Nicotinum

Volume IV — Main text

NiCOtinum, alkaloid derived from Tabacum, Cj(,Hj^Nj.

1. Pravin^s. — 1. Falck and Wachknfeld proved N. on themselves in doses of 0"2 to 0*3 mgrm. It caused frequent eructations, nausea, weariness, drowsiness. A third prover and Wachenfeld experienced after 004 headache and vertigo^ with trembling and oppression of chest. (HusEMANN, Planxtnsloffe^ p. 470.)

2. Reil look of 1st dil. of N., at first i dr., increasing the dose gndually by i dr. till he reached 15 dr. After i dr. he experienced ilieht scraping and burning in tongue and throat, headache in forehead 2nd temples, coming on after 10 m. and tasting i h., with slight symptnms of dysphagia. After 2 dr. these symptoms were more intense, at sime time moderate vertigo and transient pains in r. arm, thigh, and leg. After 3 dr. extreme weakness in lower extremities, dazedness of head, slight lachrymation, heaviness of eyelids, and after another dose peat eructation and trembling. After 4 dr. frequent need to draw a deep breath on account of oppression of chest. After 10 dr. throbbing in temporal arteries, indisposition to mental work, dilated pupils, weakness of vision, and hiccup. During the 16 d. the proving lasted the stools were delayed, the pulse and respiration very irregular, sometimes Slicker, sometimes slower. Urine not much increased. {Ibid,)

3. DwoRZAK and Heinrich proved N, in doses of i, 2, 2i,and 4^ ■iiilligrams. In all doses it caused a sharp burning sensation on tongue, 'craping in fauces, and in the larger doses as though a sharp brush was <ltiwn through oesophagus to stomach; increased saliva. Immediately 'ensation of warmth commencing in stomach quickly spreading over chest and heart and extending as in a stream to finger and toe tips. Along with this great excitement, in smaller doses generally marked headache, feeling of an aura in superior maxilla; from the larger doses peat confusion and heaviness of head, vertigo, stupid feeling, sleepilesj, indistinct vision with great sensitiveness of eyes to light, imperfect hearing with feeling as if ears were stuffed with cotton wool, rapid *fld laboured breathing, oppression, feeling as if a foreign body were 'tickine behind sternum, dryness of fauces. About 10 minutes after ^ larger doses uncommon feeling of weakness and exhaustion, so that

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the head could with difficulty be kept upright, pale tace; feiturts distorted, extremities very cold ; the coldness began in tips of fingers and toes and spread equally over trunk, premonitions of syncope with commencing loss of senses and consciousness. A disagreeable feeling in stomach spread upwards and downwards, causing eructation, nausea, inclination to vomit and actual vomiting with some relief; the sensation spread downwards over whole intestinal canal,abdomen distended, urgent call to stool, with discharge of flatus and urine and relief throughout the whole body, which, however, did not last long. In the first half of the and. h. one of the provers had clonic spasms throughout the whole body which increased for 40 m. and lasted altogether about I h. The extremities began to tremble, this trembling spread further until the whole body shook violently, the muscles of respiration were most affected, the respiration was laboured and tightened, each expiration consisted of a series of short impulses in rapid succession, the air was as it were jerked out of the thorax ; the inspiration was similar. In the other provcr during this period there occurred uncommon muscular weakness, very laboured breathing, and on one occasion rigor. The gastric symptoms, eructations and inclination to vomit were repeated several times; vomiting brought some relief; the coldness of the extremities was repeated in the same proportion -, from the tips of the fingers a feeling of formication spread at first to wrist, later to elbow. After 3 h. the intensity of the symptoms abated, there only remained confusion and heaviness of head, feeling of great weakness and emptiness of stomach and intestines, great exhaustion and drowsiness. A cup of tea and a roll were eaten without appetite. When going home both the provers felt uncommonly weak ; their gait was unsteady, and on reaching home they felt very cold ; in one of them the above-described spasms returned with urgent call to urinate, and much urine passed. Both passed a restless sleepless n., felt hot and excited ; and all next d. they were very ill, — inability to fix their mind on any subject, great exhaustion, drowsiness, violent headache, anorexia and desponding humour. The next n., though they slept well, did not completely relieve their sufferings on the 3rdd. In one of the provers the amount of urine was considerably increased ; in both, the skin was dry. The pulse at first, even after small doses, was accelerated, and the larger the dose the quicker it became ; it then varied much, so that it was sometimes several beats faster and then as many^ or more beats slower, and this variation went on but not with any ret^tlfl larity. But it always commenced with acceleration. In both there was a great loathing for tobacco-smoke. One, a smoker, thought to mitigate his sufferings by a pipe, but he could not take more than a few puffs ; the other, a non-smolcer, was very much affected by the smoke of a pipe in his vicinity. In both the expired air had a smell of alcohol (qu. nicotin ?) perceptible to themselves and to those abouCj them. {ScHKor TfLehri. d. Pharm.^ 577-) ■

