Cocainum hydrochloricum

Volume II — Main text

Cocainum.-An alkaloid obtained from coca, I. Provings.-1 . External Application.-a. Conjunctiva.-When I dr. of a 4 per cent. solution (and the same is true of much weaker solutions) is introduced into the eye, a slight burning sensation is felt. A m. or two later, the cornea and conjunctiva become anesthetic, and lose all reflex excitability ; the finger can be placed over them, and the conjunctiva taken up with the forceps, without causing any unpleasant sensations. At the same time there is a feeling of tension in the lids, and the eye seems protruded, as in a case of Graves' disease. The conjunctiva becomes exceedingly pale. These phenomena last for about 10 m., and gradually disappear. In from 10 to 15 m. the pupil begins to dilate, and there is slight paresis of accommodation. Mydriasis is never present to any great extent, but it lasts for some h. after the anæsthesia has disappeared. b. Nasal Mucous Membrane.-When applied to the mucous membrane of the nose, a 4 per cent. solution produces, in a few seconds, a sense of numbness which grows more marked as the applications are repeated. If they are renewed at intervals of 5 m. for 15 or 20 m., at the expiration of that time the mucous tissue may be cut or cauterised without any well-defined sensations, unless the instruments enter very deeply into the submucous tissue. Very soon after cocain has been applied, the membrane looks pale and turns almost white, so anæmic does it become. It retracts in a marked manner even if it were swelled before the application. But although its primary action produces anæsthesia and anæmia of the membrane, there occur secondary effects ofgreat swelling and hyperæsthesia ofthe parts treated, and these symptoms are even more prominent than they were before the drug was applied. (Fourn. ofAm. Med. Assoc., Feb., 1886. ) 2. Inasmuch as the writer-whose nervous system is of an almost unfortunate degree of sensitiveness-has taken doses of the hydrochlorate, equivalent in the aggregate to no less than 32 gr. of cocain itself, within the space of 3 h. without (as the present lines sufficiently prove) a fatal result following, this remarkable body cannot fairly be classed among the poisonous alkaloids. Among the chief symptoms induced

were increased cerebral activity, mounting at intervals into the region of delirium, the latter tendency always subservient to a powerful effort of the will. This continued for 5 h., the heart action and breathing being meanwhile slightly increased, but not to any painful extent. At first the muscular powers seemed to be enhanced, heavier weights being lifted without undue stress than is ordinarily the case, while the reflective faculties-as instanced by ability to read and form conclusions upon novel scientific matter-seemed stimulated. An h. after the entire quantity named had been taken, the sensibility of the limbs to external influences-which had gradually diminished from the first-became materially lowered, and neither pinches, pricks, nor slight burns with a heated wire could be felt upon the fleshy portions of the arms or legs. The trunk, however, never lost its sensibility to pain in any marked degree. Slight convulsive movements and a sensation of bodily torpor succeeded, giving way about the 8th h. to increased somnolency. No special desire or distaste for food was noticeable, but sleep overcame all other symptoms between 10 and 11 h. from the commencement, and continued for 13 h. afterwards ; a slight feeling of dizziness was experienced on waking, but this gradually went off, and had entirely disappeared 24 h. later. ( Brit. and Colonial Druggist, 1885, p. 36.) 3. M. D. HAGE, jun., M.D., of Richmond, Va., reports the following proving upon himself. At 4.45 p.m. pulse 88, before beginning experiment. At 5, gr. in 6 minims of water injected in l. forearm on radial side, just about where external cutaneous nerve from brachial pierces through ante-brachial fascia. At 5.14, some slight tingling in little finger, which may have been caused by resting arm heavily upon knee. At 5.15, gr. was injected about in. apart from the first. At 5.30, gr. more. No pain on insertion of hypodermic needle. At 5.40, pulse 110, slight perspiration on forehead, and a little nervousness. At 5.45, gr.. No special symptoms except slight restlessness. At 6.5, gr. was injected without once feeling needle. Whole 1. arm feels numb and heavy ; hands moist and cool ; pupils dilated immediately after injection. At 6.10, pulse 114, slight ringing in ears, and vacant feeling in stomach. At 6.30. gr. was injected ; needle not felt. Pulse 120. Very dry feeling in mouth and throat. At 6.40, pulse 114. I have a drowsy, sleepy feeling, and head feels heavy. Respiration 25 ; temperature 100°. Pupils well dilated, r. more so than 1. Face is slightly flushed, and skin moist and clammy. At 6.50, a large sewing-needle was slowlyintroduced in. straight through skin, fascia, and supinator longus muscle without least pain and only slight feeling of pressure, but when it reached periosteum it caused intense pain, as if something was gnawing at it. At 7, gr. more was administered. Pulse 120. Hands cold. At 7.35, took hypodermically another gr. Pulse 120. Great ease in breathing. Marked perspiration on forehead. At 7.45, pulse 120 ; temperature 100° ; respiration 28. Hands still cold, and slight headache. Area of complete insensibility is well defined, and measures 2 by 4 inches, having elliptical form. All of above injections were put in a space about size of a ten-cent piece, needle directed towards elbow, and skin held

