin is
crystalline, the crystals containing 2 atoms of water. Its
melting-point is given as 220·6°; the crystals are soluble in water
(254 parts cold, 27·4 parts boiling), they are not soluble in
benzene, and with difficulty in ether; 1 part of antiarin requiring
2792 parts of ether.
The watery solution is not precipitated by metallic salts. On
warming with dilute mineral acids, antiarin splits up into a resin
and sugar. Concentrated sulphuric acid gives with antiarin a
yellow-brown solution, hydrochloric and nitric acids strike no
distinctive colours.
§ 549. =Effects.=--Antiarin is essentially a muscular and a heart
poison. When given in a sufficient dose, it kills a frog in from
half an hour to an hour. Its most marked effect is on the cardiac
muscle, the heart beats more and more slowly, and at last stops, the
ventricle being firmly contracted. As with digitalin, there is a
very marked prolongation of the systole, and as with digitalin,
after the beats have ceased, a forcible dilatation of the ventricle
will restore them (Schmiedeberg). It is doubtful whether by
physiological experiment antiarin could be differentiated from
digitalin.
§ 550. =Separation of Antiarin.=--In any case of poisoning by
antiarin, it would be best to extract with alcohol, evaporate,
dissolve the alcoholic extract in water, precipitate with lead
acetate, filter, free the filtrate from lead, and then, after
alkalising with ammonia, shake the filtrate successively with
petroleum ether, benzene, and a small quantity of ether in the
manner recommended at page 247, _et seq._ The liquid, now freed from
all fatty, resinous, and alkaloidal bodies, is neutralised and
evaporated to dryness in a vacuum, and the dry residue taken up with
absolute alcohol, filtered, the alcohol evaporated at a very low
temperature, and finally the extract dissolved in a small quantity
of water, and submitted to physiological tests.
§ 551. =The Active Principles of the Hellebores.=--The Christmas rose
(_Helleborus niger_), as well as _H. viridis_, _H. fœtidus_, and, in
short, all the species of hellebore, are poisonous, and if the root is
treated with alcohol, from the alcoholic extract may be separated two
glucosides, _helleborin_ and _helleborein_.
=Helleborin= is in the form of white, glittering needles, which, if
placed on the tongue, are almost tasteless, but if dissolved in alcohol,
and then tasted, give a burning, numbing sensation. By boiling with zinc
chloride, helleborin splits up into sugar and a resin--_helleboresin_.
Concentrated sulphuric acid dissolves the crystals with the production
of a beautiful red colour; on standing, the solution after a while
becomes colourless, and a white powder separates.
=Helleborein= forms colourless crystals, mostly consisting of fine
needles; they have a bitter taste, excite sneezing, and are very
hygroscopic. The crystals easily dissolve in water and dilute alcohol,
but are with difficulty soluble in absolute alcohol, and not soluble in
ether. They dissolve in fatty oils. Helleborein splits by the action of
mineral acids into sugar and amorphous _helleboretin_.
=Helleboretin= is in the moist condition of a beautiful violet-blue
colour, becoming, when dried at 100°, dirty green. Concentrated
sulphuric acid dissolves it with the production of a brown-yellow
colour, which on standing passes into violet and then into brown.
Marmé separated from _H. fœtidus_, in addition, a white, intensely
odorous substance, but too small in quantity to thoroughly investigate
its properties.
§ 552. There is little doubt that hellebore owes its properties to the
glucosides just described. There are several instances of poisoning by
hellebore root,[583] and by the pharmaceutical preparations, but none of
poisoning by the pure active principles. Morgagni mentions a case in
which 2 grms. (nearly 31 grains) of the watery extract of _H. Niger_
caused death within eight hours; and Ferrari saw, after the use of the
wine in which the root had been boiled, two persons poisoned with a like
result. A more recent case was recorded by Felletar, in 1875, in which a
person died from an infusion of hellebore; there was, however, old
standing heart-disease, so that there may be a doubt as to the real
cause of death in this instance. Schauenstein mentions a case in which
the roots of hellebore were accidentally used in soup, but the bitter
taste prevented any quantity being eaten. The physiological action,
especially of helleborein, is that of an intense heart poison, and the
symptoms produced by the hellebores are so strikingly like those of the
digitalins that it might be difficult to distinguish clinically between
them. In any case of poisoning, the active principle must be separated
in the form of an alcoholic extract, and identified as a heart poison by
physiological experiment.
[583] There used to be a tincture officinal in our pharmacopœia; the
root of _H. viridis_ is officinal in the German pharmacopœia, maximum
single dose, ·3 grm.; maximum total quantity in twenty-four hours, 1·2
grm. The tincture is also officinal on the Continent.
§ 553. =Euonymin= is found in a resin obtained from the _Euonymus
atropurpureus_; it is crystalline, crystallising in colourless,
cauliflower-like masses consisting of groups of stellate needles,
which are soluble in water, but with difficulty in alcohol. It is a
glucoside, and a powerful heart poison, 1 mgrm. causing the heart of
a frog to cease in diastole.[584]
[584] Schmiedeberg, _op. cit._, from unpublished researches of Professor
H. Meyer, Dorpat.
§ 554. =Thevetin= (C₅₄H₄₈O₂).--A glucoside which has been separated
from the Thevetia nereifolia, and perhaps also from the _Cerbera
Odallam_. It is soluble in 124 parts of water at 14°, and is easily
soluble in spirit, but not in ether. It is coloured by sulphuric
acid red-brown, passing into cherry-red, and then, in a few hours,
into violet. On boiling with diluted acids, it splits up into sugar
and theveresin. Both thevetin and theveresin are powerful heart
poisons.[585]
[585] Husemann, _Archiv f. exper. Path. u. Pharmakol._, Bd. v., S. 228,
1876.
2. SUBSTANCES PARTLY CRYSTALLISABLE BUT WHICH ARE NOT GLUCOSIDES.
§ 555. =Strophantin= is a very poisonous substance which belongs
physiologically to this group, but does not seem to be a glucoside.
It is soluble in water and in alcohol, less so in ether and
chloroform. It is found in the _kombé_, _manganja_, _inée_, or
_onaje_, a West African poison derived from the _Strophanthus
hispidus_ of the family of _Apocynaceæ_. The poison has been
investigated by several observers.[586]
[586] _Digitoxin_ (see _ante_, p. 420) belongs to this group.
Dr. Fraser considers, from his experiments, (1) That strophantin
acts primarily on the heart, producing, as an end result, heart
paralysis, with permanence of the ventricular systole. (2) He found
the pulmonary respiration to continue in cold-blooded animals many
minutes after the heart was paralysed. (3) The striped muscles of
the body are affected, and twitches occur in them; their tonicity is
exaggerated, and finally their functional activity is destroyed.
This change is referred to an action on the muscular structure
itself, independent of that upon the heart, and also independent of
the cerebro-spinal nervous system. (4) The reflex action of the
spinal cord is suspended after the heart is paralysed, but the motor
conductivity of the spinal cord and of the nerve trunks continue
after the striped muscles of the body are paralysed. (5) The
lymph-hearts of the frog continue to contract for many minutes after
the blood-heart has been paralysed.
§ 556. =Apocynin.=--In the root of _Apocynum cannabinum_ a
non-crystallisable substance, soluble in alcohol and ether, but not
soluble easily in water, has been separated and found to have a
physiological activity similar to that of the digitalins.[587]
[587] Hardy et Callois, “_Sur la matière active du Strophanthus Hispidus
ou Inée_,” _Gaz. Med. de Paris_; Pelikan, _Compt. Rend._, t. 60, p.
1209, 1815; Sharpey,_ Proc. Roy. Soc._, May, 1865; Fagge and Stevenson,
_Pharm. Journ._, p. 11, 1865-66; Fraser, _Journ. of Anatom. and Phys._,
also _Proc. of Roy. Soc. of Edin._; Poillo and Carville, _Arch. de
Physiol. Norm. et Pathol._, 1872; G. Valentin, _Zeitschr. et.
Biologie._, x. 133, 1874.
3. NON-CRYSTALLISABLE GLUCOSIDES ALMOST INSOLUBLE IN WATER.
§ 557. =Scillain, or Scillitin=, a glucoside which has been
separated from the bulbs of the common squill. It is insoluble or
nearly so in water, but easily dissolves in alcohol. It is little
soluble in ether. It acts upon the heart, and is poisonous.
=Adonidin=, a very similar substance, has been separated from the
root of the _Adonis vernalis_ (Nat. Ord. _Ranunculaceæ_), to which
the name of adonidin has been given.[588] It is an amorphous,
colourless substance, without odour; soluble in alcohol, but with
difficulty soluble in ether and water. It is precipitated by tannin,
and on saponification by mineral acids, splits up into sugar and a
substance soluble in ether. The effects on animals are identical
with those of digitalin. The root has been used recently in
medicine, and found to slow the heart and increase the urinary
secretion; in this also it is like digitalis.
[588] Cervello, _Archiv für exp. Path. Pharm._, 1882, p. 338.
§ 558. =Oleandrin.=--Oleander leaves contain two
chemically-different, nitrogen-free substances. The one is probably
identical with digitalein; but as this is not certain, Schmiedeberg
proposes to call it provisionally _neriin_. The other active
substance is essentially the same as the oleandrin of Lukomske[589]
and Betelli.[590] Oleandrin has basic properties, and is separated
in the form of an amorphous mass, soluble in alcohol, ether, and
chloroform, and slightly soluble in water. Schmiedeberg obtained a
third product from African leaves, which he calls _nerianthin_.
This, on treatment with sulphuric acid and bromine, gives a
beautiful colour peculiar to oleander leaves. It is very similar in
physiological and chemical properties to digitalin, and is probably
derived by decomposition from one of the principles already
described. There is also a product similar to digitaliresin.
[589] _Repert. de Chimie de Wurtz et Bareswill_, t. iii. p. 77, 1861.
[590] _Bull. Med. di Bologna_, t. xix. p. 321, 1865.
The active principles of the oleander are separated by digestion of
the leaves with alcohol of 50 per cent., and precipitating the
alcoholic extract with lead acetate and ammonia. The first
precipitate is yellow, and is probably composed of a tannin-like
substance; the next precipitate is white, consisting of the lead
compound of neriin. The precipitates are filtered off, and the
filtrate concentrated; nerianthin, after a while, separates in light
flocks, and the filtrate from this contains some of the other
products.
§ 559. =Neriin or Oleander Digitalin.=--Neriin is, in the presence
of much free mineral acid, precipitated by potass-bismuth iodide, a
reaction first pointed out by Marmé,[591] as useful in the isolation
of the helleborins; or it may be precipitated by tannin, and then
the precipitate decomposed by dissolving in alcohol, and evaporating
it to dryness with zinc oxide on the water-bath. It is next
extracted by absolute alcohol, and precipitated by the addition of
much ether. The further purification consists of resolution in
alcohol, and fractional precipitation by ether. If, however, the
potass-bismuth iodide process is used, the liquid must be acidified
strongly with sulphuric acid, and the precipitate washed with
diluted sulphuric acid. The precipitate may be decomposed by baryta,
filtered, and the filtrate freed from baryta by carbon dioxide; the
filtrate from this contains neriin with baric iodide; it is
therefore treated with silver sulphate, then again with baryta, next
with carbon dioxide, and also with SH₂ to get rid of the last trace
of silver.
