Physostigma Venenosum

[CALABAE BEAN". NATURAL ORDER, LEGUMINOS^.]

The calabar bean, also called ordeal-bean, is found in western Africa. It is a large, climbing perennial, "with a woody stem of two inches diameter, and sometimes fifty feet in length. Its large leaves are pinnately trifoliate, with ovate acuminate leaflets. Its papitionaceous flowers are in pendulous racemes, the stock of which is covered with tuber-like knots.

Each flower is about an inch in length, and of a pale-pink or purplish color, beautifully veined. The legume, when full grown, is about seven inches in length, elliptico-oblong, with a short, curved point, stipitate, dehiscent, and containing two or three seeds. The seeds, which are oblong and

VOL. II. — 38.

G10 PHYSOSTIGMA VElsENOSUM.

somewhat reniform, are from one to one inch and three-eights in length, by about three-quarters of an inch in breadth, their convex edge marked by a long, sulcate hilum, extending as a deep furrow from one extremity of the seed to beyond the other. The exterior of the seed is somewhat rough, with a dull polish. Its color is a deep chocolate-brown, somewhat lighter on the raised edges of the furrow. The seeds weigh, on an average, sixty-seven grains."

It is called ordeal-bean because the natives administer it to per- sons suspected of crime. We are told that, in a public trial, the accused is compelled to eat up a few beans in their natural state, while others are being pounded to pulp, well mixed with water and then given him by the mouth and in form of an enema. If the poison is rejected by the mouth' and bowels, the accused criminal is cleared ; fatal consequences are absolute proof of guilt.

Pereira gives the following summing-up of the physiological effects of the drug: "1. The calabar bean, when acting as a poison, may produce death, either by paralysis of respiration — asphyxia — or by diminishing the frequency of the heart's action, and then finally stopping its contractions — syncope. 2. The paraly- sis resulting, seems to be due to an action upon the spinal cord as a reflex centre. 3. Its cardiac effect is most probably due, not to an increase of the inhibitory power of the vagus, but by paralyzing the exciting ganglia of the heart. 4.

Physostigma, however, after a time paralyzes the motor or afferent spinal nerves, its action com- mencing in the peripheric extremities, like conium and curare. 5. The effects on the smaller blood vessels are : first, contraction, and afterward, dilatation. Large doses at once arrest cardiac move- ment; smaller doses makes them grow feeble less quickly. 6. The pupil is found alternately to dilate and contract ; at the moment of death it is contracted, but immediately afterward it is dilated.

Ap- plied to the eye-ball, it produces a somewhat painful sensation of tension in the ciliary region, contraction of. the pupil, myopia, and astigmatism, with frequent congestion of the conjunctival vessels, pain in the supra-orbital region and twitching of the orbicularis palpebrarum muscles."

Dr. Edwards, an eminent chemist of Liverpool, Eng., applied a few drops of an ethereal extract of calabar bean to a frog's back, by insertion under the skin. In a short time the auimal manifested an indisposition to move and became very quiet. In the course of an hour it became unable to jump, or to change the position in which the limbs were placed; in about two hours it became perfectly lhic-

PHYSOSTIGMA VENEXOSUM. 611

cid, and insensible to any external irritation ; although stimulated by strychnine, it was incapable of being roused to muscular exertion, and soon expired, having previously exhibited very irregular respira- tion and pulsation. A second portion was exhibited to a mouse, which became soon paralyzed in its limbs, and died after a few hours. A third portion was introduced into the circulation of a mouse, by the ear, and after twenty-four hours the poison operated fatally, by causing complete paralysis of the limbs and senses, and the animal died of syncope.

Eserine is the crystallizable principal of the seed. Fifteen grains of eserine dissolved in a small quantity of water, and mixed with a few drops of acetic acid, was injected in the skin of the groin of a vigorous young dog. About six minutes after the injection, the dog became dull, uttered some plaintive cries, looked for a dark place and lay down behind a stove. He yawned repeatedly, put his tongue out and carried his paws to his mouth, as if he wished to remove some foreign substance from the buccal cavity.

The hair and the skin became now distinctly agitated as if by light chills, which soon became general and increased in severity until a full trembling continued to affect the whole body, the extremities and the head. The animal soon scpiatted down on his hind-quarters, then on his paws, and it seemed as if he could not move any longer. In fact, he could not change his position when disturbed. Sponta- neous movements took place, and it seemed that the impossibility to move was due to the continued state of trembling, which seized the whole body of the animal.