between fingers in usual way. Sensibility is perfect for in. above the point of insertion, but here the line is very sharply drawn, which might point to the fact that the cocain was carried to the extremities by the arterioles. Moderate degrees of heat and cold were not noticed in the slightest. A lump of ice placed on arm was not felt until some of it had melted and trickled down on ulnar side. A piece of metal heated almost to redness-in fact, so hot as to scorch the hairs and raise blisters -could only be felt after contact of 2 to 3 seconds, when pain, although not intense, was dull and perceptible. At 8.5, gr. was injected, with needle pointing towards fingers. At 8.12, pulse 120; temp. 100° ; and resp. 28. Area of insensibility has a pear shape, and measures 4 by 6 in. At 8.30, another + gr. injection. Pulse 116. Continued dryness about throat, and extreme ease in breathing, with inclination to sigh frequently. At 9, still another + gr. injection. Pulse 116 ; temp. 99. A needle introduced down to bone in several places caused not a particle of pain. Pupils equally dilated and responsive to light. Slight twitching of muscles in various parts of body. Headache is quite severe. At 9.25, pulse 120. Head full and heavy. Respiration principally thoracic, very superficial, and delightfully easy. Anæsthetic area undiminished. No feeling of nausea or dizziness at any time. Hands still cold and clammy. Sensibility of mucous membrane of eye, mouth, and nose not perceptibly diminished. There is continued dryness of throat. There is feeling of great wakefulness, accompanied by weakness in the legs when walking. At 11 , general symptoms are much less marked. Area of insensibility greatly decreased. Headache much better ; only superficial breathing continues. Résumé. In 4 h., gr. 4 in zij of water were injected into1. forearm, resulting in a complete anesthetic area measuring 4 to 6 in., and extending to in. in depth ; headache, clammy perspiration on forehead and hands, the latter cold ; dilatation of pupils, weakness of legs, accelerated pulse, rise of temperature, very superficial breathing, and dryness in mouth and throat. (Virginia Med. Monthly, Aug., 1886.) 4. Dr. EDWARD MCCARTHY proved drug under Dr. Hage's supervision. Before beginning experiment, pulse was 68, and temperature 991° F. At 2.40 p.m., gr. dissolved in 2 teaspoonfuls of water was taken by mouth. It has a very bitter taste, similar to quinine but without the rough feeling. At 2.45, slight nervous feeling, with some little warmth in stomach. At 2.50, gr. more was taken. Pulse 64. At 2.55, warmth in stomach more marked. At 3, another gr. was taken. Pulse 64 ; temp. 99° ; tongue feels a little numb on end ; pupils slightly dilated ; some warmth in pharynx. At 3.10, yet another gr. was taken. Pulse 60, and weaker ; respiration 24. At 3.15, feels in very good spirits, and rested. At 3.20, another gr. was taken. Pulse 56 ; temp. 99° ; resp. 24. Warmth in stomach decidedly more marked. Describes his feelings as " very good ; similar to that after a big drink of whisky." On walking about room, feels light ; face flushed. Up to now 2½ gr. in all have been taken. At 3.25, after walking, feeling of exhilaration passes off. At 3.30, gr. more is taken. Pulse 60. Describes his feelings as " glorious all over the body, with stimulating waves rushing through the limbs." Says he is

intoxicated . A drowsy feeling 5 m. before has given way to one of great energy. The flushed face and dilatation of pupils come and go. At 3.40, took still another gr. Pulse 64 ; temp. 98. At 3.45, every breath feels stimulating. At 3.50, another gr. is taken. Pulse 65. Taste of drug not so bitter as at first. Mouth and tongue are very dry. At 4, some slight tremor in all fingers when outstretched. Pulse 76 ; temp. 98 °. No headache or dizziness, but continued happy exhilarated feeling ; and as no grave symptoms were present, it was decided to give 3 gr. more, in I gr. doses every 15 m. At 4.10, I gr. in 2 teaspoonfuls ofwater was swallowed. Pulse 76 ; temp. 98 °. All superfluous movements with arms and legs, such as gesticulations and strides around room, are very pleasant, in fact irresistible. Has a constant desire to undertake vast feats of strength, and feels like haranguing. At 4.15, pulse 88 ; tongue anæmic and dry. Same delightful sensations have full sway ; feels as if nothing he could see or hear would depress him. At 4.20 I gr. more is taken. Pulse 66 ; resp. 28. Pleasant tremors shooting through whole body. At 4.25, with closed eyes, and toes together, body has a pendulum-like motion laterally. Marked tremor of outstretched fingers, and disposition to sigh ; and he is unable to draw deep breath. At 4.35, final dose is taken. Pulse 88 ; temp. 99°. He is very talkative ; talk is not disconnected, but repetition of same idea over and over, because words fail to express delightful sensations. At 5.20, feeling of exhilaration fast wearing off; is sober but feels foolish. At 7.30, has had no hunger although last meal was at 8.30 a.m. Seven grains were taken in the course of 5 h. After 2 gr . first5.effects were felt, and after M. LANDESBERG, M.D.,2 gr. intoxication of New was produced. York, reports following (Ibid.) observations made upon himself :-He administered to himself, being in good health and of usual normal spirits and disposition, a subcutaneous injection of gr. of muriate of C. (Merck), repeating dose after 5 m., as no effect whatever had taken place in interval. About 5 m. after last injection he felt slight dizziness, pricking sensation in the tips of fingers, and slight pressure in the epigastrium-all of which symptoms passed off within 10 m. He was able to continue the literary work in which he was engaged, but with some effort. He laboured under slight drowsiness and limbs became heavy. Action of heart was rather retarded. Face was pale, sensibility of cornea normal, that of mucous membrane of globe slightly reduced. Pupils regular. Normal condition was reestablished after h. of rest, during which time he had full control of mental faculties. After 4 d. experiment was repeated, using at once 2 gr. for hypodermatic injection. Hardly had 2 m. elapsed after administration when heart was felt beating and blood rushing to head, which was quickly followed by sensation of fulness and roaring in latter and by noises in the ears . There was confusion of thought and impairment offaculty of volition. A feeling ofgreat uneasiness invaded whole body, and slight twitching movements were felt in toes and fingers, with sensation of numbness. Feeling of nausea and pressure in epigastrium was very marked. Acme of paroxysm lasted for over 5 m., after which face was very pale and covered with cold perspiration. Eyeballs were somewhat sunken into orbit ; pupils enlarged, but of normal reflex VOL. II . 18