The filtrate will also contain some oleandrin which, by evaporating
slowly in a vacuum, separates gradually in the form of a clear,
resinous mass. It can be filtered off, and the neriin then may be
precipitated pure by fractional precipitation. Its physiological
action is the same as that of digitalein.
[591] _Zeitschr. f. rat. Med._ (3 R.), Bd. xxvi., S. 1, 1866.
§ 560. The nerium oleander has several times caused grave symptoms
of poisoning, and they have usually fairly agreed with those
produced by foxglove. For example, Maschka[592] relates the case of
a boy, two years old, who ate two handfuls of the nerium oleander.
The effects commenced in ten minutes, the child was uneasy, and
vomited. In six hours a sleepy condition came on; the face was pale,
the skin cold, the pupils contracted, and the pulse slow and
irregular. After the sickness the boy woke up, but again fell
asleep, and this occurred frequently; coffee was given, which
appeared to do good. The pulse was intermittent. On the following
day the child was still ill, with an intermittent pulse, frequent
vomiting, feebleness, sleeplessness, and dilatation of the pupil;
there was no diarrhœa, on the contrary, the bowels were confined. On
the third day recovery followed.
[592] _Vierteljahrsschrift f. gericht. Med._, Bd. ii., No. 17, 1860.
_Brit. and For. Med. Chir. Review_, vol. xxvi. p. 523, 1860.
In an Indian case,[593] the symptoms were altogether peculiar, and
belonged rather to the convulsive order. A wood-cutter, aged
thirty-five, near Kholapore, took, for the purpose of suicide, a
little over an ounce of the expressed juice of the oleander. The
symptoms began so rapidly that he had not time to walk five yards
before he fell insensible; he was brought to the hospital in this
state; the face on his arrival was noticed to be flushed, the
breathing stertorous, there were violent spasmodic contractions of
the whole body, more marked on the left than on the right side. The
effect of this was remarkable. During the intervals of the spasm,
the patient lay evenly on his back, and when the convulsions
commenced the superior contraction of the left side threw him on to
the right, in which position he remained during the paroxysm, after
the subsidence of which he fell back into his old position. The
evacuations were involuntary and watery; the man was insensible,
with frequent convulsions of the kind described, for two days, but
on the third day became conscious, and made a good recovery.
[593] _Transac. of Med. and Phys. Soc. of Bombay_, 1859.
In any case of poisoning, the methods by which neriin and oleandrin
are separated from the plant can be applied to separate them from
the tissues with more or less success. Here, as in all the other
digitalin-like glucosides, physiological tests are alone of value in
the final identification.
§ 561. =The Madagascar Ordeal Poison.=--To this group may also
belong the poison of the _Tanghinia venenifera_, a tree in the
Island of Madagascar, the fruit of which is used as an ordeal
poison. It may be obtained in crystals; it is insoluble in water,
and very poisonous. The upas of Singapore is also said to contain
with strychnine a glucoside similar to antiarin.
4. SUBSTANCES WHICH, WITH OTHER TOXIC EFFECTS, BEHAVE LIKE THE
DIGITALIS.
§ 562. =Erythrophlein= is an alkaloid, not a glucoside, and is
obtained from the bark of the _Erythrophlœum guineense_ (West
Africa). It acts on the heart like digitalis, and has also effects
similar to picrotoxin.
III.--Saponin--Saponin Substances.
§ 563. The term “saponin” of late years has been applied to a class of
glucosides which possess the common property of being poisonous, and,
when dissolved in water, forming solutions which froth on shaking like
soap-suds.
The substances which have these properties are not all of the same
series chemically, but those of the general formula, C_{n}H_{2n-8}O₁₀,
are most numerous, and the following is a list:--
Name. Formula.
Saponin, senegin, }
Quillaja-sapotoxin, }
Sapindus-sapotoxin, } C₁₇H₂₆O₁₀.
Grypsophila-sapotoxin, }
Agrostemma-sapotoxin, }
Saponin II., digitonin, saporubrin, assamin, C₁₈H₂₈O₁₀.
Saponin III., quillajic acid, polygalic acid, } C₁₉H₃₀O₁₀.
Herniari-saponin, }
Cyclamin, sarsaparilla-saponin, C₂₀H₃₂O₁₀.
Sarsa-saponin, C₂₂H₃₆O₁₀.
Parillin, C₂₆H₄₄O₁₀.
Melanthin, C₂₉H₅₀O₁₀.
Possibly also dulcamarin C₂₂H₃₄O₁₀ and syringen C₁₇H₂₆O₁₀ may belong to
this series.
There are some 150 distinct plants which thus yield saponins; a few of
these plants are as follows:--_Saponaria officinalis_, _Gypsophila
struthium_, _Agrostemma githago_ (corn cockle), _Polygala senega_,
_Monimia polystachia_, the bark of _Quillaja saponaria_, and
_Chrysophyllum glycyphleum_.
The saponin separated from _Saponaria_, and from the corn cockle will be
here described.
§ 564. =Properties.=--Saponin is a white amorphous powder, very soluble
in water, to which it gives the curious property of frothing just like
soap solution. To obtain this effect there must be at least 1 mgrm. in 1
c.c. of liquid. Saponin is neutral in reaction, it has no odour, but
causes sneezing if applied to the mucous membrane of the nose; the taste
is at first sweet, and then sharp and acrid. It is almost entirely
insoluble in absolute alcohol, but dissolves in hot alcohol of 83° to
separate again nearly completely on cooling. It is precipitated by basic
lead acetate, and also by baryta water, but in each case it is advisable
to operate on concentrated solutions. Picric acid, mercuric chloride,
and alkaloidal “group reagents” give no precipitate. When a little of
the solid substance is treated with “Nessler” reagent, there is a
greenish or yellow colour produced. A drop of strong sulphuric acid,
mixed with a minute quantity of saponin, strikes slowly a bright red
colour, which, on heating, deepens to maroon-brown. Nordhausen sulphuric
acid shows this better and more rapidly. If saponin is boiled with
dilute acid it breaks up into sapogenin and sugar, and therefore the
liquid after neutralisation reduces “Fehling.” This reaction is probably
after the following equation:--
2C₁₇H₂₆O₁₀ + 2H₂O = 2C₈H₁₁O₂ + 3C₆H₁₂O₆.
Sapogenin may be separated by evaporating the neutralised liquid to
dryness, treating the dry residue with ether, which dissolves out the
sapogenin, and finally recovering the substance from the ethereal
solution, and crystallising it from hot alcohol. Crystals are readily
obtained if the alcoholic solution is allowed to evaporate
spontaneously. A solution of saponin exposed to the air gets turbid, and
develops carbon dioxide; not unfrequently the solution becomes mouldy.
§ 565. =Effects.=--Pelikan[594] has studied the effects of various
saponins on frogs. One to two drops of a saturated watery solution of
saponin applied subcutaneously to the leg, caused, in from five to six
minutes, great weakness, accompanied by a loss of sensibility; but
strong mechanical, chemical, or electrical stimuli applied to the foot
excited reflex action, for the ischiatic nerve still retained its
functions. Nevertheless, from the commencement, the excitability of the
poisoned muscles was much weakened, and just before death quite
disappeared. Section of the ischiatic nerve delayed the phenomena.
Curarine did not seem to have any effect on the poisonous action. A
concentrated solution applied to the heart of a frog soon arrests its
beats, but weaker doses first excite, and then retard.[595]
[594] _Berl. klin. Wochschr._, 36, 186.
[595] J. Hoppe, _Nervenwirkung der Heilmittel_, H. 4, 37.
The author has studied the general action of saponin on kittens,
insects, and infusoria. Small doses, such as from 13 to 32 mgrms. (⅕ to
½ grain), were injected beneath the loose skin of the back of the neck
of a kitten, when there were immediate symptoms of local pain. In from
five to ten minutes the respiration notably quickened, and the animal
fell into a lethargic state, with signs of general muscular weakness;
just before death the breathing became very rapid, and there were all
the signs of asphyxia. The pathological appearances after death were
fulness in the right side of the heart, and intense congestion of the
intestinal canal, the stomach generally being perfectly normal in
appearance, and the kidneys and other organs healthy. The least fatal
dose for a kitten seems to be 13 mgrms., or ·04 grm. to a kilogram.[596]
[596] The action of saponin when applied in concentrated solution to
flies is that of an intense irritant. There is protrusion of the sucker,
and progressive paralysis. The common infusoria live for some time in
dilute solutions of saponin--this is also true of some of the higher
forms; for example, a _Cyclops quadricornis_ seemed in no way affected
by a 2 per cent. solution.
§ 566. =Action on Man.=--The effects of saponin on man have been but
little studied; it has been administered by the mouth in doses of from
·1 to ·2 grm., and in those doses seems to have distinct physiological
effects. There is increased mucous secretion, and a feeling of nausea;
but neither diaphoresis nor diuresis has been observed. From the
foregoing study it may be predicated that 2·6 grms. (40 grains), if
administered subcutaneously to an adult, would endanger life. The
symptoms would be great muscular prostration, weakness of the heart’s
action, and probably diarrhœa. In fatal cases, some signs of an irritant
or inflammatory action on the mucous membranes of the stomach and
intestines would be probable.
§ 567. =Separation of Saponin.=--Saponin is separated from bread, flour,
and similar substances by the process given at p. 153, “Foods.” The
process essentially consists in extracting with hot spirit, allowing the
saponin to separate as the spirit cools, collecting the precipitate on
a filter, drying, dissolving in cold water, and precipitating with
absolute alcohol. In operating on animal tissues, a more elaborate
process is necessary. The author has successfully proceeded as
follows:--The finely divided organ is digested in alcohol of 80 to 90
per cent. strength, and boiled for a quarter of an hour; the alcohol is
filtered hot and allowed to cool, when a deposit forms, consisting of
fatty matters, and containing any saponin present. The deposit is
filtered off, dried, and treated with ether to remove fat. The insoluble
saponin remaining is dissolved in the least possible quantity of water,
and precipitated with absolute alcohol. It is also open to the analyst
to purify it by precipitating with baryta water, the baryta compound
being subsequently decomposed by carbon dioxide. Basic lead acetate may
also be used as a precipitant, the lead compound being, as usual,
decomposed by hydric sulphide; lastly, a watery solution may be shaken
up with chloroform, which will extract saponin. By some one of these
methods, selected according to the exigencies of the case, there will be
no difficulty in separating the glucoside in a fairly pure state. The
organ best to examine for saponin is the kidney. In one of my own
experiments, in a cat poisoned with a subcutaneous dose of saponin (·2
grm.), evidence of the glucoside was obtained from the kidney alone. The
time after death at which it is probable that saponin could be detected
is unknown; it is a substance easily decomposed, and, therefore, success
in separating it from highly putrid matters is not probable.
§ 568. =Identification of Saponin.=--An amorphous white powder, very
soluble in water, insoluble in cold alcohol or ether, having glucosidal
reactions, striking a red colour with sulphuric acid, imparting a
soap-like condition to water, and poisonous to animals, is most probably
a saponin.
DIVISION III.--CERTAIN POISONOUS ANHYDRIDES OF ORGANIC ACIDS.
I.--Santonin.
