Jaborandi

Volume III — Main text

JABORANDI.

Pilocarpus pennatifolius. Nat. Ord., Rutacete.

I. Provings. — I. When 6 grm. of the powdered leaves are given in infusion, very soon the face becomes red ; the temporal arteries throh more strongly j then there is a peculiar feeling of heat in the mouth and on the face, and the flow of saliva begins. In a little while the forehead becomes moist, and the face more red ; then beads of perspiration appear on forehead, cheeks, and temples. The flow of saliva increases, all the salivary glands successively contributing to this effect) the mouth is filled with immense quantities of fluid, and expectoration is incessant -, at the same time perspiration covers the face and neck ; then the whole body becomes red and moi$t, and a pleasant warmth is experienced ; in a few m. perspiration breaks out over the entire surface, and soon runs down on all sides. Meantime other symptoms have supervened. The eyelids first become moist, then the lachrymal secretion gradually augments, and, after collecting in the canthi, rolls slowly down the cheeks ; at the same time there is a copious discharge from the Schneiderian membrane, increased by the tears which escape through the nasal canals; moreover, there is increased activity of the mucous glands of the pharynx, trachea, and bronchi. All these eflPects reach their maximum of intensity in about J h. after taking the drug, continuing thus for 30 or 40 m. Lying on one side, that the saliva may run more freely, the patient spits 10 or 15 times a m. ; the flow is so rapid that he can hardly speak \ the salivary glands are enlarged, and the mouth becomes hotter. The body is bathed in perspiration.

»7

■

ashirt is wet through in a few seconds. Then a feeling of comfort or of weakness, as the case may be, is experienced. Thirst is intense. The pupils are slightly contracted. By degrees the excessive activity of the secretory processes is diminished ; in ij or i^ h. the lachrymation, the nasal discharge, the bronchial expectoration, and finally the flow of saliva and the perspiration are notably lessened, and the parts involved gradually return to their normal condition. When the perspiration and salivation have ceased the subject is prostrated and drowsy. The parts which secreted so copiously are now very dry, t-specially the mouth and pharynx. There is also much thirst. {Kobitt^£tu{Us phys. et thtrat, sur le "Jabarandi^ '875.)

1. We made four experiments on 3 healthy lads (with a slight exception noted farther on) »t. 8 — 12. We gave 30gr. of the infused drug with the dregs, and kept the lads in bed covered with their usual amount of bedclothes- We carefully examined the effect of the medicine on the sweating, salivary and bronchial secretions, pulse, respirations, and temperature. The lad on whom two of the experiments were made was slightly feverish (994° to 996°) .

a. In 3 instances the drug produced perspiration ; one lad's skin remained quite dry throughout the experiment. In 2 perspiration occurred in 10 — 15 m. ; in the 3rd case it was delayed for 35 m., became profuse in 20 — 35 m. more, continued thus for 30 — 90 m., and remained slight from 2 — 4^ h.

b. There was some salivation in all cases, and in 2 it was profuse ; but in the lad on whom 2 observations were made the effect on the salivary glands was very slight. The salivation was much more profuse in the lad whose skin remained dry. The salivation, when it occurred to a marked extent, began simultaneously with the sweating, was greatest when the sweating was most profuse, and lasted as long as it continued. In the lad who failed to perspire the salivation became profuse in 15 m., and so continued during 3 J h., and then in a less degree for 7 h.

c. We noticed an increase in the bronchial secretion, indicated by a loose cough, only in the lad on whom two observations were made, and in whom but a slight increase of salivary secretion occurred. The bronchial secretion was much more abundant in the 1st than in the 2nd observation ; indeed in the 2nd there was very tittle cough.

d. In each observation a decided fall in the temperature occurred. In 2 cases during sweating the fall amounted to 1°, and in another it reached 26^, The observation was begun in the afternoon and continued till c. The reduction of the temperature persisted for the rest of the d. ; but in the two m. observations the lowest temp, was reached about i^ h. after the administration of the medicine. In i case the fall began immediately j in another in 40 m., in another in 80 m. In the lad whose skin remained unperspiring there was a fall of o6^, which, beginning 45 m. after the administration of the medicine, lasted only 2^ h.

e. In each experiment the pulse became considerably quicker, 4.0 — 50 beats, reached its quickest 25 — 80 m, after administration, and acceleration continued more than 4 h. No close relation existed between the rapidity of pulse and fall of temperature. The heart beat

against the chest with increased force, there was distinct throbbing of the carotids, and the pulse was full as welt as quick. In one lad, whose pulse was intermittent, the medicine entirely removed this irregularity.