action and accommodative power. Objects appeared slightly dim, but of normal proportions . Retraction and co-ordination of muscles were not changed. Sensibility of cornea and conjunctiva was greatly diminished. Pulse was feeble, arterial tension and action of the heart slightly reduced. Felt tired and worn out, unable to concentrate his thoughts, or to struggle against the creeping drowsiness. Half an h. after injection went to bed, labouring under nausea, general prostration and slight attack of hemicrania. Sound sleep during whole n. brought about perfect recovery. 6. In order to find out whether there is any similarity between the appearance of an eye under the influence of cocain and that noted in Graves' disease, I have made several observations. In a paper before the Ophthalmological Society in January, 1885, I called attention to the fact that cocain produced an enlargement of the palpebral fissure by acting on both upper and lower lids. Also in the Centralblattfür Med. Wissenschaft,for March 14th, 1885, I recorded the fact that distinct proptosis occurred often on using cocain, especially when the eye was deeply under its influence ; this I noted first in experiments on rabbits. The staring look of the eye in Graves' disease, and the increased amount of sclerotic shown, is well seen in the cocainised eye. The absence of the normal involuntary winking of the lids is to be noted in both Graves' disease and the cocainised eye. If care is taken that the drug reaches the upper lid, Graefe's symptom is often well marked, the lid halting on looking down ; sometimes the difference appears as much asin. ( JESSOP, Trans. of Ophthalmological Soc. , vi, 123.) II. Poisonings.- 1. An apothecary intending to commit suicide extracted 24 gr. of a crystallized substance from 2 lb. of coca leaves, and took it in beer, followed by 2 small glasses of brandy. For a time he felt well and soon went to sleep, but woke with gripings of the stomach, burning pains in the palate, dryness of the mouth and throat, dizziness, great weakness of the whole body, perfect consciousness, pulse and temperature normal. After taking 11 gr. of morphia he fell asleep and awoke well, though no urine passed for 24 h. (PLOSS, Varges' Zeitschrift, 1863, p. 222.) 2. A woman æt. 25, of good constitution, had been using a 2 per cent. solution of cocain for hay-fever. Her vial being exhausted, her husband, without a prescription, procured from a druggist two 5 gr. vials of the muriate of cocain, full strength, of which Mrs. S-, about 5 p.m., applied two thirds of the contents of one bottle to both nostrils with a small glass insufflator. In 15 or 20 m. she became dizzy, her vision became dark, a sinking sensation occurred, with great weakness. When Dr. Kennicott was called, h. later, he found patient in a semi-comatose condition, from which she was easily aroused, but answered questions with difficulty. When so aroused, her mind was clear. Her temperature was above normal ; skin was hot and dry. Radial pulse was very rapid, and so weak as to be scarcely discernible. Pupils widely dilated. Deglutition and articulation difficult. There was some dyspnea. She complained of dryness of fauces, and bitter taste in mouth ; also of cold shivers, and teeth chattered, although temperature was still above normal. Later she became drowsy ; eyes were closed, and muscles of

face affected. There was great weakness ; she could not support head. There was dyspnea, but it was not severe. There was some nausea, but she did not vomit. Extremities were cool, and head clear when aroused. She recovered in about 3 h. under stimulants (brandy and ammonia) and digitalis. Heat and friction were applied to extremities and heat over epigastrium. (KENNICOTT, Chicago Med. Fourn. and Exam., Oct. , 1885.) 3. SCHILLING records a case of severe cocain poisoning in which after the intragingival injection of 2 dr. of a 20 per cent. solution of this drug motion and sensation entirely disappeared ; complete amaurosis and deafness were present. The patient could swallow well, and called to her husband, who was absent, complaining of cold and darkness. Schilling attributed the condition to contraction of the cerebral vessels. (N. Y. Med. News, March, 1886.) 4. John B- took, Nov. 9th, 1886, at 12.10 p.m., 4ths gr. C. hydrochl. At 12.30, severe cramps of stomach, nausea, throbbing and bursting feeling in head, failure of sight, loss of use of legs, incoherent speech, confusion of ideas, drowsiness, could always answer questions when roused ; appeared drunk and became quite helpless. Brandy given but vomited. At 12.50 commenced to sweat profusely, clothes soaked through, sweat streamed down face and body ; head steaming. Pupils normal. Sweating was followed by severe prostration, shivering, feeling of impending death. At intervals cramps in stomach, retching and vomiting of clear mucus, with relief. At 1.15, pulse intermittent every fifth beat ; cyanosis of face, intense feeling of suffocation over cardiac region. Pulse from 80 to 86. At 1.45 p.m., cramps in legs and feet, especially dorsal aspect of r. foot, tingling and numbness of hands. Later, pupils dilated. The vomiting and cramps ceased at 4 p.m. (unless food was taken), the drowsiness, prostration, throbbing headache lasted till 6 p.m. , when he got warm and was relieved. Great weakness and swimming of head all n. Next d. still weak, continual vomiting, dry, leathery feeling in mouth, loss of taste, partial loss of power in legs, tingling and numbness of fingers, especially r. hand. The symptoms commenced 36 h. after taking the C., and most of them disappeared in 24 h. The weakness of legs lasted 3 d.,the tingling of fingers longer. Could not write till 6th d., as he could not feel pain in his fingers. (KELHAM, Lancet, Jan. 1st, 1887.) 5. There are also recorded a large number of cases in which toxic effects have followed the use of muriate of C. in ophthalmic surgery. In some cases the symptoms have been transient, consisting of pallor of face, giddiness, and sweating of face or neck ; in others there has been dyspnea, feeling ofgreat prostration, malaise and apathy, lasting sometimes for several d. Vomiting and headache have been rarely present. In one case the application of 15 dr. of a 2 per cent. solution to the conjunctiva was followed by tottering gait, difficulty of speech, confusion of mind and extraordinary restlessness ; and in another, the subconjunctival injection of about 8 dr. ofa 3.5 per cent. solution produced convulsions and loss of consciousness. In this class of cases the strength of the solutions used varied from 2 to 4 per cent. The quantity generally varied from 2 to 4 drops. The subjects were