§ 569. Santonin (C₁₅H₁₈O₃) is a neutral principle extracted from the
unexpanded heads of various species of _Artemisia_ (Nat. Ord.
_Compositæ_). The seeds contain, according to Dragendorff, 2·03 to 2·13
per cent. of santonin, and about 2·25 per cent. of volatile oil, with 3
per cent. of fat and resin. Santonin forms brilliant, white, four-sided,
flat prisms, in taste feebly bitter. The crystals become yellow through
age and exposure to light; they melt at 169°, and are capable of being
sublimed; they are scarcely soluble in cold water, but dissolve in 250
parts of boiling water, freely in alkaline water, in 3 parts of boiling
alcohol, and in 42 parts of boiling ether. Santonin is the anhydride of
santonic acid (C₁₅H₂₀O₄). Santonin unites with alkalies to form
santonates. Sodic santonate (C₁₅H₁₉NaO₄ + 3½H₂O) is officinal on the
Continent; it forms colourless rhombic crystals, soluble in 3 parts of
cold water.
§ 570. =Poisoning by Santonin.=--Eighteen cases of poisoning, either by
santonin or santonin-holding substances, which F. A. Falck has been able
to collect, were nearly all occasioned by its use as a remedy for worms.
A few were poisonings of children who had swallowed it by accident. With
one exception those poisoned were children of from two to twelve years
of age; in five the flower heads, and in thirteen santonin itself was
taken. Of the eighteen cases, two only died (about 11 per cent.).
§ 571. =Fatal Dose.=--So small a number of children have died from
santonin, that data are not present for fixing the minimum fatal dose.
·12 grm. of santonin killed a boy of five and a half years of age in
fifteen hours; a girl, ten years old, died from a quantity of flower
heads, equal to ·2 grm. of santonin. The maximum dose for children is
from 65 to 194 mgrms. (1 to 3 grains), and twice the quantity for
adults.
§ 572. =Effects on Animals.=--Experiments on animals with santonin have
been numerous. It has first an exciting action on the centres of nerves
from the second to the seventh pairs, and then follows decrease of
excitability. The medulla is later affected. There are tetanic
convulsions, and death follows through asphyxia. Artificial respiration
lessens the number and activity of the convulsions, and chloroform,
chloral hydrate, or ether, also either prevent or shorten the attacks.
§ 573. =Effects on Man.=--One of the most constant effects of santonin
is a peculiar aberration of the colour-sense, first observed by Hufeland
in 1806. All things seem yellow, and this may last for twenty-four
hours, seldom longer. According to Rose, this apparent yellowness is
often preceded by a violet hue over all objects. If the lids are closed
while the “yellow sight” is present, the whole field is momentarily
violet. De Martiny,[597] in a few cases, found the “yellow sight”
intermit and pass into other colours, _e.g._, after ·3 grm. there was
first the yellow perception, then giving the same individual ·6 grm.,
all objects seemed coloured red, after half an hour orange, and then
again yellow. In another patient the effect of the drug was to give
“green vision,” and in a third blue.
[597] _Gaz. des Hôpit._, 1860.
Hufner and Helmholtz explain this curious effect as a direct action on
the nervous elements of the retina, causing them to give the perception
of violet; they are first excited, then exhausted, and the eye is
“violet blind.” On the other hand, it has been suggested that santonin
either colours the media of the eye yellow, or that there is an increase
in the pigment of the _macula lutea_. I, however, cannot comprehend how
the two last theories will account for the intermittency and the play of
colours observed in a few cases. To the affections of vision are also
often added hallucinations of taste and smell; there is headache and
giddiness, and in fourteen out of thirty of Rose’s observations vomiting
occurred. The urinary secretion is increased. In large and fatal doses
there are shivering of the body, clonic, and often tetanic convulsions;
the consciousness is lost, the skin is cool, but covered with sweat, the
pupils dilated, the breathing becomes stertorous, the heart’s action
weak and slow, and death occurs in collapse--in the case observed by
Grimm in fifteen hours, in one observed by Linstow in forty-eight hours.
In those patients who have recovered, there have also been noticed
convulsions and loss of consciousness. Sieveking[598] has recorded the
case of a child who took ·12 grm. (1·7 grain) santonin; an eruption of
nettle rash showed itself, but disappeared within an hour.
[598] _Brit. Med. Journ._, 1871.
§ 574. =Post-mortem Appearances.=--The _post-mortem_ appearances are not
characteristic.
§ 575. =Separation of Santonin from the Contents of the Stomach,
&c.=--It is specially important to analyse the fæces, for it has been
observed that some portion goes unchanged into the intestinal canal. The
urine, also, of persons who have taken santonin, possesses some
important peculiarities. It becomes of a peculiar yellow-green, the
colour appearing soon after the ingestion of the drug, and lasting even
sixty hours. The colour may be imitated, and therefore confused with
that which is produced by the bile acids; a similar colour is also seen
after persons have been taking rhubarb. Alkalies added to urine coloured
by santonin or rhubarb strike a red colour. If the urine thus reddened
is digested on zinc dust, santonin urine fades, rhubarb urine remains
red. Further, if the reddened urine is precipitated by excess of milk of
lime or baryta water and filtered, the filtrate from the urine reddened
by rhubarb is colourless, in that reddened by santonin the colour
remains. Santonin may be isolated by treating substances containing it
with warm alkaline water. The water may now be acidified and shaken up
with chloroform, which will dissolve out any santonin. On driving off
the chloroform, the residue should be again alkalised, dissolved in
water, and acidified with hydrochloric acid, and shaken up with
chloroform. In this way, by operating several times, it may be obtained
very pure. Santonin may be identified by its dissolving in alcoholic
potash to a transitory carmine-red, but the best reaction is to dissolve
it in concentrated sulphuric acid, to which a very little water has
been added, to warm on the water-bath, and then to add a few drops of
ferric chloride solution to the warm acid; a ring of a beautiful red
colour passing into purple surrounds each drop, and after a little time,
on continuing the heat, the purple passes into brown. A distinctive
reaction is also the production of “iso-santonin”; this substance is
produced by warming santonin on the water-bath with sulphuric acid for a
few hours, and then diluting with water; iso-santonin is precipitated,
and may be crystallised from boiling alcohol. Iso-santonin melts at
138°; it has the same composition as santonin. It is distinguished from
santonin by giving no red colour when treated with sulphuric or
phosphoric acids.
II.--Mezereon.
§ 576. =The Daphne Mezereum= (L.).--Mezereon, an indigenous shrub
belonging to the _Thymeleaceæ_, is rather rare in the wild state,
but very frequent in gardens. The flowers are purple and the berries
red. Buckheim isolated by means of ether an acrid resin, which was
converted by saponifying agents into _mezereic acid_; the acrid
resin is the anhydride of the acid. The resin is presumed to be the
active poisonous constituent of the plant, but the subject awaits
further investigation. There are a few cases of poisoning on record,
and they have been mostly from the berries. Thus, Linné has recorded
an instance in which a little girl died after eating twelve berries.
The symptoms observed in the recorded cases have been burning in the
mouth, gastroenteritis, vomiting, giddiness, narcosis, and
convulsions, ending in death. The lethal dose for a horse is about
30 grms. of powdered bark; for a dog, the œsophagus being tied, 12
grms.; but smaller doses of the fresh leaves may be deadly.
DIVISION IV.--VARIOUS VEGETABLE POISONOUS PRINCIPLES--NOT ADMITTING OF
CLASSIFICATION UNDER THE PREVIOUS THREE DIVISIONS.
I.--Ergot of Rye.
§ 577. Ergot is a peculiar fungus attacking the rye and other
graminaceous plants;[599] it has received various names, _Claviceps
purpurea_ (Tulasne), _Spermœdia clavus_ (Fries), _Sclerotium clavus_
(D.C.), &c. The peculiar train of symptoms arising from the eating of
ergotised grain (culminating occasionally in gangrene of the lower
limbs), its powerful action on the pregnant uterus, and its styptic
effects, are well known.
[599] Some of the _Cyperaceæ_ are also attacked.
The very general use of the drug by accoucheurs has, so to speak,
popularised a knowledge of its action among all classes of society, and
its criminal employment as an abortive appears to be on the
increase.[600]
[600] The Russian peasantry use the drug for the same purpose. _Vide_
Mackenzie Wallace’s “Russia,” i. p. 117.
The healthy grain of rye, if examined microscopically in thin sections,
is seen to be composed of the seed-coating, made up of two layers,
beneath which are the gluten-cells, whilst the great bulk of the seed is
composed of cells containing starch. In the ergotised grain, dark
(almost black) cells replace the seed-coat and the gluten-cells, whilst
the large starch-containing cells are filled with the small cells of the
fungus and numerous drops of oil.
§ 578. =The chemical constituents of ergot= are a fixed oil,
trimethylamine, certain active principles, and colouring-matters.
The =fixed oil= is of a brownish-yellow colour, of aromatic flavour and
acrid taste; its specific gravity is 0·924, and it consists chiefly of
palmitin and olein; it has no physiological action.
=Trimethylamine= is always present ready formed in ergot; it can also be
produced by the action of potash on ergot.
With regard to the =active principles of ergot= considerable confusion
still exists, and no one has hitherto isolated any single substance in
such a state of purity as to inspire confidence as to its formula or
other chemical characters. They may, however, be briefly described.
C. Tamet[601] has separated an alkaloid, which appears identical with
Wenzel’s _ergotinine_. To obtain this the ergot is extracted by alcohol
of 86°, the spirit removed by distillation, and the residue cooled; a
resin (which is deposited) and a fatty layer (which floats on the
surface) are separated from the extractive liquor and washed with ether;
the ethereal solution is filtered and shaken with dilute sulphuric acid,
which takes up the alkaloid; the aqueous solution of the substance is
then filtered, rendered alkaline by KHO, and agitated with chloroform.
The ergotinine is now obtained by evaporating the chloroform solution,
care being taken to protect it from contact with the air. It gives
precipitates with chloride of gold, potassium iodohydrargyrate,
phosphomolybdic acid, tannin, bromine water, and the chlorides of gold
and platinum. With moderately concentrated SO₄H₂, it gives a
yellowish-red coloration, changing to an intense violet, a reaction
which does not occur if the alkaloid has been exposed to the air. The
composition of the base is represented by the formula C₇₀H₄₀N₄O₁₂, and a
crystalline sulphate and lactate have been obtained.[602]
[601] _Compt. Rendus_, vol. xxxi. p. 896.
[602] _Compt. Rendus_, April 1878.
Wenzel’s =Ecboline= is prepared by precipitating the cold watery extract
of ergot with sugar of lead, throwing out the lead in the usual way by
hydric sulphide, concentrating the liquid, and adding mercuric chloride,
which only precipitates the ecboline. The mercury salt is now decomposed
with hydric sulphide, and after the mercury precipitate has been
filtered off, the filtrate is treated with freshly precipitated
phosphate of silver, and refiltered; lastly, the liquid is shaken up
with milk of lime, again filtered, and the lime thrown out by CO₂. The
last filtrate contains ecboline only, and is obtained by evaporation at
a gentle heat. It is an amorphous, feebly bitter substance, with an
alkaline reaction, forming only amorphous salts.