/*. In those instances in which sweating toolc place the foce became flushed, and this was most marked when the perspiration was greatest. The flush involved the cheeks and ears. It soon passed away, and was succeeded by pallor, while yet the perspiration continued very free.

g. In 3 cases the medicine produced considerable drowsiness, the lads falling asleep during the observations. They were also a little sick, faint, and prostrate. The lad who failed to perspire vomited ; the perspiration, therefore, was not due to nausea, nor, indeed, did they complain of it. The vomiting came on suddenly, and was not repeated. (Ringer and Gould, Practitioner^ xiii, 387.)

1. a. We have recently made 37 careful observations ^ 30on adults, act. 20 — 45 ; 17 on children, set. 3—10. To the adults we gave 60 gr. ; to the children 30 and sometimes 60. These investigations have led to the detection of several new and interesting effects of J. They show us that children are very little affected by the drug. In 2 cases only was the sweating abundant, in 8 it was slight, in 7 altc^ether absent. Salivation was generally absent, and never more than to make the mouth a little moister than usual ; and soon with the other efiecta. In the adults the effects were as heretofore described. M. Robin finds that the tears and the nasal secretion are increased, but in only 4 of our cases was such augmentation appreciable. In 1 1 cases complaint was made of pain over the pubes, and in some instances this was severe, and was generally accompanied by a strong desire to pass water, which afforded relief. A good deal of trembling, especially of the upper extremities, followed in 2 instances after the administration. One man com» plained of much throbbing of the head the d. following the experiment. Many patients complained of feeling alternately hot and cold, or chilly. (^ne patient to whom we gave it was a nursing woman. Her milk, previously scanty, was greatly increased in quantity during the action of the dru^.

b. Mr. John Tweedy, having applied the extract to his own eye, finds that it causes contraction of pupil \ tension of the accomodative apparatus, with approximation of nearest and farthest points of distinct vision ; and amblyopic impairment of vision from diminished sensibility of retina. The efl^ect reaches its maximum in 40 m., and goes off in I \ h. (Ibid., Lancet^ '875, i, 157.)

1. John W — , aet. 17, drank, at 10.30 a.m., an infusion of ^iss. Just before taking drug skin was dry, temp, in axilla 9825°, pulse 90. At II. lo temp, was 979°, pulse 104. Skin was moist over whole body, face and forehead perspiring profusely. At this time he com plained that mouth was filling with water, and said there was mist before eyes. At 1 1.40 temp, was same, pulse 96. Skin was perspiring profusely \ salivation continued. He said he could not see anything on the other side of the ward, a distance of about 25 ft. \ he could see anyone standing by the side of his bed perfectly distinctly. Pupils uere unaltered. At 12.10 temp, was 96*6°, pulse 90, skin less moist, no derangement of vision, no salivation. At I skin was of natural

a9

moisture, temp. 96*8°, pulse 96. (Sawver, Bnt. Med, youm.y 1875,

i, 174.)

1. Dr. Hull took 3] of leaves in infusion. The first effect, which came on about 8 m. after drinking the infusion, and chewing and swallowing about one half of the leaves, was a profuse flow of saliva, which continued about 3 h. During this time at least 30 or 40 oz. must have flowed. Following closely upon this came diaphoresis, which was extremely profuse, the perspiration running off in drops and saturating everything. In about i h. sudden and severe pain wasexpenenced in the bladder, shooting down to the urethra, and causing exclamations. This was followed by cutting pain in the lower bowel, though there was no tendency to diarrhcea j it became so severe as to necessitate an opium suppository, which affordeo great relief. About this time (i h. after taking drug) cardiac irregularity was noticed, with great weakness and rapidity of action, and u nervous restless condition, with constant yawning. There was gradually developed a dimness of vision i and soon surrounding objects, beyond a couple of inches from the eye, became indistinct. A watch held closely could be read with ease. This condition lasted several h., when nausea came on, followed by severe vomiting, ejecting the contents of the stomach, finally bile, and then passing off as a continued retching. The unpleasant effects were counteracted by the administration of whiskey, about jij in water ; and he fell asleep to awake next m. in a weak Janguid state, with excessive dryness of mouth and continued thirst, (Phil. Med, Times,

vii, +34-)