in some cases feeble, aged women ; in others they were strong and healthy individuals, both male and female. (Communicated by the Hughes Medical Club of Massachusetts, to which the Eds. are indebted for most of the material relating to cocain.) 6. Six cases have occured to Dr. Keyser, in which the development of panophthalmitis was directly traceable to the use of cocain locally during operation. The strength of the solutions used varied from 2 to 4 per cent ; those used in at least 3 ofthe cases were known to be fresh, and microscopic examination showed no micrococci or deleterious substance to cause the inflammation. In reviewing his cases, Dr. K- notices that the inflammation arose just or much like that after the use of the jequirity in trachoma, except that there was more swelling of the ocular conjunctiva, and even more than and somewhat different from that in panophthalmitis traumatica. In the latter the inferior part of the bulbar conjunctiva is much more swollen than the superior part, which really has very little swelling at first, being only well and fully injected, while in the cases after the use ofcocain, the superior part ofthe conjunctiva was as much swollen as the inferior. The whole cædematous condition of the bulbar conjunctiva was especially marked. Dr. K- suggests that this condition may be pathognomonic of the action ofthe cocain in the inflammation which may occur in the reaction that takes place from the blanched condition of the vessels and tissues caused by its use. (Therapeutic Gazette, Jan., 1885.) III. Experiments on animals. -1 . When a frog has been poisoned with cocain by hypodermic injection (about oth gr. being used) the almost immediate result is to lessen the heart-beats to 10 or 12 per m., its action at the same time becoming irregular and intermittent. If this dose be not exceeded, the animal may recover in a few h., but if it be increased to gr., the beats are lowered to 6 or 8 per m., the heart becomes engorged with blood, and its action laboured and irregular ; the rhythmical action of the auricles and ventricles is disturbed, and long pauses occur between the contractions of the ventricles. It is curious to observe that the ventricles are earlier and more severely affected than the auricles, and ultimately (if the dose be lethal) cease to pulsate before a similar effect has been produced on the latter. If applied locally to the heart carefully exposed, a drop or two of the 4 per cent. solution rapidly produces a cessation of the heart's action, a similar application of salt water having no such effect, showing the result to be due to the drug and not to shock. Injected into a ventricle the same result is achieved even more rapidly and certainly. The heart is arrested in systole. Its influence on the respiratory system is rather less marked, but there is a decided stimulus at first with increased rapidity of respiratory movements, followed by slowing and ultimate arrest of function. If large doses be used, the period of increased action may be absent, and immediate slowing take place, resulting in arrest after a full inspiration. With reference to the nervous system, it appears in small doses to act as a stimulant to the spinal cord, increasing its reflex irritability. When larger doses are given this irritation may be absent, or at any rate much shortened, and there is almost immediate lessening of the irritability of the reflexes,

and finally loss of response to electrical stimulation. Small doses heighten the irritability of the sensory fibres of nerves without having any effect on the motor filaments. Large doses completely paralyse the sensory, and much diminish the sensitiveness of the motor filaments. Tactile reflexes are much diminished. The pneumogastrics are completely paralysed after even moderate doses, but their inhibitory fibres are not perceptibly affected by small doses. Applied locally to the nerve-trunks, after a transient period of increased irritability, the nerve becomes depressed and finally paralysed, and if the solution be strong this effect may be almost instantaneous. Ifthe exposure of the nerve to the solution be not too protracted, its irritability will return after the lapse of a few h. If a nerve-muscle preparation be made from a frog poisoned by cocain, the irritability of the nerve is found to be much diminished (this is also true of the muscle), and a stronger current is required to produce a contraction than in the normal frog. The muscular pulsations are shorter and less powerful, and it is impossible to produce tetanic contractions if the amount of the drug given be at all large. If the interrupted current be passed through the nerve for some time, there are caused several short, feeble, quick contractions and then nothing further. If the nerve from a nerve-muscle preparation be immersed for a few seconds in a solution of cocain and then be removed, it is found that the irritability is very much increased. The slightest touch of a steel instrument throws the muscle into violent tetanic contractions. If the nerve be now again immersed, the irritability becomes very much diminished, and is finally lost to all forms of stimulation. The drug has, moreover, a marked action on the power ofco-ordination,which is particularly noticeable after moderate doses. Small doses of cocain have but little effect when injected into voluntary (striated) muscles, but large doses diminish their excitability very decidedly, and the character of the muscular contraction called forth is greatly altered. The contractions are shorter, slower, and more feeble, and the muscular excitability is soon exhausted. The local action of cocain on muscular tissue is very similar to that found in general poisoning. The general effect of cocain would appear from the above observations to be twofold (apart from its local anæsthetic action on the skin, mucous membrane, and eye) : in small doses it seems to act as a stimulant, but in larger doses the depressant effect which may follow even small doses is immediate and marked in its outset, and culminating in cessation of function. This remark applies to its action on most of the organs. It also paralyses the vagi, and applied locally to any of the more highly constituted organs or tissues, causes a temporary cessation of their functional activity. (GUBB, Medical Press 2. Dr. and Circular, HERMANN Marchof11th M. BIGGE, New , 1885.) York, has just completed an inquiry into the physiological action of cocain on the common frog, and has arrived at conclusions which may be summed up as follows : a. It has a powerful local anæsthetic action on the skin, mucous membrane, and the eye. It usually produces mydriasis . b. It has a depressant action on the heart, reduces the force and

