Aconitinum

Volume I — Main text

Aconitintllll. — An alkaloid con tamed in A. napelliis, and also in all other species of Aconitum save the lycoctonum. The German and French preparations differ widely in strength, as seen in two of the cases of poisoning which follow ; the former is amorphous, the latter crystalline. What is commonly called "English Aconitine " i$ a secret preparation of Morson's and is believed to be made from the A. ferox. The alkaloid most abundant in this plant differs somewhat from ordinary aconitine in chemical composition, and has been called " pseudo-aconitine ;" and SchrofFs statement that the ferox causes much dyspnoea but no facial neuralgia is supported by the comparative results of the provings of Harley and Hottot respectively- The aconitine of Messrs. T, and H. Smith, of Edinburgh, seems identical with thatof Morson ; but the preparation of the British Pharmaco[>oeia is made from the A, napellus, and would represent that of the French and German observers,

1, Provings, — i. Dworzack, — Immediately after taking it, eructa* tions and rumbling In bowels ; head and face became suddenly warm ; warmth extended over rest of body, was most intense in region of stomach, and was accompanied by sweat. Then arose peculiar drawing, pressing sensation in cheeks, upper jaws, forehead, in short through whole tract of trigeminus^ increasing by degrees in intensity, alternating with actual pain, which, at first occasional and fugitive, finally became steady and severe. Pulse at beginning, coincioently with accession of warmth, was more frequent ; but soon after sank below regular standard, was small, weak, and at times dicrotic. Pupil showed at first an unusual mobility, was at one moment greater, at another smaller, but finally became so much dilated that only a small ring of iris could be seen. Fulness of head becomes more marked ; there sets In ringing in ears and feeling of pressure there, giddiness, and distraction. Flow of ideas is sluggish, long reflection impossible, and power of attention much impaired. After slightest mental exertion the head- and face-ache become very intense. There is a certain amount of relaxation in the limbs, and every muscular exertion— such, for instance, as going upstairs — is accompanied by unusual fatigue and prostration, and by increase of pain in head and face. Flow of urine very much increased.

As regards difference of symptoms according to different dosage, — eructations, rumbling in bowels, drawing stretching feeling in trigeminal tract, and primary rise and subsequent fall of pulse, were always present. A dose of 0^004 gramme was always followed by heat, tightness, and pain in head, lasting only a few hours ; while after O'oi gramme the symptoms recurred the day following trial on any attempt at mental or bodily activity. After 002 and 003 grammes, pulse sank to two thirds of normal! standard^ and remained thus low for more than 24 h,, and for same length of time continued also pain in face and head, feeling of fatigue, weakness of memory, &c. Not until second day after experiment, when these doses were given, did condition become normal. (Schroff, Prager Fierteljy ii.)

1. Heinrich. — 005 gramme. Taste disagreeable and disgustingly bitter \ m 10 m/burning sensation on tip of tongue and on lipsi pulse

at first accelerated, but afterwards became slower^ falUng In i| h. to 47 — 5^ ; whole body warm, perspiration set in, head dull and heavy, and therewith exhaustion and weakness ; crawling sensation in the face, and feeling as if epidermis were scaling off ; on skin appeared red spots as if from punctures i pupils dilated, pain in head and face, roaring in cars, weakness of muscles, and difficulty of respiration. Eructations and rumblings in bowels did not set in till 2 h. after dose had been taken. After supper burning sensation all over mucous membrane of mouth. The head- and face-ache lasted all the evening, as did also the debility ; sleep disturbed* Day after proving pain in head and face returned, together with forgetfulness and trembling of legs.

Even from smaller doses these symptoms were constant, — acceleration of pulse at first and retardation afterwards, burning on tongue, and pain in face and head (particularly In the course of the supra-orbitaJ nerve). A dose of 0*01 gramme was followed besides by inclination to cough, cough with easy expectoration, dryness in throat, eructation and exhaustion. {Ibid,)

3, HoTTOT. — Effects (of preparation known by his name) on self and two others,

a. When a, is applied to a sensitive part of skin, whether in solution in alcohol or as a pommade, it soon produces feeling of warmth, then of burning, accompanied with sharp pains and itchings ; later on^ one experiences weight and numbness in parts affected, they seem to be compressed by a heavy weight ; at other times skin seems as though heaved up and contracted by muscles beneath ; its colour is not modified ; there is anaesthesia. These symptoms last several hours, sometimes a whole day . they are never followed by general disturbances.

if. Almost immediately after taking 3 milligrammes internally one experiences all over buccal mucous membrane sensation of acridity and heat,, which travels rapidly to throat and later to stomach. This feeling soon becomes more and more acute; there is burning and numbness of lips, tongue and pharynx ; at same time occurs salivation, often very abundant. To these local effects general phenomena are soon superadded i one first experiences malaise, feebleness, weight about head ; then nausea, frequent yawning, oppression, and very pronounced muscular enfeeblcment. Pulse rises, but to a slight extent only. Skin is moist. One is sensible of creeping^ on various parts of the body, and more particularly on the face and extremities. After a variable space of time depression increases, there is headache, often darting pains in face, sometimes accompanied by vomiting. Muscular enfeeblcment greater, creeping? more palpable, especially during immobility j limbs are as though benumbed, face tense and swollen ; pulse falls, respiration is difficult, sensation of burning in throat becomes painful; profuse perspirations. Later on there is general prostration ; bruised feeling in limbs; difficulty in grasping objects; the least effort exhausts, one feels enervated; respiration is slow and deep, pulse markedly lowered. Mind remains cJear; rarely any tendency to sleep; pupil dilated, but far less energetically than by atropine ; dilatation develops slowly and mostly ceases under influence of brilliant light. These symptoms last from 10 to 16 h., little by little pulse rises, respiration becomes more