1. Experiment by Wm. Martindale on himself; from 60 gr. of bruised leaf in 5 oz. boiling water, macerated 15 m. Took dose at 11. 30 p.m. ; in 5 m. felt a glow, increased circulation, uneasiness in head, became restless and secretion of saliva began to increase; in 15 m. perspiring freely. Salivation and perspiration continued profuse until sight became blurred — at a distance of 4 ft. could see a face, but could not distinguish the eyes; at 12.15 near objects could be seen distinctly, but not distant ones } pupils slightly dilated; pulse 96, rising to 104. Temp, not taken. Shivering came on about this time and the excessive perspiration ("a Turkish bath was nothing to it") continued from all parts of the body ; spirit and water was administered. Saliva required constant ejection ; there was a kind of collapsed feeling to the cheeks. The speech was so affected that articulation was both difficult and indistinct, i a.m., vomiting ensued and was encouraged ; it was followed by diminution of the symptoms, and after changing clothes and taking more spirits, at 1.40 fell asleep and slept quietly until 6 a.m. Felt squeamish all next d. The saliva collected was distinctly alkaline and measured 16 oz. ; more escaped, which was not measured, (Pharmaceut. Journ., 3rd ser., v., 561.)

2. a. W. L. Watkins, M.D., *et. 23, health good, not affected easily by drugs. Dec. ist, 1H75, took 5 dr. of 5x dil. m. and e, without effect, and repeated dose 3 times next d. with same result ; which also followed use of 4th for 3 following d. On 6th, began to take 3X. On 1st d. no symptoms were noticed -, but on 7th, i h. after m. dose, felt slight uneasiness in head, which during forenoon increased

to pain in occiput, extending to forehead, and lasting till lite in afternoon. Did not take e. dose, but repeated med. before breakfast next d. About I h. after aching began in lower part of occipuc, which increased in severity for 2 h., when it gradually passed off*. OuriiMP forenoon throat felt dry and inflamed ; everything swallowed cauaea scraping sensation. P.m., inflammation increased ; tonsils slighdy swollen and jaws a little stiff*. This soreness lasted 2 d. On llni took same m. and e. After latter dose felt restless and anxious ; dull pajn in 1. occipuc ; for 2 h. after going to bed could not set to sleqi, on account of anxious and oppressed feeling in chest. Aner going to sleep dreamed of accidents and frights, which woke him up twice during n. Next m. quite a sore-throat, smarting pain ; dull headache, mostly on ). ; breathing hurried. Sore-throat and headache lasted till he went co bed ; next m. headache had gone, but throat was still sore. The feeling wore off gradually during d., and next m. he quite well. On 15th repeated dose i h. before break&st, for v^idi it seemed to take away all appetite, but 2 h. later he became veiy hungry. Usual headache came on towards noon, but did not alEfect appetite for dinner. Did not sleep well, from restlessness and sensa* tion of firm pressure on chest, with hurried breathing. Next d*, exhausted feeling ; no headache in m., but it came on during d,, and lasted till he went to bed.

^. On 19th began to take 2x. After 10 dr., in 2 h. heavy dull pain in lower occiput, worse on 1. side ; prostration of strength, even a short walk causing weariness, hurried breathing, and palpitation. These symptoms lasted 4 d., headache going olt first. On 24th, repeated dose. Same symptoms, with pain in cardiac region and anxiety. These symptoms lasted 5 d., becoming less severe each d. On Jan. 5th took ix,and repeated it at n. without anyefFiect. On 6th repeated dose. In about 2 h. return of symptoms of head and heart, with weakness, which lasted 3 d. After this repeated same dose with like result. On 13th took 10 dr. of tinct. This caused headache and suffocative feeling. Repeated dose next m. About noon there suddenly came on throbbing pains in forehead and vertex ; then in chest and around heart, increasing in severity as those in became less, heavy pressure on chest, hurried breathing, and fftat prostration. The symptoms became so bad that he was obliged to go to bed ; for ^ h. after so doing could only breathe with great difficulty* and with pains about heart there was severe palpitation. This conation remained at its height for 2 h., and then gradually abated, so that he was able to get up in the e. and study. For two weeks subse* quently he had the headache almost every d. about noon, and the exhaustion had barely disappeared by the end of this time. [Am, Oht^ xiii, 345)