1. Poisonings. — I. A young gentleman, poisoned by his brotherin-law, died in 5 m. after ingestion of the poison. His symptoms before death are unknown, but there is reason to believe that they consisted mainly of tetanic convulsions. The P.M. appearances

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le of corrosion in face and in alimentary canal zs far as duodenum. was found in stomach. (Tardiei;, op. cit.)

1. A marine officer, for some time melancholic, was found dead in IIS room. The body showed remarkable rigidity, and this continued »longer than its usual time ; the surface was of a palish colour. A small of N. solution was nearly empty. There were no signs of irrica- )n in alimentary canal, {/bid.) III. Experimtnts on animals. — i. a. According to NuNNELEY, I or 2 m. after the injection of v^ under the skin, a frog falls into a state ~' rigid spasm ; shortly after the eye becomes insensitive, and twitches occur in the limbs, except in that into which the injection had been made, in which the reflex power is abolished, although it is not so in the animal generally for i — 2 h. The heart beats regularly, but more and more slowly, until after death it remains in diastole filled with blood.

b. Melier gave i — 8 dr. doses to dogs and cats, generally hypodermically. The breathing was, in most of the cases, affected first, and is noted as difficult and anxious ; the pupils were dilated, and the animal staggered in walking. Violent erforts at defalcation were observed in several cases, and a copious discharge of urine, apparently followed by relief. At a more advanced period there was vomiting, and a slavering of frothy or ropy mucus ; at variable stages from the commencement, agitation and trembling, and in several instances a lively movement of the ears. When death occurred, it was immediately preceded by signs of complete exhaustion, and more remotely by convulsions. The exhaustion or paralysis appeared to affect the posterior extremities chiefly.

c. Very carefully conducted experiments were subsequently instituted, among others, by Albers, Kolliker, Bernard, and van Praag. They agree in their main results, which may be thus epitomized ; — N. uniformly renders the respiration slower, after having, in some instances, increased its frequency 9 the larger the dose the more speedily does the former effect ensue. The breathing has generally a very characteristic peculiarity, which consists in a hissing sound, and is probably owing to a spasmodic contraction of the larynx and air-tubes. The pulse, like the breathing, becomes slower after being accelerated. The muscular apparatus of various parts of the body is affected with alternate tonic and clonic spasms, and the eyeballs usually protrude, and are spasmodic4lly drawn upwards and outwards. General relaxation succeeds these phenomena, with a tremulous movement of particular muscles or of the whole body. In some cases which are more rapidly fatal, no spasmodic movements are observed, but immediate and complete prostration, with the tremulousness before mentioned. When the poison acts most promptly, the animal sometimes perishes without any convulsive or muscular agitation whatever. In general, its application does not elicit signs of pain, and the effect in some instances is to destroy sensibility. The pupils are uniformly dilated under its primary action, but afterwards may become contracted.* Sometimes, but not generally,

• HmscHMANN, who perturmed (Bull, dt Th&,, Ixv, 561) many experimenis on animals with this alkaloid, afHniis that it always contracts and never dilates the pupil.

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there is abundant saltvarion. In experiments which did not destroy life, and in these only, was there vomiting and purging ; yet recovery is possible without these symptoms. (Stillk, op. cit.)