frequency of its pulsations, and finally paralyses it (first the ventricle and then the auricle) in diastole. c. In small doses it at first slightly increases the number of the respirations, then decreases them, and in large doses diminishes them rapidly from the first, finally causing death from a paralysis of respiration. d. It at first slightly heightens and then greatly depresses the reflex action of the spinal cord in small doses. Large doses depress from the first. e. Both large and small (not very small) doses have a depressant action on the motor nerves . f. It paralyses the pneumogastric nerve. g. Doses of moderate size diminish the excitability of the striated muscles . h. The local application of cocain to any of the more highly constituted organs or tissues causes a temporary cessation of their functional activity. i. From the local and constitutional action on the different organs and tissues, it is rendered probable that its general action is wholly a local one, exercised on all parts for which it has a chemical Aren-Jamim1885 17

1. Dr. BOLDT, before the New York ork Pathological Society, reported that after the injection of 11 minims of a 33 per cent. solution into a cat weighing 7 lb., death took place in 12 m . First effect, leaping gait with dragging of extremities, followed by convulsions ; between convulsions animal lay with limbs straightened, head turned up and backward. Cheyne-Stokes respiration ; temperature in rectum after death 104°. Autopsy showed vessels of the pia mater of both brain and cord intensely congested, extravasation of blood into fourth ventricle and anterior part of medulla, and very minute extravasations all through substance of brain. Lungs collapsed. R. ventricle of heart overdistended. Grey substance of cord over-filled with blood, resembling a bloody sponge. Death seemed to have taken place through the respiratory centre. These experiments were made in the presence of Drs . Spitzka, Waldstein, and Brill. (N. Y. Med. Record, Dec. 24th, 1885. )

Volume IV — Appendix

COCAINUM.

(Sec vol. ii, pp. 170, 747.)

I. 7. Dr. Da Costa, in experimenting with C. hypodermically gives the following results ; No effects were produced until at least v\ viij of a 4 per cent, solution were injected ; in some instances gr

"i was used. The general sensibility was only slightly alterei

t

The temp, rose, not abruptly however, from i*^ to t^^, and was main*' tained thus for several h. The effect on the circulation was to render the pulse fuller and stronger, while its rate may be increased or dinit' nished ; in a few instances no change in frequency was noticed. In the sphygmographic tracing, the higher vertical line of ascent and the ; more pointed summit showed increased force of cardiac contraction ;h while the sudden fall in the line of descent, and a well-marked dicrotic^ wave, indicated rather a lessened than an increased arterial tension. Pupils were speedily dilated, and uncertainty of vision was complained of. {N. nri Med. Times, June, 1885.)

1. I began with i gr. (hypodermically) at n. The result was pleasant ; I felt happy — happier than before on that d. But I did not sleep until 4 a.m., and had a severe headache. The exhilaration ws about equal to that given by two or three glasses of champagne. Next m. I took 2 gr. with the same result, and — in addition — an inordinate disposition to write. I wrote 8 — 10 pages of foolscap, and thought it was unusually good — the best I had ever written, in fact ; but when f read it over next m., though each sentence was complete, the ideas were incoherent. The 3rd n. I took 3 gr. My energy then turned to talking ; I made speeches to myself. Still, I could restrain myself; I had a splitting headache. After 4 — 5 d, I injected 6 gr., 3 into each arm. I was upset } I did not lose my relation to events, but could not sleep. After 3 n. I injected 8 gr. with the same result. The next n. I put in 18 gr. in six injections. I am not sure I was conscious of what I did after that ; I was intensely exhilarated. I got to bed »otne> how. When I rose things were generally mixed ; I had not arranged my papers, &c., as usual ; I presume, from appearances, I had had a pretty lively time all by myself. I had headache, and my heart but so that I could feel it and hear it when I raised my arm. But there were none of the horrible effects attributed to cocaine, no disposition towards violence. I acquired no habit, and left off easily. (Hammond, N. r. Med^ourn., xliv, 637.)

II. 8. Ten gr. were injected in an inebriate. The action of the C. ensued in 15 — 25 seconds, arriving at its height in less than an h,; in 2 h. effects were almost gone, and reaction gradually followed. The drug had a very decided effect upon the heart, pulse gradually rising from its normal standard to 120—130. Appetite was destroyed j

%

alio obstinate constipation was produced, lasting many d. and hard to overcome. The secretion of urine was arrested for the time, and the sexual function suspended. (Bauer, N. T. Med. Record^ 1885.)

1. A young woman snuffed up about 3 gr. of the muriate. In 15 — 20 m. she became dizzy, vision grew dark, and a sinking sensation occurred, with great weakness. The doctor found her in a semicomatose condition, from which, however, she was easily roused to a clear mind. Temp, was above normal, skin hot and dry } pulse very rapid and so weak as to be scarcely discernible. Pupils were widely dilated. Deglutition and articulation were difficult. There was some dyspnoea. She complained of dryness of fauces and bitter taste in mouth; also of cold shivers, her teeth chattering. Later she became drowsy; eyes were closed and muscles of face affected. There was great weakness, she could not support her head ; also some nausea, but she did not vomit. She recovered in about 3 h. imder stimulants and digitalis. (Kbnnicott, Ibid.)

2. Preparatory to an intranasal operation, pledgets of C. were introduced into the nostrils on several occasions. On each application the patient, a man of 35, mentioned a cold, " gone," relaxed feeling about the external genitals, and a sensation as if the penis were absent. Towards end of treatment he noticed a permanent weakness of the sexual organs, and finally seminal losses and impotence set in, and continued until the C. was entirely withheld. (Schadle, Medical RtgisttTy Aug. nth, 1888.)