1. Dr. W. Irving Thayer, act. 39, in perfect health, save that he has 3 papescent stools daily. July 20th, 1875, took repeated doses of 5 — 30 dr. of 1st dil. without effect. 2ist. — Same result from i^ diL taken in same way (up to 60 dr.). 22nd. — Made a tinct. of i to 5, and took it after same manner, without effect ; but his sleep for this and the last 2 n. was early and profound. 23rd. — At 9 a.m. 5 dr., and at

3»

I I

10 a.m. TO dr. of ttnct. In \ h. after last dose dull heavy distress in pyloric region of stomach, as though some hard, indigestible substance were lying there. At 11.30, 10 dr., followed by same symptoms, but most acute. At 2 p.m. 5 dr., and at 4 p.m. 10 dr., which last in 20 m. slightly increased pain in stomach ; but a full meal at 5 at once relieved it. 24th. — Two stools to-day instead of usual three, first constipated. At 9 and 10 a.m. 15 dr., and after 2nd dose distress at stomach, — a burning pain rather than the dyspeptic ache he experienced yesterday. At 1 1 a.m. 35 dr., and at 9 p.m. 40 dr. This m., also yesterday, noticed bright red spot on r. cornea, near iris; and in both eyes a vascular appearance, as from cold or overwork ; pupil normal. 25th, — In usual state, 26th. — At 8.30 a.m. 30 dr., at 10.30 a.m. 30 dr., and at 2 p.m. 80 dr. In ^ h. after last dose, copious perspiration; pulse (normally 80) 108; temp. 97°. At 3 p.m. 30 dr. At 5, overpowered with sleep while reading; slept i h, j after waking, found cornea injected and quite red. 27th. — k^yc less red, 28th. — At 2.15 and 3.15 p.m. 75 dr. After 2nd dose pulse 94. At 4.15 p.m. 100 dr. in i h, gentle glow on face, as from exposure to sun and wind ; slight increase in colour. 5, whites of eyes vascular again. 29th.— For last 3 d. stools have come only twice daily, but of same consistence. On 30th two stools, but exceedingly difficult to evacuate, consisting of long, large, and very dark faeces, 31st. — Between 6.30 a.m. and I p.m. 8 stools, watery, yellow, and coming with a gush. Felt an emptiness with this diarrhoea, but no pain whatever. At 1 took 15 dr., and repeated dose at 2. At 3.25 another similar stool. At 5 took 25 dr. At 5.25 stool as before, and again at 6 i pulse then 100, temp, normal. Felt a little weak, chilly up and down back ; glad to go to bed about 7.30 ; eyeballs sore on movement; dull throbbing ache at front and top of head. At 9 another stool. Feverish heat now, beginning in face, extended all over body ; pulse 100. Fell asleep at 9.30, and spent one of the most wretched n. he ever experienced j smart fever, increased pain in head, general malaise (no thirst), very restless, talking, moaning, with some delirium. Stool at I a.m. Took belladonna, with some relief to fever and restlessness i but sleep disturbed by many distressing dreams. Ate a light breakfast. Headache, eyeballs very sore, tongue slightly furred. At 10 a.m. took some china. Stool at 2 p.m., yellow, better digested, but coming with gush. Eyelids stiff and very heavy after an hour's nap, very profound (as sleep has generally been since beginning proving) ; also considerable distress in stomach and lower half of oesophagus, — this was removed by pulsatilla. 2nd. — Slept quietlv and very profoundly i eyes in m. sore on movement. Five painless but waterv stools. On 4th, continuing to have 5 to 10 similar stools daily, took gambogia 3, two doses of which cured it. (Trans, of N. K State Horn, Med. So€„ N. S. ii, 122),