The most recent research by Dragendorff on ergot tends to show that
Wenzel’s alkaloids, ergotinine and ecboline, are inactive. Dragendorff
describes also (_a._) _Scleromucin_, a slimy substance which goes into
solution upon extraction of the ergot with water, and which is again
precipitated by 40 to 45 per cent. alcohol. It is colloidal and soluble
with difficulty in water. It contains nitrogen, but gives no albuminoid
reaction, nor any reaction of an alkaloidal or glucosidal body; it
yields to analysis--
8·26 per cent. Water.
26·8 „ Ash.
39·0 „ Carbon.
6·44 „ Hydrogen.
6·41 „ Nitrogen.
(_b._) =Sclerotic Acid.=--A feebly-acid substance, easily soluble in
water and dilute and moderately concentrated alcohol. It passes, in
association with other constituents of the ergot extract, into the
diffusate, when the extract is submitted to dialysis; but after its
separation in a pure state it is, like scleromucin, colloidal. It is
precipitated by 85 to 90 per cent. alcohol, together with lime, potash,
soda, silica, and manganese; but after maceration with hydrochloric
acid, the greater part of the ash constituents can be separated by a
fresh precipitation with absolute alcohol. The sample gave 40·0 per
cent. of carbon, 5·2 per cent. hydrogen, 4·2 per cent. nitrogen, 50.6
per cent. oxygen, with 3·4 per cent. of ash. Sclerotic acid forms with
lime a compound that is not decomposed by carbonic acid, and which upon
combustion leaves from 19 to 20 per cent. of calcium carbonate. Both
these substances are active, although evidently impure. Sclerotic acid
is sold in commerce, and has been employed subcutaneously in midwifery
practice in Russia and Germany for some time.
The inert principles of ergot are--(1.) A red colouring matter,
_Sclererythrin_, insoluble in water, but soluble in dilute and strong
alcohol, ether, chloroform, dilute solutions of potash, ammonia, &c. It
can be obtained by dissolving in an alkali, neutralising with an acid,
and shaking up with ether. Alcoholic solution of sclererythrin gives
with aluminium sulphate, and with zinc chloride, a splendid red mixture;
with salts of calcium, barium, and many of the heavy metals, it gives a
blue precipitate; the yield is only ·1 to ·05 in a thousand parts.
(2.) Another colouring-matter, dissolving in concentrated sulphuric acid
with the production of a fine blue violet colour, the discoverer has
named _Scleroidin_. This is not soluble in alcohol, ether, chloroform,
or water, but dissolves in alkaline solutions, potash producing a
splendid violet colour; yield about 1 per 1000.
(3, 4.) Two crystalline substances, which may be obtained from ergot
powder, first treated with an aqueous solution of tartaric acid, and the
colouring-matters extracted by ether. One Dragendorff names
_Sclerocrystallin_ (C₁₀H₁₀O₄); it is in colourless needles, insoluble in
alcohol and water, with difficulty soluble in ether, but dissolving in
ammonia and potash solutions. The other crystalline substance is thought
to be merely a hydrated compound of sclerocrystallin. Both are without
physiological action.
Kobert recognises two active substances in ergot, and two alone; the one
he calls _sphacelic acid_, the other _cornutin_.
§ 579. =Detection of Ergot in Flour= (see “Foods”).--The best process is
to exhaust the flour with boiling alcohol. The alcoholic solution is
acidified with dilute sulphuric acid, and the coloured liquid examined
by the spectroscope in thicker or thinner layers, according to the depth
of colour. A similar alcoholic solution of ergot should be made, and the
spectrum compared. If the flour is ergotised, the solution will be more
or less red, and show two absorption bands, one in the green, and a
broader and stronger one in the blue. On mixing the original solution
with twice its volume of water, and shaking successive portions of this
liquid with ether, amyl alcohol, benzene, and chloroform, the red
colour, if derived from ergot, will impart its colour to each and all of
these solvents.
§ 580. =Pharmaceutical Preparations.=--Ergot itself is officinal in all
the pharmacopœias, and occurs in grains from ⅓ to 1 inch in length, and
about the same breadth, triangular, curved, obtuse at the ends, of a
purple colour, covered with a bloom, and brittle, exhibiting a pinkish
interior, and the microscopical appearances already detailed. Ergot may
also occur as a brown powder, possessing the unmistakable odour of the
drug. A liquid extract of the B.P. is prepared by digesting 16 parts of
ergot in 80 parts of water for twelve hours, the infusion is decanted or
filtered off, and the digestion repeated with 40 parts of water; this is
also filtered off, and the residue pressed, and the whole filtrate
united and evaporated down to 11 parts; when cold, 6 parts of rectified
spirit are added, and, after standing, the liquid is filtered and made
up to measure 16. A tincture and an infusion are also officinal; the
latter is very frequently used, but seldom sold, for it is preferable to
prepare it on the spot. The tincture experience has shown to be far
inferior in power to the extract, and it is not much used. Ergotin is a
purified extract of uncertain strength; it is used for hypodermic
injection; it should be about five times more active than the liquid
extract.
§ 581. =Dose.=--The main difficulties in the statement of the medicinal
dose, and of the minimum quantity which will destroy life, are the
extreme variability of different samples of ergot, and its readiness to
decompose. A full medicinal dose of ergot itself, as given to a woman in
labour, is 4 grms. (61·7 grains), repeated every half hour. In this way
enormous doses may be given in some cases without much effect. On the
other hand, single doses of from 1 to 4 grms. have caused serious
poisonous symptoms. The extract and the tincture are seldom given in
larger doses than that of a drachm as a first dose, to excite uterine
contraction. In fact, the medical practitioner has in many cases to
experiment on his patient with the drug, in order to discover, not only
the individual susceptibility, but the activity of the particular
preparation used. From the experiments of Nikitin, it is probable that
the least fatal dose of sclerotic acid for an adult man is 20 mgrms. per
kilogrm.
§ 582. =Ergotism.=--Ergotised cereals have played a great part in
various epidemics, probably from very early times, but the only accurate
records respecting them date from the sixteenth century. According to
Dr. Tissot,[603] the first recorded epidemic was in 1596, when a
strange, spasmodic, convulsive disease broke out in Hessia and the
neighbouring regions. It was probably due to spurred rye. In
Voigtländer, the same disease appeared in 1648, 1649, and 1675; in 1702
the whole of Freiberg was attacked. In Germany and in France successive
epidemics are described throughout the eighteenth century. In France, in
1710, Ch. Noel, physician at the _Hôtel Dieu_, had no less than fifty
cases under treatment at the same time.
[603] Dr. Tissot in _Phil. Trans._, vol. lv. p. 106, 1765. This is a
Latin letter by Dr. Baker, and gives a good history of the various
epidemics of ergotism.
It is generally said that in 1630, Thuillier, in describing an ergot
epidemic which broke out in Cologne, first referred the cause of the
disease to spurred rye.
It is interesting to inquire into the mortality from this disease. In
1770, in an epidemic described by Taube, in which 600 were affected, 16
per cent. died. In a nineteenth-century epidemic (1855), in which,
according to Husemann, 30 were ill, 23·3 per cent. died. In other
epidemics, according to Heusinger, out of 102, 12 per cent. died;
according to Griepenkerl, out of 155, 25 or 16 per cent. died; and,
according to Meyer, of 283 cases, 6 per cent. died.
There are two forms of chronic poisoning by ergot--one a spasmodic form,
the other the gangrenous form.
§ 583. =The convulsive form of ergotism= mostly begins with some
cerebral disturbance. There are sparks before the eyes, giddiness,
noises in the ears, and a creeping feeling about the body. There is also
very commonly anæsthesia of the fingers and toes, and later of the
extremities, of the back, and even of the tongue. Diarrhœa, vomiting,
colic, and other signs of intestinal irritation seldom fail to be
present; there are also tetanic spasms of the muscles, rising in some
cases to well-marked tetanus; epilepsy, faintings, aberrations of
vision, amaurosis, and amblyopia are frequent; the skin becomes of a
yellow or earthy colour, and is covered with a cold sweat; boils and
other eruptions may break out; blebs, like those caused by burns or
scalds, have in a few cases been noticed. Death may occur in from four
to twelve weeks after the eating of the spurred grain from exhaustion.
In those individuals who recover, there remain for some time weakness,
contractions of groups of muscles, anæmia, or affections of vision.
§ 584. =The Gangrenous Form of Ergotism.=--In this form there is
generally acute pain in the limb or limbs which are to mortify; and
there may be prodromata, similar to those already described. The limb
swells, is covered with an erysipelatous blush, but at the same time
feels icy cold; the gangrene is generally dry, occasionally moist; the
mummified parts separate from the healthy by a moist, ulcerative
process; and in this way the toes, fingers, legs, and even the nose, may
be lost. During the process of separation there is some fever, and
pyæmia may occur with a fatal result.
Fontenelle described a case in which a rustic lost all the toes of one
foot, then those of the other; after that, the remnant of the first
foot, and lastly the leg. But probably the most extraordinary case of
gangrene caused by the use of ergot is that which occurred at Wattisham,
Suffolk, in the family of a labouring man named John Downing. He had a
wife and six children of various ages, from fifteen years to four
months. On Monday, January 10, 1762, the eldest girl complained of a
pain in the calf of her left leg; in the evening, her sister, aged 10,
also experienced the same symptoms. On the following Monday, the mother
and another child, and on Tuesday, all the rest of the family except the
father became affected. The pain was very violent. The baby at the
breast lived a few weeks, and died of mortification of the extremities.
The limbs of the family now began to slough off, and the following are
the notes on their condition made by an observer, Dr. C. Wollaston,
F.R.S., on April 13:--
“The mother, aged 40. Right foot off at the ankle, the left leg
mortified; a mere bone left, but not off.
“Elizabeth, aged 13. Both legs off below the knees.
“Sarah, aged 10. One foot off at the ankle.
“Robert, aged 8. Both legs off below the knees.
“Richard, aged 4. Both feet off at the ankle.
“Infant, four months old, dead.”
The father was also attacked a fortnight after the rest of the family,
and in a slighter degree--the pain being confined to the fingers of his
right hand, which turned a blackish colour, and were withered for some
time, but ultimately got better.
As a remarkable fact, it is specially noted that the family were in
other respects well. They ate heartily, and slept soundly when the pain
began to abate. The mother looked emaciated. “The poor boy in particular
looked as healthy and florid as possible, and was sitting on the bed,
quite jolly, drumming with his stumps.” They lived as the country people
at the time usually lived, on dried peas, pickled pork, bread and
cheese, milk, and small beer. Dr. Wollaston strictly examined the corn
with which they made the bread, and he found it “very bad; it was wheat
that had been cut in a rainy season, and had lain in the ground till
many of the grains were black and totally decayed.”[604]
[604] In the _Phil. Trans._ for 1762 there are two strictly concordant
accounts of this case; and in the parish church of Wattisham, there is
said to be a memorial tablet, which runs as follows:--“This inscription
serves to authenticate the truth of a singular calamity which suddenly
happened to a poor family in this parish, of which six persons lost
their feet by a mortification not to be accounted for. A full narrative
of their case is recorded in the Parish Register and _Philosophical
Transactions_ for 1762.”