of tongue, gencril

9 JO. Burning of

9,15. Cre^-pin*^ m

free, strength nllic^;, suspended appetite revivor fn x word everrthing gets into good ouIlt again. The sympturas which pctsisc to the Jait arc acridity of throaty weight about head, and prostmiion,

f, ObiiTvathn. — 8.30 a.m. Six granules of a. of \ milligramme each; pulse 68- 8.40- Feeling of heat in stomach* 8.50, General malaise, yawnings, eructationSf turns of nau»ea, 9. Gfemt heat of I stomach; pubc 76; burning sensation at tip L debility, muscular cnfccblcmctit, turns of nausea. I lips, throaty and whole buccal mucous membrane. f face and fore-arms ; pulse 84, 9.30. Oppression, headac ' ^jcridity and burning of throat much more marked, *ah ^^Bcneraj depression, great muscular cnfecblement, sweats ; pulse W \ ^^urns of nausea, vomiting. 11. Creeplngs in face, which seems swollen r and tense, also in fore- arms and hands, which are benumbed and ' heavy; pulse 60. 12. Breathing irksome ; pain at temple and along course of supra-orbital nerve \ abundant perspirations \ |>wpil n« _ dilated ; burning sensation very painful in whole mouth and larynx ; lips benumbed \ abundant salivation, entire want of appetttc^ occasional^ nausea. l p.m. Same symptoms ; complete prostration of strengtii heavy gait, general enervation, slight tendency to sleep. 3 p.m. Headache with constriction at the temples, pupil dilated, respiration diflScuk ; pulse 52. 5 p.m. Same symptoms \ sensibility appears to diminish especially in hands and cheeks ; mind is clear, no drowsiness. 7 p.i The symptoms appear to amend, the head clears, the creeping^ dimini^l the depression is less \ pulse 60. 8 p.m. There is marked improv ment ; respiration easier, acridity, dryness and burning of the throat less pronounced ; there is, however, feebleness and general lassitude i pupil remains dilated ; pulse 68. 8,30. Easy sleep without agitation or dreams. The following day on waking there remain no traces of the effects of a.

One notes in this observation that the irritant action of the a«

I upon the mucous membranes of the mouth and pharynx made ii:u;lf

^|klt only-gradually. This is owing to the fact that the a., having been

conveyed directly into the stomach in the form of granules, could only

exert its irritant action mediately ; when, on the contrary, it is taken

in solution, and is consequently in direct contact with the mucous

membrane, its local effects make themselves felt almost instantly.

(UAcomtinettseseffetSy 1863.)

1. J. Harley. — Subject of following observations was m large btit lethargic man, aged 54, lamed by chronic sciatica. Pupils were a little unequal \ at a given light r. was |, 1. ^. Pulse was 66, regular^ of good volume and power; respirations 16 to 17.

In order to test the value of the following observations, I watched the effect of complete rest of mind and body on the respiration and pulse during 2^ h. as he sat still without once rising from his seat. After I J h. pulse was 61, of initial volume and power, respirations 16 j there was slight somnolency. After 2^ h. pulse was 58, not changed appreciably in volume and power, and respirations were 15; pupds were unchanged.

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tf. The Y^th of a grain of a.,* taken by mouth at intervals of 3 d., always caused slight tingling in mouth and face^ coming on within I h. and lasting for 2 or 3 h. On another occasion, after gr. YTT'i ^ ^^^^^ glowing feeling in addition was perceptible throughout body, and there was a little somnolency. On another occasion, gr* Y^ converted glowing feeling into a numbing glow — a comfort able feeling as if he were going oft* to sleep, and, if he did not move about, actual somnolency. These effects attained their maximum 2 h. after dose j he felt warmer while they continued, and there was at the time and afterwards some difficulty in voiding urine.

L Pulse being 66 and respirations 17, he took gr, y^, and did not rise from chair for 3 h. After 40 m, pulse 60, unchangedj respirations 17; somnolency coming on. After i| h,, pulse 58, unchanged; respirations 16; pupils unchanged. Had slept for 20 m. ; a generil glow pervaded body. After 3 h. pulse 56, unchanged, unaffected by deep inspirations ; respirations 16, regular. The glow and somnolency continued, and he had dozed several limes ; tongue and pupils unchanged, and he felt comfortable throughout.

€, On another occasion, after sitting still for ij h., at the end of which time pulse was 60, respirations 17 to 16, I gave him gr. j^y^. After li h. pulse 54, unchanged in volume and power; tongue and pupils unchanged. After 3 h, pulse 52, of initial volume and power i respirations 16, natural j pupils very slightly dilated (?). He felt warm and dozed much after the medicine.

</. He then took gr. -^ repeatedly, at intervals of 3 d.^ at 9 a.m. The effects were uniform. The medicine " upset him '' very much all d. ; he felt languid and sleepy ; could not hold his head up or keep his eyes open. He was giddy, and could not walk across room without help ; vision was hazy ; erect position induced nausea. He could not cat much on the medicine days on account of a difficulty of swallowing and a pain in back of neck and behind jaws in parotid region, so that in eating he had to press back of neck with hand. A glowing, tingling feeling pervaded the body, and there was a burning feeling in the gullet, as if a hot coal were there. The tingling in mouth and face came on within ^ h., the somnolency after i J or 2 h. At first he slept for I h,, but afterwards sleep was dreamy and broken* Giddiness, dimness of vision and muscular weakness were most marked within 6th and joth h. There was always some dysuria, and occasionally retention with hypogastric pain. Nausea was generally a prominent symptom, and pain in neck often remained until next d.