Respiration became more and more difficult. The movements of the sides were jerking and evidently participated in the general trembling which had seized the muscles of the chest as well as the diaphragm. Asphyxia developed rapidly now, showing itself by steadily increasing dyspnoea, by swelling and drawing out of the tongue, which wras constantly trembling, and by the continual drivelling of abundant gluey froth. The trembling of the head, which was kept in a bending position, gave way to a striking of the chin on the floor and there was loud and continual chattering of the teeth.

Experiments at different times, and in different parts, showed sen- sibility well preserved, even nearly up to the period of asphyxia. The persistency of the reflex action was retained to the last, showing itself by increased trembling in the excited extremity or by energetic winking when the cornea was touched. A few minutes before death, about half an hour after the operation, the trembling left the hind- quarters and fixed itself more in the chest and head, and localized itself in the latter up to the last breath.

Autopsy, immediately performed, showed the lungs highly con- gested, and studded on the pleural surface with a great many wine- colored spots; large emphysematous bullae existed on their sharp borders, and the bronchial tubes were full of a frothy liquid. Th*J

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swollen heart was soft to the touch ; the tissue was black and, in fact, infiltrated with large quantities of black blood, which, after incision, ran out under pressure, as from a sponge. The right ventricle con- tained a diffluent clot, the other cavities only a little fluid blood. The small intestines were found in a state of contraction, showing in places circular constrictions. The large intestine was distended and full of fecal matter, which seemed to have accumulated under the influence of peristaltic motions continually developed under the action of the poison (the animal had two stools during the experi- ment ; constant rumbling was heard in its bowels, and one could see through the abdominal walls the contractive motions of the bowels).

The bladder was contracted and absolutely empty, the animal hav- ing passed water several times before death. The liver, like the heart and lungs, showed signs of great congestion.

Dr. Ohristison carefully chewed and swallowed a piece of the seed of the Calabar bean, which weighed about twelve grains. He de- scribes the effects as follows : A slight giddiness, which occurred in fifteen minutes, was ascribed to the force of the imagination, and I proceeded to take a warm shower-bath, which process might take five or six minutes more. The giddiness was then very decided, and was attended with the peculiar indescribable torpidity over the whole frame, which attends the action of opium and Indian hemp in me- dicinal doses.

Being now quite satisfied that I had got hold of a very energetic poison, I took immediate means of getting rid of it by swallowing the shaving water I had just been using, by which the stomach was effectually emptied. Nevertheless, I presently became so giddy, weak and faint, that I was glad to lie down supine in bed. The faintness continuing great, but without any uneasy feeling, I rung for my son * * * who sent for a medical friend Dr. Simpson, who was the nearest, reached me in a few minutes, within forty min- utes after I ate the seed, and found me very prostrate and pale, the heart and pulse extremely feeble and tumultuously irregular ; my condition altogether very like that induced by profuse flooding after delivery, but my mental faculties quite entire, and my only sensa- tion that of extreme xaintness, not, however, unpleasant.

Dr. Simp- son judged it right to proceed at once for Dr. Douglas Maclagan, as a toxicological authority, and returned with him in a very few min- utes. In his absence, feeling sick, I tried to raise myself on my elbow to vomit, but failed.

I made a second, more vigorous effort, but scarcely moved. At once it struck me — "This is not debility, but volition is inoperative." In a third effort I was more nearly successful ; and in the fourth, a resolute exercise of the will, I did succeed. But I could not vomit ; the abdominal muscles acted too feebly, nor were they much aided by a voluntary effort to make them act. I then gave up the attempt and fell back, comforting myself with the reflection that vomiting was unnecessary, as the stomach had been thoroughly cleared.

At the same time the sick-

PHYSOSTIGMA YENESTOSUM. 6U

ness ceased, and it never returned. There were now slight twitches across the pectoral muscles. I also felt a sluggishness of articula- tion, and to avoid any show of this, made a strong effort of the will to speak slowly and firmly, through fear of alarming my son, who was alone with me.

Dr. Maclagan, on his arrival, thought my state very like the effects of an overdose of aconite. Like Dr. Simpson, he found the pulse and the action of the heart very feeble, frequent and most irregular ; the countenance very pale, the prostration great, the mental facul- ties unimpaired, unless perhaps it might be that I felt no alarm where my friends saw some reason for it.