1. a. Drascme experimented on a number of patients with infusion of 3J. Some took it cold, some hot ; some took it all at once, some by instalments. In all there occurred increase of salivary secretion and perspiration. The salivation always occurred, and was so copious that in some cases as much as 200 — 300 ccm. of saliva were collected in

2 — 3 h. ; it was of neutral reaction, sp. gr. 1 002, containing mudi albumen. The increased secretion began to appear in 10^15 m. after taking medicine. The perspiration generally appeared first on fine and chest, in numerous large drops. It lasted 2 — 3 h. ; not longer, however, than the saJivation. Both sometimes occurred whether the medicine was swallowed cold or hot, but in the latter case the perspin* tion was more copious. The patients had at the same time a feeling of increased warmth and face became red and turgid. The temp, at the commencement of the action rose from some tenths to 1° C, but afterwards fell rather below normal. In the beginning pulse was slightly quickened, but later it became slower. Sphygmographic tracings showed a very considerable contraction of the arteries during the action of the medicine. In some patients transient derangements ot vision were observed, and only in a few slight contraction of the pupils. The urinary secretion was not increased but rather diminished. In some cases there was urging to urinate, and a tickling sensation in urethra. No effect was produced on the bowels, but some patients had eructations, nausea, and inclination to vomit ^ these symptoms only occurred when die whole drachm was swallowed at once. There were no after-S3rmptonii& h. When the drug was given in tincture, the salivation always ensued, but the perspiration was not always present. When 5ij of tinct., corresponding to 3j ^^ infusion, were taken, salivation and perspiration were very copious. Visual derangements were very slight or sometimes absent altogether. The tinct. seemed to be not so certain in its action as the infusion. {Zeitsch, d. allg, 'ister, Jp^thtJkmrm

1. a. Among the incidental effects which have been observed, mention should first be made of the vomiting which occun from \ h. to I h. after taking the drug, and which is always preceded by prolonged nausea. It is extremely annoying and exhausting to the patient, lasts for a long time, and may readily lead to dangerous collapse. In 41 experiments Riegel observed it 18 times, and 10 times nausea without vomiting. Lohrisch, in 30 cases, saw violent vomiting 12 times, and nausea with inclination to vomit 22 times. The nausea showed itsdf sometimes immediately, sometimes \ h. and even later, after takiiMr the medicine.

b. After the nausea and vomiting, increased frequency of micturition is the most common symptom, occurring in about 40 per cent, of the cases. It appears so suddenly, and the desire is so great, that the patients are absolutely unable to resist it. Now and then a burning pain in the urethra and small of the back is also noticed, which is ao intense as to draw loud cries of suffering from the patients.

c. The disturbances of vision so frequently noticed are also worthy of mention. The patients state that they are unable to see distinctly because there seems to be a veil before their eyes. A few authors daia also to have observed dilatation (? contraction. — Eds.) of the pupils in these cases, but Riegel was not able to confirm this statement.

d. In addition to these incidental effects, there also occur not infrequently hiccup, dizziness, headache, with a kind of stupc^tion, and in some cases, a more or less intense chilliness appearing nesr the

p

close of the sweating, and also gastric and abdominal pains. After the cessation of the sweating, these symptoms come to an end. In verv weak persons collapse without vomiting is occasionally observetf, (Lew IN, &!>. at.)

III. Experiments on animals. — i. a. In animals which perspire, it has been possible co ascertain that all the secretions connected with the alimentary canal — the bile and pancreatic juice, as well as the saliva — are increased. In dogs it produces a copious and sangumolent diarrhcea. The urinary secretion, besides, is augmented in dogs ; and there exists also an abundant flow of nasal and conjunctival mucus. Introduced into the stomach or into the crural veins, J. dilates the pupil (this, however, fails to occur when the sympathetic is divided in the neck). In toxic doses, J. retards considerably the beats of the hcirt, and sometimes ends by arresting them completely in diastole like muscarine. Applied directly, however, to the heart of the frog, J. arrests the heart in systole like digitaline. Atropine destroys its effects on the heart, and also arrests its salivation and sweating. The temperature of the animals experimented upon is generally elevated.

b. An infusion of lo grm. of powdered leaves in 90 grm. of water was injected into the crural vein of a dog, in three portions, 2 — 3 m. apart. Some instants after first injection, saliva began to flow abundantly, and its eyes filled with tears. A little later, vomiting was pro. duced, then diarrhcea. Sanguinolent mucus escaped from the nostrils. Pulse was small, unequal, lOO; pupils at first enlarged, but soon returned to normal state. The animal trembled and appeared very feeble. It died during n. P.M. — Intense congestion of mucous membrane of stomach and bowels ; brain and its membranes also congested. There were ecchymotic points in lung, especially below pleuf«e. (VutPiAN, Path. Exp.^ i.)