I kept him under observation for 3 h. after one dose, but could detect no appreciable effect on either pulse, pupils, or breathing. At the end of this time pulse was 60, of good volume and power, a trifle more compressible perhaps than before the dose j but this will always be found the case after a long rest of mind and body, and with a tendency to sleep. The respirations 1 7, regular and easy ; tongue and pupils unchanged.

e. These observations were repeated on two other adult males with

• The pure crystallised aconitia of Mr. Morson, or of Messrs. T. and H. Smithy of Edinburgh, was employed in every case.

uniform results* Doses ranging from gr. ^ to gr. |^ alwap produce decided aconitism, general numbness and tingling^ but most marked in face and throat ; nausea, giddiness, somnolency, and muscular weakness* This latter is always a prominent effect, an4 strongly re^moles ihe condition induced by hemlock*

f. F* G — , aged 12, a well-dcvcloped boy, afflicted with cpilepsr. T1)e j^th of a grain given repeatedly at intervals uf 3 d. produced following effects :

After I h. tingling pricking sensation running up legs to spine and head, and tingling of fingers ; much giddiness and somnolency, but sleep disturbed by frequent awakings. After 2 h. unable to walk or even stand without great exertion, and on rising from recumbent posture was unable to sec for a m,, and there was nausea. The effects lasted for 7 or 8 h., after which he slept quite comfortably, and felt quite well the next d. I was unable to discover any influence on the breathing, pulse, pupils| or tongue, nor was there any diminution of temperature.

This observation was repeated with uniform results on another boy, aged 9, [St. Thomas's H&sp, Reports^ v, 146,)

1. Reil dissolved gr. i^ In 200 drops of alcohol, and took from 5 to ^o drops (gr. ^ to -J^), diluted with water, in gradually increasing doses* He experienced feeling of fulness in cheeks and temples, which by degrees was exchanged for a painful sense of tension, fortnication, and prickling ; the temples throbbed, the head ached, the eyes felt strained, the pupils were dilated, the sight was obscure, there wm$ oppressed and sighing breathing, ringing in the ears, and increased urination. There was also a sense of heat in the stomach, with eruc* tacion, and, for 3 d. following, nocturnal pollutions to which the experimenter was not accustomed. (Still^, Mat. Med,^ ii, 31 1 .♦)

2. Poisonings. — t. A gentleman took gr 24. He must have fallen almost immediately, and struck his head against the furniture ; either the poison or the blow must have caused violent vomiting, as the floor of his room was found Hooded with vomited matter ; in 8 h. patient was fearfully collapsed, skin cold, sweating, and quite pale heart's action almost imperceptible ; pupils acted \ no paralysis i intellect unimpaired ; he suffered from severe vomiting, which recurred every % or 3 m., and was performed by a sudden jerking action of abdominal muscles, accompanied by a loud shout, probably dependent upon a sudden contraction of the diaphragm. Every attempt to swallow was followed by the spasmodic contractions so characteristic of hydrophobia, but they were not renewed by the sight of water. All these convulsive movements, however, were easily excited by simply touching him« Stimulants with opium were administered. He passed the night in spasms and exhaustion, but his intellect was perfect, even vivid \ after a hard struggle seemed out of danger next d, (Golding fiiRo, Lancet^ January 1st, 1848.)

3. H. L—- , labourer, was given, for a periodical hemicranta (he

^ Referred to * Mat, Med. d« rein, cbem. Pflanzen&toffe/ p. 16, but tlui work sot nccesaibk.^ — Eds,

nj

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being otherwise well), a solution of nitrate of a. in tincture of cheno* podium, which he was to take in increasing doses.

a, March Hth^ at 7 p.m., took 5 drops (= 0-0004). Complained immediately of constricting and burning sensation extending from mouth to stomach. Feeling chilly, went to bed. At 9 p.m. look 20 drops, and experienced same sensation more severely. 15 m. later felt very sick and complained of fear that he would die; ice-cold sensation creeps up from his feet j in praecordial region an oppressive anguish, and excessive bitter and burning anguish in throat. His whole body is bedewed with a cold, clammy sweat j he cannot see any more; is dizzy and deaf. 15 m. later he vomited copiously, with gradual decrease of all the symptoms, and sleep followed. During whole time felt fearfully exhausted as if paralysed, with great difficulty of breathing. His wife says that his breathing was audibly rattling, but that consciousness was undisturbed. No urination during night nor any inclination thereto. Next m. felt tolerably well, and took a cup of cofFee and an egg without any inclination to vomit. At 8 a.m. took 20 drops, and shortly afterwards the same symptoms reappeared. He grew cold, had sensation of anguish in pr;ecordial and gastric region, breathing oppressed, was deaf and blind, and felt great malaise. His wife says that twitchings and spasms over whole body set in, especially in face. 20 m. after taking dose spontaneous vomiting occurred, with relief of all the symptoms.