I had, in fact, no uneasy feeling of any kind, no pain, no numbness, no prickling, not even any sense of suffering from the great faintness of the heart's action ; and, as for alarm, though conscious I had got more than I had counted on, I could also calculate, that if six grains had no effect, twelve could not be deadly when the stomach had been so well cleared out. Presently my limbs became chill, with a vague feeling of discomfort. But warmth to the feet relieved this, and a sinapism over the whole abdomen was peculiarly grateful when it commenced to act.

Soon afterward the pulse improved in volume, but not in regularity. I was now able to turn in bed, and happening to get upon the left side, my attention was, for the first time, directed to the extremely tumultuous action of the heart, which compelled me to turn again on the back, to escape the strange sensation. Two hours after the poison was swallowed I became drowsy, and slept for two hours more ; but the mind was so active all the while that I was not conscious of having been asleep.

On waking, the tumul- tuous action of the heart continued. In an hour more, however, I took a cup of strong coffee, after which I speedily felt an indefinable change within me, and on examining the condition of the heart, I found it had become perfectly and permanently regular. For the rest of the forenoon I felt too weak to leave my bed ; and on getting up, after a tolerable dinner, I was so giddy as to be glad to betake myself to the sofa for the evening. Next morning, after a sound sleep, I was quite welh (From the report on physostigma of Dr.

T. F. Allen to Am. Inst.

Horn., 1877.)

Dr. Frazer sums up the effects of small doses, from six to ten grains, as follows : In about five minutes, a peculiar feeling in the epigastrium immediately below the sternum. This is very slight at first, but gradually increases in intensity until it becomes almost painful. Eructation takes place in a short time, and always occurs during an aggravation of this sensation.

This continues at intervals for a considerable time, and is, by and by, complicated by a feeling of dyspncea. Dizziness is soon after experienced, and in a little while a degree of powerlessness in the muscles of the extremities.

614 PIITSOSTIGMA VENENOSUM.

If a somewhat larger dose be taken, as in Professor Christison's experiment, twitches occur in the pectoral muscles, and the dizzi- ness is much augmented. I have also further experimented and noted a dimness of vision, a supposed increase in the salivary secre- tion, or at least an accumulation of fluid in the mouth, and a marked, though slight, perspiration. At this stage attempts to walk,. or even to move the limbs, are difficult and may be unsuccessful, while at the same time consciousness is perfectly retained.

These symptoms reach a certain climax, and then gradually decline, dizzi- ness being generally the most persistent, and they almost entirely subside after a night's rest. The heart's action in Dr. Christison's case was described as becoming irregular and tumultuous. The same irregularity has been observed in some cases which have come under my notice, and in many, the cardiac contractions have been found to diminish in number.

In one experiment, eight grains of the powdered kernel in one and a half hours reduced the pulse twenty beats. When the extract is applied to the eyeball, it imme- diately causes a copious secretion of tears, and in about five minutes a distinct contraction of the pupils, confined to the side of the appli- cation. In about thirty minutes after the application, the pupil becomes a mere speck, but still retains a certain degree of mobility. It continues in this state for twelve or fifteen hours, but a greater or less degree of contraction of the pupil may continue for five or six days.

A slight headache or dimness of vision, with myopia in the affected side, are almost always produced, but these only continue for one or two hours at the commencement. When the extract is applied to the edges and outer surfaces of the eyelids, there is produced, in addition to the contracted pupil, a degree of immobility of the eyelids. When either extract or tincture is applied to the skin, a local action is caused. In about half an hour a dis- tinct diminution in -the sensibility occurs, and the skin may be pricked, very little pain only being excited.

(Trans. Am. Inst, of Horn., 1874, p. 186.)

Roeber (Berlin, 1868,) sums up the action of physostigma upon the heart and spinal nervous system as follows: "1. The chief action of the bean consists of a depression and final annihilation of the excitability of the ganglionic elements of the spinal cord ; and its operation especially affect the groups of cells in the anterior horns of the gray matter which conduct impulses from the brain to the periphery, and then also attacks the elements of the gray matter

PHYSOSTIGMA YENENOSUM. 615

in the posterior horns which transmit sensation of pain to the brain. 2. By this functional lesion of the gray matter a complete loss of the motor and reflex activity of the spinal cord is produced, likewise a loss of sensibility to pain ; while the sense of touch, and the so-called muscular sense, are retained until the death of the animal. 3. Besides this action on the cord, calabar bean possesses a special power over the movements of the heart, which in small doses it merely retards, but in large doses completely arrests. 4.