1. From the yet more recent researches of Traubc, Rosenthil, Kroclcer, Erlcnmeyer, and SchrofF may be derived the following; r^sumi'. N. paralyses the brain, producing loss of consciousness lind (»• voluntary movement, after a more or less brief interval of excitement- The primary action on the cord is exciting, and produces clonic suicJ tonic convulsion , this is followed by paralysis, the cord becomes insensible to direct and to reflex irritation, apparently from affection of the

f;rey matter of the anterior cornua. The motor nerve-trunks arc buC ittle affected, but their terminals in the muscular substance are at firsc strongly irritated and then paralysed. Small doses affect the heart in s. double manner, the vagus branches being in comparison slightly, the^ cardiac motor nerves much more powerfully affected ; the excitement isP followed by paralysis. If the vagus be divided, N. nevertheless acts on the peripheral vagus-twi'gs, and the ganglionic apparatus in connectior« with them. The cardiac muscular structure does not appear to be directly affected. Respiration is at first quickened, and there may even be tetanus of the inspiratory muscles ; apparently this action is exerted upon the nerve termini among the muscles, for section of the vagi does not prevent it. The respiratory excitement also is followed by paralysis. A very constant lowering of superficial temperature has been observed by Tscheschichin, which probably depends on rapid cooling of the body in consequence of vaso-motor paralysis. Intestinal peristalsis is hurried, and there may even be intestinal tetanic spasms, while in women there are vigorous contractions of uterus. The action on the pupil has been much disputed, but the most recent and reliable researches seem to prove that N. produces contraction of the circular fibres of the iris. (Phillips, op. cit.)

1. M. Stas, who had charge of the case forming II. I, made experiments with the N. found in stomach of the murdered man.

a. The tongue of a siskin was touched with a capillary-tube containing a minute quantity of the alkaloid. In a very short time the bird shook its head and fell into tetanic convulsions. It died in 2 m. 40 seconds, falling on to r. side. In another similar experiment on a bird of this kind, the tetanus was immediate, and the death occurred in 30 seconds.

b. A fraction of a drop was placed on the tongue of a vigorous pigeon. The convulsions came on after a few seconds, and death after I m. 15 seconds. (Taroieu, tf^. «V.)

1. Dr. Hobart Amory Hare has received the Fiske Fund prize for an essay on " The Physiological and Pathological Effects of the Use of Tobacco." His conclusions are as follows : I. Tobacco-smoking docs not decrease the urine eliminated, but rather increases it. 2. Tobacco does retard tissue waste. 3. Tobacco and its alkaloid cause convuN sions in the primary stage of the poisoning, by depressing the reflex inhibitory centres tn the cord. 4. It causes palsy in the second stage, by paralysing {a) the motor nerve-trunks, {h) the motor tract of the spinal cord. 5. The sensory nerves are not affected by the drug. 6.

Nicotinr contracts the pupil, by stimulating the oculo-motor and paralysing the sympathetic, this action being peripheral. 7. Nicotine, primarily, lowers the blood -pressure and pulse rate; secondarily, increases pressure and rate ; thirdly, decreases pressure. 8. The primary lowering of pressure and rate ia due to pneumogastric stimulation, associated with vaso-motor dilatation. 9. The secondary stage is due to vaso-motor constriction and pneumogastric palsy. 10. The third stage is due to vaso-motor dilatation returning. 11. Death, in poisoning from this drug, is due to failure of respiration, the action of the drug being centric, j 2. The blood-corpuscles are broken up and CTtUated by the action of the poison. 13. In death from nicotine pwwning the blood shows changes in spectra. 14. Death can be brought about by the cutaneous absorption of nicotine. 15. Tobacco incccases intestinal peristalsis in moderate amounts, and produces tetanoid intestinal spasms in poisonous doses, i6. The liver seems to destroy the poison, although this destruction is participated in by any Kt of capillaries in other parts of the body. 17. Tobacco-smoking increas« the pulse-rate, and decreases arterial pressure. {Therap. Gaz., Jin. 15th, 1886.)