h. At 1 1 a.m. ao drops ; same symptoms. With every dose state during intervals became worse. He felt continually weaker and more exhausted, with all energy lost, and sense as if paralysed. In the afternoon again 20 drops, with same result. Increasing constriction of mouth and fauces after doses. At 9.30 p.m. again 20 drops. Though medicine was always diluted with water, he drank now an extra quantity of cold water to prevent vomiting, and did not throw up dose. He went to bed, and soon fell asleep. Sleep restless, rather a slumber only. Between 11 and 12 he felt very sick, and called out, full of anguish: **So chilly, my chest, my chest, I feel awfully chilly, what shall I do ? I am poisoned.*' Now genuine convulsions in hands, and face set in. He was totally blind and deaf. His eyes closed, his lips dry and fissured, his tongue stift", he could not his mouth, he felt chilly and as if dying ; breathing became rattling and moaning, quick. More severe convulsions alternated with quieter intervals. Draughts of strong hot tea were given half-hourly. His taste was entirely gone, so that he did not know whether the tea was hot or cold. 5 m. after drinking vomited copiously, with great rattling in chest. All this time he remained perfectly conscious. About 15 m. after having vomited felt some relief. With every subsequent vomiting, aided by copious draughts of hot tea, amelioration increased and chest felt more free. The symptoms gradually abated, and for an hour he enjoyed a quiet sleep with easy respiration. On waking he complained only of weakness. He passed no urine during the o., though he tried to do so towards m.

r. During 1 6th felt moderately well, but for pressure on chest, and sense of fatigue. At 6 p.m. 10 drops only. Immediately lost all

arms were

open

IH

taste , burning in mouth and stomach returned ; felt chilly — In 9hoft« all the symptoms returned, only in a more moderate degree, till vomiling 15 — 20 m. afterwards again brought relief. No more medtctne

d, L — further affirms that he felt during the Intoxication a heaviness as of lead all over the body, always relieved by vomiting. During entire poisoning his colour was cadaverous. On t7lh still complained of burning constricting sensation in mouth and fauces, his taste altered^ band his vision unusual. A few days later complained of unwonted f difficulty of breathing ; his taste is not as good as usual, and the teeth arc more sensitive when biting. The urine also passes only in drops^ and less easily. No more nemicrania. (BuscHER^ in Bert, klin, Wochenschri/t^ 1880.)

1. Dr. Meyer, the physician who prescribed for the foregoing^ drank 50 or 60 drops of the mixture in the wife^s presence to assure her of its harmlessness. It seems that the alkaloid used was Petit's, which is 170 times stronger than Fricdlander^s^ the latter being intended by the prescriber. Hence his patient's peril and his own death. He was found dead 5 h. after taking dose. At the autopsy 43 h. later, the body was strikingly pale and the jaws firmly closed.

Internal Examination. — Diaphragm on both sides reaches fifth rib ; muscles of bright red colour ; omentum pale and anaemic ; caecum partly filled with gas, partly with solid and fluid contents, its colour pale, no injected vessels visible. Duodenum from below upwards more injected, of darker colour as it approaches stomach, but mucous membrane intact. Interior of stomach strongly hyper^mic and brightened from intense vascular injection. Spleen of twice its size^ of dark, nearly black-red colour : incised it ts full of blood, soft and friable. Liver enlarged, exterior smooth, dark, posterior part nearly black : incised seen to be full of blood, but otherwise normal. Kidneys equally hyper^mtc. The fluid contents of the abdominal cavity thin fluid and of bright cherry red colour. Right ventricle holds much bright red thin fluid blood ; coronary arteries full of blood ; in pericardium much bloody serous fluid. The very voluminous brain, even in Its membranes, ^ry hyper^mic : sinuses full of thin bright red blood. In hemispheres sub-arachnoid extravasations here and there. The grey substance of brain shows on surface of section small red blood points, the whole very hypcraemic, less so in the medullary substance.^ [jbid.)

1. a. N — , aged 62, of good constitution ; never sick save some slight colds. After having felt well the day previous, went to bed March 20th, 1880, feeling unusually cold, and later felt an anxious pressure on the chest. An hour later, his wife heard him moaning, and found him in spasms, though fully conscious. As his state grew worse, Dr. Buscher was called at 3 a.m. He found the patient in bed, very restless but cjuite conscious. Skin very pale and cold, especially in extremities, which are bedewed with cold clammy sweat ; radial pulse very small, irregular, dicrotous, sometimes it can scarcely be fislt. Sounds of heart

• The post-mortem exaTnt nation of the lad Malcolm John, poi^ncd with a. by Lamson in 1881^ disrrlosed a precisely suuilar stale of stomachy duodenum, liver, iplftcn aod kidncyji.— Eds.

■

only heard at apex, and scarcely distinguishable ; heart's action very wealc, irregular and quiclc. Breathing very laborious, short, very irregular, superficial, sometimes 40 per m., a few m. later much slower. Pupils contracted, with sluggish reaction; features spasmodically distorted, especially about mouth (facics hippocraticj) ; swallows without lifficultyi patient complains of terrible praecordial anguish ; throws Pliimself continually around in bed; conscious; very irritable and quick in his rephes,

L During my observation of patient (Dr» B. writes) a sudden change took place. The extremities turned colder ; heartsounds and pulse disappeared. His skin turned of a marble colour, face somewhat turgescent, pupils dilated, conjunctiva became injected, whole body bathed in cold, clammy sweat; breathing more laborious and super iicial; tracheal rattling sets in; a peculiar, clear, short moaning is heard* Beginning in fingers, then in face, tonic spasms, trismus ; after a while, clonic convulsions over whole body. Consciousness is lost* This convulsive paroxysm lasted about 5 or 6 m., durmg which we expected his death every second. It then abated ; skin took on a better colour; a warmer sweat occurred; pulse could again be felt; sounds of heart became more clear, and its action, though irregular, at some moments was full and strong, Consciousness returned ; opened eyes, and said, '^ I must have slept and had bad dreams." He tried to remove a mildly burning night lamp, as the light felt disagreeable. This amelioration lasted 15 m. (though the prsecordial anguish and chilliness continued), and then the convulsions returned in same manner as before, followed by relaxation with same phenomena. During this attack respiration nearly stopped, and the pupils were found insensible to light.