§ 585. =Symptoms of Acute Poisoning by Ergot.=--In a fatal case of
poisoning by ergot of rye, recorded by Dr. Davidson,[605] in which a
hospital nurse, aged 28, took ergot, the symptoms were mainly vomiting
of blood, the passing of bloody urine, intense jaundice, and stupor. But
in other cases, jaundice and vomiting of blood have not been recorded,
and the general course of acute poisoning shows, on the one hand,
symptoms of intense gastro-intestinal irritation, as vomiting, colicky
pains, and diarrhœa; and, on the other, of a secondary affection of the
nervous system, weakness of the limbs, aberrations of vision, delirium,
retention of urine, coma, and death.
[605] _Lancet_, Sept. 30, 1882.
§ 586. =Physiological Action as shown by Experiments on Animals.=--In
spite of numerous experiments on animals and man, the action of the
ergot principles remains obscure. It has been found in medicine to exert
a specific action on the uterus,[606] causing powerful contractions of
that organ, especially in labour. It is also a hæmostatic, and is used
to check bleeding from the lungs and other internal organs of the body.
This hæmostatic action, as well as the extraordinary property possessed
by ergot, of producing an arrest or disturbance of the circulation
inducing gangrene has naturally led to the belief that ergot causes a
narrowing in the calibre of the small arteries, but this has not
received the necessary experimental sanction. Holmes,[607] Eberty,
Köhler,[608] and Wernick,[609] all observed a contraction in the part to
which the ergot was applied, both in frogs and in warm-blooded animals;
but L. Hermann,[610] although he made many experiments, and used the
most different preparations, never succeeded in observing a contraction.
It would also seem reasonable to expect that with a narrowing of the
vessels, which means a peripheral obstruction, the blood-pressure would
rise, but on the contrary the pressure sinks, a fact on which there is
no division of opinion.
[606] In a case in which the author was engaged, a dabbler in drugs,
having seduced a young woman, administered to her a dose of ergot which
produced a miscarriage, and for this offence he was convicted. The
defence raised was that ergot is a common medicine used by physicians in
the treatment of amenorrhœa, and other uterine affections. Although in
itself this statement was perfectly true, as a defence it was
invalidated by the large dose given, the fact of the seduction, and the
other circumstances of the case.
[607] _Archiv d. Physiol. Norm. u. Pathol._, iii. p. 384.
[608] _Ueber die Wirkungen des Secale Cornutum_, Dissert. Halle, 1873.
[609] _Arch. f. pathol. Anat._, lvi. p 505.
[610] _Lehrbuch der exper. Toxicologie_, Berlin, 1874, p. 386.
Nikitin has made some researches with pure sclerotic acid, which
certainly possesses the most prominent therapeutic effects of ergot; but
since it is not the only _toxic_ substance, it may not represent the
collective action of the drug, just in the same way that morphine is not
equivalent in action to opium. Cold-blooded animals are very sensitive
to sclerotic acid; of the warm-blooded the carnivoræ are more sensitive
than the herbivoræ. The toxic action is specially directed to the
central nervous system--with frogs, the reflex excitability is
diminished to full paralysis; with warm-blooded animals reflex
excitability is only diminished, and continues to exist even to death.
The temperature falls, the breathing is slowed, and the respiration
stops before the heart ceases to beat; the peristaltic action of the
intestines is quickened, and the uterus (even of non-pregnant animals)
is thrown into contraction. The terminations of the sensory nerves are
paralysed by the direct action of sclerotic acid, but they remain intact
with general poisoning. The heart of frogs is slowed by sclerotic acid.
Eberty observed that this slowing of the heart (he used ergotin) was
produced even after destruction of the spinal cord; he therefore
considered it as acting on the inhibitory nerve apparatus of the heart
itself. Rossbach, using Wenzel’s ecbolin, has also studied its action on
the heart of the frog, and observed that the slowing affected the
ventricles rather than the auricles, so that for one ventricle-systole
there were two contractions of the auricles; besides which, the
contractions themselves were peculiar and abnormal in character. The
cause of death from sclerotic acid seems to be paralysis of the
respiration. It is said not to affect animal fœtal life. With regard to
the effects produced by feeding animals with ergotised grain,
experiments made during the last century have proved that it produces a
gangrenous disease, _e.g._, C. Salerné mixed one part of spurred rye
with two of good barley, and fed pigs with the mixture; a few days
afterwards the pigs perished with dilated, hard, and black bellies, and
offensively ulcerated legs; another pig fed entirely on the rye, lost
its four feet and both ears.
Kobert[611] has investigated the effects produced on animals by
“sphacelic acid,” and by “cornutin.” Sphacelic acid appears to cause
gangrene, like ergot, and Kobert believes that in “sphacelic acid” is to
be found the gangrene-producing substance. In cases of death
putrefaction is rapid, the mucous membrane of the intestine is swollen,
and the spleen enlarged. If the mucous membrane of the intestine is
examined microscopically, a large quantity of micro-organisms are found
in the vessels, in the villi, between the muscular bundles and in the
deeper layers of the intestinal walls; this is evidence that the
protective epithelial cells have been destroyed. The mesentery of cats,
pigs, and fowls, contains numerous small extravasations of blood. The
organs generally, and especially the subcutaneous cellular tissue, are
tinged with the colouring matters of the bile; this Kobert considers as
evidence of weakened vitality of the red blood corpuscles. The walls of
the blood-vessels show hyaline degeneration, and give with iodine a
quasi-amyloid reaction. The vessels are often partly filled with a
hyaline mass, in which, at a later date, a fine black pigment appears.
These pigmented hyaline masses probably occlude the vessels, and hence
cause gangrene.
[611] _Lehrbuch der Intoxicationen_, by Dr. Rudolph Kobert, Stuttgart,
1893.
Cornutin, according to Kobert, first excites the vagus; consequently
there is slow pulse and heightened blood pressure; then it paralyses the
vaso-motor centre, and the pulse is accelerated. Severe convulsions,
preceded by formication, follow. Paralysis of the extensor muscles, with
permanent deformity, may result. Cornutin stimulates the uterus to
contraction, but it does not act so well in this respect alone as when
given with sphacelic acid. In animals poisoned with cornutin, no special
pathological changes of a distinctive nature have been described.
§ 587. =Separation of the Active Principles of Ergot from Animal
Tissues.=--There has been no experience in the separation of the
constituents of ergot from the organs of the body; an attempt might be
made on the principles detailed in page 425, but success is doubtful.
II.--Picrotoxin, the Active Principle of the Cocculus indicus (Indian
Berry, Levant Nut).
§ 588. The berries of the _Menispermum cocculus_ comprise at least three
definite crystalline principles: _menispermine_,[612] _paramenispermine_
(nitrogen containing bases), and _picrotoxin_, which possesses some of
the characters of an acid.
[612] _Menispermine_ (C₁₈H₂₄N₂O₂?), discovered in 1834 by Pelletier and
Courbe, is associated with a second named _paramenispermine_. The
powdered berries are extracted by alcohol of 36°; the picrotoxin removed
by hot water from the alcoholic extract; the menispermine and
paramenispermine dissolved out together by acidulated water, and from
this solution precipitated by ammonia. The brown precipitate is
dissolved by acetic acid, filtered, and again precipitated by ammonia.
This precipitate is dried, treated with cold alcohol, to separate a
yellow resinous substance, and lastly with ether, which dissolves out
the menispermine, but leaves the paramenispermine.
Menispermine forms white semi-transparent, four-sided, truncated prisms,
melting at 120°, decomposed at a higher temperature, insoluble in water,
but dissolving in warm alcohol and ether. Combined with 8 atoms of water
it crystallises in needles and prisms. The crystals are without any
taste; in combination with acids, salts may be formed.
_Paramenispermine_ forms four-sided prisms, or radiating crystalline
masses, melting at 250°, and subliming undecomposed. The crystals are
soluble in absolute ether, insoluble in water, and scarcely soluble in
ether.
_Paramenispermine_ dissolves in acids, but apparently without forming
definite salts.
§ 589. =Picrotoxin= (C₃₀H₃₄O₁₃) was discovered in 1820 by Boullay. It is
usually prepared by extracting the berries with boiling alcohol,
distilling the alcohol off, boiling the alcoholic residue with a large
quantity of water, purifying the watery extract with sugar of lead,
concentrating the colourless filtrate by evaporation, and crystallising
the picrotoxin out of water.
Picrotoxin crystallises out of water, and also out of alcohol, in
colourless, flexible, four-sided prisms, often arborescent, and
possessing a silky lustre. They are unalterable in the air, soluble in
150 parts of cold, and 25 parts of boiling water, dissolving easily in
acidified water, in spirit, in ether, in amyl alcohol, and chloroform.
They are without smell, but have an extremely bitter taste. Caustic
ammonia is also a solvent.
The crystals are neutral in reaction. They melt at 192°-200° C. to a
yellow mass; at higher temperatures giving off an acid vapour, with a
caramel-like odour, and lastly carbonising. Picrotoxin in cold
concentrated sulphuric acid dissolves with the production of a beautiful
gold-yellow to saffron-yellow colour, which becomes on the addition of a
trace of potassic bichromate, violet passing into brown. An alcoholic
solution turns a ray of polarised light to the left [α]_{D} = -28·1°.
Picrotoxin behaves towards strong bases like a weak acid. Its compounds
with the alkalies and alkaline earths are gummy and not easily obtained
pure. Compounds with quinine, cinchonine, morphine, strychnine, and
brucine can be obtained in the crystalline condition. Dilute sulphuric
acid transforms it, with assimilation of water, into a weak gummy-like
acid, which corresponds to the formula C₁₂H₁₆O₆. Nitric acid oxidises it
to oxalic acid. Nitropicrotoxin and bromopicrotoxin, C₃₀H₃₃(NO₂)O₁₃, and
C₃₀H₃₂Br₂O₁₃, can by appropriate treatment be obtained.
Concentrated aqueous solutions of alkalies and ammonia decompose
picrotoxin fully on warming. It reduces alkaline copper solution, and
colours bichromate of potash a beautiful green. The best test for its
presence is, however, as follows:--The supposed picrotoxin is carefully
dried, and mixed with thrice its bulk of saltpetre, the mixture
moistened with sulphuric acid, and then decomposed with soda-lye in
excess, when there is produced a transitory brick-red colour. For the
reaction to succeed, the picrotoxin should be tolerably pure.
Solutions of picrotoxin are not precipitated by the chlorides of
platinum, mercury, and gold, iodide of potassium, ferro- and
ferri-cyanides of potassium, nor by picric nor tannic acids.
§ 590. =Fatal Dose.=--Vossler killed a cat in two hours with a dose of
·12 grm. (1·8 grain); and another cat, with the same dose, died in 45
minutes. Falck destroyed a young hound with ·06 grm. (·92 grain) in 24
to 26 minutes. Given by subcutaneous or intravenous injection, it is, as
might be expected, still more lethal and rapid in its effects. In an
experiment of Falck’s, ·03 grm. (·46 grain), injected into a vein,
destroyed a strong hound within 20 minutes; ·016 grm. (·24 grain)
injected under the skin, killed a guinea-pig in 22 minutes; and ·012
grm. (·18 grain) a hare in 40 minutes. Hence it may be inferred that
from 2 to 3 grains (12·9 to 19·4 centigrms.) would in all probability,
be a dangerous dose for an adult person.