3. A man suffering from chronic tubercular disease of kidneys and urinary passages took by mistake 20 gr. of C. in 5J of water. What the initial effects were is not known, for it was not till nearly an h. had elapsed that the nurse, hearing patient make some unusual noise, had her attention drawn to him. It is said that there was some arching of the back resembling opisthotonos, and a convulsive movement of the limbs. Consciousness was to some extent retained almost up to the fatal issue, which occurred in about an h. after swallowing the solution. The P.M. appearances were mainly those of the patient's disease ; but it may be mentioned that lungs and brain were congested, with some serous effusion beneath arachnoid, and that cavities of heart were neither contracted nor dilated, and all contained bloodclot. {Lancety Feb. 9th, 1889.)

4. M. Magnan, at the Societe de Biologie, lately described 3 cases of chronic poisoning by C. characterised by marked mental and sensory disturbance. The first was one where C. had been substituted for morphia for relief of renal colic. After 2 mo. use of the drug patient began to suffer from illusions of sight and hearing and neuromuscular irritability. He discontinued the C. for 6 mo., reverting to morphia; but on resuming it the illusions recurred, patient feeling imaginary blows on body, or something under skin, with a certain degree of analgesia. At end of a short time he had an epileptic seizure. In the second case, one of hepatic colic, the same substitution of C. for morphia had been effected, and produced very similar effects, also terminating in an attack of epilepsy. The third case also presented hallucinations of sight and hearing, sensation of foreign bodies beneath

the skin, and slight analgesia. M. Magnan pointed out that in its action on sensation and the sensory organs C. seemed to resemble the alcohols and absinthe rather than morphia, writh this difference, th« whereas the influence of C. poisoning seemed to operate on theccnbnl cortex from the occipital lobes forwards, alcohol and absinthe appeared to affect the cortex in the reverse order. {Ibid.)

1. A retired druggist had for many years been a hopeless victim to the morphia habit. This drug was suddenly withdrawn, and hypo* dermic injections of I — \ gr. of C, twice daily, were substituted. The result was brilliant and marvellously rapid. The craving (of morphia immediately ceased, and the distressing phenomena usually following the sudden cessation of the use of the drug failed to manifest themselves. But I was somewhat alarmed at ascertaining that a co^r^ spending demand for C. was rapidly developing itself. I sought (0 diminish the quantity, and finally to disallow the use, of the new poison, but in vain. He daily became more and more enthralled, often taking 20 — 30 gr. daily. About this time he sustained a severe concussion of the spine, and came under my daily observation. I found the teeth implicated in the ravages wrought by the drug, decay and absorption of the roots occurring. The appetite was completely abolished ; there was sense of dryness of mouth and fauces, but they were moist on inspection. Although very little nourishment was taken, the body did not emaciate in any corresponding degree. Insomnia was the rule, and one not followed by the exhaustion ordinarily thus produced. Nausea, and excitation of the sexual functions, added to the patient's distress ; and visual and auditory hallucinations, and illusions of i painful character, made him fear that at every pass he would encoujotcr some dread object. (Banding, A^. T. Med. Journ.^ 1885.)

Volume IV — Supplement

COCAINUM,

(See vol ii pp. 270, 7475 Vol iv, ps 556.)

1. 1. a. Dr. J. H. Way, at 6 p.m., injected gr. } under skin of forearm. No result appearing, injection was repeated in 15 m, At 6.30, general symptoms not having appeared, gr. } was taken. In 10m, he became restless, resp. 30, shallow and sighing; pulse 120. There was aphasia, and increasirig precordial oppression, Ir was now about 6.50. My pupils were dilating slowly; mental faculties perfectly clear and collected ; no pain in head or other part of body ; respiration reduced to normal frequency, but very shallow and sighing ; pulse 140, and barely perceptible at wrist. I walked the room for 3—4 m., when I grew weak and exhausted, and was compelled to lie down on the Jounge. At 7.20 my condition was almost that of collapse. Pupils were now widely dilated ; mouth dry, and a sensation as of a foreign body in pharynx ; resp. same, and only 11 per m,; pulse 180, very feeble and fluttering ; extremities cold; body was warm to touch, but my sensations were thove of intense cold. T'was placed in front of a

fire, and my body enveloped in heavy woollen blankets, while

»y feet and hands were briskly rubbed, A sense of impending disso-

*tion came over me — not a feeling of fear, but a conviction that my

^ndition was such that death was inevitable. My mind was perfectly

Lr, and I gave my attendants all directions as to my care. I took

|uent doses of ammonia and digitalis ; the former seemed to be of

•"^at advantage. At 7.30 mv condition was worse, and myself and

'Pendants were momentarily expecting my death. My extremities

-^nied to lose all power of either motion or sensation. I struggled

'Sainst this with all my will-power and would call for frequent doses

**' ammonia, which would give me (so it seemed) suiBcient strength to

*^<^\e. Painful emesis occurred twice, each time being attended with

J^ction of about 2 oz. of frothy matter, which soon evaporated^

having only a small white residuum. Resp. was now only 9 per m.,

^*^d exccedmgly shallow ; carotid pulse faintly beating at 200, radial

pulse entirely imperceptible, and no cardiac impulse felt on palpation.