Cn Fully conscious again, he replied to question how he felt : "Pretty fair, only I feel a terrible anguish in the gastric and cardiac region, and it is dreadfully cold.*' The anguish he believed to be diaphragmatic. No other pain ; of his whole body he feels only these regions and his head, all other parts seem as if filled with lead ; no headache or vertigo, only some deafness.

d. Immediately after taking a large cup of strong coffee, copious lyomiting* A second cup, shortly after taken, remains, as also ether ^ven in full doses and strong Spanish wine* Vesicants aJid sinapisms Jong medulla and on the extremities. Another exactly similar conirulsive attack occurred, but lighter and shorter than before. With returning consciousness he complains now of deathly lassitude. Requested to state his sensations before the convulsions set tn, he replies ; ** I get colder and colder, become blind and deaf; I feel as one sleeping and dreaming," Now continuous severe vomiting occurs, during which convulsions decrease in duration and strength, and intervals of relaxation lengthen. At 5 a.m. danger seemed to have passed, and at 7 nothing remained but some praecordial anguish and sensation of coldness, with slight spasms. At 10, after a refreshing sleep, he awoke welL He did not urinate till noon, when 200 grammes, of dark colour, were passed.* {Ibid.)

• It b merely »aid| with reference to this case, that the ijuantity of tbc drug ukco

in. Expertmenfs on Ammali, — i, VoK Praeg* The foUowiog trt hjft c«)llclu« siom from variouii cxpcrimentf ;

Respiration was more or lets retarded In the mammifcrse ; bcatingi of heart become irregular; mu&cles arc relaxed; there is exces^kivc fceblencts and inrrtiaif horror of au movement (so to speak) in the most acute cac« paralysis of all the muscles is the most frequent symptom. The action of a. h tbu to depress the muscular system without previous excitation. The brain wis evidently attacked, in three ca&cs loss of consciousness, and in all a certain apathy was pnrseot^ in one case complete anaesthesia ; eves become very sensitive, pupils dilated. Stomacti presents symptoms common to all poisonings, retching, vomiting, &c. Urinary ^stem was affected (ischuria) in one out of i } experiments t estivations. With dogs, mean length of intoxication was 5 h. 10 m, : greatest length, a8 h. 40 m, ; least, 1 1 m* Largest dose was 1 grs. : i4 grs. injected into jugular occasioned death in 11 m. With birds, general depression of muscular system; dilated pupil was only seen in one case, salivation in one case. With frogs« very speedy adynamia bOon followed by paralysisi loss of reflex irritability, and complete ansesthesia ; hind paws, front paws, hnally muscles of head^ were successively paralysed ; in one ca^e, respi* ration was suddenly suspended, in another it was, on the contrary, stimulated ; heart preserved its reflex irritability just as long as in cases where the heart is simply cut out* With fi^h, same symptoms on part of muscle*, dyspnoea and diminution of respiratory movements*. Post-mortem examination showed membranes of brain very much congested, as well as brain itself, jugulars distended with blood. The blood varied, in some cases viscid and uncoagulated, in others there were firm Hbrinous dots as after natural death. (/'irM^c'/ Archi*Vt vii, 43S.)

a. Harley made 9 experiments with hypodermic injections of alkaloid in borates, dogs and cats. His results (which he considers to present '* the most perfect uniformity ") he sums up thus :

a, Aconitia affects a portion of the cnmio-spinal axis tn the same maimer that strychnia affects the whole.

b. The focus of the action is the medulla about the roots of the pneumogastric hypoglossal, and spinal accessory nerves. Thence its influence radiates along the cranio.spinal axis with rapidly-diminishing intensity, as far forwards as the centres of the third nerve, and as far downwards as the origin of the phrenic. The centres about the focus of action are more or less in a state of constant excitation, while those towards the limits are sometimes in a slate of depression and sometimes in one of excitation ; thus, for example, during a spasm the pupils may be completely contracted, but in the intervals^ and always after moderate doses, they may be slightly dilated. And so also with the di:iphragm ; it is enfeebled by small doses^ and it alternately affected by spasm and exhaustion after large ones. Occasionally, however, and during the more violent suffocative spasms, the muscles of the whole of the anterior part of the body, including the anterior extremities, are involved in the attack,

f. Beyond the limiti above indicated it exercises a depressing influence on the cranio-spinal axis, almost amounting to paralysis.

d. The action of the alkaloid on the sensory function appears to be co-extensive and co-equal with that on the motor function the area for intense action having the name limits, beyond which the anarsthesiant action rapidly diminishes in intensity. Thus, while the head and neck are deprived of sensation, the rest of the surface is only partially affected, and the sensibility of the further parts of the body only slightly or not at all disordered. {Op. ciL)

3, Dyce Ducicworth. Experiments on cats and rabbits, with preparations of Mor&on and Smtcb. Given internally it occasions in the firtt instance a scnsabon of intense tingling in tongue and fauces, and almost immediately there supervenes an extremely abundant secretion of saliva^ the involuntary flow of this liquid seeming to prove that at the same time the influence of the will upon the act of deglutition i$ almoiit entirely effaced ; the re^-piratory functions are troubled in their turn, respiration becomes laborious and spasmodic, and is accompanied by cries more or lest.