§ 591. =Effects on Animals.=--The toxic action of picrotoxin on fish and
frogs has been proposed as a test. The symptoms observed in fish are
mainly as follows:--The fish, according to the dose, show uncertain
motions of the body, lose their balance, and finally float to the
surface, lying on one side, with frequent opening of the mouth and
gill-covers. These symptoms are, however, in no way distinguishable from
those induced by any poisonous substance in the water, or by many
diseases to which fish are liable. Nevertheless, it may be conceded that
in certain cases the test may be valuable--if, _e.g._, beer be the
matter of research, none of the methods used for the extraction of
picrotoxin will be likely to extract any other substance having the
poisonous action described on fish, so that, as a confirmatory test,
this may be of use.
Frogs, under the influence of picrotoxin, become first uneasy and
restless, and then somewhat somnolent; but after a short time tetanic
convulsions set in, which might lead the inexperienced to imagine that
the animal was poisoned by strychnine. There is, however, one marked
distinction between the two--viz., that in picrotoxin poisoning an
extraordinary swelling of the abdomen has been observed, a symptom
which, so far as known, is due to picrotoxin alone. The frog is,
therefore, in this instance, the most suitable object for physiological
tests.
Beer extract containing picrotoxin is fatal to flies; but no definite
conclusion can be drawn from this, since many bitter principles (notably
quassia) are in a similar manner fatal to insect life.
§ 592. =Effects on Man.=--Only two fatal cases of poisoning by
picrotoxin are on record. In 1829 several men suffered from drinking rum
which had been impregnated with _Cocculus indicus_; one died, the rest
recovered. In the second case, a boy, aged 12, swallowed some of a
composition which was used for poisoning fish, the active principle of
which was _Cocculus indicus_; in a few minutes the boy experienced a
burning taste, he had pains in the gullet and stomach, with frequent
vomiting, and diarrhœa. A violent attack of gastro-enteritis supervened,
with fever and delirium; he died on the nineteenth day. The
_post-mortem_ signs were those usual in peritonitis: the stomach was
discoloured, and its coats thinner and softer than was natural; there
were also other changes, but it is obvious that, as the death took place
so long after the event, any pathological signs found are scarcely a
guide for future cases.
§ 593. =Physiological Action.=--The convulsions are considered to arise
from an excitation of the medulla oblongata; the vagus centre is
stimulated, and causes spasm of the glottis and slowing of the heart’s
action during the attack. Röhrig also saw strong contraction of the
uterus produced by _picrotoxin_. According to the researches of Crichton
Browne, _chloral hydrate_ acts in antagonism to picrotoxin, and prevents
the convulsions in animals if the dose of picrotoxin is not too large.
§ 594. =Separation from Organic Matters.=--Picrotoxin is extracted from
aqueous acid solutions by either chloroform, amyl alcohol, or ether; the
first is the most convenient. Benzene does not extract it, if employed
in the same manner. On evaporation of the solvent the crude picrotoxin
can be crystallised out of water, and its properties examined.
R. Palm[613] has taken advantage of the fact that picrotoxin forms a
stable compound with freshly precipitated lead hydroxide, by applying
this property as follows:--the solution supposed to contain picrotoxin
is evaporated to dryness, and the extract then taken up in a very little
water, acidified and shaken out with ether. The ether is evaporated,
the ethereal extract dissolved in a little water, the aqueous solution
filtered through animal charcoal, and precipitated by means of lead
acetate, avoiding excess. The solution is filtered and shaken with
freshly prepared lead hydroxide. The lead hydroxide is dried and tested
direct for picrotoxin; if it does contain picrotoxin then on adding to
it concentrated H₂SO₄ a beautiful saffron yellow is produced as bright
as if the substance was pure picrotoxin.
[613] _J. Pharm._, (5), xvii. 19-20.
III.--The Poison of Illicium Religiosum--A Japanese Plant.
§ 595. A new poison belonging to the picrotoxin class has been
described by Dr. A. Langaard. In 1880, 5 children in Japan were
poisoned by the seeds of the _Illicium religiosum_; 3 of the
children died. Dr. Langaard then made various experiments on animals
with an active extract prepared by exhaustion with spirit, and
ultimate solution of the extract in water. Eykmann has also
imperfectly examined the chemistry of the plant, and has succeeded
in isolating a crystalline body which is not a glucoside; it is
soluble in hot water, in chloroform, ether, alcohol, and acetic
acid, but it is insoluble in petroleum ether; it melts at 175°, and
above that temperature gives an oily sublimate. Langaard’s
conclusions are that all parts of the plant are poisonous. The
poison produces excitation of the central apparatus of the medulla
oblongata and clonic convulsions analogous to those produced by
picrotoxin, toxiresin, and cicutoxin. Before the occurrence of
convulsions, the reflex excitability of frogs is diminished, the
respiratory centre is stimulated, hence frequency of the
respiration. Small doses cause slowing of the pulse through
stimulation of the vagus and of the peripheral terminations of the
vagus; in the heart the functional activity is later diminished.
Small doses kill by paralysing the respiratory centre, large by
heart paralysis. The proper treatment seems to be by chloral
hydrate, for when animals are poisoned by small lethal doses it
appears to save life, although when the dose is large it has no
effect.--_Ueber die Giftwirkung von Japanischem Sternanis_
(_Illicium religiosum_, Sieb.), _Virch. Archiv_, Bd. lxxxvi., 1881,
S. 222.
IV.--Picric Acid and Picrates.
§ 596. =Picric Acid=,
OH
/
C₆H₃N₃O₇, or C₆H₂
\\\
(NO₂)₃
is trinitrophenol; it forms a number of salts, all of which are more or
less poisonous. Picric acid is much used in the arts, especially as a
dye. The pure substance is in the form of pale yellow crystals, not very
soluble in cold water, but readily soluble in hot water, and readily
soluble in benzene, ether, and petroleum ether. The solution is yellow,
tastes bitter, and dyes animal fibres, such as wool; but it can be
washed out of plant fibres such as cotton.
§ 597. =Effects of Picric Acid.=--Picric acid and its salts have a
tendency to decompose the elements of the blood, and to produce
methæmoglobin; picric acid is also an excitor of the nervous system,
producing convulsions. To these two effects must be added a third; in
acid solution it has a strong affinity for albumin, so that if it meets
with an acid tissue it combines with the tissue, and in this way local
necroses are set up. The action on albumin is somewhat weakened by the
reduction in the body of part of the picric acid to picraminic acid
C₆H₂(NO₂)₂NH₂OH, a substance that does not so readily form compounds
with albuminous matters. Doses of 0·5 to 0·9 grm. (about 8 to 14 grains)
may be taken several days in succession without marked symptoms.
Ultimately, however, what is known as “picric jaundice” appears, the
conjunctiva and the whole skin being stained more or less yellow. The
urine, at first of a dark yellow, is later of a red brown colour.
Dyspepsia, with flatulence and an inclination to diarrhœa have been
noticed. A single dose of a gramme (15·4 grains) caused in a case
described by Adler[614] pain in the stomach, headache, weakness,
diarrhœa, vomiting of yellow matters, quickening and afterwards slowing
of the pulse; the skin was of a brown yellow colour, and there were
nervous symptoms. The urine was ruby red. In both fæces and urine picric
acid could be recognised. The excretion of picric acid continued for six
days. A microscopical examination of the blood showed a diminution of
the red blood corpuscles, an increase in the white. Chéron[615] has
described a case in which the application of 0·45 grm. (6·9 grains) to
the vagina produced yellowness of the skin in an hour, and the urine was
also coloured red. Erythema, somnolence, burning and smarting in the
stomach and in the kidneys were also noticed.
[614] _Wiener. med. Woch._, 1880, 819.
[615] J. Chéron, _Journ. de Thêr._, 1880, 121.
§ 598. =Tests.=--Picric acid is easily separated from either tissues or
other organic matters. These are acidified with sulphuric acid and then
treated with 95 per cent. alcohol; the alcohol is filtered off,
distilled, and the residue treated with ether; this last ethereal
extract will contain any picric acid that may be present.
If the ether extract contains much impurity, it may be necessary to
drive off the ether, and to take up the residue with a little warm
water, then to cool, filter through a moistened filter paper, and test
the aqueous solution. Picric acid, warmed with KCN and KHO gives a
blood-red colour, from the production of iso-purpurate of potash.
Ammoniacal copper sulphate forms with picric acid yellow-green crystals
which strongly refract the light. If a solution of picric acid be
reduced by the addition of a hydrochloric acid solution of stannous
chloride, the subsequent addition of ferric chloride produces a blue
colour, due to the formation of amidoimidophenol hydrochloride
C₆H₂OH(NH₂)(NH)₂HCl.
V.--Cicutoxin.
§ 599. The _Cicuta virosa_, a not very common umbelliferous plant
growing in moist places, is extremely poisonous. It is from 3 to 4 feet
in height, with white flowers; the umbels are large, the leaves are
tripartite, the leaflets linear lanceolate acute, serrate decurrent; the
calyx has five leaf-like teeth, the petals are obcordate with an inflex
point; the carpels have five equal broad flattened ridges with solitary
stripes. Böhm[616] succeeded, in 1876, in separating an active principle
from this plant. The root was dried, powdered, and exhausted with ether;
on evaporation of the ether the extract was taken up with alcohol, and
after several days standing the filtrate was treated with petroleum
ether; after removing the petroleum, the solution was evaporated to
dryness in a vacuum; it was found to be a resinous mass, to which was
given the name _cicutoxin_. It was fully soluble in alcohol, ether, or
chloroform, and was very poisonous, but what its exact chemical nature
may be is still unknown.
[616] _Arch. f. exp. Path._, Bd. v., 1876.
§ 600. =Effects on Animals.=--Subcutaneously injected into frogs,
cicutoxin acts something like picrotoxin, and something like the barium
compounds. Ten to fifteen minutes after the injection the animal assumes
a peculiar posture, holding the legs so that the thigh is stretched out
far from the trunk, and the leg at right angles with the thigh;
voluntary motion is only induced by the strongest stimuli, and when the
frog springs, he falls down plump with stiffly stretched-out limbs. The
frequency of breathing is increased, the muscles of the abdomen are
thrown into contraction, and the lungs being full of air, on mechanical
irritation there is a peculiar loud cry, depending upon the air being
forced under the conditions detailed through the narrow glottis. Tetanic
convulsions follow, gradually paresis of the extremities appears, and,
lastly, full paralysis and death; these symptoms are seen after doses of
from 1 to 2 mgrms. The lethal dose for cats is about 1 centigrm. per
kilo. Diarrhœa, salivation, and frequent breathing are first seen, and
are followed by tonic and clonic convulsions, then there is an interval,
during which there is heightened excitability of reflex action, so that
noises will excite convulsions. Small doses by exciting the vagus slow
the pulse; larger doses quicken the pulse, and raise the arterial
pressure. Cicutoxin is supposed to act specially on the medulla
oblongata, while the spinal cord and the brain are only secondarily
affected.
§ 601. =Effects on Man.=--F. A. Falck was able to collect thirty-one
cases of poisoning by cicuta; of these 14 or 45·2 per cent. died. The
symptoms are not dissimilar to those described in animals. There are
pain and burning in the stomach, nausea, vomiting, headache, and then
tetanic convulsions. These, in some cases, are very severe, and resemble
those induced by strychnine; but in a few cases there is early coma
without convulsions. There is also difficulty or absolute impossibility
of swallowing. In fatal cases the respiration becomes stertorous, the
pulse small, the pupils dilated, and the face cyanotic, and death occurs
within some four hours, and in a few cases later. The _fatal dose_ is
unknown.