1. a. General nervous system. — Injected under skin of frogs Jaborandi causes tetanic convulsions, not unlike those of strychnia. These continue after removal of brain, but cease with destruction of spinal cord. In 2 dogs narcotised with morphia, and in 2 rabbits to which chloral had been given, no convulsions occurred. The difference between the frog and the mammal may have been a question of dose. No marked effect on the irritability of the motor nerves or of the muscles was noticed.

b. Circulation. — In the dogs and rabbits (narcotised as above) injection of Jaborandi into jugular vein was followed at once by distinct slowing of pulse. No initial quickening (as observed by Dr. Ringer in human subject) was observed. The pulse was diminished to one third of its previous rate. In the rabbit the effect rapidly reached its maximum intensity and speedily diminished. During the height of the effect stimulation of the pneumogastric nerve produced the ordinary inhibitory results, the heart's action ceasing in diastole and recommencing on the withdrawal of the stimulus. In the case of the frog the injection of atropine was necessary to cause the heart to begin work again. Jaborandi, while acting similarly in this respect to physostigma, does not so rapidly exhaust the inhibitory fibres. A rapid but not very great fall of blood-pressure occurred in the dog and rabbit. If the web VOL. 111. 3

of the frog's foot be examined after injection under skin of back Ot Jaborandi, the arteries arc seen to dilate and the capillaries and veins to become full and red. The rapidity of the flow dtminishes considerablyj sometimes amounting to complete stasis over the whole or the greater part of the web, while the heart is beating ao per m. The stasis gives way partially when the heart is revived Dy atropine. The same stasis was observed whether the sciatic nerve was divided or incnct. After the injection of Jaborandi into the jugular vein the vessels of the ear on the side on which the sympathetic was intact were dilated, but less so than on the side where the nerve was divided. Stimulation of the divided nerve caused contraction and pallor as usual. The traciag of the blood pressure was remarkable for the great flattening of the respiratory curves^ a flattening which could not be explained hy changes in the respiratory movements.

f. Secreting organs. — In the dogs and rabbits, very soon after injection, a thick viscid mixture of mucus and saliva dropped from the mouth and clear fluid ran from eyes and nose. When a cannula wai placed in the submaxillary duct a flow of saliva like chorda-saliva soon took place. The secretion soon reached a maximum and speedily declined. It was unafl^ected by previous division of the chorda tympani and was therefore peripheral in its mechanism. The Jaborandi seemed rapidly to exhaust the gland, as electric stimulation of the chorda tympani was followed by a much smaller flow than if Jaborandi had not been used. In the frog a viscid secretion from the mouth and from the whole surface of the skin occurred. In the dog, after death, a large quantity of mucus was found in the trachea and bronchi and much acid fluid in the stomach. Jaborandi appears to inci the peristaltic action of the intestines. (Langley, Brit, Mid. Ji 1875, ii, 241.)

Volume IV — Appendix

JABORANDI.

(See vol. iii, p. 16.)

II. I . Dr. Wauth of Liege, who has great belief in the efficacy of J. as a stimulant of the mammary functions, mentions a case which has recently occurred in his practice, showing that inconvenience may occasionally arise from the administration of this drug. He prescribed 10 dr. of the fluid extract every 4 h. for a patient whose milk had ceased for a fortnight, with satisfactory results, the secretion being re-established. After a time, however, the patient began to suffer from extreme nervous excitement, accompanied by a fixed idea that she should murder all her family with a hatchet. On the J. being stof^d, these alarming symptoms disappeared, and with them the activity of the mammary glands. {Laneety Dec. 24/A, 1887.)