was unknown. No statement is made as to any being taken at all ; but it ts put forward with the other as a case of poisoning with aconitine, and its s^mj toms are such as would be thus caused, — Eds,

rigorous according to the dose employed. One then observes vomitings, wTirrh may referred to a disturbance in the functions of the vagu*^, because in iht ejcaminaiiun poisoned animals one finds no lesion of the stomach. Later stiil, sensation is ntirciy suspended ; the animal, as if mad, tosses itself about wildly, makes vain ^attempts to walkf takes proiligious leaps, and then falls on its side in a state of prostration^ interrupted from time to time by convulsions; lastly, as ulterior phcno^ rDena^ one observes the relaxation and growing embarrassment of the respiration, and, finally, a general and complete paralysis and death. Pupils in dnt phases of poisoning are more or less contracted they dilate^ on the contrary, extremely a or 3 ro. before ath, and remain in this condition at the moment when animal expires; after death bey arc sometimes dilated, while at others one observes m one or in both of them the alternatives of dilatation and contraction, and these variations sometimes do not cease till 12 h. after death. When, instead of giving a* internally, Fleming injected a solution of it into the veins, the dilatation of the pupil supervened almost immeliately without being preceded by a contraction, which seems to be due to the fact "hat the poison acts then with a greater rapidity. The contraction again is very transient^ and is rapidly succeeded by dilatation, when a. h given internally in ^sufficient quantity to kill rapidly. (Brit. Med. Jaurn,^ 18^1, i, iH*)

4, Mackenzie. Conclusions from numerous experiments:

a. Aconite and aconitia act primarily on the respiration, by thdr infiuence on the respiratory centre and peripheral sensory branches of the vagus.

b. They have no direct action on the heart, and only affect this viscus secondarily, through the medium of the lungs.

c. Their action on the nervous system consist! in firstly irritating, and secondly

Earalysing the peripheral sensory nerves and post, roots of the spinal nerves. They ave no direct action on the brain or the vaso-motor nerves. They increase the irriiability of the peripheral motor nerves and of the motor columns of the cord,

d* They do not induce muscular paralysis, but, on the contrary^ increase the irritability of voluntary muscle,

t. They induce convulsions, mainly through their augmenting the irritability of ^ibe anterior columns of the cord, the motor nerves, and the muscles, f^ They firstly increase and wcondly diminish temperature. g. Death ensues from asphyxia and respiratory collapse. (Proftilioner^ xx, xxli,)

5, tf. Aconitinc is a narcotico- acrid poison whose irritating properties manifest themselves especially in the mucous membranes,

h, Aconitine acts on the nervous centres, and successively on the medulla, the d^ and the brain.

r. The symptoms apoear Jo the following order i abolition of respiration, of general sensibility, of reflex sensibility, of voluntary motion.

d. Aconitine disturbs the functions of the heart by acting on the cardiac sub^ fftance itself,.

r. The effects of the poison on the peripheric nerves succeed to those it exerts on ^thc central organs.

/I The excitability of the nervous filaments, motor or sensory, disappears from their terminal extremities sooner than from their trunks* (Liegeois et HoTTOT, y&um. de Phymhsii^ iv, 5x0. i86i.) ^

6, tf. As mechanical arrest of the circulation destroys sensation before voluntary motion, and as aconitia is a powerful heart poison, it occurred to us that perhaps it

'might paralyse by arresting the heart. Our experiments, however, disprove this surmise^, for general and complete paraly^^is ensues far quicker after aconitia poisoning than after mechanical arrest of the circulation.

b. Since, after complete paralysis, the motor nerves still readily conduct impresiions and the muscles contract upon galvanic stimulation, it is evident that the paralysis depends on the influence of the aconitia on the central nervous system.

r. Later, the poison abolishes the excitability of the motor nerves and the muscles, and also of the sensory ner*cs j and this effect, we have shown, is not due to its paralysing action on the heart. It must therefore act directly on the tissues.

d. Docs aconitia affect all the tissues in an equal degree, or has it an especial action on certain tissues ? It it manifests the same affinity for all tissues, then iheir functional afEnity should cease in the order of their activity, and the phenomena

should be of the same kind and occur in the same gradation a.^ after simple arrest of the circulation by extirpation of the heart. This, however, does not happen ; for, after arre<>t of the circulation, we find that sensation continues as long, or almost as long, as voluntary power ; but after poisoning by aconitia sensation is speedily aboli^hcd. Thuh, in our experiments, sensation was destroyed, on an average, in 4 m., while voluntary power continued 20 m. We must conclude, therefore, that aconitia has an especial action on some part of the sensory apparatus.

e. Does it act on the afferent nerves, on the sensory tract of the cord, or on theaensory perceptive centre of the brain ? According to Liegeois and Hottot it firtt paralyses the centre and then the nerves. While we think their experiments are open to objection, we think probably their conclusion that aconitia abolishes sensation by its influence on the brain is correct ; and we shall also show that the early loss ok reflex action is likewise due to its effect on the brain, for in brainless frogs it abolishes reflex sensation much more slowly.

f. We must conclude, we think, that probably aconitia has a special action on the sensory perceptive centre. A^ain, we must admit that it has an especial action upon the heart. Hence, whilst it is a poison to all tissues it is especially poisonous to some. (Ringer and Murkell, Journal qf Physiology, i, 232.)