•^ind still clear; suffered no pain.

i, "After about ii h. of this condition, I inhaled 3 dr. of nitrite of Ainyl. A marked improvement in the cardiac action was now noted. *esp. increased to 14. j pupils contracted to normal ; and skin became moist and warm. At ro radial pulse returned, and, though 14.0, was hill. Resp. was of normal frequency and almost normal vigour. At 1 1 pulse was 120. Suffered at this time from dull aching in lumbar region, and sense of great weakness and prostration. Half an h. later very copious diuresis took place. At I a.m., save for exhaustion, I was quite well. I was now put to bed, where I slept soundly til! 8. Next d. 1 suffered much annoyance from dryness in pharynx, and also from muscular weakness." {Therap, Gazette, 1888, p. 16,)

II. 14. Dr. W., jet. about 30, of excellent physique, began use of muriate upon nasal and pharyngeal mucous membrane for hay-fever, gradually increasing dose to 5 gr., which he had in e., when the hayfever was usually most distressing. This dose gave almost immediate relief from it, and produced sense of mental stimulation as from champagne. He was almost at once seized with desire for brain-work, and would pass greater part of n. reading and writing on professional topics, experiencing a keenness of perception and a mental vigour greater than normal. Towards m. he would fall asleep, and next d. would have no appetite and but little desire for work. He soon had a very irregular and rapid action of the heart, and passed by rapid stages to a condition of deplorable neurasthenia. He had little desire for food, thickly-coated tongue, feeble digestion, considerable emaciation^ scanty urine — much of the time loaded with uric acid and urates. There was also dyspncea. The stools for some time were chalky ; skin was dry and pallid ; pupils dilated ; reflexes, especially the patellar, much increased j muscular powers greatly diminished, He continued the use of the drug 10 d., and then left it off. The profound depression of the nervous system followed upon its stoppage. The depression gradually passed away j bur it was four months before he could resume the practice of his profession. (Brower, Medical Agt^ 1886, p. 27.) 5. Dr. B., set. 35, of neuropathic temperament, at one time in

the habit of using opium largely, began the use of C. in gr. doses, being at the time much run down by professional work. It gave him such a sense of well-being as he had never experienced from any agent before, the sense of complete repose and self-satisfaction being much more marked and agreeable than that derived from opium. He gradu ally increased the dose till he consumed (by hypodermic injection) about 15 gr.ad. These doses soon began to produce mental disturbance; he became irritable, quarrelsome, impetuous, and considered himself possessed of a mission to revolutionise medical practice, claimin to be able to cure all dscases by C.. He gave it indiseriminately to all, his patients, and to the members of his family. He was formerly a modest man of science; but now became bold and unscientific in his methods, engaged in law-suits, went about carrying a pistol and frequently displaying it in public places, threatening vengeance on all who dared doubt the correctness of his various extravagant statements, and becoming a perfect terror in his neighbourhood. The same general deterioration as before noticed was manifest in his case—extreme pallor and dryness of skin, great emaciation, loss of appetite, and no desire for sleep, so that for at least one week he did not assume the recum~ bent posture, "My repeated efforts to persuade him to stop the use of the drug were unsuccessful ; he went from bad to worse, until his friends thought it best to restrain him. In the asylum the C. was gradually withdrawn, but his mental extravagance continued unabated. oh 4, While the physiological and clinical literature of cocaine has attained already truly enormous dimensions, the chapter on morbid lesions arising under the influence of the alkaloid remains yet almost untouched, Hence the practitioner cannot help feeling very grateful to Dr Vasily M. Zantehevsky of St, Petersburg, who has just published an ably written experimental work (St. Petersburg Inaugural Dissertation, 1888, p. 9 5 analysed by Dr. V. Idelson, London Med. Record, Dee. 20th, 1888), aiming to hl up an important gap in our knowledge of a drug which undoubtedly represents the most brilliant acquisition of modern therapeutics. Dr. Zantchevsky’s experiments, conducted under the guidance of Professor N. P. Ivanovsky, were made on healthy adult dogs (animals which are fairly sensitive in regard to cocaine, as Professor Anrep has first pointed out) into which (usually Merck’s, sometimes Bochringer's) Rydrochlorate of cocaine was injected hypo dermically. In one group the effects of lethal doses, and in another chronic poisoning, were studied.

a, Acute poisoning was induced in five animals whose body’s weight varied from 1000 to roo grm. (about 10 Ibs.), by injecting from “15 (about two grains) to °27 grm. (or -03 per t kilo.) of cocaine, the animals dying in from 25 to 60 m. after the injection. The train of toxic symptoms was fairly uniform. For a few m. after the injection the dog either did not present anything abnormal, or fell into a kind of stupor; then appeared dilatation of pupils, restlessness, extreme dyspncra, and acceleration of pulse, and, in 15 m., attacks of clonic spasms, lasting for half am. or so, and alternating with paroxysms of typical ‘Cheyne-Stokes’s breathing 3 later on there supervened complete general

anaesthesia, dilatation of the palpebral slit, congestion of the conjunctiva, lachrymation, cyanosis^ loss of consciousness, incontinence of urine and feces, stertorous breathing, tremor of the whole body, and progressive ^failure and retardation of cardiac action.

b. Chronic poisoning was brought about in four dogs (weighing from 5600 to 8200 grm.) by injecting cocaine in doses gradually ascending from three or four (about '2 per i kilo.) to ten or sixteen centigrammes a day, the whole amount taken during the experiment varying from 108 to 78 grm., and death ensuing in from 43 to 107 d. The initial small doses gave rise to acceleration of breathing and pulse, fleeting (15 m.) general restlessness, also consecutive weakness of the animaPs hind limbs, mydriasis, and rise of the rectal temperature ('3° to *5° C), the symptoms disappearing in about 3 h. Increased doses produced the same but more pronounced and prolonged symptoms. The 7-centigramme doses induced sometimes manege movements of 2 or 3 m. duration, with extreme restlessness, followed in 4 h. or so by as extreme weakness and lassitude. The 8-centigramme doses gave rise to stupor, with high dyspnoea, acceleration of the pulse, and mydriasis, of 2 — 3 h. duration. The i-decigramme doses caused a complete narcosis, rise of the rectal temperature (1° C), decrease of general sensibility, and other symptoms of acute poisoning. In two of the animals there occurred several attacks of clonic spasms. Both of them died suddenly after a convulsive paroxysm, with consecutive profound prostration. The other two sank gradually from progressive extreme cachexia (which, however, was more or less pronounced also in the former two dogs).