§ 602. =Separation of Cicutoxin from the Body.=--An attempt might be
made to extract cicutoxin from the tissues on the same principles as
those by which it has been separated from the plant, and identified by
physiological experiments. In all recorded cases, identification has
been neither by chemical nor physiological aids, but by the recognition
of portions of the plant.
VI.--Æthusa Cynapium (Fool’s Parsley).
§ 603. This plant has long been considered poisonous, and a number of
cases are on record in which it is alleged that death or illness
resulted from its use. Dr. John Harley,[617] however, in an elaborate
paper, has satisfactorily proved the innocence of this plant, and has
analysed the cases on record. He has experimented on himself, on
animals, and on men, with the expressed juice and with the tincture. The
results were entirely negative: some of the published cases he refers to
conium, and others to aconite.
[617] _St. Thomas’ Hospital Reports_, N.S., 1875.
VII.--Œnanthe Crocata.
§ 604. =The Water Hemlock.=[618]--This, a poisonous umbelliferous plant,
indigenous to England, and growing in moist places such as ditches, &c.,
is in flower in the month of August. It resembles somewhat celery, and
the root is something like the parsnip, for which it has been eaten. All
parts of the plant are said to be poisonous, but the leaves and stalks
only slightly so, while the root is very deadly. We unfortunately know
nothing whatever about the active principles of the plant, its
chemistry has yet to be worked out. M. Toulmouche (_Gaz. Méd._, 1846)
has recorded, as the expert employed in the case, an attempt to murder
by using the _œnanthe_ as a poison; a woman scraped the root into her
husband’s soup with evil intent, but the taste was unpleasant, and led
to the detection of the crime. The root has been mistaken several times
for parsnip and other edible roots, and has thus led to poisonings. The
case of 36 soldiers poisoned in this way, in 1758, has been recorded by
Orfila; there was one death. In 1803 three soldiers were poisoned at
Brest--1 died. In Woolwich Bossey witnessed the poisoning of 21 convicts
who ate the roots and leaves of the plant--6 died. In 1858 there were
several sailors poisoned in a similar way--2 died; while there have been
numerous cases in which the plant has been partaken of by children.
[618] The earliest treatise on poisoning by the water-hemlock is by
Wepfer. _Cicutæ Aquat. Historia et Noxæ_, 1679; for cases see
Trojanowsky, _Dorp. med. Ztg._, 1875; Meyer, _Med. Zeitg. f. Preussen_,
1842; Schlesier in Casper’s _Wochenschrift_, 1843; Maly, _Œster. med
Wochenschr._, 1844; Badgeley, _Montreal med. Gaz._, 1844; Lender,
_Viertelj. f. ger. Med._, 1865; Gampf, _Cöln. Pharm. Zeitg._, 1875; and
the treatises of Taylor and others.
§ 605. The effects of the poison may be gathered from a case of
poisoning[619] which occurred in 1882 at Plymouth; a Greek sailor, aged
thirty, found on the coast what he considered “wild celery,” and ate
part of the root and some of the stem. Two hours after this he ate a
good meal and felt perfectly well, but fifteen minutes later he suddenly
and violently vomited; the whole contents of the stomach were completely
evacuated. In five minutes he was completely unconscious, and had
muscular twitchings about the limbs and face. There was a copious flow
of a thick tenacious mucus from the mouth which hung about the lips and
clothing in viscid strings. Twenty-four hours after the poisoning he was
admitted into the South Devon Hospital apparently semi-comatose; his
legs dragged, and he had only feeble control of them; the extremities
were cold, but there was general free sweating. He could be roused only
with difficulty. There were no spasms, the pupils were dilated and
sluggish, the respiration only 14 per minute. Twelve hours after
admission he became warmer, and perspired freely; he slept continuously,
but could easily be roused. On the following day he was quite conscious,
and made a good recovery. Two companions who had also eaten a smaller
quantity of the hemlock dropwort, escaped with some numbing sensations,
and imperfect control over the extremities. In the Woolwich cases the
symptoms seem to have been something similar; in about twenty minutes,
one man, without any apparent warning, fell down in strong convulsions,
which soon ceased, although he looked wild; a little while afterwards
his face became bloated and livid, his breathing stertorous and
convulsive, and he died in five minutes after the first symptoms had set
in. A second died with similar symptoms in a quarter of an hour; a third
died in about an hour, a fourth in a little more than an hour; two other
cases also proved fatal, one in nine days, the other in eleven. In the
two last cases there were signs of intestinal irritation. The majority
of the others fell down in a state of insensibility with convulsions,
the after-symptoms being more or less irritation of the intestinal
canal.
[619] _Lancet_, Dec. 18, 1882.
§ 606. =Post-mortem Appearances.=--It was noticed in the Woolwich cases
that those who died quickly had congestion of the cerebral vessels, and,
in one instance, there was even extravasation of blood, but the man who
died first of all had no congestion of the cerebral vessels. The lining
membrane of the wind-pipe and air tubes was intensely injected with
blood, and the lungs were gorged with fluid blood; the blood in the
heart was black and fluid. The stomach and intestines were externally of
a pink colour. The mucous membrane of the stomach was much corrugated,
and the follicles particularly enlarged. In the two protracted cases the
stomach was not reddened internally, but the vessels of the brain were
congested.
VIII.--Oil of Savin.
§ 607. The leaves of the _Sabina communis_ (_Juniperus Sabina_), or
common savin, an evergreen shrub to be found in many gardens, contains a
volatile oil, which has highly irritant properties. Savin leaves are
occasionally used in medicine, maximum dose 1 grm. (15·4 grains). There
is also a tincture--maximum dose 3 c.c. (about 45 mins.)--and an
ointment made by mixing eight parts of savin tops with three of yellow
wax and sixteen parts of lard, melting and digesting for twenty minutes,
and then straining through calico. The oil, a tincture, and an ointment,
are officinal pharmaceutical preparations.
The oil of savin is contained to the extent of about 2 per cent. in the
leaves and 10 per cent. in the fruit. It has a peculiar odour, its
specific gravity is ·89 to ·94, and it boils at 155° to 160°. An
infusion of savin leaves (the leaves being drunk with the liquid) is a
popular and very dangerous abortive.
It is stated by Taylor that oil of savin has no abortive effect, save
that which is to be attributed to its general effect upon the system,
but this is erroneous. Röhrig found that, when administered to rabbits,
it had a very evident effect upon the pregnant uterus, throwing it into
a tetanic contraction. The action was evident after destruction of the
spinal cord. The plant causes great irritation and inflammation, whether
applied to the skin or taken internally. The symptoms are excruciating
pain, vomiting, and diarrhœa, and the person dies in a kind of collapse.
In a case in which the author was engaged some years ago, a woman,
pregnant by a married man, took an unknown quantity of infusion of savin
tops. She was violently sick, suffered great pain, with diarrhœa, and
died in about 26 hours. The pharynx was much reddened, and the gullet
even congested; the stomach was inflamed, and contained some greenish
matter, in which the author was able to detect savin tops, as well as to
separate by distillation a few drops of a strong savin-like smelling
oil. The time which would elapse between the swallowing of the poison
and the commencement of the pain was an important factor in this case,
for the man was accused of having supplied her with the infusion. From
the redness of the pharynx, and, generally, the rapid irritation caused
by ethereal oils, the author was of opinion that but a few minutes must
have passed between the taking of the liquid and the sensation of
considerable burning pain, although it is laid down in some works, as
for example Falck’s _Toxicologie_, that commonly the symptoms do not
commence for several hours. Symptoms which have been noticed in many
cases are--some considerable irritation of the urinary organs, such as
strangury, bloody urine, &c.; in a few cases vomiting of blood, in
others anæsthesia, convulsions, and coma. Death may occur within 12
hours, or may be postponed for two or three days.
§ 608. =Post-mortem Appearances.=--More or less inflammation of the
bowels, stomach, and intestinal tract, with considerable congestion of
the kidneys, are the signs usually found.
§ 609. =Separation of the Poison and Identification.=--Hitherto reliance
has been placed entirely on the finding of the savin tops, or on the
odour of the oil. There is no reliable chemical test.
IX.--Croton Oil.
§ 610. Croton oil is an oil expressed from the seeds of _Croton
tiglium_, a plant belonging to the natural order _Euphorbiaceæ_, growing
in the West Indies. The seeds are oval in shape, not unlike castor-oil
seeds, and about three-eighths of an inch in length. Both the seeds and
the oil are very poisonous. The chemical composition of croton oil can
scarcely be considered adequately settled. The most recent view,
however, seems to be that it contains a fixed oil (C₉H₁₄O₂) with certain
glycerides.[620] On saponifying and decomposing the soap a series of
volatile fatty acids can be distilled over, the principal of which are
methyl crotonic acid, with small quantities of formic, acetic,
iso-butyric, valeric, and perhaps propionic, and other acids.[621] The
peculiar properties of croton are due rather to the fixed oil than to
the volatile principles. The only officinal preparation in the British
pharmacopœia is a “_croton oil liniment_,” containing one part of croton
oil to seven of equal parts of oil of cajuput and rectified spirit.
[620] G. Schmidt, _Arch. Pharm._ [3] 13, 213-229. Schlippe, Liebig’s
_Annalen_, 105, 1. Geuther and Fröhlich, _Zeitschrift f. Chem._, 1870,
26 and 549; _Journ. Chem. Society_, March 1879, p. 221.
[621] Benedikt has found 0·55 per cent. of unsaponifiable matter in
croton oil. Lewkowitsch gives the iodine value 101·7 to 104·7, and
solidifying point as 18·6°-19·0°. (_Cheml. Analysis of the Oils, Fats,
and Waxes_, by R. Benedikt, translated and enlarged by J. Lewkowitsch,
London, 1895.)
§ 611. =Dose.=--The oil is given medicinally as a powerful purgative in
doses up to 65 mgrms. (about a grain). It is used externally as an
irritant or vesicant to the skin. A very dangerous dose would be from
fifteen to twenty times the medicinal dose.
=Effects.=--Numerous cases of poisoning from large doses of croton oil
are recorded in medical literature, but the sufferers have mostly
recovered. The symptoms are pain, and excessive purging and vomiting.
In the case of a chemist,[622] who took half an ounce of impure croton
oil instead of cod-liver oil, the purging was very violent, and he had
more than a hundred stools in a few hours; there was a burning pain in
the gullet and stomach, the skin was cyanosed, the pupils dilated, and
great faintness and weakness were felt, yet the man recovered. A child,
aged four, recovered from a teaspoonful of the oil given by mistake
directly after a full meal of bread and milk. In five minutes there were
vomiting and violent purging, but the child was well in two days. A
death occurred in Paris, in 1839, in four hours after taking two and a
half drachms of the oil. The symptoms of the sufferer, a man, were those
just detailed, namely, burning pain in the stomach, vomiting, and
purging. Singularly enough, no marked change was noticed in the mucous
membrane of the stomach when examined after death. An aged woman died in
3 days from a teaspoonful of croton-oil embrocation; in this case there
were convulsions.
[622] _Revue de Thérapeut._, May 1881.