1. a. BoEHM injected minimal doses (5 — 20 mgr.) of aconitinummuriaticum into the lymphatics of the thigh of frogs, and observed after a few m. on the exposed heart that the contractions became irregular. These irregularities appeared first in the auricles. After a while the disorder increased to cardiac spasms. The heart, full to overflowing in all its parts, made peculiar vermiform peristaltic motions, and with such celerity that it was impossible to follow its course. These spasms set in in irregular paroxysms, interrupted at first by longer, after a while by shorter perioda, during whicli the hearths beat was more or less regular and rhythmical ; still it could be observed that the activity of the ventricles was much inferior to that of the auricles, the latter giving 3 to 6 times as many beats as the ventricles. After these alternations of spasm and rh)thmical contractions had lasted more or less time^ according to size of dose, the picture gradually changed. The heart began to stand still relaxed in half diastole for an increasingly longer time after 6 or 8 regular beats. These pauses in the beginning lasted only 10 to 1 5 seconds ; but when mechanical and other irritations were avoided their duration gradually became longer, and the interrening beats of the heart became always weaker and more superficial ; still, if verylarve doses were not given, it was always some time before the action of the heart entirely ceased. Even after several h. he observed from time to time weak contractions in the auricles, when the action of the ventricles had already perfectly ceased. In the last stage of their activity the ventricles show only quite superficial movements^ The heart gives the impresMon that its muscles haa lost their ability to obey the regular rhythmical irritation or impulse to motion. After 5 to 7 h. the last vestige ofmotion had ceased.

b. Experiments with fractions of a milligramme constantly showed a mo-e or lesa considerable acceleration of the beat of the heart (10 to 30 in m.). In some cases the acceleration diminished and the heart recovered itself fully, but it mostly formed the first stage of a series of manifestations, gradually more and more approximating tfie

f)icture of poisoning with larger doses, as already shown. After the acceleration had asted about 10 m. with perfect regularity of the hearths motion the already describe4 spasms set in, but far more decided and outspoken than with larger doses. Auricles and ventricles equally take part in these spasms, which always set in suddenly and without preceding irregularities in the beat of the heart. The chief event in the rhythmic beat of the heart, the alternation of systole and diastole at regular intervals, has ceased, and it is nearly impossible to describe the ensuing phenomena. The muscle labours in vain to expel its contents — it throws them, as it were, from one corner of the heart to another — and thus a systole, limited to small spaces, rolls in vermicular motion over the whole heart. A stage of exhaustion follows this second stage of spasm gradually, but in longer time, passing over into a cessation of the heart-heats.

f. ** We must also " (writes Boehm) " examine in what relation this poison stands to the vag^is and the inhibitory centre. Our experiments were made m the usual way, by dividing the exposed nerve, testing its excitability, and then poisoning the animal. The excitation after the poisoning produces yet for some time an

trident retardation, but not a cessation of the hearths raotion, and finally all the influence of the vagus on the number of the heart's beats cca5e5. If we irritate mechanically or by electricity the heart which has ceased to beat under the action of aconitinc, we usually set no eflVct by applying the irritation at the apex of the ventricles, whereas an irritation at the auricles frequently produces rhythmical contractions of auricles and ventricles,

d, *' Poisoning by aconitine may therefore be divided In its action on the heart into three stages— i, a stage of acceleration ot the beats of the heart ; 1, a stage of spasms of the heart \ 3, a stage of cessation of movement in the heart.

I #. ** We did not know till now any poison which produced with certainty a direct

' acceleration of the beat of the heart m frog*. Atropine, from which we might expect such an effect a f^rtori^ and which really shows it in mammalia in a high degree, leaves the number of heart's beats unaltered in the frog. It seems, therefore, that the diminution of resistance solely, the so called paralysis of inhibitory centra, J» not by itself able to increase the number of the pulsations. It rather seems that in the frog it still needs a direct irritation of the excito^motor centres to clfect nn acceleration ; and this is probably what caused the acccicration in the fir«t stage ot aconitine poisoning,

/. ** Experiments prove, furthermore, that aconitine gradually diminishes down to zero the excitability of the inhibitory nervous !>ystem, This diminution may contribute to the occurrence of the acceleration in the first f-tagc, but is, I beiievc, of more importance to the second stage, i.e. the occurrence of the spasmodic peristaltic c^ardiac movements. The cause of the rhythm of the heart's movements is now generally supposed to stand in forces which arise in the so-called inhibitory centres, and a* it were oppose themselves, as though they were obstacles to be overcome, to the motorial impulses which arc continually proceeding from the automatic motor centres* In order to overpower them, the latter must acquire a certain potential energy, which, when the obstacles are overcome, passes over into vital tbrce. After each movement some time passes till the necessary sum of potential energy is again accumulated, and thus arise the regular pauses between the beats of the heart and the rhythm. The number of beats, therefore, in a given time depends on the amount ot the elastic resistance forming in the inhibitory centra, and on the power and quantity of motor impulses developing in the automatic centra. This rhythm ceases in the cardiac spasms of aconitine. The motor impulses fiiil to be garnered up to a certain degree, and they are not restrained by a sufficiently strong resisting power, but let loose these irregular movements. Even a very strong irritation of the exci to- motor centres would not suffice to produce these spasms, because, according to the above theory, the resistance emanating from the inhibitory centres must cause a cessation oi the motion after each overpowering of it. The irritation of the excito-motor centres is necessary for the rapid succession of motor impulses, but a paralysis of the inhibitory organs is necessary for the »spasms ; and this we witness perfectly in this stage of the action of aconitine,

g. *^li may be asked, why then does not such a state produce tetanus of the heart, as all conditions for it are present f But there is an important obstacle to a lasting tetanic systole in this case. The excitation of the motor centres, which, as we arc as yet bound to believe, lie scattered in various parts of the heart, must take

i place with a certain simultaneousness in order to produce a regvdar cardiac contraction. Aconitine abolishes such regularity, for we see in the spasms caused by it the different parts of the heart contracting one after another without regular succes^tion or co-ordmation. Thus the heart never contracts In toto, the blood is pushed from the most contracted part» to those less so, producing here and there a transient systole.