c. Morbid lesions, either in acute or in chronic poisoning by cocaine, did not represent anything characteristic or pathognomonic. A. Macroscopical examination. — In acute poisoning there were ipvariably found all those alterations which occur in cases of fatal asphyxia, — such as dark fluid blood, engorgement of the thoracic veins, dilatation of the r. auricle and ventricle of the heart, venous congestion and oedema of the lungs, extravasations under the pleurae, pericardium, endocardium, and gastric mucous membrane, cyanotic liver, contracted spleen, moderate hypersemia of the brain and spinal cord, and a more intense one of their meninges. The same changes were present also in those two cases of chronic poisoning which had terminated suddenly, while in the two eminently cachectic cases there were detected extreme anaemia and dryness of all organs except the brain, medulla oblongata, spinal cord, and cerebro-spinal meninges, which were intensely congested. B. Microscopical examination. — Blood did not present any structural changes. Lungs : In acute cases there was dilatation of the alveolar vessels, with extravasations and occasional collapse of the alveoli ; opaque swelling of the alveolar epithelium j hyperxmia and extravasations in bronchioles. Liver : In acute poisoning there was found opaque swelling and granularity of hepatic cells ; hydropic and granular degeneration of the epithelium uf gall-ducts i serous infiltration of the interlobular connective tissue ; engorgement of the interlobular and central veins, with occasional small-sized extravasations in their neighbourhood ; and a distinct increase of glycogen in hepatic

cells, (The latter statement is in accord with Professor Tarkhan- Mouravof?’s observations, according to which large doses of cocaine rapidly give rise in dogs to glycosuria of about five hours’ duration ; vide the Firnal dla Normal. i, Patolog. Histoleg., etc. vol. vi.) In chronic intoxication, Dr. Zantchevsky found atrophy and albuminoid degeneration of hepatic cells, atrophy of the interstitial tissue, and atrophic attenuation of vascular walls. Heart presented considerable lesions in every one of the cases. In acute poisoning there was found initial signs of albuminoid degeneration of muscular fibres; minute extravasations in the subpericardal and ina leset degree, in the suben docardial and interstitial connective tissue ; tumefaction of the endothelium of capillaries ; opaque swelling and (non-fatty) granularity of many cardiac ganglia, with indistinctness of their nuclei. - In cachectic chronic cases the degenerative (albuminoid and fatty) changes were still more pronounced, the muscular fibres having lost their striz and being intensely granular, while the vessels were empty and their walls atrophied ; the cardiac ganglia presented extensive fatty degeneration and atrophy of their cells with vacuolization of the protoplasm, their nuclei being extremely indistinct. The medulla oblongata, especially the spinal cord, proved to have undergone still more profound altera~ tions, In acute cases there was invariably met albuminoid degenera~ tion of ganglionic cells ofthe medulla oblongata, anterior and posterior horns, Clarke’s columns and Roland’s gelatinous substance, the spinal changes being specially pronounced in the regions of the cervical and lumbar enlargements. There were found, further, dilatation of perivascular spaces, small extravasations in the gray matter, and occasionally mucoid degeneration of the epithelium of the central canal, In chronic poisoning, side by side with the same (but more intense and more extensive) degenerative lesions, there were detected hyaline degenera~ tion of nerve-cells in the spinal gray matter, engorgement of veins and capillaries (eopecially in the gray substance), and such. changes. of vascular walls as proliferation of their nuclei and hyaline degeneration, with consecutive varicosity of the diseased vessels, All those lesions in the medulla and spinal cord had a circumscribed character,—that is, were scattered in a patch-like manner over various districts of the organs. Dr. Zantchevsky is inclined to think that ‘ the degenerative changes arising in the nerve-centres under the influence of cocaine may be partly explained (apart from a still obscure specific action of the alkaloid on the nerve-elements) by a disturbance in the circulation of the central nervous system, which is caused by the drug. In acute poisoning cocaine brings about, in the first instance, rise of the bloodtension, with a consecutive diminution in the supply of arterial blood ; a subsequent fall of the blood-tension and a synchronous disturbance of breathing lead to a profound alteration of the blood in regard to its gaseous ingredients : hence the altered blood becomes an additional irritant agent; and hence there arise disturbances in the nutrition and degenerative changes of the nerve-cells.” It would be superfluous, of course, to dwell on the extreme sensibility of the nerve-tissue towards any slight deviation in the circulation or the composition of blood. In conclusion, Dr. Zantchevsky draws attention to a close similarity

between the morbid lesions in the nerve-centres as found by him in the cases of cocaine-poisoning, and those detected by Dr. Cziz in cases of acute and chronic poisoning by morphia and atropia {Meditz. Pribavl. k'Morsk. Shorn.^ May and June, 1883), the difference being only a quantitative one ; the former are somewhat milder comparatively with the Utter. Perhaps there exists a still greater similarity between the alterations caused by cocaine and those found in the nerve-centres and their blood-vessels in starvation (as described by Drs. V. Mankovsky, LoHd. Med. Record^ Feb., 1884, p. 73, and V. Rosenbach in his St. Petersburg Inaugural Dissertation^ 1883). Judging from that analogy. Dr. Zantchevsky arrives at the general conclusion that *' the cause of these degenerative changes which occur in chronic poisoning by cocaine should be sought in disturbed nutrition of cellular elements, which, in its turn, depends upon lesions of vascular walls, caused by a direct action of the alkaloid." (Therap. Gazette^ 1889, p. 112.)