The interference with respiration, which is especially produced by small doses, is either the consequence of a sudden interference with the heart's action, or is produced by a destruction of the motor power of the respiratory muscles from paralysis of the spinal cord. 5. The poison increases the secretion of tears and of saliva. 6. The increase of defecation observed in poisoning with calabar bean is the result of a tetanus of the stomach and intestines, the cause of which is not yet fully determined. 7.

The motor and sensory nerves are not affected at the commencement or in the development of the affec- tions of the cord ; at a later stage there follows a paralysis or hastened death of the intra-muscular termini of these nerves. 8. The fibrillary muscular twitching occurring soon after the adminis- tration of the poison, which are especially striking in mammalia, may be explained by a local irritation of them, caused by paralysis of the motor nervi-termini. 9. The pupils are strongly contracted both in the external and in the internal use in large doses of calabar bean extract; but as to the cause of this it will be necessary to insti- tute more exact inquiries."

Practical experience in homoeopathic practice teaches that the effect of physostigma upon the pneumogastric nerve is worthy of particular attention, since these effects, such as : oppression on the chest, labored and sighing respiration, etc, form prominent features of pathological conditions in which physostigma, applied under the homoeopathic law, has demonstrated great therapeutic value.

Permit me to quote again from the interesting and exhaustive report of Dr. Allen, to which reference has already been made : Experiments made by Mr. Bowman on himself showed astigmatism, so that horizontal lines became indistinct, while vertical ones remained clear; this was neutralized by concave 14 cylindrical.

" Syrupy extract applied to the eye caused instantly a copious dis- charge of tears ; in five minutes the pupil began to contract ; in ten minutes pupil -J^. inch in diameter, vision imperfect, distinct vision

616 PHYSOSTIGJIA VENENOSUil.

impossible, slightly painful sensation in the supraorbital region ; thirty minutes, the pupil a mere speck, vision nearly lost, with some redness and photophobia; in 'four hours dim vision disappeared, but the pupil remained contracted for five days. Another application produced, in addition, marked immobility in the lids, with disagree- able sensation of dryness, and an inversion of the upper lid on closing the eye.

Graefe On carefully watching the progress of the myosis (con- traction of the pupil) the iris is seen to contract convulsively with little jerks or twitches ; they are very small and rapid jerks, and would easily escape observation. While the iris was under the in- fluence of physostigma, in all its stages it was sensitive to light, that is, it would contract still more from a sudden strong light, even when the myosis had reached a high grade. This seems to show that the sensibility of the retina remains unaffected.

The myosis lasts from two to four days. After the myosis has passed off, there is usually mydriasis of a slight degree for several days, especially during the morning hours; this seems to depend upon a kind of fatigue of the sphincter, which passes off during the day under the reflex stimulus of light. Bright daylight seems like twilight, the result of the largely contracted field of vision. The action on accommodation consists in the approximation of the far point (my- opia) and also of the near point.

This contraction does not usually progress steadily, but by spasms or jerks (just as the pupil con- tracts) ; the far point is approximated sooner than the near point* If a very weak solution is used so that the accommodation is not markedly affected, we find that on attempting to use binocular vision, as in reading, a disturbance exists, consisting of pain, blurring and straining, so that one eye must be closed, which is relieved by a weak concave glass ; it seems as though the ordinary will, impulse, caused too great an action of the accommodation.

The phenomena of the accommodation last much longer than does the myosis. The approximation of the near point lasts longer than that of the far point. Visual acuteness often sinks to one-half the normal under its use. Letters seem in constant motion, and can only be seen at a large visual angle.

One observer could bring his vision with perfect clearness to -the normal, but only with very great and painful exertion. The circulation in the fundus of the globe is not affected. Toward the end of the myotic action there is expe- rienced a painful tension, partly in the equator of the ball, partly in

PHTSOSTIGMA VEXENOSUM. 617

the ciliary region. Nervous aching in the whole ball, which extend along the supraorbital nerves, and over half the head.

Experiments on a man without any iris : his vision was |-, with the use of a positive cylindrical glass ^ (hypercpic astigmatismus). Eanges of accommodation ^ .5. At 2:58, instillation of extract of physostigma, followed by slight biting in the conjunctiva, which passed off in a minute. At 3:7, myopia -^L; near point remains at 5|- inches, though accommodation is reduced to -£■ |-: from the time the myopia gradually increases, and soon a slight nearing of the near point begins, with no trace of pain.