/r. *' We wish to draw attention to a remarkable consonance between the action of higher degrees of heat and that of aconitine. Cyon tbund that the heart, when exposed to gradually higher and higher temperatures, is retarded at first in its pulsations, and then accelerated. After reaching their acme, the beats become irregular, and symptoms set in similar to aconitine spasms, and finally the heart stands still in diastole. When Cyon, before the warming process, paralysed by curare the ends 01 the vagus, the primary retardation failed to appear, acceleration immediately set in,

i followed by spasms and cessation. The action ot higher temperatures on the heart, preceded by poisoning with curare, exactly corresponds with the symptoms o£

a$ ati irritation of the excUoinkibitoiy ocrvotu sj

, SDft

pMOomg hy acofiidiie ; mod we mu&t consider both motor heart centres combtiied with a paralym of the oC tome^ IS yet tmJcjiowi^ rtgubiting mechiinisin.

f. ** The cdBtioD of motioii of the heart tn diastole m the third stage of poisoiilug bf aconitiiic i» clearly a cessation from weariness^ The heart shows all the characters of an organ serci -paralysed and weaned out by excess of activity and irritation which may still by strong stimuli be spurred to transient activity, but which left to itself, gradually entirely loses its vital qualities*

y. « We consider alM> of importance the change which the strip<fd musoilar ■ubftance, apart from the nerve-centres situated on it, undergoes under the action ot the poison. This presumption is confirmed by the ^tctthat the auricles, which haire, as is well known, no striped muscles, cannot be brought fully to a cessation by aconitine ; they still beat, though weakly, for hours after the death of the remainder of the heart. As aconitine shows a very severe action on all other striped muscles, we must suppose a complication of two actions on the hearty and it is probable that ^ we have fo consider the fatter action as the most important cause of the cessation of motion in the ventricles by aconitine. That the impulses for rhythmical motion ^ emanating from the motor centra have not ceased, and consequently that their cessation cannot be the cause of the cessation of movement in the ventricles, is proved by the continuance of rhythmical motion in the auricles, which, if our explanation of the action of aconitine be correct, are not accessible to the action of this poison on the striped muscular substance.' (Boehm, Other Herxgi/U.)

Volume I — Appendix

AconitinuiD. — To introductory statement add — [Experiments recently made by Bohm •^how that the ** pseudaconitini" from A. ferox, is when applied locally of considerable anaesthetic power, dimini'*hing capacity of recognising differences of temperature and separation of points of contact, Slc Brit. Journ, oj Horn., xli, 185,]

Volume IV — Appendix

ACONITINUM.

(See vol. i, p. 118.)

The cases of poisonine, Nos. 2 to 4, taken from the Berlin klin. ff^tchtnschrifi., are referred by that journal to a Dutch periodical, the Ntierl. Ttjdschrifi voor Gtnteskunde^ 1880, No. 16. To this we have not been able to get access. In the Bull, de la Soc. de Thérapeutique for 1883, however (p. 3), Dr. Dujardin>Beaumetz mentions the cases, and gives an account of Dr. Meyer's symptoms during life, which the German version omits. They were as follows : —

The toxic effects began to show themselves in | h. After 4 h. Dr. Tresling found him pale ; pulse small and irregular, but not accelerated ; skin cold ; pupils contracted. There was sense of burning in mouth, and of constriction from throat to abdomen ; patient complained of precordial anxiety, and of heaviness and weakness of limbs, especially legs. Pupils suddenly dilated, and vision was lost, but it returned as they became once more contracted. Vomiting was excited, but there soon came on acute congestion of head, and therewith convulsions and stertorous breathing. M — then complained of deafness, and of humming now in one, and now in other, ear. After a subcutaneous injection of ether, pupils dilated again, and vision was lost ; then vomitings recurred, and prolonged and violent convulsions. A second injection was made, but patient could not be restored to consciousness \ pupils did not react to light ; respiration became slow and laboured, and spite of electricity more and more difficult ; heart grew feebler, and in 5 h. after taking poison M — was dead. P.M. showed great pallor of skin and muscles, while internal organs were strongly congested, save colon, rectum, and bladder, which were anaemic. Heart was in diastole. At certain spots in arachnoid exudation was found, and there was bloody serum in ventricles, and a sanguineous exudation on the choroid plexus.

• Dr. Althaus describes a skin eruption, beginning like herpes but then assuming the appearance of pemphigus, spreading all over face and body, with aphthx in mouth and fauces, and hzmorrhage from bowels, as resulting from the drug. He does not say how it was given, or m what disease. {Lemctty 1877, i, 94.)

A renewed comparison of our presentation of the cases with tha in the fVochtnschriJi makes the following corrections desirable : P. 124, 1. 21. After "colour " supply " when cut," and for " csecur read " colon."

„ 1. 25. For " brightened " read «* bright red." P. 1 25, 1. 14. For « clear" read « shrill."

„ I. 31. For " it is •• read *' am."