In the case of _Reg._ v. _Massey and Ferraud_,[623] the prisoners were
charged with causing the death of a man, by poisoning his food with
jalap and six drops of croton oil. The victim, with others who had
partaken of the food, suffered from vomiting and purging; he became
better, but was subsequently affected with inflammation and ulceration
of the bowels, of which he died. In this case it was not clear whether
the inflammation had anything to do with the jalap and croton oil or
not, and the prisoners were acquitted. In a criminal case in the United
States, a man, addicted to drink, was given, when intoxicated, 2 drachms
of croton oil in a glass of whisky. He vomited, but was not purged, and
in about twelve hours was found dead. The mucous membrane of the stomach
and small intestines proved to be much inflamed, and in some parts
eroded, and croton oil was separated from the stomach.
[623] _Orfila_, t. i. p. 108.
§ 612. =Post-mortem Appearances.=--Inflammation of the stomach and
intestines are the signs usually found in man and animals.
§ 613. =Chemical Analysis.=--The oil may be separated from the contents
of the stomach by ether. After evaporation of the ether, the blistering
or irritant properties of the oil should be essayed by placing a droplet
on the inside of the arm.
X.--The Toxalbumins of Castor-Oil Seeds and of Abrus.
§ 614. =The Toxalbumin of Castor-Oil Seeds.=--In castor-oil seeds,
besides the well-known purgative oil, there exists an albuminous body
intensely poisonous, which has been carefully investigated by
Stillmark,[624] under the direction of Kobert.[625] Injected into the
circulation it is more poisonous than strychnine, prussic acid, or
arsenic; and since the pressed seeds are without taste or smell, this
poison has peculiar dangers of its own.
[624] H. Stillmark, _Dorp. Arb._, Bd. iii., 1889.
[625] Kobert’s _Lehrbuch_, 453-456.
It is essentially a blood poison, coagulating the blood.
The blood, if carefully freed from all fibrin, is yet again brought to
coagulation by a small amount of this body.
If castor-oil seeds are eaten, a portion of the poison is destroyed by
the digestive processes; a part is not thus destroyed, but is absorbed,
and produces in the blood-vessels its coagulating property. Where this
takes place, ulcers naturally form, because isolated small areas are
deprived of their blood supply. These areas thus becoming dead, may be
digested by the gastric or intestinal fluids, and thus, weeks after,
death may be produced. The symptoms noted are nausea, vomiting, colic,
diarrhœa, tenesmus, thirst, hot skin, frequent pulse, sweats, headache,
jaundice, and death in convulsions or from exhaustion. Animals may be
made immune by feeding them carefully with small doses, gradually
increased.
The _post-mortem_ appearances are ulceration in the stomach and
intestines. In animals the appearances of hæmorrhagic gastro-enteritis,
with diffuse nephritis, hæmorrhages in the mesentery and so forth have
been found.
§ 615. =Toxalbumin of Abrus.=--A toxalbumin is found in the _Abrus
precatorius_ (Jequirity) which causes quite similar effects and
symptoms. That it is not identical is proved by the fact that, though
animals may become immune by repeated doses of Jequirity against
“Abrin,” the similar substance from castor-oil seeds only confers
immunity against the toxalbumin of those seeds, and not against abrin;
and similarly abrin confers no immunity against the castor albumin.
Either of these substances applied to the conjunctiva produces
coagulation in the vessels and a secondary inflammation, to
which in the case of jequirity has been given the name of
“jequirity-ophthalmia.”[626]
[626] Heinr. Hellin, _Der giftige Eiweisskorper-Abrin u. seine Wirkung
auf das Blut. Inaug.-Diss._, Dorpat., 1891.
The general effect of these substances, and, above all, the curious fact
that a person may acquire by use a certain immunity from otherwise fatal
doses is so similar to poisonous products evolved in the system of
persons suffering from infectious fevers, that they have excited of late
years much interest, and a study of their methods of action will throw
light upon many diseased processes.
At present there are no chemical means of detecting the presence of the
toxalbumins mentioned. Should they be ever used for criminal purposes,
other evidence will have to be obtained.
XI.--Ictrogen.
§ 616. =Ictrogen.=--Various lupins, _e.g._, _Lupinus luteus_, _L.
angustifolius_, _L. thermis_, _L. linifolius_, _L. hirsutus_, contain a
substance of which nothing chemically is known, save that it may be
extracted by weakly alkaline water, and which has been named “ictrogen”;
this must not be confused with the alkaloid of lupins named “lupinine,”
a bitter tasting substance. In large doses a nerve poison. Ictrogen has
the unusual property of acting much like phosphorus. It causes yellow
atrophy of the liver, and produces the following symptoms:--Intense
jaundice; at first enlargement of the liver, afterwards contraction;
somnolence, fever, paralysis. The urine contains albumen and the
constituents of the bile. After death there is found to be
parenchymatous degeneration of the heart, kidneys, muscles, and liver.
If the animal has suffered for some time the liver may be cirrhotic.
Hitherto the cases of poisoning have been confined to animals. Many
thousands of sheep and a few horses and deer have, according to Kobert,
died in Germany from eating lupin seeds. Further information upon the
active principles of lupins may be obtained by referring to the
following treatises:--G. Schneidemuhl, _Die lupinen Krankheit der
Schafe_; _Vorträge f. Thierärzte_. Ser. 6, Heft. 4, Leipzig, 1883. C.
Arnold and G. Schneidemuhl, _Vierter Beitrag zur Klarstellung der
Ursache u. des Wesens der Lupinose_, Luneburg, 1883; Julius Löwenthal,
_Ueber die physiol. u. toxicol. Wirkungen der Lupinenalkaloide,
Inaug.-Diss._, Königsberg, 1888.
XII.--Cotton Seeds.
§ 617. Cotton seeds, used as an adulterant to linseed cake, &c., have
caused the death of sheep and calves. Cotton seeds contain a poison of
which nothing is chemically known, save that it is poisonous. It
produces anæmia and cachexia in animals when given in small repeated
doses.
After death the changes are, under these circumstances, confined to the
kidney; these organs showing all the signs of nephritis. If, however,
the animal has eaten a large quantity of cotton seeds, then there is
gastro-enteritis, as well as inflammation of the kidneys.
XIII.--Lathyrus Sativus.
§ 618. Various species of vetchlings, such as _L. sativus_, _L. cicera_,
_L. clymenum_, are poisonous, and have caused an epidemic malady in
parts of Spain, Africa, France, and Italy, among people who have eaten
the seeds. The symptoms are mainly referable to the nervous system,
causing a transverse myelitis and paraplegia. In this country it is
chiefly known as a poisonous food for horses; the last instance of
horse-poisoning by lathyrus was that of horses belonging to the Bristol
Tramways and Carriage Company.[627] The company bought some Indian peas;
these peas were found afterwards to consist mainly of the seeds of
_Lathyrus sativus_, for out of 335 peas no fewer than 325 were the seeds
of _Lathyrus_. The new peas were substituted for the beans the horses
had been having previously on the 2nd November, and the horses ate them
up to the 2nd December. Soon after the new food had been given, the
horses began to stumble and fall about, not only when at work, but also
in their stalls; to these symptoms succeeded a paralysis of the larynx;
this paralysis was in some cases accompanied by a curious weird
screaming, which once having been heard could never be forgotten; there
was also gasping for breath and symptoms of impending suffocation. A few
of the horses were saved by tracheotomy. Some died of suffocation; one
horse beat its brains out in its struggles for breath; 127 horses were
affected; 12 died.
[627] Bristol Tramways and Carriage Company _v._ Weston & Co., _Times_,
July 17, 1894.
The above train of symptoms has also been recorded in similar cases;
added to which paralysis of the lower extremities is frequent. After
death atrophy of the laryngeal muscles, wasting of the nervus recurrens,
and atrophy of the ganglion cells of the vagus nucleus as also of the
multipolar ganglion cells in the anterior horns of the spinal cord have
been found.
The active principle of the seeds has not been satisfactorily isolated.
The symptoms suggest the action of a toxalbumin. Teilleux found a resin
acid; Louis Astier a volatile alkaloid, and he explains the fact that
the seeds, after being heated, are no longer poisonous by the
dissipation of this alkaloid.
XIV.--Arum--Bryony--Locust Tree--Male Fern.
§ 619. =Arum maculatum=, the common cuckoo-pint, flowering in April and
May, and frequent in the hedges of this country, is extremely poisonous.
Bright red succulent attractive berries are seen on a single stalk, the
rest of the plant having rotted away, and these berries are frequently
gathered by children and eaten. The poison belongs to the class of acrid
irritants, but its real nature remains for investigation.
Some of the species of the same natural order growing in the tropics are
far more intensely poisonous.
§ 620. =The Black Bryony.=--_Tamus communis_, the black bryony, a common
plant by the wayside, flowering in May and June, possesses poisonous
berries, which have been known to produce death, with symptoms of
gastro-enteritis. In smaller doses the berries are stated to produce
paralysis of the lower extremities.[628]
[628] Contagne, _Lyon med._, xlvi., 1884, 239.
§ 621. =The Locust Tree.=--The _Robinia pseudo-acacia_, a papilionaceous
tree, contains a poison in the leaves and in the bark. R. Coltmann [629]
has recorded a case in China of a woman, twenty-four years of age, who,
at a time of famine, driven by hunger, ate the leaves of this tree. She
became ill within forty-eight hours, with high fever; the tongue swelled
and there was much erysipelatous-like infiltration of the tissues of the
mouth; later the whole body became swollen. There was constipation and
so much œdema of the eyelids that the eyeballs were no longer visible.
Recovery took place without special treatment. Power and Cambier[630]
have separated from the bark an albumose, which is intensely poisonous,
and is probably the cause of the symptoms detailed.
[629] _Medical and Surgical Reporter_, lxi., 1889.
[630] _Pharm. Journ._, 1890, 711.
§ 622. =Male Fern.=--An ethereal extract of _Aspidium Filix mas_ is used
as a remedy against tape worm.
Poullson[631] has collected up to the year 1891 sixteen cases of
poisoning by male fern; from which it would appear that 7 to 10 grms.
(103 to 154 grains) of the extract may be fatal to a child, and 45 grms.
(rather more than 1½ oz.) to an adult. The active principle seems to be
filicic acid and the ethereal oil. Filicic acid, under the influence of
saponifying agencies, breaks up into butyric acid and phloroglucin.
[631] _Arch. exp. P._, Bd. 29.
The symptoms produced are pain, heaviness of the limbs, faintness,
somnolence, dilatation of the pupil, albuminuria, convulsions, lock-jaw,
and collapse. In animals there have also been noticed salivation,
amaurosis, unsteady gait, dragging of the hind legs, dyspnœa, and
paralysis of the breathing centres. The _post-mortem_ appearances which
have been found are as follows:--Redness and swelling with hæmorrhagic
spots of the mucous membranes of the stomach and intestines; acute œdema
of the brain and spinal cord with petechia in the meninges; the kidneys
inflamed, the liver and spleen congested, and the lungs œdematous.
There is no characteristic reaction for male fern; the research most
likely to be successful is to attempt to separate from an ethereal
extract filicic acid, and to decompose it into butyric acid and
phloroglucin; the latter tinges red a pine splinter moistened with
hydrochloric acid.