At 3:20, myopia is JL; near point 5 inches; accommodation only JL; visual acuteness diminished to |-. (This diminution of visual acuteness in this case is not dependent on contracted pupil, as had been supposed in other cases Dr. T.

F. Allen). At 3:30, myopia -i. ^; near point 4|- inches; accommodation only ^L; vision very indistinct at a distance on account of large dispersion circles. 3:42, accommodation the same; myopia begins to diminish. 3:45, accommodation ^-; myopia JL.; near point the same. 3:50, accommodation i-; myopia -J^.; near point a little further. 4:12, accommodation i; myopia-^; near point 5 inches. 4:50, accommodation ^ |- (nearly normal) ; near point 5 inches ; myopia only -^L-. The action on the ciliary muscle seems entirely independent of the pressure of the iris.

Pereira states that physostigma is useful in erysipelas, various neuralgic affections, rheumatic fever, aeute bronchitis, delirium tremens, tetanus, epilepsy, chorea, and that it acts as an antidote in poisoning by strychnine.

We may use calabar bean in the treatment of the following diseases :

TETANUS with heavy, tumultuous action of the heart whose every beat is distinctly perceptible in the chest and temple ; feeling of constriction in the chest ; even of impending suffocation ; feeling of unsteadiness, which can be overcome, in part at least, by strong mental effort.

The regular school have used the calabar bean extensively and somewhat successfully in the treatment of tetanus. Their author- ities, however, differ greatly as to its value. Trousseau and Pidoux, for instance, are somewhat cautious in admitting its efficacy. Dr. Navarry, in a thesis on tetanus, states that of eighteen cases reported, twelve were cured by calabar bean, with the possible exception of one case in which the cure could not be wholly attributed to the medicine.

618 PHTSOSTIGMA VENENOSUM.

Dr. C. H. von Tagen (Horn. Times, August, 1880,) says: "Our experience with the remedy has been such that we regard it as an invaluable agent, both for traumatic and symptomatic tetanus, like- wise trismus.

We have safely guided through to a favorable termination, with this remedy, seven cases of the traumatic form of combined trismus and tetanus, accompanied with marked opisthot- onus, resulting from unusually severe mechanical injuries ; also, two cases of symptomatic tetanus, accompanying cerebro-spinal men- ingitis; the two latter occurring in children aged five and seven years. The former — or seven cases — were six adults, their ages ranging from twenty-eight to forty-nine, and a lad of sixteen years. * * * We have noted in all the cases treated by this remedy that a strong indication for its use is a marked contraction of the pupils of the eyes.

CHOREA of the right side; a feeling, as if the tongue were swollen and paralyzed. (Dr. Burgher, Trans. Am. Inst. Horn.) 1877, p. 295.)

VERTIGO with dimness of sight; heavy pain in the frontal region of the head ; at times pulsating ; worse after motion and reading ; sighing respiration.

PARALYSIS with feeling of great weakness along the whole length of the spine, and in the lower extremities ; trembling of the body ; pressive headache ; copious urination ; sighing respiration ;

Physostigma is an important drug in the hands of the skilled ocu- list. Its action upon the pupil of the eye, causing as prompt con- traction as atropine causes dilatation of the pupil, brings it into frequent requisition in ophthalmic surgery. According to Donders and Graefe the previous application of calabar bean renders the operation for glaucoma comparatively easy in cases where the pupil of the eye is excessively dilated.

In cases of injury to the cornea, where hernia of the iris is feared, the external application of eserin is said to prevent the hernia, or to reduce it if it already exists ; this is done by mere mechanical action. (In an operation for cataract, a small piece of the iris that was caught in the incision, was drawn back by the use of eserin.)

PHYSOSTIGMA VENENOSUM. 619

Atropia, dropped into an healthy eye, diminishes the intraocular pressure in the vitreous chamber, when that pressure is above the normal degree.

Calabar, on the contrary, increases the pressure in the vitreous chamber, but diminishes it in the aqueous.

It is acknowledged that these chambers are entirely separated from each other.

Prom the above conclusions it follows that atropia overcomes the

620 PHYTOLACCA DECAXDRA.

lethal effects of physostigma, by stimulating the respiratory function ; but it is certainly very doubtful whether physostigma is of any practical service in poisoning by atropia.